Bone Marrow MRI

Lia Angela Moulopoulos
Vassilis Koutoulidis
Bone Marrow MRI
A Pattern-Based Approach
123
Bone Marrow MRI
Lia Angela Moulopoulos • Vassilis Koutoulidis
Bone Marrow MRI

A Pattern-Based Approach
Lia Angela Moulopoulos Vassilis Koutoulidis
Professor of Radiology and Chair Assistant Professor of Radiology
1st Department of Radiology 1st Department of Radiology
University of Athens School of Medicine University of Athens School of Medicine
Athens Athens
Greece Greece
ISBN 978-88-470-5315-1 ISBN 978-88-470-5316-8 (eBook)

DOI 10.1007/978-88-470-5316-8
Springer Milan Heidelberg New York Dordrecht London
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To my father, a scientist. With love and admiration.
LAM
To my father, Constantinos Koutoulidis, M.D., who passed away during the

writing of this book.
To Olga and our children, Constantinos and Ariadne. With unstinting love
and gratitude.
VK
Preface
Why a Pattern-Based Approach?
Bone marrow, responsible for blood cell production, is a dynamic, ever-shifting, continuously
adapting organ. Dynamic changes commence from the moment hematopoietic tissue appears
in the cavities of the fetal long bones at approximately the 10th to 11th week of gestation in
humans. They continue after birth until the adult pattern of red/yellow marrow distribution is
reached at about 25 years of age. After this point, bone marrow fat continues to increase slowly
in an orderly, predictable way. Reconversion of yellow marrow into red marrow may occur at
any time point when the needs for hematopoiesis increase. All these processes, which alter the
composition of bone marrow, complex as they are, can be simplified and better understood by
using a pattern-based approach. Patterns are repeatedly recognized when studying both bone
marrow physiology and pathology. Orderly patterns predict the way red marrow converts into
yellow marrow at the skeletal level as well as at the level of each individual bone. When yellow
marrow reconverts into red marrow, patterns reverse from the above are observed. Familiarity
with the patterns of normal bone marrow changes is essential to identify the presence of dis-
ease. Conditions that affect bone marrow by infiltrating it with inflammatory or neoplastic cells
do so in ways that may be schematically presented with patterns. MRI provides an excellent
means of visualizing these patterns of normal and abnormal marrow.
We find this pattern recognition approach very useful because it provides an organized way
of MR image interpretation. Pattern assignment facilitates the learning of bone marrow MRI
as it links imaging appearances to underlying pathophysiological changes. It is interesting that
discrete patterns of disease are also reflected in more advanced MRI techniques such as
Dynamic Contrast-Enhanced MRI and Diffusion-Weighted MRI. In certain clinical entities,
MRI patterns may also have important prognostic value.
We did not set out, therefore, in this book to provide an exhaustive list of MRI features of
every single disease that may affect bone marrow. We chose instead this pattern-based
approach, which we have found very useful over the years, both for teaching purposes and in
day-to-day clinical practice. The first chapters of the book address the anatomy and physiology
of bone marrow as well as normal marrow MRI. A chapter is then devoted to the analysis of
the different MRI patterns of abnormal marrow, and extensive differential diagnosis lists are
provided. The most important disease entities affecting the marrow are presented in the next
chapters in a uniform fashion. The relevant clinical information is provided first, followed by
findings on other imaging modalities; finally, the MRI findings of each disease are presented
in detail. Apart from the discussion of imaging features, we have tried to emphasize the clinical
implications of MRI findings and the way in which they may affect patient management and
treatment. Common diagnostic dilemmas, such as benign versus malignant vertebral fracture
vii
viii Preface
and treated inactive marrow versus residual active disease, are addressed in separate chapters.
With the help of key points highlighting the most important information and a large number of
richly annotated figures, we hope to make the challenging task of bone marrow MRI interpre-
tation a little bit easier for the reader and as exciting as it is for us.
Lia Angela Moulopoulos

Vassilis Koutoulidis
Acknowledgments
We would like to thank the following:

Our families for their love and understanding and for putting up with us during our intermi-
nable preoccupation with “The Book.”
The MRI technologists at our institution (Miltiadis Ioannidis, Maria Roussaki, Virginia
Mantikou) for their commitment and excellent work.
The clinical staff in the Department of Clinical Therapeutics—Division of Hematology/
Oncology of the University of Athens School of Medicine led by Professor Meletios A.
Dimopoulos for their hard work and support.
From Springer, Antonella Cerri for embracing our project with enthusiasm and conviction,
Andrea Ridolfi for his expert assistance and encouragement during the writing of the book,
and Magesh Rajagopalan and Sushil Kumar Sharma for a first-rate production job.
And, lastly:
LAM wishes to thank VK, a challenging and inspiring partner for all those shared moments of
creative thinking and fun.
VK would like to thank LAM: a mentor, a friend, and the best writing partner he could ever
hope for.
ix
Contents
1 Νormal Bone Marrow: Anatomy, Function, Conversion,

and Reconversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Normal Bone Marrow: Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1.1 Bone Marrow Types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1.2 Vascular Anatomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1.3 Cellular Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 Normal Bone Marrow: Function. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3 Age-Related Changes in Bone Marrow Composition: Red to Yellow
Marrow Conversion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.4 Reconversion of Yellow to Red Marrow. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2 MRI of the Normal Bone Marrow: Pulse Sequences . . . . . . . . . . . . . . . . . . . . . . 7
2.1 T1-Weighted Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.2 T2-Weighted Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.3 Chemical-Shift Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.4 Contrast-Enhanced Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
2.5 Diffusion-Weighted Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3 MRI of the Normal Bone Marrow: Anatomic Sites . . . . . . . . . . . . . . . . . . . . . . . 25
3.1 Spine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.2 Pelvis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.3 Extremities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.4 Rib Cage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
3.5 Skull . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
4 The Abnormal Bone Marrow: MRI Patterns. . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
4.1 Focal Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
4.1.1 Hyperintense Focal Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
4.1.2 Hypointense Focal Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
4.1.3 Signal-Void Focal Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
4.2 Variegated Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
4.3 Diffuse Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
4.3.1 Hyperintense Diffuse Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
4.3.2 Hypointense Diffuse Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
4.3.3 Signal-Void Diffuse Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
4.4 Regional Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
4.4.1 Hyperintense Regional Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
4.4.2 Hypointense Regional Pattern. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
xi
xii Contents
5 MRI of the Abnormal Bone Marrow: Focal Pattern . . . . . . . . . . . . . . . . . . . . . . 57

5.1 Hemangioma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
5.1.1 Clinical Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
5.1.2 Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
5.1.3 Magnetic Resonance Imaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
5.2 Metastases: Focal Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5.2.2 Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
5.3 Multiple Myeloma: Focal Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
5.3.2 Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
5.4 Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
5.4.2 Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
6 MRI of the Abnormal Bone Marrow: Diffuse Pattern . . . . . . . . . . . . . . . . . . . . 101
6.1 Metastases: Diffuse Pattern. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
6.2 Multiple Myeloma: Diffuse Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
6.3 Lymphomas and Leukemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
7 Bone Marrow Edema Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
7.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
7.2 Transient Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
7.3 Regional Migratory Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
7.4 Complex Regional Pain Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
7.5 Calcineurin Inhibitor Pain Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
7.6 Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
7.7 Differential Diagnosis of Reversible Versus Irreversible
Bone Marrow Edema Pattern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
8 Benign Versus Malignant Vertebral Fractures. . . . . . . . . . . . . . . . . . . . . . . . . . . 127
8.1 Clinical Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
8.2 Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
8.3 Magnetic Resonance Imaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
8.3.1 Signal Intensity Characteristics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
8.3.2 Morphologic Characteristics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
8.3.3 Quantitative Characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
8.3.4 Findings at Other Spinal Levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
8.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
9 MRI of Bone Marrow Posttreatment Changes . . . . . . . . . . . . . . . . . . . . . . . . . . 143
9.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
9.2 Effect of Treatment on Normal Bone Marrow . . . . . . . . . . . . . . . . . . . . . . . . . 143
9.2.1 Effect of Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
9.2.2 Effect of Chemotherapy and Hematopoietic Growth Factors. . . . . . . . 144
9.2.3 Bone Marrow Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Contents xiii
9.3 Effect of Treatment on Abnormal Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

9.3.1 Conventional MR Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
9.3.2 Advanced MRI Techniques. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
9.4 MRI Assessment of Complications of Treatment. . . . . . . . . . . . . . . . . . . . . . 154
9.4.1 Post-radiotherapy Fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
9.4.2 Osteonecrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
9.4.3 Bone Marrow Necrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
10 Bone Marrow MRI: A Quick Guide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
10.1 Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
10.2 Focal Bone Marrow Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
10.3 Diffusely Abnormal Bone Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
10.4 Vertebral Compression Fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
10.5 Posttreatment Assessment of Bone Marrow Malignancies. . . . . . . . . . . . . . . 166
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Νormal Bone Marrow: Anatomy,
Function, Conversion, 1
and Reconversion
1.1 Normal Bone Marrow: Anatomy differences in fat and water content account for the distinct
appearance of red and yellow marrow on MR images.
Bone marrow is the organ responsible for blood cell produc-
tion in humans. It is also the fourth largest organ of the body
by weight, following bone, muscle, and fat [1]. It is estimated Key Points
that, in humans, bone marrow accounts for approximately • Significant differences in chemical composition
4–5 % of the total body weight [2, 3]. Marrow is soft and exist between red marrow and yellow marrow
pulpy and fills the osseous medullary cavities. The latter con- • Red marrow composition: 40 % water, 40 % fat,
sist of multiple small spaces between trabeculae and larger and 20 % protein
cavities within the shafts of long bones. Although the evolu- • Yellow marrow composition: 15 % water, 80 % fat,
tionary processes that led to confinement of hematopoiesis to and 5 % protein
the osseous medullary cavities are not yet fully understood,
there is a rapidly evolving field of research examining the
close association between skeletal and hematopoietic tissue
(e.g., the role of endosteal osteoblasts in regulating the Key Point
hematopoietic microenvironment through their interaction • Distinction of red and yellow marrow on MRI is
with hematopoietic stem cells) [4, 5]. based on differences in fat and water content
1.1.1 Bone Marrow Types

1.1.2 Vascular Anatomy
Two types of bone marrow exist, varying in composition and
function: red (hematopoietic, active) and yellow (fatty, inac- Arterial supply to the bone marrow is derived largely from
tive) marrow. The red color of hematopoietic marrow is due the nutrient artery. In long bones, one or two main nutrient
to the presence of hemoglobin in red cells and their progeni- arteries enter the bony cortex obliquely through nutrient
tors which together with white cells and platelets account for foramina leading into nutrient canals. The artery courses to
60 % of its bulk, the rest being composed of fat cells [6, 7]. the center of the medullary cavity, where it divides into
Yellow marrow is made almost entirely (95 %) of fat with ascending and descending branches that run parallel to the
very few hematopoietic elements and owes its color to carot- long axis of the bone. These give rise to multiple smaller
enoid pigments which are found in fat cells [8, 9]. Bone mar- radial branches which extend outwards, to the inner surface
row fat cells are smaller than their extraosseous counterparts; of the cortex. There, they give off branches to a mesh of thin-
red marrow fat cells contain slightly more unsaturated fatty walled sinusoids which spread in between the fat cells of the
acids than those of yellow marrow. The aforementioned dif- marrow. Additionally, nutrient artery-derived capillaries
ferences in the cellular composition between the two types enter into the haversian canals of the cortex, anastomose
of marrow are also reflected in their chemical composition. with intracortical capillaries (i.e., marrow vascularity com-
Red marrow consists of approximately 40 % water, 40 % fat, municates with bone vascularity), and reenter the marrow
and 20 % protein, whereas yellow marrow contains approxi- cavity to open into the sinusoids [5]. The sinusoids finally
mately 15 % water, 80 % fat, and 5 % protein [6]. These drain into a large central venous sinus and from there to the
variations in chemical composition and, in particular, the emissary veins. Hematopoiesis occurs in hematopoietic
L.A. Moulopoulos, V. Koutoulidis, Bone Marrow MRI: A Pattern-Based Approach, 1

DOI 10.1007/978-88-470-5316-8_1, © Springer-Verlag Italia 2015
2 1 Normal Bone Marrow: Anatomy, Function, Conversion, and Reconversion
Fig. 1.1 Bone marrow Periosteal artery

vasculature: schematic
representation. Note the Radial
anastomoses between radial arteries
branches of the nutrient artery and Cortical bone Venous sinuses
branches derived from periosteal
arteries. Also note the sinusoids
formed from the above branches.
Hematopoiesis occurs in the
intersinusoidal tissue spaces Hematopoietic
tissue spaces
(Reprinted with permission from
Travlos [10]) Central
vein
Central
artery
Nutrient artery
Nutrient vein
cords located in the extravascular spaces between the sinu- 1.1.3 Cellular Organization
soids [10] (Fig. 1.1).
Differences between red and yellow marrow extend to Bone marrow has traditionally been considered to consist of
their vascularization. This has very important implications two distinct lineages: the hematopoietic tissue proper and
regarding localization of bone marrow diseases, both malig- the supporting marrow stroma [12, 13]. Hematopoietic cells
nant and nonmalignant. Red marrow has a rich vascular sup- and stromal cells are organized in solid cords, separated by
ply with a dense sinusoidal network, whereas yellow marrow sinusoids [14]. The barrier between the sinusoids and the
vascularization is markedly decreased. During the physio- cords is the trilaminar sinus wall which consists of a luminal
logic conversion of red to yellow marrow, significant changes layer of endothelial cells, a thin basement membrane, and an
occur regarding the marrow vasculature. The nutrient artery incomplete outer lining of adventitial reticular cells cover-
decreases in size, and the dense network of sinusoids is grad- ing approximately 60 % of the sinusoidal abluminal sur-
ually replaced by sparsely arranged capillaries, venules, and face [5]. Bone marrow stromal cells include macrophages,
veins [11]. The accumulating adipocytes of yellow marrow lymphocytes, endothelial cells, and reticular cells [14].
are derived from the adventitial reticular cells that form the Endothelial cells completely line the luminal surface of the
outer lining of the sinusoidal wall. The large adipocytes that sinusoids. They display overlapping or interdigitating
replace the reticular cells compress the sinus wall, causing unions which allow changes in the luminal size of the sinus
collapse of the sinusoid. Thus, sinusoids running among fat [15]. Adventitial reticular cells are the direct progenitors of
cells in yellow marrow are excluded from blood flow [5]. bone marrow adipocytes. Long, thin processes project from
Conversely, when reconversion of yellow to red marrow their cell body into the adjacent tissue, providing a scaffold
occurs, the nutrient artery enlarges and space between sinu- for stromal and hematopoietic cells [14]. Bone marrow adi-
soids is reformed through lipolysis. Thus, pressure upon the pocytes develop by lipogenesis from the adventitial reticular
sinus wall is lifted, previously collapsed sinusoids dilate, and cells. Any reduction of hematopoietic cell mass, either age
blood flow resumes through their lumen [5, 11]. related or not, is followed by rapid accumulation of lipid
within reticular cells, which then convert into adipocytes
[5]. The hematopoietic cells are not randomly arranged but
Key Points
demonstrate a particular organization within bone marrow
tissue [16]. The erythroblastic islands are mainly located
• Red to yellow marrow conversion is associated with close to the sinusoidal wall, as are megakaryocytes.
a decrease in intramedullary blood flow Granulocyte precursors are positioned deeper, in the subcor-
• Reconversion of yellow to red marrow is associated tical regions of the cords [14]. Following maturation, the
with an increase in intramedullary blood flow hematopoietic cells traverse the wall of the sinusoids and
enter the blood circulation (Fig. 1.2).
1.3 Age-Related Changes in Bone Marrow Composition: Red to Yellow Marrow Conversion 3
Adventitial cells
Arteriole
Endothelial cells
Sinus Endothelial
cells
Megakaryocyte
Fat cell
Erythroblastic
islet
Fig. 1.2 Bone marrow structure: schematic representation.

Note the structured organization of hematopoietic cells, the sinusoidal wall consisting of endothelial and adventitial cells, and the sinusoidal lumen
where mature hematopoietic cells are released to enter the blood circulation (Reprinted with permission from Valdez et al. [14])
1.2 Normal Bone Marrow: Function macrophages and megakaryocytes are also produced [22]. A
second hematopoietic wave also arises in the yolk sac and con-
The role of the bone marrow in blood cell production was not sists of “definitive” erythroid progenitors that enter the blood-
recognized until the second half of the nineteenth century. In stream and seed the fetal liver. The third wave of hematopoiesis
1868, Ernst Neumann and Giulio Bizzozero independently arises from hematopoietic stem cells (HSCs) produced within
published reports that eventually led to the recognition of bone a number of intraembryonic sites, including the aorta-gonad-
marrow as the site of definite hematopoiesis [17, 18]. Neumann, mesonephros (AGM) region. The HSCs that form in these tis-
in a preliminary report published in October of that year, sues consecutively seed the fetal liver, spleen, and bone
described the presence of nucleated red blood cells in the bone marrow, producing all hematopoietic lineages [21]. The fetal
marrow sap of humans and rabbits by squeezing bone. Two liver is the main site of hematopoiesis during mid-gestation.
communications by Bizzozero with similar observations soon Hematopoiesis in fetal long bones begins by gestational
followed. In subsequent papers, Neumann, a pathologist with a week 10–11 (before initiation of hematopoiesis in the verte-
persistent interest in bone marrow research, postulated a com- brae) and remains confined to the diaphyseal region until week
mon stem cell origin for all hematopoietic cells [19]. Moreover, 15 [23]. From week 16 onward, hematopoietic cells are also
he discriminated between hematopoietically active red marrow found at the diametaphyseal junction and in the metaphysis
and inactive yellow marrow and, in 1882, was the first to itself [24]. The bone marrow takes over from the liver as the
describe the process by which red marrow progressively con- major site of hematopoiesis after the 24th week of gestation.
verts to yellow marrow from the peripheral towards the axial
skeleton (which is why red to yellow marrow conversion is
sometimes referred to as “Neumann’s law”) [20]. 1.3 Age-Related Changes in Bone Marrow
Hematopoiesis occurs in several waves during embryonic Composition: Red to Yellow Marrow
and fetal development and arises from multiple shifting ana- Conversion
tomical sites, bone marrow being the last of them [21].
Hematopoiesis begins in the blood islands of the extraem- Fetal bone marrow is entirely red. At birth, possibly triggered
bryonic yolk sac at the end of gastrulation. This so-called by changes in temperature, vascular supply, and oxygen ten-
“primitive” hematopoiesis is largely erythropoietic, although sion, the process of red to yellow marrow conversion starts.
This process continues through life and follows a predictable marrow but within months undergoes transformation to
pattern which was first described by Ernst Neumann in 1882 yellow marrow [33]. Adipose conversion thereafter pro-
and has since been extensively studied and mapped [1, 11, ceeds to the diaphysis, distal metaphysis, and proximal
20, 25, 26]. metaphysis. The proximal metaphyses of the humeri and
Red to yellow marrow conversion follows an orderly femora are, therefore, the last parts of the appendicular
pattern from the peripheral towards the central skeleton skeleton to undergo fatty transformation. Although varia-
[1]. It begins in the terminal phalanges of the feet and tions exist, by the age of 25 years, the adult pattern of red/
probably the hands at birth, when all marrow is hemato- yellow marrow distribution has been reached. At that time
poietic [27]. Although the causes and mechanisms of this hematopoietically active red marrow is found in the spine,
centripetal regression of active hematopoietic tissue have ribs, sternum, pelvis, skull, and to a lesser degree, in the
been the subject of investigation for many years, they are proximal metaphyseal regions of the femora and humeri
still not completely understood. The predilection of red [1, 25].
marrow for the central skeleton was initially explained by
the higher tissue temperature and increased vascularity of
the central skeleton compared to the distal extremities. Key Points
These observations date back to the 1930s [28, 29]. Today, The adult pattern of red/yellow marrow distribution
these hypotheses have been questioned, and there is a con- • Red marrow is restricted to the axial skeleton (spine,
tinuous search for other triggering factors for the red to sternum, ribs, pelvis, skull) and to the proximal
yellow marrow conversion process (cytokines, hormones) metaphyses of the femora and humeri
[15, 30, 31]. • The pattern is reached around the age of 25 years
It has also been suggested that the far larger number of
mesenchymal stem cells (MSCs) lining the trabeculae of the
cancellous bones of the central skeleton (extensively devel-
oped trabecular system, thin cortex) compared with the tubu- It must be noted that, in the axial skeleton, yellow mar-
lar bones of the extremities (few trabeculae, thick cortex) row conversion does not stop after the adult pattern of
may also play a role in the red to yellow marrow conversion bone marrow distribution is reached. With aging there is a
process. MSCs are precursors of both bone-forming cells slow and steady increase of marrow fat content in the
and hematopoietic microenvironment cells. According to spine. Data obtained from histologic studies have shown a
this hypothesis, the MSC population in tubular bones decrease of red marrow volume in vertebral bodies from a
becomes exhausted rather early, whereas in centrally located mean of 58 % in the first decade of life to 29 % by the
cancellous bones, the relatively large number of MSCs con- eighth decade, with a concomitant increase in the percent-
tinues to provide newly differentiated hematopoietic micro- age of adipose cells [34]. More recently, MR spectroscopy
environment, thus maintaining red bone marrow throughout has been used as a reliable noninvasive tool for quantifica-
life [32]. tion of marrow fat content in different age groups [35, 36].
Within each individual bone, red to yellow marrow con- Results have shown that the relative proportion of fat in the
version follows an orderly, well-defined sequence: yellow vertebral bone marrow increases with age from 24 % in the
marrow first appears in the epiphyses, then in the diaphysis, age group of 11–20 years to 54 % in the group of >61 years
and lastly in the metaphyses, distal followed by proximal. [35]. Moreover, it has been shown that, although males
The pattern of marrow conversion is similar in distal and show a gradual, steady rise in marrow fat content through-
proximal long bones, except that the rate of conversion is out life, in females there is a sharp increase in vertebral
more rapid in the distal long bones [11]. marrow fat content between 55 and 65 years of age, fol-
lowing menopause [37]. As a result of this, from 65 to at
least 85 years, marrow fat content is higher in females than
Key Points males, which is a reversal of the pattern seen in subjects
Red to yellow marrow conversion patterns younger than 60 years when males tend to have more mar-
• Skeleton: peripheral → central row fat.
• Long bones: epiphysis → diaphysis → distal metaph-
ysis → proximal metaphysis
Key Point
The cartilaginous epiphysis lacks marrow until it begins • In the axial skeleton, red to yellow marrow conver-
to ossify by means of endochondral ossification. The newly sion proceeds throughout life
formed secondary ossification center initially contains red
References 5
1.4 Reconversion of Yellow to Red

Marrow Key Points
Reconversion of yellow to red marrow: causes

Bone marrow is regarded as a dynamic organ not only in the • Marrow infiltration/replacement disorders (metas-
sense that it undergoes lifelong age-associated changes in its tases, hematologic disorders)
composition (i.e., red to yellow marrow conversion) but also • Severe anemia
because, under specific circumstances, these changes are • Chronic heart failure
reversible. Indeed, yellow marrow may readily reconvert to • Hematopoietic growth factors
red marrow under various conditions that cause increased • Extensive irradiation (reconversion occurs in the
demands for hematopoiesis [8, 11, 38]. At the cellular/micro- nonirradiated skeleton)
vascular level, this reconversion is characterized by the • Long-distance running
reverse sequence of events that occur during physiologic red • High-altitude living
to yellow marrow conversion: loss of the large marrow fat • Heavy smoking
cells through lipolysis allows previously collapsed sinusoids • Obesity
to expand, with blood flow resuming through their lumen
and perisinusoidal hematopoiesis restored [5]. A reverse
pathway to that of adipose conversion is also observed at the
larger scale. Thus, reconversion begins in the axial skeleton References
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MRI of the Normal Bone Marrow:
Pulse Sequences 2
The first step towards the interpretation of MR images of the

bone marrow is getting familiar with the appearance of the
normal marrow, including expected age-related changes [1].
Differences in fat and water content are primarily responsi-
ble for the different signal intensities of red and yellow bone
marrow on MR images. In this chapter, normal bone marrow
MRI is discussed, in terms of findings on the different pulse
sequences.
2.1 T1-Weighted Imaging
T1-weighted spin-echo images are most suited for the initial

study of bone marrow. The short T1 relaxation time of fat
protons which exist mostly in hydrophobic CH2 groups and
compose the bulk of yellow marrow accounts for its high
signal intensity on T1-weighted sequences (Fig. 2.1). Red
marrow signal intensity is lower than that of fatty marrow,
because of decreased fat content and increased cellularity
(Fig. 2.2). The net signal intensity of bone marrow on
T1-weighted MR images depends on the relative proportions
of fatty and red marrow.
Diseased bone marrow typically has lower signal inten-
sity than fatty marrow on T1-weighted images because it is
more cellular and contains greater amounts of water and
lesser amounts of fat (Fig. 2.3). An abnormal process may,
therefore, have comparable signal intensity to red marrow
on T1-weighted images making difficult the distinction
between pathology and normal hematopoietic marrow
(Fig. 2.4). Several attempts have been made to differentiate
bone marrow involvement from normal red marrow by com-
paring marrow signal intensity to various structures in the
body. A hypointense to intervertebral disc bone marrow
(hyperintense disc sign) was one of the first signs that was
described as suggestive of diseased bone marrow [2]
Fig. 2.1 Yellow marrow, high T1 signal intensity.
(Fig. 2.5). Both nondegenerated intervertebral discs and
Sagittal T1-weighted image of the lumbosacral spine of a 65-year-old
muscles have since then been employed as potential internal woman shows high-signal-intensity vertebrae due to predominance of
standards for the assessment of bone marrow status yellow marrow

8 2 MRI of the Normal Bone Marrow: Pulse Sequences
Fig. 2.2 Red marrow, low T1 signal intensity.

Sagittal T1-weighted image of the thoracic spine of a 25-year-old man
shows low-signal-intensity vertebrae due to predominance of red marrow
Fig. 2.4 Low T1 signal intensity, normal red marrow.

woman shows low-signal-intensity vertebrae due to age-related pre-
dominance of red marrow
(Fig. 2.6). Carroll et al. concluded that bone marrow signal

intensity equal to or lower than that of disc or muscle on
T1-weighted images at 1.5 T is abnormal with a 98 % (disc)
and 94 % (muscle) accuracy [3]. Corresponding accuracy
values at 3 T were higher when bone marrow was compared
to muscle (89 %) than when it was compared to disc (78 %)
[4]. It should be noted, though, that in the first year of life,
normal red marrow may be hypointense to disc due to its
Fig. 2.3 Low T1 signal intensity, malignant bone marrow. hypercellularity (Fig. 2.7). After age 5, in approximately
Sagittal T1-weighted image of the lumbosacral spine of a 59-year-old 90 % of children, bone marrow signal intensity is higher
man with multiple myeloma and 67 % bone marrow plasmacytosis than that of disc [5].
shows low-signal-intensity marrow due to diffuse malignant infiltration
2.2 T2-Weighted Imaging 9
Fig. 2.5 Hyperintense disc a c

sign.
b
Sagittal T1-weighted images of
the spine in three different
patients with bone marrow
metastases from breast cancer
(a), neuroblastoma (b), and small
cell lung cancer (c) show diffuse,
low-signal-intensity bone
marrow. In all three cases, the
intervertebral discs are
hyperintense to the abnormal
marrow
Fig. 2.6 Normal bone marrow, a b

internal standards.
(a) Sagittal T1-weighted image
of the lumbosacral spine of a
25-year-old man with
predominantly red marrow:
although spinal marrow has
relatively low signal intensity, it
is still hyperintense to the
intervertebral discs. (b) Axial
T1-weighted image of the same
individual at the level of L3
shows that normal marrow is also
hyperintense to adjacent psoas
muscles (asterisks)
Key Points 2.2 T2-Weighted Imaging

• Red marrow signal intensity lower than that of non-
Fat protons have a long T2 relaxation time, less however than
degenerated disc or muscle on T1-weighted images
that of water protons. Therefore, on T2-weighted spin-echo
is abnormal
(SE) images, the signal intensity of fat is lower than that of
• Exception: infants
rich in water proton structures, i.e., nondegenerated disc,
On T2-weighted images with fat saturation, foci composed

almost entirely of fat cells, such as focal fatty marrow or
Modic II degenerative endplate changes, will be of lower sig-
nal intensity compared to those which contain red marrow
alone or both red and yellow marrow (Figs. 2.10 and 2.11).
Fat suppression may be achieved with application of
either a chemically selective fat-saturation technique or an
inversion recovery technique [1]. The chemically selective
fat-saturation technique consists of application of a radiofre-
quency pulse which selectively suppresses the signal of fat
protons. The smaller the chemical shift between fat and
water protons (i.e., the lower the magnetic field applied), the
more difficult it is to selectively suppress fat. Field inhomo-
geneity (presence of metal, interfaces of tissues with pro-
nounced differences in proton density such as air and bone,
off isocenter imaging, large field of view) will cause insuffi-
cient suppression of fat; increasing the bandwidth or setting
the frequency direction parallel to a metallic prosthesis may
render the susceptibility artifact less pronounced. On
T2-weighted images with chemically selective fat saturation,
yellow marrow signal intensity will be lower than that of
muscle, red marrow will have approximately the same signal
intensity with muscle, and most pathologic lesions tend to be
hyperintense to muscle [1].
Short inversion time inversion recovery (STIR) techniques
apply a 180° pulse to invert magnetization of all tissues being
imaged. When the inverted longitudinal magnetization of fat
has reached the null point after a delay time called inversion
time (TI), a 90° RF pulse is applied generating signal from
all, other than fat, tissues. Optimal TI for fat suppression is
130–170 ms for 1.5 T scanners. Because nonfatty tissues
Fig. 2.7 Normal bone marrow, child.
recover their longitudinal magnetization more slowly than
Sagittal T1-weighted image of the lumbosacral spine of a 2-year-old fat, the signal-to-noise ratio (SNR) of this sequence is less
boy shows that spinal marrow is hyperintense to the intervertebral discs than that of the chemically selective fat-saturation techniques.
(Image courtesy of Ioannis Nikas, M.D., Children’s Hospital “Aghia Contrast resolution is, however, very good because tissues
Sophia”, Athens, Greece)
with long T1 and T2 relaxation times appear very bright [7].
Although with this sequence fat suppression is more homoge-
muscle, and most disease entities affecting the bone marrow neous, signal from tissues with similar relaxation times to fat
[6]. Fatty marrow signal intensity is similar to or slightly (blood, paramagnetic contrast, mucoid or proteinaceous
lower than that of subcutaneous fat. Red marrow has an material, melanin) may be suppressed.
intermediate signal intensity on T2-weighted SE images,
which is lower than that of most abnormal bone marrow pro-
cesses. Differentiation of red and yellow marrow is not as
Key Points
easy as on T1-weighted images.
On fast spin-echo (FSE) sequences, the signal intensity of • T2-weighted fast spin-echo sequences should not
fat remains relatively high unless fat suppression techniques be used for imaging of the bone marrow without fat
are employed, rendering these sequences not useful for the suppression
study of bone marrow as both normal fat-containing marrow • Fat suppression of T2-weighted images can be
and water-rich lesions will manifest with increased signal achieved with chemically selective fat saturation or
intensity. Lesion conspicuity is, therefore, greatly increased with an inversion recovery (STIR) technique
on fat-suppressed T2-weighted sequences (Figs. 2.8 and 2.9).
2.2 T2-Weighted Imaging 11
Fig. 2.8 Multiple myeloma, a b c

variegated pattern.
Comparison of T2-weighted
images with and without fat
suppression
58-year-old man with multiple
myeloma shows innumerable
small, focal, hypointense lesions.
Arrows point to representative
lesions. (b) On corresponding
T2-weighted FSE image, the
myeloma lesions are
hyperintense and imperceptible
from the high signal intensity
background marrow. (c) On
corresponding STIR image, the
myeloma lesions are
hyperintense and easily
recognized on a background of
suppressed marrow signal
(arrows)
Fig. 2.9 Bone metastases, lung

a b c
cancer. Comparison of
T2-weighted images with and
without fat suppression
61-year-old woman shows
multiple, hypointense focal
lesions. Arrows point to
representative lesions. (b) On
corresponding T2-weighted FSE
image, the metastatic foci are
imperceptible from the high
signal intensity background
marrow. (c) On corresponding
STIR image, metastatic lesions
are hyperintense and easily
recognized on a background of
suppressed marrow signal
(arrows)
a c
Fig. 2.10 T2-weighted images with fat suppression, focal fatty sponding axial T2-weighted FSE image without fat suppression, foci of
marrow. fatty marrow are still visible (arrows). (c) On corresponding axial
(a) Axial T1-weighted image of the pelvis of a 50-year-old woman T2-weighted fat-suppressed image, the signal intensity of the fatty mar-
shows foci of fatty marrow in the iliac bones (arrows). (b) On corre- row foci (arrows) is lower than that of background marrow
a b c
Fig. 2.11 T2-weighted images

with fat suppression, Modic II
degenerative endplate change.
hyperintense Modic II
degenerative endplate change at
L4, presenting as focal fat
(arrow). (b) On corresponding
sagittal T2-weighted image
without fat suppression, the
Modic II endplate change
remains hyperintense (arrow).
(c) On sagittal STIR image, the
signal intensity of the Modic II
change is slightly hypointense to
bone marrow (arrow)
2.3 Chemical-Shift Imaging 13
2.3 Chemical-Shift Imaging protons in water is 3.5 ppm (parts per million), and it cor-
responds to 224 Hz at a magnetic field strength of 1.5 T and
Many diagnostic dilemmas with MR imaging of the bone to 447 Hz for 3 T units [9]. Because water precesses faster,
marrow arise in the presence of red marrow; red marrow sig- there will be times after excitation when fat and water spins
nal intensity may be close to that of abnormal lesions on both will be in-phase (i.e., their transverse magnetization vec-
T1- and T2-weighted sequences. Chemical-shift (in-phase tors will point to the same direction) and times when they
and opposed-phase) imaging may help establish the presence will be 180° out-of-phase (i.e., their transverse magnetiza-
or absence of red marrow by exploiting the fact that water tion vectors will point to opposite directions). At 1.5 T, fat
protons precess slightly faster than fat protons [1, 8]. and water protons are in-phase and out-of-phase every
Inside the MR scanner, spins precess at frequencies 2.25 ms. In other words, they will be out-of-phase 2.25 ms
determined by the strength of the net magnetic field (Bnet). after excitation, in-phase at 4.5 ms, out-of-phase at 6.75 ms,
The main component of Bnet is the scanner’s static magnetic and so forth. On out-of-phase images, in voxels which con-
field (B0), but the electronic environment in tissues under tain both water and fat, there is a cancellation of signal
study may also contribute to Bnet by producing local mag- because their respective transverse magnetizations are in
netic fields. The difference in precessional frequency con- opposed phase. Conversely, on in-phase images, the trans-
ferred by the environment is known as the chemical shift verse magnetization vectors of water and fat protons add
[9]. The chemical shift most relevant to clinical imaging is together to produce a strong signal.
the one between fat protons and water protons [10]. The One of the major clinical applications of chemical shift is in
additional local field generated by the electron clouds of fat bone marrow imaging. Since normal red marrow is composed
molecules causes spins within adipose tissue to precess of almost equal amounts of water and fat (about 40 % each,
slightly slower than spins within water. This small differ- see Sect. 1.1), it will suffer significant signal loss on out-of-
ence in resonant frequency between protons in fat and phase images (Fig. 2.12). This is helpful in distinguishing
a b c
Fig. 2.12 Chemical-shift

imaging, normal red marrow.
29-year-old healthy woman
shows intermediate (higher than
intervertebral disc) signal
intensity of predominantly red
marrow. (b, c) Sagittal in-phase
(b) and out-of-phase (c) images
of the lumbosacral spine in the
same patient. There is
homogeneous signal loss on the
out-of-phase image in keeping
with normal marrow
between red marrow and infiltrated marrow since the latter

does not contain fat and will, therefore, not demonstrate signal Key Points
loss (Figs. 2.13 and 2.14). Caution is warranted in older • Chemical-shift imaging is useful in distinguishing
individuals, in whom, because of abundant, age-related fatty between red marrow and infiltrated marrow
marrow, there may be no obvious signal loss on visual inspec- • On opposed-phase images, red marrow exhibits sig-
tion of opposed-phase images (although signal loss is noted nal loss due to the coexistence of fat and water pro-
when regions of interest (ROIs) are placed and signal intensity tons in its voxels
measurements are obtained) (Fig. 2.15). Opposed-phase • Infiltrated marrow does not contain fat and there-
images must always be interpreted in conjunction with other fore does not exhibit signal loss on opposed-phase
sequences (T1, STIR), since a lesion that does not show signal images
loss may simply represent a focal area of fatty marrow
(Fig. 2.16).
Fig. 2.13 Chemical-shift

a b c
imaging, diffuse pattern of
abnormal marrow.
54-year-old woman with plasma
cell leukemia shows diffuse
abnormal bone marrow which is
hypointense to the intervertebral
discs. (b, c) Sagittal in-phase
same patient. There is no signal
loss of the marrow on the
out-of-phase image in keeping
with diffuse malignant infiltration
without residual fat
Fig. 2.14 Chemical-shift a b c

imaging, focal pattern of
abnormal marrow.
myeloma shows two hypointense
focal lesions at the lateral
elements of L3 and L1 (white
arrows). A Modic II degenerative
endplate change is seen at L4
(open arrow). (b, c) Sagittal
in-phase (b) and out-of-phase (c)
images of the lumbosacral spine
in the same patient. The two
focal lesions show no signal loss
on the out-of-phase image, in
keeping with malignant
infiltration (white arrows). Note
pronounced signal drop of the
remaining marrow. The
degenerative end plate is
hyperintense because of its fatty
composition (open arrow)
2.3 Chemical-Shift Imaging 15

imaging, normal fatty marrow.
high-signal-intensity of fatty
marrow. (b, c) Sagittal in-phase
same patient. There is no
significant signal loss on the
out-of-phase image. In this case,
this is due to normal,
predominantly fatty marrow and
not to a diffuse pattern of
abnormal marrow

imaging, malignant lesion
versus focal fat.
(a) Sagittal out-of-phase image
46-year-old woman with a focal
pattern of multiple myeloma.
There are two foci, at L1 and
L4, that do not demonstrate
signal loss (long arrows). Also
note areas of high signal intensity
around the basivertebral vessels
corresponding to normal fatty
marrow (short arrows).
(b, c) Sagittal T1-weighted
(b) and STIR (c) images of the
same patient: the L1 lesion is
hypointense on T1 and bright on
STIR (myeloma lesion), whereas
the L4 lesion is hyperintense
on T1 and isointense on STIR
(focal fat)
2.4 Contrast-Enhanced Imaging careful comparison with pre-contrast fat-suppressed images

is performed.
Contrast-enhanced images of the bone marrow may be With dynamic contrast-enhanced (DCE) MR imaging,
obtained with T1-weighted sequences with or without fat T1-weighted images of the bone marrow are repeatedly
suppression. Enhancement of marrow varies widely in obtained after the bolus intravenous injection of paramagnetic
healthy adults (3–59 %, mean 21 % ± 11 %) and decreases contrast, with a temporal resolution in the order of seconds or
progressively with advancing age [11] (Fig. 2.17). In most milliseconds [11, 14–16]. Peak enhancement of normal red
cases, these changes in contrast enhancement are almost marrow occurs within the first minute after the injection of
imperceptible on visual inspection (Fig. 2.18). In children contrast, gradually and smoothly. Time-intensity curves (TIC)
less than 10 years of age and, particularly, those less than 2, are generated from values obtained by ROI placement on the
spinal marrow may enhance intensely. Factors that contrib- dynamic images. Two patterns of TIC characterize the normal
ute to increased bone marrow enhancement in children bone marrow: in the first pattern, which is more frequently
include a more pronounced vascular supply and an extensive observed, the initial rise of contrast and reach of peak enhance-
extracellular space [12]. Apart from bone marrow, there are ment is followed by mild contrast washout, whereas, in the
other normal bone structures which enhance in children but second pattern, a plateau is reached with no obvious washout
not in adults: cartilaginous vascular channels in the epiphy- of contrast [17] (Fig. 2.21). Bone marrow perfusion decreases
ses, fibrovascular tissue in the posterior distal femoral with age and with increasing fat content reflecting the gradual
metaphysis (posterior metaphyseal stripe), and spongiosa in conversion of the vascular red marrow to the relatively avascu-
newly formed bone [13]. lar fatty marrow [16, 18, 19].
Contrast-enhanced MR images should always be inter-
preted in conjunction with non-enhanced T1-weighted
images; a presumably enhancing lesion may turn out to be Key Points
just an island of fatty marrow when pre-contrast images are • In children younger than 10 years of age, spinal
reviewed. Conversely, enhancing lesions may be missed if marrow may enhance intensely
pre-contrast images are not obtained since they may become • In adults, enhancement of normal bone marrow var-
isointense to adjacent, unaffected marrow (Fig. 2.19). ies (mean 21 % ± 11) and decreases with age
Lesion conspicuity is increased when fat suppression is • On DCE-MRI, normal marrow shows gradual and
applied to post-contrast images (Fig. 2.20). However, on fat- smooth enhancement with low maximal peak and
suppressed contrast-enhanced images, it may be difficult to mild or no apparent contrast washout
decide whether a lesion enhances mildly or not at all unless
a b
Fig. 2.17 Contrast

