Cardiac Phase-Resolved T2* Magnetic Resonance Imaging Reveals Differences Between Normal Hearts and a Humanized Mouse Model of Hypertrophic Cardiomyopathy

<b>Background/Objectives</b>: While T₂^* mapping effectively assesses cerebral blood oxygenation, its utility for capturing cardiac phase-dependent myocardial changes in hypertrophic cardiomyopathy (HCM) is underexplored. This study investigates T₂^* dynamics in an HCM mouse model, to validate T₂^* as a clinically relevant biomarker for improved HCM diagnosis and treatment monitoring. <b>Methods</b>: A cardiac-specific <i>Mybpc3</i> 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 <i>Mybpc3</i>-KI (HCM) groups. The cardiac function was assessed using self-gated multi-slice 2D CINE imaging. To investigate myocardial T₂^* 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. <b>Results</b>: <i>Mybpc3</i>-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, <i>p</i> < 0.01) and reduced ejection fraction (HCM = 38.55 ± 5.39% vs. WT= 72.53 ± 3.95%, <i>p</i> < 0.01). Myocardial T₂^* was significantly elevated in HCM across all cardiac phases (HCM = 12.14 ± 1.54 ms vs. WT = 7.93 ± 1.57 ms, <i>p</i> = 0.002). Strong correlations were observed between myocardial T₂^* and LV mass (rho = 0.88, <i>p</i> = 0.03). <b>Conclusions</b>: T₂^* was elevated in HCM with increased LV mass, highlighting the potential of T₂^* MRI as a sensitive biomarker for distinguishing healthy mice from those with HCM and revealing possible myocardial abnormalities.