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Annals of Physical and Rehabilitation Medicine 59 (2016) 161–169

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Review

Imaging for osteoarthritis


D. Hayashi a, F.W. Roemer a,b, A. Guermazi a,*
a
Department of Radiology, Boston University School of Medicine, 820 Harrison Avenue, FGH Building 3rd Floor, Boston, MA 02118, United States
b
Department of Radiology, University of Erlangen-Nuremberg, D-91012 Erlangen, Germany

A R T I C L E I N F O A B S T R A C T

Article history: Osteoarthritis (OA) is a widely prevalent disease worldwide and, with an increasing ageing society, is a
Received 1st November 2015 challenge for the field of physical and rehabilitation medicine. Technologic advances and implementa-
Accepted 17 December 2015 tion of sophisticated post-processing instruments and analytic strategies have resulted in imaging
playing a more and more important role in understanding the disease process of OA. Radiography is still
Keywords: the most commonly used imaging modality for establishing an imaging-based diagnosis of OA. The need
Osteoarthritis for an effective non-surgical OA treatment is highly desired, but despite on-going research efforts no
Imaging
disease-modifying OA drugs have been discovered or approved to date. MR imaging-based studies have
Radiography
MR imaging
revealed some of the limitations of radiography. The ability of MR to image all relevant joint tissues
Ultrasound within the knee and to visualize cartilage morphology and composition has resulted in MRI playing a key
CT role in understanding the natural history of the disease and in the search for new therapies. Our review
PET will focus on the roles and limitations of radiography and MRI with particular attention to knee OA. The
use of other modalities (e.g. ultrasound, nuclear medicine, computed tomography (CT), and CT/MR
arthrography) in clinical practice and OA research will also be briefly described. Ultrasound may be
useful to evaluate synovial pathology in osteoarthritis, particularly in the hand.
ß 2015 Elsevier Masson SAS. All rights reserved.

Knee osteoarthritis is a major public health problem that muscle, subarticular bone marrow and synovium, and thus can
primarily affects the elderly. Almost 10% of the United States show the knee as a whole organ three-dimensionally. In addition, it
population suffers from symptomatic knee osteoarthritis by the can directly help in the assessment of cartilage morphology and
age of 60 [S1]. In total, the health care expenditures of this composition. The advantages and limitations of conventional
condition have been estimated at US$ 186 billion annually radiography, MRI and other techniques such as ultrasound, nuclear
[S2]. Despite this there are no approved interventions that medicine, computed tomography (CT) and CT arthrography in the
ameliorate structural progression of this disorder. imaging of osteoarthritis in both clinical practice and research are
The increasing importance of imaging in osteoarthritis for described in this review article.
diagnosis, prognostication and follow-up is well recognized by
both clinicians and osteoarthritis researchers. While conventional 1. Conventional radiography
radiography is the gold standard imaging technique for the
evaluation of known or suspected osteoarthritis in clinical practice Radiography is the simplest, least expensive and most
and research, it has limitations that have become apparent in the commonly deployed imaging modality for OA. It enables detection
course of large magnetic resonance imaging (MRI)-based knee of OA-associated bony features such as osteophytes, subchondral
osteoarthritis studies [1,2]. Pathological changes may be evident in sclerosis and cysts [3]. Radiography can also determine joint space
all structures of a joint with osteoarthritis although traditionally width (JSW), which is a surrogate for cartilage thickness and
researchers have viewed articular cartilage as the central feature meniscal integrity in knees, but direct visualization of these
and as the primary target for intervention and measurement. Of articular structures is not possible. Despite this limitation, slowing
the commonly employed imaging techniques, only MRI can assess of radiographically detected joint space narrowing (JSN) remains
all structures of the joint, including cartilage, meniscus, ligaments, the only structural end point currently approved by the U.S. Food
and Drug Administration to demonstrate efficacy of disease-
* Corresponding author. Tel.: +16174143893. modifying OA drugs in phase III clinical trials. OA is radiographi-
E-mail address: guermazi@bu.edu (A. Guermazi). cally defined by the presence of marginal osteophytes

http://dx.doi.org/10.1016/j.rehab.2015.12.003
1877-0657/ß 2015 Elsevier Masson SAS. All rights reserved.
162 D. Hayashi et al. / Annals of Physical and Rehabilitation Medicine 59 (2016) 161–169