enhancement of normal red
marrow.
the cervical spine of a 34-year-
old healthy man before (a) and
after (b) contrast administration
show very mild enhancement
of the marrow. When ROI
measurements were obtained, a
mean increase of 10 % in marrow
signal intensity was observed
after contrast administration
2.4 Contrast-Enhanced Imaging 17
Fig. 2.18 Contrast enhancement of

a b
normal red marrow, mosaic pattern.
Sagittal T1-weighted images of the
lumbosacral spine of a 48-year-old
healthy man before (a) and after (b)
contrast administration show multiple,
hypointense foci without obvious
enhancement, representing rests of red
marrow
a b c
Fig. 2.19 Focal lesions, value

of pre-contrast images.
Sagittal T1-weighted images
55-year-old woman with multiple
bone metastases from breast
cancer, before (a) and after
(b) contrast administration.
A prominent T1 hypointense
metastatic lesion at L5 becomes
almost imperceptible on the
post-contrast image (arrow).
On the STIR image (c), the lesion
is easily seen as a hyperintense
focus (arrow)
a b
Fig. 2.20 Contrast enhancement, value of fat suppression. lesion at the posterior aspect of the femoral shaft which enhances and
Axial T1-weighted images of the right femur of a 49-year-old woman becomes almost indiscernible from surrounding marrow on the post-
with bone metastases from small cell lung cancer, before (a) and after contrast image (arrow). The lesion becomes more conspicuous when
(b) contrast administration. There is a small T1 hypointense metastatic fat suppression is applied to the contrast-enhanced image (c, arrow)
Pattern 1
Pattern 2
6
4
dDCE/dt
dDCE/dt
Fig. 2.21 Normal bone 125

marrow perfusion,
time-intensity curves. 100
Fitted time-intensity curves
DCE
DCE
(bottom) and corresponding first 75

derivative curves (top) of normal
bone marrow from two different 50
healthy individuals. Time-
intensity curves show smooth rise 25
of contrast and low peaks of
enhancement with mild 0
0 50 100 150 200
(pattern 1) or no obvious
(pattern 2) contrast washout TIME (t)
2.5 Diffusion-Weighted Imaging 19
2.5 Diffusion-Weighted Imaging barrier to diffusion and probably contribute to the restricted
diffusion of normal bone marrow, albeit less than fat [23].
Diffusion-weighted imaging (DWI) was initially established
as a valuable clinical tool for imaging of the brain. A series
of advances in MR technology—including the development Key Points
of high-gradient amplitudes and parallel imaging—allowed • ADCs of normal bone marrow are low (approxi-
the expansion of its use in many other body regions, includ- mate range, 0.2–0.5 × 10−3 mm2/s)
ing the bone marrow. DWI derives its contrast mainly from • ADCs of yellow marrow are lower than those of red
differences in the diffusivity of water molecules in the tissue, marrow
thus providing information on the microscopic structure and • ADCs of normal bone marrow decrease with age
organization of biological tissue. • The negative correlation between fat content and
The contrast provided by DWI can be assessed qualita- diffusivity is probably the main explanation for the
tively. Thus, in one of the first applications of DWI in the above observations
spine, a steady-state free precession sequence (SSFP) was
proposed to differentiate between benign and malignant ver-
tebral fractures based on visual inspection [20]. Quantitative It becomes evident from the above that any pathologic pro-
analysis of DWI can be achieved by calculating the apparent cess that replaces normal marrow and destroys bone trabecu-
diffusion coefficient (ADC) values from images with two or lae will appear as an area of increased diffusivity (i.e., higher
more different diffusion weightings. Measuring ADC values ADC values) relative to the restricted diffusion of normal
allows more specific tissue characterization and can provide marrow. In other words, unlike malignant tumors in soft tis-
valuable information for a wide range of marrow pathology. sues like the brain or the liver, which usually appear as areas
The most frequently used sequences for quantitative DWI of of—more or less—restricted diffusion compared to surround-
the bone marrow are echo planar imaging (EPI) and turbo ing normal tissue, marrow-replacing lesions are seen as areas
spin echo (TSE). EPI sequences are probably the most com- of increased diffusivity compared to the very low diffusion of
monly used for bone marrow diffusion studies. They have normal background marrow [23]. Benign osteoporotic verte-
very short acquisition times and are, therefore, less sensitive bral fractures are also seen as areas of increased diffusivity,
to motion compared to SE and TSE sequences. A very when imaged in the acute phase. In fact, mean ADCs of acute
important advantage of EPI is that it seems to provide more benign vertebral fractures are reported to be significantly
accurate ADC measurements than other sequences. Its main higher than those of their malignant counterparts. This is pre-
drawbacks are low signal-to-noise ratios and a propensity for sumably due to the presence of marrow edema in the acute
geometrical distortions, especially in the thoracic and cervi- phase of benign fractures, which exhibits increased water dif-
cal spine [21, 22]. fusivity. Conversely, tumor hypercellularity in malignant
ADC values of normal bone marrow have been reported fractures impedes diffusivity. It should be stressed that the
in many studies. When reviewing these studies, the follow- aforementioned significant differences in ADCs between
ing conclusions are consistent: (1) ADCs of normal bone benign and malignant fractures apply only when cases of
marrow are very low, significantly lower than those of soft acute benign fractures are considered (i.e., when abundant
tissues, such as the liver or muscle. In most studies, they have marrow edema is present). In the subacute phase of an osteo-
been reported in the range of 0.2–0.5 × 10−3 mm2/s. (2) ADC porotic fracture, ADCs progressively decrease until they
values of yellow marrow are lower than those of red marrow. reach the very low values of a chronic collapse [22].
(3) There is a decrease of normal bone marrow ADC values In most studies, mean ADC values of malignant marrow
with aging [21, 23–25] (Figs. 2.22 and 2.23). lesions, including malignant fractures, vary between 0.7 and
There are probably many factors influencing the diffusiv- 1.2 × 10−3 mm2/s. Reported ADC values of acute benign frac-
ity of water molecules in bone marrow, but as shown by the tures range from 1.0 to 2.0 × 10−3 mm2/s [23, 27]. There is evi-
above results, fat content probably plays a critical role. As a dence, albeit in small-sample studies, that in the diffuse pattern
hydrophobic material, fat may act as a physical barrier to the of malignant marrow involvement, mean ADCs are lower and
free diffusion of water molecules [23] (Fig. 2.24). Since fat may overlap with those of normal marrow. ADC measure-
is the major component of yellow marrow (≈80 %) and a ments in diffuse disease possibly depend on the relative pro-
significant component of red marrow (≈40 %), this could portion of normal and abnormal cells in the marrow. Caution
explain both the overall very low diffusion of bone marrow is warranted therefore when interpreting results in the gray
and the lower diffusion of yellow compared to red marrow. zone between 0.5 and 0.7 × 10−3 mm2/s. This is especially rel-
In a similar way, the steady increase of fatty marrow content evant in children, who tend to have higher normal ADCs due
throughout life may help explain the decrease of ADC val- to the presence of hypercellular marrow with low fat content.
ues with aging [25]. This negative correlation of ADC and ADC measurements are not useful in distinguishing between
fat has also been established in studies of osteoporosis [19, infectious and malignant marrow lesions, since infectious
26]. Apart from adipose cells, bone trabeculae also act as a spondylitis exhibits values within the malignant range [23].
It must be noted that discrepancies in ADC values of both

Key Points normal and abnormal bone marrow exist among various
• Range of main ADC values of normal and abnor- studies, due to differences in the pulse sequences and the dif-
mal bone marrow, from lowest to highest (overlaps fusion weightings (i.e., b-values) used. In order for bone
may exist between consecutive categories): Yellow marrow DWI to gain wider acceptance, a consensus on these
marrow → red marrow → diffuse malignant technical parameters should be reached. Standardization,
disorders → focal malignant lesions (including especially concerning b-values, is mandatory for results
malignant fractures) → acute benign fractures among studies to be comparable.
• Infectious spondylitis lesions have ADCs similar to
malignant lesions
b x
10–3
2
1.8
1.6
1.4
1.2
0.8
0.6
0.4
0.2
Fig. 2.22 DWI of the normal bone marrow, young adult. a healthy 24-year-old woman. Mean ADC value of the lumbar vertebrae
Diffusion-weighted images with b-values 0, 150, 250, 500, and was 0.481 × 10−3 mm2/s
750 s/mm2 (a) and ADC parameter map (b) of the lumbosacral spine of
2.5 Diffusion-Weighted Imaging 21
–3
x 10
2
b
1.8
1.6
1.4
1.2
0.8
0.6
0.4
0.2
Fig. 2.23 DWI of the normal bone marrow, elderly individual. healthy 70-year-old woman. Mean ADC value of the lumbar vertebrae
Diffusion-weighted images with b-values 0, 150, 250, 500, and 750 s/ was 0.257 × 10−3 mm2/s
mm2 (a) and ADC parameter map (b) of the lumbosacral spine of a
–3
x10
2
b
1.5
0.5
Fig. 2.24 DWI of the abnormal bone marrow. 54-year-old woman with plasma cell leukemia. Mean ADC value of the
Diffusion-weighted images with b-values 0, 150, 250, 500, and 750 s/ lumbar vertebrae was 1.033 × 10−3 mm2/s
mm2 (a) and ADC parameter map (b) of the lumbosacral spine of a
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MRI of the Normal Bone Marrow:
Anatomic Sites 3
Fatty marrow is easy to recognize on Τ1-weighted MR

images. Red marrow, however, has to be distinguished from Key Point
abnormal marrow, and this is one of the main challenges for • Spinal bone marrow is hypointense to intervertebral
bone marrow MR imaging. It is imperative to know where discs in the first few months of life
to expect red marrow in each age group or where red mar-
row may reappear under certain conditions. A low-signal-
intensity femoral diaphysis on T1-weighted images is likely The gradual increase in the signal intensity of spinal bone
normal at age 5, but it is definitely abnormal at age 17. marrow reflects the increase in fat content, a process that
Likewise, in a 60-year-old individual, a low-signal-inten- continues throughout life. The distribution of yellow marrow
sity spine on T1-weighted images is an abnormal finding, in the spine may not, however, be homogeneous; four differ-
whereas in a 25-year-old subject, it could be related to the ent patterns of yellow marrow deposition in the spine have
presence of normal red marrow. been described based on MR images [3]:
Red/yellow marrow distribution is best studied on Pattern 1: Fatty marrow of variable thickness is seen surrounding
T1-weighted images. Therefore, in this chapter, all MR the basivertebral vein and parallel to it (Fig. 3.3).
observations are based on T1-weighted images. Pattern 2: Fatty marrow appears along the vertebral endplates.
This pattern is more frequently seen in the lumbar and cer-
vical spine, which provide major support to the body and
3.1 Spine are more often subjected to mechanical stress resulting in
degenerative changes (Modic II endplate changes) than the
In the first month of life, the vertebral bodies are oval thoracic spine which is assisted by the rib cage (Fig. 3.4).
shaped and the cartilaginous plates large. On T1-weighted Pattern 3: Rounded or oval-shaped foci of fat are seen
images, the cartilaginous plates have very high signal throughout the spine. In this pattern, distinct fatty marrow
intensity. The intervertebral discs appear isointense to foci intermingle with red marrow giving the spine a
muscle (Fig. 3.1). The signal intensity of the vertebral mosaic-like appearance (Fig. 3.5). Foci of fat may become
bodies during the first months of life is lower than that of more confluent, alternating with smaller ill- or well-
disc or muscle, reflecting the hypercellular, fat-poor com- defined rests of red marrow (Fig. 3.6).
position of red marrow. From then on, gradually, the car- Pattern 4: Homogeneous fatty spine (Fig. 3.7). This pattern
tilaginous plates become less prominent and their signal is most helpful when searching for bone marrow lesions,
intensity drops; the vertebral bodies become more squared since it facilitates their detection as hypointense foci
and their signal intensity increases, from the endplates against a “bright” background.
towards the center. Early observations from the MRI lit- In some cases, there may be a combination of patterns,
erature stated that vertebral bodies are hypointense to most often 2 and 3. Pattern 4 is more frequently observed
intervertebral discs in the majority of children under age 1 in older individuals.
due to the presence of hypercellular marrow. In our experi-
ence and according to more recently published data, red to Key Point
yellow marrow conversion in the spine occurs earlier, and
• In the spine, four patterns of fatty marrow deposi-
by 6 months, in most children, the signal intensity of the
tion are described: basivertebral, endplate, mosaic,
vertebral bodies is at least isointense to the intervertebral
and homogeneous
discs [1, 2] (Fig. 3.2).

26 3 MRI of the Normal Bone Marrow: Anatomic Sites
Fig. 3.1 Normal spinal bone marrow, 2 months.

Sagittal T1-weighted image (left) of the spine of a
2-month-old boy shows biconvex shape of
vertebral bodies with large hyperintense
cartilaginous endplates (square). Matching
T2-weighted image (right) is shown for
comparison. Also shown is tethered cord with
spina bifida and lipocele (asterisk) (Courtesy of
Ioannis Nikas, M.D., Children’s Hospital “Aghia
Sophia,” Athens, Greece)
a b
Fig. 3.2 Normal spinal bone marrow,

8 and 26 months.
spine of an 8-month-old boy (a) and a
26-month-old girl (b) show that the
vertebral bodies are at least isointense to
the intervertebral discs. Note the more
square-shaped appearance of the
vertebrae in b (Courtesy of Ioannis
Nikas, M.D., Children’s Hospital
“Aghia Sophia,” Athens, Greece)
3.1 Spine 27
Fig. 3.3 Spinal red to yellow marrow a b

conversion, pattern 1 (basivertebral).
Sagittal T1-weighted image (a) and
detailed view (b) of the lumbosacral
spine of a 25-year-old woman show
hyperintense fatty marrow (arrows)
around basivertebral vessels
Fig. 3.4 Spinal red to yellow marrow conversion, pattern 2 (endplate).

Sagittal T1-weighted image of the lumbosacral spine of a 59-year-old woman shows
hyperintense fatty marrow along the inferior endplates of L2 and L3 (Modic II degenerative
endplate changes, white arrows). Also note Modic I degenerative change along the superior
endplate of S1 (black arrow)
Fig. 3.5 Spinal red to yellow a b

marrow conversion, pattern 3
(mosaic, distinct).
the lumbosacral spine of a
58-year-old woman (a) and a
48-year-old woman (b) show
multiple, well-defined,
hyperintense foci of yellow
marrow (arrows)
a b c
Fig. 3.6 Spinal red to yellow

marrow conversion, pattern 3
(mosaic, confluent).
the lumbosacral spine in three
different individuals show
confluent areas of fatty marrow
with residual, small, well-defined
(a) or ill-defined (b, c)
hypointense red marrow foci
3.3 Extremities 29
Fig. 3.8 Red to yellow marrow conversion, sacrum.

Axial T1-weighted image of the pelvis of a 40-year-old man shows
hyperintense fatty marrow in the sacral wings (white arrows) and
hypointense red marrow (black arrows) in the central part of the sacrum
Key Point
• Rests of red marrow in the pelvis are symmetric,

well-defined, and may contain a central focus of fat
3.3 Extremities
Fatty marrow in the long bones first appears in the epiphy-

seal ossification centers, within 6 months after the appear-
ance of the secondary center of ossification on radiographs;
Fig. 3.7 Spinal red to yellow marrow conversion, pattern 4 secondary ossification centers appear around 3–6 months of
(homogeneous).
age in girls and around 4–7 months of age in boys. Fatty
woman shows homogeneous high signal intensity of fatty marrow marrow in the ossification center of the epiphysis is seen as
a T1 bright spot surrounded by low-signal-intensity carti-
lage. Therefore, after the first few months of life, diffuse low
3.2 Pelvis signal intensity of the epiphysis is considered abnormal.
After the epiphyses, fatty conversion proceeds to the diaph-
The pelvis, as part of the central skeleton, is a site of persis- ysis, followed by the distal and, finally, the proximal
tent red marrow in the adult. Ricci et al. described islands of metaphysis.
fatty marrow first appearing at the superomedial aspect of the By age 5, and as early as year 1, yellow marrow is detected
acetabulum and later in the iliac bones and around the sacro- in the femoral diaphysis; by age 10, the femoral diaphysis is
iliac joints [3]. Marrow heterogeneity of the acetabulum and homogeneously fatty. In the distal metaphysis of the femur,
anterior iliac bone with increased deposition of fatty marrow fatty marrow is first seen in early childhood [7, 8]. The exact
is common in adolescents [4]. In the sacrum, presence of temporal evolution of red to yellow marrow conversion var-
fatty marrow is more pronounced in the periphery of the ies greatly, but, by age 15, the distal metaphysis should be
sacral wings, presumably because of the peripheral to central predominantly fatty (Fig. 3.9). Residual, flame-shaped red
pattern of red to yellow marrow conversion in the skeleton marrow foci with their base at, or adjacent to, the distal fem-
[5] (Fig. 3.8). oral and proximal tibial physis may be seen in children with
In older adults, red marrow foci may persist in the pelvis; an otherwise fatty metaphysis; these have margins parallel to
these red marrow islands are almost always symmetric and the long axis of the bone; they are symmetric and their signal
well-defined, and they may contain a central focus of fat [6]. intensity is always higher than that of muscle [2].
a d
Fig. 3.9 Red to yellow marrow conversion, femur. centers. (c) Fatty conversion of the proximal and distal epiphyseal ossi-
Coronal T1-weighted images of the proximal femora of a 3-month-old fication centers has occurred. (d) Fatty marrow is present in the distal
boy (a), a 7-month-old boy (b), and a 13-month-old boy (c). Coronal femoral and proximal tibial epiphyseal ossification centers (white
T1-weighted images of the knee of a 5-year-old boy (d). Coronal arrows) as well as in the femoral diaphysis (black arrows). Red marrow
T1-weighted images of the femora of a 14-year-old boy (e). (a) There is is still present in the distal femoral metaphysis. (e) Fatty marrow is
homogeneous, low signal intensity of the entirely cartilaginous proxi- present in the diaphyses and distal metaphyses (Images a–c, e Courtesy
mal epiphyses (arrows). (b) Lower signal intensity red marrow of Ioannis Nikas, M.D., Children’s Hospital “Aghia Sophia,” Athens,
has appeared in the recently formed proximal epiphyseal ossification Greece)
3.3 Extremities 31
a
Key Points
• Low T1 signal intensity in the epiphyses is abnor-

mal after the first few months of life
• Low T1 signal intensity is likely abnormal in the
femoral diaphysis after age 10 and in the femoral
distal metaphysis after age 15
In the proximal femur, three patterns of red to yellow

marrow conversion were described by Ricci et al. [3]. In pat-
tern 1, fatty marrow is present in the epiphysis and apophy-
ses only (pattern 1a) or it may also extend as triangular areas
to the intertrochanteric zone (pattern 1b) (Fig. 3.10). The
frequency of this pattern decreases with age. In middle-aged
adults, pattern 2 predominates with multiple foci of fatty
marrow appearing in the intertrochanteric zone in addition to
changes of pattern 1. Finally, pattern 3 consists of homoge- b
neous fatty marrow throughout the proximal femoral
metaphysis, and it is more common in the elderly.
In the humerus, fatty conversion begins within the first
year of life, and by 6 years of age, diaphyseal fatty transfor-
mation is almost complete. Between 11 and 15 years of age,
the process of red to yellow marrow conversion of the distal
metaphysis is also completed in most individuals [9]. In the
proximal humeral metaphysis of the adult, a zone of red
marrow may persist; occasionally, red marrow may also be
seen in the subarticular surface of the humeral head
(Fig. 3.11).
Although in adults red marrow may or may be not be seen
in the proximal femoral and humeral metaphyses, in chil-
dren, absence of red marrow in these areas is most likely
abnormal and should raise suspicion of aplastic anemia or
other marrow depletion disorders [7].
Key Points
Fig. 3.10 Red to yellow marrow conversion, proximal femur.
• In adults, persistent low T1 signal intensity in the (a) Coronal T1-weighted image of the pelvis of a 16-year-old boy
proximal femoral and humeral metaphyses may be shows fatty marrow in the femoral epiphyses and apophyses, with
a normal finding, representing red marrow extensive red marrow (arrows) in the intertrochanteric zones (conver-
• In children, absence of low T1 signal intensity in sion pattern 1a). (b) Coronal T1-weighted image of the pelvis of a
49-year-old man shows fatty marrow in the femoral epiphyses and
the proximal femoral and humeral metaphyses is apophyses, with triangular extensions (asterisks) medial and lateral to a
likely abnormal narrow, hypointense intertrochanteric red marrow zone (conversion pat-
tern 1b)
Red marrow persists in the scapulae, ribs, sternum, and clav-

icles of the adult, to various degrees [9].
3.5 Skull
During the first 2 years of life, the process of fatty conversion

begins in the skull, starting with the facial bones (maxilla,
mandible), proceeding to the base of the skull and finally the
calvarium [1]. By age 15, the process of red to yellow mar-
row conversion is complete in most individuals. Caution is
warranted when reviewing sagittal images of the skull. On
midline sections, the parietal bones often appear heteroge-
neous due to the sagittal suture; this appearance should not
be mistaken for residual red marrow rests or an abnormal
process [10] (Fig. 3.12).
In the clivus, fatty transformation is usually recognized
by age 3–6. The process of conversion is completed by age
15, although, in adolescent females, the clivus may still have
an heterogeneous appearance [1, 11]. A low-signal-intensity
clivus in an adult of either sex is most likely abnormal.
Key Points
Fig. 3.11 Red to yellow marrow conversion, proximal humerus.
Coronal T1-weighted image of the shoulder of a 28-year-old healthy • In the skull, fatty marrow first appears in the facial
individual shows residual red marrow in the metaphysis (asterisk) and
subarticular surface (arrows) of the humerus
bones, followed by the skull base and finally the
calvarium
• Hematopoietic marrow foci may persist in the cal-
3.4 Rib Cage varium of healthy adults, more frequently in the
parietal bones
Red to yellow marrow conversion begins in the scapulae, • A low-signal-intensity clivus in an adult of either
during the first year of life [1]. In the sternum, ribs, and clav- sex is most likely abnormal
icles, MRI findings of fatty conversion are seen at ages 6–10.
3.5 Skull 33
a b
Fig. 3.12 Red to yellow marrow conversion, skull.

Midsagittal (a, b) and parasagittal (c) T1-weighted images of the skull of a 42-year-old man. Heterogeneity of parietal bones, only shown on the midline
images (arrows in a, b), is caused by the sagittal suture of the skull and should not be confused with red marrow rests or a marrow infiltrating disorder
References 7. Moore SG, Dawson KL (1990) Red and yellow marrow in the femur:
age-related changes in appearance at MR imaging. Radiology
175:219–223
1. Foster K, Chapman S, Johnson K (2004) MRI of the marrow in the
8. Waitches G, Zawin JK, Poznanski AK (1994) Sequence and rate
paediatric skeleton. Clin Radiol 58:651–673
of bone marrow conversion in the femora of children: are accepted
2. Laor T, Jaramillo D (2009) MR imaging insights into skeletal matu-
standards accurate? Am J Roentgenol 162:1399–1406
ration: what is normal? Radiology 250:28–38
9. Zawin JK, Jaramillo D (1993) Conversion of bone marrow in the
3. Ricci C, Cova M, Kang YS et al (1990) Normal age-related patterns
humerus, sternum, and clavicle: changes with age on MR images.
of cellular and fatty bone marrow distribution in the axial skeleton:
MR imaging study. Radiology 177:83–88
10. Schick RM (1991) Normal age-related changes in bone marrow in
4. Dawson KL, Moore SG, Rowland JM (1992) Age-related changes
the axial skeleton at MR imaging. Radiology 179:877
in the pelvis: MR and anatomic findings. Radiology 183:47–51
11. Okada Y, Aoki S, Barkovich AJ et al (1989) Cranial bone marrow
5. Duda SH, Laniado M, Schick F et al (1995) Normal bone mar-
in children: assessment of normal development with MR imaging.
row in the sacrum of young adults: differences between sexes seen
on chemical-shift MR imaging. Am J Roentgenol 164:935–940
6. Levine CD, Schweitzer ME, Ehrlich SM (1994) Pelvic marrow in
adults. Skeletal Radiol 23:343–347
The Abnormal Bone Marrow: MRI
Patterns 4
The signal intensity of bone marrow on MR images depends its distribution on T1-weighted MR images [2, 3]. We use the
on the balance among fat, water, and bony trabeculae. term regional pattern to describe a fourth MR pattern, which
Normal patterns of red to yellow marrow conversion in rela- is assigned to a diffuse signal alteration that involves only
tion to age and gender and variations in these patterns part but not the entire volume of the imaged marrow.
depending on daily habits (e.g., smoking, long-distance run- An MRI pattern is further characterized according to the
ning), chronic illnesses (e.g., severe anemia), and body habi- signal intensity of the abnormal bone marrow process on
tus (obesity), via the process of reconversion, have already T1-weighted images as hypointense, if its signal intensity is
been discussed in Chap. 1. In this chapter, the MRI patterns lower than, or equal to, that of muscle or nondegenerated
of the abnormal bone marrow will be analyzed. When deal- intervertebral disc, or hyperintense, if its signal intensity
ing with MR images of bone marrow disorders, pattern rec- approximates that of fat. Bone-producing lesions have a sig-
ognition is an essential step of the diagnostic process. nal intensity equal to that of cortical bone due to the absence
Analysis of the MRI pattern of involvement permits a clas- of moving protons; these very hypointense lesions as well as
sification of marrow disorders which is based on imaging intraosseous gas collections are characterized as signal void
findings rather than on clinical or laboratory information; it [3]. The terms hypointense, hyperintense, isointense, low sig-
narrows down the differential diagnosis and aids distinction nal intensity, and high signal intensity as used in this chapter
of a “leave alone” finding from one that needs follow-up or refer to T1-weighted images, unless otherwise specified.
further work-up. Pattern assignment may also have impor- MRI patterns are usually defined on images of the central
tant clinical implications regarding prognosis in certain con- skeleton and mostly the spine, since both inflammatory and
ditions, such as multiple myeloma and certain types of neoplastic disorders preferentially involve the richly vascu-
leukemia, as will be discussed in the relevant chapters [1]. lar red marrow rather than the relatively avascular fatty mar-
T1-weighted MR images are most suited for pattern rec- row which is abundant in the peripheral skeleton. When
ognition in the diseased marrow, because the high signal findings in the central skeleton are ambiguous, it may be of
intensity of fatty marrow provides a natural background for value to extend imaging to the peripheral skeleton; a low-
lesion detection, as most bone marrow abnormalities are rich signal-intensity spine in a 40-year-old individual may be a
in water but not in fat. The majority of diseases that affect the normal finding, but a low-signal-intensity femoral diaphysis
bone marrow occur in adults, in whom fatty marrow is in the same person is certainly abnormal.
already present in the extremities and increases with age in
the central skeleton.
As an abnormal process grows in the medullary cavity, it 4.1 Focal Pattern
may replace or infiltrate normal bone marrow (marrow-
replacing disorder, infiltrating disorder), and it may do so The focal bone marrow pattern consists of one or more well-
either contiguously, without intervening areas of spared mar- defined foci of abnormal signal intensity on a background of
row, affecting all sites that contain hematopoietic marrow normal marrow; these foci range in size from a few millime-
(diffuse involvement) or focally, with abnormal aggregates ters to a few centimeters. Focal lesions may be hyperintense
amidst normal marrow (focal lesions). The bone marrow to red marrow with a similar signal intensity to that of
may even have a variegated appearance with innumerable extraosseous fat (hyperintense focal pattern), hypointense or
small focal lesions on a background of normal-appearing isointense to muscle or nondegenerated disc (hypointense
marrow. Accordingly, a diffuse, focal, or variegated pattern focal pattern), or isointense to cortical bone (signal-void
is assigned to an abnormal bone marrow process, based on focal pattern) [2, 3].

36 4 The Abnormal Bone Marrow: MRI Patterns
4.1.1 Hyperintense Focal Pattern conversion (e.g., mosaic or basivertebral pattern of red
to yellow marrow conversion in the spine) (Figs. 4.1 and
Hyperintense focal patterns almost always represent benign 4.2). Hyperintense foci related to fatty marrow conversion
processes. They are often related to foci of fatty mar- may also appear along the vertebral end plates as part of
row resulting from heterogeneous red to yellow marrow the degenerative process of an intervertebral disc (Modic
a b
c d
Fig. 4.1 Hyperintense focal pattern, normal variant-mosaic.

Hyperintense focal pattern due to multiple fatty deposits (arrows) in three different patients with a mosaic pattern of red to yellow marrow conver-
sion. (a) Axial T1-weighted image of the pelvis of a 52-year-old woman with pelvic inflammatory disease. (b, c) Axial (b) and sagittal (c) images
of the lumbosacral spine of a 58-year-old woman. (d) Sagittal T1-weighted image of the lumbosacral spine of a 54-year-old woman
4.1 Focal Pattern 37
type II degenerative endplate changes) [4] (Fig. 4.3). bone marrow hyperintensity; a geographic, low-signal-
Hemangiomas are another frequent and benign cause of a intensity rim surrounding the hyperintense focus is pathog-
hyperintense focal pattern (Fig. 4.4). High signal intensity nomonic of such a lesion (Fig. 4.6).
on fat-suppressed T2-weighted images, when present, as Malignant hyperintense focal bone marrow patterns
well as identification of intralesional hypertrophied bony may be caused by melanoma metastases or hemorrhagic
trabeculae distinguish these lesions from islands of fatty myelomatous lesions; however, both are extremely rare [5,
marrow. Another, less common, benign bone tumor which 6] (Fig. 4.7).
manifests as a hyperintense focal lesion is an intraosseous
lipoma; this tumor has a characteristic appearance on con-
Key Points
ventional radiographs and CT (well-defined sclerotic bor-
der, absence of trabeculae within bony lucency, dystrophic Hyperintense focal pattern: common causes
calcifications at sites of fat necrosis) (Fig. 4.5). • Focal fatty marrow
Focal lesions of neoplastic or infectious origin may • Hemangiomas
become partially or completely hyperintense when, during • Modic II degenerative endplate changes
the healing process, fatty marrow reappears from adjacent, • Bone infarcts (osteonecrotic lesions)
unaffected bone marrow. A bone infarct (or osteonecrotic • Healing lesions (neoplastic or infectious)
lesion depending on location) is yet another cause of focal
a b
Fig. 4.2 Hyperintense focal

pattern, normal variant-
basivertebral.
Hyperintense focal pattern due to
fatty deposits around the
basivertebral vessels (arrows).
Sagittal T1-weighted image of the
lumbosacral spine (a) and axial
T1-weighted image at the level of
L5 (b) of a 38-year-old man
Fig. 4.3 Hyperintense focal pattern, a b

Modic II degenerative endplate
changes.
Hyperintense focal pattern due to Modic
II changes along the vertebral endplates.
(a) Sagittal T1-weighted image of the
woman shows hyperintense fatty
endplate changes at L3–L4 (long
arrows). Hypointense, type I
degenerative endplate changes are also
present at L2–L3 (short arrows).
(b) Sagittal T1-weighted image of the
woman shows Modic II endplate
changes at L4–L5 (long arrows). Also
shown is coexisting mosaic pattern of red
to yellow marrow conversion with
multiple fatty foci throughout the spine
(short arrows)
Fig. 4.4 Hyperintense focal pattern, hemangioma.

Sagittal T1-weighted image of a 55-year-old man with prostate cancer shows typical
hyperintense hemangioma of L1 (long arrow) with extensive fatty stroma. Also shown is
bone metastasis at L2 (short arrow)
a b
Fig. 4.5 Hyperintense focal pattern, intraosseous lipoma. humeral metaphysis. On corresponding axial T1-weighted image with
Axial (a) and coronal (b) T1-weighted images of the shoulder of a fat suppression (c), the signal of fat is suppressed, and the lesion
31-year-old man show a hyperintense focal lesion (arrows) in the (arrows) becomes almost isointense to surrounding bone marrow
a b
Fig. 4.6 Hyperintense focal pattern, bone infarcts. subarticular surface of both femoral heads (arrows). (b, c) Axial
(a) Axial T1-weighted image of the pelvis of a 57-year-old woman with T1-weighted images of the pelvis of a 21-year-old man with multiple bone
avascular necrosis of the femoral heads after radiotherapy for cervical can- infarcts following steroid therapy for Hodgkin lymphoma show hyperin-
cer shows hyperintense foci surrounded by hypointense rim in the tense lesions surrounded by hypointense rim in both iliac bones (arrows)
Fig. 4.7 Hyperintense focal

pattern, hemorrhagic a b c
myelomatous lesions.
(a, b) Sagittal T1-weighted
images of the thoracic spine of a
30-year-old man with newly
diagnosed multiple myeloma,
before (a) and after (b) contrast
administration, show
hyperintense focal lesions at
several levels presumably due to
hemorrhagic plasma cell
infiltrates. Arrows point to
representative lesions. The
remaining marrow is diffusely
hypointense due to anemia-
related reconversion.
(c) Resolution of the
hyperintense signal on a
posttreatment T1-weighted
image 1 year later (arrows)
confirms hemorrhagic nature of
the lesions
4.1.2 Hypointense Focal Pattern
In an adult, hypointense marrow foci are a common finding,

and they are often due to rests of hematopoietic marrow. The
signal intensity of such red marrow foci is higher than that
of adjacent muscles or nondegenerated intervertebral discs,
although, occasionally, it may be equal to them, particularly
in young adults (Fig. 4.8). Compared to malignant bone mar-
row lesions, foci of red marrow have less distinct borders.
A focus of fat in the center of a hypointense focal bone mar-
row lesion (bull’s eye sign) is characteristic of a red marrow
rest as it reflects the centrifugal pattern of red to yellow mar-
row conversion, at cross section [7].
An atypical hemangioma is a diagnosis applied to an
incidental, solitary, hypointense focal marrow lesion, when
all other diagnoses have been excluded and the patient has
no known history of malignancy (Fig. 4.9). Other benign
primary bone tumors, such as osteoblastoma, aneurysmal
bone cyst, and enchondroma among others, may present as
hypointense foci. These tumors, as well as most primary
malignant bone tumors, usually have characteristic findings
on conventional radiographs, CT, and MRI and rarely pres-
ent as a diagnostic dilemma.
Bone metastases and hematologic malignancies are the
most common malignant causes of focal hypointense pat-
terns; such lesions are usually well-defined, with a sharp
transition zone to adjacent uninvolved marrow, and they are
hypointense to disc and muscle. They occur more often in
older individuals, in whom fatty marrow is abundant in the Fig. 4.8 Hypointense focal pattern, red marrow.
central skeleton, and thus are easily depicted as “holes in the Sagittal T1-weighted image of the lumbosacral spine of a 48-year-old
marrow” (Figs. 4.10 and 4.11). man shows multiple, hypointense red marrow foci on a background of
fatty marrow (mosaic pattern of bone marrow conversion)
Key Points
Hypointense focal pattern: common causes
• Red marrow rests
• Atypical hemangiomas
• Metastases
• Hematologic malignancies
Fig. 4.9 Hypointense focal pattern,

atypical hemangioma.
a b
thoracic spine of a 25-year-old healthy
man shows a hypointense lesion (arrow)
at the posterior aspect of the body of T7.
(b) On corresponding sagittal STIR
image, the lesion (arrow) is hyperintense
to marrow
a b

bone metastases.
lumbosacral spine of a 53-year-old man
with colon cancer (a) and a 62-year-old
woman with lung cancer (b) show
multiple hypointense focal lesions
throughout the spine against a
background of apparently normal fatty
marrow, consistent with bone metastases

a b
multiple myeloma.
lumbosacral spine of a 57-year-old woman
(a) and a 68-year-old man (b) with multiple
myeloma show hypointense spinal focal
lesions (arrows) against a background of
apparently normal fatty marrow, consistent
with plasma cell deposits
4.1.3 Signal-Void Focal Pattern association with POEMS syndrome (Fig. 4.14). A high-
intensity halo on T2-weighted images (T2 halo sign) has
The signal intensity of signal-void focal lesions is lower than been described in patients with prostate cancer as a helpful
that of hypointense focal bone marrow lesions, similar to that sign in differentiating osteoblastic metastases from benign
of cortical bone, and it may be produced by osteosclerotic bone islands [7] (Fig. 4.15).
processes or air. Signal-void focal lesions have well-defined
borders, and they remain of low signal intensity on all MR
sequences due to the absence of mobile protons.
Key Points
Enostosis (bone island) is a common cause for a benign
signal-void focal lesion (Fig. 4.12). Rare causes of signal- Signal-void focal pattern: causes
void focal lesions include mastocytosis and osteopoikilosis. • Enostosis (bone island)
Intravertebral gas is specific for osteonecrosis complicating a • Osteoblastic metastases
benign vertebral compression fracture and manifests as a • Osteoblastic lymphomatous lesions
signal-void lesion [8] (Fig. 4.13). • Sclerotic myelomatous lesions (rare)
Malignant focal lesions with signal void include osteo- • Vertebral osteonecrosis with intravertebral gas
blastic metastases, osteoblastic lymphomatous focal lesions, • Osteopoikilosis, mastocytosis
and rare sclerotic myelomatous lesions more often seen in
Fig. 4.12 Signal-void focal a

pattern, enostosis.
b
lumbosacral spine of a 7-year-old girl shows a
single, oval-shaped, signal-void focal lesion at
the L4 vertebral body (arrow) in keeping with
osteosclerosis due to enostosis (image
courtesy of Ioannis Nikas, M.D., Children’s
Hospital “Aghia Sophia,” Athens, Greece).
(b, c) Axial T1-weighted MR image of the
right hip (b) of a 59-year-old man shows an
enostosis in the femoral head (arrow) with
characteristic spiculated margin. Also shown
is corresponding CT image (c)
Fig. 4.13 Signal-void focal pattern, vertebral osteonecrosis.

Sagittal T1-weighted image of the lumbosacral and lower thoracic spine of a 67-year-old
woman with osteoporotic vertebral compression fractures shows two signal-void foci (arrows)
in the collapsed L1 and T9 vertebral bodies, in keeping with intravertebral air due to
osteonecrosis
Fig. 4.14 Signal-void focal

a c
pattern, osteoblastic
metastases.
(a, b) Coronal (a) and axial (b)
T1-weighted images of the
pelvis of a 58-year-old man
with prostate cancer show a
signal-void focal pattern due to
osteoblastic metastases
(arrows). (c, d) T1-weighted
sagittal (c) and axial (d) images
of the thoracic spine of a
61-year-old woman with breast
cancer show a signal-void
metastatic lesion involving the
body and right lateral pedicle of
T1 (arrows)
d
a b c d
Fig. 4.15 Osteoblastic metastases, T2 halo sign. lesions of the T10, T11, and L1 vertebral bodies (solid arrows). On the
Sagittal T1-weighted (a, b) and corresponding STIR (c, d) images of STIR images, a hyperintense halo (T2 halo sign) is seen at the periphery
the thoracic spine of a 76-year-old man with prostate cancer and bone of the lesions (solid arrows). A recent compression fracture of T8 is
metastases. On the T1-weighted images, there are signal-void focal also noted (open arrow)
4.2 Variegated Pattern
A variegated (microfocal, “salt and pepper”) pattern con-

sists of innumerable small, alternating, hyperintense, and
hypointense foci. This pattern may be seen in cases of
both normal and abnormal marrow. In the former, the var-
iegated appearance (also called “mosaic”) is caused by
alternating high- and low-signal-intensity foci that repre-
sent normal rests of fatty and red marrow, respectively
(Fig. 4.16). A variegated pattern may also be seen with
osteolytic metastatic disease and multiple myeloma,
where the innumerable hypointense foci represent malig-
nant deposits (Fig. 4.17). Osseous osteoblastic metastases
and osteopoikilosis may present with innumerable foci,
isointense to cortical bone (signal void) in a variegated
pattern.
Key Points
Variegated pattern: causes
• Heterogeneous marrow conversion and recon-
version
• Osteolytic metastases, multiple myeloma
• Osteoblastic metastases, osteopoikilosis (signal
void)
Fig. 4.16 Variegated pattern, normal marrow.
healthy woman shows multiple alternating foci of low (red marrow) and
high (fatty marrow) signal intensity
4.3 Diffuse Pattern 47
Fig. 4.18 Hyperintense diffuse pattern, normal spine.

