Quantification of Cardiomyocyte Hypertrophy by Cardiac Magnetic Resonance

Abstract

Background—: Cardiomyocyte hypertrophy is a critical precursor to the development of heart failure. Methods to phenotype cellular hypertrophy noninvasively are limited. The goal was to validate a cardiac magnetic resonance–based approach for the combined assessment of extracellular matrix expansion and cardiomyocyte hypertrophy. Methods and Results—: Two murine models of hypertension (n=18, with n=15 controls) induced by l - N ^G -nitroarginine methyl ester (L-NAME) and pressure overload (n=11) from transaortic constriction (TAC) were imaged by cardiac magnetic resonance at baseline and 7 weeks after L-NAME treatment or up to 7 weeks after TAC. T1 relaxation times were measured before and after gadolinium contrast. The intracellular lifetime of water ( τ ic ), a cell size–dependent parameter, and extracellular volume fraction, a marker of interstitial fibrosis, were determined with a model for transcytolemmal water exchange. Cardiomyocyte diameter and length were measured on FITC–wheat germ agglutinin–stained sections. The τ _ic correlated strongly with histological cardiomyocyte volume-to-surface ratio ( r =0.78, P r =0.75, P P ic between 2 and 7 weeks after TAC. Conclusion—: The τ _ic measured by contrast-enhanced cardiac magnetic resonance provides a noninvasive measure of cardiomyocyte hypertrophy. Extracellular volume fraction and τ _ic can track myocardial tissue remodeling from pressure overload.