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T1 Mapping Detects Pharmacological Retardation of Diffuse Cardiac Fibrosis in Mouse Pressure-Overload Hypertrophy

Stuckey, DJ; McSweeney, SJ; Thin, MZ; Habib, J; Price, AN; Fiedler, LR; Gsell, W; ... Schneider, MD; + view all (2014) T1 Mapping Detects Pharmacological Retardation of Diffuse Cardiac Fibrosis in Mouse Pressure-Overload Hypertrophy. Circulation: Cardiovascular Imaging , 7 (2) pp. 240-249. 10.1161/CIRCIMAGING.113.000993. Green open access

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Abstract

Background: Diffuse interstitial fibrosis is present in diverse cardiomyopathies and associated with poor prognosis. We investigated whether magnetic resonance imaging-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 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 T1 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 T1 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, T1 mapping can be used to assess antifibrotic therapeutic strategies.

Type: Article
Title: T1 Mapping Detects Pharmacological Retardation of Diffuse Cardiac Fibrosis in Mouse Pressure-Overload Hypertrophy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/CIRCIMAGING.113.000993
Publisher version: https://doi.org/10.1161/CIRCIMAGING.113.000993
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: cardiovascular MRI, T1 mapping, pressure overload, animal model cardiovascular disease, late-gadolinium enhancement
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging
URI: https://discovery.ucl.ac.uk/id/eprint/10089832
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