Key result
Self-gated DCE-MRI detects slower aortic root contrast washout with progressing atherosclerosis in mice.
Why the study?
High-risk atherosclerotic plaques feature active inflammation and leaky microvessels, requiring techniques to assess longitudinal changes in endothelial permeability during disease progression.
Does self-gated DCE-MRI with compressed sensing reconstruction detect longitudinal changes in aortic root endothelial permeability and correlate with plaque macrophage density during atherosclerosis progression in Apoe-/- mice?
Does self-gated DCE-MRI with compressed sensing reconstruction detect longitudinal changes in aortic root endothelial permeability and correlate with plaque macrophage density during atherosclerosis progression in Apoe-/- mice?
Self-gated black-blood DCE-MRI with compressed sensing enables noninvasive longitudinal quantification of contrast washout kinetics in the mouse aortic root during atherosclerosis progression, though single-slice washout rates showed only weak correlation with plaque macrophage density.
Answers are grounded in this paper and cite their sources.
Self-gated DCE-MRI supports longitudinal aortic permeability monitoring in atherosclerotic mice; leaves open macrophage correlation and human translation.
High‐risk atherosclerotic plaques are characterized by active inflammation and abundant leaky microvessels. We present a self‐gated, dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) acquisition with compressed sensing reconstruction and apply it to assess longitudinal changes in endothelial permeability in the aortic root of Apoe −/− atherosclerotic mice during natural disease progression. Twenty‐four, 8‐week‐old, female Apoe −/− mice were divided into four groups (n = 6 each) and imaged with self‐gated DCE‐MRI at 4, 8, 12, and 16 weeks after high‐fat diet initiation, and then euthanized for CD68 immunohistochemistry for macrophages. Eight additional mice were kept on a high‐fat diet and imaged longitudinally at the same time points. Aortic‐root pseudo‐concentration curves were analyzed using a validated piecewise linear model. Contrast agent wash‐in and washout slopes ( b 1 and b 2 ) were measured as surrogates of aortic root endothelial permeability and compared with macrophage density by immunohistochemistry. b 2 , indicating contrast agent washout, was significantly higher in mice kept on an high‐fat diet for longer periods of time ( p = 0.03). Group comparison revealed significant differences between mice on a high‐fat diet for 4 versus 16 weeks ( p = 0.03). Macrophage density also significantly increased with diet duration ( p = 0.009). Spearman correlation between b 2 from DCE‐MRI and macrophage density indicated a weak relationship between the two parameters (r = 0.28, p = 0.20). Validated piecewise linear modeling of the DCE‐MRI data showed that the aortic root contrast agent washout rate is significantly different during disease progression. Further development of this technique from a single‐slice to a 3D acquisition may enable better investigation of the relationship between in vivo imaging of endothelial permeability and atherosclerotic plaques' genetic, molecular, and cellular makeup in this important model of disease.
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Calcagno et al. (2022) studied Atherosclerosis (preclinical Apoe-/- mouse model) (n=32). Self-gated dynamic contrast-enhanced MRI (DCE-MRI) with compressed sensing reconstruction (after 16 weeks of high-fat diet) vs. 4 weeks of high-fat diet (and ex vivo CD68 macrophage immunohistochemistry) was evaluated on Aortic root contrast agent washout slope (b2) as a surrogate of endothelial permeability (r = 0.41 (Spearman correlation with weeks on high-fat diet), p=0.03). Self-gated DCE-MRI detected slower aortic root contrast washout between 16 and 4 weeks of high-fat diet in Apoe-/- mice.
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