Fig. 4.17 Variegated pattern, multiple myeloma. Sagittal T1-weighted image of the lumbosacral spine of a 70-year-old
Sagittal T1-weighted image of the lumbar spine of a 70-year-old man woman shows diffuse high signal intensity of normal fatty marrow
with multiple myeloma shows multiple alternating foci of low (myeloma
deposits) and high (fatty marrow) signal intensity
4.3 Diffuse Pattern Key Points
A diffuse pattern is diagnosed when the signal intensity of the Hyperintense diffuse pattern: causes
entire bone marrow is altered without intervening areas of • Normal pattern in older individuals (increased
normal signal intensity. In a hyperintense diffuse pattern, the marrow fat content)
abnormal marrow is hyperintense to red marrow and isoin- • Marrow depletion (aplastic anemia)
tense to extraosseous fat. In a hypointense diffuse pattern,
abnormal marrow is hypointense or, occasionally, isointense
to muscle and nondegenerated intervertebral discs. 4.3.2 Hypointense Diffuse Pattern
In adults, this pattern is diagnosed when bone marrow signal

4.3.1 Hyperintense Diffuse Pattern intensity is diffusely low, lower than or equal to the signal of
muscle or nondegenerated discs (Fig. 4.19). In children and
A diffuse hyperintense marrow pattern may be a normal find- young adults, a diffusely low-signal-intensity spine may be
ing in older adults, reflecting very high marrow fat content dis- related to the presence of normal hypercellular red marrow.
tributed in a homogeneous fashion (Fig. 4.18). An abnormal In these individuals (but not in infants) signal intensity of
hyperintense diffuse bone marrow pattern is seen with marrow normal red marrow may be equal to, but never lower than,
depletion, typically in patients with aplastic anemia. The pan- that of muscle or discs. It must be noted that an endplate with
cytopenia which characterizes this hematologic disorder leads a Modic type II degenerative change or a hemangioma may
to marked marrow hypocellularity and increased fat content, be spared by a diffuse marrow-replacing process (Figs. 4.20
resulting in diffuse high signal on T1-weighted images. and 4.21).
Fig. 4.19 Hypointense diffuse pattern, multiple myeloma.

man with multiple myeloma shows diffuse low signal intensity of Fig. 4.20 Hypointense diffuse pattern, spared Modic II changes.
abnormal marrow, equal to that of the intervertebral discs Sagittal T1-weighted image of the lumbosacral spine of a 51-year-old
man with multiple myeloma shows diffuse low signal intensity of
abnormal marrow with sparing of Modic II endplate changes at several
levels (arrows)
Reconversion of yellow to red marrow due to daily habits
(e.g., intense physical exercise), underlying pathologic con- fuse bone marrow patterns (Fig. 4.26). Gaucher’s disease is a
ditions (e.g., severe anemia), or treatment with hematopoi- metabolic disorder in which bone marrow is replaced by
etic growth factors may also be responsible for a hypointense abnormal histiocytes containing glucocerebrosides, and it
diffuse bone marrow pattern (Figs. 4.22 and 4.23). may manifest with diffuse T1 hypointensity. Metastatic dis-
Differential diagnosis of diffusely infiltrated marrow from ease, particularly from small round cell primary tumors, may
red marrow reconversion can at times be challenging. In rarely manifest with a diffuse hypointense bone marrow pat-
order to reach a correct diagnosis, careful interpretation of tern (Fig. 4.27).
the other pulse sequences and review of the patient’s history
are required (Fig. 4.24).
Key Points
Lymphoproliferative disorders (leukemia, lymphoma,
multiple myeloma) may manifest with a diffuse hypointense Hypointense diffuse pattern: causes
pattern. Hypointense diffuse bone marrow patterns may be • Normal pattern in young individuals (increased red
homogeneous as in patients with leukemia or heterogeneous marrow content)
with superimposed focal areas of even lower signal intensity, • Red marrow reconversion
a pattern commonly seen in patients with lymphoma; focal • Lymphoproliferative disorders
low-signal-intensity areas, against a background of diffusely • Myeloproliferative disorders
hypointense marrow, may be related to denser aggregates of • Myelodysplastic syndromes
malignant cells (Fig. 4.25). Myeloproliferative diseases • Gaucher’s disease
(polycythemia vera, mastocytosis, myelofibrosis) and myelo- • Metastases (rarely)
dysplastic syndromes may also present with hypointense dif-
Fig. 4.21 Hypointense diffuse pattern, a b

spared hemangiomas.
Sagittal T1-weighted (a) image of the
lumbosacral spine of a 70-year-old with multiple
myeloma shows diffuse low signal intensity of
abnormal marrow sparing sites of vertebral
hemangiomas (arrows). Corresponding STIR
image (b) shows hyperintense signal of
hemangiomas
Fig. 4.22 Hypointense diffuse pattern, red marrow reconversion.

Sagittal T1-weighted image of the lumbosacral spine of a 45-year-old healthy woman who
is a martial arts expert shows diffuse low-signal-intensity red marrow (isointense to
intervertebral discs)
Fig. 4.23 Hypointense diffuse pattern, red marrow reconversion.

Sagittal T1-weighted image of the lumbosacral spine of a 62-year-old woman with lung cancer on
chemotherapy and concomitant administration of hematopoietic growth factors (G-CSF and erythropoi-
etin) shows diffuse hypointense marrow pattern due to red marrow hyperplasia
a b c
Fig. 4.24 Hypointense diffuse pattern, red marrow reconversion; imaging shows marked drop of marrow signal intensity on the out-of-phase
combination of findings on different pulse sequences. image (c) compared to the in-phase image (d). On the ADC map (e) derived
Sagittal T1-weighted (a) image of the lumbosacral spine of a 72-year-old from diffusion-weighted images, the mean ADC value of L1 to L5 was
woman with severe anemia shows hypointense bone marrow, almost isoin- 0.448 × 10−3 mm2/s. On the contrast-enhanced T1-weighted image (f), there
tense to the intervertebral discs and unexpected for patient’s age. On the is almost imperceptible (approximately 10 %) signal increase. All of the
STIR image (b), bone marrow becomes mildly hyperintense. Chemical-shift above findings are consistent with the presence of red marrow
Fig. 4.24 (continued)

d e f
Fig. 4.25 Heterogeneous hypointense diffuse pattern, lymphoma. Fig. 4.26 Hypointense diffuse pattern, polycythemia vera.
Sagittal T1-weighted image of a 42-year-old woman with stage IV lym- Sagittal T1-weighted image of the lumbosacral spine of a 57-year-old
phoma shows diffuse hypointense abnormal marrow with several super- woman with polycythemia vera shows diffuse, homogeneous, hypoin-
imposed focal lesions of even lower signal intensity (arrows) tense bone marrow
Fig. 4.27 Hypointense diffuse pattern, metastases.

Sagittal T1-weighted image of the thoracic spine of a 32-year-old man
with gastric cancer and bone marrow metastases shows diffuse homo- Fig. 4.28 Diffuse signal-void pattern, hemosiderosis.
geneous hypointense marrow pattern Sagittal T1-weighted image of the lumbosacral spine of a 51-year-old
man with chronic lymphocytic leukemia and a history of multiple blood
transfusions shows diffuse signal-void bone marrow pattern. Note
4.3.3 Signal-Void Diffuse Pattern extramedullary involvement with enlarged retroperitoneal lymph nodes
Hemosiderosis (secondary hemochromatosis) occurs when

hemosiderin is deposited in the reticuloendothelial cells, in 4.4.1 Hyperintense Regional Pattern
most cases as a result of multiple transfusions, therefore
affecting the spleen, liver, and bone marrow. The ferric iron A hyperintense regional bone marrow pattern is seen after
of hemosiderin is responsible for the drop in bone marrow radiation therapy, which causes marrow depletion; it is con-
signal intensity because of its T1 and T2 shortening effects fined to the radiation field with a sharp zone of transition to
[9] (Fig. 4.28). the non-irradiated bone marrow (Figs. 4.29 and 4.30).
Key Point Key Point
Signal-void diffuse pattern: cause Hyperintense regional pattern: cause

• Hemosiderosis • Radiation therapy
4.4 Regional Pattern 4.4.2 Hypointense Regional Pattern
In a regional bone marrow pattern, a specific, small or large, A hypointense regional bone marrow pattern is frequently
area of the marrow is affected in a more or less diffuse man- seen with infiltrating bone marrow processes and is usually
ner due to a regional cause, such as irradiation, inflammatory characterized by a wide zone of transition. The abnormal
and infectious processes and trauma. bone marrow is heterogeneous and mildly to moderately
4.4 Regional Pattern 53
Fig. 4.30 Hyperintense regional pattern, bone marrow irradiation.

Sagittal T1-weighted image of the cervical spine of a 57-year-old man
with multiple myeloma who was treated with radiation of the upper
cervical spine 10 years previously shows hyperintense regional pattern
(between white arrows) involving the C1, C2, and C3 vertebrae. Note
incidental hemangioma of T2 (black arrow)
Fig. 4.29 Hyperintense regional pattern, bone marrow irradiation.

Sagittal T1-weighted image of the lumbosacral spine of a 51-year-old tumors may be responsible for a regional hypointense pat-
woman with a history of cervical cancer treated with irradiation of the tern (Fig. 4.32). Modic type I degenerative endplate
pelvis shows hyperintense regional pattern extending from the sacrum
to the upper third of L4. Note sharp zone of transition (arrow) from
changes also present with an edema-like regional hypoin-
irradiated marrow to non-irradiated red marrow tense pattern; these lesions are usually easily recognized
by their unique appearance and specific location
(Fig. 4.33). Osteomyelitis and infectious or inflammatory
hypointense to fat but hyperintense to muscle and nondegen- processes of the joints are often associated with reactive
erated intervertebral discs. Areas of low signal intensity edema of adjacent bones manifesting with a regional
(infiltrating process) may alternate with areas of high signal hypointense pattern. In spondylodiscitis, characteristic
intensity (fatty marrow). In fact, changes on T1-weighted changes of the involved intervertebral disc point to the
images may be so subtle that this pattern is best recognized correct diagnosis (Fig. 4.34).
on T2-weighted images with fat suppression. The heteroge-
neous appearance of the regional hypointense pattern is
explained by the fact that—unlike a marrow-replacing
Key Points
process—the infiltrating process does not completely replace
normal bone marrow, but rather intermingles and coexists Hypointense regional pattern: causes
with it. • Bone marrow edema syndrome
A regional hypointense pattern is characteristically • Trauma
observed in bone marrow edema syndrome (transient • Edema associated with bone tumors
osteoporosis, regional migratory osteoporosis, complex • Modic type I degenerative endplate changes
regional pain syndrome) and osseous trauma (bone bruise, • Osteomyelitis (including spondylodiscitis)
fracture) (Fig. 4.31). Edema associated with benign (e.g., • Inflammatory or infectious joint disease
osteoid osteoma) or malignant (e.g., osteosarcoma) bone
a b
Fig. 4.31 Hypointense regional pattern, sacral insufficiency fracture. cervical cancer who was treated with radiation therapy 1 year earlier
Axial T1-weighted image (a) and corresponding T2-weighted image show regional hypointense bone marrow pattern of the left sacral ala
with fat saturation (b) of the pelvis of a 62-year-old woman with due to recent insufficiency fracture (arrows)
a b
Fig. 4.32 Hypointense

regional pattern, tumor-
related edema.
Sagittal T1-weighted image (a)
eosinophilic granuloma shows
regional hypointense pattern of
the L3 vertebral body with
extension to the pedicle (arrow),
representing edema related to
the presence of the tumor.
Corresponding STIR image (b)
shows hyperintense tumor and
edema (arrow)
4.4 Regional Pattern 55
Fig. 4.33 Hypointense regional pattern, Modic I degenerative end-

plate changes. Sagittal T1-weighted image of the lumbosacral spine of
a 67-year-old woman shows hypointense areas parallel to the inferior
endplate of L4 and the superior endplate of L5, consistent with Modic I
changes
a b c
Fig. 4.34 Hypointense

regional pattern,
spondylodiscitis.
Sagittal T1-weighted image
(a) of the lumbosacral spine of
a 69-year-old woman who
underwent exenterosis for
advanced cervical cancer
2 years earlier shows regional
hypointense pattern involving
most of the L4 and L5 vertebral
bodies. On corresponding STIR
image (b), the abnormal
vertebral bodies and the
intervertebral disc become
hyperintense. Contrast-
enhanced, fat-suppressed
T1-weighted image (c) shows
intense enhancement of the
abnormal bone marrow and
parts of the disc. Final
diagnosis was Klebsiella
osteomyelitis
References 5. Mc Menamin DS, Stuckey SL, Potgieter GL (2007) T1 hyperintense

vertebral column melanoma metastases. AJNR Am J Neuroradiol
28:1817–1818
1. Moulopoulos LA, Dimopoulos MA, Kastritis E et al (2012) Diffuse
6. Hanrahan CJ, Shah LM (2011) MRI of spinal bone marrow: part 2,
pattern of bone marrow involvement on magnetic resonance imaging
T1-weighted imaging-based differential diagnosis. Am J Roentgenol
is associated with high risk cytogenetics and poor outcome in newly
197:1309–1321
diagnosed, symptomatic patients with multiple myeloma: a single
7. Schweitzer ME, Levine C, Mitchell DC et al (1993) Bull’s-eyes and
center experience on 228 patients. Am J Hematol 87:861–864
halos: useful MR discriminators of osseous metastases. Radiology
2. Moulopoulos LA, Varma DG, Dimopoulos MA et al (1992) Multiple
188:249–252
myeloma: spinal MR imaging in patients with untreated newly diag-
8. Libicher M, Appelt A, Berger I et al (2007) The intravertebral vac-
nosed disease. Radiology 185:833–840
uum phenomenon as specific sign of osteonecrosis in vertebral com-
3. Vande Berg BC, Malghem J, Lecouvet FE, Maldague B (1998)
pression fractures: results from a radiological and histological study.
Classification and detection of bone marrow lesions with magnetic
Eur Radiol 17:2248–2252
resonance imaging. Skeletal Radiol 27:529–545
9. Queiroz-Andrade M, Blasbalg R, Ortega CD et al (2009) MR imag-
4. Modic MT, Steiberg PM, Ross JS et al (1988) Degenerative disc
ing findings of iron overload. Radiographics 29:1575–1589
disease: assessment of changes in vertebral bone marrow with MR
imaging. Radiology 166:193–199
MRI of the Abnormal Bone Marrow:
Focal Pattern 5
5.1 Hemangioma or—more frequently—on CT and MRI exams. It is difficult

to accurately estimate the percentage of hemangiomas that
5.1.1 Clinical Background produce symptoms. This is not only because asymptomatic
lesions are very common findings but also because in many
Hemangioma of the bone is a relatively common lesion, and patients with back pain and/or neural deficits, who present
in the vast majority of cases, it is an incidental imaging find- with imaging findings of typical hemangioma without
ing. The two most common locations are the spine and the aggressive features, it is not always possible to determine if
skull. The long bones are affected less often [1]. In this chap- the hemangioma is responsible for the clinical symptoms.
ter, we discuss the vertebral hemangioma (VH), which is a Some authors, therefore, distinguish three categories of ver-
frequent finding on MRI studies of the bone marrow (i.e., tebral hemangiomas based on clinical presentation: asymp-
axial skeleton studies) and can, rarely, have an atypical imag- tomatic, symptomatic, and compressive [2, 7]. The second
ing appearance which must be differentiated from other, category (symptomatic hemangiomas) includes hemangio-
more sinister, pathology. Vertebral hemangiomas are also mas without obvious associated neural compression in
interesting clinically, because in a small minority of cases, patients who are, however, symptomatic; these patients
they can behave as aggressive lesions compressing neural exhibit mostly back pain, even though it is not always clear
elements and requiring prompt treatment. whether their symptoms are related to the hemangioma or
The incidence of vertebral hemangioma, based on large not [7].
autopsy series, is 10–12 %, with a slight female predomi- The third category (compressive hemangiomas) consists
nance [2–4]. Considering the number of very small heman- of locally aggressive lesions which present with symptoms
giomas that are incidentally detected by CT or MRI, it is of spinal cord and/or nerve root compression and require
likely that the true incidence is even higher [5]. Vertebral treatment. Compression is caused by bone expansion,
hemangiomas are frequently multiple and their prevalence extraosseous soft-tissue extension in the epidural space, ver-
seems to increase with age. The most common location is the tebral collapse, epidural hematoma, or a combination of the
thoracic followed by the lumbar spine. Most lesions involve above [8]. In some rare cases without obvious anatomic evi-
part or all of the vertebral body, although, occasionally, a dence of compression, neurological symptoms have been
hemangioma may extend to the pedicles and rarely to the attributed to local blood flow disturbances with spinal cord
spinous process [3]. Osseous hemangiomas are not consid- ischemia [9]. Compressive hemangiomas can occur in
ered true neoplasms with malignant potential, but rather patients of any age, with a peak prevalence in young adults
developmental malformations or hamartomas [6]. They are [4]. Approximately 90 % occur in the thoracic spine, and
classified as cavernous or capillary depending on the pre- most of those are located from T3 to T9 [10]. Involvement of
dominant type of vasculature. On histologic examination, the posterior vertebral elements is much more frequent with
besides the thin-walled vascular channels, they are com- compressive hemangiomas [11]. As far as cellular composi-
posed of sparse, thickened trabeculae and an intervening tion is concerned, a correlation between the amount of fat
stroma containing various amounts of adipose tissue. The present in the intervening stroma and the aggressiveness of
trabecular thickening is probably related to compensatory the lesions has been found; imaging and pathologic studies
reinforcement of the residual osseous network adjacent to have shown an inverse relationship between the amount of
the vascular channels which have caused bone resorption [1]. fat and the number of vessels present in the intervening
The vast majority of vertebral hemangiomas are asymp- stroma of vertebral hemangiomas [7, 12]. Aggressive lesions
tomatic lesions, discovered incidentally on plain radiographs tend to have less fat and more vascular stroma. Conversely,

58 5 MRI of the Abnormal Bone Marrow: Focal Pattern
fat-rich hemangiomas correspond to the much more com- a

mon asymptomatic type of hemangioma. This is in accor-
dance with angiographic studies which have demonstrated
dramatic hypervascularization in most compressive heman-
giomas. Some authors have suggested that low fat content in
itself (as evidenced by soft-tissue density on CT and low sig-
nal on T1-weighted MR images) may indicate a potentially
aggressive lesion [13]. Pregnancy is a recognized risk factor
for the development of a compressive hemangioma from a
previously existing asymptomatic lesion. Although the natu-
ral history is not fully understood, this development possibly
occurs as a result of pregnancy-related increased blood flow
and volume in the hemangioma, most commonly during the
third trimester [9].
There is no consensus in the literature regarding the most
appropriate therapy for compressive hemangiomas, partly
due to the small number of these lesions. Treatment options
include a variety of surgical techniques, vertebroplasty,
direct ethanol injection, embolization, radiotherapy, and a
combination of the above [13]. Due to the extreme hypervas-
b
cularization of most compressive hemangiomas and the risk
for massive intraoperative bleeding, preoperative transarte-
rial embolization is strongly recommended [14].
5.1.2 Imaging
The sparse, abnormally thickened, trabeculae are responsible

for the appearance of typical vertebral hemangiomas on
plain radiographs and CT. On radiographs, they usually pres-
ent with prominent vertical striations (or sometimes with a
“honeycomb” pattern) and intact cortical bone [4]. On axial
CT images, these vertically oriented trabeculae produce the
classic polka dot sign, consisting of sparsely arranged punc-
tate areas of sclerosis (Fig. 5.1). CT is much more sensitive Fig. 5.1 Vertebral hemangioma, CT.
than plain radiographs for the detection of hemangiomas Axial CT image (a) of T12 of a 60-year-old man with a vertebral hem-
[10]. Moreover, CT allows assessment of the stroma between angioma shows the typical polka dot sign representing reinforced tra-
beculae (arrow). Reconstructed sagittal CT image (b) nicely displays
the thickened trabeculae. As shown by Laredo et al, typical the vertically oriented, sparsely arranged trabeculae
asymptomatic hemangiomas demonstrate complete or pre-
dominantly fatty stroma with negative attenuation values at
CT [7]. In contrast, compressive hemangiomas show soft- cortex, and extraosseous soft-tissue extension [10]. On
tissue attenuation between the thickened trabeculae, consis- selective arteriography, most compressive hemangiomas
tent with prominent vascular stroma. Most so-called demonstrate intense and extensive hypervascularity,
symptomatic hemangiomas (i.e., hemangiomas in patients whereas asymptomatic hemangiomas show few or no
with back pain of uncertain origin) display fat attenuation abnormal vessels [10, 11].
values within the intervening stroma at CT. In a small subset
of patients with symptomatic hemangioma, however, soft-
tissue attenuation values predominate in the stroma, indicat- 5.1.3 Magnetic Resonance Imaging
ing a potentially aggressive lesion which requires close
follow-up. As with most bone marrow lesions, relative fat and water
Compressive VHs have a wide spectrum of appearances composition is responsible for the imaging appearance of
at CT, and it may be difficult to make a specific diagnosis vertebral hemangioma at MRI. Linear signal-void areas rep-
based on imaging findings. CT may reveal aggressive resenting reinforced trabeculae, when present, are an addi-
features, such as lytic areas, expanded borders, indistinct tional distinguishing feature.
5.1 Hemangioma 59
Most hemangiomas (asymptomatic, typical) display the Pathologic studies have shown that the high T1 signal of ver-
following MRI features: intermediate to high signal intensity tebral hemangiomas is related to the presence of fatty stroma,
on T1W images (i.e., equivalent or superior to that of adja- whereas the vascular component of the lesion is mostly
cent normal marrow) and intermediate to high signal inten- responsible for the high T2 signal [12]. The relation between
sity on T2W images (i.e., slightly or markedly superior to high T1 signal and increased fat content has also been
that of adjacent normal marrow) (Figs. 5.2 and 5.3). observed in studies comparing MRI findings with CT attenu-
a c
Fig. 5.2 Vertebral hemangioma,

T1 hyperintense.
Sagittal (a) and axial (b) T1-weighted
images of the lumbosacral spine of a
55-year-old man with prostate cancer
show typical hemangioma (long arrow
in a, arrows in b) with hyperintense fatty
stroma and hypointense reinforced bony
trabeculae involving the body and left
pedicle of L1. Also noted is a
hypointense bone metastasis at L2 (short
arrow in a). On the corresponding
sagittal STIR image (c), the hemangioma
is partly hyperintense (arrow)
ation measurements [7]. On T2 fat-suppressed/STIR images, dropout on such sequences (Fig. 5.4). Other than high T1
typical hemangiomas retain some high signal due to their signal intensity, the more specific additional feature of hem-
vascular component (Figs. 5.2 and 5.3). This is in contradis- angioma at MRI is the presence of linear
tinction to foci of fatty marrow, which exhibit marked signal and/or punctate signal-void areas representing the reinforced
Fig. 5.3 Vertebral

hemangioma, T1 isointense.
a b c
Sagittal (a) T1-weighted image
hemangioma, isointense to
normal marrow at S1 (black
arrow). Hyperintense
hemangioma is also noted at L3
(white arrow). Both lesions are
hyperintense on the
T2-weighted image (b, arrows)
and retain some high signal on
the STIR image (c, arrows)
a b
Fig. 5.4 Focal fat, signal

dropout on STIR.
Sagittal T1-weighted (a) image of the
woman shows several hyperintense foci
(arrows) corresponding to focal fat. On
the sagittal STIR image (b), these foci
exhibit signal dropout and become
hypointense to surrounding marrow
(arrows)
5.1 Hemangioma 61
trabeculae. Although specific, this sign is not as frequently This appearance, which may mimic a malignant lesion, is
seen as its CT equivalent, the polka dot sign. The signal-void due to a significantly low proportion of adipocytes and an
areas, when present against a background of high T1 and abundance of vessels and interstitial edema. Signal-void
high T2 signal, give vertebral hemangiomas a characteristic areas, if present, may point to the correct diagnosis and
“mottled” appearance, highly suggestive of VH [15]. On should be sought carefully in lesions that are T1 hypointense
post-contrast T1-weighted images, most typical hemangio- [8]. When dealing with such atypical lesions, correlation
mas demonstrate some enhancement, ranging from not per- with CT and/or close imaging follow-up is warranted, espe-
ceptible/minimal to moderate. This enhancement is more cially in patients with a known malignancy (Fig. 5.6).
conspicuous on fat-suppressed sequences. Low signal intensity on T1-weighted images is very com-
monly seen in compressive hemangiomas. In a review arti-
cle, low T1 signal intensity was found to be present in 48 %
Key Points of 25 cases of compressive lesions, and in smaller-sample
• Typical vertebral hemangiomas demonstrate high series, this percentage is often even higher [8]. In the same
T1 signal article reviewing the imaging findings of compressive verte-
• On STIR, vertebral hemangiomas retain some high bral hemangiomas, the polka dot sign was found at CT in
signal, unlike areas of focal fatty marrow which 80 % of 41 cases. It is, indeed, generally accepted that CT
exhibit signal dropout allows a specific diagnosis to be made in a larger percentage
• Thickened trabeculae may be seen as linear/punc- of patients with compressive lesions than MRI. Compressive
tate signal-void areas lesions with atypical features that are initially imaged with
MRI should, therefore, be further evaluated with CT. Other
MRI characteristics of compressive hemangiomas include
Occasionally, hemangiomas with no signs of aggressive- markedly high signal on T2 and avid contrast enhancement,
ness (e.g., expansion, soft-tissue mass, compression) may both nonspecific. MRI is the best method to demonstrate the
appear hypointense to marrow on T1W images (Fig. 5.5). aggressive characteristics of compressive hemangiomas,
a b
Fig. 5.5 Atypical

hemangioma, T1 hypointense.
(a) of the thoracic spine of a
25-year-old man shows small,
atypical hypointense
hemangioma at the vertebral
body of T7 (arrow). On the
STIR image (b), the lesion is
markedly hyperintense (arrow)
Fig. 5.6 Atypical

hemangioma, value of CT. a b c
a 60-year-old man shows a
predominantly hypointense
lesion at L2 (arrow). The lesion
is markedly hyperintense on the
STIR image (b, arrow) and
enhances avidly on the
T1-weighted post-contrast
fat-saturated image (c, arrow).
Axial CT image (d) at the level
of the lesion shows typical
end-on reinforced trabeculae
(polka dot sign) of osseous
hemangioma (arrow)
namely the presence and extent of extraosseous soft tissue, 5.2 Metastases: Focal Pattern
the compression of spinal cord and/or nerve roots and the
presence of epidural hematoma (Fig. 5.7). 5.2.1 Clinical Background
The majority of cancer patients with solid primary tumors

Key Points
will ultimately develop metastatic disease to the bones, most
• A minority of vertebral hemangiomas demonstrate of them via hematogenous spread. Only few of the circulat-
atypical MRI features: low T1 signal, very intense ing tumor cells survive the host’s defense mechanisms and
contrast enhancement, and in some cases extraosse- manage to reach the bone marrow vasculature. An even
ous soft-tissue extension smaller fraction of tumor cells will escape the marrow vascu-
• These atypical hemangiomas may be indistinguish- lature by destroying the vascular basement membrane. Once
able from a malignant lesion on MRI in the bone marrow, they interact with hematopoietic and
• Correlation with CT may aid diagnosis stromal cells, initiating a vicious cycle of tumor growth and
• MRI is the best exam to demonstrate the aggressive bone destruction (seed and soil theory) [16]. Osteoclast acti-
features of compressive hemangiomas (soft-tissue vation resulting in bone resorption is achieved through the
mass, neural compression) release of various tumor-derived factors. In turn, bone
resorption leads to the release of growth factors which
5.2 Metastases: Focal Pattern 63
Fig. 5.7 Compressive

hemangioma, MR images. a b c
Sagittal T1-weighted (a),
T2-weighted (b) and STIR
(c) images of the lumbosacral
spine of a 31-year-old woman
who presented with acute onset
low back pain at the immediate
post-partum period. L2 is
collapsed with low T1 and high
T2 signal intensity. Reinforced
vertical trabeculae, better seen
on the T2W image, are
suggestive of hemangioma.
Note soft-tissue mass in the
anterior epidural space causing
thecal sac compression
promote tumor proliferation. It, therefore, seems that the the bone marrow. It does not require bone loss or a perile-
interaction between specific tumor cells and the bone mar- sional reaction to identify bone metastases but may depict
row microenvironment determines the development of bone lesions which are confined to the marrow, before they affect
metastases [17]. the bony substrate.
The skeleton is one of the most frequent sites of metastatic MRI may detect lytic bone metastases in patients with
disease, and bone metastases are associated with increased negative radiographs, CT or bone scans. This is explained
morbidity [18]. The vast majority of patients with bone by the fact that over 30 % of bone loss must occur before a
metastases have primary tumors of the breast, prostate, thy- lesion becomes apparent on CT images and a much higher
roid, lung, kidney, and pancreas. Lung, breast, and prostate percentage of bone loss (about 50 %) is required for osteoly-
cancers, which are the most common human cancers, display sis to become evident on plain radiographs. CT will ade-
increased avidity for the skeletal system. Bone metastases quately depict cortical destruction by a metastatic lesion,
are characterized as osteolytic or osteoblastic depending on but it may miss lesions confined to the marrow of spongious
whether there is bone resorption or bone formation, respec- bones (vertebrae, iliac bones) unless marked trabecular
tively. Actually, at any metastatic site there is a spectrum of destruction has occurred [19]. Osteoporosis and degenera-
bone tumor activity, ranging from pure lysis to pure sclero- tive osteoarthropathy may, at times, be difficult to distin-
sis. It is the predominant feature which determines the char- guish from bone metastases [20]. Caution is required,
acterization of a bone metastasis as osteolytic or particularly with the increasing use of whole-body CT
osteoblastic. (WBCT) for skeletal assessment, not to diagnose small
intracortical hypodense foci as bone metastases when, in
fact, they may represent normal structures such as vessels.
5.2.2 Imaging As with MRI, we should refrain from characterizing lesions
smaller than 5 mm.
Conventional radiographs, computed tomography (CT), Bone scans detect bone metastases with increased sensi-
skeletal scintigraphy, [(18)F]-fluoro-2-D-glucose positron tivity and much earlier than plain radiographs. However,
emitting tomography (FDG-PET), and MRI may all be aggressive bone metastases with rapid bone destruction or
employed in the work-up of skeletal metastases, each with bone metastases at an early stage lack the osteoblastic reac-
specific indications. Conventional radiographs, CT, and skel- tion which is responsible for the radiotracer uptake and may,
etal scintigraphy depend on changes in bone turnover for therefore, not show on a bone scan [21]. Small intramedul-
lesion detection, and FDG-PET assesses metabolic activity. lary metastases may fail to incite sufficient bone remodeling,
MRI is the only imaging modality which directly visualizes and a mild increase in uptake may be obscured by the more
intense uptake of normal cortical bone. The vertebrae and the 5.2.3 Magnetic Resonance Imaging
long bones are bones with large marrow cavities, and conse-
quently involvement of the cortex by bone metastases that The spine is the most common site for bone metastases
lodge in the bone marrow will occur later in the course of the because of the abundance of red marrow. The thoracic spine
disease [22]. This explains why in a study comparing bone is more often affected, followed by the lumbar and, lastly, the
scintigraphy to MRI in patients with disseminated metastatic cervical spine. Spinal metastases initially involve the verte-
disease, bone scans identified the majority of spinal meta- bral body. The past belief that bone metastases show a predi-
static lesions involving the vertebral cortex but only a third lection for the pedicles was due to the fact that destruction of
of those in a subcortical location and none of the purely the pedicles was more easily detected on conventional radio-
intramedullary lesions [23]. Bone scans, on the other hand, graphs in comparison to destruction of the vertebral body [22,
may fare better than MRI in the assessment of bones with 32]. The increase in the fatty component of the bone marrow
limited marrow cavities such as the ribs or in the depiction of which occurs with age, central skeleton included, facilitates
small intracortical metastases. False-positive bone scans are the diagnosis of metastases even of very small size, with MRI
common, for example, in cases of degenerative disc disease (Fig. 5.8). In older adults, hypointense metastases are easily
and fractures, quite frequent findings in the elderly popula- recognized against a background of hyperintense fatty mar-
tion which is also the age group more likely to harbor bone row on T1-weighted MR images. In children and young
metastases [24, 25]. adults, red marrow predominates in the central skeleton and
There is still ongoing discussion regarding the value of the sensitivity of MRI for the detection of vertebral metasta-
whole-body MRI (WBMRI) versus FDG-PET/CT for the ses may be somewhat lower. For example, it has been found
detection of skeletal metastases. Both modalities are more that metastases from neuroblastoma are detected with greater
accurate than bone scans in detecting bone metastases, and accuracy after the first year of life, because at that age some
both offer the advantage of complete TNM staging. Most amount of fatty marrow has appeared in the spine [33].
authors conclude that both WBMRI and FDG-PET/CT are
robust imaging modalities for screening for osseous metas-
tases provided that, in the case of FDG-PET/CT, investi-
gated primary tumors are FDG-avid [26–29]. Indeed, a
relative drawback of FDG-PET/CT in this setting is the
poor FDG avidity of certain tumors such as prostate can-
cer, myxoid gastrointestinal tumors, low-grade sarcomas,
and renal cell carcinoma [30]. On the other hand, FDG-
PET/CT may be used as a problem-solving tool for inde-
terminate MRI lesions. Although MRI is extremely
sensitive in detecting marrow lesions its specificity is rela-
tively poor. For example, an atypical hemangioma, which
may simulate a bone metastasis on MRI, will show no
metabolic activity on FDG-PET. Recently, whole-body
FDG-PET/MRI combining the metabolic and morphologic
information of PET and MRI has emerged as a promising
new technique for the evaluation of malignant bone lesions,
including metastases [31].
Key Points
• Plain radiography and, to a lesser degree, CT

require significant bone loss before a lytic bone
metastasis becomes evident
• Scintigraphy detects bone remodeling associated
with a bone metastasis
• MRI can depict metastases confined to the bone
marrow before any bone destruction occurs Fig. 5.8 Bone metastases, high sensitivity of MRI.
• FDG-PET/CT and WBMRI are both robust modali- man with metastatic lung cancer shows multiple metastases, including
ties for screening of skeletal metastases several of a few mm size (arrows). The very small lesions are easily
seen against a background of hyperintense fatty marrow
heterogeneous signal intensity due to coexistence of hyperin-

Key Points tense foci of normal fatty marrow with hypointense foci of bone
Location of vertebral metastases marrow edema (Figs. 5.11 and 5.12). Low-signal-intensity focal
• Thoracic > lumbar > cervical lesions on a T1-weighted sequence may also represent red mar-
• Vertebral body > posterolateral elements row rests. The signal intensity of red marrow rests is usually
higher than that of disc or muscle (Fig. 5.13). A centrally located
hyperintense focus (bull’s eye sign), if present, is an indicator of
hematopoietic marrow. However, additional sequences (STIR,
In the large majority of patients, osseous metastases manifest chemical-shift imaging, post-contrast T1-weighted) may be
with a focal rather than a diffuse MR pattern. The most impor- required to confidently differentiate between the two.
tant sequence for determining the presence and pattern of bone Osteoblastic metastases are very hypointense because of pau-
metastases is the T1-weighted sequence. On T1-weighted city of moving protons. Their signal intensity may approximate
images, osteolytic metastases appear as well-defined, round- or that of cortical bone (signal-void focal pattern) (Fig. 5.14). An
oval-shaped foci which are hypointense and, less often, isoin- enostosis (bone island) may appear quite similar to an osteo-
tense to muscle or intervertebral discs (Fig. 5.9). Hyperintense blastic metastasis on T1-weighted images, but it displays homo-
bone metastases are extremely rare and have been reported geneous, very low signal intensity on all pulse sequences.
only in association with melanoma (Fig. 5.10) [34]. The signal Radiating bony streaks (thorny border) when present are also
intensity of metastatic lesions is homogeneous because they characteristic of an enostosis (Fig. 5.15).
destroy bony trabeculae and replace normal bone marrow in
contiguity, rather than intermingle with it. This may be a use-
ful sign in differentiating bone metastases from bone marrow a b
edema on T1-weighted images; bone marrow edema shows
Fig. 5.10 Bone metastases, rare hyperintense appearance.

Sagittal T1-weighted image (a) of the lumbosacral spine of a 43-year-
Fig. 5.9 Bone metastases, hypointense focal pattern. old man with metastatic melanoma shows multiple hyperintense
Sagittal T1-weighted image of the lumbosacral spine of a 53-year-old metastases. T1-weighted image with fat saturation (b) shows very high
man with metastatic colon cancer shows multiple focal bone metasta- signal intensity of metastatic lesions in keeping with melanin or
ses, hypointense relative to the intervertebral discs hemorrhage
Fig. 5.11 Heterogeneous low T1

signal, bone marrow edema. a b
Sagittal T1-weighted image (a) of the
woman with a compressive fracture of
L2 following heavy weight lifting. There
is heterogeneous signal intensity of most
of the vertebral body due to hypointense
edema intermingling with hyperintense
normal fatty marrow (arrow). A
low-signal-intensity fracture line is seen
adjacent to the inferior endplate. On
sagittal STIR (b), marrow edema
appears hyperintense (arrow)
On STIR images, bone metastases of an osteolytic nature Chemical-shift imaging is not helpful for the evaluation of
become hyperintense. Red marrow rests, either become osteoblastic metastases.
imperceptible or appear mildly hyperintense to background On contrast-enhanced T1-weighted images without fat
marrow; occasionally a focus of red marrow may appear saturation, untreated osteolytic lesions become iso- or hyper-
moderately hyperintense on STIR images. Osteoblastic intense to normal marrow. A more than 40 % enhancement
metastases show either no or mild heterogeneous increase in on post-contrast T1-weighted images is characteristic of
signal intensity (Fig. 5.16). The T2 halo sign which consists malignancy [37]. Osteolytic metastases may not be discern-
of a hyperintense rim surrounding a very low-signal-intensity ible on the enhanced images unless careful comparison with
lesion on STIR images, when present, is a very specific addi- the pre-contrast images is made or fat suppression is applied
tional feature of an osteoblastic metastasis (Fig. 5.17). The (Fig. 5.19). Unlike osteolytic metastases, osteoblastic depos-
hyperintense rim is believed to be caused by fluid, filling the its usually show mild or no obvious contrast uptake
area of destroyed bony trabeculae around the metastatic (Fig. 5.20).
focus [35]. On diffusion-weighted images with high b-values, lytic
With chemical-shift imaging, most bone metastases show bone metastases are hyperintense and easily recognized.
no or less than 20 % signal loss on out-of-phase images [36]. Their ADC values are high, often higher than 1.0 × 10−3 mm2/s,
In fact, osteolytic metastases may even show a small increase because they exhibit increased diffusivity relative to the very
in signal intensity and appear hyperintense on the out-of- restricted diffusion of normal fat-containing marrow
phase compared to the in-phase images (Fig. 5.18). This is in (Fig. 5.21) [38]. Osteoblastic metastases are generally char-
contradistinction to red marrow rests which usually show a acterized by more pronounced diffusion restriction (i.e.,
more than 20 % signal dropout on opposed-phase imaging. lower ADC values) than osteolytic lesions because of new
Fig. 5.12 Homogeneous low

T1 signal, bone metastases. a b
a 62-year-old woman with lytic
bone metastases from lung
cancer shows multiple
metastatic foci with
homogeneous low signal
intensity. On sagittal STIR
(b), metastases are hyperintense
a b c
Fig. 5.13 Red marrow rest,

hyperintense to intervertebral
discs.
(a) of the lumbosacral spine of a
multiple osteoporotic
compression fractures of
different ages at L2–L5. There
is a hypointense focus at T12
(arrow) which has higher signal
intensity than the intervertebral
discs. On the out-of-phase
image (b), the lesion shows
signal dropout, and on STIR (c)
there is no signal hyperintensity.
The findings are consistent with
a red marrow rest
a b
Fig. 5.14 Bone metastases, signal-void focal pattern. of a 62-year-old man with transitional cell carcinoma (TCC) of the
(a) Coronal T1-weighted image of the pelvis of a 58-year-old man with bladder shows expansile, very low-signal-intensity osteoblastic bone
prostate cancer shows multiple very low-signal-intensity (signal void) metastasis (arrows)
skeletal metastases (arrows). (b) Axial T1-weighted image of the skull
a b
Fig. 5.15 Enostosis (bone island), signal-void focal pattern. (arrow) with typical radiating streaks also shown on corresponding CT
Axial T1-weighted image (a) of the pelvis of a 59-year-old man image (b)
shows very low-signal-intensity bone island at the right femoral head
Fig. 5.16 Lytic and blastic

bone metastases, appearance a b
on STIR.
Sagittal T1-weighted (a) and
STIR (b) images of the thoracic
spine of a 65-year-old man with
prostate cancer and both lytic
and blastic bone metastases.
Osteoblastic metastasis (long
arrow) shows low signal
intensity on STIR. Osteolytic
metastases (short arrows)
appear markedly hyperintense
on STIR
a b
Fig. 5.17 Osteoblastic

metastasis, T2 halo sign.
Magnified sagittal T1-weighted
image (a) of the thoracic spine of
a 72-year-old man with prostate
cancer shows a very low-signal-
intensity osteoblastic metastasis
at T11 (arrow). (b) On STIR,
there is a rim of high signal
intensity (T2 halo sign)
surrounding the predominantly
low-signal-intensity metastasis
(arrow)
Fig. 5.18 Osteolytic

a b
metastases: chemical-shift
imaging.
out-of-phase (b) images of the
lumbosacral spine of a 64-year-
old man with prostate cancer and
lytic bone lesions. Metastatic
lesions (arrows) appear
hypointense on the T1-weighted
image. On the out-of-phase
image, they do not show signal
loss, appearing hyperintense to
normal marrow (arrows)
a b c
Fig. 5.19 Osteolytic

metastases: increased lesion
conspicuity on post-contrast
fat-suppressed T1-weighted
images.
Sagittal T1-weighted (a),
post-contrast T1-weighted (b),
and post-contrast fat-suppressed
T1-weighted (c) images of the
lumbosacral spine of a
55-year-old woman with breast
cancer. Several small
hypointense skeletal metastases
are observed on the
T1-weighted image (arrows).
On the post-contrast
T1-weighted image, they are
indistinguishable from normal
marrow, but they are clearly
seen on the contrast-enhanced
image with fat suppression
(arrows)
Fig. 5.20 Blastic versus lytic a

metastases: differences in contrast
b
enhancement.
Sagittal T1-weighted (a) and post-contrast
fat-suppressed T1-weighted (b) images of
the lumbosacral spine of a 74-year-old
man with prostate cancer and mixed
skeletal metastases. There is minimal
increase in the signal intensity of the
predominantly blastic lesions at L2 and
L4 on the post-contrast image (solid
arrows). Predominantly lytic lesions at
T12 and L5 show more pronounced
enhancement (open arrows)
a b c d
Fig. 5.21 Osteolytic metastases, diffusion-weighted imaging. patient as in Fig. 5.18). The arrows point to the two larger lesions. The
Sagittal T1-weighted image (a), diffusion-weighted images with metastases are very hyperintense on the high b-value DW image. ADC
b-value 0 (b) and b-value 750 (c) and ADC map (d) of a 64-year-old values of the L1 and L4 lesions are 0.910 × 10−3 and 1.180 × 10−3 mm2/s,
man with prostate cancer and multiple osteolytic metastases (same respectively (d)
Key Points • Moderately to markedly hyperintense on STIR

Osteolytic Metastases: typical MRI appearance • >40 % enhancement on post-contrast T1-weighted
(Fig. 5.22) images
• Hypointense to intervertebral discs and muscle on • No or <20 % signal loss on out-of-phase images
T1-weighted images • High ADC values (often higher than 1.0 × 10−3 mm2/s)
a b c d
e f g h
Fig. 5.22 Osteolytic metastases, typical MRI appearance. contrast-enhanced image (d). On the out-of-phase image (e), there is no
(a–e) Sagittal T1-weighted image (a) of the lumbosacral spine of a significant signal loss of the lesions. (f–h) Sagittal T1-weighted image (f)
53-year-old man with skeletal metastases from colon cancer shows sev- of the lumbosacral spine of a 29-year-old woman with breast cancer
eral focal lesions which are hypointense to the intervertebral discs. On shows multiple low-intensity (iso- or hypointense to the discs) bone
STIR (b), the lesions become markedly hyperintense. On the post-con- metastases. On the diffusion-weighted image with b-value 750 (g), the
trast T1-weighted image (c), they enhance and become almost isointense metastases appear as high-intensity lesions. ADC values calculated from
to normal marrow; lesion conspicuity increases on the fat-suppressed, the corresponding ADC map (h) ranged from 0.9 to 1.9 × 10−3 mm2/s
Key Points • Mild or no hyperintensity on STIR (look for T2 halo sign)

Osteoblastic metastases: typical MRI appearance (Fig. 5.23) • Mild or no enhancement on post-contrast T1-weighted
• Very hypointense on T1-weighted images (similar to images
cortical bone) • ADC values may overlap with those of normal marrow
a b c
Fig. 5.23 Osteoblastic metastases, typical MRI appearance. enhancement is noted on the post-contrast image (c, long arrow). There
Sagittal T1-weighted image (a) of a 69-year-old man with prostate can- is an associated epidural soft-tissue component (short arrow on a, b, c)
cer shows a very low-signal-intensity metastasis at L4 (long arrow). and a compression fracture of L5
There is no hyperintensity on STIR (b, long arrow), and minimal
bone formation; occasionally their ADC values overlap with

those of normal marrow.
Bone metastases may break through the cortical bone and
present with an extraosseous soft-tissue component. Cortical
destruction is easily diagnosed when the markedly low signal
of cortical bone is lost (Fig. 5.24). Occasionally, extraosseous
extension of a metastatic bone lesion may occur without evi-
dence of gross cortical or trabecular destruction. This is usually
observed in metastases from small round cell tumors, such as
neuroblastoma, small cell lung carcinoma, Ewing’s sarcoma,
and rhabdomyosarcoma, possibly reflecting the permeative
nature of these tumors. A similar pattern of extraosseous soft-
Fig. 5.24 Extraosseous extension of bone metastasis: loss of corti-
tissue extension with apparent preservation of cortical bone cal low signal intensity on T1-weighted imaging.
integrity has also been classically described in bone marrow Axial T1-weighted image of the pelvis of a 43-year-old man with meta-
lymphoma [39]. T1-weighted images are best suited for the static malignant nerve sheath tumor shows right iliac bone metastasis
diagnosis of tumor extending to the epidural space or interver- with destruction of the bony cortex seen as loss of normal cortical sig-
nal void and large associated extraosseous soft-tissue mass (asterisks).
tebral foramina (Fig. 5.25). The draped curtain sign is caused Also seen is small round hypointense bone metastasis in the right pos-
by tumor spreading to the right and left of the meningovertebral terior iliac wing
ligament which attaches the anterior surface of the dural sac to
the posterior longitudinal ligament (Fig. 5.26) [40]. compression by epidural tumor may cause hyperintense signal
Symptomatic cord compression occurs in 10–20 % of patients in the spinal cord on T2-weighted images; contrast enhance-
with vertebral metastases (Fig. 5.27) [41]. Long-standing ment of the cord may or may not be present.
Fig. 5.25 Bone metastasis,

a b
foraminal extension.
STIR (b) images of the
lumbosacral and lower thoracic
with endometrial cancer show
metastasis at T12 with
extraosseous extension in the
left T12-L1 intervertebral
foramen completely replacing
foraminal fat (arrow)
Fig. 5.26 Anterior epidural mass: the draped curtain sign.