Fig. 1. The Kellgren-Lawrence classification is a composite scale of OA severity taking into account primarily the radiographic OA features of marginal osteophytes and joint
space narrowing in the AP radiograph. A. Kellgren-Lawrence grade 1. Minimal, equivocal osteophytes are observed at the medial joint margins (large arrows). Note that, so-
called notch osteophytes at the centre of the joint (small arrow) are not considered in the Kellgren-Lawrence scale. B. Kellgren-Lawrence grade 2 is characterized by presence
of at least one definite marginal osteophyte (arrow) without evidence of joint space narrowing. C. Kellgren-Lawrence grade 3 knees exhibit signs of definite joint space
narrowing (black arrows) and marginal osteophytes (white arrows). The amount of joint space narrowing is not taken into account. D. Kellgren-Lawrence grade 4 is defined by
bone-to-bone contact and complete obliteration of the joint space (black arrows). Note definite marginal osteophytes in addition (white arrows).

[S3]. Worsening of JSN is the most commonly used criterion for the tibiofemoral, lateral tibiofemoral, and patellofemoral). A recent
assessment of structural OA progression and the total loss of JSW study using data from the OA Initiative and the OARSI atlas for
(‘‘bone-on-bone’’ appearance) is one of the indicators for joint semiquantitative grading of JSN demonstrated that centralized
replacement. radiographic reading is important from the point of observer
We now know cartilage loss is not the only contributor to JSN reliability, as even expert readers seem to apply different
but that changes in the meniscus such as meniscal extrusion and thresholds for JSN grading [7].
meniscal substance loss are also causative factors. The lack of
sensitivity and specificity of radiography for the detection of OA- 1.2. Quantitative assessments
associated articular tissue damage, and its poor sensitivity to
change longitudinally are other limitations of radiography. JSW is the distance between the projected femoral and tibial
Changes in knee positioning can also be problematic in longitu- margins on the anteroposterior radiographic image. Measure-
dinal studies and can affect the quantitative measurement of ments may be performed manually or in a semi-automated fashion
various radiographic parameters including JSW. Despite these using computer software. Quantification using image processing
limitations, radiography is still the gold standard for establishing software requires a digital image, whether digitized plain films or
an imaging-based diagnosis of OA and for assessment of structural images acquired using fully digital modalities such as computed
modification in clinical trials of knee OA. radiography and digital radiography. Minimum JSW is the
standard metric, but the use of location-specific JSW has also
1.1. Semiquantitative assessments been reported [S4]. Using software analysis of digital knee
radiographic images, measures of location-specific JSW were
The severity of radiographic OA can be assessed with shown to be comparable with MR imaging in detecting OA
semiquantitative scoring systems. The Kellgren and Lawrence progression [8]. Various degrees of responsiveness have been
(KL) grading system [4] is a widely accepted scheme for defining
radiographic OA based on the presence of a definite osteophyte
(grade 2). However, KL grading has its limitations; in particular, KL
grade 3 includes all degrees of JSN, regardless of the actual extent.
Fig. 1 depicts representative examples of the different KL grades as
shown on the AP radiograph. Recently, the so-called atrophic
phenotype of knee OA that is characterized by definite joint space
narrowing without concomitant osteophyte formation has gained
increasing attention as a potential risk factor for more rapid
progressive OA, which may be considered a potential adverse event
in so-called anti-nerve growth factor (NGF) drug trials, a class of
new promising antianalgesic compounds currently under investi-
gation [5]. Although this phenotype is rare, it needs special
attention in the research community as it potentially also is a
reflection of more rapid disease progression [6]. Fig. 2 shows an
example of the atrophic phenotype of radiographic OA.
The Osteoarthritis Research Society International (OARSI) atlas
[3] provides image examples for grades for specific features of OA
Fig. 2. Kellgren-Lawrence 3 knees with definite joint space narrowing (arrowheads)
rather than assigning global scores according to definitions like the but only minimal osteophyte formation (arrow) are considered to represent the so-
KL grading system. The atlas grades tibiofemoral JSW and called atrophic phenotype of knee OA. This subtype of radiographic knee OA may be
osteophytes separately for each compartment of the knee (medial a reflection of more rapid disease progression.
D. Hayashi et al. / Annals of Physical and Rehabilitation Medicine 59 (2016) 161–169 163

