Electrochemical impedance spectroscopy to characterize inflammatory atherosclerotic plaques
Fei Yu1, Xiaohu Dai, Tyler Beebe
1Biomedical Engineering and Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Insights
This study introduces an electrochemical impedance spectroscopy (EIS) method for characterizing atherosclerotic plaque inflammation. The novel technique accurately detects lipid-rich, unstable plaques, addressing a critical unmet need in cardiovascular disease prediction.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Electrochemistry
Background:
- Atherosclerotic cardiovascular disease is a leading cause of death globally.
- Predicting active, high-risk atherosclerotic lesions remains a significant clinical challenge.
- Current diagnostic methods lack the ability to precisely characterize plaque inflammation and lipid content.
Purpose of the Study:
- To develop and validate an electrochemical strategy for characterizing the inflammatory state of atherosclerotic plaques.
- To utilize Electrochemical Impedance Spectroscopy (EIS) with concentric bipolar microelectrodes to differentiate plaque types.
- To establish a non-invasive method for identifying metabolically active atherosclerotic lesions.
Main Methods:
- Developed an electrochemical strategy using concentric bipolar microelectrodes for endoluminal measurements.
- Employed equivalent circuit modeling to simulate and analyze vessel impedance at the electrode-tissue interface.
- Performed EIS measurements on human arterial explants (coronary, carotid, femoral) and validated findings with histology and immunohistochemistry.
Main Results:
- Tissue resistance, calculated via equivalent circuit modeling, was significantly elevated in oxidized low-density lipoprotein (oxLDL)-rich thin-cap atheromas and fatty streaks compared to lesion-free regions.
- Elevated tissue resistance was also observed in the calcified core of fibrous atheromas.
- EIS demonstrated sensitivity in detecting oxLDL-rich lesions and specificity in distinguishing them from oxLDL-absent fibroatheromas.
Conclusions:
- Electrochemical Impedance Spectroscopy (EIS) offers a sensitive and specific method for characterizing atherosclerotic plaque composition and inflammatory status.
- This technique can differentiate between metabolically active (oxLDL-rich) and stable (oxLDL-absent) atherosclerotic lesions.
- The developed EIS strategy holds promise for improving the prediction and management of high-risk atherosclerotic cardiovascular disease.
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.
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