Atherosclerosis is a progressive asymptomatic disease that has the highest rate of death and morbidity in the United States. High macrophage infiltration and thin cap fibroatheromas are known to be the precursor lesions of plaque rupture. Lipid-laden macrophages called foam cells are formed by the uptake of lipids within the plaque. These foam cells eventually die forming a necrotic core. Ruptured plaques are characterized by a necrotic core with an overlying thin-ruptured cap highly infiltrated by macrophages. Imaging modalities capable of identifying macrophage clusters in atherosclerotic plaques could be used for plaque vulnerability assessment. In this study, Multispectral Fluorescence Lifetime Imaging (FLIM) is used to retrieve information of biochemical markers present in atherosclerotic tissue. Here, we present a computational methodology that makes use of FLIM-based biochemical plaque features in order to identify macrophage/foam cells in atherosclerotic plaques. In the proposed methodology, the FLIM lifetime map obtained from a spectral channel of 494 ± 20.5 nm provides information about the accumulation of macrophages, which produce long lifetimes (>6 ns). This methodology was validated against histopathological assessment (CD68 staining specific for macrophages) in terms of statistical correlation, a 10-fold cross validation (sensitivity = 88.45%; specificity= 91.21%), and receiver operating characteristic (ROC AUC = 0.91) analyses.
Jose D. Rico-Jimenez, Michael J. Serafino, Xi Chen, Sebina Shrestha, Wihan Kim, Brian L. Walton, Brian E. Applegate, and Javier A. Jo, "Automatic detection of macrophages/foam cells in coronary atherosclerotic plaques based on fluorescence lifetime imaging (FLIM) (Conference Presentation)," Proc. SPIE 10471, Diagnostic and Therapeutic Applications of Light in Cardiology 2018, 1047105 (Presented at SPIE BiOS: January 27, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2288606.5751476014001.
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