Research ArticleAtherosclerosis

Detecting human coronary inflammation by imaging perivascular fat

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Science Translational Medicine  12 Jul 2017:
Vol. 9, Issue 398, eaal2658
DOI: 10.1126/scitranslmed.aal2658

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Picturing plaques and imaging inflammation

To determine risk of future coronary artery disease, calcium content in vascular plaques is typically evaluated by coronary calcium scoring, which uses computerized tomography (CT) imaging. To detect inflammation and subclinical coronary artery disease (soft, noncalcified plaques), Antonopoulos et al. developed an alternative metric called the perivascular CT fat attenuation index (FAI). The perivascular FAI uses CT imaging of adipose tissue surrounding the coronary arteries to assess adipocyte size and lipid content. Larger, more mature adipocytes exhibit greater lipid accumulation, which is inversely associated with the FAI. Inflammation reduces lipid accumulation and slows preadipocyte differentiation. Imaging pericoronary fat in human patients after myocardial infarction revealed that unstable plaques had larger perivascular FAIs than stable plaques and that the FAI was greatest directly adjacent to the inflamed coronary artery. The perivascular FAI may be a useful, noninvasive method for monitoring vascular inflammation and the development of coronary artery disease.

Abstract

Early detection of vascular inflammation would allow deployment of targeted strategies for the prevention or treatment of multiple disease states. Because vascular inflammation is not detectable with commonly used imaging modalities, we hypothesized that phenotypic changes in perivascular adipose tissue (PVAT) induced by vascular inflammation could be quantified using a new computerized tomography (CT) angiography methodology. We show that inflamed human vessels release cytokines that prevent lipid accumulation in PVAT-derived preadipocytes in vitro, ex vivo, and in vivo. We developed a three-dimensional PVAT analysis method and studied CT images of human adipose tissue explants from 453 patients undergoing cardiac surgery, relating the ex vivo images with in vivo CT scan information on the biology of the explants. We developed an imaging metric, the CT fat attenuation index (FAI), that describes adipocyte lipid content and size. The FAI has excellent sensitivity and specificity for detecting tissue inflammation as assessed by tissue uptake of 18F-fluorodeoxyglucose in positron emission tomography. In a validation cohort of 273 subjects, the FAI gradient around human coronary arteries identified early subclinical coronary artery disease in vivo, as well as detected dynamic changes of PVAT in response to variations of vascular inflammation, and inflamed, vulnerable atherosclerotic plaques during acute coronary syndromes. Our study revealed that human vessels exert paracrine effects on the surrounding PVAT, affecting local intracellular lipid accumulation in preadipocytes, which can be monitored using a CT imaging approach. This methodology can be implemented in clinical practice to noninvasively detect plaque instability in the human coronary vasculature.

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