Upasana Upadhyay Bharadwaj1, Amir M. Pirmoazen1, Zehra Akkaya1, John A. Lynch2, Gabby B. Joseph1, Sharmila Majumdar1, Valentina Pedoia1, and Thomas M. Link1
1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, 2Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States
Synopsis
Intramuscular fat is an important
biomarker for knee osteoarthritis. Quantitative analysis on routine clinical
imaging (T1-weighted MRI) is not feasible without pixel-level annotation,
leading to the adoption of Goutallier classification, a semi-quantitative
grading system that is time-consuming and has variable reproducibility. This study
automates binarized Goutallier classification on patients (n=50) from the Osteoarthritis
Initiative cohort with a two-staged process: deep-learning 3D segmentation of quadriceps
and hamstrings (dice scores of 0.89[0.88,0.90] and 0.84[0.83,0.87],
respectively) followed by histogram features for classification of
intramuscular fat (0.93[0.92,0.95] AUROC). With model-reader kappa (0.64[0.61,0.68])
comparable to inter-reader kappa (0.61[0.59,0.64]), our approach shows promise
for end-to-end automation.
Background
Strong associations between thigh adiposity, muscle quality. and knee
osteoarthritis have been previously established1. Although a number
of algorithmic approaches exist for quantifying intramuscular fat (intraMF) on
magnetic resonance imaging (MRI), they rely on chemical shift-based water/fat
separation sequences2-5. While standard sequences, such as T1-weighted
MRI, do not allow true quantification of intraMF1, they can be used
for semi-quantitative assessment by the Goutallier Classification (GC) system6-9;
but prior studies also report that the GC system has moderate interobserver
variability and can be time-consuming10. Deep learning is a
promising technology for automated and consistent analysis of fatty
infiltration, with notable examples from the supraspinatus muscle11.
In this study, we propose a two-staged pipeline that leverages deep learning
for 3D segmentation of thigh muscle, followed by computer assisted
classification of intraMF for end-to-end automated analysis of thigh muscle,
which has heretofore not been investigated.Methods
Figure 1 provides an
overview of the overall methodology and the deep learning pipeline.
Study Cohort
A subset of 50 MRI
studies of bilateral thighs were selected at random from the Osteoarthritis Initiative
(OAI) cohort12 with approximately uniform distribution of cases
across MRI scanners, age, sex, and BMI. Axial T1-weighted images were labeled
with freeform annotations of muscle groups – quadriceps and hamstrings – over
15 consecutive slices starting 10cm proximal to the distal epiphysis of the
right femur and extending 7.5cm proximally using a research annotation platform
(MD.ai). Each muscle was graded by a board-certified, musculoskeletal-trained radiologist
(R1) and a radiology trainee (R2) using the GC system (Figure 2). Imaging
examples of freeform annotations and GC grades are presented in Figure 3. The
studies (n=50) were partitioned into random patient-level splits of train
(n=30), validation (n=10), and test (n=10).
Thigh Muscle Segmentation
Two distinct 3D
convolutional neural networks, based on the V-Net architecture, were developed one
for each muscle group. The models were trained on a single NVIDIA Tesla V100 32
GB GPU in mixed precision for 100 epochs with batch size of 16, learning rate
of 0.0001 using the ADAM optimizer in TensorFlow. The most performant model on
the validation set was selected for subsequent analysis. Each side was
preprocessed with pixel intensities normalized to [0, 1] and resized to a volume
of 128x128x15 pixels, resulting in an augmented set of volumes for training
(n=60 thighs: 30 studies x 2 sides), validation (n=20), and test (n=20).
Goutallier Classification
Histogram-based features
(distribution of pixel intensities across 10 uniform bins between 0.0 and 1.0)
were extracted from model-generated segmentations over the entire cohort and
collapsed into train (n=120 features: 30 studies x 2 sides x 2 muscles), validation
(n=40), and test (n=40) of histogram features. A logistic regression model was trained
to predict binarized fat infiltration by collapsing GC grades into normal: GC ≤
1 and fat infiltration: GC ≥ 2.
Statistical Analysis
Segmentation models were
evaluated using the Sorensen-Dice coefficient on the test set for each muscle volume,
across both sides (n=20 sides). Goutallier classification was evaluated using
area under the receiver operating characteristic curve (AUROC). Pairwise
agreement between R1, R2 and the model was characterized using Cohen’s kappa
scores.Results
A total of 200 muscle
volumes (50 patients x right and left thigh for 2 muscle groups) were graded,
of which none were assigned GC grade 0 or 4, 111 volumes were assigned grade 1,
87 were assigned grade 2, and 2 were assigned grade 3. After binarization, 111
volumes were labeled normal and 89 as indicative of fat infiltration.
Thigh muscle
segmentation was favorable with dice scores of 0.89 [0.88, 0.90] and 0.84 [0.83,
0.87] for quadriceps and hamstrings, respectively. Figure 4 illustrates model generated
segmentation for each muscle group. Goutallier classification using histogram features
had an AUROC of 0.93 [0.92, 0.95]. Agreement between R1-R2, model-R1, and
model-R2 were 0.61 [0.59, 0.64], 0.64 [0.61, 0.68], and 0.67 [0.64, 0.71],
respectively.Discussion
To our knowledge, this is
one of the first end-to-end automated approaches to classifying intramuscular
fat on T1-weighted MRI of the thigh. Our model achieves moderate-to-high
model-reader agreements of 0.64 [0.61, 0.68] and 0.67 [0.64, 0.71], which is
comparable to the inter-reader agreement of 0.61 [0.59, 0.64] on the same cases.
The system is enabled by a 3D segmentation model that is performant for quadriceps
(0.89 [0.88, 0.90]) and hamstrings (0.84 [0.83, 0.87]) followed by a logistic
regression classifier trained on histogram features.
Our study was constrained
to a small sample size with the following limitations. While simplified GC
systems have been reported before, very few studies assess binarized grades13.
Limited samples also necessitated histogram-based features; a deep-learning
based classification model was attempted but had the tendency to overfit due to
a small training set. Similarly, two separate segmentation models were required
– one for each muscle group – instead of a single, multi-class network. Lastly,
our analysis is focused on two prominent muscle groups – segmentation of
anisotropic muscle groups may be more challenging and is work in progress.
In conclusion, our study
provides evidence that a deep-learning system can automate the evaluation of
intramuscular fat from T1-weighted MRI of the thigh with potentially high
accuracy, and comparable to that of radiologists.Acknowledgements
This study was funded by the NIH (National Institute of
Arthritis and Musculoskeletal and Skin Diseases grants R01-AR078917). We would
like to thank the faculty and staff of the Coordinating Center of the OAI at
the NIH and UCSF for their invaluable assistance with patient selection,
statistical analysis, and technical support. The OAI is a public-private partnership comprised of five contracts
(N01-AR-2-2258; N01-AR-2-2259; N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262)
funded by the National Institutes of Health, a branch of the Department of
Health and Human Services and conducted by the OAI Study Investigators. Private
funding partners include Pfizer, Inc.; Novartis Pharmaceuticals Corporation;
Merck Research Laboratories; and GlaxoSmithKline. Private sector funding for
the OAI is managed by the Foundation for the National Institutes of Health.References
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