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Sci Transl Med. 2017 Jul 12;9(398). pii: eaal2658. doi: 10.1126/scitranslmed.aal2658.

Detecting human coronary inflammation by imaging perivascular fat.

Author information

1
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
2
Cardiothoracic Directorate, Oxford University Hospitals National Health System (NHS) Foundation Trust, Oxford, UK.
3
Oxford Centre of Research Excellence, British Heart Foundation, Oxford, UK.
4
Department of Cardiothoracic Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
5
Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
6
1st Department of Cardiology, Athens University Medical School, Athens, Greece.
7
Medizinische Klinik 2, Universitätsklinikum Erlangen, Erlangen, Germany.
8
Oxford Biomedical Research Centre, National Institute of Health Research, Oxford, UK.
9
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. antoniad@well.ox.ac.uk.

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.

PMID:
28701474
DOI:
10.1126/scitranslmed.aal2658
[Indexed for MEDLINE]

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