Molecular cartilage pathology following anterior cruciate ligament reconstruction: a systematic review of MRI studies

Background Anterior cruciate ligament (ACL) injury increases the risk of post-traumatic osteoarthritis. Although ACL reconstruction (ACLR) restores mechanical stability, cartilage matrix abnormalities may persist and can be detected using quantitative and compositional magnetic resonance imaging (MRI). Objectives To synthesize MRI evidence on tibiofemoral cartilage compositional changes after ACLR, identify factors associated with worse cartilage outcomes, and summarize methodological quality and limitations of the evidence. Methods Embase, PubMed, Web of Science, Scopus, and Cochrane Library were searched for studies published between 2000 and 2025 that evaluated tibiofemoral cartilage after ACLR using quantitative or compositional MRI. Two reviewers performed screening, data extraction, and risk-of-bias assessment. Meta-analysis was restricted to outcomes with sufficient comparability across studies; other outcomes were synthesized narratively. Results Thirty-five studies were included. Across cohorts, ACLR knees generally demonstrated elevated cartilage T2 relaxation times and elevated T1 ρ values compared with contralateral or healthy control knees, consistent with persistent cartilage matrix alteration. Abnormalities were most frequently reported in weight-bearing medial compartment regions and were more consistently observed at longer follow-up intervals. Meniscal pathology and altered biomechanics were repeatedly associated with less favorable compositional or structural cartilage outcomes. Evidence regarding graft type and rehabilitation strategy was limited and heterogeneous, and causal inferences could not be made. Meta-analysis was feasible only for a subset of T2 comparisons and suggested higher tibiofemoral T2 in ACLR knees, with substantial between-study heterogeneity. Limitations Considerable variability in MRI protocols, regions of interest, and reporting limited pooling. Several studies may represent overlapping cohorts, and many analyses were underpowered. Conclusion MRI evidence indicates that biochemical cartilage abnormalities commonly persist after ACLR, particularly in the medial tibiofemoral compartment. Standardized imaging protocols and long-term longitudinal studies linking MRI biomarkers to clinical outcomes are needed. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251156314 , PROSPERO CRD420251156314.