# Super Resolution Ultrasound Imaging of Vasa Vasorum to Characterize the Progression of Atherosclerotic Plaques and Predict Rupture Vulnerability

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $694,630

## Abstract

PROJECT SUMMARY
 Acute coronary syndromes and strokes together constitute a leading cause of morbidity and mortality in the
United States and Europe, approximately 80% of which are caused by atherosclerotic plaque (AP) rupture.
Over the past decade, extensive efforts have been made to identify a rupture-prone AP. Among others,
infiltration of dense neovascularization arising from vasa vasorum (VV) into the AP core plays a critical role in
AP rupture. Postmortem studies revealed key involvement of VV in AP. However, a persistent lack of a
noninvasive, high-resolution imaging tool to longitudinally assess abnormal microvascular expansion remains a
critical barrier to adequate in-vivo investigation on how VV affects AP progression and contributes to eventual
rupture. To address this dire unmet need, we propose an innovative transcutaneous super resolution
ultrasound (SRU) imaging. The technology development in this project seeks to shift the current US imaging
approach in identifying microvessels of AP from “intravascular” to a “fully noninvasive transcutaneous” imaging
approach. This is only possible by achieving unprecedented high spatial resolution at large depth, breaking
acoustic diffraction limit of the ultrasound frequency that governs spatial resolution. Our group has performed
in-depth feasibility studies where SRU imaging successfully identified neomicrovessels in cholesterol-fed rabbit
AP, evaluated against µCT and histology. Additionally, areas requiring further technical optimization were
identified. Such technology developments and preliminary data thus far rigorously support our overarching
hypothesis that enhanced and optimized SRU will accurately stage plaque progression and identify rupture-
prone plaques by directly measuring VV changes with exquisite detail. To test the hypothesis, we will use a
well-established, clinically relevant cholesterol-fed rabbit AP rupture model, which has shown the most
similarity to human plaque pathology including VV neovascularization, to validate the novel SRU system to 1)
Successfully quantify changes in vessel density and 2) Identify rupture-prone AP. To achieve these goals, we
propose the following specific aims: 1) To develop enhanced SRU at high frequency using a commercial small
animal imaging probe 2) To determine if VV changes estimated by SRU correlate with AP progression and are
predictive of AP rupture. The immediate outcomes of the proposed work are an affordable noninvasive small
animal SRU imaging tool and it’s validation on a clinically relevant rabbit AP model, which also can be used for
other important small animal disease models, which are associated with microvessel abnormality such as
cancer angiogenesis and kidney diseases to name a few. With proper adaptations into a clinical mid frequency
probe and validation in clinical settings in future, this work will lead to our long-term translational goal to
integrate SRU in a facile manner into the current clinical standard of carotid...

## Key facts

- **NIH application ID:** 10374343
- **Project number:** 1R01HL157465-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** KANG KIM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $694,630
- **Award type:** 1
- **Project period:** 2022-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374343

## Citation

> US National Institutes of Health, RePORTER application 10374343, Super Resolution Ultrasound Imaging of Vasa Vasorum to Characterize the Progression of Atherosclerotic Plaques and Predict Rupture Vulnerability (1R01HL157465-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10374343. Licensed CC0.

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