Electrochemical impedance spectroscopy to characterize inflammatory atherosclerotic plaques

Abstract

Despite advances in diagnosis and therapy, atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality in the Western world. Predicting metabolically active atherosclerotic lesions has remained an unmet clinical need. We hereby developed an electrochemical strategy to characterize the inflammatory states of high-risk atherosclerotic plaques. Using the concentric bipolar microelectrodes, we sought to demonstrate distinct Electrochemical Impedance Spectroscopic (EIS) measurements for unstable atherosclerotic plaques that harbored active lipids and inflammatory cells. Using equivalent circuits to simulate vessel impedance at the electrode–endoluminal tissue interface, we demonstrated specific electric elements to model working and counter electrode interfaces as well as the tissue impedance. Using explants of human coronary, carotid, and femoral arteries at various Stary stages of atherosclerotic lesions ( n = 15), we performed endoluminal EIS measurements ( n = 147) and validated with histology and immunohistochemistry. We computed the vascular tissue resistance using the equivalent circuit model and normalized the resistance to the lesion-free regions. Tissue resistance was significantly elevated in the oxLDL-rich thin-cap atheromas (1.57 ± 0.40, n = 14, p < 0.001) and fatty streaks (1.36 ± 0.28, n = 33, p < 0.001) as compared with lesion-free region (1.00 ± 0.18, n = 82) or oxLDL-absent fibrous atheromas (0.86 ± 0.30, n = 12). Tissue resistance was also elevated in the calcified core of fibrous atheroma (2.37 ± 0.60, n = 6, p < 0.001). Despite presence of fibrous structures, tissue resistance between ox-LDL-absent fibroatheroma and the lesion-free regions was statistically insignificant (0.86 ± 0.30, n = 12, p > 0.05). Hence, we demonstrate that the application of EIS strategy was sensitive to detect fibrous cap oxLDL-rich lesions and specific to distinguish oxLDL-absent fibroatheroma.