Axial T1-weighted image of a 69-year-old man with prostate cancer
and an osteoblastic metastasis at L5 shows associated soft-tissue mass
in the anterior epidural space spreading to the left and to the right of
the meningovertebral ligament, resembling a draped curtain (solid
arrows). Also note left paraspinal soft-tissue mass (open arrows)
Fig. 5.27 Bone metastasis,

cord compression. a b
STIR (b) images of the thoracic
with lung cancer shows
metastatic lesion involving the
posterolateral elements of T6
with associated soft-tissue mass
in the posterior epidural space
(asterisk), causing marked
compression of the spinal cord
(arrow). A chronic compression
fracture of T5 is also seen
The occasional occurrence of peripheral skeletal metasta- isolated peripheral metastases confined to the bone marrow
ses led to the evaluation of whole-body MRI (WBMRI) for are extremely unusual; rarely, intracortical bone metastases
bone metastases screening. Initially, WBMRI was performed may be observed in the periphery without involvement of the
utilizing T1-weighted and STIR sequences; more recently axial skeleton.
Diffusion-Weighted Imaging (DWI) was added to oncology Although MRI is very sensitive in detecting skeletal
protocols. Meta-analysis of data from 11 WBMRI studies metastases even of small size, its ability to differentiate
showed a pooled sensitivity of 89.9 % and a pooled specific- them from other malignant bone marrow lesions or to diag-
ity of 91.8 % for the detection of bone metastases [42]. The nose the neoplasm of origin is more limited. Bone metasta-
implementation of DWI to WBMRI seems to increase its ses are quite similar in appearance with foci of multiple
sensitivity and positive predictive value for the detection of myeloma, both of which affect mainly the elderly popula-
bone metastases [43]. However, even though the sensitivity tion. When bone metastases occur close to the endplates, the
increases, the specificity of WBMRI may be compromised differential diagnosis may also include Modic I degenera-
by the addition of DWI [42]. In the case of bone metastases tive endplate changes and spondylodiscitis. Modic I changes
from prostate cancer, DWI with high b-values shows display signal intensity similar to metastases (low on
increased lesion conspicuity compared to STIR, because the T1-weighted and high on T2-weighted images), but they are
pronounced osteoblastic component and reparative bone for- typically located along the vertebral endplates on both sides
mation of these lesions decreases T2 relaxation time; on the of a degenerated disc. However, occasionally, they may be
other hand, for breast cancer bone metastases, DWI and more focal and unilateral and difficult to distinguish from a
STIR seem to have similar sensitivities [44]. DWI is there- metastatic lesion. On high b-value DWI, Modic I changes
fore recommended for WBMRI protocols of prostate cancer. show either no high signal or linear high signal at the inter-
WBMRI detects more lesions than MRI limited to the spine; face of normal with abnormal marrow (referred to as the
the clinical impact of the surplus data, however, is not clear. claw sign), while osseous changes related to metastases and
In a study of prostate carcinoma patients, comparing spondylodiscitis both show increased signal intensity
WBMRI to MRI of the axial skeleton (AS-MRI covering the (Figs. 5.28, 5.29, and 5.30) [46, 47]. Spondylodiscitis is
cervicothoracic and lumbosacral spine as well as the pelvis additionally characterized by T2 hyperintensity and contrast
and proximal femora), peripherally located metastases visi- enhancement of the intervertebral disc; osseous, intradiscal,
ble at WBMRI were only present in patients who also har- or soft-tissue abscesses, when present, are pathognomonic
bored metastases in the axial skeleton [45]. In our experience, of infection.
Fig. 5.28 Modic I

degenerative endplate a b c
changes: absence of high
signal on diffusion-weighted
imaging.
Sagittal T1-weighted (a), STIR
(b), and diffusion-weighted
b-value 500 (c) images of the
68-year-old woman with Modic
I degenerative endplate changes
at L4–L5 (arrows).
Degenerative changes are
hypointense on the T1-weighted
image and mildly hyperintense
on STIR; they appear
hypointense on the diffusion-
weighted image
a b c
Fig. 5.29 Modic I

degenerative endplate
changes: claw sign on
diffusion-weighted imaging.
(b), and diffusion-weighted
b-value 750 (c) images of the
65-year-old woman with Modic
I degenerative endplate changes
at L2–L3. Degenerative
changes are hypointense on the
T1-weighted image and
hyperintense on STIR (arrows).
On the diffusion-weighted
image, linear hyperintensity is
seen at the interface of normal
and abnormal marrow (claw
sign) (arrows)
5.3 Multiple Myeloma: Focal Pattern for 13 % of hematologic malignancies and 1 % of all can-
cers. Median age at presentation is 70 years, and men are
5.3.1 Clinical Background affected slightly more often than women [48–50].
Multiple myeloma is characterized by the presence of
Multiple myeloma is a hematologic malignancy caused by ≥10 % abnormal plasma cells in the bone marrow and
proliferation of a single clone of plasma cells in the bone ≥3 g/100 ml serum monoclonal protein (with or without the
marrow. It affects 5–6/100,000 individuals/year and accounts presence of monoclonal protein in the urine). The presence
5.3 Multiple Myeloma: Focal Pattern 77
a b c d
Fig. 5.30 Spondylodiscitis: high signal on diffusion-weighted imaging. hypointense on the T1-weighted image (a, arrows), hyperintense on
Sagittal T1-weighted (a), STIR (b), contrast-enhanced fat-suppressed (c), STIR (b, arrows), and show marked contrast enhancement (c). Also noted
and diffusion-weighted b-value 500 (d) images of the lumbosacral spine on c is marked peripheral enhancement of the L5–S1 intervertebral disc
of a 44-year-old woman with L5–S1 spondylodiscitis following surgery in keeping with intradiscal abscess. On the diffusion-weighted image,
for prolapse of the pelvic organs. Inflammatory changes of L5 and S1 are there is pronounced hyperintensity of the marrow changes (d, arrows)
or absence of end-organ dysfunction manifesting with hyper- The biology of multiple myeloma is complex because of
calcemia, renal insufficiency, anemia, or bone lesions the various genetic abnormalities of plasma cells [50]. These
(referred collectively by the acronym CRAB) classifies abnormal cells interact with the microenvironment of the
myeloma as symptomatic or asymptomatic (smoldering) bone marrow and cause both neoplastic cell proliferation
disease. and bone resorption. Myeloma cells initially attach to bone
A monoclonal gammopathy of uncertain significance marrow cells and extracellular matrix proteins. Through a
(MGUS) is an asymptomatic, premalignant proliferation of series of events, mediated by the release of various cyto-
monoclonal plasma cells (<10 % plasma cells in the bone kines and growth factors, tumor growth and angiogenesis is
marrow and <3 g/100 ml monoclonal protein in the serum) induced and the balance between osteoblast and osteoclast
which is believed to precede the development of multiple formation is disrupted. The bone marrow microenvironment
myeloma with an annual risk of about 1 % [51]. A mono- itself actually plays an active role, assisting neoplastic pro-
clonal gammopathy of borderline significance (MGBS) liferation [53].
differs from MGUS in the percentage of bone marrow plas-
macytosis (10–30 %). Plasma cell disorders are believed to
form a continuum, progressing from MGUS to asymptom- Key Point
atic myeloma, and eventually to symptomatic multiple • The bone marrow microenvironment actively sup-
myeloma [52]. ports the growth of neoplastic plasma cells
The first widely used system for staging multiple myeloma

Key Points
is the Durie-Salmon staging system, introduced in 1975 [54].
• Multiple myeloma is a hematologic malignancy It is based on values of monoclonal protein, hemoglobin, and
caused by proliferation of a single clone of plasma calcium, assessment of renal function, and number of lesions
cells in the bone marrow on skeletal surveys. In 2003, the Durie-Salmon PLUS sys-
• It is believed to evolve from a premalignant mono- tem for the staging of multiple myeloma acknowledged the
clonal gammopathy contribution of cross-sectional imaging relying mainly on
the number of focal lesions larger than 5 mm or the grade
(mild/moderate/severe) of diffuse involvement on MRI or occur before a lytic lesion becomes apparent on radiographs;
PET studies [55]. It did not include laboratory parameters the extent of bone disease on WBXR is, therefore, underesti-
except for the serum creatinine level. A third staging system, mated [54]. Newer imaging techniques (CT, MRI, PET, and
the International Staging System (ISS), introduced in 2005, PET-CT) detect about 80 % more bone lesions compared to
offers increased reproducibility compared to the Durie- skeletal radiographs [60]. Another drawback of WBXR,
Salmon PLUS system since it is based on more objective besides low sensitivity, is the difficulty of these patients who
criteria, i.e., values of serum β2-microglobulin and albumin are often elderly and may suffer from pain to cooperate for
[56]. It cannot, however, be used for therapeutic risk this lengthy examination which requires multiple
stratification, neither does it accurately reflect tumor burden. exposures.
Most investigators currently propose the combined use of
the Durie-Salmon staging system and the ISS in clinical tri-
Key Point
als [48].
• Newer imaging techniques (CT, MRI, PET) detect
up to 80 % more bone lesions compared to WBXR
Key Points
in multiple myeloma patients
• The Durie-Salmon PLUS staging system for multi-
ple myeloma relies mainly on cross-sectional imag-
ing findings (MRI or PET) Whole-body, low-dose, multidetector CT (WBLDCT)
• The International Staging System (ISS) relies on has recently emerged as a more sensitive, quick, and tolera-
laboratory findings (serum β2-microglobulin and ble means of skeletal assessment for multiple myeloma
albumin levels) patients with an average effective dose slightly higher
than that of a WBXR [61]. When compared to WBXR,
WBLDCT identifies more lesions and is, therefore, more
Although multiple myeloma remains an incurable dis- accurate in the staging of patients with multiple myeloma
ease, novel treatment strategies have led to a 30 % 10-year [62] (Fig. 5.31). Lytic cortical lesions (produced by medul-
survival rate for those patients who present before the age of lary aggregates, which erode and eventually destroy the
60 years [57]. Cytogenetic abnormalities are the cutting edge cortex) are easily detected, even when very small. Using
of research for multiple myeloma and together with mono- WBLDCT, the detection rate of spinal osteolytic lesions can
clonal protein, serum LDH, and β2-microglobulin levels are be increased by as much as seven times compared with the
the most important factors for the diagnosis of high-risk ver- WBXR [63]. Visualization of extraosseous soft-tissue
sus low-risk disease [50]. masses is an additional advantage of CT over plain radiogra-
phy. Furthermore, WBLDCT can easily detect myeloma
Solitary Bone Plasmacytoma deposits confined to the medullary cavity of long bones, as
Solitary bone plasmacytoma is a rare tumor accounting for hyperdense (focal or diffuse) lesions on a background of
less than 5 % of plasma cell dyscrasias [58]. Its diagnosis low-density, fat-rich marrow (Fig. 5.32). Due to its fat con-
requires histologic evidence of monoclonal plasma cells, tent, the medullary cavity of the long bones exhibits density
absence of systemic symptoms related to myeloma, negative values in the negative range (usually between −30 and −100
skeletal survey, and negative bone marrow biopsy. If present, Hounsfield Units) on CT. Cutoff values of 0 HU (for focal
a small component of M-protein should disappear after areas of density increase) and 20 HU (for diffuse density
definitive treatment with local radiotherapy. Ten-year overall increase) have been proposed for the diagnosis of myeloma-
survival for patients with SBP is 50–70 %. About 50 % of tous deposits in the medullary cavities of long bones,
patients progress to multiple myeloma within 10 years after although these values need to be validated in further studies
initial diagnosis [59]. [64]. Mean density for myelomatous hyperdense medullary
lesions has been reported to be 55 ± 25 HU [65]. Myeloma
medullary cavity lesions should be differentiated on CT from
5.3.2 Imaging red marrow hyperplasia (e.g., in the setting of anemia, che-
motherapy, hematopoietic growth factor administration),
Bone lesions are the hallmark of multiple myeloma. The which may also manifest with increased density in the med-
whole-body skeletal radiographic survey (WBXR), a basic ullary cavity. WBLDCT is less sensitive for the detection of
part of the initial Durie-Salmon staging system, includes a small bone marrow infiltrates confined within spongious
posteroanterior view of the chest; anteroposterior and lateral bone (vertebrae, iliac bones), without cortical involvement.
views of the spine, skull, humeri, and femora; and an antero- In cases where myeloma infiltration of the spongiosa is not
posterior view of the pelvis. At least 30 % bone loss must associated with significant trabecular destruction, CT may be
Fig. 5.31 Multiple myeloma. Assessment of bone

disease with whole-body low-dose CT (WBLDCT).
a b
(a) Coronal multiplanar reconstructed (MPR) image from
a WBLDCT of a 52-year-old man with newly diagnosed
multiple myeloma. Multiple lytic lesions are seen in the
skull, spine, and left iliac bone (arrows). (b) Sagittal
multiplanar reconstructed (MPR) image from a WBLDCT
of a 41-year-old man with newly diagnosed multiple
myeloma shows multiple spinal lytic lesions (arrows)
negative. This explains the higher sensitivity of MRI over Many studies have demonstrated high sensitivity and speci-
WBLDCT, in the axial skeleton. The advantage of MRI is ficity of PET-CT in the staging of multiple myeloma, compa-
more evident in cases of diffuse marrow involvement, where rable to those of MRI and, as expected, much higher than
myeloma infiltrates may coexist with hematopoietic and those of WBXR. An obvious advantage of PET-CT is its
fatty elements, within more or less preserved cancellous whole-body scan ability, which allows identification of
bone. A study comparing whole-body MRI (WBMRI) with lesions outside the field of view of spinal MRI. In patients
WBLDCT showed lower sensitivity for CT with understag- with a presumed diagnosis of solitary bone plasmacytoma,
ing of a statistically significant number of patients [61]. CT PET-CT identifies more sites of disease than MRI of the
is, however, the modality of choice to assess bone stability spine. On the other hand, MRI is the gold standard for assess-
and fracture risk. It should be performed when vertebro- ment of the spine, where disease is often underestimated by
plasty is considered, to ensure that the posterior cortex of the PET-CT [66]. The prognostic value of PET-CT, both at base-
vertebral body is intact. line and after treatment, has been demonstrated in recent
FDG-PET/CT detects metabolically active tissue with studies; the number of focal lesions, the degree of FDG-
high glucose demand and has been advocated both for initial avidity, and the presence of extramedullary disease have
staging and for treatment response assessment in multiple been shown to be strong predictors of clinical outcome [67,
myeloma patients. The CT component of the exam allows 68]. Furthermore, since PET can distinguish between active
precise anatomic localization of the hypermetabolic lesions. disease and nonviable tumor, it is a very useful tool to assess
Fig. 5.32 Detection of

myeloma deposits within the
a
medullary cavity of long
bones with whole-body
low-dose CT (WBLDCT).
Axial slice through the distal
diaphysis of the femora (a) and
coronal multiplanar
reconstructed (MPR) image
(b) from a WBLDCT of a
65-year-old woman with newly
diagnosed multiple myeloma. A
large myeloma deposit within
the medullary cavity of the right
femur is seen as a hyperdense
lesion (105 HU) with associated
endosteal scalloping (arrows).
Note normal low-density
appearance (approximately −40
HU) of fatty marrow at the
corresponding level of the left b
femur
treatment response. Lack of widely accepted standardized bone marrow may show one of four patterns: normal, focal,
criteria, both qualitative (visual assessment) and quantitative variegated, or diffuse [70]. Reported frequencies of MRI pat-
(SUV values), for the interpretation of imaging findings, terns in myeloma patients vary, but in most studies, a focal
remains an important limitation of PET-CT in multiple pattern is the most common. In a large series of 142 symp-
myeloma. tomatic myeloma patients, reported frequencies of MRI pat-
terns were as follows: focal 50 %, diffuse 28 %, variegated
14 %, and normal 8 % [71]. Abnormal MRI patterns are seen
5.3.3 Magnetic Resonance Imaging in 80–100 % of patients with symptomatic myeloma,
30–50 % of patients with asymptomatic (smoldering)
MRI directly depicts diseased bone marrow, regardless of myeloma and less than 20 % of patients with MGUS accord-
whether bone destruction is present or not. It is not unex- ing to data obtained from MRI studies limited to the central
pected, therefore, that bone marrow MRI shows lesions in skeleton [70, 72–74]. Most MRI data regarding frequency of
over 50 % of multiple myeloma patients who have a negative MRI patterns in myeloma patients are derived from studies
WBXR [69]. In patients with multiple myeloma, MRI of the of the spine. It is not surprising that more recent work with
Fig. 5.34 Multiple myeloma, variegated MRI pattern.

Sagittal T1-weighted image of the lumbosacral spine of a 70-year-old man
Fig. 5.33 Multiple myeloma, focal MRI pattern. with multiple myeloma shows innumerable, tiny hypointense bone marrow
Sagittal T1-weighted image of the lumbosacral spine of a 67-year-old lesions. Normal-appearing marrow can be seen on the background
woman with multiple myeloma shows well-defined, hypointense
lesions on a background of apparently normal marrow (arrows)
equal to or lower than that of muscle or nondegenerated
whole-body MRI (WBMRI) identifies a higher number of intervertebral discs, possibly depending on the degree of
abnormal patterns in patients with multiple myeloma and bone marrow plasmacytosis. A lesion must be at least 5 mm
MGUS; 23 % of patients with MGUS, for example, were for a confident diagnosis to be made. The number of the
found to have a focal pattern on WBMRI in one study [75]. lesions varies from one to multiple. The presence of innu-
merable foci throughout the marrow defines the variegated
pattern (Fig. 5.34). Both the focal and the variegated pattern
Key Points are distinguished from the diffuse pattern by the persistence
• The focal pattern is the most frequent MRI pattern of normal-appearing, high-signal-intensity marrow.
in symptomatic multiple myeloma
• In symptomatic multiple myeloma, MRI is abnor-
Key Point
mal in 80–100 % of patients
• In asymptomatic multiple myeloma, MRI is abnor- • On T1-weighted images, focal myelomatous lesions
mal in 30–50 % of patients are well-defined and hypointense to normal-appear-
ing marrow
As stated throughout this volume, MRI bone marrow pat-

terns are defined on T1-weighted images. The focal pattern Focal bone marrow lesions are easy to recognize on
of multiple myeloma consists of lesions which are well- T1-weighted images of the peripheral skeleton, where fat
defined and hypointense to intervening, normal-appearing predominates in the adult (Fig. 5.35). In the spine, even small
marrow (Fig. 5.33). The signal intensity of the lesions is lesions can be clearly seen if a pattern 4 of normal spinal
a b
Fig. 5.35 Increased T1 conspicuity of focal lesions: background of readily seen against a background of fatty marrow. (b) On correspond-
fatty marrow, peripheral skeleton. ing STIR image, focal myelomatous lesions become hyperintense to
(a) Coronal T1-weighted image of the femora of an 80-year-old woman suppressed fatty marrow
with multiple myeloma shows multiple, small hypointense focal lesions
marrow (homogeneous, fatty spine) is present (Fig. 5.36).

However, in patients with heterogeneous spinal marrow due
to either a mosaic pattern of red to yellow marrow conver-
sion (pattern 3 of normal spinal marrow) or to heterogeneous
red marrow reconversion (e.g., in the setting of chronic ane-
mia), it is not easy to assess with T1-weighted images alone
whether hypointense foci are due to red marrow rests or to a
focal/variegated multiple myeloma pattern. Transient red
marrow hyperplasia occurs in the first few months after che-
motherapy, particularly with the adjunct use of hematopoi-
etic growth factors; it most often manifests in a diffuse
manner, but focal patterns of reconversion are occasionally
seen. For all the above reasons, it is important to remember
that careful review of all pulse sequences besides T1-weighted
images is mandatory to avoid misdiagnosis.
Key Points
• Low-signal-intensity lesions on T1-weighted

images may be due to normal red marrow
• Other sequences need to be reviewed to confirm the
diagnosis of a focal myelomatous pattern
On STIR or T2-weighted images with fat saturation, focal

myelomatous lesions become hyperintense to uninvolved
marrow and adjacent muscles, unlike red marrow rests
which, most often, remain isointense to muscle (Fig. 5.37). Fig. 5.36 Increased T1 conspicuity of focal lesions: background of
fatty marrow, spine.
Occasionally, foci of hematopoietic marrow may become
hyperintense to muscle on STIR images; in such cases, woman with multiple myeloma shows a small hypointense focal lesion of
chemical-shift imaging may be useful to support the T12 (arrow) against a background of predominantly fatty spinal marrow
a b c d
Fig. 5.37 Decreased T1 conspicuity of focal lesions due to mosaic lesions (arrows) are discerned on a background of suppressed marrow
pattern of background marrow: value of STIR. signal. For comparison, images (c, d) of an 82-year-old man with a
On the T1-weighted image of the lumbosacral spine of a 63-year-old mosaic pattern of bone marrow due to anemia and not to malignant
woman with multiple myeloma (a), a mosaic bone marrow pattern is deposits are shown. Although, the T1-weighted image (c) is quite com-
noted; the presence of focal lesions cannot be readily assessed. On the parable to (a), on the corresponding STIR image (d), there are no focal
corresponding STIR image (b), hyperintense, focal myelomatous areas of hyperintensity
diagnosis of red marrow rests (Fig. 5.38). A more than 20 % to show no enhancement. A more than 40 % increase in sig-
signal loss on out-of-phase compared to in-phase images is nal intensity on post-contrast images has been proposed as
diagnostic of red marrow; focal myelomatous lesions show an indicator of malignant infiltration of the bone marrow
no or less than 20 % signal intensity loss, or they may even [37] (Fig. 5.42). Enhanced images should always be com-
show an increase in signal intensity, on out-of-phase images pared with pre-contrast ones, since a presumably enhancing
[36] (Fig. 5.39). focus may actually be a T1 hyperintense lesion, such as a
hemangioma. The addition of fat suppression to the contrast-
enhanced T1-weighted sequence increases lesion conspicu-
Key Points
ity (Fig. 5.43). Contrast administration should be deferred in
• On STIR images, focal myelomatous lesions are the setting of severe chronic renal function impairment
hyperintense to muscle (GFR < 30 ml/min/1.73 m2) or acute renal injury, because of
• On out-of-phase images, focal myelomatous lesions the risk of systemic nephrogenic fibrosis [76]. Plasma cell
show an increase or a less than 20 % decrease in infiltrates may break through the bony cortex and manifest
signal intensity compared to in-phase images with an extraosseous mass (Fig. 5.44). T1-weighted images
provide good contrast between the tumor and the high-
signal-intensity epidural or foraminal fat and are, therefore,
Some investigators consider contrast-enhanced MR quite suited for the study of tumor in the spinal canal
images optional for the initial evaluation of multiple (Fig. 5.44). Contrast-enhanced images, however, occasion-
myeloma. However, we believe that they are helpful in the ally define more clearly the extent of an extraosseous mass
differentiation of focal or variegated myeloma patterns from and may help separate it from normal structures which on
normal mosaic bone marrow patterns. Careful comparison of T1-weighted images have similar signal intensities (epidural
pre- and post-contrast T1-weighted images will show no or vascular plexus, perineural cysts, muscles).
very mild enhancement of normal red marrow (Fig. 5.40); Angiogenesis is an index of tumor growth, and in myeloma
malignant lesions will show moderate to marked enhance- patients it marks the transition from MGUS to multiple
ment in the vast majority of cases (Fig. 5.41). In untreated myeloma (angiogenic switch theory) [77]; an increased total
patients, it is extremely rare for a myelomatous focal lesion vascular area and microvessel density found on bone marrow
a b
Fig. 5.38 T2 hyperintense red marrow foci: value of chemical-shift foci are seen on the T1-weighted image (a). Most of them become hyper-
imaging. intense on the T2 fat-suppressed image (b). Marked signal dropout on the
Axial images of the pelvis of a 41-year-old multiple myeloma patient out-of-phase image (c), and lack of significant enhancement on post-
with chemotherapy-related red marrow hyperplasia. Several hypointense contrast images (not shown) established the diagnosis of red marrow rests
a b c
Fig. 5.39 Focal multiple myeloma pattern: chemical-shift imaging. signal intensity on the out-of-phase image (solid arrows in c) compared
Sagittal T1-weighted (a), in-phase (b), and out-of-phase (c) images of to the in-phase image. Normal marrow exhibits a marked drop of signal
the lumbosacral spine of a 66-year-old man with multiple myeloma. intensity on the out-of-phase image. Note that a Modic II degenerative
Focal myelomatous lesions at the left pedicle of L1 and L3 are hypoin- end-plate change at L4 (open arrow in a), composed mostly of fat, does
tense on the T1-weighted image (solid arrows in a) and show increased not exhibit signal dropout on the out-of-phase image (open arrow in c)
specimens of patients with myeloma compared to those with marrow malignancies derived from DCE-MRI studies differ
MGUS support the theory of the angiogenic switch [78, 79]. significantly from those of normal marrow, and they are char-
Dynamic contrast-enhanced MRI (DCE-MRI) is a functional acterized by an early, steep, and high rise which reflects the
technique which provides an indirect but noninvasive means pronounced neovascularity of the tumor and a steep washout
of studying changes in tissue microcirculation; in contrast to which results from the presence of a small interstitial compart-
bone marrow biopsy, it provides information on a large vol- ment [80]. DCE-MRI studies in patients with plasma cell dys-
ume of bone marrow. Time-intensity curves (TIC) of bone crasias have shown a gradual increase in microcirculation
Fig. 5.40 Normal marrow,

mosaic pattern: absence of a b c
significant contrast
enhancement.
a 44-year-old healthy woman
shows multiple, ill-defined
hypointense foci of red marrow
against a background of fatty
marrow. The appearance of the
bone marrow does not change
on the contrast-enhanced image
(b), and there are no foci of
enhancement on the contrast-
enhanced image with fat
suppression (c)
a b
Fig. 5.41 Multiple myeloma, variegated pattern:

marked contrast enhancement.
Sagittal T1-weighted image (a) and contrast-enhanced
T1-weighted image with fat suppression (b) of the
lumbosacral spine of a 54-year-old man with multiple
myeloma. An heterogeneous appearance of the spine is
noted on the T1-weighted image suggesting the presence
of bone marrow involvement. On the contrast-enhanced
image, innumerable, small, strongly enhancing foci are
seen throughout the spine confirming the diagnosis of a
variegated pattern of multiple myeloma
from MGUS to symptomatic myeloma, in accordance with the Annual Meeting, December 2014, San Francisco, U.S.A.)
angiogenic switch theory [81, 82] (Fig. 5.45). Moreover, a sig- Identification of myeloma patients with increased angiogene-
nificant correlation has been found between perfusion param- sis by means of DCE-MRI may, therefore, have important
eters derived from TIC curves and levels of angiogenic factors prognostic and therapeutic implications in the future.
(angiopoietin-2 and angiopoietin-1/angiopoietin-2 ratio) in Diffusion-weighted imaging (DWI) provides additive
the serum of patients with newly diagnosed multiple myeloma information to morphologic imaging. Apparent diffusion
(data presented at the American Society of Hematology coefficient (ADC) values of normal bone marrow are very
Fig. 5.42 Multiple myeloma,

focal pattern: contrast
a b c
enhancement.
Sagittal T1-weighted image (a),
contrast-enhanced T1-weighted
image (b), and contrast-
enhanced T1-weighted image
with fat suppression (c) of the
66-year-old man with a focal
The focal lesions (arrows in a)
show typical, moderate to
marked enhancement on the
contrast-enhanced images
(contrast uptake varies between
57 to over 100 %)
a b c

focal pattern: value of
contrast-enhanced images
with fat suppression.
Sagittal T1-weighted image (a),
image (b), and contrast-
enhanced T1-weighted image
with fat suppression (c) of the
63-year-old woman with a focal
The lesions are hardly seen on
the T1-weighted image. They
enhance and become
imperceptible from normal
marrow on the enhanced
T1-weighted image, whereas
they are optimally visualized on
the fat-suppressed contrast-
enhanced image (arrows)

epidural extension of tumor: a b
value of T1-weighted images.
Sagittal T1-weighted image of
the lumbosacral spine (a) and
axial T1-weighted image at the
level of the sacrum (b) of a
69-year-old woman with
multiple myeloma. Note sacral
mass with extraosseous
extension to the right sacral
foramen, easily recognized by
obliteration of the high signal
foraminal fat (white arrow).
Compare with normal high
signal of left foraminal fat
(black arrows)
low (approximately 0.2–0.5 × 10−3 mm2/s), due mainly to the

abundance of fat cells and the resultant very low diffusivity
of water protons within the bone marrow. On the other hand,
myelomatous lesions which infiltrate and destroy the marrow
appear as high-intensity lesions on diffusion-weighted
images and have high ADC values (Fig. 5.46). Mean ADC
values of 0.875 ± 0.187 × 10−3 mm2/s have been reported for
focal myelomatous lesions in a small sample study [83].
According to our experience the upper limit of the range is
higher with mean ADC values commonly exceeding
1.0 × 10−3 mm2/s (data presented at the American Society of
Hematology Annual Meeting, December 2014, San
Francisco, U.S.A.) (Fig. 5.47).
Magnetic Resonance Imaging in Multiple

Myeloma: Prognostic Value
Fig. 5.45 Asymptomatic versus symptomatic multiple myeloma: Cytogenetic abnormalities and elevated serum levels of β2-
DCE-MRI, time-intensity curves. microglobulin and LDH, together with advanced age, are
Fitted time-intensity curves of the bone marrow of a patient with
important adverse prognostic factors for patients with mul-
asymptomatic myeloma (yellow curve) and a patient with symptomatic
myeloma (red curve). TIC of patient with symptomatic disease shows tiple myeloma [69]. In patients with symptomatic disease, an
early, steep rise, high peak, and pronounced contrast washout abnormal MRI study of the bone marrow is an independent
Fig. 5.46 Multiple myeloma, focal pattern: diffusion-weighted old man with multiple myeloma (same patient as in Fig. 5.42) and
imaging. several focal lesions. ADC values of the lesion at the spinous process
Diffusion-weighted images with b-values 0, 150, 250, 500, and of T12 and the vertebral body of L4 were 1.106 × 10−3 mm2/s and
750 s/mm2 (a) and ADC map (b) of the lumbosacral spine of a 66-year- 1.197 × 10−3 mm2/s, respectively (arrows)
prognostic factor, associated with increased tumor burden

and shorter survival [37, 70, 71, 84]. In patients with a focal
MRI pattern, the presence of more than seven focal lesions is
an adverse feature which, when associated with high-risk Key Points
cytogenetic abnormalities, defines patients with shorter • An abnormal MRI of the bone marrow is an inde-
5-year survival times (37 % versus 76 % for those without pendent adverse prognostic factor for patients with
either of the two adverse prognostic features) [69]. A diffuse symptomatic multiple myeloma
MRI pattern is associated with poorer survival; if combined • A diffuse MRI pattern is associated with poorer sur-
with ISS stage III and high-risk cytogenetics, it identifies a vival particularly if combined with ISS stage III and
subgroup of patients with very dismal prognosis who may high-risk cytogenetics
benefit from treatment with novel agents [85].
Fig. 5.47 Multiple myeloma, focal pattern: diffusion-weighted old woman with a focal pattern of multiple myeloma (same patient as in
imaging. Fig. 5.33). Multiple hyperintense lesions are seen on the diffusion-
Diffusion-weighted images with b-values 0, 150, 250, 500, and weighted images. The ADC value of the lesion at L2 (arrow) is
750 s/mm2 (a) and ADC map (b) of the lumbosacral spine of a 67-year- 1.533 × 10−3 mm2/s
In a study of asymptomatic myeloma with WBMRI, the prognostic factor for progression to symptomatic disease
presence of a focal lesion pattern and, particularly, the [86]. Patients with asymptomatic myeloma and an abnor-
presence of more than one focal lesion was the strongest mal spinal MRI have also been found to have a shorter
a b
Fig. 5.48 Multiple myeloma, sclerotic foci, POEMS. focal lesions (signal-void focal pattern) (arrows) on a background of dif-
Coronal (a) and axial (b) T1-weighted images of the pelvis of a 47-year-old fusely hypointense bone marrow due to anemia. Radiograph of the left
woman with multiple myeloma and POEMS show markedly hypointense femur (c) confirms the presence of osteosclerotic lesions (arrows)
time to disease progression compared to those with a nor- that an abnormal MRI is an independent prognostic factor
mal spinal MRI exam [87]. A recent study found that MRI for progression to symptomatic disease requiring treat-
limited to the spine is able to identify patients with asymp- ment [75].
tomatic multiple myeloma at risk for progression to symp-
tomatic disease. In this study, patients with more than one Sclerotic Myeloma
focal lesion on spinal MRI had a probability of progres- Sclerotic focal lesions occur in about 3 % of myeloma
sion of about 70 % within 2 years from diagnosis, whereas patients (signal-void focal pattern). They may occur in asso-
the rate was 11 % for those with no focal lesions [88]. ciation with POEMS (polyneuropathy, organomegaly, endo-
Patients with MGUS and an abnormal MRI of the bone crinopathy, monoclonal protein, and skin lesions) or
marrow progress earlier to multiple myeloma compared to Schnitzler syndrome (bone pain, chronic non-pruritic urti-
patients with MGUS and a normal MRI [73]. Some inves- caria, and monoclonal protein). Skeletal radiographs and CT
tigators even consider patients with MGUS and an abnor- show sclerotic, sometimes spiculated, lesions or mixed scle-
mal MRI to belong in the asymptomatic myeloma group rotic/lytic focal lesions. Lesions are hypointense on both T1-
[89]. WBMRI studies in patients with MGUS have shown and T2-weighted MR images [90, 91] (Fig. 5.48).
5.4 Lymphoma 91
a
Key Point
• Sclerotic lesions are rare in multiple myeloma, and

they usually occur in association with POEMS or
Schnitzler syndrome
Solitary Bone Plasmacytoma (SBP)

The most frequent location of SBP is the spine; the verte-
bral body is more often involved than the posterolateral
elements. SBP preferentially destroys the cancellous bone,
sparing the cortex which may even become sclerotic. This
slow-growing, expansile tumor causes compensatory
thickening of osseous trabeculae in an attempt to support
the hollow vertebra; the thickened trabeculae project from
the cortex inwards resembling the sulci of the brain, an b
image which has been likened to a “mini brain” (Fig. 5.49).
The mini brain sign may also be observed in plasmacyto-
mas located at other sites of the skeleton [92]. SBP is
hypointense and hyperintense on T1- and T2-weighted
images, respectively, and shows intense contrast enhance-
ment (Fig. 5.50). The mini brain sign is not observed with
bone metastases or malignant primary bone tumors and is
almost pathognomonic of SBP, possibly reflecting its less
aggressive nature [93]. MRI of the bone marrow may iden-
tify additional focal lesions in about a third of patients
with the clinical diagnosis of SBP. These patients seem to
have a shorter time to progression to multiple myeloma
compared to those with no additional lesions on MR
images [58, 94, 95].
Key Points
c
• MRI of the bone marrow may show additional
lesions in 30 % of patients with a clinical diagnosis
of SBP
• The MRI mini brain sign is characteristic of SBP
5.4 Lymphoma
5.4.1 Clinical Background
Lymphomas are broadly divided into two major categories,

