T ₁ Mapping Detects Pharmacological Retardation of Diffuse Cardiac Fibrosis in Mouse Pressure-Overload Hypertrophy

Abstract

Background— Diffuse interstitial fibrosis is present in diverse cardiomyopathies and associated with poor prognosis. We investigated whether magnetic resonance imaging-based T 1 mapping could quantify the induction and pharmacological suppression of diffuse cardiac fibrosis in murine pressure-overload hypertrophy. Methods and Results— Mice were subjected to transverse aortic constriction or sham surgery. The angiotensin receptor blocker losartan was given to half the animals. Cine-magnetic resonance imaging performed at 7 and 28 days showed hypertrophy and remodeling and systolic and diastolic dysfunction in transverse aortic constriction groups as expected. Late gadolinium-enhanced magnetic resonance imaging revealed focal signal enhancement at the inferior right ventricular insertion point of transverse aortic constriction mice concordant with the foci of fibrosis in histology. The extracellular volume fraction, calculated from pre- and postcontrast T 1 measurements, was elevated by transverse aortic constriction and showed direct linear correlation with picrosirius red collagen volume fraction, thus confirming the suitability of extracellular volume fraction as an in vivo measure of diffuse fibrosis. Treatment with losartan reduced left ventricular dysfunction and prevented increased extracellular volume fraction, indicating that T 1 mapping is sensitive to pharmacological prevention of fibrosis. Conclusions— Magnetic resonance imaging can detect diffuse and focal cardiac fibrosis in a clinically relevant animal model of pressure overload and is sensitive to pharmacological reduction of fibrosis by angiotensin receptor blockade. Thus, T 1 mapping can be used to assess antifibrotic therapeutic strategies.

Extracellular volume fraction in coronary chronic total occlusion patients

“…Based on previous studies, several T1 mapping approaches, including non-contrast T1 value, post-contrast T1 value and ECV, have been histologically-validated to have good correlation with the amount of collagen volume fraction both in animal models [23,24] and humans [12,13,25,26], therefore are increasingly accepted as an index of DMF. DMF commonly affect diastole first and subsequently systolic performance [5].…”

High field magnetic resonance imaging of rodents in cardiovascular research

“…T1-mapping is commonly acquired with a sequence based on the look-locker method although some authors described SNAPSHOT-FLASH Inversion Recovery (SNAP-IR) [24,124] or variable flip angle [39] strategies for the acquisition. In mouse, the acquisition is mainly made in combination with a contrast agent, gadolinium [24,39,138] or manganese [8,77,87,88,168,169]. Up to now, the technique has been successfully applied to murine models of myocardial infarction [24,39,168], cardiac hypertrophy [8,138] and dystrophinopathy [77].…”

“…In mouse, the acquisition is mainly made in combination with a contrast agent, gadolinium [24,39,138] or manganese [8,77,87,88,168,169]. Up to now, the technique has been successfully applied to murine models of myocardial infarction [24,39,168], cardiac hypertrophy [8,138] and dystrophinopathy [77]. Various applications have been studied: quantification of infarct size [24,39,168], identification of potentially salvageable myocardium [168] and evaluation of monocyte and macrophage spatiotemporal kinetics [107] in the vicinity of a myocardial infarction site, quantification of focal and diffuse fibrosis [138], or detection of changes in Ca 2?…”

Risk Stratification in Patients With Aortic Stenosis Using Novel Imaging Approaches

“…[51][52][53] Late gadolinium enhancement relies on a difference in signal intensity between normal and focal regions of myocardial fibrosis. It is therefore not an optimal technique for assessing interstitial fibrosis, which is more uniformly distributed and does not provide the necessary signal contrast for visualization.…”