Improving characterization of hypertrophy-induced murine cardiac dysfunction using four-dimensional ultrasound derived strain mapping

Mouse models of cardiac disease have become essential tools in the study of pathological mechanisms, but the small size of rodents makes it challenging to quantify heart function with noninvasive imaging. Building off recent developments in high-frequency four-dimensional ultrasound (4DUS) imaging, we have applied this technology to study cardiac dysfunction progression in a murine model of metabolic cardiomyopathy. Cardiac knockout of carnitine palmitoyltransferase 2 (Cpt2 M-/- ) in mice hinders cardiomyocyte bioenergetic metabolism of long-chain fatty acids, and leads to progressive cardiac hypertrophy and heart failure. The proposed analysis provides a standardized approach to measure localized wall kinematics and simultaneously extract metrics of global cardiac function, LV morphometry, regional circumferential strain, and regional longitudinal strain from an interpolated 4D mesh of the endo- and epi-cardial boundaries. Comparison of metric changes due to aging suggest that circumferential strain at the base and longitudinal strain along the posterior wall are most sensitive to disease progression. We further introduce a novel Hybrid Strain Index (HSI) that incorporates information from these two regions and may have greater utility to characterize disease progression relative to other extracted metrics. Future work will look to apply these methods to additional disease models and further demonstrate the utility of metrics derived from 4DUS imaging and strain mapping.