Routine MRI Signal Intensity as a Surrogate of Subchondral Bone Healing: Validation Against Micro-CT and Histology in an Ovine Model.

Background/Objectives: To test whether routine T1-weighted spin-echo (T1-SE) and proton-density fast spin-echo (PD-FSE) MRI signal intensity (SI) can index bone regeneration after osteochondral scaffold implantation by correlating MRI metrics with micro-CT and histology. Methods: Twenty-eight sheep with bilateral trochlear defects were evaluated in separate cohorts at 30, 180, and 365 days (n = 7, 11, and 10, respectively). One knee received a tri-layered resorbable scaffold; the contralateral defect was left empty. MRI (T1-SE, PD-FSE) was read by two blinded musculoskeletal radiologists using 10-point Likert scales (T1: apparent mineralization; PD: SI normalization). Contrast-to-noise ratio (CNR) between repair-bone and reference bone was computed. MRI measures were correlated with micro-CT (new bone volume; trabecular bone volume) and histology (ICRS subchondral bone reconstruction; new bone; filling). Results: Likert ratings on both T1-SE and PD-FSE correlated with micro-CT new bone volume and trabecular bone volume and with histological measures of repair. PD-FSE CNR was inversely associated with micro-CT new bone volume and trabecular bone volume (both p < 0.001), indicating lower CNR with greater bone regeneration, whereas T1-SE CNR showed no significant associations. Inter-reader agreement was excellent (ICC 0.947 individual; 0.973 average), with good-to-excellent intra-reader reliability (0.920-0.963). Conclusions: Reader-based Likert assessment on both sequences and PD-FSE CNR provide complementary, non-invasive markers of subchondral bone regeneration, supporting MRI for radiation-free follow-up and endpoint selection in future translational studies. T1-SE CNR did not track incremental mineralization and should not be used as a stand-alone quantitative marker in early healing.