Osteoarthritis (OA) is a chronic degenerative disorder of joints and is the most common reason leading to total knee joint replacement (TKR). In this work, we developed an automated OA-relevant imaging biomarker identification system based on MR images and deep learning (DL) methods to predict knee OA progression. Our results indicate that the combination of multiple MR images with different contrast and resolution provides the best model to predict TKR with AUC 0.88±0.01.
Dataset and Methods
Sagittal intermediate-weighted fat-saturated Turbo Spin Echo(TSE) images and sagittal 3D double-echo steady-state (DESS) with water excitation images from Osteoarthritis Initiative5 are used for this study. TSE images provides information about cartilage loss, ligament integrity, meniscal tears and subchondral bone marrow. DESS images provide information about total joint cartilage morphology, bone area and shape, and osteophytes. Table 1 shows the acquisition parameters of both sequences.
718 case-control pairs (age: 63±12 years, BMI: 29±6.6 kg/m2, 274/444 male/female split) were selected from OAI dataset by propensity score matching6 on individuals based on the baseline variables: age, BMI, gender and race. Cases were defined as individuals who received a medically confirmed TKR after baseline. We defined controls as individuals who did not receive a TKR in either knee on the 108-month visit.
We developed two 3D models with a binary target variable to predict TKR using structural MRI. TSE images were used to design TSE-model using 5 consecutive convolution blocks. DESS images were used to design DESS-model using 8 consecutive resnet blocks7 (Figure 1). Our third model combines the output of first two models by averaging the subjects probability of receiving TKR (Ensemble-model). Using the demographic and clinical data, we developed a reference logistic regression model (LR-clinical)8 with baseline age, gender, race, BMI, KOOS Quality of Life score9 and WOMAC pain score10 as features. In order to understand the CNN’s learning behavior, we presented occlusion maps to get the discriminative image regions used by a CNN to identify the subjects TKR outcome.
Receiver operating curve (ROC) analysis of designed models is shown in Figure 2. Both TSE and DESS models achieved the area under the ROC curve (AUC) of 0.86±0.01 that is significantly higher than the LR-clinical model (AUC: 0.77±0.02, p<0.01). Incorporating the output of the DL models into LR-clinical model improved the prediction performance (AUC: 0.88±0.02).
Figure 3 and 4 shows a visualization of the regions in which TSE-model and DESS-model uses to make a decision with high impact, respectively. The heat map overlaid on the exemplary MR images were generated by systematically occluding the portions of the input image and monitoring the output of a classifier.11 Figure 4 clearly shows that the TSE-model model pays attention to the locations on which where OA has immediate impacts, such as cartilage, as the probability of the correct class drops significantly. More interestingly, as indicated by the green arrow in the second row, TSE-model also uses the information from the front of the knee cap where prepatellar bursitis was diagnosed for this patient. For this patient, we found that both cartilage and bursa were playing a role in models decision for TKR probability. In addition, DESS-model incorporates the complementary information from cartilage, posterior intercondylar notch and posterior cruciate ligament to predict the TKR outcome for the Subject 2 (Figure 4).
1. Carballido-Gamio J et al. Magn Reson Med. 2011;65(4):1184-1194. doi:10.1002/mrm.22693
2. Kazakia GJ et al. Osteoarthritis Cartilage. 2013;21(1):94-101. doi:10.1016/j.joca.2012.09.008
3. Wang L and Regatte RR. J Magn Reson Imaging. 2014;00. doi:10.1002/jmri.24677
4. Neogi T et al. Arthritis Rheum. 2013;65(8):2048-2058. doi:10.1002/art.37987
5. Peterfy CG et al. Osteoarthr Cartil. 2008;16(12):1433-1441. doi:10.1016/j.joca.2008.06.016
6. Rosenbaum PR and Rubin DB. Biometrika (1983) 70:4155
7. He, Kaiming, et al. "Deep residual learning for image recognition." Proceedings of the IEEE conference on computer vision and pattern recognition. 2016
8. Hochberg, M.C. et al. Osteoarthritis and Cartilage (2013) Volume 21, S11.
9. Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)—Development of a Self-Administered Outcome Measure. J Orthop Sport Phys Ther. 1998;28(2):88-96. doi:10.2519/jospt.1998.28.2.88
10. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation Study of WOMAC: A Health Status Instrument for Measuring Clinically Important Patient Relevant Outcomes to Antirheumatic Drug Therapy in Patients with Osteoarthritis of the Hip or Knee. J Rheumatol. 1988;15(12):1833-1840. doi:10.1186/1471-2474-13-168.
11. Zeiler, M. D., & Fergus, R. (2014). In European conference on computer vision (pp. 818-833). Springer, Cham.
12. Eckstein F, Kwoh CK, Boudreau RM, et al. Quantitative MRI measures of cartilage predict kneereplacement: A case-control study from the Osteoarthritis Initiative. Ann Rheum Dis. 2013;72(5):707-714. doi:10.1136/annrheumdis-2011-201164.
13. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing areas under two or more correlated reciever operating characteristics curves: a nonparamentric approach. Biometrics. 1988;44(3):837–845.