Automatic framework for evaluating osteoarthritic cartilage severity: high-resolution cartilage thickness mapping and scoring

Objectives To develop and validate an automatic, scalable framework for assessing the femoro-tibial osteoarthritic cartilage severity using high-resolution cartilage thickness maps (CTh-Maps) and a cartilage thickness scoring system (CTh-Score).

The Osteoarthritis Initiative (OAI) cohort of 4796 subjects was analyzed. A 3D-UNet was trained to segment femoro-tibial bones and cartilages using MRI from baseline, 1-, 2-, 3-, 4-, 6- and 8-year follow-ups. CTh-Maps were created for each knee. A ResNet model trained on CTh-Maps assigned a CTh-Score ranging from 0 (healthy cartilage) to 100 (end-stage OA). The reproducibility of the CTh-Score was evaluated in a test/retest setup. Its validity was assessed by examining the correlation with expert evaluations of cartilage loss (MOAKS grading) and association to OA severity (KL grade) in both OAI and external dataset. The CTh-Score sensitivity to OA structural progression was examined.

The framework generated CTh-Maps for the entire OAI, forming the “OAI CTh-Maps” dataset. Both CTh-Maps and CTh-Score showed excellent reproducibility (ICC>0.98). The CTh-Score demonstrated strong correlations (r=0.81) with expert assessments of cartilage loss and strong associations to OA severity, including in the external dataset. The CTh-Score either increased or remained stable for almost all subjects at 8-year follow-up. The CTh-Score showed great sensitivity to change, significantly increasing between each timepoint, up to 6 years prior to KL progression.

CTh-Maps and CTh-Score represent a novel approach to analyze cartilage at imaging. Their scalability, reproducibility and sensitivity to osteoarthritic cartilage severity provide significant opportunities for earlier OA detection, better disease monitoring, and therapeutic window identification. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was funded by the Swiss National Science Foundation, Switzerland (SNSF Grant #CRSII5177155 & CRSII222725). The authors thank the Osteoarthritis Initiative (OAI) investigators, clinical staff and participants at each of the clinical centres and at the coordinating centre for their important contributions in acquiring the publicly available clinical and imaging data. The OAI is a public private partnership comprising five contracts (N01AR22258; N01AR22259; N01AR22260; N01AR22261; N01AR22262) funded by the NIH and conducted by the OAI Study Investigators. Private funding partners of the OAI include Merck Research Laboratories, Novartis Pharmaceuticals Corporation, GlaxoSmithKline, and Pfizer. Private sector funding for the OAI is managed by the Foundation for the NIH. 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 openly available human data that were originally located at: https://www.nia.nih.gov/research/resource/osteoarthritis-initiative-oai 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 Data Availability All data produced in the present study are available upon reasonable request to the authors