OA-MAP: Evidence-Grounded Multi-Agent Multimodal Framework for Interpretable Knee Osteoarthritis Progression

Purpose: To develop an interpretable and trustworthy AI framework that combines deep learning based MRI Osteoarthritis Knee Score (MOAKS) prediction with interpretable statistical modeling to study structure-pain relationships at scale using data from the Osteoarthritis Initiative (OAI). Materials and Methods: We first developed a deep learning framework to predict MOAKS features directly from knee MRIs and incorporated conformal prediction to provide prediction uncertainty quantification. This uncertainty-aware strategy enables explicit filtering of model outputs, retaining only high-confidence MOAKS predictions at the knee level. Second, we applied a longitudinal latent class mixed model (LCMM) to examine associations between key structural abnormalities and four complementary knee pain measurements. Results: Among the three MRI-defined abnormalities (i.e., bone marrow lesions (BML), cartilage loss (CART), and meniscal extrusion (ME)), our framework substantially improved the Matthews correlation coefficient (MCC) and some other metrics. For example, MCC increased from 0.69 to 0.91 for BML, from 0.45 to 0.80 for CART, and from 0.59 to 0.89 for ME. Using these high-confidence predictions, we expanded the sample size to 2,175 knees for the LCMM analysis. Two distinct pain trajectories were identified (rapid and stable pain progression). The estimated odds ratios (95% CI) for the rapid progression group were 1.62 (1.12-2.35) for BML, 1.83 (1.24-2.70) for CART loss, and 2.50 (1.75-3.57) for ME. Conclusion: These results highlight the importance of these structural abnormalities as risk factors for pain and functional progression in osteoarthritis.

Grading knee osteoarthritis (KOA) on plain radiographs is poorly reproducible across readers. A single-grade disagreement on the Kellgren-Lawrence (KL) scale can alter surgical management or redirect a patient from conservative therapy to intra-articular injection. Meanwhile, deep learning models that outperform human readers often offer no explanation for their decisions. We present Knee-xRAI, a pipeline that decomposes the grading process by mimicking clinical radiological workflows. It independently measures joint space narrowing (JSN), osteophytes, and subchondral sclerosis, then combines these findings into an explainable KL grade. Specifically, a U-Net++ architecture quantifies JSN via contour segmentation, an SE-ResNet-50 multi-task network grades osteophytes per anatomical site on the OARSI scale, and a hybrid texture-CNN detects binary sclerosis. This pipeline yields a 50-dimensional feature vector evaluated via an XGBoost-SHAP classifier (Path A, audit) and a ConvNeXt hybrid predictor (Path B, deployed). On 8,260 OAI-derived radiographs, the JSN module achieved a Dice score of 0.8909 and an mJSW ICC of 0.8674. Path A reached a QWK of 0.6294 and an AUC of 0.8046, confirming the structured feature vector carries substantial diagnostic signal. Path B achieved a QWK of 0.8436 and an AUC of 0.9017. SHAP analysis identifies JSN as the dominant feature, with osteophytes adding a consistent increment and sclerosis contributing marginally. Removing JSN evidence collapses KL3-KL4 recall while early grades remain intact, aligning with the KL diagnostic criteria. Knee-xRAI grounds every prediction in an auditable chain of measured radiographic findings, providing clinical transparency at the point of care.

Background and objective. Conventional Deep Learning (DL) approaches for Knee Osteoarthritis (KOA) grading rely on one-hot labels, which fail to capture both the ordinal uncertainty of Kellgren--Lawrence (KL) and Calcium Pyrophosphate Deposition Disease (CPPD) severity scores and the asymmetric relationship between the two scales observed in clinical practice. Methods. We retrospectively collected 2172 knee X-ray images, including 968 radiographs jointly annotated for KL and CPPD severity. An ordinal DL framework based on soft-labelling was developed for both tasks, replacing one-hot targets with unimodal probability distributions centred on the annotated grade. Four formulations were investigated: binomial, beta, triangular, and exponential. Results. All soft-labelling strategies consistently outperformed the nominal baseline. For CPPD grading, the triangular formulation achieved the highest Quadratic Weighted Kappa (QWK) and the lowest Mean Absolute Error (MAE) (QWK = 0.796; MAE = 0.438), while the beta formulation yielded the most balanced class-wise performance considering Average MAE (AMAE) and Maximum MAE (MMAE) across classes (AMAE = 0.458; MMAE = 0.573). For KL grading, the beta-based approach provided the best overall performance, achieving the highest QWK together with the lowest MAE and class-wise errors (QWK = 0.777; MAE = 0.529; AMAE = 0.523; MMAE = 0.775). Statistical analysis demonstrated significant improvements over conventional one-hot supervision (p < 0.001).