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Contents lists available at ScienceDirect

Injury
journal homepage: www.elsevier.com/locate/injury

Review

Musculoskeletal trauma imaging in the era of novel molecular

methods and artificial intelligence
Michail E. Klontzas a,b, Georgios Z. Papadakis b,c,d, Kostas Marias c,e,
Apostolos H. Karantanas a,b,c,d,∗
a
Department of Medical Imaging, Heraklion University Hospital, Crete, 70110, Greece
b
Advanced Hybrid Imaging Systems, Institute of Computer Science, Foundation for Research and Technology (FORTH), N. Plastira 100, Vassilika Vouton
70013, Heraklion, Crete, Greece
c
Computational Biomedicine Laboratory (CBML), Foundation for Research and Technology Hellas (FORTH), 70013, Heraklion, Crete, Greece
d
Department of Radiology, School of Medicine, University of Crete, 70110 Greece
e
Department of Electrical and Computer Engineering, Hellenic Mediterranean University, 71410, Heraklion, Crete, Greece

a r t i c l e i n f o a b s t r a c t

Article history: Over the past decade rapid advancements in molecular imaging (MI) and artificial intelligence (AI) have
Accepted 15 September 2020 revolutionized traditional musculoskeletal radiology. Molecular imaging refers to the ability of various
Available online xxx
methods to in vivo characterize and quantify biological processes, at a molecular level. The extracted
Keywords: information provides the tools to understand the pathophysiology of diseases and thus to early detect,
Magnetic resonance imaging to accurately evaluate the extend and to apply and evaluate targeted treatments. At present, molecular
Musculoskeletal system/injuries imaging mainly involves CT, MRI, radionuclide, US, and optical imaging and has been reported in many
Hybrid positron-emission Tomography/MR clinical and preclinical studies. Although originally MI techniques targeted at central nervous system dis-
imaging orders, later on their value on musculoskeletal disorders was also studied in depth. Meaningful exploita-
Neural networks tion of the large volume of imaging data generated by molecular and conventional imaging techniques,
Deep learning requires state-of-the-art computational methods that enable rapid handling of large volumes of informa-
Artificial intelligence
tion. AI allows end-to-end training of computer algorithms to perform tasks encountered in everyday
clinical practice including diagnosis, disease severity classification and image optimization. Notably, the
development of deep learning algorithms has offered novel methods that enable intelligent processing of
large imaging datasets in an attempt to automate decision-making in a wide variety of settings related to
musculoskeletal trauma. Current applications of AI include the diagnosis of bone and soft tissue injuries,
monitoring of the healing process and prediction of injuries in the professional sports setting. This re-
view presents the current applications of novel MI techniques and methods and the emerging role of AI
regarding the diagnosis and evaluation of musculoskeletal trauma.
© 2020 Elsevier Ltd. All rights reserved.

Introduction tion on a more specific "level", based on the molecular pathophys-

Imaging of musculoskeletal (MSK) trauma has rapidly evolved
over the past decade. Advances in imaging methods have revolved
around two main axes: (i) molecular imaging (MI) and (ii) artificial
intelligence (AI), which have opened new horizons for the diagno-
sis and treatment of MSK trauma. MI aims at providing informa-
Abbreviations: MI, Molecular Imaging; MRI, Magnetic Resonance Imaging; PET,
Positron Emission Tomography; DWI, Diffusion Weighted Imaging; DTI, Diffusion
Tensor Imaging; AI, Artificial Intelligence, MSK, Musculoskeletal.
∗
Corresponding author: Chairman – Department of Medical Imaging, University
Hospital of Heraklion, Voutes, 71110, Heraklion, Crete, Greece.
E-mail addresses: miklontzas@ics.forth.gr (M.E. Klontzas),
gzpapadakis@gmail.com (G.Z. Papadakis), kmarias@ics.forth.gr (K. Marias),
karantanas@uoc.gr, akarantanas@gmail.com (A.H. Karantanas).
iological processes rather than the morphologic finding of one or
more structures, i.e. a bone tumor. On the turn of the century, the
ability of various imaging methods to unravel the molecular paths
of many disorders, opened a new window in the science of imag-
ing [1–4]. More precisely, MI techniques and methods, monitor and
record the spatial and temporal alterations of molecular or cellular
processes for diagnostic or therapeutic applications [5]. The first MI
method was the radioactive iodine, 131 I [6]. Currently, MI includes
optical imaging mostly performed in preclinical research, nuclear
methods (PET, SPECT) alone or combined in hybrid imaging with
CT or MRI, and purely radiological methods such as CT, US and MRI
[1]. All the above, may involve the injection of various agents. CT
and US extract information which is based on the administration of
contrast media, they are limited by radiation the former and lack

https://doi.org/10.1016/j.injury.2020.09.019
0020-1383/© 2020 Elsevier Ltd. All rights reserved.

