Two-Point Stretchable Electrode Array for Endoluminal Electrochemical Impedance Spectroscopy Measurements of Lipid-Laden Atherosclerotic Plaques

Abstract

Four-point electrode systems are commonly used for electric impedance measurements of biomaterials and tissues. We introduce a 2-point system to reduce electrode polarization for heterogeneous measurements of vascular wall. Presence of endoluminal oxidized low density lipoprotein (oxLDL) and lipids alters the electrochemical impedance that can be measured by electrochemical impedance spectroscopy (EIS). We developed a catheter-based 2-point micro-electrode configuration for intravascular deployment in New Zealand White rabbits. An array of 2 flexible round electrodes, 240 μm in diameter and separated by 400 μm was microfabricated and mounted on an inflatable balloon catheter for EIS measurement of the oxLDL-rich lesions developed as a result of high-fat diet-induced hyperlipidemia. Upon balloon inflation, the 2-point electrode array conformed to the arterial wall to allow deep intraplaque penetration via alternating current (AC). The frequency sweep from 10 – 300 kHz generated an increase in capacitance, providing distinct changes in both impedance (Ω) and phase (ϕ) in relation to varying degrees of intraplaque lipid burden in the aorta. Aortic endoluminal EIS measurements were compared with epicardial fat tissue and validated by intravascular ultrasound and immunohistochemistry for plaque lipids and foam cells. Thus, we demonstrate a new approach to quantify endoluminal EIS via a 2-point stretchable electrode strategy.

Ultrasonic transducer-guided electrochemical impedance spectroscopy to assess lipid-laden plaques

“…The imaging window distal to the balloon provided matched acoustic impedance, enabling the high-frequency transducer (45 MHz) to visualize the vessel lumen and 2-point electrode to align with the plaques. Thus, we introduced the first IVUS-guided EIS sensor to detect intraplaque oxLDL with reduced standard deviation (from 1.04 to 0.54 kΩ on average for magnitude) and increased statistical significance (from p < 0.07 to p < 0.0001 for magnitude) compared to non-guided results [15, 41, 53]. Prior to deployment in vivo , the sensors were heparinized in 1000 U/ml heparin to minimize adverse interactions between the sensor and blood.…”

“…Statistically significant results were obtained by the IVUS-guided EIS measurement ( p < 0.0001 for magnitude and p < 0.005 for phase within 15 kHz), whereas measurements without the guidance reduced the significance ( p < 0.07 for magnitude and p < 0.4 within 15 kHz) (Figure 5). Without guidance, measurement at random sites caused large variation and low significance in existing publications as well, where lower boundary of lesion sites overlapped the upper boundary of control [15, 41]. …”

“…Two-point electrode EIS sensor was designed for a high specific measurement with deep tissue penetration [41]. The EIS sensor is flexible but non-stretchable, which bends with the balloon while keep the sensor dimension and remain robust.…”

“…The divergence of electrical impedance between the oxLDL-laden plaque and healthy vessel provides a sensitive and specific assessment of atherosclerotic lesions. We developed a catheter-based 2-point micro-electrode configuration for intravascular deployment in NZW rabbits [41]. An array of 2 flexible rectangular electrodes, 3 mm in length by 300 μm in width, and separated by 300 μm, was microfabricated and mounted on an inflatable balloon catheter for EIS measurement of oxLDL-rich lesions.…”

“…Upon balloon inflation by air pressure, the 2-point electrode array conformed to the arterial wall to with alternating current (AC) excitation. The frequency sweep from 100 – Hz 300 kHz generated distinct changes in both impedance (Ω) and phase (ϕ) in relation to varying degrees of intraplaque oxLDL burden in the aorta [41]. …”