Abstract

Objective While microCT evaluation of atherosclerotic lesions in mice has been formally validated, existing image processing methods remain undisclosed. We aimed to develop and validate a reproducible image processing workflow based on phosphotungstic acid-enhanced microCT scans for the volumetric quantification of atherosclerotic lesions in entire mouse aortas. Approach and Results. 42 WT and 42 apolipoprotein E knockout mouse aortas were scanned. The walls, lumen, and plaque objects were segmented using dual-threshold algorithms. Aortic and plaque volumes were computed by voxel counting and lesion surface by triangulation. The results were validated against manual and histological evaluations. Knockout mice had a significant increase in plaque volume compared to wild types with a plaque to aorta volume ratio of 0.3%, 2.8%, and 9.8% at weeks 13, 18, and 26, respectively. Automatic segmentation correlated with manual (r2 ≥ 0.89; p < .001) and histological evaluations (r2 > 0.96; p < .001). Conclusions The semiautomatic workflow enabled rapid quantification of atherosclerotic plaques in mice with minimal manual work.

Highlights

  • The ApoE-/- mouse is the most commonly used animal model for studying atherosclerosis

  • Aortic and plaque volumes were computed by voxel counting and lesion surface by triangulation

  • Knockout mice had a significant increase in plaque volume compared to wild types with a plaque to aorta volume ratio of 0.3%, 2.8%, and 9.8% at weeks 13, 18, and 26, respectively

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Summary

Introduction

The ApoE-/- mouse is the most commonly used animal model for studying atherosclerosis. Histological methods are the reference for quantifying atherosclerosis in preclinical models [2]. The aortic root (Paigen) method is predominantly used [3], only a limited area of the aorta is analyzed; alternately, the en face method can evaluate lesions along the whole aorta [4]. Adequate characterization of the heterogeneity of atherosclerotic lesions within the aorta would, require a tight series of tissue sections, but a true three-dimensional method would be the obvious alternative

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