Cellular Imaging of Human Atherosclerotic Lesions by Intravascular Electric Impedance Spectroscopy

Abstract

BackgroundNewer techniques are required to identify atherosclerotic lesions that are prone to rupture. Electric impedance spectroscopy (EIS) is able to provide information about the cellular composition of biological tissue. The present study was performed to determine the influence of inflammatory processes in type Va (lipid core, thick fibrous cap) and Vc (abundant fibrous connective tissue while lipid is minimal or even absent) human atherosclerotic lesions on the electrical impedance of these lesions measured by EIS.Methods and ResultsEIS was performed on 1 aortic and 3 femoral human arteries at 25 spots with visually heavy plaque burden. Severely calcified lesions were excluded from analysis. A highly flexible micro-electrode mounted onto a balloon catheter was placed on marked regions to measure impedance values at 100 kHz. After paraffin embedding, visible marked cross sections (n = 21) were processed. Assessment of lesion types was performed by Movats staining. Immunostaining for CD31 (marker of neovascularisation), CD36 (scavenger cells) and MMP-3 (matrix metalloproteinase-3) was performed. The amount of positive cells was assessed semi-quantitatively. 15 type Va lesions and 6 type Vc lesions were identified. Lesions containing abundant CD36-, CD31- and MMP-3-positive staining revealed significantly higher impedance values compared to lesions with marginal or without positive staining (CD36+455±50 Ω vs. CD36- 346±53 Ω, p = 0.001; CD31+436±43 Ω vs. CD31- 340±55 Ω, p = 0.001; MMP-3+ 400±68 Ω vs. MMP-3- 323±33 Ω, p = 0.03).ConclusionsAtherosclerotic lesions with abundant neovascularisation (CD31), many scavenger receptor class B expressing cells (CD36) or high amount of MMP-3 immunoreactivity reveal significantly higher impedance values compared to lesions with marginal or no detection of immunoreactivity. Findings suggest that inflammatory processes in vulnerable plaques affect the impedance of atherosclerotic lesions and might therefore be detected by EIS.

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

“…We characterize the stretchable sensors in terms of distinct changes in impedance and phase spectra in response to balloon inflation pressure. Our 2-point approach represents an advancement to the previously proposed linear 4-point electrode arrays 28, 29, 30 , which preclude detection of small and non-homogeneous lesions. Thus, we demonstrate a simplified 2-point electrode configuration to advance the electrochemical impedance measurements for intraplaque lipid-laden lesions.…”

“…However, fat tissue is anhydrous and thus, a poor conductor. The high lipid content, including negatively charged active lipids such as oxidized low density lipoprotein (oxLDL) 27 and foam cells present in the plaque change the endoluminal electrochemical properties that can be measured by EIS 17,28,29,30 …”

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

“…(Streitner et al 2012; Streitner et al 2009; Yu et al 2011b; Yu et al 2011c) We and others have established a quantitative correlation between tissue impedance and atherosclerotic lesions in terms of active lipid content (oxLDL). Streiners et al .…”

“…deployed impedance sensor by using a linear 4-point electrode configuration into ex vivo human coronary arteries, and demonstrated that inflammatory process in advanced vulnerable plaques (Type V) engendered an elevated tissue impedance. (Streitner et al 2012) However, the linear 4-electrode configuration poses two main constraints: 1) the large size of 4-electode array (1.4mm in the entire length) limits its capability to assess large lesions; and 2) the linear-arrays entails a limited spatial resolution to assess small and non-homogeneous lesions. For these reasons, we proposed the concentric bipolar microelectrodes to provide high spatial resolution (0.5mm diameter) and symmetric tissue impedance.…”

“…(Streitner et al 2012; Streitner et al 2009; Yu et al 2011b) Elevated electrochemical impedance spectroscopy (EIS) signals are associated with metabolically active lesions in both ex vivo (Hsiai et al 2002; Li et al 2012a) and in vivo models. (Konings et al 1997; Streitner et al 2012; Streitner et al 2009; Suselbeck et al 2005; Yu et al 2011b; Yu et al 2011c)_ENREF_24 When the microelectrodes are in contact with endoluminal surface, EIS signals are reproducible and independent of lumen diameters, blood viscosity, and the flow rate. (Yu et al 2011b) For this reason, we integrated EIS with high-frequency ultrasound and shear stress to assess lipid-laden atherosclerotic lesions…”