Hodgkin lymphoma (HL) with a crude incidence rate of
3/100,000 and non-Hodgkin lymphomas (NHL), which are
approximately eight times more common [96]. They are a Fig. 5.49 Solitary bone plasmacytoma, mini brain sign.
heterogeneous group of disorders with many distinct Axial T1-weighted (a) and T2-weighted (b) images of a 52-year-old
subtypes, which are classified according to the 2008 World woman with solitary bone plasmacytoma of L4 show an expansile
Health Organization scheme. Lymphoma is a tissue-based lesion with abnormal signal intensity at the body and right pedicle.
There are multiple, peripheral linear hypointensities resembling the
diagnosis, and in most types, excisional lymph node sulci of the brain. Corresponding CT image (c) shows that the linear
biopsy is the standard of care for accurate histopathological hypointensities represent thickened cortical struts
classification [97]. Following histologic diagnosis, the next

a
step is clinical staging which is essential for optimal treat-
ment planning. Clinical staging of most types of lymphoma
is achieved by physical examination, imaging (CT or FDG-
PET/CT), and bone marrow biopsy. Additional procedures
(MRI of the CNS, lumbar puncture, endoscopy, etc.) are
required for the staging of a few specific subtypes. Staging
of most types of lymphoma is based on the Ann Arbor clas-
sification, which takes into account the number and location
of involved sites and the types of lesions (nodal and extrano-
dal) [98, 99]. The four-stage Ann Arbor classification was
originally developed for HL alone. Its use was later extended
to NHL as well, although some specific NHL types (e.g.,
gastric MALT lymphoma, primary CNS lymphoma, etc.)
b cannot be staged using the Ann Arbor system. Assessing
bone marrow status at initial presentation is of great impor-
tance because marrow involvement indicates the presence of
the highest Ann Arbor stage (stage IV) and this may have an
impact on prognosis and treatment. Bone marrow involve-
ment is found in 4–14 % of patients with HL and in 20–40 %
of NHL patients [100, 101]. It is especially common in
indolent (low grade) B-cell NHLs.
Blind trephine bone marrow biopsy (BMB) of the poste-
rior iliac crest has been for many years the standard method
for assessing bone marrow status in lymphoma. BMB is an
invasive procedure, which may be associated with anxiety
and pain, and carries a very small risk of complications
(mainly hemorrhage) [102]. More importantly, BMB suffers
c from sampling errors, since it only examines a very small
volume of the bone marrow blindly. Therefore, focal lym-
phomatous marrow involvement may be missed by
BMB. This is highlighted by multiple studies which have
demonstrated that 10–60 % of patients with unilateral posi-
tive BMB have a negative biopsy of the contralateral iliac
crest [101]. Regarding HL, the 1989 Cotswolds report on
the evaluation and staging of patients with Hodgkin disease
recommends to restrict BMB to patients with stage III and
IV disease (as determined by CT) as well as to stage II
patients with adverse factors and only if a positive biopsy
finding would affect treatment [98]. This is in accordance
with the generally low incidence of bone marrow involve-
Fig. 5.50 Solitary bone plasmacytoma, MRI appearance. ment in patients with HL, particularly in those otherwise
Axial T1-weighted (a), STIR (b), and fat-suppressed T1 contrast- (i.e., based on CT findings) considered to have early-stage
enhanced (c) images of a 43-year-old woman with solitary bone plasma- disease [100, 103, 104]. Other guidelines however, such as
cytoma involving the right iliac bone. The expansile tumor is hypointense
those issued in 2011 by the European Society for Medical
on T1, hyperintense on STIR, and enhances strongly. Peripheral, linear
low signal intensities represent thickened cortical struts Oncology still recommend the use of BMB in all newly
5.4 Lymphoma 93
diagnosed patients with HL [105]. BMB is still standard in 96.9 and 99.7 %, respectively). Moreover, the weighted sum-
NHL, in which there is a risk of bone marrow involvement mary proportion of FDG-PET/CT-negative patients with a
with a histology discordant from the diagnostic lymph node positive BMB among all cases included in the reviewed stud-
histology [106]. ies was 1.1 %. Based on these data the authors suggested that
FDG-PET/CT may be an appropriate method to replace
BMB in newly diagnosed Hodgkin lymphoma (Fig. 5.51).
5.4.2 Imaging Data are less clear regarding diffuse large B-cell lym-
phoma (DLBCL), the most common type of high-grade
Imaging plays a central role in initial lymphoma staging. CT NHL. Results from a recent study suggest that FDG-PET/CT
remained the standard modality for this purpose for many has a high level of accuracy for identifying bone marrow
years, and it is still widely used owing to its extensive avail- involvement in DLBCL [110]. On the other hand, bone mar-
ability, easiness to perform, and relatively low cost [97]. row involvement in DLBCL may be discordant (small cell)
Disadvantages of CT as a staging modality include its inabil- compared to the diagnostic lymph node histology, a phenom-
ity to detect pathologic changes in normal-sized structures, enon which may have prognostic significance and which
such as involvement of normal-sized lymph nodes or diffuse obviously cannot be demonstrated by FDG-PET/CT.
involvement of a normal-sized spleen. Moreover, it cannot Although bone marrow involvement is much more preva-
easily diagnose lesions that have poor contrast with sur- lent in indolent lymphomas compared with HL and DLBCL,
rounding tissue, as may be the case with focal lymphoma- in many cases FDG-PET/CT is falsely negative. In indolent
tous lesions in parenchymal organs like the liver or spleen lymphoma, marrow infiltration is often diffuse and may be
[97]. Finally CT has a very low detection rate for lymphoma- difficult to detect against background marrow metabolic
tous bone marrow involvement. FDG-PET/CT has emerged activity [111]. Low FDG avidity of some histologic types
as a very sensitive functional imaging modality for accurate may be another cause. In any case, FDG-PET/CT is not cur-
pretreatment staging, interim evaluation, and posttreatment rently recommended for the routine baseline staging of indo-
final response assessment of lymphoma patients. FDG-PET lent lymphomas, and BMB is still the gold standard for bone
is more sensitive than CT at baseline staging, because it can marrow evaluation.
diagnose disease in normal-sized lymph nodes and has a
higher detection rate for extranodal sites, including bone
marrow. 5.4.3 Magnetic Resonance Imaging
Over the years, a number of studies have investigated
whether the use of FDG-PET/CT for initial staging of lym- MRI is a sensitive method for the diagnosis of bone marrow
phoma may obviate the need for BMB [107, 108]. Most of involvement in lymphoma, and it can be used to assess bone
these have focused on patients with HL. In the largest study, marrow status at baseline staging. On MRI, lymphoma of the
454 HL patients were staged by both FDG-PET/CT and marrow may present with a focal or a diffuse pattern. A focal
BMB. FDG-PET/CT identified bone marrow lesions in 18 % pattern is frequently observed in HL and high-grade NHL
of patients, whereas the BMB was positive in only 6 %. No [112] (Fig. 5.52). The appearance is nonspecific: focal
patient with PET/CT-assessed stage I or II disease had a pos- lesions are hypointense on T1-weighted images, hyperin-
itive BMB. More importantly, BMB upstaged only five tense on STIR/T2-weighted fat-suppressed images and high
patients, and this was from stage III to stage IV with no mod- b-value DWI, and they display contrast enhancement. In
ification in treatment strategy. In other words, BMBs were indolent (low grade) NHLs, the pattern of marrow involve-
performed in 454 HL patients of this study without a single ment is frequently diffuse [112]. The abnormal marrow is
therapeutic consequence [107]. These results were confirmed diffusely hypointense on T1-weighted imaging (with signal
in a 2014 meta-analysis of nine studies comprising 955 intensity lower than that of nondegenerated intervertebral
patients with newly diagnosed Hodgkin lymphoma [109]. discs and muscle) and hyperintense on STIR/T2-weighted
This systematic review showed that FDG-PET/CT has very fat-suppressed images. Diffuse enhancement is seen on post-
high sensitivity and specificity in detecting bone marrow contrast T1-weighted images, and no signal loss is noted on
involvement in newly diagnosed HL (pooled estimates of opposed-phase imaging.
Fig. 5.51 Hodgkin

lymphoma, PET-CT. a b
PET-CT images (a, b) of a
newly diagnosed Hodgkin
lymphoma show multiple
focal hypermetabolic bone
marrow lesions in the spine
and left iliac bone (Images
courtesy of Vassilios
Prassopoulos M.D., Hygeia
Hospital, Athens, Greece)
a b c
Fig. 5.52 Lymphoma, bone

marrow involvement: focal
pattern.
(a) of the lumbar spine of a
60-year-old man with stage IV
Hodgkin lymphoma shows
multiple hypointense focal bone
marrow lesions. The lesions are
hyperintense on the STIR image
(b) and enhance on the post-
contrast T1-weighted image with
fat suppression (c)
5.4 Lymphoma 95
A systematic review of 11 studies-including two using and/or follow-up MRI and FDG-PET) determined that
Whole-Body MRI (WBMRI)- investigated the sensitivity of seven out of eight cases that were positive on both WBMRI
MRI for the detection of bone marrow involvement in and FDG-PET and negative on BMB were true positives for
patients with lymphoma. Eight studies showed sensitivities bone marrow involvement, with one case remaining
ranging from 89 to 100 %. In the three studies with lower unresolved.
sensitivities (50, 60, and 67 %), MRI was performed at Results of a recent study have shown that WBMRI find-
lower magnetic fields (1 and 0.5 T), and/or the imaging pro- ings may have prognostic implications in patients with newly
tocol was limited to a T1-weighted sequence only [101]. diagnosed DLBCL [116]. Patients with marrow involvement
The development of WBMRI technology somewhat renewed on WBMRI had poorer progression-free survival and overall
the interest in MRI as a means to evaluate bone marrow survival compared with WBMRI-negative patients. It must
involvement at initial staging of lymphoma, and a number be noted, however, that the detection of bone marrow lesions
of studies investigating this issue have appeared [113–116]. by WBMRI did not have impact on treatment decisions in
The most frequently used sequences in WBMRI for lym- this study, because all patients positive for marrow involve-
phoma staging are T1-weighted and STIR. A prospective ment on WBMRI had already been classified as stage III or
study investigating the role of WBMRI for diagnosing bone IV. Interestingly the prognostic significance of MRI had
marrow involvement in lymphoma found that DWI offered been demonstrated in an older study of 56 patients with dif-
no additional value over conventional sequences [114]. The ferent histologic types of lymphoma, who had undergone
largest prospective study comparing WBMRI with FDG- BMB of the posterior iliac crest and MRI of the femur at the
PET/CT for the detection of bone marrow involvement in time of diagnosis. Patients with a positive femoral MRI and
lymphoma concluded that there was no significant differ- a negative BMB had a significantly shorter overall survival
ence in sensitivity between the two methods [115]. Based on than did those with a negative MRI and negative BMB [117].
these results the authors concluded that neither WBMRI nor Further prospective research is needed to better define the
FDG-PET has high-enough sensitivity to replace BMB, and prognostic implications of bone marrow MRI findings in
they proposed using them as complementary, rather than lymphoma and their potential additional value to well-estab-
alternatives, to biopsy. It must be noted though that their lished clinical prognostic models.
cohort included patients with many different types of lym- Apart from its role in baseline lymphoma staging, bone
phoma, both aggressive and indolent. FDG-PET showed marrow MRI may be used as a problem-solving tool in equiv-
significantly higher sensitivity in aggressive lymphoma than ocal cases (e.g., when FDG-PET is inconclusive and treatment
in indolent lymphoma (83.3 % versus 12.5 %). Interestingly, depends on bone marrow findings). It is also the imaging
WBMRI showed comparable differences in sensitivity modality of choice to evaluate possible spinal cord compres-
between aggressive and indolent lymphoma types (88.9 % sion from an extraosseous soft-tissue lymphomatous mass.
versus 23.5 %). An explanation for this observation may be Soft-tissue masses accompanying bone marrow infiltration by
that in their image analysis the authors considered only lymphoma often have a characteristic appearance with no
focal, and not diffuse, abnormal marrow signal as positive obvious destruction of the cortical bone, reflecting the perme-
for lymphomatous involvement, whereas it has been previ- ative nature of the tumor (Fig. 5.53). This appearance, with
ously reported that a diffuse MRI pattern is frequently tumor on either side of a preserved bony cortex, has been
observed in indolent non-Hodgkin lymphomas [112]. Both termed the wrap-around sign [39, 118]. Recognition of this
WBMRI and FDG-PET suggested bone marrow involve- sign on spinal MRI images of patients who present with neu-
ment in several cases in which BMB was negative. Post rological symptoms and no known history of malignancy may
hoc analysis (using a combination of pretreatment CT direct work-up towards a possible diagnosis of lymphoma.
a b
c d
Fig. 5.53 Lymphoma, focal pattern of marrow involvement with images before (c) and after (d) contrast administration, at the level of
extraosseous soft-tissue mass. L4, show the draped curtain sign caused by the epidural mass (arrows).
Sagittal T1-weighted image (a) of the lumbosacral spine of a 60-year- On all images note that the soft-tissue masses are associated with pre-
old woman with non-Hodgkin lymphoma shows three focal hypoin- served bony architecture and no overt cortical destruction (wrap-around
tense bone marrow lesions (solid arrows) at L3, L4, and L5 with sign). Also note post-laminectomy changes at L4 with associated soft-
associated anterior epidural soft-tissue masses (open arrows). On the tissue edema and extensive lymphomatous infiltration of the paraspinal
post-contrast sagittal T1-weighted image with fat suppression (b), bone muscles
marrow lesions and epidural masses enhance. Axial T1-weighted
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MRI of the Abnormal Bone Marrow:
Diffuse Pattern 6
6.1 Metastases: Diffuse Pattern become hypointense to the enhancing marrow; a more than
40 % increase in signal intensity on post-contrast images is
A diffuse MRI pattern is not common with bone metasta- consistent with metastatic marrow. On quantitative DWI,
ses. The abnormal bone marrow is hypo- or isointense to the ADC values of diffusely infiltrated marrow are higher than
intervertebral discs or to muscle on T1-weighted images, those of normal red marrow. Although results vary among
quite similar to diffuse bone marrow patterns of other eti- studies depending on pulse sequence type and b-values used,
ologies (Fig. 6.1). Rarely, widespread osteoblastic metastatic a threshold of 0.655 × 10−3 mm2/s has been proposed to sepa-
disease may present as very hypointense (signal void) dif- rate normal from malignant marrow with sensitivity and
fuse pattern (Fig. 6.2). The signal intensity of the abnormal specificity values of 90 % and 93 %, respectively [1].
marrow in diffuse metastatic disease is more often hetero-
geneous. If the metastases are limited to the bone marrow
with little or no trabecular destruction, skeletal scintigraphy
and CT may be negative. Bone metastases from small round
cell tumors such as neuroblastoma, Ewing’s sarcoma, rhab-
domyosarcoma, small cell lung cancer and carcinoid are
the ones most often associated with a diffuse MRI pattern
(Fig. 6.3). This is attributed to the permeative nature of these
tumors which may diffusely infiltrate the marrow without
significant alteration of the bony architecture.
A diffuse pattern of metastatic bone disease appears
hypointense on T1-weighted images and hyperintense on
STIR and shows contrast enhancement (Fig. 6.4). Diffuse
metastatic disease must be differentiated from hyperplastic
red marrow, as both may appear isointense to the interverte-
bral discs on T1-weighted images. Marrow that is hypoin-
tense to disc (hyperintense disc sign) strongly favors
metastatic disease over red marrow reconversion (Fig. 6.5).
Signal heterogeneity on T1-weighted images is more charac-
teristic of metastatic disease. Other sequences must be care-
fully reviewed to reach a confident diagnosis. On STIR, the
signal intensity of malignant marrow increases to varying
degrees depending on the percentage of bone marrow malig-
nant infiltration. It must be noted that, in such cases, as there
is no normal marrow for comparison, hyperintensity on
STIR images may be hard to appreciate. On chemical-shift
out-of-phase images, a more than 20 % signal drop is strongly
Fig. 6.1 Hypointense diffuse pattern, osteolytic metastases.
suggestive of hyperplastic red marrow. On contrast-enhanced
images of diffuse marrow metastatic disease, the relationship woman with breast cancer and lytic bone metastases shows diffusely
between marrow signal and disc signal reverts, and the discs hypointense marrow with signal heterogeneity

102 6 MRI of the Abnormal Bone Marrow: Diffuse Pattern
Fig. 6.2 Signal void diffuse pattern, osteoblastic metastases.

Sagittal T1-weighted image of the lumbosacral spine of a 60-year-old man with prostate
cancer shows signal void diffuse pattern due to very low-signal osteoblastic metastases com-
pletely replacing the bone marrow
a b
Fig. 6.3 Hypointense diffuse pattern,

metastatic small round cell tumors.
Sagittal T1-weighted images of the spine
of a 38-year-old man with small cell lung
cancer (a) and a 22-year-old woman with
neuroblastoma (b) show diffuse low signal
intensity of bone marrow due to metastases.
Hyperintense focus at L3 in (b) represents
small hemangioma, spared by the diffuse
malignant process
6.1 Metastases: Diffuse Pattern 103
a b c d
e f g
Fig. 6.4 Hypointense diffuse pattern, metastatic disease. the out-of-phase image. On the post-contrast image, the malignant mar-
Sagittal T1-weighted (a), STIR (b), out-of-phase (c), post-contrast row enhances and becomes hyperintense to the discs. On the high
T1-weighted (d), diffusion-weighted with b-value 0 (e), and b-value b-value diffusion-weighted image, metastatic disease manifests with
750 (f) images and ADC map (g) of the lumbosacral spine of a 49-year- diffuse heterogeneous hyperintense signal. Mean ADC value of the five
old woman with breast cancer and diffuse bone metastases. Abnormal lumbar vertebrae is 0.839 × 10−3 mm2/s. Also noted on the contrast-
marrow is diffusely hypointense (lower signal compared to interverte- enhanced image is meningeal enhancement in keeping with leptomen-
bral discs) with heterogeneity on the T1-weighted image and hyperin- ingeal carcinomatosis
tense with heterogeneity on STIR. There is no loss of signal intensity on
Fig. 6.5 Hypointense diffuse malignant

a b
pattern, value of hyperintense disc sign.
thoracic spine of a 65-year-old man with
prostate cancer shows two very
hypointense focal osteoblastic metastases
(arrows). The rest of the marrow shows
diffuse hypointensity with lower signal
compared to the intervertebral discs
(hyperintense disc sign) due to osteolytic
metastases. On STIR (b), the osteolytic
metastases become markedly hyperintense
while the osteoblastic metastases (arrows)
show a mild increase in signal intensity
The diffuse pattern of metastatic bone disease is diag- versus 51 months and 52 months for patients with focal and
nosed on MR images of the axial skeleton. In patients with variegated myeloma patterns, respectively [4]. More recently,
advanced bone metastatic disease, red marrow reconversion it was shown that high-risk cytogenetic abnormalities, a most
may occur in the peripheral skeleton, in response to an adverse prognostic factor for this disease, are more frequent
increased need for hematopoiesis; red marrow may then be in myeloma patients with a diffuse MRI pattern (50 %) than
visualized in the periphery, at sites occupied by fatty marrow in those with focal or variegated patterns (31 %) [5].
in the healthy adult. In such cases, the diffuse pattern of bone Furthermore, it has been shown that 80 % of myeloma
metastases may eventually extend to involve the peripheral patients with a diffuse MRI pattern have moderate or high-
skeleton. Metastatic involvement of the epiphyses and grade angiogenesis on bone marrow biopsy versus 66 % of
apophyses is, however, very rare and when present, indicates those with a normal and 41 % of patients with a focal MRI
extreme tumor burden (Fig. 6.6). pattern [6]. Diffuse marrow involvement was found to be an
adverse prognostic factor, regardless of ISS stage or plasma
cell infiltration, even in patients treated with novel antiangio-
6.2 Multiple Myeloma: Diffuse Pattern genic agents.
A diffuse MRI pattern of multiple myeloma is less frequent

than a focal pattern, according to most studies. It is associ-
Key Point
ated with increased tumor burden and a poorer prognosis [2].
Myeloma patients with a diffuse MRI pattern of involvement • A diffuse MRI pattern of involvement in multiple
have higher ISS stage, more severe anemia and hypercalce- myeloma patients is associated with higher tumor
mia, and significantly higher values of β2-microglobulin and burden, increased angiogenesis, high-risk cytoge-
bone marrow plasmacytosis [3, 4]. Median survival for netics, and shorter median survival
patients with diffuse marrow involvement is only 24 months
6.2 Multiple Myeloma: Diffuse Pattern 105
a b
Fig. 6.6 Diffuse malignant pattern, peripheral skeleton involvement.

Coronal T1-weighted images of the hips (a) and tibiae (b) of a 58-year-old woman with breast cancer and diffuse bone metastases involving the
peripheral skeleton. Tumor burden is very high with abnormal low signal extending to the femoral and tibial epiphyses, more pronounced in the
right proximal femur and left distal tibia
A diffuse pattern of myelomatous involvement of the absence of—or less than 20 %—signal loss. In patients with
bone marrow is diagnosed when low signal intensity marrow pronounced bone marrow plasmacytosis, signal intensity
(iso- or hypointense to intervertebral discs or muscle) is may be higher on out-of-phase compared to in-phase images
observed on T1-weighted images, without any intervening (Fig. 6.12).
normal appearing marrow. Pattern assignment is based on In patients with a diffuse pattern, the bone marrow shows
T1-weighted images of the spine (Fig. 6.7). Diffuse involve- various degrees of enhancement. A helpful sign to diagnose
ment of the bone marrow may be hard to detect, if the per- diffuse enhancement visually is the reversal of the
centage of bone marrow plasmacytosis is lower than 20 % marrow-to-disc signal intensity relation on the post-contrast
[7] (Fig. 6.8). In our experience, this percentage may be even images (Fig. 6.13). Problems in visual interpretation may arise
higher (Fig. 6.9). In these cases (patients with a normal con- in cases of very mild enhancement. It has been shown that in
ventional MRI study and low to moderate bone marrow plas- myeloma patients with less than 20 % plasmacytosis, bone
macytosis), advanced MRI techniques, such as DCE-MRI marrow enhancement does not differ significantly from that of
and DWI, may detect abnormal changes at the microvascular normal controls (25 ± 11 % versus 21 ± 11 %) [8]. On the other
and cellular level, respectively (see below). A diffuse pattern hand, a more than 40 % contrast uptake of the bone marrow is
is less frequently associated with extraosseous soft tissue, almost certainly due to diffuse malignant infiltration [7].
compared to the focal pattern. Dynamic contrast-enhanced MRI (DCE-MRI) evaluates
On T1-weighted images, the diffuse pattern of multiple changes in microcirculation. Time-intensity curves (TIC) of
myeloma, is usually homogeneous, unlike diffuse patterns the bone marrow in patients with multiple myeloma are char-
observed in metastatic disease and lymphoma where hetero- acterized by an early and steep rise, high peak, and promi-
geneity of the diffusely involved marrow is often present nent washout (Fig. 6.14). DCE-MRI is of value in patients
(Fig. 6.10). On STIR images, the marrow may appear more with low-burden diffuse disease which may not be apparent
heterogeneous than on T1-weighted images, with diffuse on conventional MRI; quantitative analysis of the TIC may
signal increase and presence of even more hyperintense dis- identify patients with normal T1-weighted images who may
crete areas (Fig. 6.11). On out-of-phase images, there is actually have diffuse disease with low tumor mass. Perfusion
a b c
d e f g
Fig. 6.7 Multiple myeloma, diffuse pattern. intensity is low, equal to lower than that of the intervertebral discs. On
Sagittal T1-weighted (a), STIR (b), in-phase (left) and out-of-phase STIR, diffuse hyperintensity of the marrow is noted. There is no signal
(right) (c), post-contrast T1-weighted (d), and diffusion-weighted with dropout on the out-of-phase image. Diffuse contrast uptake is observed
b-value 0 (e) and b-value 750 (f) images and ADC map (g) of the lum- on the post-contrast T1-weighted image. The marrow is diffusely
bosacral spine of a 52-year-old man with multiple myeloma and diffuse hyperintense on the high b-value image. Mean ADC value of the five
marrow involvement. On the T1-weighted image, marrow signal lumbar vertebrae is 0.917 × 10−3 mm2/s
Fig. 6.8 Low bone marrow

plasmacytosis, normal pattern. a b c
(b), and T1-weighted
contrast-enhanced (c) images
72-year-old woman with
asymptomatic multiple
myeloma and 12 % bone
marrow plasmacytosis. There is
no obvious signal abnormality
on the T1-weighted and STIR
images. No perceptible contrast
uptake is noted on the
enhanced image
a b c d
Fig. 6.9 Moderate bone marrow plasmacytosis, normal pattern. the T1-weighted and STIR images. Marked signal dropout is noted on
Sagittal T1-weighted (a), STIR (b), in-phase (left) and out-of-phase the out-of-phase image (with the exception of areas of focal fat along
(right) (c), and post-contrast T1-weighted (d) images of the lumbosa- basivertebral vessels and at the spinous process of L3). On the enhanced
cral spine of a 58-year-old woman with multiple myeloma and 40 % image, there is no perceptible contrast uptake
bone marrow plasmacytosis. There is no obvious signal abnormality on
Fig. 6.10 Multiple myeloma, diffuse pattern: T1-weighted

images. a b
(a) Sagittal T1-weighted image of the lumbosacral spine
of a 54-year-old man with multiple myeloma shows dif-
fuse low signal intensity of the bone marrow. The abnor-
mal marrow is isointense to the intervertebral discs. (b)
Sagittal T1-weighted image of the lumbosacral spine of a
64-year-old woman with multiple myeloma shows diffuse
low signal intensity of the bone marrow. The abnormal
marrow is iso- to hypointense compared to the interverte-
bral discs
a b
Fig. 6.11 Multiple myeloma, diffuse pattern: hetero-

geneous appearance on STIR.
Sagittal T1-weighted (a) and STIR (b) images of the
lumbosacral spine of a 51-year-old man with multiple
myeloma and diffuse marrow involvement. The
T1-weighted image shows diffuse low signal intensity of
the bone marrow. On the STIR image, bone marrow
appears heterogeneous with multiple hyperintense
focal lesions
Fig. 6.12 Multiple myeloma, diffuse pattern: hyper-

intensity on out-of-phase images. a b
Sagittal in-phase (a) and out-of-phase (b) images of the
lumbosacral spine of a 64-year-old woman with a dif-
fuse pattern of multiple myeloma and 85 % bone mar-
row plasmacytosis (same patient as in Fig. 6.10b). There
is higher marrow signal on the out-of-phase than on the
in-phase image
parameters indicating increased angiogenesis have also been the American Society of Hematology Annual Meeting,
observed in occasional patients with MGUS or asymptom- December 2014, San Francisco, U.S.A.). These measure-
atic (smoldering) multiple myeloma and normal T1-weighted ments possibly depend on the relative proportion of normal
images [9]. Further large-sample studies could determine if and abnormal cells in the marrow (Fig. 6.15). It should be
increased angiogenesis identified by DCE-MRI is of prog- noted that there may be some overlap between the lower end
nostic value and could define a subgroup of patients who of the above range and ADC values of normal marrow, par-
could benefit from early treatment. ticularly if red marrow hyperplasia is present. Calculation of
Diffusion-weighted imaging (DWI) is an adjunct tool in ADC values may be helpful in patients with a low percentage
evaluating patients with suspected diffuse marrow involve- of bone marrow plasmacytosis and normal-appearing mar-
ment. In order to obtain accurate quantitative information, row on conventional MRI.
multiple b-values should be applied. We perform most DWI A diffuse MRI pattern due to plasma cell infiltration may
studies with 5 b-values ranging from 0 to 750 s/mm2. be quite similar in appearance to that caused by other malig-
Moreover, because of the inherent noise of the EPI DWI nancies, such as metastatic disease, lymphoma, or leukemia.
sequence and the resulting marrow heterogeneity, ADC In metastases and lymphoma, superimposed focal lesions are
values may vary throughout the spine; we have concluded a common finding (Fig. 6.16). In leukemia, diffuse homoge-
that calculation of mean ADC values from multiple vertebral neity is the rule, both on T1-weighted and STIR images
bodies more accurately represents tumor burden in diffuse (Fig. 6.17). Finally, it is important to remember that pro-
multiple myeloma. Mean ADC values (± SD, × 10−3 mm2/s) nounced red marrow reconversion due to severe anemia or
of patients with a diffuse myeloma pattern are 0.821±0.149 the therapeutic use of hematopoietic growth factors may
(range 0.642-1.017), according to our own data (presented at mimic a diffuse pattern of malignant marrow involvement.
Fig. 6.13 Multiple myeloma, diffuse pattern: reversal

of marrow-to-disc signal intensity on contrast-enhanced a b
images.
Sagittal T1-weighted (a) and contrast-enhanced
T1-weighted (b) images of the lumbosacral spine of a
64-year-old woman with multiple myeloma and diffuse
marrow involvement (same patient as in Figs. 6.10b
and 6.12). On the T1-weighted image, abnormal
marrow is hypointense to the intervertebral discs. On
the contrast-enhanced image, the enhancing marrow
becomes hyperintense to the discs
Fig. 6.14 Multiple myeloma, diffuse pattern: DCE-

MRI time-intensity curve.
Fitted time-intensity curve (TIC) of the bone marrow of
a patient with a diffuse pattern of multiple myeloma.
TIC shows early, steep rise, high peak, and pronounced
contrast washout
Fig. 6.15 Multiple myeloma, diffuse pattern: diffusion-weighted woman with a diffuse pattern of multiple myeloma (same patient as in
imaging. Fig. 6.14). Mean ADC value of the five lumbar vertebrae is
Diffusion-weighted images with b-values 0, 150, 250, 500, and 750 0.788 × 10−3 mm2/s
s/mm2 (a) and ADC map (b) of the lumbosacral spine of a 57-year-old
Fig. 6.16 Metastatic disease, diffuse pattern: inhomogeneity of

abnormal signal on T1-weighted images.
Sagittal T1-weighted image of the lumbosacral spine of a 47-year-old Fig. 6.17 Leukemia, diffuse pattern: homogeneity of abnormal
woman with breast cancer metastatic to the bone marrow. There is dif- signal on T1-weighted images.
fuse, inhomogeneous low signal intensity of the abnormal bone marrow Sagittal T1-weighted image of the lumbosacral spine of a 42-year-old
woman with chronic myelogenous leukemia. The abnormal bone mar-
row is homogeneously hypointense
6.3 Lymphomas and Leukemias MRI. Although, on MRI, lymphomatous involvement of the
bone marrow may present with either a focal or a diffuse pat-
Bone marrow involvement in lymphoma indicates the high- tern, very few reports have focused on the prevalence of
est stage (stage IV), according to the Ann Arbor classifica- these patterns and their prognostic implications. It has been
tion. For many years, the standard method for bone marrow reported that Hodgkin lymphoma and aggressive non-
assessment in most lymphoma types has been blind trephine Hodgkin lymphoma mostly present with a focal pattern,
bone marrow biopsy (BMB) of the posterior iliac crest. The whereas in indolent lymphomas, the MRI pattern of involve-
results from many studies suggest that, in Hodgkin lym- ment is frequently diffuse [11]. As the value of MRI in the
phoma (HL), initial staging with FDG-PET/CT may obviate assessment of diffuse lymphoma patterns is not well defined,
the need for BMB [10]. BMB upstages only a very small MRI appearances of bone marrow lymphoma are collec-
proportion of HL patients initially staged with FDG-PET/ tively discussed in Chap. 5.
CT, with very few, if any, requiring treatment modification. Leukemias usually present with a diffuse or a normal pat-
Results are less clear in other lymphoma types although tern of bone marrow involvement on MRI (Fig. 6.17). Signal
FDG-PET/CT may also play an important role in assessment intensity of leukemic marrow is homogeneously low on
of bone marrow status in patients with diffuse large B-cell T1-weighted images (usually lower than that of interverte-
lymphoma. BMB is still the gold standard for bone marrow bral discs or muscle) due to a combination of marrow
evaluation in indolent lymphomas. The most recent literature replacement by cancer cells and compensatory hematopoie-
regarding the role of MRI in assessing bone marrow involve- sis. The abnormal bone marrow is hyperintense on STIR
ment in lymphoma has focused on the role of whole-body images and enhances homogeneously after the administration
References 113
of paramagnetic contrast. A normal bone marrow MRI pat- patients with chronic myelogenous leukemia (CML) and
tern does not exclude leukemic infiltration because, at the only rarely in patients with other myeloproliferative disor-
early stages of the disease, there may not be sufficient ders [19]. Granulocytic sarcoma may affect any tissue, more
replacement of fat cells to alter T1 signal. Even with the frequently the breast, subcutaneous soft tissue, and bone.
application of quantitative techniques, MRI failed to detect In a small number of patients (about 1 %), it may involve
marrow involvement in 41 % of 23 patients with chronic the spine, most often the epidural or paraspinal spaces, and
lymphocytic leukemia (CLL) [12]. A focal pattern of bone rarely the spinal cord itself, possibly after spread of the
marrow involvement is rarely observed in patients with leu- leukemic cells through the haversian canals of the affected
kemia. It has been more often described in patients with leu- bone [20]. On MRI, the signal intensity of this tumor fol-
kemic relapse after treatment; in one study involving children lows the signal intensity of the abnormal marrow on all
with acute lymphocytic leukemia (ALL), a focal instead of a sequences. Chloromas must be differentiated from spondy-
diffuse MRI pattern was observed in all eight patients with lodiscitis and hematomas, both of which may complicate
bone marrow relapse [13]. AML. Enhancement of the intervertebral disc and/or the
Quantitative MRI has been applied to patients with leuke- presence of a peripherally enhancing abscess are signs of
mia, in an attempt to assess the status of the bone marrow infection. Hematomas show characteristic time-dependent
noninvasively. Early studies of patients with chronic lym- signal intensity changes reflecting the magnetic properties of
phocytic leukemia (CLL) showed significantly prolonged T1 the hemoglobin breakdown products.
relaxation times for leukemic marrow; when the bone mar-
row abnormality was also observed in the femoral head in
addition to the central skeleton, T1 relaxation times were
significantly higher, suggestive of increased tumor burden in References
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be significantly prolonged in patients with acute leukemias; sion weighted MRI for imaging metastatic and myeloma bone dis-
they tended to normalize in patients who achieved remission ease and assessing reproducibility. Eur Radiol 21:1713–1718
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Bone Marrow Edema Pattern
7
7.1 Introduction Vande Berg et al. reported that when discreet subchondral
changes are absent on MR images of patients with a bone
The regional bone marrow pattern, as already discussed in marrow edema pattern of the hip, the imaging abnormality
Chap. 4, is further divided into hyperintense and hypointense and clinical symptoms invariably resolve [3]. The presence
regional bone marrow pattern. The former is related to prior of subchondral hypointense areas, at least 4 mm thick, on
radiation therapy and is discussed in Chap. 8. The latter is T2-weighted and on fat-suppressed contrast-enhanced
due to bone marrow edema of various causes. Marrow edema T1-weighted images is highly predictive of irreversible
associated with tumors and inflammatory/infectious diseases changes (mainly osteonecrosis) [3].
is beyond the scope of this book. Instead, in this chapter we
will focus on the transient bone marrow edema syndrome
which often presents a diagnostic challenge as it may lack Key Points
characteristic associated findings suggestive of a specific MRI findings of transient bone marrow edema pattern
diagnosis. • Moderately low T1 signal intensity
In 1988, Wilson et al. used the term “transient bone mar- • High T2 signal intensity
row edema pattern” to describe changes of the bone marrow • Homogeneous contrast enhancement
observed on MR images of the hip or knee in ten patients • Complete resolution of changes on follow-up MRI
with debilitating joint pain; in all of their patients, symptoms
resolved spontaneously, and biopsy results in half of them
were not diagnostic of a specific disease entity [1]. Since The terminology regarding the different manifestations of
then, there has been extensive research on the appearance bone marrow edema pattern may be confusing with investi-
and causes of a bone marrow edema (BME) pattern on MR gators using either the term transient osteoporosis or tran-
images of the hip, but also of the knee and other joints. sient bone marrow edema syndrome (or interchangeably
On T1-weighted images, bone marrow edema manifests both) to describe a transient, self-limiting disorder of the hip
with moderately low signal intensity (higher than that of (and less often other joints) with or without radiographic
muscle or intervertebral discs) with a wide and poorly osteopenia. Apart from transient osteoporosis, there are
defined zone of transition to normal marrow. The pattern on other, more rare, disorders which manifest with a transient
T1-weighted images is often heterogeneous with areas of bone marrow edema pattern (and are also occasionally
normal marrow signal intensity intermingling with the low- referred to under the generic term transient bone marrow
signal edema. On T2-weighted images, there is an increase edema syndrome). They include the migratory form of tran-
in signal intensity, more obvious on STIR or fat-suppressed sient osteoporosis, called regional migratory osteoporosis.
T2-weighted images. On T1-weighted images obtained after Complex regional pain syndrome, which does not consis-
contrast administration, the abnormal marrow enhances tently manifest with bone marrow edema, is discussed
homogeneously. There should be no sharp or curvilinear together with transient osteoporosis mainly because of simi-
interfaces of abnormal to normal marrow suggestive of an larities in clinical presentation. A rare disorder, calcineurin
underlying abnormality, such as a bone tumor [2]. inhibitor pain syndrome, may also be associated with tran-
The most important task when a bone marrow edema pat- sient bone marrow edema. Bone marrow edema related to
tern is observed on MR images is to determine whether it is trauma (bone bruises, fractures) is most often self-limited,
transient (reversible), related to a self-limiting disorder, or resolving without any sequelae, although, on occasion, it
associated with an irreversible, more serious, pathology. may lead to epiphyseal collapse. In contrast, a bone marrow

