Serial Cross‐Sectional Mapping of Bone Marrow Microenvironment Remodelling During Fracture Repair Using Multiparametric MRI and Histopathology

Restoring bone marrow microenvironment (BMM) homeostasis is critical for fracture healing, yet non‐invasively tracking physiological events like apoptosis, angiogenesis and matrix remodelling remains challenging. This study evaluated multiparametric 7.0T MRI (T2 mapping and proton density‐weighted imaging [PDWI]) for in vivo tracking of BMM spatiotemporal remodelling during natural and pharmacologically accelerated bone repair. Utilizing a rat tibial drill‐hole injury model ( N = 36), we compared a natural healing control with a Huoxue Qiangji Decoction (HQD) intervention group. Serial high‐resolution sagittal MRIs were acquired at days 7, 14 and 21, with signal intensity ratios (SIR) normalized to ipsilateral intact marrow using ITK‐SNAP. Distance correlation (dCor) analysis explored non‐linear dependencies between MRI metrics and histological features (c‐cas3, Masson's trichrome and day‐14 CD31/Ki67 expression). Results showed distinct MRI signal trajectories, with earlier homeostatic stabilization in the accelerated healing group. Spatiotemporal mapping revealed closely mirrored non‐linear dependencies between MRI and histology. Specifically, T2 mapping SIR mirrored early‐stage apoptosis (dCor = 0.527) and mid‐term cellular proliferation (Ki67, dCor = 0.732). Concurrently, PDWI reflected dynamic trends of mid‐term angiogenesis (CD31, dCor = 0.637) and late‐stage collagen deposition (dCor = 0.480). In conclusion, normalized multiparametric MRI provides complementary macroscopic insights into BMM histological progression, highlighting its potential as an objective, non‐invasive translational tool for monitoring musculoskeletal healing.