Please cite this article as: M.E. Klontzas, G.Z. Papadakis, K. Marias et al., Musculoskeletal trauma imaging in the era of novel molecular
methods and artificial intelligence, Injury, https://doi.org/10.1016/j.injury.2020.09.019
JID: JINJ
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of specific clinical results the latter, and thus they will not be dis-
cussed herein.
Hybrid imaging and MRI are the cornerstones of MI. Although
central nervous system disorders attracted the research initially,
quite promptly, the capabilities of MI on MSK disorders were ex-
plored as well [7]. Among the most widely used methods, hybrid
PET/CT and diffusion weighted imaging (DWI) with MRI were the
ones initially applied. Inflammatory disorders, osteoarthrtitis, and
tumors were the most common groups of disorders studied. MSK
trauma drew attention later on.
AI applications on medical imaging involve computer algo-
rithms which allow for the detection of specific patterns related
to human disease [8]. Algorithms are usually trained with a set of
labelled images corresponding to diseased or normal subjects and
then tested on new (unseen) images regarding their accuracy in
deciding whether the disease is present. In particular, the devel-
opment of deep learning algorithms, such as convolutional neural
networks, has revolutionized such tasks allowing computers decide
alone which image features discriminate between disease and nor-
mal, reaching accuracies similar to practicing radiologists for the
diagnosis of MSK disease including fractures and soft tissue in-
juries [9,10].
This review will explore the current state-of-the art on MI and
AI applications on MSK trauma, in an attempt to highlight the po-
tential of novel imaging methods to revolutionize patient care.
Magnetic resonance imaging
The shift from conventional structural/anatomic imaging to-
wards extracting information relative to genetic, molecular and fi-
nally pathophysiological level, is targeting the best diagnosis and
treatment. MI has been considered to be the next great advance
for imaging and a promising arm of clinical practice on behalf of
radiologists in the future [11].
The main technique of MI based on MRI, is diffusion weighted
imaging (DWI). This technique provides information on the water
random or Brownian motion at a molecular level, between distinct
biologic tissues, including MSK structures [12]. The diffusion prop-
erties of water within various tissues [13]. Thus, apparent diffusion
coefficient (ADC) can quantify this spatial anisotropy by encoding
the diffusivity in 3 spatial dimensions. The ADC map demonstrates
these differences with different gradient encoding setting, known
as "b-values". Diffusion tensor imaging (DTI) is an MRI method
which is able to study the microstructure of tissues by quantify-
ing the diffusion of water molecules and its anisotropy in various
directions.
Initially, MI was focused on discriminating pathologic due to
malignancy from osteoporotic fractures in the spine [14,15]. Osteo-
porotic fractures are associated with substantial amounts of bone
marrow edema and hemorrhage and thus generate high ADC val-
ues on DWI. Neoplastic tissue, i.e. primary tumors, metastatic dis-
ease and multiple myeloma, contain less fluid and, therefore, gen-
erate a low ADC value. In a recent meta-analysis, the pooled sen-
sitivity and specificity were 0.92 and 0.917 respectively for differ-
entiating benign and malignant compression fractures in the spine
[16]. Later studies reported on the value of DWI on soft tissue tu-
mors, muscle aging, neurography and spinal cord myelopathy [17–
21].
Magnetization transfer (MT) imaging is an MRI DWI technique
that can be used for tissue contrast in cases that 1 H protons are
present in three distinct states [22]: bound to macromolecules, in
free water and in water in the hydration layer which corresponds
to intermediate status in - between the macromolecules and the
free water. MT is based on the application of an off-resonance RF
pulse which has a different frequency as compared with the Lar-
mor of the free water protons [22]. As a result, this pulse saturates
Please cite this article as: M.E. Klontzas, G.Z. Papadakis, K. Marias et al., Musculoskeletal trauma imaging in the era of novel molecular
methods and artificial intelligence, Injury, https://doi.org/10.1016/j.injury.2020.09.019
[m5G;September 22, 2020;3:0]
the protons bound to the macromolecules but they have no influ-
ence on the free water protons.