observed depending on the degree of OA severity, length of the


follow-up period, and the knee positioning protocol [S4] [8]. Mea-
surements of JSW obtained from knee radiographs have been
found to be reliable, especially when the study lasted longer than
two years and when the radiographs were obtained with the knee
in a standardized flexed position [S5].
The role of malalignment in OA disease process has been
described in the literature. A clinical trial showed that varus
malalignment negated the slowing of structural progression of
medial JSN by doxycycline [S6]. Valgus malalignment of the lower
limb was shown to increase the risk of disease progression in knees
with radiographic lateral knee OA [9]. Malalignment might be a
target for prevention of radiographic knee OA as determined by JSN
in overweight and obese women [10].

2. Other radiography-based techniques

Interestingly, two older methods – tomosynthesis and bone


texture analysis – have experienced a revival recently. Tomosyn-
thesis generates an arbitrary number of cross-sectional images
from a single pass of the X-ray tube. A recent study showed that
tomosynthesis is more sensitive in the detection of osteophytes
and subchondral cysts than radiography, using 3T MRI as the
reference [11]. Moreover, tomosynthesis was shown to offer
excellent intrareader reliability regardless of the reader experience
Fig. 3. Subchondral bone marrow lesions (BMLs) are commonly observed in knees
[12]. Quantification of JSW using tomosynthesis has also been with OA. These are a reflection of increased loading and particularly large BMLs may
reported [S7]. Bone texture analysis extracts from conventional be responsible for pain and structural progression. BMLs are visualized as ill-
radiographs information on two-dimensional trabecular bone defined areas of hyperintensity in the subchondral bone (arrows).
texture that relates directly to three-dimensional bone structure. It
has been shown that bone texture may be a predictor of particularly prone to this type of artifact [25]. To ascertain optimal
progression of tibiofemoral OA [13]. assessment of MRI-derived data, trained musculoskeletal radio-
logists should be consulted when designing imaging-based OA
3. MRI studies or when interpreting data from the studies.

Because of the high cost, MRI is not routinely used in clinical 3.2. Semiquantitative MRI scoring systems for knee OA
management of OA patients. However, MRI has become a key-
imaging tool for OA research [14–16] thanks to its ability to assess A detailed review of semiquantitative MRI assessment of OA has
pathology in structures not visualized by radiography i.e. articular been published [15]. In addition to the three well-established
cartilage, menisci, ligaments, synovium, capsular structures, fluid scoring systems – the Whole Organ Magnetic Resonance Imaging
collections and bone marrow [2,17–21]. With MRI the joint can be Score (WORMS) [26], the Knee Osteoarthritis Scoring System
evaluated as a whole organ and multiple tissue changes can be (KOSS) [S8], and the Boston Leeds Osteoarthritis Knee Score
monitored simultaneously; pathologic changes of pre-radiograph- (BLOKS) [S9] – a new scoring system called the MR Imaging
ic OA can be detected; and biochemical changes within joint Osteoarthritis Knee Score (MOAKS) [27] was most recently
tissues such as cartilage can be assessed before morphologic published. Of the three systems, WORMS and BLOKS have been
changes become evident. An MRI-based definition of OA is widely disseminated and used, but these scoring systems both
available [22]. In addition, with MRI, OA can be classified into have strengths and weaknesses. MOAKS provides a refined scoring
hypertrophic and atrophic phenotypes, according to the size of tool for cross-sectional and longitudinal semiquantitative MRI
osteophytes and concomitant presence or absence of JSN assessment of knee OA. It includes semiquantitative scoring of
[6]. Importantly, the use of MRI has led to significant findings pathological features: bone marrow lesions; subchondral cysts;
about the association of pain with bone marrow lesions [23] and articular cartilage; osteophytes; Hoffa synovitis and synovitis-
synovitis [24], with implications for future OA clinical trials. Fig. 3 effusion; meniscus; tendons and ligaments; and periarticular
shows an example of typical large bone marrow lesions that are features such as cysts and bursitides.
commonly seen in conjunction with severe cartilage damage and The use of within-grade changes for longitudinal assessment is
may be responsible for pain in OA. commonly applied in OA research using semiquantitative MRI
approaches [28]. Within-grade scoring describes progression or
3.1. Technical considerations improvement of a lesion that does not meet the criteria of a full
grade change but does represent a definite visual change in
It should be emphasized that investigators need to select comparison to the previous visit. A recent study demonstrated that
appropriate MR pulse sequences for the purpose of each study. For within-grade changes in semiquantitative MRI assessment of
example, focal cartilage defects and bone marrow lesions are best cartilage and bone marrow lesions are valid and their use may
assessed using fluid-sensitive fast spin echo sequences (e.g. T2- increase the sensitivity of semiquantitative readings for detecting
weighted, proton density-weighted or intermediate-weighted) longitudinal changes in these structures [28].
with fat suppression [14,17]. Moreover, MRI may sometimes be Synovitis is an important feature of OA and is associated with
affected by artifacts that mimic pathological findings. For example, pain [24]. Although synovitis can be evaluated with non-contrast-
susceptibility artifacts can be misinterpreted as cartilage loss or enhanced MR imaging by using the presence of signal changes in
meniscal tear. Gradient recalled-echo sequences are known to be the Hoffa fat pad or joint effusion as an indirect marker of synovitis,
164 D. Hayashi et al. / Annals of Physical and Rehabilitation Medicine 59 (2016) 161–169

