Cardiac CEST-MRI reveals early biochemical changes in transgenic models of early mitochondrial dysfunction and hypertrophic cardiomyopathy

Motivation: Hypertrophic cardiomyopathy is the most common inherited cardiovascular disorder and the most common cause of sudden cardiac death in people under 35. Early biochemical changes are currently undetectable, leading to diagnosis only in late disease stages. Goal(s): Is it possible to detect early biochemical changes in transgenic models of HCM using CEST-MRI? Approach: Using a recently developed method for ungated, preclinical cardiac CEST-MRI, two transgenic models of early HCM, heterozygous littermates, and WT mice were imaged and multiple CEST contrasts were analyzed. Results: Despite small sample sizes, differences in both creatine and amide CEST contrasts are becoming apparent between MyHC mutants and controls. Impact: Early biochemical changes associated with hypertrophic cardiomyopathy are currently undetectable with conventional imaging. CEST-MRI and associated CEST contrasts allow for these changes to be detected and studied.