title: A volumetric method for quantifying atherosclerosis in mice by using microCT: comparison to en face.
abstract: Precise quantification of atherosclerotic plaque in preclinical models of atherosclerosis requires the volumetric assessment of the lesion(s) while maintaining in situ architecture. Here we use micro-computed tomography (microCT) to detect ex vivo aortic plaque established in three dyslipidemic mouse models of atherosclerosis. All three models lack the low-density lipoprotein receptor (Ldlr(-/-)), each differing in plaque severity, allowing the evaluation of different plaque volumes using microCT technology. From clearly identified lesions in the thoracic aorta from each model, we were able to determine plaque volume (0.04-3.1 mm(3)), intimal surface area (0.5-30 mm(2)), and maximum plaque (intimal-medial) thickness (0.1-0.7 mm). Further, quantification of aortic volume allowed calculation of vessel occlusion by the plaque. To validate microCT for future preclinical studies, we compared microCT data to intimal surface area (by using en face methodology). Both plaque surface area and plaque volume were in excellent correlation between microCT assessment and en face surface area (r(2) = 0.99, p<0.0001 and r(2) = 0.95, p<0.0001, respectively). MicroCT also identified internal characteristics of the lipid core and fibrous cap, which were confirmed pathologically as Stary type III-V lesions. These data validate the use of microCT technology to provide a more exact empirical measure of ex vivo plaque volume throughout the entire intact aorta in situ for the quantification of atherosclerosis in preclinical models.
authors.affiliation: Department of Metabolic Disorders, Amgen Inc., Thousand Oaks, California, United States of America. dlloyd@amgen.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Lloyd
authors.forename: Joan
authors.initials: J
authors.lastname: Helmering
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Kaufman
authors.forename: James
authors.initials: J
authors.lastname: Turk
authors.forename: Matt
authors.initials: M
authors.lastname: Silva
authors.forename: Sergio
authors.initials: S
authors.lastname: Vasquez
authors.forename: David
authors.initials: D
authors.lastname: Weinstein
authors.forename: Brad
authors.initials: B
authors.lastname: Johnston
authors.forename: Clarence
authors.initials: C
authors.lastname: Hale
authors.forename: Murielle M
authors.initials: MM
authors.lastname: Véniant
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging / Q000473:pathology; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed / Q000379:methods*