Fig. 4. Comparison of inflammatory manifestations of disease using non-enhanced and contrast-enhanced sequences. A. Axial intermediate-weighted fat-suppressed MRI
shows homogeneous hyperintensity within the joint cavity consistent with grade 2 effusion-synovitis by MOAKS and WORMS (asterisk). Note: BML in the posterior lateral
femoral condyle consistent with traction edema at the insertion of the anterior cruciate ligament (arrows). B. Corresponding T1-weighted fat-suppressed image after
intravenous contrast administration clearly differentiates between intra-articular joint fluid depicted as hypointensity (asterisk) and true synovial thickening visualized as
hyperintense contrast enhancement of the synovial membrane (arrows). Note that BMLs are similarly depicted on T2-weighted fat-suppressed and T1-weighted contrast-
enhanced fat-suppressed MRI (arrowheads).

only contrast-enhanced MR imaging can reveal the true extent of Scoring System (HOAMS) is available for use in observational
synovial inflammation [29]. Scoring systems of synovitis based on studies and clinical trials of hip joints [35]. In HOAMS, fourteen
contrast-enhanced MR imaging have been published [24], and articular features are assessed: cartilage morphology, subchondral
these could potentially be used in clinical trials of new OA drugs bone marrow lesions, subchondral cysts, osteophytes, acetabular
that target synovitis. Fig. 4 shows a direct comparison between labrum, synovitis (scored only when contrast-enhanced sequences
non-enhanced and contrast-enhanced MRI for the visualization of are available), joint effusion, loose bodies, attrition, dysplasia,
synovitis and joint effusion. trochanteric bursitis/insertional tendonitis of the greater trochan-
Other available semiquantitative MRI scoring systems related ter, labral hypertrophy, paralabral cysts and herniation pits at the
to knee OA include Cartilage Repair Osteoarthritis Knee Score supero-lateral femoral neck. HOAMS demonstrated satisfactory
(CROAKS) [30] and Anterior Cruciate Ligament Osteoarthritis Score reliability and good agreement concerning intra- and inter-
(ACLOAS) [31], which can be applied to research studies focusing observer assessment. Recently another system was introduced
on these structures. Specifically for imaging of cartilage repair that uses a similar approach [36]. Direct comparisons of HOAMS
tissue, MRI Observation Cartilage Repair Tissue (MOCART) scoring and SHOMRI in regard to responsiveness and validity are missing
is available and has been applied to research studies involving to date.
cartilage repair surgery [32].
3.5. Quantitative analysis of articular cartilage and other tissues
3.3. Semiquantitative MRI scoring system for hand OA
Quantitative measurement of cartilage morphology segments
the cartilage image and exploits the three-dimensional nature of
Radiography is still the modality of choice for assessment of
hand OA in a clinical setting but the use of more sensitive imaging MRI data sets to evaluate tissue dimensions (such as thickness and
volume) or signal as continuous variables. Examples of nomencla-
techniques such as ultrasound and MRI is becoming more common
in OA research [S10]. A semiquantitative MRI scoring system for ture for MRI-based cartilage measures and strategies for efficient
analysis of longitudinal changes in subregional cartilage thickness
hand OA features called the OMERACT Hand Osteoarthritis
Magnetic Resonance Scoring System (HOAMRIS) is available and were proposed by Eckstein et al. [37] [S12]. Quantitative cartilage
morphometry has been widely applied in OA studies [S13]
offers high reliability and responsiveness [S11]. Scored pathologi-
cal features include synovitis, erosions, cysts, osteophytes, JSN, [38]. Quantitative measures of articular cartilage structure, such
as cartilage thickness loss and denuded areas of subchondral bone
malalignment and bone marrow lesions. Using these scoring
systems, Haugen et al. showed that MRI could detect approxi- have been shown to predict an important clinical outcome, i.e.
knee replacement [S13]. Quantitative MRI analysis can also be
mately twice as many joints with erosions and osteophytes as
conventional radiography (P < 0.001) [33] and that moderate/ applied to evaluate non-cartilage tissues in the joint including
menisci [S14], bone marrow lesions [S15], synovitis [S16] and joint
severe synovitis, bone marrow lesions, erosions, attrition and
osteophytes were associated with joint tenderness independently effusion [S17]. However, using segmentation approaches for ill-
of each other [34]. These studies demonstrated that some of the defined lesions such as bone marrow lesions is more challenging
semiquantitatively assessed MRI features of hand OA may be than segmentation of clearly delineated structures such as
potential targets for therapeutic interventions. cartilage, menisci and effusion.

3.6. Compositional MRI


3.4. Semiquantitative MRI scoring system for hip OA
Compositional MRI allows visualization of the biochemical
The hip joint has a spherical structure and its very thin covering properties of different joint tissues. It may be sensitive to early,
of articular hyaline cartilage makes MRI assessment of the hip pre-morphologic changes that cannot be visualized on conven-
much more difficult than the knee. A whole organ semiquantitative tional MRI. Compositional MRI has been mostly applied for
multi-feature scoring system called the Hip Osteoarthritis MRI ultrastructural assessment of catilage, although the technique can
D. Hayashi et al. / Annals of Physical and Rehabilitation Medicine 59 (2016) 161–169 165