Other MI MRI techniques include T1 and T2 relaxation, T1rho
and delayed enhancement (dGemric), which have been applied for
cartilage evaluation and perfusion imaging which primarily relates
to MSK tumor imaging. During the last decade, research has been
performed on tissues involved in MSK trauma. Following the wide
clinical use of 3T scanners, there are evolving applications related
to sports and trauma.
Muscles
Skeletal muscles is an emerging application of DWI with vari-
able clinical indications including rotator cuff tears with subse-
quent atrophy and fatty infiltration, various myopathies and den-
ervation [23]. The contribution of DWI is primarily the early diag-
nosis which may influence, or modify the treatment planning, tai-
loring a personalized rehabilitation strategy. In addition, DTI mea-
surements may show evolution of the injury which is not appar-
ent with the routinely used fluid sensitive sequences [24] (Fig. 1).
Other clinical applications of DTI include muscle changes induced
by strenuous exercise in marathon runners, muscle denervation
and fatty infiltration as well as muscle strength evaluation [25,26].
Bone marrow
Bone bruise or bone contusion is a sequela of acute trauma,
well shown on plain MRI utilizing fluid sensitive sequences, which
is demonstrated with high signal intensity bone marrow edema
(BME). Bone bruise is reflecting the mechanism of injury and
thus contributes to better understand which other injuries are ex-
pected to occur. Initial reports showed increased diffusivity of mar-
row injury after trauma with trabecular disruption allowing in-
creased movement or diffusion of interstitial water and the mag-
nitude of diffusion change relates to the severity of injury [27].
ADC maps have been shown to be more sensitive for detect-
ing trauma-induced BME as compared with the fluid sensitive se-
quences [28] (Fig. 2).
Chronic overload may result in pubic osteitis in athletes who
complain of groin pain. The presence of BME, is suggesting activ-
ity of the disease. DWI has been applied to quantitatively evaluate
the severity of this injury [29]. DWI is currently explored regard-
ing its ability to provide reliable biomarkers on cellular density and
microvascular perfusion, without administering any contrast intra-
venously [30].
Cartilage
Cartilage is often involved in the context of MSK trauma and as
there is no natural regenerating ability, newer techniques of carti-
lage repair have been developed. The most commonly used quanti-
tative MR biomarkers include the T2 relaxation time measurements
which are showing primarily the collagen disruption and the de-
layed Gd-enhanced MRI which evaluate glycosaminoglycan concen-
tration [31]. T1rho values increase with the loss of glucosaminogly-
cans and with cartilage softening without administration of para-
mangetic contrast agents [32]. All the above non-invasive tech-
niques, are expected to show the biochemical alterations which oc-
cur after hyaline cartilage repair surgery (Fig. 3).
Nerves
A combination of 2D and 3D plain pulse sequences along with
the application of DWI-DTI, provides imaging of peripheral nerves,
also known as MR neurography (MRN) [33]. Nerve injury can be
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Fig. 1. Coronal fat-suppressed T2w image of the injury (left), DTI (b-value 0 s/mm2) images (middle) and reconstructed Mean Diffusivity (MD) maps (right) at three different
time points for a representative athlete. Time point 1: within one week after sustaining the injury; Time point 2: 2 weeks after the first examination; Time point 3: within
10 days after the athlete resumed full training at pre-injury intensity.
(Courtesy of Dr. J.R. Monte, MD and Prof. M. Maas, MD, PhD, Amsterdam UMC).
studied with MRN and classified according to Sunderland’s clas-
sification, which has impact on treatment planning. Advanced 3D
reconstruction techniques along with high field scanners equipped
with powerful gradients, allow high resolution volumetric imaging,
known as tractography (Fig. 4). The application of MRN has been
shown to reduce surgeries up to 17% and substantially increases
confidence of surgeons in the overall management of the patients
[34]. Another possible clinical application of DWI in trauma, is the
spinal cord injury without radiographic abnormalities (SCIWORA).
There are reports in patients with SCIWORA syndrome which sug-
gest that DWI may provide information when there is no altered
signal intensity on T2W MR images [35].
PET-MRI
Positron emission tomography (PET) is the cutting-edge nuclear
medicine MI technique, which allows targeting, visualization and
quantification of biochemical processes at the cellular and sub-
cellular level, via the three-dimensional (3-D) reconstruction of
the bio-distribution of various particles that are radiolabeled with
positron-emitting isotopes. In the previous decades, technological
advances enabled the development of hybrid PET/CT and PET/MRI
systems, setting new standards in the management of various dis-
ease entities, both benign and malignant (Fig. 5). The capability
of simultaneously visualizing several disease-related molecular tar-
gets by means of positron emitting-radiopharmaceuticals, while
anatomically characterizing lesions with CT or MRI, together with
the intrinsic quantitative capabilities of PET, offer incremental diag-
nostic information, enabling accurate, highly efficient and person-
alized treatment strategies, facilitating modern, precision medicine
approaches.
