Detecting human coronary inflammation by imaging perivascular fat
Detecting human coronary inflammation by imaging perivascular fat
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DOI：
10.1126/scitranslmed.aal2658
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发表时间：
2017-07-12
影响因子：
17.1
通讯作者：
Antoniades, Charalambos
中科院分区：
文献类型：
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作者：
Antonopoulos, Alexios S.;Sanna, Fabio;Antoniades, Charalambos
血管炎症的早期检测将允许部署用于预防或治疗多种疾病状态的靶向策略。由于血管炎症是无法检测到常用的成像方式，我们假设，血管周围脂肪组织（PVAT）诱导的血管炎症的表型变化可以量化使用一种新的计算机断层扫描（CT）血管造影方法。我们表明，发炎的人血管释放细胞因子，防止脂质积累的PVAT衍生的前脂肪细胞在体外，离体和体内。我们开发了一种三维PVAT分析方法，并研究了453例接受心脏手术的患者的人体脂肪组织外植体的CT图像，将体外图像与外植体生物学的体内CT扫描信息联系起来。我们开发了一种成像指标，CT脂肪衰减指数（FAI），描述脂肪细胞脂质含量和大小。FAI在检测组织炎症方面具有极好的灵敏度和特异性，如通过正电子发射断层扫描中18F-氟脱氧葡萄糖的组织摄取所评估的。在273名受试者的验证队列中，人体冠状动脉周围的FAI梯度识别了体内早期亚临床冠状动脉疾病，并检测了PVAT的动态变化，以响应急性冠状动脉综合征期间血管炎症和炎症易损动脉粥样硬化斑块的变化。我们的研究表明，人体血管对周围PVAT产生旁分泌效应，影响前脂肪细胞中的局部细胞内脂质积聚，这可以使用CT成像方法进行监测。这种方法可以在临床实践中实施，以非侵入性地检测人体冠状动脉血管系统中的斑块不稳定性。
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.