also be used to assess other tissues such as the menisci or content in the central aspect of the cartilage of the central medial
ligaments. Detailed reviews on this topic have been published femoral condyle.
recently [39,40]. Compositional MRI of cartilage matrix changes Novel compositional techniques have been further explored,
can be performed using advanced MRI techniques such as delayed including in vivo diffusion tensor imaging [S19], T2* mapping [46],
gadolinium-enhanced MRI of cartilage (dGEMRIC), T1 rho, and T2 ultra-short echo time-enhanced (UTE) T2* mapping [47], and
mapping [S18]. Of these, the first two take advantage of the sodium imaging [48]. These techniques show promise, but are still
concentration of highly negatively charged glycosaminoglycans at an early stage of research and development.
(GAGs) in healthy hyaline cartilage; loss of these GAGs in focal
areas affected by possible early disease can be visualized. Both 4. Ultrasound
dGEMRIC and T1 rho focus on charge density in cartilage. In
contrast, T2 concentrations are affected by a complex combination Ultrasound imaging enables real time, multiplanar imaging at
of collagen orientation and hydration of cartilage. relatively low cost. It offers reliable assessment of OA-associated
Compositional MRI techniques are currently not routinely used features, including inflammatory and structural abnormalities,
in clinical practice and remain research tools that are available only without contrast administration or exposure to radiation [49]. Limi-
at a limited number of institutions. Nevertheless, they have been tations of ultrasound include that it is an operator-dependent
applied in clinical trials and observational studies. A recent technique and that the physical properties of sound limit its ability
placebo-controlled double-blind pilot study of collagen hydroly- to assess deep articular structures and the subchondral bone.
sate for mild knee OA demonstrated that the dGEMRIC score Ultrasound is useful for evaluation of cortical erosive changes
increased (meaning higher GAG content and better cartilage and synovitis in inflammatory arthritis. In OA, the major advantage
status) in tibial cartilage regions of interest in patients receiving of ultrasound over conventional radiography is the ability to detect
collagen hydrolysate, and decreased in the placebo group, with a synovial pathology. Current generation ultrasound technology can
significant difference being observed at 24 weeks [41]. Crema et al. detect synovial hypertrophy, increased vascularity and the
showed that a decrease in dGEMRIC indices was associated with an presence of synovial fluid in joints affected by OA [49]. The
increase in cartilage thickness in the medial compartment of the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OME-
knee, suggesting that an increase in cartilage thickness may also be RACT) Ultrasonography Taskforce defined synovial hypertrophy on
related to a decrease in proteoglycan concentration [42]. Souza ultrasound as ‘‘abnormal hypoechoic (relative to subdermal fat,
