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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.

A Volumetric Method for Quantifying Atherosclerosis in Mice by Using MicroCT: Comparison to En Face