title: Assessment of Myocardial Fibrosis in Mice Using a T2*-Weighted 3D Radial Magnetic Resonance Imaging Sequence.
abstract: BACKGROUND
  Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis.
  
  
  OBJECTIVE
  To goal of this paper was to explore the use of a T2*-weighted radial sequence for the visualization of fibrosis in mouse heart.
  
  
  METHODS
  C57BL/6 mice were studied with MI (n = 20, replacement fibrosis), transverse aortic constriction (TAC) (n = 18, diffuse fibrosis), and as control (n = 10). 3D center-out radial T2*-weighted images with varying TE were acquired in vivo and ex vivo (TE = 21 μs-4 ms). Ex vivo T2*-weighted signal decay with TE was analyzed using a 3-component model. Subtraction of short- and long-TE images was used to highlight fibrotic tissue with short T2*. The presence of fibrosis was validated using histology and correlated to MRI findings.
  
  
  RESULTS
  Detailed ex vivo T2*-weighted signal analysis revealed a fast (T2*fast), slow (T2*slow) and lipid (T2*lipid) pool. T2*fast remained essentially constant. Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts. T2*slow correlated with the presence of diffuse fibrosis in TAC hearts (r = 0.82, P = 0.01). Ex vivo and in vivo subtraction images depicted a positive contrast in the infarct co-localizing with the scar. Infarct volumes from histology and subtraction images linearly correlated (r = 0.94, P<0.001). Region-of-interest analysis in the in vivo post-MI and TAC hearts revealed significant T2* shortening due to fibrosis, in agreement with the ex vivo results. However, in vivo contrast on subtraction images was rather poor, hampering a straightforward visual assessment of the spatial distribution of the fibrotic tissue.
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Bastiaan J
authors.initials: BJ
authors.lastname: van Nierop
authors.affiliation: Soft Tissue Biomechanics and Engineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Noortje A M
authors.initials: NA
authors.lastname: Bax
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Jules L
authors.initials: JL
authors.lastname: Nelissen
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands; Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Fatih
authors.initials: F
authors.lastname: Arslan
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Abdallah G
authors.initials: AG
authors.lastname: Motaal
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Larry
authors.initials: L
authors.lastname: de Graaf
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Jaco J M
authors.initials: JJ
authors.lastname: Zwanenburg
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Luijten
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D005355:Fibrosis; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051379:Mice