title: T₁ 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 T1 mapping could quantify the induction and pharmacological suppression of diffuse cardiac fibrosis in murine pressure-overload hypertrophy.
  
  
  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.
authors.affiliation: British Heart Foundation Centre of Research Excellence, National Heart and Lung Institute.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stuckey
authors.forename: Sara J
authors.initials: SJ
authors.lastname: McSweeney
authors.forename: May Zaw
authors.initials: MZ
authors.lastname: Thin
authors.forename: Josef
authors.initials: J
authors.lastname: Habib
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Price
authors.forename: Lorna R
authors.initials: LR
authors.lastname: Fiedler
authors.forename: Willy
authors.initials: W
authors.lastname: Gsell
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Prasad
authors.forename: Michael D
authors.initials: MD
authors.lastname: Schneider
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D003287:Contrast Media; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis / Q000175:diagnosis / Q000517:prevention & control; D019786:Gadolinium DTPA; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D019808:Losartan / Q000008:administration & dosage*; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D003287:Contrast Media; D019808:Losartan; D019786:Gadolinium DTPA
keywords: T1 mapping; animal model cardiovascular disease; cardiovascular MRI; late-gadolinium enhancement; pressure overload