Charting Aging Trajectories of Knee Cartilage Thickness for Early Osteoarthritis Risk Prediction: An MRI Study from the Osteoarthritis Initiative Cohort

Knee osteoarthritis (OA), a prevalent joint disease in the U.S., poses challenges in terms of predicting of its early progression. Although high-resolution knee magnetic resonance imaging (MRI) facilitates more precise OA diagnosis, the heterogeneous and multifactorial aspects of OA pathology remain significant obstacles for prognosis. MRI-based scoring systems, while standardizing OA assessment, are both time-consuming and labor-intensive. Current AI technologies facilitate knee OA risk scoring and progression prediction, but these often focus on the symptomatic phase of OA, bypassing initial-stage OA prediction. Moreover, their reliance on complex algorithms can hinder clinical interpretation. To this end, we make this effort to construct a computationally efficient, easily-interpretable, and state-of-the-art approach aiding in the radiographic OA (rOA) auto-classification and prediction of the incidence and progression, by contrasting an individual’s cartilage thickness with a similar demographic in the rOA-free cohort. To better visualize, we have developed the toolset for both prediction and local visualization. A movie demonstrating different subtypes of dynamic changes in local centile scores during rOA progression is available at . Specifically, we constructed age-BMI-dependent reference charts for knee OA cartilage thickness, based on MRI scans from 957 radiographic OA (rOA)-free individuals from the Osteoarthritis Initiative cohort. Then we extracted local and global centiles by contrasting an individual’s cartilage thickness to the rOA-free cohort with a similar age and BMI. Using traditional boosting approaches with our centile-based features, we obtain rOA classification of KLG ≤ 1 versus KLG = 2 (AUC = 0.95 , F1 = 0.89 ), KLG ≤ 1 versus KLG ≥ 2 (AUC = 0.90 , F1 = 0.82 ) and prediction of KLG2 progression (AUC = 0.98 , F1 = 0.94 ), rOA incidence (KLG increasing from < 2 to ≥ 2 ; AUC = 0.81 , F1 = 0.69 ) and rOA initial transition (KLG from 0 to 1; AUC = 0.64 , F1 = 0.65 ) within a future 48-month period. Such performance in classifying KLG ≥ 2 matches that of deep learning methods in recent literature. Furthermore, its clinical interpretation suggests that cartilage changes, such as thickening in lateral femoral and anterior femoral regions and thinning in lateral tibial regions, may serve as indicators for prediction of rOA incidence and early progression. Meanwhile, cartilage thickening in the posterior medial and posterior lateral femoral regions, coupled with a reduction in the central medial femoral region, may signify initial phases of rOA transition. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Research reported in this study was supported by the National Institutes of Health (NIH) under award number AR072013 (TY. L., B. C. and M. N.) and R01MH116527 (TF. L. and H.Z.). We also acknowledge support from NIH/NIAMS P30AR072580 (AE. N and YM. G). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used (or will use) ONLY openly available human data that were originally located at: I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.