Elevated electrochemical impedance in the endoluminal regions with high shear stress: Implication for assessing lipid-rich atherosclerotic lesions

Abstract

Background Identifying metabolically active atherosclerotic lesions remains an unmet clinical challenge during coronary intervention. Electrochemical impedance (EIS) increased in response to oxidized low density lipoprotein (oxLDL)-laden lesions. We hereby assessed whether integrating EIS with intravascular ultrasound (IVUS) and shear stress (ISS) provided a new strategy to assess oxLDL-laden lesions in the fat-fed New Zealand White (NZW) rabbits. Methods and Results A micro-heat transfer sensor was deployed to acquire the ISS profiles at baseline and post high-fat diet (HD) in the NZW rabbits (n=8). After 9 weeks of HD, serum oxLDL levels (mg/dL) increased by 140-fold, accompanied by a 1.5-fold increase in kinematic viscosity (cP) in the HD group. Time-averaged ISS (ISSave) in the thoracic aorta also increased in the HD group (baseline: 17.61±0.24 vs. 9 weeks: 25.22±0.95 dyne/cm2, n=4), but remained unchanged in the normal diet group (baseline: 22.85±0.53 dyne/cm2 vs. 9 weeks: 22.37±0.57 dyne/cm2, n=4). High-frequency Intravascular Ultrasound (IVUS) revealed atherosclerotic lesions in the regions with augmented ISSave, and concentric bipolar microelectrodes demonstrated elevated EIS signals, which were correlated with prominent anti-oxLDL immuno-staining (oxLDL-free regions: 497±55 Ω, n = 8 vs. oxLDL-rich lesions: 679±125 Ω, n = 12, P < 0.05). The equivalent circuit model for tissue resistance between the lesion-free and ox-LDL-rich lesions further validated the experimental EIS signals. Conclusions By applying electrochemical impedance in conjunction with shear stress and high-frequency ultrasound sensors, we provided a new strategy to identify oxLDL-laden lesions. The study demonstrated the feasibility of integrating EIS, ISS, and IVUS for a catheter-based approach to assess mechanically unstable plaque.

Blood flow modulation of vascular dynamics

“…For this reason, disturbed flow, including oscillatory flow, preferentially and geometrically occurs in the lateral wall of branching points (Figure 1). This atherogenic flow promotes vascular oxidative stress and inflammatory responses to initiate atherosclerosis [8]. …”

Stretchable electrochemical impedance sensors for intravascular detection of lipid-rich lesions in New Zealand White rabbits

“…Foam cells were identified by Sudan black stain, lipids with oil-red-O (Holvoet et al, 2001; Holvoet, Vanhaecke, Janssens, Van de Werf, & Collen, 1998; Verhamme et al, 2002), macrophages with anti-CD68 antibody, and oxLDL with mAb4E6 (Holvoet et al, 1998) as previously published (F. Yu, Ai, et al, 2011; Fei Yu et al, 2012). …”

“…Using equivalent circuits to simulate frequency-dependent changes in vessel impedance magnitude and phase, we have established specific electric elements in the working and counter electrode interfaces (F. Yu, Ai, et al, 2011; Fei Yu et al, 2012). When an alternating voltage (AC) is applied to the lesion site, the current can be detected and frequency-dependent electric impedance ( Z ) can be calculated.…”

A Review of Intravascular Ultrasound-based Multimodal Intravascular Imaging

“…This technology also has the potential for implementation in a catheter-based device to help differentiate the cellular composition of vulnerable plaques. 73 Furthermore, it has already been proposed that a plaque's vulnerability can be predicted by assessing the biomechanical properties of the coronary artery wall. 74 For this reason, high-resolution elastography techniques are rapidly being developed toward this goal in offering precise mapping of the vessel wall's biomechanical information onto structural IVUS or OCT images to detect vulnerable plaques.…”