Quantification of Cardiomyocyte Hypertrophy by Cardiac Magnetic Resonance: Implications on Early Cardiac Remodeling
Background—Cardiomyocyte hypertrophy is a critical precursor to the development of heart failure. Methods to phenotype cellular hypertrophy non-invasively are limited. The goal was to validate a CMR-based approach for the combined assessment of extracellular matrix expansion and cardiomyocyte hypertrophy.
Methods and Results—Two murine models of a) hypertension (N=18, with N=15 controls) induced by L-NG-Nitroarginine Methyl Ester (L-NAME) and b) pressure-overload (N=11) from transaortic constriction (TAC), were imaged by CMR at baseline and 7-weeks after L-NAME treatment, or up to 7 weeks following TAC. T1 relaxation times were measured before and after gadolinium contrast. The intracellular lifetime of water (τic), a cell size dependent parameter, and extracellular volume fraction (ECV), 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. τic correlated strongly with histologic cardiomyocyte volume-to-surface ratio (r=0.78, P<0.001) and cell volume (r=0.75; P<0.001). Histological cardiomyocyte diameters and cell volume were higher in mice treated with L-NAME compared to controls (P<0.001). In the TAC model, CMR and histology showed an cell hypertrophy at two weeks post TAC, without significant fibrosis at this early time point. Mice exposed to TAC demonstrated a significant, longitudinal, and parallel increase in histological cell volume, volume-to-surface ratio, and τic, between 2 and 7 weeks after TAC.
Conclusions—The intracellular lifetime (τic) measured by contrast-enhanced CMR provides a non-invasive measure of cardiomyocyte hypertrophy. ECV and τic can track myocardial tissue remodeling from pressure overload.
- Received December 5, 2012.
- Revision received July 19, 2013.
- Accepted July 24, 2013.