title: Generation and 3-Dimensional Quantitation of Arterial Lesions in Mice Using Optical Projection Tomography.
abstract: The generation and analysis of vascular lesions in appropriate animal models is a cornerstone of research into cardiovascular disease, generating important information on the pathogenesis of lesion formation and the action of novel therapies. Use of atherosclerosis-prone mice, surgical methods of lesion induction, and dietary modification has dramatically improved understanding of the mechanisms that contribute to disease development and the potential of new treatments. Classically, analysis of lesions is performed ex vivo using 2-dimensional histological techniques. This article describes application of optical projection tomography (OPT) to 3-dimensional quantitation of arterial lesions. As this technique is non-destructive, it can be used as an adjunct to standard histological and immunohistochemical analyses. Neointimal lesions were induced by wire-insertion or ligation of the mouse femoral artery whilst atherosclerotic lesions were generated by administration of an atherogenic diet to apoE-deficient mice. Lesions were examined using OPT imaging of autofluorescent emission followed by complementary histological and immunohistochemical analysis. OPT clearly distinguished lesions from the underlying vascular wall. Lesion size was calculated in 2-dimensional sections using planimetry, enabling calculation of lesion volume and maximal cross-sectional area. Data generated using OPT were consistent with measurements obtained using histology, confirming the accuracy of the technique and its potential as a complement (rather than alternative) to traditional methods of analysis. This work demonstrates the potential of OPT for imaging atherosclerotic and neointimal lesions. It provides a rapid, much needed ex vivo technique for the routine 3-dimensional quantification of vascular remodelling.
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Kirkby
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute.
authors.forename: Lucinda
authors.initials: L
authors.lastname: Low
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute.
authors.forename: Junxi
authors.initials: J
authors.lastname: Wu
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute.
authors.forename: Eileen
authors.initials: E
authors.lastname: Miller
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute.
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
authors.affiliation: University/ BHF Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute; phadoke@staffmail.ed.ac.uk.
authors.forename: Patrick W F
authors.initials: PW
authors.lastname: Hadoke
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000473:pathology / Q000601:surgery; D021621:Imaging, Three-Dimensional / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D041622:Tomography, Optical / Q000379:methods*