et al. [43] demonstrated that acute loading of the knee joint but sometimes may be isoechoic or hyperechoic) intra-articular
resulted in a significant decrease in T1 rho and T2 relaxation times tissue that is non-displaceable and poorly compressible and which
of the medial tibiofemoral compartment and especially in cartilage may exhibit Doppler’’ [S20]. Although this definition was devel-
regions with small focal defects, suggesting that changes of T1 rho oped for use in rheumatoid arthritis, it may also be applied to OA
values under mechanical loading may be related to the because the difference in synovial inflammation between OA and
biomechanical and structural properties of cartilage. Hovis et al. rheumatoid arthritis is largely quantitative rather than qualitative
reported that light exercise was associated with low cartilage [49].
T2 values but moderate and strenuous exercise was associated A preliminary ultrasonographic scoring system for features of
with high T2 values in women, suggesting that activity levels can hand OA published in 2008 [50] included evaluation of grey-scale
affect cartilage composition [44]. In an interventional study synovitis and power Doppler signal in 15 joints of the hand. These
assessing the effect of weight loss on articular cartilage, features were assessed for their presence/absence and if present
Anandacoomarasamy et al. reported that improved articular were scored semiquantitatively using a 1–3 scale. Overall, the
cartilage quality was reflected as an increase in the dGEMRIC reliability exercise demonstrated moderately good intra- and
index over one year for the medial but not the lateral compartment inter-reader reliability. This study showed that an ultrasound
[45], highlighting the role of weight loss in possible clinical and outcome measure suitable for multicenter trials assessing hand OA
structural improvement. Fig. 5 shows an example of a knee with a is feasible and likely to be reliable, and has provided a foundation
prevalent meniscal tear and corresponding decrease in GAG for further development.

Fig. 5. Compositional MRI. A. Sagittal fat-suppressed proton density-weighted image shows a horizontal meniscal tear at the posterior horn of the medial meniscus reaching
the undersurface of the mensicus (arrow). B. Corresponding color-coded T1-weighted dGEMRIC image after intravenous contrast administration shows a decrease of the
dGEMRIC index in the weight bearing part of the medial femoral condyle coded in red (arrows) representing early cartilage degeneration reflected as a decrease in
glucosaminoglycan content compared to the posterior parts of the femoral cartilage that are coded in yellow and green.
166 D. Hayashi et al. / Annals of Physical and Rehabilitation Medicine 59 (2016) 161–169

Fig. 6. Assessment of meniscal extrusion by ultrasound. A. Coronal ultrasound screenshot of the medial tibiofemoral compartment shows an extruded body of the medial
meniscus under weight bearing conditions (arrows). B Corresponding coronal fat-suppressed proton density-weighted MRI shows extrusion to a lesser extent (arrows) due to
the prone positioning for the MRI acquisition.

