Novel magnetic resonance imaging marker of diffuse myocardial fibrosis in hypertensive heart disease: the role of transcytolemmal water-exchange

Abstract

Summary Transcytolemal water exchange and its effect on myocardial T1 relaxation can, if neglected, lead to a significant underestimate of the myocardial extracellular volume fraction, a novel marker of diffuse fibrosis. Background LGE may fail to detect diffuse fibrosis in several cardiac conditions. A novel approach uses the myocardial extracellular volume-fraction (MECVF), measured as distribution volume of a gadolinium constrast, as a marker of extracellular expansion. Previous studies have assumed the fast-exchange (FX) limit for the transcytolemal waterexchange, yet the administration of an extracellular-agent can create significant transcytolemal T1-differences, and cause an underestimation of extracellular volume fraction under the FX assumption. We hypothesized that the quantitative measure of MECVF with using a 2-site H-exchange model (2SX-model) correlates positively with the extracellular volume fraction, while the FX approach underestimates extra-cellular matrix expansion in a rodent model of hypertensive heart disease and diffuse myocardial fibrosis created by administration of L-NAME. Methods L-NAME(3mg/ml) or placebo was administered respectively to 22(bw=36.9±2.3g) and 15(bw=37.6±2.5g) wildtype mice. Animals were imaged at baseline and 7weeks after treatment on a 4.7T small-animal MRI-system. T1(#of T1’s>5/mouse) was quantified with a modified Look-Locker gradient-echo-cine technique, before and after fractionated Gd-DPTA administration (mean max. R1 in blood post-contrast=5.0±2.26 1/s). MECVF obtained from the T1 measurements with the 2SX and FX-models, and by using blood hematocrit to adjust the partition coefficient. Connective tissue volume fraction (CTVF) was measured using Masson’s trichrome.