# Electrochemical Impedance Spectroscopy to Assess Metabolically Active Plaque

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $432,085

## Abstract

ABSTRACT
Cardiometabolic disorders, including hyperlipidemia, obesity, and pre-diabetes, constitute the rising epidemic
in the US. These silent disorders progress to chronic diseases, including atherosclerosis. Metabolically active
plaques prone to rupture contain high levels of oxidized lipids and M1 macrophages. While rupture of individual
plaques is the primary underlying mechanism of myocardial infarction and stroke, real-time detection of the
vulnerable plaques prone to rupture remains an unmet clinical challenge. During the previous funding cycle, we
demonstrated the sensitivity and specificity of electrochemical impedance spectroscopy for oxidized low
density lipoprotein (oxLDL)-laden macrophages (foam cells) in the subendothelial layers of plaques in fat-fed
New Zealand White (NZW) rabbits, based on integration of 3 intravascular sensing modalities; namely, shear
stress sensor (SSS), ultrasound (IVUS), and electrochemical impedance spectroscopy (EIS). This strategy
allowed initial detection in area of disturbed flow, then visualization by IVUS, and then electrochemical
characterization by EIS. Vessel walls harboring oxLDL in the macrophages or foam cells exhibit a significant
increase in the frequency-dependent EIS magnitude, and these macrophages induce matrix metalloproteinase
(MMP) which destabilizes the calcified fibrous cap. We further deployed 3-D EIS sensors in Yucatan mini-pigs
undergoing right carotid artery ligation to establish the changes in EIS parameters caused by 12 weeks of high-
fat diet. For the next funding cycle, we seek to demonstrate that high 3-D EIS lesions are prone to rupture and
embolization. The routine measurement of Fraction Flow Reserve (FFR), defined as the ratio of pressure
across the stenotic lesions (Pdownstream/Pupstream) during coronary catheterization, determines the indication for
intervention in the significant, ischemia-causing coronary stenoses. For FFR ≥ 0.8, patients are treated with
medical therapy; for FFR ≤ 0.8, patients are referred for coronary revascularization. However, the predictors
for metabolically active, albeit non-obstructive, lesions prone to rupture remain undefined. In this context, our
multi-disciplinary team aims to make the fundamental translation of electrochemical impedance spectroscopy
(EIS) in the pre-clinical swine models and to test the hypothesis that 3-D EIS mapping of endoluminal oxLDL-
laden macrophages advances our ability to detect human atherosclerotic lesions prone to embolization. To test
our hypothesis, we have three Specific Aims. In Aim 1, we will determine in vivo 3-D electrochemical
properties to enhance detection of oxLDL-laden plaque. In Aim 2, we will establish 3-D EIS mapping in
rupture-prone plaque in swine. In Aim 3, we will compare EIS with near-infrared spectroscopy for oxLDL-
laden plaque. Overall, establishing 3-D electrochemical mapping of lipid-laden lesions in a swine model of
plaque rupture provides a pre-clinical strategy to identify metabol...

## Key facts

- **NIH application ID:** 9916814
- **Project number:** 5R01HL118650-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Tzung K Hsiai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,085
- **Award type:** 5
- **Project period:** 2014-07-10 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9916814

## Citation

> US National Institutes of Health, RePORTER application 9916814, Electrochemical Impedance Spectroscopy to Assess Metabolically Active Plaque (5R01HL118650-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9916814. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*