Cardiac phase-resolved T(2)* magnetic resonance imaging reveals differences between normal hearts and a humanized mouse model of hypertrophic cardiomyopathy

BACKGROUND/OBJECTIVES: While T(2)* mapping effectively assesses cerebral blood oxygenation, its utility for capturing cardiac phase-dependent myocardial changes in hypertrophic cardiomyopathy (HCM) is underexplored. This study investigates T(2)* dynamics in an HCM mouse model, to validate T(2)* as a clinically relevant biomarker for improved HCM diagnosis and treatment monitoring. METHODS: A cardiac-specific Mybpc3 genetic mouse model, closely mirroring human HCM, was used with 12 young mice (6–11 weeks old), including both male and female wild-type (WT) and Mybpc3-KI (HCM) groups. The cardiac function was assessed using self-gated multi-slice 2D CINE imaging. To investigate myocardial T(2)* variations across the cardiac cycle, multi-gradient echo (MGE) imaging was employed. This approach used retrospective gating and continuous acquisition synchronization with pulse oximetry at 9.4 T small animal MRI. RESULTS: Mybpc3-KI mice demonstrated left-ventricular (LV) hypertrophy compared to WT (HCM = 50.08 ± 4.68 µm/g vs. WT = 45.80 ± 20.07 µm/g, p < 0.01) and reduced ejection fraction (HCM = 38.55 ± 5.39% vs. WT= 72.53 ± 3.95%, p < 0.01). Myocardial T(2)* was significantly elevated in HCM across all cardiac phases (HCM = 12.14 ± 1.54 ms vs. WT = 7.93 ± 1.57 ms, p = 0.002). Strong correlations were observed between myocardial T(2)* and LV mass (rho = 0.88, p = 0.03). CONCLUSIONS: T(2)* was elevated in HCM with increased LV mass, highlighting the potential of T(2)* MRI as a sensitive biomarker for distinguishing healthy mice from those with HCM and revealing possible myocardial abnormalities.