Marcu Laura, Jo Javier A, Fang Qiyin, Papaioannou Thanassis, Reil Todd, Qiao Jian-Hua, Baker J Dennis, Freischlag Julie A, Fishbein Michael C
University of California Davis, Department of Biomedical Engineering, Davis, CA 95616, USA.
Atherosclerosis. 2009 May;204(1):156-64. doi: 10.1016/j.atherosclerosis.2008.08.035. Epub 2008 Sep 6.
Plaque with dense inflammatory cells, including macrophages, thin fibrous cap and superficial necrotic/lipid core is thought to be prone-to-rupture. We report a time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) technique for detection of such markers of plaque vulnerability in human plaques.
The autofluorescence of carotid plaques (65 endarterectomy patients) induced by a pulsed laser (337 nm, 0.7 ns) was measured from 831 distinct areas. The emission was resolved spectrally (360-550 nm range) and temporally (0.3 ns resolution) using a prototype fiber-optic TR-LIFS apparatus. Lesions were evaluated microscopically and quantified as to the % of different components (fibrous cap, necrotic core, inflammatory cells, foam cells, mature and degraded collagen, elastic fibers, calcification, and smooth muscle cell of the vessel wall).
We determined that the spectral intensities and time-dependent parameters at discrete emission wavelengths (1) allow for discrimination (sensitivity >81%, specificity >94%) of various compositional and pathological features associated with plaque vulnerability including infiltration of macrophages into intima and necrotic/lipid core under a thin fibrous cap, and (2) show a linear correlation with plaque biochemical content: elastin (P<0.008), collagen (P<0.02), inflammatory cells (P<0.003), necrosis (P<0.004).
Our results demonstrate the feasibility of TR-LIFS as a method for the identification of markers of plaque vulnerability. Current findings enable future development of TR-LIFS-based clinical devices for rapid investigation of atherosclerotic plaques and detection of those at high-risk.
含有密集炎症细胞(包括巨噬细胞)、薄纤维帽和浅表坏死/脂质核心的斑块被认为易于破裂。我们报告了一种时间分辨激光诱导荧光光谱(TR-LIFS)技术,用于检测人类斑块中这种斑块易损性标志物。
使用脉冲激光(337 nm,0.7 ns)测量65例接受动脉内膜切除术患者的颈动脉斑块的自发荧光,测量区域达831个不同部位。使用原型光纤TR-LIFS仪器对发射光进行光谱分辨(360 - 550 nm范围)和时间分辨(0.3 ns分辨率)。对病变进行显微镜评估,并对不同成分(纤维帽、坏死核心、炎症细胞、泡沫细胞、成熟和降解的胶原蛋白、弹性纤维、钙化以及血管壁平滑肌细胞)的百分比进行量化。
我们确定,在离散发射波长处的光谱强度和时间相关参数(1)能够区分(敏感性>81%,特异性>94%)与斑块易损性相关的各种成分和病理特征,包括巨噬细胞浸润到内膜以及薄纤维帽下的坏死/脂质核心,并且(2)与斑块生化成分呈线性相关:弹性蛋白(P<0.008)、胶原蛋白(P<0.02)、炎症细胞(P<0.003)、坏死(P<0.004)。
我们的结果证明了TR-LIFS作为一种识别斑块易损性标志物方法的可行性。当前的研究结果有助于未来开发基于TR-LIFS的临床设备,用于快速研究动脉粥样硬化斑块并检测高危斑块。