116 7 Bone Marrow Edema Pattern
edema pattern due to osteonecrosis or osteoarthritis is usu- marrow hypoxia and self-limiting bone marrow edema (tran-
ally irreversible, leading to permanent changes of the joint. sient osteoporosis) or to bone marrow anoxia and irreversible
It is beyond the scope of this book to discuss bone marrow changes (osteonecrosis) [11]. Impaired vasomotor response
edema patterns related to osseous lesions such as bone within the bone marrow and microtrauma have also been
tumors, frank bone fractures, or arthropathies because in implicated in the pathogenesis of the bone marrow edema
such cases the imaging findings are not confined to the bone syndrome.
marrow and changes involving the bony substrate or carti- Histology specimens from patients with the classic MRI
lage usually point to the correct diagnosis. The discussion findings of bone marrow edema syndrome show interstitial
will focus on disorders manifesting with a pure bone marrow edema, fat cell destruction, fibrovascular changes, and
edema pattern. The MRI signs which distinguish a reversible increased, non-mineralized, bone formation with absence of
disorder that should be left alone from an irreversible condi- osteoclastic activity [12]. The radiolucency observed on
tion which may require prompt treatment will be addressed. radiographs of some patients with TOH is related to the pres-
ence of non-mineralized osteoid and not to true osteoporosis;
the increased osteoid formation also explains the elevated
7.2 Transient Osteoporosis tracer uptake on bone scintigrams. Histopathological changes
of transient bone marrow edema syndrome and stage 1 and 2
Transient osteoporosis (TO) is a self-limiting disorder which avascular necrosis as classified by Arlet and Ficat may be
manifests with arthralgia and evidence of delayed osteopenia similar, apart from the new bone formation in the former [13,
on radiographs. It most often affects the hip, followed by the 14]. The increased osteoid production may actually present
knee, ankle, and foot joints; rarely, it may affect the upper an attempt for repair and healing which inhibits the develop-
extremity and spine [4]. ment of avascular necrosis and suggests reversibility of the
Transient osteoporosis of the hip (TOH) was first reported syndrome [12]. Although, transient bone marrow edema syn-
in 1959 by Curtiss and Kincaid, who observed changes of drome was, at times, considered to be an early, reversible
transient demineralization of the hip in three women in the form of avascular necrosis, most investigators agree that it is
third trimester of pregnancy [5]. Most cases of TOH, how- a separate entity, with different clinical, imaging, and histo-
ever, affect middle-aged men. In women, it almost exclu- pathological manifestations.
sively occurs during late pregnancy or the early postpartum In the vast majority of patients with TOH, conventional
period. An association of TOH with cirrhosis and type IV radiographs are normal at presentation. However, radio-
hyperlipoproteinemia has been reported [6, 7]. Although graphs obtained after the fourth week show osteopenia in
TOH has not been associated with a triggering event in the most patients, affecting initially only one side of the joint,
majority of cases, minor trauma may be a predisposing fac- with preservation of the subchondral bone and joint space
tor. In one study, 30 % of patients with TOH reported unusu- (unlike osteoarthritis); in these cases, bone density returns to
ally increased physical activity prior to onset of pain [8]. normal long after clinical symptoms subside [15]. On skele-
Arthralgia related to TO can be debilitating and is exacer- tal scintigraphy, nonspecific increased tracer uptake occurs
bated by weight bearing. The first few weeks, the pain is early, within 48 h of onset of pain, long before periarticular
intense and movement may be impaired; subsequently, a pla- osteopenia appears on skeletal radiographs [16].
teau is reached for about 2 months, and then the pain sub- On MR images of patients with TOH, abnormal signal
sides and resolves within 6–12 months from diagnosis. There intensity of the bone marrow appears as early as scintigraphic
are no laboratory findings suggestive of transient bone mar- uptake [17]. An ill-defined (wide zone of transition to normal
row edema; ESR may be elevated, and there may be urinary marrow) area of moderately low signal intensity on
excretion of calcium, fluoride, and hydroxyproline. T1-weighted images and moderate to very high signal inten-
The etiology of TO remains uncertain. It has been hypoth- sity on STIR images is seen in the femoral head and, in most
esized that bone marrow edema results from obstruction of patients, extends to the neck and intertrochanteric region. The
venous outflow due to either increased intramedullary pres- edema spares the subchondral marrow in about 23 % of cases;
sure, capillary thrombosis, or both [9]. Venous congestion the acetabulum may sometimes be involved (17 % of patients
results in capillary leakage and interstitial accumulation of in one study), and in most cases a small joint effusion is pres-
fluid; edema is, therefore, more pronounced in capillary-rich ent [2, 18, 19]. After contrast administration, there is moder-
areas like the metaphyses of long bones, the vertebral bodies, ate to marked enhancement of the abnormal marrow (Fig. 7.1).
and the small bones of the wrist and midfoot [10]. The same An MR perfusion study has shown that the peak enhancement
pathogenetic mechanism of increased intramedullary pres- in TOH is delayed (occurring 40 s after the first pass of con-
sure may also be responsible for osteonecrosis; the ischemic trast), a finding which may be related to the elevated pressure
insult, depending on its severity, may either lead to bone within the congested bone marrow [18].
7.2 Transient Osteoporosis 117
a b
Fig. 7.1 Transient osteoporosis of the hip, MR imaging. increase in the signal intensity of the abnormal marrow (large arrow).
Coronal T1-weighted image (a) of a 48-year-old man who presented On the fat-suppressed post-contrast T1-weighted image (c), edematous
with acute left hip pain shows hypointense bone marrow edema in the marrow enhances intensely (arrow). Note the presence of a small joint
head, neck, and intertrochanteric zone of the left femur (arrow). On the effusion (small arrows on b)
corresponding fat-suppressed T2-weighted image (b), there is marked
Absence of hypointense areas in the subchondral bone mar- Osteonecrosis (ON) or avascular necrosis of the femoral
row on MR images of the hip ensures reversibility of imaging head more commonly affects young adults. It is more fre-
findings and complete resolution of clinical symptoms. quent in men than women with a 7:3 ratio [21]. Osteonecrosis,
Occasionally though, thin hypointense subchondral lesions either idiopathic or secondary to a variety of conditions, is
may be observed in patients with TOH due to subarticular characterized by local ischemia which leads to necrosis of
insufficiency microfractures related to the demineralization trabecular bone and bone marrow and eventually to collapse
[20]. When the thickness of these areas is equal to or exceeds of the articular surface. The femoral head is more prone to
4 mm, there is a strong possibility for lesion irreversibility [3]. osteonecrosis compared to other osseous sites, because of its
It must be stressed that the diagnosis of TOH is established relatively poor vascular supply. At presentation, symptoms
with certainty only after demonstration of complete resolution of ON of the femoral head may be insidious with vague pain
of imaging findings and/or clinical symptoms (Fig. 7.2). at the hip, thigh, and gluteal region.
a b
c d
Fig. 7.2 Transient osteoporosis of the hip, MRI follow-up. hyperintensity at the intertrochanteric region. At the time of the second
Coronal STIR image (a) of the hip of a 32-year-old man with acute left MRI, the patient’s symptoms had markedly improved. Coronal STIR
hip pain shows pronounced hyperintense marrow edema involving the image (c) of a 44-year-old man with acute left hip pain shows hyperin-
head and neck of the left femur (arrow). A left joint effusion is also tense bone marrow edema in the head and neck of the left femur
present. Follow-up STIR image (b) obtained 3 months later shows (arrow). Follow-up STIR image (d) obtained 9 months later shows
almost complete resolution of abnormal signal with minimal residual complete resolution of the edema
Osteonecrosis of the femoral head does not present with a (corresponding to the radiolucent crescent sign seen on plain
pure bone marrow edema pattern. Bone marrow edema is a radiographs) is also, when present, strongly indicative of ON.
late feature of this disorder, associated with worsening of pain Transient osteoporosis of the knee (transient BME of the
and a more dismal prognosis [22]. According to one study of knee) is a distinct clinical entity. It presents with acute onset
200 patients with early findings of ON of the femoral head, of pain without prior trauma and manifests with a bone mar-
bone marrow edema never occurred before the appearance of row edema pattern on MR images, which by definition
the characteristic band-like sign which consists of a band of resolves completely at follow-up. According to a large study
abnormal signal intensity at the interface of necrotic and nor- comparing MRI findings at presentation with final outcome,
mal marrow [23]. On non-fat-suppressed T2-weighted spin- features which favor the diagnosis of transient osteoporosis
echo images, the abnormal interface is seen as two rims, a of the knee over osteonecrosis include extension of edema to
low-signal-intensity outer rim and a high-intensity inner rim the non-weight-bearing surface of the bone and sparing of
(double line sign) [24]. On STIR or fat-suppressed FSE the subchondral marrow (found, respectively, in 44.9 % and
T2-weighted images and on contrast-enhanced fat-suppressed 37.7 % of patients with a final diagnosis of transient osteopo-
T1-weighted images, it is seen as a single high-intensity rim rosis of the knee) (Fig. 7.3) [25]. In the same study, almost
(bright band sign). A subchondral fracture with high T2 signal half of patients with BME of the knee associated with a T2
7.2 Transient Osteoporosis 119
a b
Fig. 7.3 Transient osteoporosis of the knee, MR imaging. ittal (b) and coronal (c) fat-suppressed proton density images, the signal
Sagittal T1-weighted image (a) of a 50-year-old man with acute knee intensity of the abnormal marrow is markedly increased (arrow). Note
pain shows low-intensity marrow abnormality involving the non- sparing of the subchondral region (open arrow in c) which, when pres-
weight-bearing area of the lateral femoral condyle (arrow). On the sag- ent, is characteristic of transient osteoporosis
hyperintense subchondral fracture were finally diagnosed serum alkaline phosphatase and hypophosphatemia have
with transient osteoporosis; therefore, according to this occasionally been reported in patients with RMO [8]. The
study, in the knee (unlike the hip), the presence of a subchon- disorder typically proceeds from proximal to distal joints
dral fracture does not exclude the diagnosis of transient [35]. Rarely migration of bone marrow edema occurs within
osteoporosis. the same joint, from one femoral condyle to the other in the
Spontaneous osteonecrosis of the knee (SONK), first knee or to adjacent bones of the foot and ankle (Fig. 7.4).
described by Ahlback in 1968, may present with acute bone Time intervals between episodes of arthralgia range from 2
marrow edema [26]. It mostly affects elderly women, has no to 12 months, with a second episode occurring even before
known cause, and is not associated with any of the known complete resolution of pain.
risk factors for osteonecrosis. Development of microfrac- The imaging findings of RMO are similar to those of TO;
tures in osteoporotic bone which then lead to osteonecrosis it is the migratory feature which establishes the diagnosis of
is the most popular theory for the development of SONK RMO. Because of their similar behavior and imaging mani-
[25, 27]. Patients with SONK present with symptoms simi- festations, both RMO and transient osteoporosis of the hip
lar to those of osteoarthritis or meniscal injury. Indeed, are believed to belong to the same spectrum of disease. It has
osteonecrosis of the knee is present in 10 % of patients with been suggested that systemic osteoporosis may play a caus-
osteoarthritis [28]. On MR images, SONK presents with dif- ative role in RMO, and, therefore, bone densitometry is rec-
fuse bone marrow edema. It affects mostly the weight-bear- ommended in these patients [33, 36].
ing surface of the medial femoral condyle (in contrast to
transient osteoporosis which often involves the non-weight-
bearing parts of the knee). Articular collapse at presentation Key Points
or during the evolution of the disorder is characteristic of
Regional migratory osteoporosis
SONK and excludes the diagnosis of transient BME [24].
• Typical transient BME pattern
Furthermore, generalized osteopenia is present in patients
• Affects almost exclusively the lower extremities
with SONK, but it is unusual in a patient with transient
• Migration occurs to a neighboring joint or within
BME.
the same joint
Treatment of transient osteoporosis of the hip includes
• May be associated with systemic osteoporosis
analgesic drugs and restricted weight bearing. Bisphosphonates
are routinely used as they may reduce pain and duration of
symptoms [29]. The use of core decompression to expedite
recovery and for patients with debilitating pain is controver-
sial considering the self-limiting nature of this disorder [30]. 7.4 Complex Regional Pain Syndrome
In pregnant women with transient osteoporosis, restriction of
weight bearing until reconstitution of normal bone density is Complex regional pain syndrome (CRPS), also known as
strictly recommended to avoid fractures of the hip, which reflex sympathetic dystrophy, algoneurodystrophy, or
have, occasionally, been reported [31]. Sudeck’s atrophy, has been grouped together with tran-
sient osteoporosis and regional migratory osteoporosis
since all three entities manifest with arthralgia and osteo-
7.3 Regional Migratory Osteoporosis penia/osteoporosis. Due to difficulties in diagnosing this
disorder, the incidence of CRPS is hard to determine. In a
Regional migratory osteoporosis (RMO), first described by large population-based study, the overall incidence rate of
Duncan in 1969, manifests with arthralgia migrating to a CRPS was 26.2 per 100,000 person/years with a female to
neighboring joint or, more rarely, to another site within the male ratio of 3.4:1 [37].
same joint. It affects almost exclusively the lower extremi- CRPS occurs after trauma or surgery and rarely, it may be
ties [32]. Although rare, RMO is more common than idiopathic. It is divided to CRPS-1 where no neural damage
reported in the literature. Many patients, initially diagnosed is evident and CRPS-2 where pain is related to an identifiable
with transient osteoporosis, suffer recurrence of the disorder nerve injury. This syndrome involves the small bones and
in the same or other joints and therefore actually represent soft tissues of the hands and, less frequently, the feet. The
cases of RMO. In fact, 5–41 % of patients with transient early (inflammatory, 1–7 weeks) phase of CRPS is character-
osteoporosis initially involving the hip joint will develop ized by burning pain which usually affects the entire limb,
RMO [33]. trophic changes of the skin (redness, swelling, thickening,
RMO mostly affects middle-aged men. There are no warmth, hair growth), as well as sensory-motor and auto-
known predisposing factors for this disorder, although an nomic disturbances; symptoms are disproportionate to the
increased incidence of smoking or low dietary calcium intake triggering event, and they have been attributed to dysregula-
among patients with RMO has been observed [34]. Increased tion of the central and autonomic nervous system [38]. In the
7.4 Complex Regional Pain Syndrome 121
a b
c d
Fig. 7.4 Regional migratory osteoporosis, MR images. tion of the edema. Nine months after the initial MRI, the patient pre-
Coronal (a) and sagittal (b) fat-suppressed proton density images of the sented with new-onset pain of the same knee. Coronal (c) and sagittal
knee of a 52-year-old man with acute knee pain show hyperintense (d) fat-suppressed proton density images of the knee show intra-articu-
bone marrow edema involving the medial femoral condyle (arrow). On lar migration of the bone marrow edema to the lateral femoral condyle
follow-up MRI 3 months later (not shown), there was complete resolu- (arrow)
second (dystrophic, 2–24 months) phase of the disorder, pain Typical radiographic changes of CRPS consist of patchy,
diminishes, skin temperature drops, and there is loss of hair initially periarticular, osteoporosis of the affected extremity
and perhaps tremor of the affected limb. In the chronic (atro- together with subperiosteal bone resorption. Changes on
phic) phase, the skin may become cyanotic and cold with radiographs appear about 2 weeks after onset of pain. Three‐
muscle atrophy. phase bone scintigraphy is highly sensitive for the diagnosis
a b
Fig. 7.5 Complex regional pain syndrome of the ankle, MR images. aspect of the talus (arrow). Sagittal fat-suppressed proton density image
Sagittal T1-weighted (a) image of the ankle of a 45-year-old man with (b) shows hyperintense signal of the affected marrow with minimal
intense burning ankle pain and a history of blunt trauma to the foot adjacent soft-tissue edema (arrow)
shows heterogeneous hypointense bone marrow edema at the anterior
of CRPS. Different scintigraphic diagnostic criteria, both

qualitative and quantitative, have been described. The most • Plain radiographs show periarticular osteoporosis
suggestive pattern of CRPS consists of increased flow on the • A triple phase bone scan has a high negative predic-
angiographic phase, increased blood pool activity, and dif- tive value for CRPS
fusely increased periarticular uptake on delayed images. • MRI shows soft-tissue changes and less often bone
Many authors have found that the diffuse increased activity marrow edema
in the delayed images is the most sensitive scintigraphic find-
ing in CRPS [39, 40].
At the early phase of CRPS, MRI shows increased T2 sig-
nal and contrast enhancement of the periarticular soft tissues.
Small joint effusions may be present. MRI findings of mus- 7.5 Calcineurin Inhibitor Pain Syndrome
cle atrophy indicate irreversibility of the disease. Results on
the presence of bone marrow edema on MRI studies of Calcineurin inhibitor pain syndrome (CIPS), also known
patients with CRPS are conflicting. In one study of patients as posttransplant distal limb syndrome, is a rare, self-lim-
with CRPS of the foot, bone marrow edema was described in iting bone marrow edema syndrome of the lower extremi-
almost half of patients during the early inflammatory phase ties which affects mostly renal but also other organ
of the disease, but in none during the later, dystrophic phase transplant patients receiving calcineurin inhibitor drugs
(Fig. 7.5) [41]. Other investigators, however, reported only (tacrolimus and cyclosporine) for immunosuppression.
soft-tissue changes on MR images of patients with CRPS Grotz et al. reported CIPS in nine solid (eight renal, one
[38, 42]. Results of a recent meta-analysis study support the heart) transplant patients, an incidence of 1 % of their
use of three-phase bone scan to rule out CRPS because of its study population [44]. It is now known that this syndrome
high negative predictive value and greater sensitivity com- may occur with solid organ or hematopoietic stem cell
pared to both MRI and bone radiographs [43]. transplantation. It has also been reported in a patient with
adult-onset Still’s disease who was under treatment with
calcineurin inhibitor drugs [45].
CIPS affects the joints of the lower extremities, and it is
Key Points
almost always bilateral and symmetric. It manifests with
Complex regional pain syndrome severe pain, 3 weeks to 14 months after the transplant, and
• Affects the hands and less frequently the feet symptoms may last for over a year. Pain is preceded by intol-
• Manifests with excruciating pain and skin changes erable pruritus without a skin rash. The levels of the immu-
nosuppressive drugs in the serum of patients with CIPS may
7.6 Trauma 123
or may not be elevated; pain, however, subsides within 7.6 Trauma

2 weeks from discontinuation of the calcineurin inhibitors.
The pathogenesis of BME related to calcineurin inhibi- Bone bruises were first described by Mink in 1987, on MR
tors is not known. It is hypothesized that these drugs, through images of the knee [49]. They are manifestations of occult
a vasogenic or neurotoxic effect, cause alterations in vascu- injury to the bone, resulting from direct or indirect trauma or
lar permeability and perfusion. Bone scintigraphy shows from altered stress, which cause microfractures of bony tra-
uptake at the affected joints accentuated at the tarsus [46]. beculae without disruption of the cortical bone. Limited his-
MRI shows findings of bone marrow edema which involve topathological studies of posttraumatic bone bruises have
the joints of the lower extremities and are strikingly shown microfractures of cancellous bone, edema, hemor-
symmetric [47, 48]. rhage, and fragments of cartilage and trabecular bone in
between intact lamellar bone [50]. Bone bruises are associ-
ated with protracted pain [51]. Their incidence in a large
study involving 434 patients with acute injury to the knee
Key Points
was 20 %, most of them associated with anterior cruciate
Calcineurin inhibitor pain syndrome ligament injury [52]. In a more recent study of 664 patients
• Affects transplant recipients (mostly renal) with subacute knee complaints, the incidence of bone bruises
• Manifests with severe pain preceded by pruritus on MR images was 18.7 % [53]. In the ankle, a 27 % inci-
without skin changes dence of bone bruises, affecting mostly the medial part of the
• MRI shows bilateral, symmetric bone marrow talus, was reported in 95 patients with inversion injuries [54].
edema in the lower extremity joints, especially of On MR images, bone bruises cannot be distinguished
the feet from transient bone marrow edema; it is the history of trauma
which establishes the diagnosis of the former (Figs. 7.6 and
a b
Fig. 7.6 Bone bruise, MR imaging. (solid arrows). Also shown are a tear of the posterior horn of the
Sagittal (a) and coronal (b) fat-suppressed proton density images of the medial meniscus (open arrow) and fluid in the suprapatellar bursa
knee of a 64-year-old woman with a history of recent knee trauma (asterisk)
show extensive geographic bone bruise of the medial tibial condyle
a b
Fig. 7.7 Bone bruise, MR imaging. condyles (solid arrows). Also shown are small bone bruise of the
Sagittal (a) and coronal (b) fat-suppressed proton density images (b) of medial femoral condyle (arrowhead), tear of the anterior cruciate liga-
the knee of a 25-year-old man show reticular bone bruise of the tibial ment (open arrow), and small joint effusion (asterisk)
7.7). Bone bruises manifest with ill-defined low signal inten- and grade three lesions are characterized by disruption or
sity on T1-weighted images and high signal intensity on depression of the contour of the cortex [56].
T2-weighted images because of the increased free water con- Bone bruises resolve without residual bone marrow
tent of posttraumatic hemorrhage. STIR or fat-suppressed abnormality within months from the traumatic event.
T2-weighted images facilitate the detection of the abnormal Osteochondral injuries may be associated with bone bruises
signal intensity and estimate its extension more accurately. in a significant percentage of patients; it has been reported
Even though several attempts have been made to classify that geographic lesions are more likely to be associated with
bone bruises according to their shape and location, some osteochondral sequelae [55]. Bone bruises most frequently
authors believe that these classifications are confusing and resolve in a centripetal pattern or, less often, towards the
do not provide useful information relative to the pathogene- joint margin [57].
sis or prognosis of these lesions. Most of the literature on A bone marrow edema pattern may be observed on MR
bone bruises has focused on the knee and, in particular, on images of asymptomatic athletes without a precedent trau-
bone bruises related to trauma of the anterior cruciate liga- matic event. In such cases, the edema is a result of altered
ment. Vellet et al., for example, described three patterns of biomechanics in relation with the sport performed. Bone
bone bruises of the knee: geographic, reticular, and linear. remodeling ensues and leads to microfractures of bony tra-
Geographic lesions, which were large, coalescent, and in beculae and bone marrow edema. Ultimately, with continued
contact with the articular surface, were the most common overload of a specific bone, a stress fracture may develop.
lesions in their series of 120 patients with knee injuries [55]. Thus, a bone marrow edema pattern in the knee has been
Costa-Paz et al. have proposed a three-grade classification: observed in 41 % of asymptomatic basketball players and in
grade one lesions are reticular bone bruises which are located 13.6 % of asymptomatic marathon runners [58, 59]. In
at a distance from the joint surface, grade two lesions are asymptomatic soccer players, edema-like changes affecting
geographic bone bruises contiguous to the articular surface, the symphysis pubis are a common finding [60].
References 125
osteonecrosis, and osteoarthritis (both irreversible). Other enti-

ties which present with a bone marrow edema pattern are usu-
ally easily recognized in the appropriate clinical context. A
step-by-step approach to the differential diagnosis of a bone
marrow edema pattern is presented below.
1. Assess the integrity of the articular cartilage. Cartilaginous
erosions and deformity of the articular surface favor
irreversibility as in osteoarthritis (look for osteophytes,
joint space narrowing, subchondral cysts) or osteonecro-
sis (look for band-like sign, normal joint space).
2. Assess the subchondral bone for the presence of the band-
like signal characteristic of osteonecrosis (double line
sign and bright band sign on non-fat-suppressed
Fig. 7.8 Fracture-associated marrow edema, MR imaging. T2-weighted and STIR/fat-suppressed T2-weighted
Axial STIR image of a 72-year-old woman with treated multiple
myeloma in remission who presented with new-onset pain due to insuf-
images, respectively).
ficiency fractures shows hyperintense bone marrow edema of the right 3. Assess the subchondral bone for fractures. T2 hyperin-
ischial bone surrounding a subtle low-intensity fracture line (arrow). tense subchondral fractures strongly suggest irreversibil-
Note associated soft-tissue edema (asterisk). Also shown is high-inten- ity, most commonly osteonecrosis. Low-intensity lesions
sity edema surrounding a left ischial bone fracture (open arrow) with
displacement of the bony fragments
less than 4 mm thick may represent small insufficiency
fractures associated with transient osteoporosis; these
microfractures are surrounded by marrow edema in con-
Bone fractures may present with a bone marrow edema trast to osteonecrotic lesions where edema occurs distal to
pattern on MR images. Careful search may reveal the frac- the necrotic area.
ture amidst the edematous marrow, as a thin line which is 4. Deformity of the epiphyseal contour is more marked and
hypointense on both T2-weighted and contrast-enhanced fat- more frequent with osteonecrosis.
suppressed T1-weighted images (Fig. 7.8). Less often, frac-
tures may have a speckled appearance. When subchondrally
located, they must be differentiated from lesions related to
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Benign Versus Malignant Vertebral
Fractures 8
8.1 Clinical Background definition of a vertebral body compression fracture (cutoffs

of 15–25 % vertebral body-height loss have been used in dif-
Determining whether the cause of an acute vertebral com- ferent studies). It is interesting to note that, while vertebral
pression fracture (VCF) is benign or malignant has impor- compression fractures are so common, they are underre-
tant clinical implications and can often be challenging. This ported by radiologists on imaging studies, especially CTs of
is especially true in elderly patients who are prone to develop the chest and/or abdomen performed for other reasons. The
osteoporosis-related fractures but are also more likely to mean reporting rate (on the original reports) of incidentally
carry an undiagnosed malignancy, as well as in cancer detected VCFs was 8.1 % in the multidetector CT (MDCT)
patients with no known bone metastases who present with an studies of the aforementioned meta-analysis [6]. The ten-
acute VCF. Traumatic vertebral fractures, which do not pose dency of many radiologists who specialize in body imaging
a differential diagnosis problem, will not be addressed in this to evaluate the spine only on the axial slices of a chest or
chapter. abdominal CT study (and not on sagittal reconstructed
Clinical symptoms are not useful for the distinction images), where vertebral body-height loss is very difficult to
between benign and malignant VCFs. It is well established appreciate, is one of the reasons for these surprisingly low
that many imaging-detected VCFs go unnoticed clinically. reporting rates. Another possible explanation is the limited
Those that are symptomatic manifest with back pain, regard- awareness of the clinical importance of VCFs among many
less of their etiology. The pain may be severe and debilitat- radiologists [7].
ing, and it is typically centered at the fracture level [1]. The Benign VCFs may be acute or chronic. Acute VCFs have
distinction between benign and malignant VCFs, therefore, been variably defined in different studies as those less than
relies solely on imaging and especially MRI, which is the 2 months, 10 weeks, or 3 months old since onset of pain
modality of choice in this setting [2]. ascribed to the fracture [8–13]. In a less time-specific but
A VCF occurs when the strength of a vertebral body is perhaps more accurate manner, an acute benign VCF can
exceeded by the combined axial and bending loads exerted be defined as one in which the fracture reparative process is
on the spine [1]. Osteoporosis, a condition in which bone active, with associated bone marrow edema. It is precisely
strength is compromised, is the leading cause of VCFs. in this time frame that the differential diagnosis problem
Vertebral fractures are the most common type of osteopo- with malignant fractures may arise, as the reparative activity
rotic fracture, exceeding the rate of hip fractures [3]. may lead to confusing imaging results. Chronic (i.e., healed)
Although more common in women, the incidence of VCF is VCFs, on the other hand, do not pose a diagnostic problem on
high in men too, and it increases with age in both sexes [3, MRI because they are characterized by resolution of edema
4]. The incidence of imaging-detected VCFs (which is higher and restoration of normal bone marrow signal intensity.
than the incidence of symptomatic fractures) varies depend- VCFs may result from malignant tumor infiltration (by
ing on the study used. It has been reported to be as high as metastases or hematologic malignancies), but the rate of
26 % on radiographs of women 50 years old or older [1, 5]. occurrence is hard to assess accurately [1]. In the case of
In a meta-analysis of 12 imaging studies (using plain radio- metastases, most, if not all, of the vertebral marrow must be
graphs or multidetector CT), the prevalence of incidental replaced by tumor for a compressive fracture to occur [14,
vertebral fractures ranged from 9.5 to 35 % (mean 21.1 %) 15]. The skeletal system is one of the most common sites of
[6]. Others have found a somewhat lower incidence of VCFs metastases; the spine is most frequently affected, because it is
in chest and/or abdominal CTs, although it must be noted rich in vascular red marrow [14]. Up to 39 % of all bone
that the prevalence depends also on the threshold used for the metastases have been reported to occur in the spine, although

128 8 Benign Versus Malignant Vertebral Fractures
this percentage may vary depending on tumor type [16]. Such

metastases may cause a reduction in the individual vertebral
body strength, which in turn may result in an acute pathologic
fracture. It must be noted that the distinction between benign
and malignant vertebral fractures is less clear in the case of
multiple myeloma. Tumor-induced osteoporosis related to
production of osteoclast-activating factors through interac-
tions of abnormal plasma cells with the bone marrow micro-
environment is a characteristic feature of this disease. Unlike
most cases of metastases, in myeloma patients, vertebral col-
lapse may occur in the absence of extensive replacement of
the marrow [17]. In other words, benign-appearing VCFs in
multiple myeloma may be due either to osteoporosis alone or
to the coexistence in the same vertebra of osteoporosis and
low-burden marrow plasmacytosis [14]. A fracture with typi-
cal characteristics of benignancy rules out metastatic disease
but not myeloma as a causative agent.
A common clinical scenario, where a newly diagnosed
vertebral compression fracture presents as a critical diagnos-
tic challenge, is in patients with a primary malignancy and
no previously known bone metastases. In such patients––
especially older ones who are more likely to be osteopenic
and/or patients treated with drugs inducing osteopenia—
compression fractures may occur in the absence of bony
metastases, as a result of osteoporosis-related bone weaken-
ing [14]. In fact, it has been shown that up to one-third of
vertebral compression fractures in patients with known
malignancies are benign [18]. Accurate differentiation is
obviously very important in this group of patients for appro-
priate staging, prognostication, and treatment planning. In a Fig. 8.1 Intravertebral vacuum cleft sign, plain radiography.
different clinical context, a neoplastic vertebral fracture may Lateral view of the thoracic spine of a 60-year-old woman shows a
compressed thoracic vertebral body with gas beneath the anterior aspect
be the first manifestation of malignancy. Incorrectly diagnos-
of its superior endplate (arrow)
ing such a fracture as benign may significantly delay appro-
priate diagnostic work-up and treatment initiation.
retrospective analysis of plain radiographs of the spine, the
intravertebral vacuum cleft sign was detected in 18.9 % of
8.2 Imaging osteoporotic vertebral fractures and in 0 % of metastatic verte-
bral fractures [23]. Although the presence of gas in a fractured
Although acute VCFs are frequently imaged initially with spi- vertebral body practically excludes metastasis as an underly-
nal radiographs, the limitations of plain radiography for the ing cause, it does not exclude the presence of multiple
differentiation of benign from malignant VCFs are well recog- myeloma. In the aforementioned study of plain radiographs,
nized. A highly specific radiographic sign for a benign fracture the sign was observed in 6.4 % of vertebral fractures in patients
worth mentioning is the intravertebral vacuum cleft sign. This with multiple myeloma [23]. On plain radiography, the sign is
consists of a linear or semilunar radiolucency within a frac- more conspicuous with extension stress views obtained in a
tured vertebral body, adjacent to the collapsed endplate [19] lateral decubitus position, because the walls of the cleft are
(Fig. 8.1). The lucency represents gas (nitrogen) located within drawn apart [20]. In the standing position, the walls of the cleft
an intravertebral cleft. Although its pathogenesis is not com- are apposed and the sign is usually not observed. The gas pre-
pletely understood, the cleft most probably corresponds to an sumably originates from the surrounding tissues as a result of
area of ischemic bone necrosis as a result of nonunion of frac- low pressure generated within the cleft [19].
tured bone. Osteonecrosis was found in selected biopsied Although CT is not considered the examination of choice
cases [20–22]. Presence of an intravertebral vacuum cleft is, for the characterization of VCFs, it has been studied in this
therefore, considered diagnostic of avascular necrosis in asso- setting, and multiple valuable signs have been described. CT
ciation with a fractured vertebra. Moreover, its presence is findings reported to be associated with a benign VCF are cor-
highly suggestive of the benign nature of the fracture, as has tical fractures of the vertebral body without cortical bone
been repeatedly demonstrated in the literature. In a large destruction (the so-called puzzle sign, consisting of small
8.2 Imaging 129
gaps in the cortical bone with all the respective bone frag- appreciated on coronal images (Fig. 8.5). Despite the ability
ments still visible and fitting together like a puzzle), retropul- of CT to demonstrate even very small collections of gas, none
sion of a bone fragment into the spinal canal, fracture lines of the metastatic VCFs in two CT studies demonstrated the
within the cancellous bone, an intravertebral vacuum cleft sign, thus confirming its high specificity for benignancy [10,
sign, and a thin (<10 mm), diffuse circumferential (i.e., sur- 25]. CT findings associated with a malignant VCF are
rounding the entire anterolateral outer surface of the vertebral destruction of the cortical bone of the vertebral body, destruc-
body) paraspinal soft-tissue mass [10] (Figs. 8.2 and 8.3). tion of the cancellous bone of the vertebral body, destruction
Regarding the intravertebral vacuum cleft sign, its detection of a pedicle, a focal paraspinal soft-tissue mass, and an epi-
rate is, as expected, much higher on CT than on plain radio- dural soft-tissue mass [10] (Fig. 8.6). All the abovementioned
graphs [24]. As with plain radiographs, it is most commonly signs are better depicted with thin-collimation MDCT which
seen as a linear gas collection adjacent and parallel to the provides great anatomic detail (e.g., for the evaluation of cor-
fractured endplate (Fig. 8.4). Occasionally the gas collection tical bone) and allows for the use of sagittal and coronal mul-
may have a transverse (left to right) linear configuration, best tiplanar reconstructions [25].
a b
c d
Fig. 8.2 Benign vertebral compression fracture, CT findings. gaps (arrows in a, b) and fitting bone fragments (puzzle sign). Also
Axial CT images of the lumbar spine of a 65-year-old man with an seen are fracture lines traversing cancellous bone (arrows in c) and thin,
acute osteoporotic fracture of L3 show cortical fractures with small diffuse circumferential paraspinal soft-tissue mass (arrows in d, e)
Fig. 8.2 (continued)
Fig. 8.4 Intravertebral vacuum cleft sign, CT.

Reconstructed sagittal CT image of the spine of a 72-year-old woman
with an osteoporotic fracture of T12 shows intravertebral vacuum cleft
sign, with accumulation of gas beneath the superior endplate (arrow)
Bone scintigraphy is not useful in the differentiation of

VCFs since both benign and malignant fractures display
nonspecific increased tracer uptake. Moreover, increased
tracer activity may persist in benign fractures for up to
2 years after the initial event [26].
The role of FDG-PET in the differential diagnosis of
benign and malignant VCFs has not been extensively evalu-
ated. Theoretically, malignant vertebral fractures must dis-
play increased FDG uptake due to the metabolic activity of
tumor cells, whereas benign osteoporotic fractures are not
expected to significantly accumulate FDG. Two retrospec-
tive studies with 33 and 96 patients concluded that there is a
statistically significant difference in mean standardized
uptake value (SUV) between benign and malignant vertebral
compression fractures [27, 28]. In the first study, mean SUV
was 1.9 ± 0.97 (range 0.7–4.9) for benign and 3.9 ± 1.52
(range 2.2–7.1) for malignant fractures. The authors reported
that the accuracy of FDG-PET in differentiating benign from
Fig. 8.3 Benign vertebral compression fracture, retropulsion of malignant compression fractures was 92 % [27]. In the sec-
bony fragment. ond study, mean SUV was 2.38 ± 1.90 (range 1.9–6.0) for
Reconstructed sagittal image obtained from a whole-body CT of a
benign and 6.29 ± 3.50 (range 2.6–14.4) for malignant frac-
68-year-old man shows osteoporotic fracture of a thoracic vertebral
body with retropulsion of a posterosuperior bony fragment into the spi- tures. Based on these data the most reliable threshold for
nal canal (arrow) SUV was found to be 4.25, which yielded a sensitivity of
8.2 Imaging 131
Fig. 8.5 Intravertebral vac-

uum cleft sign, CT. a b
Reconstructed sagittal (a) and
coronal (b) images obtained
from a whole-body CT study of
a 62-year-old woman with a
chronic sclerotic fracture of T8
presenting with acute back pain
due to further collapse
demonstrate intravertebral
vacuum cleft sign (arrows).
The transverse left to right
linear configuration of the gas
collection is well shown on the
coronal image
a b
Fig. 8.6 Malignant vertebral

compression fracture, CT
findings.
Axial (a) and reconstructed
sagittal (b) CT images from a
whole-body CT study of a
myeloma show compression
fracture of T9 (arrow) with
extensive destruction of
cancellous and cortical bone
85 % and a specificity of 71 % [28]. Differences in the signal abnormality specific to each type of fracture. MRI,
reported SUV measurements may be partly related to the because of its excellent soft-tissue contrast, also allows for
time interval between the fracture event and the PET exami- detailed morphologic analysis of the collapsed vertebra and
nation. For example, it has been reported that in benign trau- its surrounding tissues. This has led to the description of a
matic or surgical fractures, FDG uptake rapidly decreases large number of useful morphologic features for VCF dis-
with time and normalizes within a maximum of 3 months crimination. Finally, quantitative MRI techniques, especially
[29]. It is obvious from the abovementioned data that over- diffusion-weighted imaging and chemical-shift imaging,
laps exist in SUV measurements between the two groups of have been evaluated by investigators in an attempt to establish
fractures and that additional studies are needed to validate well-defined thresholds for objective VCF characterization.
the results and better define the role of FDG-PET as a
problem-solving tool for VCF differentiation.
8.3.1 Signal Intensity Characteristics
8.3 Magnetic Resonance Imaging Signal intensity characteristics are assessed on T1-weighted
images. STIR and contrast-enhanced sequences are considered
MRI is largely considered the imaging modality of choice to nondiscriminatory. Both acute benign and malignant vertebral
diagnose the cause of a VCF. Several articles in the peer- fractures appear homogeneously or heterogeneously hyperin-
reviewed literature have described MRI features valuable for tense on STIR. Most studies have found that visual assessment
the differential diagnosis of a VCF. A 2012 meta-analysis of contrast enhancement is not useful for fracture characteriza-
identified 31 original studies published between 1989 and tion due to significant overlaps between patterns.
2009 which reported the diagnostic performance of various
MRI features in differentiating benign from malignant VCFs, Complete Replacement of the Normal Bone
using follow-up imaging and/or biopsy as a reference stan- Marrow Signal Intensity
dard for the etiology of the VCF [2]. These features can be Complete replacement of the normal marrow signal inten-
broadly grouped in three categories: signal intensity charac- sity, seen as diffusely low signal of the entire collapsed ver-
teristics, morphologic characteristics, and characteristics tebral body on T1-weighted images, has been strongly
related to quantitative data. Signal intensity distinguishing associated with metastatic VCFs in numerous studies
features are based on the ability of MRI to directly visualize (Fig. 8.7). The reported percentage of malignant VCFs with
the bone marrow and, therefore, to define patterns of marrow total marrow replacement on T1-weighted imaging varies
a b c
Fig. 8.7 Malignant vertebral compression fracture, MRI findings. ture of a thoracic vertebral body with complete replacement of normal
(a) T1-weighted sagittal image of a 73-year-old man with lung cancer marrow intensity (arrow). Also note diffuse convexity of the anterior
and multiple bone metastases shows compression fracture of L1 (arrow) border of the compressed vertebra. (c) Sagittal T1-weighted (c) image
with diffuse convexity of its posterior border, characteristic of a malig- of the lumbosacral spine of a 57-year-old woman with multiple
nant etiology. Also note complete replacement of normal marrow myeloma and a malignant compression fracture of L2 (arrow) shows
hyperintensity. (b) Sagittal T1-weighted image of the thoracic spine of complete marrow replacement of the collapsed vertebral body and dif-
a 64-year-old man with lung cancer shows malignant compression frac- fuse convexity of the posterior and anterior vertebral border
8.3 Magnetic Resonance Imaging 133
Fig. 8.9 Chronic benign vertebral compression fracture, MRI.

T1-weighted sagittal image of a 57-year-old woman shows chronic
healed osteoporotic compression fracture of L5 (arrow) with normal
Fig. 8.8 Complete marrow intensity replacement, infrequent
marrow hyperintensity, similar to the other vertebral bodies
appearance of acute benign compression fracture.
Sagittal T1-weighted image of a 51-year-old woman with osteoporotic
compression fractures shows acute compression of L2 with complete Band-Like Abnormal Signal
replacement of normal marrow intensity (arrow) As noted above, most acute benign VCFs exhibit low T1 sig-
nal involving only part of the vertebral body, related to mar-
between 77 and 88 % [9, 13–15, 30]. The obvious explana- row edema. In some of these fractures, the edema takes the
tion is that most, if not all, of the vertebral body marrow shape of a band-like pattern of low T1 signal adjacent and
must be replaced by tumor for a metastatic compressive parallel to the depressed endplate (Fig. 8.10). The band-like
fracture to occur, thus leading to a diffusely low T1 signal abnormal signal may take one of the shapes depicted in
with no apparent spared marrow. However, apparent com- Fig. 8.11 [13]. This has been shown to be a highly specific,
plete marrow replacement does not, by itself, totally exclude albeit not very sensitive, sign for a benign vertebral fracture
the possibility of a benign fracture. Low T1 signal involving [9, 14, 21, 30, 31]. Caution is warranted to rule out nodular-
the entire vertebral body has been described in 15–21 % of ity of the band-like area of abnormal signal, which may be a
benign VCFs as well [9, 13, 14]. In acute osteoporotic frac- sign of malignancy [14].
tures the bone marrow edema associated with the fracture-
induced reactive process may occasionally occupy the entire Fluid Sign
vertebral body, thus resulting in a pattern of diffuse low T1 The MRI fluid sign consists of a linear or triangular area of
signal intensity [13] (Fig. 8.8). In fact, the extent of low T1 very high T2 signal located adjacent to the impacted endplate,
signal in osteoporotic fractures is partly time-dependent. most often along its anterior aspect [21] (Fig. 8.12). More
The closer to the onset of acute pain imaging is performed, rarely it is seen centrally within the fractured vertebral body
the more likely it is that complete low T1 signal will be [32]. The sign has been almost exclusively described in
observed. Conversely, since in this type of fracture the low benign osteoporotic fractures and is generally considered
T1 signal represents reversible edema, chronic healed frac- one of the strongest MRI predictors of VCF benignancy [33].
tures appear uniformly hyperintense on T1-weighted imag- It has been shown that the MRI fluid sign and the intraverte-
ing (Fig. 8.9). bral vacuum cleft sign, seen on plain radiographs and CT,
represent the same phenomenon [20, 32] (Fig. 8.13). The which then fills with gas from the surrounding tissues, as a
intravertebral cleft corresponds to a region of osteonecrosis result of the generated negative pressure. This produces the
associated with a non-healing vertebral fracture [22]. In the intravertebral vacuum cleft sign observed on plain radio-
standing position, the walls of the cleft are apposed. In the graphs and CT exams. If the supine positioning is prolonged
supine position, spinal extension results in gaping of the cleft (as is the case in a typical MRI exam), the gas in the cleft is
a b c d
Fig. 8.10 Acute benign vertebral compression fractures, band-like abnormality. (c, d) Sagittal T1-weighted (c) and STIR (d) images of the
abnormal signal. lumbosacral spine of a 69-year-old man with prostate cancer and an
(a, b) Sagittal T1-weighted (a) and STIR (b) images of the lumbosacral osteoblastic metastasis at L4 show acute benign fracture of L5 (arrow)
spine of a 69-year-old woman with an acute osteoporotic fracture of L3 with band-like signal abnormality
(arrow) show depression of its superior endplate with band-like signal
Fig. 8.11 Schematic represen-

tation of band-like abnormal
signal in acute osteoporotic ver-
tebral fractures.
Different patterns of band-like
signal abnormality of acute
osteoporotic vertebral fractures
on T1-weighted images. Black
corresponds to low signal
intensity representing bone
marrow edema (Reprinted
with permission from Cuénod
et al. [13])
progressively replaced by fluid originating from the adjacent intravertebral cleft depends, therefore, on time and position.
marrow edema leading to the appearance of the MRI fluid On MR images obtained immediately after supine position-
sign. This has been demonstrated in studies with sequential ing, the cleft may have a partial or complete signal-void
MR imaging [20, 32]. The presence of gas or fluid in an appearance due to the presence of air (Fig. 8.14).
Fig. 8.12 Acute benign verte-

bral compression fracture, MRI a b
fluid sign.
Sagittal STIR image (a) of the
lumbar and lower thoracic spine
of a 70-year-old woman with an
acute osteoporotic compression
fracture of T12 shows linear high
signal fluid at the anterior aspect
of the impacted superior endplate
(arrow). Also note band-like
signal abnormality of the
vertebral body on the
T1-weighted image (b). A
second acute benign compression
fracture is present at L3
a b

bral compression fracture, intra-
vertebral vacuum cleft sign (CT),
fluid sign (MRI).
Sagittal CT image of the lumbar
and lower thoracic spine (a) and
sagittal MRI STIR image of the
thoracic spine (b) of a 72-year-
old woman with an acute
osteoporotic fracture of T12
(same patient as Fig. 8.4). On
the CT image, a collection of
gas (arrow) beneath the superior
end plate of the collapsed
vertebra is seen (intravertebral
vacuum cleft sign). High signal
fluid within the cleft (arrow) is
noted on the STIR image (MRI
fluid sign)