PET/MRI merges the functional data provided by PET-imaging
with the superior anatomical characterization and soft-tissue con-
trast provided by MRI, and together with the functional MR-
sequences, lead to enhanced diagnostic imaging applications, es-
pecially in small anatomic regions with complex anatomy such as
the intra-articular space. Moreover, pediatric and pregnant patients
suffering from MSK trauma, can take advantage of the reduced ra-
diation exposure of PET/MRI compared to PET/CT. In recent years,
instrumentation advancements enabled the development of PET
detectors compatible with the high intensity MR field, allowing the
introduction into clinical practice of hybrid PET/MRI systems ca-
pable of simultaneous PET and MRI acquisition [36,37]. These ad-
Please cite this article as: M.E. Klontzas, G.Z. Papadakis, K. Marias et al., Musculoskeletal trauma imaging in the era of novel molecular
methods and artificial intelligence, Injury, https://doi.org/10.1016/j.injury.2020.09.019
[m5G;September 22, 2020;3:0]
3
vancements provide the ground for unique diagnostic imaging ap-
plications, with improved image quality, reduced PET-image noise,
substantial increase in the accuracy of the co-registration between
PET-data and MRI anatomy, correction for respiratory, heart and
bulk patient motion, and more importantly temporal synchroniza-
tion of the data acquired by the two modalities [38]. In addition,
the integration of PET and MRI data holds the potential to further
enhance the accuracy of PET-quantitative capabilities. MRI data
can contribute to improved partial volume correction (PVC) of PET
data, and advanced MRI-based PET attenuation correction methods.
Such methods can enable more precise final reconstructed images
increasing precision in the calculation of SUV (standardized up-
take value) - based metrics, which are the most widely employed
semi-quantitative PET indices , enabling longitudinal monitoring of
the activity of several molecular processes targeted by PET-tracers
[39,40].
Furthermore, intense research efforts are being currently under-
taken to develop and optimize computational pipelines for the re-
construction and processing of simultaneously acquired PET and
MRI data aiming at advanced quantitative applications. The most
widely employed PET-radiopharmaceuticals for MSK trauma imag-
ing, are 18 F-fluorodeoxyglucose (18 F-FDG) and 18 F-sodium fluoride
(18 F-NaF). 18 F-FDG is a glucose analog providing a whole-body
metabolic map of the patient. Since activated inflammatory cells
use glucose as an energy substrate, 18 F-FDG can contribute to the
assessment of MSK trauma by targeting and quantifying the injury-
associated inflammatory response [41]. A major limitation of 18 F-
FDG is the non-specific nature of it’s uptake, since cancer cells or
infectious sites also exhibit abnormally increased radiotracer activ-
ity. However, the additional data provided by the MR can help to
increase specificity, and surpass this limitation. 18 F-NaF is a bone
seeking PET-agent, which is taken up by bone through (18 F-) ions
exchange with hydroxyl ions (OH–) on the surface of the hydrox-
yapatite, leading to the formation of fluoroapatite. Abnormally in-
creased 18 F-NaF activity reflects underlying bone processes both
osteolytic and osteoblastic, which result to increased bone sur-
face exposed to the blood flow, and therefore higher availability of
binding sites for the radiotracer [42]. 18 F-NaF is the optimal PET-
radiopharmaceutical for skeletal imaging and has been widely em-
ployed in the work-up of both benign and malignant bone diseases
[43–46]. In the setting of MSK trauma 18 F-NaF can contribute to
the assessment of bone-related injuries.
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Fig. 2. A 23-year-old soccer player with a non-contact “pivot shift” injury. The fat suppressed PDw MR images in the coronal (a), axial (b) and sagittal (c,d) planes, show the
bone contusion in the lateral femoral condyle (arrows), the high grade partial tear of the anterior cruciate ligament (open arrow) and the joint effusion (arrowheads). Fusion
imaging (e) with the ADC map from the HASTE sequence (2D,TR 40 0 0 ms, TE 106 ms, ETL 256, Pixel dimension 1.91 × 1.91 mm [in plane isotropic], receiver bandwidth
390 Hz/Pixel, 8b-values [0, 50, 100, 150, 200, 500, 800, 1000]) overlapping the fat suppressed PDw MR image. The ADC values (meanx10–6 mm2/sec) are: Effusion 296.6 (1),
bone marrow 18.2 (2), bone contusion 84.4 (3). Strengths of the HASTE sequence include the visualization of the bone marrow due to lack of any fat saturation and excellent
geometry whereas its weakness is the inability to apply a maximum b-value over 10 0 0.
