Uncovering associations between data-driven learned qMRI biomarkers and chronic pain.

Knee pain is the most common and debilitating symptom of knee osteoarthritis (OA). While there is a perceived association between OA imaging biomarkers and pain, there are weak or conflicting findings for this relationship. This study uses Deep Learning (DL) models to elucidate associations between bone shape, cartilage thickness and T2 relaxation times extracted from Magnetic Resonance Images (MRI) and chronic knee pain. Class Activation Maps (Grad-CAM) applied on the trained chronic pain DL models are used to evaluate the locations of features associated with presence and absence of pain. For the cartilage thickness biomarker, the presence of features sensitive for pain presence were generally located in the medial side, while the features specific for pain absence were generally located in the anterior lateral side. This suggests that the association of cartilage thickness and pain varies, requiring a more personalized averaging strategy. We propose a novel DL-guided definition for cartilage thickness spatial averaging based on Grad-CAM weights. We showed a significant improvement modeling chronic knee pain with the inclusion of the novel biomarker definition: likelihood ratio test p-values of 7.01 × 10-33 and 1.93 × 10-14 for DL-guided cartilage thickness averaging for the femur and tibia, respectively, compared to the cartilage thickness compartment averaging.