bral compression fracture, coex- a
istence of fluid, and air within
intravertebral cleft.
Contiguous sagittal STIR images
(a) of the spine of a 67-year-old
woman with an acute osteopo-
rotic fracture of T9 show an
intravertebral cleft with
coexisting signal-void (air, open
arrow) and hyperintense (fluid,
white arrow) content along the
inferior end plate. Also note
complete replacement of normal
marrow signal in the vertebral
body due to edema.
Corresponding sagittal
T1-weighted images (b) are also
shown
8.3.2 Morphologic Characteristics replaced. When the vertebral body collapses, the compressed
tumor mass will protrude beyond the vertebral contours lead-
T1, STIR, and T1 contrast-enhanced with and without fat- ing to a smooth diffuse convexity of its borders (posterior,
saturation sequences are all valuable for the assessment of anterior, or both) [14] (Fig. 8.7). A diffuse convex posterior
morphologic characteristics. STIR and T1 contrast-enhanced border was found in 70 % of malignant vertebral collapses
with fat-saturation sequences may increase the conspicuity versus 6 % of osteoporotic collapses by Cuenod et al. and in
of pedicle involvement. Axial slices are useful for the evalu- 74 % versus 20 %, respectively, by Jung et al. [9, 13].
ation of paraspinal and epidural soft-tissue masses. Only
characteristics with a statistically significant difference in Retropulsion of a Posterior Bony Fragment
incidence between benign and malignant VCFs in more than Retropulsion of a bone fragment is associated with a benign
one published original report are discussed below. VCF. It is usually located in the posterosuperior angle of the
vertebral body (Fig. 8.15). In one study, this sign was found
Convex Posterior Border to be 100 % specific (i.e., no malignant fractures displayed
A convex posterior vertebral border has been associated with the finding) but had a very low sensitivity (16 %) [13]. In
malignancy. As already noted, for a malignant compressive another study, it had higher sensitivity (60 %), but it was
fracture to occur, most of the vertebral marrow must be found in 11 % of metastatic fractures as well [9].
Fig. 8.15 Acute benign vertebral compression fracture, retropul-

sion of posterior bony fragment.
woman with an acute osteoporotic fracture of T12 shows retropulsion
of posterior superior bony fragment (arrow). Also note band-like signal
abnormality of the vertebral body Fig. 8.16 Malignant vertebral compression fracture, involvement
of the pedicle.
Pedicle Involvement man with a malignant compression fracture of L5. There is involvement
Involvement of the pedicle on MRI has been associated of the left pedicle with abnormal signal and expansion (arrow). Also
note extensive metastasis at S1
with a malignant vertebral fracture in several studies [9,
13–15, 34] (Fig. 8.16). Nevertheless, conflicting results
have been reported in the literature, with one study showing has been noted in studies where STIR (or T2-weighted with
no statistically significant difference between benign and fat saturation) and T1-weighted contrast-enhanced with fat
malignant fractures regarding pedicle involvement [35]. It saturation, sequences have been part of the MR protocol [9,
is well established that pedicle involvement is very frequent 34, 35]. Both these sequences have been shown to increase
in metastatic VCFs, with its incidence in various studies the conspicuity of pedicle involvement in osteoporotic ver-
ranging from 69 to 88 % (greater than 80 % in the majority tebral fractures. Concerning age of fracture, a relationship
of reports) [9, 13–15, 34, 35]. In other words, in most cases between pedicle involvement on MR imaging and the dura-
of metastatic VCF, tumor has spread from the vertebral tion from pain onset in patients with osteoporotic VCFs is
body to the pedicle(s) before collapse occurs. On the other evident. A lower incidence of abnormal signal intensity of
hand, involvement of the pedicle in osteoporotic VCFs is the pedicle is expected in studies which include a large pro-
more controversial with large discrepancies observed in portion of chronic fractures in their patient population. The
different reports (incidence ranging from 0 to 64 %) specificity of pedicle involvement can be increased when
(Fig. 8.17). Differences in MRI technique are the most not only signal alteration but also expansile change in the
important reason for these inconsistencies. Differences in pedicle is considered. In one study, more than half of the
patient selection, especially regarding age of fracture, may cases of malignant VCFs with pedicle involvement also had
also play a role. A higher incidence of pedicle involvement obvious expansile change of the pedicle, whereas none of
Diffusion-Weighted Imaging
Diffusion-weighted imaging (DWI) has been evaluated
extensively for the differentiation of benign and malignant
VCFs with varying, sometimes even conflicting, results
[31, 36–43]. Both qualitative (visual evaluation of signal
alteration) and quantitative (Apparent Diffusion Coefficient
[ADC] measurement) DWI have been investigated. The
variable results in the literature can be partly explained by
technical factors, regarding pulse sequence and b-values
used. Some early studies used qualitative assessment of
DWI for VCF characterization with a steady-state free pre-
cession (SSFP) sequence and reported very good results,
with benign fractures appearing hypo- to isointense and
malignant fractures hyperintense, relative to normal verte-
bral bodies [31, 36]. Other investigators, however, found
that qualitative DWI offers no real advantage over conven-
tional MRI sequences in the characterization of vertebral
fractures. They commented that the DW-SSFP sequence is
highly influenced by the T2 shine-through effect, and thus
the findings cannot be solely attributed to differences in
Fig. 8.17 Acute benign vertebral compression fracture, involve-
ment of the pedicle. diffusion restriction [44, 45]. Patient selection bias may
Axial T1-weighted image of an 85-year-old man with an acute osteopo- also possibly explain the conflicting results in small-sam-
rotic fracture of L5 shows extension of abnormal low signal to the right ple studies. For example, metastases from prostate cancer
pedicle without expansion (arrow). Compare with normal high signal
may appear hypointense on DW-SSFP due to the presence
of left pedicle
of extensive sclerosis. Nevertheless, in a more recent study
comparing different DWI techniques, the qualitative
the benign fractures had evidence of pedicle expansion DW-SSFP sequence was once again reported to have the
[34]. In another study, deposit-like pedicle involvement highest accuracy (93.5 %) in differentiating benign from
(defined as well-circumscribed focal or nodular involve- malignant VCFs [43].
ment of the pedicle, as opposed to diffuse or ill-defined Most studies investigating the role of DWI in VCF char-
involvement) was one of the strongest predictors for VCF acterization have used quantitative techniques that allow for
malignancy [33]. the calculation of apparent diffusion coefficient (ADC) val-
ues [38–42]. These studies have shown that malignant frac-
Paraspinal Mass-Epidural Mass tures (which are characterized by dense tumor infiltration)
The presence of a paraspinal soft-tissue mass (PSTM) associ- tend to have more restricted diffusion and therefore lower
ated with a vertebral fracture has been considered indicative ADC values than acute osteoporotic fractures (in which
of malignancy [9, 14, 15, 34]. However, a high frequency of water proton mobility is increased as a result of extensive
paraspinal mass in acute osteoporotic fractures has also been interstitial edema). However, even in those studies that have
described [34]. Studies which provided characterization of shown a statistically significant difference in ADC measure-
the soft-tissue mass have shown that the pattern of paraspinal ments between the two groups, a significant overlap exists,
involvement is often different in osteoporotic and malignant and most investigators do not propose a discriminating cutoff
VCFs. The PSTM associated with malignancy is frequently value. In a study comparing different DWI techniques, a cut-
focal, whereas the PSTM in acute osteoporotic VCFs is typi- off value of 1.48 × 10−3 mm2/s was found to have a 78.3 %
cally diffuse, involving the entire anterolateral aspect of the accuracy when using a DW single-shot TSE sequence [43].
vertebral body [9, 34]. An epidural soft-tissue mass was also The authors of a meta-analysis on the MRI evaluation of
shown to be associated with malignancy [9, 13]. malignant and benign VCFs suggested that if only studies
using fat-suppressed EPI and including b-values ≥500 s/
mm2 are considered, then a reasonable cutoff for malignancy
8.3.3 Quantitative Characteristics seems to be an ADC value of 1.5 × 10−3 mm2/s or less. They
added that this proposed threshold needs to be verified by
Various studies have investigated the value of MRI quantita- additional studies [2]. In view of the above-described incon-
tive techniques for acute VCF characterization. The goal of sistencies, caution is recommended when considering DWI
such studies is to define clear-cut thresholds that reduce in this setting, and the results should not be interpreted in
observer variability, inherent in any morphologic visual isolation, but only combined with signal intensity and mor-
assessment [2]. phologic characteristics.
8.4 Conclusion 139
Chemical-Shift Imaging 8.4 Conclusion

The rationale behind the use of chemical-shift imaging (CSI)
in this clinical setting is that in malignant fractures, normal In conclusion, several MRI features are reliable for differen-
fat-containing marrow is largely or completely replaced by tiating malignant from benign VCFs. A study comparing
tumor, and therefore no significant signal dropout should four prediction models based on MRI feature analysis
occur on the opposed-phase images. Conversely, the fact that showed that it is possible to estimate the risk of malignancy
in acute osteoporotic fractures normal fat-containing marrow of a VCF by using a small number of MRI features and
is preserved should result in loss of signal on the patient age [33]. The model type that performed best in that
opposed-phase images. In other words, benign fractures are study (logistic regression) used five statistically significant
expected to have a lower signal intensity ratio (SIR, signal predictors: focal paraspinal mass and deposit-like pedicle
intensity on the opposed-phase image to signal intensity on involvement were positively correlated with VCF malig-
the in-phase image) than malignant fractures. Only a few nancy. The MRI fluid sign, other compression fractures with
studies have evaluated CSI for VCF discrimination [43, 46– normal marrow signal intensity, and older age were nega-
48]. Using a SIR of 0.80 (i.e., signal loss of 20 % on the tively correlated with VCF malignancy.
opposed-phase image) as a cutoff, with >0.80 defined as a Some of the studies mentioned in this chapter have
malignant result and <0.80 defined as a benign result, chem- reported the accuracy of MRI for VCF differentiation when
ical-shift imaging was found to have a sensitivity of 95 % combining a constellation of signal intensity and morpho-
and a specificity of 89 % in one study [47]. Nevertheless, logic features. In most studies, the overall diagnostic accu-
others—although confirming the statistically significant dif- racy of MRI exceeds 90 %, reaching as high as 95 % [9, 14,
ference between the SIR of benign and malignant fractures— 29, 34]. Although these results are impressive, it must be
have noted a significant overlap between the two groups that emphasized that, in daily practice, MRI findings may some-
does not allow the definition of a useful cutoff for discrimi- times be equivocal or atypical. In such cases, especially in
nation [43]. high-risk patients (i.e., those with a known malignancy), it
may be difficult to make important treatment decisions based
solely on the initial MRI. When faced with such a scenario,
8.3.4 Findings at Other Spinal Levels the options for further work-up are: correlation with another
imaging modality, biopsy, or short-term MRI follow-up.
Coexisting healed (i.e., displaying normal marrow signal MDCT may offer valuable additional information in cases
intensity) VCFs at other spinal levels have been associated where MRI is inconclusive [25]. For example, the puzzle
with a benign vertebral fracture [15, 33]. The presence of sign (cortical fractures with all bone fragments still visible
lesions presumably representing metastases at other spinal and no cortical destruction), when present, increases the
levels has been associated with a metastatic vertebral frac- diagnostic confidence for an osteoporotic VCF [10]. One
ture [9, 15]. study sought to combine MRI and CT findings in order to
devise a scoring system for VCF discrimination. They
Key Points
selected four MRI signs (pedicle or other posterior element
involvement, paravertebral mass, preservation of normal
• MRI features suggestive of an acute osteoporotic marrow signal, and preservation of a continuous posterior
VCF: band-like low T1 signal, fluid sign, retropul- vertebral body margin) and two CT signs (bone destruction,
sion of a vertebral bony fragment distinct fracture lines) to establish a scoring system and
• Quantitative features that favor benignancy: ADC found that it increased diagnostic accuracy [49]. The other
>1.5 × 10−3 mm2/s on DWI-EPI and SIR <0.80 on imaging modality that could theoretically be used as a
chemical-shift imaging problem-solving tool in difficult cases is FDG-PET/CT with
SUV measurement, but it is less readily available and more
costly, and its use in the specific scenario of VCFs with
equivocal MRI findings needs to be validated in further stud-
Key Points
ies. Biopsy is an option in selected cases, particularly those
• MRI features suggestive of a malignant VCF: com- with a known malignancy, when MRI findings are atypical.
plete replacement of the normal marrow signal, It is obvious that in such cases only a positive biopsy result
convex posterior vertebral border, pedicle involve- allows definitive diagnosis.
ment (especially expansile or deposit-like), focal Short-term MRI follow-up may be very useful in estab-
paraspinal mass, epidural mass lishing the correct diagnosis in difficult cases. As already
• Quantitative features that favor malignancy: ADC stated, in acute osteoporotic fractures the vertebral signal
≤1.5 × 10−3 mm2/s on DWI-EPI and SIR ≥0.80 on abnormalities are mostly due to edema and are reversible.
chemical-shift imaging Previously published data suggest that this reversal to
normal marrow signal occurs in 1–3 months after the ini-
tial painful event [13, 50]. Conversely, in untreated malig- recommend the follow-up MRI exam to be performed
nant VCFs the extent of abnormal signal will either 8–10 weeks after the initial MRI. By that time, the vast
increase or at least remain unchanged if the MRI is majority of benign osteoporotic fractures will show some
repeated after a short interval. Therefore, if biopsy cannot restoration of normal fatty marrow signal.
be performed or if it has been performed and the results
are inconclusive or if the clinical context is such that defi-
nite diagnosis can be postponed by a few weeks, a short- Key Point
term MRI follow-up to compare the extent of abnormal • In vertebral compression fractures with equivocal
signal intensity is the best option (Figs. 8.18 and 8.19). A findings on MRI, follow-up MRI may be performed
large sequential MR imaging study to more precisely at an 8–10-week interval; reduction of the extent of
define the time period necessary for resolution of signal abnormal signal intensity on T1-weighted images
abnormalities in acute benign fractures is still lacking. establishes the diagnosis of a benign fracture
Based on the published data and our own experience, we
Fig. 8.18 Benign vertebral com-

pression fracture, follow-up a b
MRI.
of a 62-year-old woman with an
fracture of T11 shows
hypointense signal involving
the entire vertebral body
(arrow). Follow-up
T1-weighted image (b) 9 weeks
later shows restoration of
normal hyperintense signal with
some hypointensity persisting
along the superior vertebral
endplate (arrow). Note interval
development of new
osteoporotic compression
fractures with band-like signal
abnormality (open arrows)
References 141
Fig. 8.19 Benign vertebral

compression fracture, follow- a b
up MRI.
of an 82-year-old man with an
fracture of L5 shows low signal
intensity involving almost the
entire vertebral body (arrow).
Follow-up T1-weighted image
(b) 10 weeks later shows
reappearance of normal
hyperintense fatty marrow with
residual hypointensity parallel
to the impacted inferior
endplate (arrow)
8. Faciszewski T, McKiernan F (2002) Calling all vertebral fractures

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MRI of Bone Marrow
Posttreatment Changes 9
9.1 Introduction With doses higher than 4,000 cGy, the microvasculature
of the bone marrow is permanently damaged and red mar-
In this chapter, the MRI appearance of the effect of treatment row regeneration does not usually occur. In patients younger
on the bone marrow will be discussed. The first part addresses than 18 years of age, however, red marrow regeneration
the post-therapy appearance of normal bone marrow. may occur, regardless of the radiation dose [7]. Fatty mar-
Radiation therapy and chemotherapy alone or in combina- row conversion is strictly confined to the radiation portals
tion with hematopoietic growth factors induce sequential which are, therefore, easily and precisely identified on
changes in the bone marrow which should be recognized and T1-weighted images (Fig. 9.1). Changes of nonirradiated
differentiated from pathologic processes. The second part bone marrow adjacent to the radiation field have been
addresses the effect of treatment on abnormal marrow and reported as well; these have been attributed to an indirect
describes the MRI findings which suggest response of a focal effect of radiation treatment, and they consist of an increase
or diffuse malignant bone marrow pattern to therapy. The in marrow fat content, to a much lesser degree, though,
final part of this chapter deals with common complications compared to that of the irradiated marrow [5]. Furthermore,
of treatment for bone marrow malignancies, such as frac- a gradual decrease in contrast enhancement of the adjacent
tures and osteonecrosis, and the rare but serious complica- nonirradiated bone marrow has been observed on dynamic
tion of bone marrow necrosis. contrast-enhanced MRI (DCE-MRI) studies, during and
after radiation therapy [8].
With lower radiation doses (usually lower than 3,600 cGy),
9.2 Effect of Treatment on Normal red marrow regeneration may occur within the radiation field
Bone Marrow [9]. This red marrow reconversion has been reported to occur
from under a year to up to 23 years after treatment [3, 7, 9,
9.2.1 Effect of Radiotherapy 10]. Hematopoietic marrow reconversion in the irradiated
spine often occurs in a band-like pattern, with red marrow
The effect of radiation therapy on the bone marrow has been appearing in the periphery of the vertebral bodies. This band-
studied on histologic specimens; early changes consist of like pattern of reconversion is more frequently observed in
cellular death and vascular congestion, and they result in children than in adults [3, 10].
edema and hemorrhage of the bone marrow [1, 2]. These
changes occur within the first few days after initiation of
treatment, with a peak around day 9, and they manifest with
Key Points
low signal intensity on T1-weighted images and high signal
intensity on STIR images, reflecting the increase in water of Effect of radiation therapy on normal bone marrow
the necrotic bone marrow [3]. • Cellular death occurs within days after initiation of
The destruction of hematopoietic elements induces fatty therapy
cell growth. Within 2 weeks of therapy, adipose cells in the • Fatty marrow appears within 2 weeks and is strictly
irradiated marrow have grown enough to cause a detectable limited to the radiation portals
increase in signal intensity on T1-weighted images [4]. • Red marrow reconversion occurs with doses lower
Conversion to fatty marrow is completed by 6–8 weeks after than 3,600 cGy, months to many years after radia-
the initiation of radiotherapy in 90 % of patients [5]. Even tion therapy
doses as low as 800 cGy result in fatty marrow conversion [6].

144 9 MRI of Bone Marrow Posttreatment Changes
a b c d
Fig. 9.1 Fatty marrow conversion after radiotherapy. the spine is due to red marrow regeneration after chemotherapy. On the
Sagittal T1-weighted image (a) of the lumbosacral spine of a 68-year- STIR image (b), radiated fatty marrow is hypointense to red marrow. On
old man with a history of radiation therapy to the pelvis for prostate the out-of-phase image (c), there is no signal dropout of the irradiated
cancer shows typical hyperintense fatty marrow in the sacrum and L5, fatty marrow, whereas red marrow in the rest of the spine shows signifi-
conforming to the radiation portals. Low signal intensity of the rest of cant signal loss. The in-phase image (d) is shown for comparison
9.2.2 Effect of Chemotherapy There have been several reports on the MRI appearance of
and Hematopoietic Growth Factors bone marrow after administration of hematopoietic growth
factors both in cancer patients and in healthy peripheral stem
The first few days after initiation of chemotherapy, bone cell donors [13–17]. In a study of patients with musculoskel-
marrow becomes necrotic and edematous, and its signal etal malignancies receiving chemotherapy with G-CSF,
intensity on T1-weighted images drops; on STIR images, the 40 % showed MRI changes consistent with red marrow
marrow signal intensity increases, and on DCE-MRI, there is reconversion [17]. Red marrow reconversion occurs about
decreased bone marrow perfusion. These changes are fol- 2 weeks after the start of the first course of G-CSF, and it
lowed by a short period of fatty marrow conversion. Three to follows a sharp increase in the levels of neutrophils. It is
four weeks into treatment, T1 signal intensity of the bone most often observed in the pelvis and proximal femora,
marrow drops again, as red marrow reappears in the central which are the last sites to undergo physiologic age-related
skeleton during the phase of hematopoietic recovery [11] red to yellow marrow conversion [13, 17].
(Fig. 9.2). Red marrow reconversion related to the administration
Granulocyte colony-stimulating factor (G-CSF), granulo- of hematopoietic growth factors most often manifests with
cyte macrophage colony-stimulating factor (GM-CSF), and a diffuse rather than a focal MRI pattern (Fig. 9.3). On
erythropoietin are hematopoietic growth factors, increas- T1-weighted images, both patterns of red marrow reconver-
ingly used as an adjunct to chemotherapy treatment for vari- sion may be quite similar in appearance to those of malignant
ous malignancies. G-CSF and GM-CSF induce proliferation marrow disease. Knowledge of the sites where these physi-
and dedifferentiation of neutrophil precursor cells and ologic changes are expected to appear and the fact that they
enhance the function of mature granulocytes. This reduces are symmetric aids the differential diagnosis of regenerating
the degree of chemotherapy-induced neutropenia and the red marrow versus malignant marrow. Review of different
number of related febrile episodes, leading to increased tol- pulse sequences in combination is very helpful for an accu-
erance to high-dose chemotherapy and shorter hospitaliza- rate diagnosis. Chemical-shift and contrast-enhanced images
tion times [12]. Erythropoietin stimulates red blood cell especially should be carefully assessed; a rule of thumb is that
production and is used to treat anemia related to various con- normal red marrow shows more than 20 % signal dropout on
ditions including chemotherapy. out-of-phase images and less than 40 % increase in signal
9.2 Effect of Treatment on Normal Bone Marrow 145
a b
Fig. 9.2 Red marrow reconversion following chemotherapy. irradiated sacrum. On the T2 fat-suppressed image (b), the marrow of
Axial T1-weighted image (a) of the pelvis of a 41-year-old man with the iliac bones appears hyperintense. The out-of-phase image (c) shows
rectal cancer treated with chemoradiotherapy shows low-intensity significant signal loss in the iliac bones consistent with red marrow
marrow in the iliac bones (arrows). Fatty marrow is present in the reconversion
intensity on post-contrast T1-weighted images. FDG-PET

imaging in patients who are receiving growth factors may • A diffuse rather than focal pattern of red marrow
show marrow uptake similar to that caused by bone marrow reconversion is more frequent in patients receiving
malignancies; however, several studies have shown that, in growth factors
most patients, bone marrow metabolic activity returns to nor- • Chemical-shift and contrast-enhanced images
mal 1 month after discontinuation of G-CSF treatment [18]. should be carefully reviewed to exclude a malignant
bone marrow pattern
Key Points
Effect of hematopoietic growth factors on normal bone

marrow 9.2.3 Bone Marrow Transplantation
• Administration of growth factors causes red mar-
row reconversion as early as 2 weeks after initiation In the immediate period after bone marrow transplantation
of treatment (BMT), edema of the bone marrow is observed on MR
images (diffuse low T1/high T2 signal). Within 3 months, a
Fig. 9.3 Effect of

hematopoietic growth factors a b c
on bone marrow.
MR images of the thoracic
spine of a 79-year-old man with
colon cancer and red marrow
reconversion after the
administration of hematopoietic
growth factors (granulocyte
colony-stimulating factor and
erythropoietin). Sagittal
T1-weighted image (a) shows
low for age signal intensity of
the bone marrow. No significant
hyperintensity is noted on the
STIR image (b). Compared to
the in-phase image (c), the
out-of-phase image (d) shows
marked drop of marrow signal
intensity. On the post-contrast
T1-weighted image (e), there is
very mild marrow enhance-
ment. The findings are
consistent with red marrow
reconversion
d e
characteristic band-like pattern is seen on T1-weighted endplates; therefore, because of increased vascularity, repop-
images of the spine, consisting of a peripheral zone (i.e., ulation of the bone marrow after transplantation is more pro-
along the vertebral endplates) of low-signal-intensity red nounced in the periphery rather than in the center of the
marrow surrounding a central area of high-signal-intensity vertebral body. The band-like pattern may persist for months
fatty marrow [19]. The band-like pattern of red and fatty before it converts to a normal adult bone marrow pattern; T1
marrow distribution may be explained by the perfusion of the signal intensity of the bone marrow of transplant patients
vertebral bodies. The terminal ramifications of the nutrient remains somewhat higher compared to matched-for-age con-
artery form a network of capillaries beneath the vertebral trols, even years after BMT [20, 21].
9.3 Effect of Treatment on Abnormal Marrow 147
9.3.1 Conventional MR Imaging

Key Points
MRI appearance of bone marrow after BMT T1-weighted images are best suited for the evaluation of
• Bone marrow edema occurs immediately after response in patients with focal patterns of bone marrow
BMT malignancies; additional sequences should be reviewed, par-
• A band-like pattern (red marrow in the periphery ticularly if the uninvolved marrow is predominantly hemato-
and fatty marrow in the center of the vertebral body) poietic because the hypointense malignant foci may not be
is observed on T1-weighted images within 3 months discernible from the low-intensity red marrow. Normalization
from BMT of signal intensity on T1-weighted and STIR images is a sign
of MRI response to therapy. However, even in responding
patients, bone marrow lesions may not resolve on posttreat-
ment MR images. In multiple myeloma patients, for exam-
ple, it has been shown that focal lesions may persist on MR
9.3 Effect of Treatment on Abnormal images for as long as 58 months after treatment, even in
Marrow clinical complete responders [26].
A good response to treatment is easily diagnosed when
The effect of treatment on bone marrow malignancies may there is a decrease in the number or size of focal lesions.
be assessed with a variety of imaging techniques. Skeletal A fatty rim displayed with high signal on T1-weighted images
radiographs show evidence of sclerosis in healing osteolytic (fatty halo sign or T1 halo sign) may appear in the periphery
lesions, but it may take 3–6 months before such changes of responding lesions (Fig. 9.4). If, however, a focal lesion
become apparent. Skeletal scintigraphy requires almost the remains unchanged on T1-weighted images, tumor activ-
same amount of time before it can accurately detect response. ity cannot be readily assessed. The signal characteristics of
The flare phenomenon which consists of increased uptake of the lesion on other MRI sequences may then provide useful
the radiopharmaceutical by newly formed bone in healing information on the effect of therapy. A high-signal-intensity
lesions may mimic active disease; false-positive results may rim at the periphery of a focal lesion on STIR images is a
occur in patients with coexisting degenerative disc disease or sign of aggressive disease, and its disappearance after therapy
other benign bone lesions, further complicating the interpre- is a sign of response [25]. A marked increase in the signal
tation of bone scans. intensity of focal malignant lesions on posttreatment STIR
Bone metastases have been considered nonmeasurable images suggests an increase in water content possibly due to
lesions by standardized response criteria, and until tumor necrosis in responding patients (Fig. 9.5). On contrast-
recently, response to therapy could not be quantified on enhanced images, absence of enhancement or delayed,
imaging studies. The revised Response Evaluation peripheral-only, enhancement of a focal lesion indicates good
Criteria in Solid Tumors (RECIST) 1.1 of 2009, however, response to treatment [27, 28] (Figs. 9.5, 9.6 and 9.7). Non-
allowed osteolytic or mixed metastases to be considered responding lesions continue to enhance early and completely.
as measurable lesions if there is an associated soft-tissue However, contrast-enhanced findings should be interpreted
component ≥1 cm; osteoblastic bone lesions remain non- with caution since myelomatous focal lesions with decreased
measurable [22]. enhancement on posttreatment MRI studies have occasion-
FDG-PET is of value in monitoring the effect of treat- ally been found to have viable tumor cells at histology [29].
ment in patients with bone marrow malignancies; it may On the other hand, in pediatric patients with treated bone
also provide important prognostic information. When marrow malignant lesions, MRI has shown persistent lesion
combined with CT or, more recently, with MRI, it pro- enhancement in spite of negative biopsies for tumor [30].
vides both anatomic and functional information. In mul-
tiple myeloma, a decrease in bone marrow activity on
FDG-PET/CT 2–4 months after initiation of treatment is a
Key Points
sign of response to therapy; on the other hand, persistent
activity after induction treatment is an adverse prognostic Focal malignant patterns: MRI findings of response
sign which may justify a change in therapy [23]. In • Appearance of a fatty rim on T1-weighted images
patients with bone metastases, a reduction in SUV mea- (fatty halo sign or T1 halo sign)
surements and an increase in CT attenuation values are • Resolution of hyperintense rim on STIR
signs characteristic of responding lesions. FDG-PET/CT • Absence of enhancement or delayed peripheral
has been found to be an independent predictor of response enhancement on post-contrast T1-weighted images
duration in patients receiving treatment for breast cancer • Decrease in size or number of lesions
with bone metastases [24, 25].
a b c
Fig. 9.4 Treatment response of bone metastases: Fatty halo sign of a 46-year-old woman who received treatment for metastatic breast
(T1 halo sign). cancer show multiple bone metastases surrounded by a fatty rim of high
Sagittal T1-weighted images of the lumbosacral spine (a, b) and axial signal intensity, indicating response (arrows)
T1-weighted images at L5 (c) and at the level of the sacroiliac joints (d)
Fig. 9.5 Focal pattern: MRI

signs of response to treatment. a b c
MR images of a 62-year-old man
with lymphoma and bone
marrow involvement, before
(a–c) and after (d–f) treatment
with chemotherapy and
irradiation of the spine. At the
time of the second MRI, the
patient had achieved a complete
response by standardized
response criteria for malignant
lymphoma. Sagittal T1-weighted
image (a) shows two focal
hypointense lesions at L5 and S1
(arrows). The lesions are mildly
hyperintense on STIR (b), and
they display homogeneous
enhancement on the post-contrast
T1-weighted image (c) (arrows).
On the posttreatment
T1-weighted image (d), the
lesions are more hypointense
(arrows). They are markedly
hyperintense on STIR (e) and
they show peripheral-only
enhancement on the post-contrast
T1-weighted image (f) (arrows).
The findings are consistent with d e f
necrotic, treated lesions. Also
note interval development of
multiple osteoporotic vertebral
fractures with typical band-like
signal abnormality along the
depressed endplates, related to
both irradiation and steroid
treatment
a b
Fig. 9.6 Focal pattern: MRI signs of response to treatment. (arrow). The lesion displays marked homogeneous contrast enhance-
Axial fat-suppressed contrast-enhanced T1-weighted images of the pel- ment. Also note multiple small enhancing myelomatous foci at the
vis of a 61-year-old man with multiple myeloma before treatment (a), sacrum and left iliac bone. After chemotherapy, there is a decrease in
at 6 months after diagnosis following completion of chemotherapy (b) the size of the lesion which now shows mainly peripheral enhancement
and at 12 months after diagnosis following local irradiation (c). The (arrow in b). Note resolution of left iliac bone and sacral lesions. After
pretreatment image shows a focal lesion at the right iliac bone and radiotherapy (c), the lesion has further decreased in size and the periph-
right sacral alum, associated with a large extraosseous soft-tissue mass eral enhancement is less perceptible (arrow)
a b
Fig. 9.7 Focal pattern: MRI signs of response to treatment. the tumor enhances homogeneously (arrow). On the post-contrast
Axial fat-suppressed contrast-enhanced T1-weighted images of the pel- image, there is peripheral-only enhancement of the iliac bone lesion
vis of a 66-year-old woman with a myelomatous lesion of the right iliac (arrow). At the time of the second MRI, the patient had achieved a
bone before (a) and after (b) chemotherapy. On the pretreatment image, complete response to treatment by standardized clinical criteria
A diffuse MR pattern in a patient with a bone marrow

Key Points malignancy who achieves a partial response to treatment
• On T1-weighted images, malignant focal marrow changes to a focal or variegated pattern on T1-weighted
lesions may persist after treatment even in good images, because fatty marrow reappears in the spine and
responders increases gradually as tumor regresses (Figs. 9.8 and 9.9). In
• Review of other sequences is necessary to evaluate complete responders, a diffuse abnormal marrow pattern may
activity revert to normal [28] (Fig. 9.10). Three to four weeks into
treatment with chemotherapy, the bone marrow may become
a b c
Fig. 9.8 Diffuse pattern: MRI

signs of response to treatment.
Pretreatment (a–c) and posttreat-
ment (d–f) images of the
lumbosacral spine of a 52-year-
old man with multiple myeloma.
The pretreatment diffuse MR
pattern converted to a focal d e f
pattern. At the time of the second
MRI, the patient had achieved a
complete response by standard-
ized clinical criteria. On the
pretreatment images, bone
marrow is diffusely hypointense
on the T1-weighted image (a)
and markedly hyperintense on
STIR (b). Moderate enhancement
is noted on the post-contrast
fat-suppressed T1-weighted
image (c). Posttreatment
T1-weighted (d), STIR (e), and
fat-suppressed contrast-enhanced
T1-weighted (f) images show
reinstitution of normal fatty
marrow in the spine. However, a
focal lesion persists at L2
(arrows). The markedly
hyperintense signal of the lesion
on the STIR image and its
predominantly peripheral
contrast enhancement indicate
response to treatment
Fig. 9.9 Diffuse pattern: MRI signs of

response to treatment. a b
lumbosacral spine of a 78-year-old man with
multiple myeloma and a diffuse pattern of
marrow involvement shows diffusely
hypointense marrow (marrow signal intensity
lower than that of intervertebral discs).
T1-weighted image after treatment (b) shows
variegated pattern of the spine with interval
appearance of multiple small foci of normal
fatty marrow, indicative of response to therapy
a b c d
Fig. 9.10 Diffuse pattern: MRI findings of response to treatment. image (a) and hyperintense on STIR (b). There is reinstitution of nor-
Pretreatment (a, b) and posttreatment (c, d) MR images of the lumbo- mal hyperintense fatty marrow signal on the posttreatment T1-weighted
sacral spine of a 71-year-old man with multiple myeloma and complete image (c) as well as normalization of signal on the posttreatment STIR
response to treatment by standardized clinical criteria. Diffuse pattern image (d)
of abnormal marrow before treatment is hypointense on the T1-weighted
hypointense on T1-weighted images, because of hematopoi- responded to treatment [31]. In another study, DCE-MRI in
etic recovery; this effect of chemotherapy is enhanced by the post-stem cell transplant myeloma patients with good response
concomitant administration of hematopoietic growth factors. to treatment showed a 75 % decrease in slope wash-in value (a
Red marrow reconstitution is distinguished from a persistent perfusion parameter reflecting tissue vascularization, perfu-
diffuse malignant pattern with the aid of additional MR sion, and capillary permeability); this correlated well with the
sequences; normal red marrow will generally show only mild current International Myeloma Working Group (IMWG)
increase in signal intensity on STIR images, more than 20 % response criteria for myeloma [32]. The close correlation of
loss of signal intensity on out-of-phase images and less than laboratory indices of disease activity with this DCE parameter
40 % enhancement on post-contrast T1-weighted images. suggests that DCE-MRI may reliably assess the effect of treat-
ment. Lin et al. reported that the change in maximal percent-
age of bone marrow enhancement (BMEmax) and the timing of
Key Points maximal enhancement of focal lesions on DCE-MRI may
Diffuse malignant patterns: MRI findings of response actually detect disease progression in myeloma patients who
• Conversion to a normal bone marrow pattern have been classified as good responders; more specifically, a
• Conversion to a focal or variegated pattern posttreatment BMEmax of more than 96.8 % and persistent
early enhancement of focal lesions were found to identify poor
responders even among patients who were clinically classified
9.3.2 Advanced MRI Techniques as good responders [33].
Diffusion-weighted imaging (DWI) appears to play a role in
Dynamic contrast-enhanced MRI (DCE-MRI) studies provide the investigation of early response to treatment of malignant
valuable qualitative and quantitative information regarding bone marrow lesions. Focal lesions which respond to treatment
treatment response in patients with bone marrow malignan- are expected to become less cellular with a decrease in signal
cies. Various perfusion parameters have been used by different intensity on high b-value images and an increase in ADC val-
investigators. In a small number of patients with hematologic ues at short-term follow-up (Fig. 9.11). On whole-body DWI of
malignancies who were treated with chemotherapy, the maxi- patients with Durie-Salmon stage III multiple myeloma,
mum percentage of contrast enhancement derived from DCE- responding focal lesions exhibited an average rise of 63.9 % in
MRI decreased 2–6 months after therapy in all patients who ADC values, within 3 weeks from initiation of treatment with
a b
Fig. 9.11 Focal pattern: response

to treatment on diffusion-weighted
imaging.
Posttreatment sagittal STIR image
(a) of the lumbosacral spine of a
72-year-old man with multiple myeloma
shows very hyperintense focal lesion at
L5 (arrow) suggestive of necrosis. The
ADC value of the L5 lesion obtained
from the posttreatment ADC map
(b, arrow) was very high (2.145 ×
10−3 mm2/s), in keeping with response to
treatment. Pretreatment ADC value of
the focal lesion was 0.781 × 10−3 mm2/s.
The patient had achieved clinical
response at the time of the second MRI
study
Fig. 9.12 Diffuse pattern: response

to treatment on diffusion-weighted a b
imaging.
Pretreatment (a) and posttreatment (b)
ADC map of the lumbosacral spine of a
71-year-old man with multiple myeloma
who presented with a diffuse pattern of
marrow involvement on initial MRI (same
patient as in Fig. 9.10). Mean ADC value
of the lumbar vertebrae calculated from
the pretreatment ADC map was 0.719 ×
10−3 mm2/s. The patient achieved a
complete response to treatment and on
the follow-up MRI marrow signal
intensity returned to normal. Mean ADC
value of the lumbar vertebrae calculated
from the posttreatment ADC map was
0.281 × 10−3 mm2/s
novel agents [34]. In patients with bone metastases from pros- MRI appearance of postirradiation fractures of the spine does
tate cancer, an increase in ADC values was detected as early as not differ from that of other benign osteoporotic vertebral frac-
1 month after initiation of treatment [35]. Treatment response tures which are discussed in detail in Chap. 8.
of a diffuse pattern of malignant infiltration of the bone marrow In women with uterine cancer treated with pelvic irradia-
with reinstitution of a normal fatty pattern on T1-weighted tion, insufficiency fractures are common, with reported frac-
images is often accompanied by a return of ADC values within ture rates of 2–89 % [36–45]. The very wide reported range
the normal range (Fig. 9.12). DWI may become a valuable tool of incidence is partly explained by differences in dose and
in the future for the early assessment of treatment response, RT technique. Post-RT fractures are more common in post-
although further studies are needed to validate the method and menopausal women because of the additive role of osteopo-
provide reproducible criteria. rosis. The time of occurrence of these fractures after RT is
highly variable. In a large study with 516 patients who
received radiation therapy for cervical cancer, the median
9.4 MRI Assessment of Complications time between the end of therapy and the detection of frac-
of Treatment tures was 14.1 months [46]. The sacrum, followed by the
medial aspect of the iliac bones, receives the major load of
9.4.1 Post-radiotherapy Fractures the human body which is transmitted through the vertebral
column; therefore, insufficiency fractures after pelvic RT
Insufficiency fractures occur under normal weight-bearing on affect primarily the sacral alae, following a vertical course.
a demineralized bone. Osteoporosis (menopausal or steroid Insufficiency fractures are multiple in the majority of patients
induced) and radiation therapy (RT) are the main predisposing treated with pelvic irradiation for cervical cancer, affect-
factors for their development. Age over 60, female sex, and ing—apart from the sacrum and iliac bones—the roof of the
low body mass index (BMI) are known risk factors. Fractures acetabulum, the pubic rami, L5, and the femoral heads [36]
may occur in any bone subjected to radiation treatment. The (Fig. 9.13). Sacral insufficiency fractures have also been
9.4 MRI Assessment of Complications of Treatment 155
a b
c d
e f
Fig. 9.13 Postirradiation insufficiency fractures. T1-weighted image (c), there is diffuse enhancement of both sacral alae
Axial T1-weighted image (a) of the pelvis of a 42-year-old woman with (solid arrows). Also present is a hypointense fracture line in the left iliac
cervical cancer 10 months after radiation therapy shows symmetric, ill- bone (open arrow) better seen in b, c, amidst bone marrow edema. In the
defined hypointense signal in the anterior portion of both sacral alae same patient, axial T1-weighted (d, e) and fat-suppressed T2-weighted
(solid arrows) in keeping with sacral insufficiency fractures. On the fat- (f, g) images of the pelvis at lower levels show insufficiency fractures of
suppressed T2-weighted image (b), bone marrow edema is extensively the right acetabulum (arrow in d, f) and of the right ischial bone (arrow
hyperintense (solid arrows), and on the fat-suppressed contrast-enhanced in e, g) with associated soft-tissue edema (asterisk in g)
g reported in 7 % of patients with rectal cancer who were

treated with RT [47].
On skeletal scintigraphy, sacral insufficiency fractures
may have the characteristic “H” appearance (vertical frac-
tures of both sacral wings and a third, horizontal fracture of
the sacral body), but findings may be nonspecific, particu-
larly with unilateral fractures, and not easy to distinguish
from bone metastases. CT is helpful because it may demon-
strate the fracture lines which are frequently bilateral and
most often involve the anterior part of the sacrum. On MRI,
ill-defined T1 hypointense and STIR hyperintense signal
(frequently bilateral and symmetric) reflecting marrow
edema is observed, and a low-intensity fracture line may be
seen paralleling the sacroiliac joint(s) (Figs. 9.13, 9.14, and
9.15). In fractures of recent onset, there is moderate to pro-
nounced enhancement of the edematous marrow. Metastatic
disease is easily ruled out on MR images in most cases; sig-
nal alteration of bone metastases is usually asymmetric,
Fig. 9.13 (continued) more homogeneously hypointense on T1-weighted images
a b
Fig. 9.14 Postirradiation insufficiency fractures. Fracture-associated edema is hyperintense on the fat-suppressed
Axial T1-weighted image (a) of the pelvis of a 62-year-old woman with T2-weighted image (b, arrows) and enhances markedly on the fat-sup-
cervical cancer treated with radiotherapy 12 months previously pressed contrast-enhanced T1-weighted image (c). Note hypointense
shows symmetric low-intensity edema of both sacral alae (arrows). fracture line of left sacral ala parallel to the left sacroiliac joint (c, arrows)
a b
c d
Fig. 9.15 Unilateral postirradiation sacral fracture, CT correlation. the anterior portion of the right sacral wing (arrow). Note hypointense
Axial T1-weighted (a), STIR (b), and fat-suppressed contrast-enhanced fracture line on all images. CT image (d) shows interruption of anterior
T1-weighted (c) images of the pelvis of a 59-year-old man with rectal right sacral cortex (arrow) and sclerosis
cancer treated with radiotherapy show abnormal bone marrow edema at
with well-defined rounded margins indicative of a growing 9.4.2 Osteonecrosis