(Courtesy of Prof. T. Maris, PhD, Dpt. of Radiology, University of Crete).

Please cite this article as: M.E. Klontzas, G.Z. Papadakis, K. Marias et al., Musculoskeletal trauma imaging in the era of novel molecular
methods and artificial intelligence, Injury, https://doi.org/10.1016/j.injury.2020.09.019
JID: JINJ
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Fig. 3. Cartilage repair surgery. Sagittal intermediate weighted (IMw) fat saturated turbo-spin-echo sequence (A) and sagittal color-coded T2-relaxation time map overlaid
on the 20 ms image of the multi-slice multi-echo spin-echo sequence (B) of a 23-year-old male patient who received matrix-associated autologous chondrocyte implantation
(MACI) with subchondral autologous bone grafting at the lateral femoral condyle of the left knee (between interrupted lines) for treatment of an osteochondral defect. Blue
color indicates low cartilage T2 relaxation times; red color indicates high cartilage T2 relaxation times. The transplant area shows perfect filling with cartilage repair tissue.
The repair tissue still demonstrates high IMw signal and higher T2 values compared to the native hyaline cartilage 1 year after surgery. The T2 signal of the MACI tissue may
be expected to decrease to nearly “normal” values within the first 1 to 2 years after surgery in cases with optimal postoperative outcomes.
(Courtesy of Dr. Pia M. Jungmann, MD, University of Freiburg).

Fig. 4. Median nerve end bulb neuroma formation following forearm amputation. (A) Coronal T2w Dixon image reveals a median nerve which is diffusely hyperintense
along the forearm (short arrows) and focally enlarged at the level of the neuroma formation (long arrow). (B) On the axial fat suppressed T2w image, the neuroma appears
as a hyperintense lobulated multilocular lesion (arrow) (C) Coronal DTI tractography image shows areas of fascicular architectural distortion (arrows) along the distal median
nerve closer to the amputation site.
(Courtesy of Prof. A. Chhabra and Dr. T. Soldatos, MSK Radiology Division UT Southwestern Medical Center, Dallas, TX, USA).

Fig. 5. (a) Axial CT image (bone window) and (b) axial fused 18
F-NaF PET/CT image of the thorax showing (arrow) a right rib fracture with intensely (SUVmax=84.5) elevated
radiotracer activity.

Please cite this article as: M.E. Klontzas, G.Z. Papadakis, K. Marias et al., Musculoskeletal trauma imaging in the era of novel molecular
methods and artificial intelligence, Injury, https://doi.org/10.1016/j.injury.2020.09.019
JID: JINJ
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Magnussen RA et al. in a cross sectional study of nineteen pa-
tients investigated the metabolic activity of anterior cruciate lig-
ament (ACL) grafts post ACL reconstruction surgery, using 18 F-
FDG PET/MRI imaging (sequential acquisition) in twenty-one knees
(two patients underwent bilateral reconstruction). The PET/MRI
data were collected at multiple time points after ACL reconstruc-
tion, revealing a significant decrease in metabolic activity of grafts
that had been placed for more than two years in comparison to
those grafts that had been in place for much shorter time pe-
riod. Furthermore, the study confirmed the capability if this hy-
brid modality to study metabolism of ACL grafts in vivo, and it’s
potential to contribute to the assessment of graft maturation, pro-
viding crucial insight into guiding the patient’s return to activity
[47].
Towards a better understanding of the bio-incorporation pro-
cedure of the ACL graft during the first year after reconstruction
surgery, Korbin S. et al. recently performed a prospective study
with six patients who underwent simultaneous 18 F-FDG PET/MRI
scans post ACL reconstruction. The study showed that although
radiotracer uptake decreases over time, there is substantial 18 F-
FDG activity twelve months after the surgical intervention ver-
sus the contralateral non-operative knee, indicative of ongoing ac-
tive underlying bio-integration processes [48]. This data empha-
sizes the need for more studies with larger number of patients
evaluating ACL-graft metabolic activity for greater post-surgical pe-
riod of time, in order to elucidate the timeline of ACL-graft bio-
incorpation, enabling a safe management strategy for the return to
full activity, especially for professional athletes.
