# Noninvasive Testing of Coronary Microvascular Reactivity Using High-resolution Free-breathing MRI

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2020 · $699,398

## Abstract

PROJECT SUMMARY
It was long taken for granted that obstructive coronary artery disease (CAD) is the primary driver of angina and
major adverse cardiac events. However, recent landmark studies have shown that up to 50% of the patients
referred for diagnostic testing have ischemia with no obstructive CAD (INOCA). A large proportion of INOCA
patients have coronary microvascular dysfunction (CMD), which even in the absence of flow-limiting stenoses
can lead to myocardial ischemia and carries a high risk of adverse events. The reference standard for
assessment of CMD is the functional coronary reactivity (CR) test, which is invasive. Despite key studies showing
value of stratifying therapy based on CR testing, the practical utility of CR testing in the INOCA population is
limited by its invasive nature, which carries serious risks even at experienced centers. Hence, a noninvasive
approach that can detect and stage the severity of CMD would be invaluable for managing INOCA patients.
Driven by this unmet need, prior studies have employed imaging approaches to index myocardial perfusion
reserve (MPR) against CR; however, the association shown to date between MPR and CR impairment has been
weak, likely due to the suboptimal sensitivity of MPR to subendocardial myocardial blood flow (MBF) deficits
which is a hallmark of CMD. Studies using invasive microsphere-based methods have established a stress
subendocardial-to-subepicardial (endo-epi) MBF gradient of larger than 1.0 in healthy animals, and shown that
it decreases well below 1 under abnormally elevated microvascular resistance. However, noninvasive detection
of endo-epi MBF gradients using existing imaging strategies is challenging because of the need to resolve MBF
transmurally. We have developed new MRI strategies aimed at overcoming key barriers for accurate evaluation
of endo-epi MBF gradients and applied them in preliminary animal and patient studies. Based on our preliminary
data, we hypothesize that in the setting of CMD, impaired microvascular CR manifests as a stress-induced endo-
epi MBF gradient, and the magnitude of this gradient significantly correlates with CMD severity. To test this
hypothesis, we propose 3 specific aims. In Aim 1, we will develop a free-breathing artifact-free MRI technique
optimized for high-resolution imaging of endo-epi MBF gradients, combined with a machine learning approach
for fully-automated objective quantification of MBF gradients. In Aim 2, we will test the hypothesis that CMD
severity can be staged on the basis of MRI-derived stress MBF gradient in a pig model of CMD. In Aim 3, we will
test the hypothesis that CMD severity in INOCA patients is highly correlated with MRI-derived stress MBF
gradient. This project brings together multiple interdisciplinary investigators with a strong collective track record
in developing cardiac imaging strategies to advance a noninvasive approach for determining CMD severity based
on the MRI-derived stress MBF gradient. Hence ...

## Key facts

- **NIH application ID:** 10037606
- **Project number:** 1R01HL153430-01
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Behzad Sharif
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $699,398
- **Award type:** 1
- **Project period:** 2020-07-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10037606

## Citation

> US National Institutes of Health, RePORTER application 10037606, Noninvasive Testing of Coronary Microvascular Reactivity Using High-resolution Free-breathing MRI (1R01HL153430-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10037606. Licensed CC0.

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