Abstract 19700: MRI Based Non-Invasive Detection of Cardiomyocyte Hypertrophy and Cell Volume Changes

Abstract

BACKGROUND: Cardiac hypertrophy results from cardiomyocyte cell hypertrophy and expansion of the extracellular matrix. To elucidate the tissue phenotype requires a combined assessment of these characteristics. The goal of this study was to validate a novel MRI-based approach for the combined assessment of extra-cellular matrix expansion and cell size.

METHODS: Hypertension was induced by L-NAME (3mg/ml) in 17 wild-type mice (body-weight=37.2±2.3g). 13 mice (body-weight=37.5±2.5g) received placebo. Transaortic constriction (TAC) was performed in 11 male-wild-type (body-weight=25.2±2.0 g) mice. Mice were imaged at baseline, 7-weeks after L-NAME treatment, and 2 weeks after TAC at ≥4.7T. T1 was quantified with a Look-Locker cine technique, pre and post gadolinium. The intra-cellular lifetime of water (τic), a-cell size dependent parameter, and the extracellular volume fraction (ECV) were determined by fitting R1 in tissue, against R1 in the blood pool, with a 2-site model for transcytolemmal water exchange. Minor (Dmin) and major (Dmaj) cell-diameters were determined by image analysis of FITC-wheat germ agglutinin stained sections.

RESULTS: The hearts of L-NAME-treated and TAC mice developed hypertrophy (LV mass: TAC 113±16 and L-NAME 163.6 μg; all p<0.05 vs. controls). τic was significantly higher in L-NAME-treated animals (0.453±0.10 s; p<0.0001) and in TAC mice (0.255±0.04 s; p<0.001), compared to controls (0.193±0.07 s). τic correlated with the minor cell diameter (r=0.77, P<0.001), the major cell-diameter (r=0.5, p=0.02), and with LV mass (r=0.76, p<0.001). ECV in L-NAME-treated mice (0.395±0.047) was significantly higher (p<0.001) than in TAC (0.248±0.033; n.s. vs. controls) mice and controls (0.269±0.029).

CONCLUSION: We validated a combined and non-invasive quantification of cell size and extra-cellular space expansion. The results in TAC mice demonstrate the ability to detect changes in cellular hypertrophy before expansion of the extracellular space and development of cardiac (interstitial) fibrosis.