Furthermore, El-Haddad et al., reported the capability of 18 F-
FDG PET/MRI to demonstrate both the exact site of meniscal tears
and the associated synovitis, together with the ability to assess
the severity of the tears and the inflammatory status of the syn-
ovial membrane. This data, could contribute to therapy assessment,
while holding potential for lower need of exploratory arthroscopies
[49]. In addition, 18 F-FDG may contribute to the differentiation
of benign osteoporotic or traumatic fractures from cancer-related
pathologic fractures, since acute traumatic fractures do not exhibit
abnormally increased 18 F-FDG activity [50–52].
18 F-NaF PET/MRI imaging can contribute to the assessment of
post-traumatic osteoarthritis (PTOA). Menedez MI et al. in a pre-
clinical study with five canine models who developed osteoarthri-
tis (OA) after ACL transection (ACLT), showed that there was no
abnormally increased 18 F-NaF activity before ACLT. However, there
was an exponential elevation of 18 F-NaF uptake by the bone in ev-
ery region of the ACLT knees at 3 and 12 weeks time points, in
comparison to the ACLT knees at baseline. Authors computation-
ally co-registered 18 F-NaF PET/CT scans with MRI data, concluding
that the employed methodology is a promising MI strategy for the
assessment of PTOA activity, in the pre-clinical setting [53].
Apart from 18 F-FDG and 18 F-NaF, efforts are made to develop
PET-radiopharmaceuticals for MSK imaging with enhanced speci-
ficity, which are radiolabeled with shorter-lived positron emitting
isotopes, enabling lower radiation exposure and faster acquisition
time [54]. These agents include 68 Ga-citrate and 68 Ga-transferrin
aiming inflammation and infection, 68 Ga-DOTA-Sialic acid-binding
immunoglobulin-like lectin-9 (68 Ga-Siglec-9) targeting synovitis,
11 C-methionine demonstrating inflammatory lesions, 11 C-PK11195
targeting the peripheral benzodiazepine receptor (PBR) contribut-
ing to periprosthetic soft tissues inflammation assessment, 18 F-
labeled leukocytes aiming at infectious and inflammatory alter-
ations, and 18 F-galacto-RGD (arginine-glycine-aspartate) targeting
angiogenesis [55]. The majority of these PET-agents have been em-
ployed in the pre-clinical setting, with promising results for future
clinical applications, that can be significantly extended through the
rapid evolvement of PET/MRI instrumentation .
Please cite this article as: M.E. Klontzas, G.Z. Papadakis, K. Marias et al., Musculoskeletal trauma imaging in the era of novel molecular
methods and artificial intelligence, Injury, https://doi.org/10.1016/j.injury.2020.09.019
[m5G;September 22, 2020;3:0]
Artificial Intelligence
Advances in computational power and the development of deep
learning algorithms have enabled the widespread application of AI
on imaging data. The advent of AI, and especially machine learning,
has resulted in a constantly increasing number of publications on
potential applications of deep learning in a variety of MSK imag-
ing settings ranging from the diagnosis of trauma, to the classifi-
cation of injuries and the prediction of future injuries as well as
the reduction of time required for trauma MRI scans [56] (Fig. 6).
Responding to the surge of AI literature, radiological societies in-
cluding the European Society of Radiology and the American College
of Radiology have created dedicated initiatives and clinically ori-
ented workshops [57,58], while new journals have been launched
to accommodate the publication of specialized literature in AI [8].
Efforts towards the application of AI on MSK trauma imaging
have been focused on a limited spectrum of commonly encoun-
tered injuries, in an attempt to achieve automation in diagnosis
and severity classification. Deep learning methods with an empha-
sis on convolutional neural networks (CNNs) have been developed
for the diagnosis of fractures and soft tissue injuries, as well as for
the monitoring of treatment outcomes and the prediction of future
injuries in high level athletes [10]. CNNs are trained using a large
number of labelled clinical images derived from a variety of imag-
ing modalities to automate diagnostic decisions, thus reducing the
workload of practicing radiologists. The need for high sample sizes
for model training is currently limiting the development of robust
deep learning models to common conditions such as meniscal and
anterior cruciate ligament injuries (ACL) as well as common frac-
tures of the upper limb, the hip and the spine [9].
