T1 Mapping Detects Pharmacological Retardation of Diffuse Cardiac Fibrosis in Mouse Pressure-overload Hypertrophy
Background—Diffuse interstitial fibrosis is present in diverse cardiomyopathies and associated with poor prognosis. We investigated whether MRI-based T1 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 (TAC) or sham surgery. The angiotensin receptor blocker Losartan was given to half the animals. Cine-MRI performed at 7 and 28 days showed hypertrophy, remodeling systolic and diastolic dysfunction in TAC groups as expected. Late gadolinium-enhanced-MRI revealed focal signal enhancement at the inferior right ventricular insertion point of TAC mice concordant with the foci of fibrosis in histology. The extracellular volume fraction (ECV), calculated from pre- and post-contrast T1 measurements, was elevated by TAC and showed direct linear correlation with picrosirius red collagen volume fraction, thus confirming the suitability of ECV as an in vivo measure of diffuse fibrosis. Treatment with Losartan reduced left ventricular dysfunction and prevented increased ECV, indicating that T1 mapping is sensitive to pharmacological prevention of fibrosis.
Conclusions—MRI 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, T1 mapping can be used to assess anti-fibrotic therapeutic strategies.
- animal model cardiovascular disease
- cardiovascular magnetic resonance imaging
- late gadolinium enhancement
- T1 mapping
- pressure overload
- Received June 11, 2013.
- Accepted January 3, 2014.