Ultrasound has been increasingly deployed for assessment of site of synovitis and bone marrow lesions associated with OA
hand OA. Kortekaas et al. showed that ultrasound-detected [56]. Additionally, there have been increasing research efforts to
osteophytes and JSN are associated with hand pain [51]. The same apply SPECT/CT for imaging of osteoarthritis [57]. A major
group of investigators also showed that ultrasound-detected signs limitation of radioisotope methods is poor anatomical resolution
of inflammation are associated with development of erosions in but there are ways to overcome it. Hybrid technologies such as
hand OA, implicating inflammation plays a role in its pathogenesis PET-CT and PET-MR imaging combine functional imaging with
and could be a therapeutic target [S21]. Ultrasound can be used to high-resolution anatomical imaging. Fig. 7 shows an example of
evaluate the therapeutic efficacy. A decrease in pain correlated PET-CT in knee OA that combines the high resolution of the CT with
with a decrease in synovial thickening and power Doppler the metabolic information of the PET. However, nuclear medicine
ultrasound score before and after weekly ultrasound-guided imaging is not commonly applied to imaging of OA in a routine
intra-articular injections of hyaluronic acid [52]. Real time fusion clinical setting.
of ultrasound and MR imaging in hand and wrist OA have been
attempted, and found a high concordance of the bony profile 6. CT
visualization at the level of osteophytes [S10].
Ultrasound has also been used to evaluate features of knee OA CT is excellent for depicting cortical bone and soft tissue
and hip OA. A cross-sectional, multicenter European study calcifications, and has an established role in assessing facet joint
analyzed 600 patients with painful knee OA, and found ultra- OA of the spine. Using a CT-based semiquantitative grading system
sound-detected synovitis correlated with advanced radiographic of facet joint OA, studies have shown a high prevalence of facet
OA and clinical symptoms and signs suggestive of an inflammatory joint OA which increases with age, and is most common at the L4–
‘‘flare’’ [53]. Ultrasound-detected inflammatory features were L5 spinal level [58] as well as associations between obesity with
positively and linearly associated with knee pain in motion in higher prevalence of facet joint OA and that between increasing
patients with equal radiographic grades of knee OA in both knees age with higher prevalence of disc narrowing, facet joint OA, and
[54], supporting the association between synovitis and knee pain, degenerative spondylolisthesis [S24]. Ionizing radiation and
which has also been reported in MR imaging-based studies [24]. limited ability of soft tissue evaluation limit the routine use of
Fig. 6 shows an example of the utility of ultrasound for the CT in clinical imaging of OA.
visualization of meniscal extrusion. An advantage of ultrasound
over MRI in regard to extrusion measurements is the possibility of 7. CT and MR arthrography
weight bearing examinations [55].
With CT or MR arthrography, assessment of cartilage damage is
5. Nuclear medicine possible with high anatomical resolution in a multiplanar fashion
[S23] [59,60]. CT arthrography is currently the most accurate
Nuclear medicine imaging with radiotracers enables imaging of method for evaluating superficial and focal cartilage damage,
active metabolism and visualization of bone turnover changes seen offering high spatial resolution and high contrast between the low-
with osteophyte formation, subchondral sclerosis, subchondral attenuating cartilage and high-attenuating superficial (contrast
cyst formation and bone marrow lesions as well as sites of material filling the joint space) and deep (subchondral bone)
synovitis [S22]. Scintigraphy with 99mTc-hydroxymethane diphos- boundaries [S23]. Fig. 8 shows an example of CT arthrography that
phonate (HDP) and positron emission tomography (PET) with delineates superficial and full thickness cartilage damage in
2-18F-fluoro-2-deoxy–D-glucose (18FDG) or 18F-fluoride (18F ) excellent fashion. CT can also depict subchondral bone sclerosis
have been used to assess OA. Bone scintigraphy can provide a and osteophytes. For subchondral changes, MR arthrography
full-body survey that helps to discriminate between soft tissues allows delineation of subchondral bone marrow lesions on the
and bone origin of pain, and to locate the site of pain in patients fluid-sensitive sequences with fat suppression [S23]. Both techni-
with complex symptoms [S23]. 18FDG-PET can demonstrate the ques enable visualization of central osteophytes, which are
D. Hayashi et al. / Annals of Physical and Rehabilitation Medicine 59 (2016) 161–169 167