Automation of fracture diagnosis has been the main focus of
AI efforts on MSK trauma imaging. The accuracy of wrist frac-
ture diagnosis by emergency physicians can reach levels close to
95% when assisted by deep neural networks as shown by Lindsey
et al. who trained a neural network to detect wrist fractures using
135,409 plain radiographs, in an attempt to increase diagnostic ac-
curacy in the emergency setting, decreasing misinterpretation rates
by 47% [59]. Similar results were achieved by Kim et al. who uti-
lized a CNN pre-trained on non-medical images, retraining its top
layer to diagnose wrist fractures using 1389 radiographs [60]. Thian
et al. achieved approximately 90% accuracy for the detection and
localization of ulnar and radial injuries [61]. Neural networks have
been also used to diagnose pediatric supracondylar fractures uti-
lizing plain films with an accuracy of 95%. As expected, the results
were less promising for the diagnosis of joint effusion or the de-
tection of random abnormalities that had never been presented to
the networks during the training phase [62]. Combining humeral,
elbow and forearm fractures in one training dataset, reduces CNN
performance due the complicated nature of the task, as shown by
Guan et al. who used a CNN on a public radiograph dataset to di-
agnose various upper limb fractures with a precision as low as 62%
[63].
Attempts to utilize deep learning for fractures of other anatom-
ical locations have focused on the femoral neck and the calca-
neus. Training of two well-known CNN architectures (AlexNet and
GoogleNet) has been compared to training of medically naïve indi-
viduals for the diagnosis of femoral neck fractures, showing com-
parable results [64], while Pranata et al. used CT scans to train
a CNN (ResNet) not only for the detection but also for the clas-
sification of calcaneal fractures with an accuracy of almost 98%
[65]. Other supervised machine learning algorithms such as sup-
port vector machines and random forests have shown promising
results for osteoporotic postmenopausal hip fracture diagnosis, alas
with limited sample sizes [66].
AI has been successfully applied to soft tissue injuries of the
knee using MRI images. CNNs have been shown to be equivalent
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Fig. 6. (A) Number of publications related to artificial intelligence applications on musculoskeletal imaging between 2001 and 2019. Numbers have been extracted from
Scopus with combinations of the keywords “artificial intelligence”, “machine learning”, “musculoskeletal imaging”, “bone”, “cartilage”, “ligament”, “tendon”, “muscle”. (B)
Distribution of artificial intelligence publication origin throughout the world according to Scopus.
to fellowhip-trained MSK radiologists for the diagnosis of menis-
cal tears [67–69]. Bien et al. developed a public dataset of 1370
knee MRIs and trained a CNN to diagnose ACL and meniscal tears
with an accuracy higher than 90% for both tasks [68]. Despite the
striking success of their model, lack of surgical tear confirmation
and the use of single MRI slices for tear evaluation, limited the
clinical relevance of their results. In an attempt to overcome these
limitations Fritz et al. used 18,520 MRI studies to train a CNN for
meniscal tear diagnosis using a complete set of coronal and sagit-
tal sequences. Model performance was compared to surgical find-
ings and the diagnosis of MSK radiologists reaching sensitivity and
specificity of approximately 90% for medial meniscal tears and less
than 70% for lateral tears [67]. Interestingly enough, model per-
formance for medial tear diagnosis was equal to the performance
of radiologists, demonstrating the great potential of AI algorithms
in the clinical setting. Pedoia et al. used CNNs for automated im-
age segmentation, diagnosis of meniscal lesions and assessment
of patellofemoral joint cartilage integrity in subjects with ACL in-
jury prior and post-reconstruction. They achieved 80% accuracy for
Whole-Organ Magnetic Resonance Imaging Score (WORMS) grad-
ing and showed that 73% of diagnostic errors happened for poste-
rior meniscal horn tears [70].
AI has been used for the diagnosis of ACL tears, demonstrat-
ing promising results. Liu et al. developed three distinct intercon-
nected CNNs to fully automate three consecutive tasks in ACL tear
diagnosis. The first CNN selected an appropriate MRI section con-
taining the ACL, the second segmented the image part contain-
ing the intercondylar notch together with the ACL and the final
one (DenseNet) decided whether the ligament was torn [71]. Their
work provided a novel pipeline for ACL tear diagnosis achieving
equivalent performance to fellowship-trained radiologists. How-
ever, partial ACL tears were excluded from the study reducing the
clinical value of their tool, since diagnostic ambiguity usually ac-
companies partial and not complete tears. ACL tear diagnosis has
been also attempted by Zeng et al. with the use of a model trained
on the gait of people with torn ACL compared to normal subjects.
Despite the high accuracy achieved with the use of gait analysis,
the value of the results is limited by the small sample size used in
their study [72].
