title: Optical projection tomography permits efficient assessment of infarct volume in the murine heart postmyocardial infarction.
abstract: The extent of infarct injury is a key determinant of structural and functional remodeling following myocardial infarction (MI). Infarct volume in experimental models of MI can be determined accurately by in vivo magnetic resonance imaging (MRI), but this is costly and not widely available. Experimental studies therefore commonly assess injury by histological analysis of sections sampled from the infarcted heart, an approach that is labor intensive, can be subjective, and does not fully assess the extent of injury. The present study aimed to assess the suitability of optical projection tomography (OPT) for identification of injured myocardium and for accurate and efficient assessment of infarct volume. Intact, perfusion-fixed, optically cleared hearts, collected from mice 7 days after induction of MI by coronary artery occlusion, were scanned by a tomograph for autofluorescence emission after UV excitation, generating >400 transaxial sections for reconstruction. Differential autofluorescence permitted discrimination between viable and injured myocardium and highlighted the heterogeneity within the infarct zone. Two-dimensional infarct areas derived from OPT imaging and Masson's trichrome staining of slices from the same heart were highly correlated (r(2) = 0.99, P < 0.0001). Infarct volume derived from reconstructed OPT sections correlated with volume derived from in vivo late gadolinium enhancement MRI (r(2) = 0.7608, P < 0.005). Tissue processing for OPT did not compromise subsequent immunohistochemical detection of endothelial cell and inflammatory cell markers. OPT is thus a nondestructive, efficient, and accurate approach for routine in vitro assessment of murine myocardial infarct volume.
authors.affiliation: BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom;
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.affiliation: BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom;
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, United Kingdom;
authors.forename: C D
authors.initials: CD
authors.lastname: Gray
authors.affiliation: BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom;
authors.forename: K
authors.initials: K
authors.lastname: McGregor
authors.affiliation: Centre for Inflammation Research, University of Edinburgh, College of Medicine & Veterinary Medicine, Queens Medical Research Institute, Edinburgh, United Kingdom; and.
authors.forename: A G
authors.initials: AG
authors.lastname: Rossi
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: H
authors.initials: H
authors.lastname: Morrison
authors.affiliation: BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; Edinburgh Preclinical Imaging, BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom;
authors.forename: M A
authors.initials: MA
authors.lastname: Jansen
authors.affiliation: BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; gillian.gray@ed.ac.uk.
authors.forename: G A
authors.initials: GA
authors.lastname: Gray
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology*; D012680:Sensitivity and Specificity; D041622:Tomography, Optical
keywords: Masson's trichrome; ejection fraction; late gadolinium enhancement magnetic resonance imaging; mouse myocardial infarction; troponin I