lesion which causes a mass effect. Chronic fractures are usu-
ally hypointense on both T1 and STIR images and lack con- Osteonecrosis (ON) is a known complication of steroid treat-
trast enhancement; in such cases, computed tomography ment, radiation therapy, bone marrow transplantation, and
shows sclerotic changes of healed fractures. chemotherapy. There are numerous other etiologic factors
for ON unrelated to treatment, trauma and alcoholism being
among the most common. ON affects areas with predomi-
Key Points
nantly fatty rather than hematopoietic marrow (appendicular
Post-RT sacral insufficiency fractures skeleton) because of their sparse vascular supply. Moreover,
• Frequently bilateral, involving anterior part of the bony sites with poor collateral vascular supply (femoral
sacrum head, distal femur, proximal tibia and humerus, lunate,
• Marrow surrounding recent fractures is T1 hypoin- scaphoid, and talus) are affected more frequently. Increased
tense, STIR hyperintense, and shows contrast bone marrow fat content in the femoral neck and intertro-
enhancement chanteric region has been demonstrated in patients with ON
• Hypointense fracture lines may be seen of the femoral head compared to age-matched controls [48].
• Unilateral, homogeneous T1 hypointense abnor- There is a tendency to use the term avascular necrosis for
mality with rounded margins may represent bone ischemic lesions that involve the epiphyses and the term
metastasis bone infarct for ischemic lesions of the diaphysis/
metaphysis.
ON has characteristic findings on MRI. Most descrip- frequently observed gas within an intraosseously displaced
tions of MRI findings of ON are related to the hip. On intervertebral disc (Schmorl’s node). Air within an intraver-
T1-weighted images, a hypointense, serpiginous, well- tebral abscess from gas-producing bacteria in patients with
defined rim surrounds the affected area of the bone marrow spondylodiscitis is infrequently observed and readily recog-
(Figs. 9.16, 9.17, and 9.18). The signal intensity of the nized due to its bubbly (rather than linear) appearance and
affected bone marrow varies depending on the evolution of the presence of other signs of spondylodiscitis (e.g., con-
the infarct. In early ON, the region surrounded by the low- trast enhancement of the intervertebral disc).
intensity rim has signal similar to that of fat. In the hip, Osteonecrosis of the jaw is a known complication of ther-
these typical changes of early ON (hypointense rim, fatty apy with bisphosphonates with the highest incidence (about
center) are important to recognize since prompt treatment 7 %) in patients treated for multiple myeloma; it may also be
with core decompression may avoid complications of ON observed in patients receiving treatment with bisphospho-
such as articular collapse or degenerative joint disease. On nates for benign osteoporosis or bone metastases. The dura-
non-fat-suppressed T2-weighted spin-echo images, the tion of therapy with bisphosphonates, previous dental
double line sign may be seen, consisting of two concentric surgery, and presence of active myeloma were found to be
rings: the outer hypointense ring corresponds to reparative the most important predisposing factors for developing
changes at the interface with the healthy bone, and the inner osteonecrosis of the jaw [53, 54].
hyperintense ring is caused by either local hyperemia or a
chemical-shift phenomenon [49]. On STIR or fat-sup-
pressed T2-weighted images, a single hyperintense rim is 9.4.3 Bone Marrow Necrosis
seen (bright band sign). The presence of a subchondral T2
hyperintense fracture (crescent sign) and/or articular col- Bone marrow necrosis is a very rare entity which compli-
lapse are signs of advanced disease. cates the course of disease in patients with malignancies. It
may occur before manifestation of malignant disease, at
diagnosis, or during the course of treatment, and it is most
Key Points frequently observed in patients with acute lymphocytic leu-
kemia [55]. Histopathological examination of specimens
• A hypointense rim surrounding fatty marrow on
with bone marrow necrosis shows loss of myeloid tissue and
T1-weighted images is characteristic of early ON
fat but preservation of the bony trabeculae [56]. Patients
• A double rim on T2 spin-echo images (double line
present with pain, fever, and fatigue. Laboratory findings
sign) or a hyperintense rim on STIR or fat-suppressed
include pancytopenia, thrombocytopenia, or anemia and
T2-weighted images (bright band sign) is character-
elevated lactate dehydrogenase and alkaline phosphatase.
istic of ON
The prognosis of bone marrow necrosis is poor; most patients
die within months from diagnosis.
On MR images, bone marrow necrosis resembles osteo-
ON has been rarely reported in the spine, most often necrosis, but it is more widespread, it affects the spine and
affecting a single vertebral body. It is attributed to ischemia pelvis (central skeleton) rather than the periarticular regions,
following nonunion of a vertebral fracture. It leads to the and it does not lead to osseous collapse [56]. Spinal lesions
development of an intravertebral cleft which may be demon- display a widespread geographic pattern which consists of
strated with various imaging modalities. Vertebral ON is patchy, serpiginous areas of varying signal intensity
strongly associated with a benign (osteoporotic) vertebral (Fig. 9.19). In some of the few cases reported in the litera-
fracture [50, 51]. On skeletal radiographs or CT, a linear ture, enhancing bands of abnormal signal intensity were
collection of gas is seen within the vertebral body, adjacent observed in the vertebral bodies surrounding a central non-
to the collapsed endplate (intravertebral vacuum cleft sign). enhancing area. The signal intensity of the central area varied
On T2-weighted MR images, after supine positioning, fluid depending on the stage of bone marrow necrosis. Widespread
may fill the cleft resulting in high signal intensity (fluid involvement of the skeleton and the above described charac-
sign) [52]. The intravertebral vacuum cleft sign as a feature teristic MRI findings should suggest the diagnosis of bone
of vertebral ON needs to be differentiated from the more marrow necrosis in the proper clinical setting.
a b
Fig. 9.16 Osteonecrosis of the hip: MRI findings. surrounding fatty marrow on the T1-weighted image (a, solid arrow)
Coronal T1-weighted (a) and T2-weighted fat-suppressed (b) images and typical hyperintense rim on the T2-weighted fat-suppressed image
of the hips of a 44-year-old man with advanced osteonecrosis of the (b, solid arrow). Advanced osteonecrosis of the right hip is hypointense
head of the right femur and early osteonecrosis of the left femoral head. on both images in keeping with sclerotic marrow (open arrows)
Early osteonecrosis of the left hip shows typical low-intensity rim
a b
Fig. 9.17 Early osteonecrosis of the hip: MRI findings. high-signal fatty marrow (arrows). Fat-suppressed T2-weighted image
Axial T1-weighted image (a) of the pelvis of a 57-year-old woman (b) shows typical hyperintense rim of osteonecrosis (bright band sign)
with a history of radiation treatment for cervical cancer shows bilateral (arrows)
early osteonecrosis, with low-intensity serpiginous rims surrounding
Fig. 9.18 Bone

infarcts, MRI findings.
a b
Sagittal T1-weighted
images (a, b) of the
knee of a 31-year-old
woman with a history of
Hodgkin lymphoma
treated with corticoste-
roids show metadiaphy-
seal infarcts with
low-intensity serpigi-
nous rims surrounding
fatty marrow (arrows).
Typical hyperintense
rims (bright band sign)
are shown on fat-sup-
pressed proton density
images (c, d)
c d
Fig. 9.19 Bone marrow

a b c
necrosis, MRI findings.
(b), and fat-suppressed
(c) images of the lumbosacral
spine and sagittal T1-weighted
(d), STIR (e), and magnified
fat-suppressed contrast-
enhanced T1-weighted (f)
images of the thoracic spine of
a 59-year-old man. The patient
had lymphoma and developed
bone marrow necrosis together
with tumor relapse, 3 months
after the last treatment. Note
patchy geographic areas of
abnormal signal intensity
involving mainly the central
and posterior aspect of all
vertebral bodies, better shown
on the STIR images as
low-signal-intensity rims. On
the contrast-enhanced images,
there are both non-enhancing
areas which correspond to
necrotic marrow and enhancing
regions which correspond to d e f
active lymphoma
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Bone Marrow MRI: A Quick Guide
10
10.1 Protocol low-signal reinforced trabeculae); otherwise, it is focal fatty

marrow. A hyperintense focal lesion which is located along a
MRI of the bone marrow can be limited to the central skele- vertebral endplate is likely to be a Modic II degenerative
ton. It should include the thoracic and lumbosacral spine and change; look for degeneration of the adjacent disc and simi-
if possible the pelvis. Remember that, in an adult, it is lar changes of the other endplate at the same level.
unlikely to find a malignant bone marrow lesion in the You should not attempt to characterize a hypointense
peripheral skeleton without central lesions. T2 weighting lesion which is smaller than 5 mm. Hypointense focal lesions
should be performed with STIR or fat-suppressed sequences. (larger than 5 mm) with higher signal intensity than that of
Always obtain chemical-shift images; they are invaluable for nondegenerated intervertebral disc or muscle are usually
determining the presence of red marrow and differentiating it benign and most frequently represent red marrow rests.
from malignant lesions. Contrast-enhanced T1-weighted A focus of high T1 signal at the center of the hypointense
images without fat suppression allow for quantitative assess- lesion, when present, is diagnostic of normal red marrow.
ment of enhancement. Contrast-enhanced T1-weighted Otherwise, other sequences and, particularly, chemical-shift
images with fat suppression increase lesion conspicuity. imaging (>20 % signal drop on out-of-phase images) and
Perfusion parameters derived from dynamic contrast- contrast-enhanced T1-weighted sequences (<40 % contrast
enhanced images can be useful in specific clinical situations, uptake) may help diagnose the presence of red marrow rests.
although their use in daily practice of nonspecialized centers If a hypointense lesion does not behave like red marrow on
is limited. Diffusion-weighted images are relatively easy to additional MRI sequences, it may be an atypical hemangi-
perform and may be evaluated qualitatively or quantitatively oma; CT images may help by showing the characteristic
(do not forget to include b-values higher than 500 s/mm2). reinforced trabeculae.
They may provide valuable information related to lesion A T1 hypointense focal lesion which is located along
characterization, treatment response, and differentiation an endplate next to a degenerated disc is likely a Modic
between benign and malignant vertebral fractures. I degenerative change. Modic I changes may be pain-
ful because an active underlying inflammatory process
is present. Spondylodiscitis may also present with T1
10.2 Focal Bone Marrow Lesions hypointense signal along the vertebral endplates. However,
the inflamed disc will be hyperintense on T2-weighted
The assignment of a bone marrow pattern is always made images, and it will enhance to some degree. The pres-
with careful review of T1-weighted images. Pattern assign- ence of extraosseous soft tissue or even a frank abscess
ment not only aids diagnosis by providing a systematic establishes the diagnosis of spondylodiscitis versus degen-
approach to image analysis but can also have prognostic erative endplate changes. Signal hyperintensity on high
implications (e.g., in multiple myeloma where a diffuse pat- b-value diffusion-weighted images favors spondylodiscitis
tern of involvement has been associated with advanced dis- over Modic I changes. A Schmorl’s node may also pres-
ease features and poor prognosis). Focal areas of abnormal ent as a focal hypointense lesion adjacent to an endplate,
signal may be hyperintense or hypointense. A hyperintense but it is easily diagnosed when there is loss of cortical
focal lesion is almost always benign. If such a lesion retains contiguity and similar signal intensity to that of the inter-
some high signal on fat-suppressed T2-weighted images, vertebral disc. Remember that metastases may also occur
then it is almost certainly a hemangioma (also look for along the endplates and look for specific signs of benign

166 10 Bone Marrow MRI: A Quick Guide
lesions. A sclerotic rim, more clearly seen on CT images, since MRI may fail to detect low percentages of malignant
but also identifiable on MR images, is unlikely to occur bone marrow infiltration (particularly with hematologic
with untreated bone metastases. malignancies).
Malignant focal bone marrow lesions are typically
hypointense to nondegenerated disc or muscle, sometimes
isointense to them but almost never hyperintense. Osteolytic 10.4 Vertebral Compression Fractures
metastases cannot be differentiated from a focal pattern of
multiple myeloma. Osteoblastic metastases present as sig- Establishing whether the cause of an acute vertebral compres-
nal void focal lesions. Remember that an enostosis (bone sion fracture is benign (osteoporotic) or malignant (metastatic in
island) may also present as a signal void focal lesion. A most cases) has important clinical implications. The differential
hyperintense rim on T2-weighted images surrounding the diagnosis relies on imaging, and MRI is the exam of choice.
signal void lesion (T2 halo sign) is diagnostic of an osteo- MRI signs favoring the diagnosis of a benign fracture are band-
blastic metastasis. Radiating bony streaks, on the other like low T1 signal parallel to the depressed endplate, a linear
hand, favor the diagnosis of enostosis. Images of malignant area of very high T2 signal adjacent to the endplate (termed the
focal marrow lesions should be carefully inspected for the fluid sign and thought to represent osteonecrosis associated with
presence of extraosseous mass impinging upon the spinal a nonhealed benign fracture), and retropulsion of a vertebral
nerves or cord. T1-weighted images are best suited for the bony fragment. MRI features indicative of a malignant fracture
evaluation of tumor extending to the epidural space or are complete replacement of the normal marrow signal, a con-
intervertebral foramina. On contrast-enhanced images, the vex posterior vertebral border, pedicle involvement (especially
addition of fat suppression facilitates the detection of expansile or deposit-like), and an associated soft-tissue mass,
extraosseous tumor. either focal paraspinal or epidural. DWI (either qualitative or
quantitative) may aid diagnosis. In patients with equivocal find-
ings, a repeat MRI 8–10 weeks after the initial exam will show
10.3 Diffusely Abnormal Bone Marrow partial restoration of normal fatty marrow signal in the vast
majority of benign osteoporotic fractures.
Diffusely hyperintense bone marrow is a normal pattern in
elderly individuals with fatty marrow predomination. A
diffuse hyperintense pattern limited to a portion of the 10.5 Posttreatment Assessment of Bone
marrow (regional hyperintense pattern) is easy to diag- Marrow Malignancies
nose, and it is related to previous irradiation of the bone
marrow, strictly conforming to the radiation portals. It is important to remember that malignant focal marrow
Images of diffusely hypointense bone marrow are more lesions may not resolve completely even on MR images of
difficult to interpret. Bone marrow which is hypointense to complete responders. A most important finding of response
intervertebral discs or muscle is definitely abnormal. If the to treatment is the appearance of fatty marrow signal inten-
signal intensity is higher than—or, occasionally, equal sity within or surrounding (T1 halo sign or fatty halo sign)
to—that of the discs or muscle, it may be due to hypercel- the abnormal bone marrow on T1-weighted images. On
lular red marrow. Carefully revise clinical history to look T2-weighted images, a marked increase in signal intensity of
for chronic anemia or other causes or red marrow recon- a malignant focal lesion is suggestive of necrosis particularly
version (administration of hematopoietic growth factors, if it is associated with lack of enhancement or peripheral-only
pronounced physical activity, etc.). Use chemical-shift and enhancement. Such changes are accompanied by a pronounced
contrast-enhanced images for verification. Diffusion- increase in ADC values in keeping with the increased diffusiv-
weighted imaging may be of value; a diffuse bone marrow ity of lesion necrosis. Diffuse malignant patterns in responding
pattern with ADC values lower than 0.5 × 10−3 mm2/s is patients convert to a normal or focal pattern due to complete or
unlikely to be malignant. Keep in mind that a normal MRI partial reinstitution of fatty marrow. Accordingly, a decrease
pattern does not exclude malignant marrow involvement in ADC values is noted on diffusion-weighted imaging.
Index
A red, 1–5
Acute lymphocytic leukemia, 113, 158 sinusoids, 1, 2, 5
Acute myelogenous leukemia, 113 stromal cells, 2, 62
ADC values. See Apparent diffusion coefficient (ADC) values vascular anatomy, 1, 2
Adult pattern of red/yellow marrow distribution, 4 yellow, 1–5
Algoneurodystrophy. See Complex regional pain syndrome (CRPS) Bone marrow edema
Anatomy of normal bone marrow, 1, 2 following bone marrow transplantation, 145, 147
Anemia, 5, 48, 50, 77, 78, 82, 83, 90, 104, 144, 158, 166 following chemotherapy, 144
Aneurysmal bone cyst, 41 following radiotherapy, 143
Angiogenesis hypointense regional pattern, 53, 54
in acute myelogenous leukemia, 113 vs metastases, 65, 66
and MRI patterns in multiple myeloma, 104 postirradiation insufficiency fractures, 54, 155–157
in multiple myeloma, 77, 83, 85, 86, 104, 105, 109 reversible vs. irreversible disorder, 125
Angiogenic factors syndrome (see Transient bone marrow edema syndrome)
in multiple myeloma, 86 trauma, 53
Angiogenic switch theory, 83, 85, 86 tumor-related, 53, 54
Angiopoietin, 86 vertebral compression fractures, 19, 127, 133–136, 139
Ann Arbor classification, 92 Bone marrow edema syndrome. See Transient bone marrow edema
Aplastic anemia, 31, 47 syndrome
Apparent diffusion coefficient (ADC) values Bone marrow necrosis, 158, 161
malignant marrow (diffuse), 101 Bone marrow transplantation (BMT), 145–147
metastases (diffuse), 103 Bone marrow types, 1
metastases (focal, osteoblastic), 66, 73 Bright band sign, 118, 125, 158–160
metastases (focal, osteolytic), 66, 71, 72 Bull’s eye sign, 41, 65
multiple myeloma (diffuse), 106, 109, 111
multiple myeloma (focal), 87–89
normal bone marrow, 19–21 C
treatment response assessment, 153, 154 Calcineurin inhibitor pain syndrome (CIPS), 115, 122, 123
vertebral compression fractures (benign vs. malignant), 138, 139 Chemical shift imaging, 13–15, 165, 166
Articular collapse, 120 diagnosis of red marrow, 50, 82–84, 101, 144, 165, 166
Avascular necrosis. See Osteonecrosis metastases, 66, 70, 103
multiple myeloma, 83, 84, 105, 106
vertebral compression fractures, 139
B Chemotherapy, 5, 50, 82, 84, 144, 145, 149–151, 153, 157
Band-like sign, 118, 125 effect on normal bone marrow, 144, 145
Bisphosphonates, 120, 158 response assessment, 149–151, 153
Bone bruises, 115, 123–125 Chronic lymphocytic leukemia, 113
osteochondral injuries, 124 Claw sign, 75, 76
Bone infarcts, 37, 40, 160. See also Osteonecrosis Clivus, 32
Bone island. See Enostosis Complex regional pain syndrome (CRPS), 53, 115, 120–122
Bone marrow (normal) Complications of treatment on bone marrow
adipocytes, 2 bone marrow necrosis, 158, 161
adventitial reticular cells, 2, 3 osteonecrosis, 157–160
cellular composition, 1 post-radiotherapy fractures, 154–157
cellular organization, 2 Contrast-enhanced imaging, 16–18
chemical composition, 1 dynamic (see Dynamic Contrast-Enhanced (DCE) MRI)
function, 3 fat suppression, 16
hematopoietic cells, 2, 3, 62 Conversion (fatty, as result of radiotherapy), 143, 144
microenvironment, 1, 4, 63, 77, 128 Conversion (red to yellow marrow), 2–4, 36, 41, 46
MRI in the extremities, 29–32
anatomic sites, 25–33 patterns, 4
pulse sequences, 7–22 in the pelvis, 29

DOI 10.1007/978-88-470-5316-8, © Springer-Verlag Italia 2015
168 Index
Conversion (red to yellow marrow) (cont.) hypointense, 35, 41–43

in the rib cage, 32 signal-void, 35, 43–46
in the skull, 32, 33 Fractures
in the spine, 25, 27, 28 bone marrow edema, 115
Crescent sign, 118, 158 post-radiotherapy insufficiency, 154–157
Cytogenetic abnormalities sacral insufficiency, 154–157
in multiple myeloma, 78, 87, 88, 104 subchondral, 118, 120, 125
trauma, 125
vertebral compression. See Vertebral compression fractures (benign
D vs. malignant)
Degenerative endplate changes
Modic I, 27, 53, 55, 75, 76, 165
Modic II, 10, 12, 14, 25, 27, 36–38, 47, 48, 84, 165 G
Diaphysis, 4, 5, 25, 29–31, 35, 80, 157 Gaucher’s disease, 48
Diffuse large B-cell lymphoma (DLBCL), 93, 95, 112 Granulocyte colony-stimulating factor (GCSF), 144
Diffuse MRI pattern, 35, 47–52 Granulocyte macrophage colony-stimulating factor (GM-CSF), 144
hyperintense, 47 Granulocytic sarcoma (chloroma), 113
hypointense, 47–52
signal-void, 52
Diffusion-weighted imaging, 19–22, 165, 166 H
ADC values, 19, 20 Hemangioma (vertebral), 37, 38, 41, 42, 47, 49, 53, 57–63
metastases, 66, 71, 72, 75, 103 atypical, 41, 42, 61, 62, 64, 165
Modic I degenerative endplate changes, 75, 76 compressive, 57, 58, 61–63
multiple myeloma, 86–89, 106, 109, 111 vs. focal fatty marrow, 37, 60, 165
red marrow, 19, 20, 50 polka dot sign, 58, 61, 62
spondylodiscitis, 77 symptomatic, 57, 58
treatment response assessment, 153, 154, 166 typical MRI appearance, 59–61
vertebral compression fractures, 138 Hematopoiesis, 1–3, 5
whole-body MRI, 75 Hematopoietic growth factors, 5, 48, 50, 82, 109, 144–146, 153, 166
Double line sign, 118, 125, 158 Hematopoietic stem cells, 1, 3
Draped curtain sign, 73, 74, 96 Hemorrhagic myelomatous lesions, 37
Durie-Salmon PLUS staging system, 77, 78 Hemosiderosis, 52
Durie-Salmon staging system, 77, 78 Hip
Dynamic contrast-enhanced (DCE) MRI, 16, 18 bone marrow edema pattern, 115
acute myelogenous leukemia, 113 osteonecrosis, 157–159
angiogenic factors, 86 regional migratory osteoporosis, 120
chemotherapy, 144 transient osteoporosis, 116–118, 120
MGUS, 85, 86 Hodgkin lymphoma, 40, 91–96, 112, 160
multiple myeloma, 85–87, 105, 109, 110 Humerus, 31, 32, 157
radiotherapy, 143 Hyperintense disc sign, 7, 101, 104
treatment response assessment, 153
I
E In-phase image. See Chemical-shift imaging
Enchondroma, 41 Internal standards, 7–9
Enostosis (bone island), 43, 44 International staging system (ISS), 78
vs. osteoblastic metastasis, 65, 68, 166 Intravertebral vacuum cleft sign, 128–131, 133–135, 158
Epiphysis 4, 5, 29, 31
ossification centers, 29, 30
Erythropoietin, 144 K
Extremities, 4, 5, 29–32 Knee
epiphyseal ossification centers, 29 bone bruise, 123, 124
femur, 29–31 bone infarct, 160
humerus, 31, 32 bone marrow edema pattern, 115
mesenchymal stem cells, 4 regional migratory osteoporosis, 120, 121
pattern of red to yellow marrow conversion, 4, 29–32 spontaneous osteonecrosis (SONK), 120
pattern of reconversion to red marrow, 5 transient osteoporosis, 118–120
F L
Fatty halo sign. See T1 halo sign Leukemia(s), 48, 109, 112, 113, 158
Femur, 29–31, 80, 95, 105 acute lymphocytic, 113, 158
osteonecrosis, 157–159 acute myelogenous, 113
transient osteoporosis, 116–118 chronic lymphocytic, 113
Fluid sign, 133, 135, 139, 158, 166 diffuse pattern, 48, 112, 113
Focal fatty marrow, 10, 12, 37, 60, 61 dynamic contrast-enhanced MRI, 113
vs. hemangioma, 37, 60, 165 focal pattern, 113
Focal MRI pattern, 35–46 MRI, 112, 113
hyperintense, 35–40 T1 relaxation times, 113
Index 169
Lipoma (intraosseous), 37, 39 Mini brain sign, 91

Lymphoma(s), 48, 51, 91–96, 109, 112 Modic I degenerative endplate changes. See Degenerative endplate
Ann Arbor staging system, 92, 112 changes
bone marrow biopsy, 92, 93, 95, 112 Modic II degenerative endplate changes. See Degenerative endplate
and bone marrow necrosis, 161 changes
diffuse large B-cell (DLBCL), 93, 112 Monoclonal gammopathy of borderline significance (MGBS), 77
diffuse pattern, 93, 105, 109, 112 Monoclonal gammopathy of uncertain significance (MGUS), 77, 80,
extraosseous mass, 95, 96 81, 83, 85, 86, 90, 109
FDG-PET/CT, 92–95, 112 prognostic value of MRI, 90
focal pattern, 93, 94, 112 MRI patterns of abnormal bone marrow, 35–55
Hodgkin, 40, 91–96, 112, 160 definitions, 35
indolent, 92, 93, 95, 112 diffuse, 35, 47–52
MRI, 93–96, 112 focal, 35–46
non-Hodgkin, 91, 95, 96, 112 hyperintense diffuse, 47
staging, 92, 93, 112 hyperintense focal, 35–40
treatment response assessment, 149 hyperintense regional, 52, 53
whole-body MRI, 95 hypointense diffuse, 47–52
wrap-around sign, 95, 96 hypointense focal, 35, 41–43
hypointense regional, 52–55
regional, 35, 52–55
M signal-void focal, 35, 43–46
Mastocytosis, 43, 48 signal-void diffuse, 52
Mesenchymal stem cells, 4 T1-weighted images for pattern recognition, 35
Metaphysis, 4, 5, 16, 29–32, 157 variegated, 35, 46, 47
Metastases, 62–75, 101–105, 165, 166 Multiple myeloma, 76–92, 104–111
as a cause of vertebral compression fracture, 127, 128 angiogenesis, 77, 83, 86
breast, 9, 17, 45, 63, 70, 72, 75, 101, 103, 105, 112, 147, 148 angiogenic factors, 86
clinical background, 62, 63 angiogenic switch theory, 83, 85, 86
diffuse pattern, 48, 52, 101–105 as a cause of vertebral compression fracture, 128
ADC values, 101, 103 asymptomatic (smoldering), 77, 80, 81, 87, 89, 90, 109
common primary tumors, 101 biology of, 77
hyperintense disc sign, 9, 101, 104 bone marrow plasmacytosis, 77, 81, 104,
MRI findings, 101–104 105, 107, 109
peripheral skeleton involvement, 104, 105 clinical background, 76–78
versus red marrow, 101 CRAB, 77
focal pattern, 41–43, 45, 46, 62–75 cytogenetic abnormalities, 78, 87, 88, 104
ADC values, 66, 71–73 diffuse pattern, 80, 104–111
axial skeleton MRI versus whole-body MRI, 75 ADC values, 109
bone scintigraphy, 63, 64 definition, 105
CT, 63 diffusion-weighted imaging, 106, 109, 111
extraosseous extension, 73–75 dynamic contrast-enhanced MRI, 105, 109, 110
FDG avidity, 64 MRI findings, 105–111
FDG-PET, 63, 64 prognostic value of MRI, 88, 104
intracortical metastases, 64, 75 versus red marrow, 109
MRI findings, 64–75 Durie-Salmon PLUS staging system, 77, 78
osteoblastic versus enostosis, 65, 68, 166 Durie-Salmon staging system, 77, 78
osteoblastic, MRI findings, 45, 46, 65, 66, 68, 69, 71, 73 FDG-PET/CT, 79, 80, 147
osteolytic versus osteoblastic, 63, 65, 66, 69, 71–73 focal pattern, 76–92
osteolytic, MRI findings, 65, 66, 69–72 ADC values, 87
seed and soil theory, 62, 63 definition, 81
spinal, 64, 127, 128 diffusion-weighted imaging, 86–89
spinal cord compression, 73, 75 dynamic contrast-enhanced MRI, 85, 86
T1 hyperintense, 37, 65 hemorrhagic focal lesions, 37, 40
versus bone marrow edema, 65–67 MRI findings, 81–87
versus Modic I degenerative endplate changes, 75, 76 prognostic value of MRI, 88–90
versus red marrow rests, 65–67 sclerotic focal lesions, 43, 90, 91
versus spondylodiscitis, 75, 77 versus red marrow rests, 82–85
whole-body MRI, 64, 75 International Staging System (ISS), 78
melanoma, 37, 65 monoclonal gammopathy of borderline significance
neuroblastoma, 64, 73, 101, 102 (MGBS), 77
prostate, 43, 45, 46, 63, 64, 68–71, 73–75, 102, 104, 138, 154 monoclonal gammopathy of unknown significance
small round cell tumors, 48, 73, 101, 102 (MGUS), 77, 80, 81, 83, 85, 86, 90, 109
treatment response assessment MRI patterns
advanced MRI techniques, 153, 154 definitions, 81
conventional MRI, 147, 148 frequencies, 80, 81
diffusion-weighted imaging, 153, 154 normal pattern, 80, 107
FDG-PET, 147 osteonecrosis of the jaw, 158
RECIST 1.1, 147 osteoporosis, 128
T1 halo sign (fatty halo sign), 147, 148 POEMS syndrome, 43, 90, 91
170 Index
Multiple myeloma (cont.) Reconversion (yellow to red marrow), 2, 5, 48–50, 82

prognostic value of MRI, 87–90 causes, 5
sclerotic, 43, 90, 91 differential diagnosis from malignant marrow, 144, 145,
Schnitzler syndrome, 90, 91 153, 166
staging, 77, 78 differential diagnosis from metastases, 101
solitary bone plasmacytoma, 78, 79, 91, 92 differential diagnosis from multiple myeloma, 109
symptomatic, 77, 80, 81, 86–90 in the peripheral skeleton, 104
treatment response assessment MRI appearance, 50, 51
focal pattern, 147, 150, 153 patterns, 5
diffuse pattern, 151–154 as a result of chemotherapy, 144, 145
with diffusion-weighted imaging, 153, 154 as a result of hematopoietic growth factors, 144–146
with dynamic contrast-enhanced MRI, 153 as a result of radiotherapy, 143, 144
systemic nephrogenic fibrosis, 83 Red (hematopoietic) marrow, 1–5
variegated pattern, 11, 80–83, 85, 104 adult pattern of distribution, 4
whole-body low-dose CT (WBLDCT), 78–80 cellular composition, 1
whole-body MRI (WBMRI), 79, 81, 89 chemical composition, 1
whole-body skeletal radiographic survey (WBXR), 78–80 chemical-shift imaging, 13, 14
Myelodysplastic syndromes, 48 contrast-enhanced imaging, 16–18
diffusion-weighted imaging (DWI), 19, 20
dynamic contrast-enhanced MRI, 16, 18
N hypercellular, 47
Neumann’s law, 3 hyperplasia. See Reconversion (yellow to red marrow)
MRI appearance, 7–20
reconversion. See Reconversion (yellow to red marrow)
O rests, 41, 46, 65–67, 82–85, 165
Opposed-phase image. See Chemical-shift imaging T1-weighted imaging, 7, 8
Osteoblastoma, 41 T2-weighted imaging, 10
Osteonecrosis, 115–118, 120, 125, 128, 134, 157–160, 166 vascularization, 2
articular collapse, 120, 158 Reflex sympathetic dystrophy. See Complex regional pain
band-like sign, 118, 125 syndrome (CRPS)
bone marrow necrosis, differential diagnosis, 158 Regional migratory osteoporosis, 53, 115, 120, 121
bright band sign, 118, 125, 158–160 Regional MRI pattern, 35, 52–55
crescent sign, 118, 158 hyperintense, 52, 53
double line sign, 118, 125, 158 hypointense, 52–55
femoral head, 117, 118, 157–159 Response Evaluation Criteria in Solid Tumors
fluid sign, 133, 135, 139, 158, 166 (RECIST), 147
intravertebral vacuum cleft sign, 128–131, 133–135, 158 Response to treatment. See Treatment response assessment
jaw, 158 Rib cage, 32
MRI findings, 118, 158–160
posttreatment, 157, 158
spontaneous osteonecrosis of the knee (SONK), 120 S
subchondral fractures, 118, 120, 125 Sacrum, 29
Osteopoikilosis, 43, 46 sacral insufficiency fractures, 154–157
Osteoporosis, Schmorl’s node, 158, 165
post-radiotherapy fractures, 154 Sclerotic myeloma
systemic, 120 POEMS, 90
transient. See Transient osteoporosis Schnitzler’s syndrome, 90
vertebral compression fractures, 127, 128 Sign
band-like, 118, 125
bright band, 118, 125, 158–160
P bull’s eye, 41, 65
Pelvis, 29 claw, 75, 76
post-radiotherapy fractures, 154–157 crescent, 118, 158
POEMS syndrome, 43, 90, 91 double line, 118, 125, 158
Polka dot sign, 58, 61, 62 draped curtain, 73, 74, 96
Polycythemia vera, 48, 51 fluid, 133, 135, 139, 158, 166
Puzzle sign, 128, 129, 139 hyperintense disc, 7, 101, 104
intravertebral vacuum cleft, 128–131, 133–135, 158
mini brain, 91
R polka dot, 58, 61, 62
Radiotherapy puzzle, 128, 129, 139
effect on normal bone marrow, 52, 53, 143, 144 T1 halo (fatty halo), 147, 148, 166
insufficiency fractures, 54, 154–157 T2 halo, 43, 46, 66, 69, 73, 166
response assessment, 149, 150 wrap-around, 95, 96
Index 171
Sinusoids, 1, 2, 5 Treatment response assessment, 147–154

Skull, 32, 33 advanced MRI techniques, 153, 154
Small round cell tumors, 48, 73, 101, 102 conventional MRI, 147–153
metastases, diffuse pattern, 101, 102 diffuse patterns, 151–154
Solitary bone plasmacytoma, 78, 79, 91, 92 diffusion-weighted imaging, 153, 154
mini brain sign, 91 dynamic contrast-enhanced MRI, 153
Spine, 25–29 FDG-PET, 147
basivertebral vein, 25, 27 focal patterns, 147–150, 153
cartilaginous plates, 25, 26 Response Evaluation Criteria in Solid Tumors (RECIST), 147
changes following bone marrow transplantation, 145, 146
effect of radiotherapy, 143
marrow fat content, 4 V
metastases, 64 Variegated MRI pattern, 35, 46, 47
mosaic-like appearance, 17, 25, 28, 36, 38, 41, 46, 82, 83, 85 Vertebral compression fracture (benign versus
patterns of yellow marrow deposition, 25 malignant), 127–141, 166
vertebral compression fractures, 127–142 acute, 127
vertebral osteonecrosis, 43, 44, 128, 134, 158 bone marrow edema, 19, 127, 133–136, 138, 139
Spondylodiscitis, 53, 55, 75, 77, 113, 158, 165 clinical background, 127, 128
Spontaneous osteonecrosis of the knee (SONK), 120 chronic, 127
Sudeck’s atrophy. See Complex regional pain syndrome (CRPS) combination of MRI and CT findings, 139
Systemic nephrogenic fibrosis, 83 CT, 128–131, 139
epidural soft-tissue mass, 129, 136, 138, 166
FDG-PET, 130, 132, 139
T fluid sign, 133, 135, 139, 158, 166
T1 halo sign (fatty halo sign), 147, 148, 166 intravertebral vacuum cleft sign, 128–131,
T1-weighted imaging 133–135, 158
bone marrow edema, 115 intravertebral cleft, 128
contrast-enhanced, 16–18 metastatic, 127–129, 132, 133, 136–139, 166
dynamic contrast-enhanced, 16, 18 MRI
extraosseous extension of bone metastasis, 73, 74 accuracy, 139
extraosseous extension of multiple myeloma, 83, 87 band-like abnormal signal, 133–135, 137, 139, 140, 166
for pattern recognition, 35 chemical shift imaging, 139
hyperintense disc sign, 7, 9, 101, 104 diffusion-weighted imaging, 19, 138, 139
infants, 8, 9 morphologic characteristics, 136–138
internal standards, 7–9 quantitative characteristics, 138, 139
leukemia, 109, 112 short-term follow-up, 139–141
metastases (diffuse pattern), 101, 102, 112 signal intensity characteristics, 132–136
metastases (focal pattern), 65, 67 statistically significant predictors, 139
multiple myeloma (diffuse pattern), 105, 108 multiple myeloma, 128, 131, 132
multiple myeloma (focal pattern), 81, 82 osteoporosis, 127, 128
multiple myeloma (variegated pattern), 81 osteoporotic, 127–131, 133–141, 166
normal bone marrow, 7–9 paraspinal soft-tissue mass, 129, 136, 138, 139, 166
spine, 25–29 pedicle involvement, 129, 136–139, 166
pelvis, 29 plain radiography, 128
extremities, 29–31 puzzle sign, 128, 129, 139
skull, 31, 32 Vertebral hemangioma. See Hemangioma (vertebral)
T2 halo sign, 43, 46, 66, 69, 73, 166 Vertebral osteonecrosis, 43, 44, 128, 134, 158
T2-weighted imaging
chemically selective fat-saturation technique, 10
fast spin echo, 10 W
fat suppression, 10–12 Whole-body low-dose CT (WBLDCT)
normal bone marrow, 9–12 multiple myeloma, 78–80
short inversion time inversion recovery (STIR), 10–12 versus MRI, 78, 79
Time-intensity curves (TIC) versus whole-body skeletal radiographic survey, 78
multiple myeloma, 85, 87, 105, 110 Whole-body skeletal radiographic survey (WBXR)
normal bone marrow, 16, 18 multiple myeloma, 78–80
Transient bone marrow edema syndrome, 53, 115, 116 Whole-body MRI (WBMRI)
Transient osteoporosis, 53, 115–120, 125 lymphoma, 95
Transient osteoporosis of the hip, 116–118, 120 metastases, 64, 75
Transient osteoporosis of the knee, 118–120 MGUS, 81, 90
Trauma, 52, 53, 115, 120, 123–125, 157 multiple myeloma, 79, 81, 89
bone marrow edema, 115 versus axial skeleton MRI for metastases, 75
bone bruises, 115, 123–125 versus FDG-PET/CT for metastases, 64
fractures, 115, 116, 125 Wrap-around sign, 95, 96
172 Index
Y diffusion-weighted imaging (DWI), 19, 20

Yellow marrow (fatty) MRI appearance, 7–20
adult pattern of distribution, 4 T1-weighted imaging, 7
cellular composition, 1 T2-weighted imaging, 9, 10
chemical composition, 1 vascularization, 2

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Lia Angela Moulopoulos

Bone Marrow MRI

ISBN 978-88-470-5315-1 ISBN 978-88-470-5316-8 (eBook)

Library of Congress Control Number: 2014956375

© Springer-Verlag Italia 2015

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

To my father, Constantinos Koutoulidis, M.D., who passed away during the

Why a Pattern-Based Approach?

Lia Angela Moulopoulos

We would like to thank the following:

1 Νormal Bone Marrow: Anatomy, Function, Conversion,

5 MRI of the Abnormal Bone Marrow: Focal Pattern . . . . . . . . . . . . . . . . . . . . . . 57

9.3 Effect of Treatment on Abnormal Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

1.1.1 Bone Marrow Types

L.A. Moulopoulos, V. Koutoulidis, Bone Marrow MRI: A Pattern-Based Approach, 1

Fig. 1.1 Bone marrow Periosteal artery

Fig. 1.2 Bone marrow structure: schematic representation.

1.4 Reconversion of Yellow to Red

Reconversion of yellow to red marrow: causes

The first step towards the interpretation of MR images of the

2.1 T1-Weighted Imaging

T1-weighted spin-echo images are most suited for the initial

L.A. Moulopoulos, V. Koutoulidis, Bone Marrow MRI: A Pattern-Based Approach, 7

Fig. 2.2 Red marrow, low T1 signal intensity.

Fig. 2.4 Low T1 signal intensity, normal red marrow.

(Fig. 2.6). Carroll et al. concluded that bone marrow signal

Fig. 2.5 Hyperintense disc a c

Fig. 2.6 Normal bone marrow, a b

Key Points 2.2 T2-Weighted Imaging

On T2-weighted images with fat saturation, foci composed

Fig. 2.8 Multiple myeloma, a b c

Fig. 2.9 Bone metastases, lung

Fig. 2.11 T2-weighted images

Fig. 2.12 Chemical-shift

between red marrow and infiltrated marrow since the latter

Fig. 2.13 Chemical-shift

Fig. 2.14 Chemical-shift a b c

Fig. 2.15 Chemical-shift a b c

Fig. 2.16 Chemical-shift a b c

2.4 Contrast-Enhanced Imaging careful comparison with pre-contrast fat-suppressed images

Fig. 2.17 Contrast

Fig. 2.18 Contrast enhancement of

Fig. 2.19 Focal lesions, value

Fig. 2.21 Normal bone 125

(bottom) and corresponding first 75

It must be noted that discrepancies in ADC values of both

Fatty marrow is easy to recognize on Τ1-weighted MR

L.A. Moulopoulos, V. Koutoulidis, Bone Marrow MRI: A Pattern-Based Approach, 25

Fig. 3.1 Normal spinal bone marrow, 2 months.

Fig. 3.2 Normal spinal bone marrow,

Fig. 3.3 Spinal red to yellow marrow a b

Fig. 3.4 Spinal red to yellow marrow conversion, pattern 2 (endplate).

Fig. 3.5 Spinal red to yellow a b

Fig. 3.6 Spinal red to yellow

Fig. 3.8 Red to yellow marrow conversion, sacrum.

• Rests of red marrow in the pelvis are symmetric,

Fatty marrow in the long bones first appears in the epiphy-

• Low T1 signal intensity in the epiphyses is abnor-

In the proximal femur, three patterns of red to yellow

Red marrow persists in the scapulae, ribs, sternum, and clav-

During the first 2 years of life, the process of fatty conversion