Department of Biomedical Engineering, Texas A& M University, College Station, TX, USA.
Autopsy and Pathology Services, Houston, TX, USA.
Atherosclerosis. 2019 Jun;285:120-127. doi: 10.1016/j.atherosclerosis.2019.04.223. Epub 2019 Apr 19.
Macrophages play an important role in the development and destabilization of advanced atherosclerotic plaques. Hence, the clinical imaging of macrophage content in advanced plaques could potentially aid in identifying patients most at risk of future clinical events. The lifetime of the autofluorescence emission from atherosclerotic plaques has been correlated with lipids and macrophage accumulation in ex vivo human coronary arteries, suggesting the potential of intravascular endogenous fluorescence or autofluorescence lifetime imaging (FLIM) for macrophage imaging. The aim of this study was to quantify the accuracy of the coronary intima autofluorescence lifetime to detect superficial macrophage accumulation in atherosclerotic plaques.
Endogenous FLIM imaging was performed on 80 fresh postmortem coronary segments from 23 subjects. The plaque autofluorescence lifetime at an emission spectral band of 494 ± 20.5 nm was used as a discriminatory feature to detect superficial macrophage accumulation in atherosclerotic plaques. Detection of superficial macrophage accumulation in the imaged coronary segments based on immunohistochemistry (CD68 staining) evaluation was taken as the gold standard. Receiver Operating Characteristic (ROC) curve analysis was applied to select an autofluorescence lifetime threshold value to detect superficial macrophages accumulation.
A threshold of 6 ns in the plaque autofluorescence lifetime at the emission spectral band of 494 ± 20.5 nm was applied to detect plaque superficial macrophages accumulation, resulting in ∼91.5% accuracy.
This study demonstrates the capability of endogenous FLIM imaging to accurately identify superficial macrophages accumulation in human atherosclerotic plaques, a key biomarker of atherosclerotic plaque vulnerability.
巨噬细胞在动脉粥样硬化斑块的发生和不稳定中发挥着重要作用。因此，对晚期斑块中巨噬细胞含量的临床影像学检查可能有助于识别未来发生临床事件风险最高的患者。动脉粥样硬化斑块内源性荧光的自发荧光发射寿命与脂质和巨噬细胞在体外人冠状动脉中的积累有关，这表明血管内内源性荧光或自发荧光寿命成像（FLIM）在巨噬细胞成像中的应用潜力。本研究的目的是定量评估冠状动脉内膜自发荧光寿命在检测动脉粥样硬化斑块表面巨噬细胞积累中的准确性。
对 23 名受试者的 80 个新鲜的尸检冠状动脉节段进行内源性 FLIM 成像。将 494±20.5nm 发射光谱带的斑块自发荧光寿命作为区分特征，以检测动脉粥样硬化斑块表面的巨噬细胞积累。根据免疫组织化学（CD68 染色）评估，将对成像冠状动脉节段内表面巨噬细胞积累的检测作为金标准。应用受试者工作特征（ROC）曲线分析选择自发荧光寿命阈值来检测表面巨噬细胞积累。
在 494±20.5nm 发射光谱带的斑块自发荧光寿命中，应用 6ns 的阈值来检测斑块表面巨噬细胞积累，准确率约为 91.5%。
本研究表明，内源性 FLIM 成像能够准确识别人动脉粥样硬化斑块中的表面巨噬细胞积累，这是动脉粥样硬化斑块易损性的一个关键生物标志物。
