# Integrating 3-D Intravascular Sensors with Fractional Flow Reserve for Lipid-Rich Plaques

> **NIH VA I01** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2020 · —

## Abstract

Integrating 3-D Micro-Electrode Sensing with Fractional Flow Reserve for Lipid-Rich Plaques
Atherosclerosis and metabolic diseases are on the rise in our veterans returning from battlefields in
Afghanistan and the Middle East. Atherosclerosis is a systemic disease; however, its manifestations tend to be
focal and eccentric, and rupture of individual plaques is the primary underlying mechanism of myocardial
infarction and stroke. Plaques prone to rupture contain high levels of oxidative stress and inflammatory activity
in part due to oxidized lipids and foam cells. Based on randomized clinical trials, American Heart Association
guidelines recommend the routine measurement of Fraction Flow Reserve (FFR), defined as the ratio of
pressure across the stenotic lesions (Pdownstream/Pupstream), to determine the indication for coronary
revascularization in patients with coronary artery disease (CAD). For FFR > 0.8, patients are treated with
medical optimization; for FFR ≤ 0.8, patients are referred for coronary revascularization, e.g., stent deployment
and antiplatelet therapy. Nevertheless, the recent five-year outcomes of the FAME (Fractional Flow Reserve
versus Angiography for Multivessel Evaluation) 2 trial revealed no difference in death or myocardial infarction
between FFR-guided percutaneous coronary intervention (PCI) and optimal medical therapy in patients with
stable CAD. Thus, real-time detection of the metabolically unstable plaque prone to rupture remains an unmet
clinical challenge. Our previous studies demonstrated that endoluminal electrochemical impedance
spectroscopy (EIS) distinguishes pre-atherogenic lesions associated with oxidative stress in fat-fed New
Zealand White (NZW) rabbits. Specifically, vessel walls harboring oxidized low density lipoprotein (oxLDL)
exhibit high EIS magnitude. In parallel, intimal monocytes and oxLDL are deleterious at all stages of
atherosclerosis, destabilizing calcific vascular nodules via induction of matrix metalloproteinases (MMP). In this
context, we seek to develop an electrochemical strategy to identify apparently stable, but metabolically active
(with FFR > 0.8) lesions containing oxLDL-laden monocyte-macrophages (foam cells), during diagnostic
angiography. We hypothesize that integrating 3-D electrochemical impedance spectroscopy with FFR
pressure sensors allows for detection of oxLDL-rich lesions to improve the accuracy of necessary
intervention. To test our hypothesis, we have three Specific Aims. In Aim 1, we will integrate a 12-point 3-D
electrode array permitting high spatial and angular resolution with pressure sensors to enhance detection of
oxLDL-laden plaque. In Aim 2, we will determine the sensitivity and specificity of 3-D EIS mapping for oxLDL-
laden, foam cell-rich atherosclerotic lesions in fat-fed vs. D-4F (an apolipoprotein A-I mimetic peptide) + fat-fed
NZW rabbits. In Aim 3, we will establish 3-D EIS mapping in rupture-prone plaque in the carotid arteries of a
pig model. Overall,...

## Key facts

- **NIH application ID:** 9892828
- **Project number:** 1I01BX004558-01A2
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** Rene R.S. Packard
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892828

## Citation

> US National Institutes of Health, RePORTER application 9892828, Integrating 3-D Intravascular Sensors with Fractional Flow Reserve for Lipid-Rich Plaques (1I01BX004558-01A2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9892828. Licensed CC0.

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