Introduction:
Atherosclerosis, a chronic inflammatory arterial disease, persists as the leading cause of acute coronary events or stroke in developed countries. Developing a reliable, reproducible, safe and simple strategy to detect lipid-rich, metabolically active, and mechanically unstable plaques remains an unmet bioengineering challenge. It is recognized that oxidized low-density lipoprotein (oxLDL) and macrophages produce changes in the electrochemical properties of vessel walls that can be measured by electrochemical impedance spectroscopy (EIS).
Hypothesis:
We tested the hypothesis that a new, 2-point intravascular micro-electrode configuration enables flexible frequency-dependent EIS characterization of lipid-rich lesions.
Methods:
A simplified yet robust sensor design with higher differentiating capability, featuring individually addressable, flexible round electrodes (Æ = 240 μm), was developed and microfabricated for intravascular EIS investigation. We documented in vivo deployment of stretchable EIS sensors for endoluminal interrogation and impedimetric investigation at multiple levels of the aortic tree characterized by differing stages of atherosclerotic disease in a New Zealand White rabbit model, compared EIS values in vivo and ex vivo, confirmed endoluminal atherosclerotic lesions by intravascular ultrasound, histology and immunohistochemistry, and obtained EIS profiles in epicardial fat tissue.
Results:
The frequency sweep revealed overlapping tissue resistivity from 1-10 kHz, but distinct capacitive property from 10-300 kHz, thereby providing complementary differentiation in both impedance (Ω) and phase (f) between healthy arteries and varying levels of atherosclerotic lesions. The EIS measurements revealed a significant increase in impedance in the presence of oxLDL-rich lesions from 5219 Ω in control to 5949 Ω in mild, 6988 Ω in moderate and 8351 Ω in severe plaque at 300 kHz (P < 0.05, n = 5 controls, n = 3 atherosclerotic). The correlation between in vivo and ex vivo analyses using Spearman was r = 0.97 (P < 0.0001, n = 8 aortic segments).
Conclusion:
We demonstrate a new, paired-electrode based EIS sensor for intravascular interrogation of lipid-laden lesions to complement diagnostic angiography.
Long-Term Analysis of In Vivo Characteristics of Recording Electrode Using Electrochemical Impedance Spectroscopy
