Quantification of Cardiomyocyte Hypertrophy by Cardiac Magnetic Resonance

• DOI: 10.1161/circulationaha.112.000438
• Publication Date: 2013-08-03T05:06:53Z
• Authors: Otavio R. Coelho-...; Ravi V. Shah; Richard Mitchell; Tomas G. Neilan; Heitor Moreno; Bridget Simonson; Raymond Kwong; Anthony Rosenzweig; Saumya Das; Michael Jerosch-H...
• Keywords: Gadolinium DTPA; Male; Ventricular Remodeling; Contrast Media; Aortic Valve Stenosis; Hypertrophy; Cardiomyopathy, Hypertrophic; Magnetic Resonance Imaging; 3. Good health; Mice; Random Allocation; 03 medical and health sciences; NG-Nitroarginine Methyl Ester; Phenotype; 0302 clinical medicine; Body Water; Hypertension; Animals; Hypertrophy, Left Ventricular; Myocytes, Cardiac; Algorithms; Biomarkers; Cell Size

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 <0.001) and cell volume ( r =0.75, P <0.001). Histological cardiomyocyte diameters and cell volumes were higher in mice treated with L-NAME compared with controls ( P <0.001). In the TAC model, cardiac magnetic resonance and histology showed cell hypertrophy at 2 weeks after 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 τ 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.