Cellular Imaging of Human Atherosclerotic Lesions by Intravascular Electric Impedance Spectroscopy

Background: Newer 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 Results: EIS 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+455650 V vs. CD36- 346653 V, p = 0.001; CD31+436643 V vs. CD31- 340655 V, p = 0.001; MMP-3+ 400668 V vs. MMP-3- 323633 V, p = 0.03)

Experimental setup of the impedance measurement system.

<p>Experimental setup of the impedance measurement system.</p

ROC curves computed by determined impedance values (at 100 kHz).

<p>ROC curves separating samples of abundant and minor/no staining with good (MMP-3) to excellent (CD31, CD36) accuracy.</p

Value of electric impedance measurements in detecting inflammatory processes defined by different markers of inflammation.

<p>Value of electric impedance measurements in detecting inflammatory processes defined by different markers of inflammation.</p

Cross section depicting an advanced lesion type Va.

<p>Movats staining, magnification 20×. LC: Characteristic lipid core. FC: Thick fibrous cap with yellow staining of collagen fibers and red-colored smooth muscle cells. M: Media. Arrow: Microhemorrhages, typically found at the lateral margin of the lipid core (red: stained fibrin).</p

A-C. Kaplan Meier survival estimation after appropriate shocks (complete follow-up).

<p>A significant association between appropriate shocks and survival is only determined in patients with ICM.</p

Comparison of VTA episodes and appropriate shocks in patients with DCM and ICM.

<p>app. shock  =  appropriate shock; DCM  =  dilated cardiomyopathy; ES  =  electrical storm; ICM  =  ischemic cardiomyopathy; VF  =  ventricular fibrillation; VT  =  ventricular tachycardia; VTA  =  ventricular tachyarrhythmia.</p

A-B. Kaplan Meier survival estimation after occurrence of appropriate shocks before median follow-up.

<p>Kaplan Meier Curves displaying that the significant effect of appropriate shocks on survival in the overall patient population is primarily driven by the ICM subgroup.</p