Probing Early Myocardial Remodeling in Response to a High-Fat Diet in Mice by Evaluation of Extracellular Volume Fraction Using 4D Retrospectively Gated Micro-CT Imaging

The objective of this study was to evaluate whether retrospectively gated 4D micro-computed tomography (µCT) can quantify extracellular volume fraction (ECV) as an early marker of myocardial fibrosis and remodeling in a high-fat diet (HFD) mouse model, and to determine its relationship with cardiac functional parameters.

Male C57BL/6J mice were assigned to control diet or high-fat diet (HFD) groups, with HFD animals imaged after 8 or 16 weeks of feeding and control animals scanned at an age-matched time point. Contrast-enhanced 4D µCT with ECG gating was performed for cardiac function analysis and pre/post-contrast imaging for ECV quantification, corrected for hematocrit. Functional measures included left ventricular (LV) volumes, ejection fraction, mitral annular plane systolic excursion (MAPSE), circumferential shortening, and dobutamine stress response.

Global LV ECV significantly increased at 8 weeks of HFD compared to controls, preceding changes in LV mass and ejection fraction. Early ECV elevation correlated with impaired lateral MAPSE, indicating subtle functional impairment despite preserved global systolic function. At 16 weeks, further remodeling was evident with increased LV mass, reduced epicardial circumferential shortening, decreased left atrial ejection area, and diminished dobutamine-induced contractile reserve.

Retrospectively gated 4D µCT provides a robust and noninvasive method for early detection of diffuse myocardial fibrosis and functional impairment in small animal models. This approach enables longitudinal studies of cardiac disease progression and therapeutic interventions, offering translational value for preclinical cardiology research.