CNNs have been also used to monitor tissue healing following
Achilles tendon reconstruction. Kapinski et al. utilized a CNN en-
semble to attempt a preliminary version of AI assisted evaluation
of the healing process and the localization of healed tissue in MRIs
[73]. Attempts to monitor tissue healing with deep learning hold
great promise for applications in regenerative medicine, where ar-
tificial tissues can be tailor-made to treat MSK injuries. In such
Please cite this article as: M.E. Klontzas, G.Z. Papadakis, K. Marias et al., Musculoskeletal trauma imaging in the era of novel molecular
methods and artificial intelligence, Injury, https://doi.org/10.1016/j.injury.2020.09.019
[m5G;September 22, 2020;3:0]
7
cases state-of-the-art imaging can be combined with AI to assess
graft integration over time and confirm treatment success [74].
Despite the fact that most AI efforts are focused on diagnos-
tic decisions, machine learning can be used for a series of other
non-trivial tasks including image quality enhancement, examina-
tion time reduction and automated MRI protocolling [9], as well as
for the prediction of future injury risk. Bertsimas et al. used demo-
graphic patient data, Glasgow Coma Scale, injury mechanism and
image data in combination with Optimal Classification Trees algo-
rithms to retrospectively assess the risk of cervical spine injuries
in pediatric patients [75], facilitating clinical decisions for patient
management in cases of diagnostic dilemmas. Prospective evalu-
ation of injury risk can significantly benefit professional sports,
where injuries are equivalent to loss of time and money. For this
reason, elite football teams such as Barcelona F.C. develop mod-
els to forecast potential injuries, avoiding the financial burden as-
sociated with player recovery [76]. Finally, AI has recently found
applications on the optimization of MI techniques such as DTI.
Deep learning and a variety of other supervised and unsupervised
machine learning algorithms have been used to reduce the time
needed for clinical grade DTI, by limiting the number of images
necessary for tensor estimation and optimizing tractographic re-
constructions [77–79]. However, such techniques have yet to be
applied to musculoskeletal trauma.
The surge of AI literature and the widespread use of deep learn-
ing technologies by medical professionals has created a need for
standardization in methodological standards in order to achieve
homogeneity in published literature and increase the quality of
results. Methodological pitfalls can result into model overfitting,
over- or underdiagnosis and misclassification errors, with a sig-
nificant impact on the quality of patient care. Acting in a proac-
tive manner to address such problems in their making, radiolog-
ical and informatics societies including the European Society of
Medical Imaging Informatics, the Society for Imaging Informatics
in Medicine, the European Society of Radiology, the Americal Col-
lege of Radiology, the Radiological Society of North America, the
American Association of Physicists in Medicine and the Canadian
Association of Radiologists, released a joint statement on AI re-
search ethics [80]. Additionally, the RSNA has released guidelines
on the minimum requirements that AI projects need to fulfill for
publication in journals supported by the society [81] and guides
on the development of high-quality clinically relevant AI projects
[82]. At the same time, the AI regulatory landscape for the use of
AI in the clinical setting is fast evolving in both sides of the At-
lantic (Food and Drug Administration (FDA) in the US and Confor-
mity assessment leading to a Conformité Européenne (CE) mark in
the EU), under their new Medical Device Regulations. While the
JID: JINJ
ARTICLE IN PRESS
8 M.E. Klontzas, G.Z. Papadakis, K. Marias et al. / Injury xxx (xxxx) xxx
FDA has already approved several AI -based software as a medical
device (SAMD), such algorithms are “locked” prior to marketing.
The adaptive nature of AI algorithms calls for more flexible regu-
latory frameworks and to this end the FDA published a proposed
framework to accommodate improvements in AI performance, ex-
tension of input data and intended use [83].
Conclusion
MSK imaging has been revolutionized by advances in MI and
AI. Both fields are still in the initial stages of development and
hold great promise for the incorporation in everyday clinical prac-
tice. Future integration of MI and AI methods can further increase
the clinical toolbox for precision MSK diagnosis. Interdisciplinary
efforts between surgeons and radiologists involved in MSK disease
diagnosis and treatment as well as physicists and computer scien-
tists can lead to further development of MI and AI with the ulti-
mate aim of providing high-quality personalized everyday patient
care.
Declaration of Competing Interest
No conflict of interest to disclose for all authors
Acknowledgements
The authors would like to thank Drs. P. M. Jungmann, MD (Uni-
versity of Freiburg), J.R. Monte, MD and M. Maas, MD, PhD (Ams-
terdam UMC), T. Maris, PhD (Dpt. of Radiology, University of Crete),
A. Chhabra, MD and T. Soldatos, MD (MSK Radiology Division UT
Southwestern Medical Center, Dallas, TX, USA) for kindly providing
high quality figures of state-of-the-art trauma MRI techniques.
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