Fig. 7. PET-CT. A. Conventional coronal CT reformation shows definite OA on the left with marginal tibial and femoral osteophytes (thin arrows) and definite medial
tibiofemoral joint space narrowing. Total knee arthroplasty of the right knee with the metal implants clearly depicted as markedly hyperdense structures (large arrows). Note
beam-hardening artifacts due to the metal hardware particularly surrounding the distal femur. B. Color-coded fusion image of PET and CT shows marked tracer uptake in the
perimensical region bilaterally representing active synovitis (large arrows). C. Corresponding axial fusion image shows synovitis also in the peripatellar recesses (small
arrows). In addition, there is marked synovitis posteriorly adjacent to the posterior cruciate ligament, the most common location of synovitis in knee OA (large arrow). To date
PET-CT does not play a relevant role for the assessment of knee OA structural changes in the clinical routine practice.

8. Conclusion

Imaging of OA has helped investigators to understand risk factors


for disease onset and progression and the interactions between
different joint tissues and peritarticular tissue changes. Despite
those research advances the role of imaging in the routine clinical
management of OA patients remains less well-defined in that
imaging findings do not always correlate with clinical symptoms.
Given such limitations, radiography is still most commonly used for
semiquantitative and quantitative evaluation of structural OA
features. MRI is currently the most important imaging modality
for OA research, and available options include semiquantitative,
quantitative and compositional analyses. Ultrasound is commonly
used in hand OA studies and is particularly useful for evaluation of
synovitis and for guidance of joint-related procedures. Nuclear
medicine, CT and CT-MR arthrography have limited roles compared
Fig. 8. CT arthrography is considered the imaging gold standard for the visualization to radiography, MRI and ultrasound.
of the articular surface integrity. After intra-articular injection of an iodine-based
contrast agent the cartilage surface can be depicted as a hypodense structure. Image
example shows a focal full thickness defect at the lateral tibia (arrow). Role of the funding source

No funding received.

associated with more severe changes of OA than marginal Disclosure of interests


osteophytes [S25]. Due to the high cost, invasive nature and
potential risk, albeit low, associated with intra-articular injection, Dr. Guermazi has received consultancies, speaking fees, and/or
arthrographic examinations are rarely used in large scale clinical or honoraria from TissueGene, OrthoTrophix, and Merck Serono and
epidemiological OA studies. is the President of Boston Imaging Core Lab (BICL), a company
168 D. Hayashi et al. / Annals of Physical and Rehabilitation Medicine 59 (2016) 161–169

providing image assessment services. Dr. Roemer is Chief Medical tibiofemoral cartilage loss during a six-month period: the joints on glucos-
amine study. Arthritis Rheum 2012;64:1888–98.
Officer and shareholder of BICL. Dr. Hayashi declares that he has no [21] Roemer FW, Guermazi A, Felson DT, Niu J, Nevitt MC, Crema MD, et al. Presence
competing interest. of MRI-detected joint effusion and synovitis increases the risk of cartilage loss
in knees without osteoarthritis at 30-month follow-up: the MOST study. Ann
Rheum Dis 2011;70:1804–9.
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Appendix A. Supplementary data of osteoarthritis on MRI: results of a Delphi exercise. Osteoarthritis Cartilage
2011;19:963–9.
[23] Zhang Y, Nevitt M, Niu J, Lewis C, Torner J, Guermazi A, et al. Fluctuation of
Supplementary data associated with this article can be found, in knee pain and changes in bone marrow lesions, effusions, and synovitis on
the online version, at http://dx.doi.org/10.1016/j.rehab.2015.12. magnetic resonance imaging. Arthritis Rheum 2011;63:691–9.
003. [24] Guermazi A, Roemer FW, Hayashi D, Crema MD, Niu J, Zhang Y, et al. Assess-
ment of synovitis with contrast-enhanced MRI using a whole-joint semiquan-
titative scoring system in people with, or at high risk of, knee osteoarthritis:
the MOST study. Ann Rheum Dis 2011;70:805–11.
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