As greater than 8 million Americans suffer from angina due to obstructive coronary artery disease (CAD) or microvascular disease (MVD), which are both associated with an increased risk for adverse cardiovascular events, accurate non-invasive assessment of the presence and functional significance of obstructive CAD and evaluation of MVD is of substantial clinical importance. While both CAD and MVD are characterized by abnormal coronary flow reserve (CFR), this parameter alone is insufficient to distinguish between these two conditions which have different management strategies. High-resolution whole-heart quantitative adenosine stress cardiac magnetic resonance (CMR) has the potential to provide a new tool to differentiate between these entities based on its ability to quantify differences between endocardial and epicardial perfusion. However, 3D quantitative adenosine stress CMR still suffers from a number of important limitations including limited spatial coverage, low in-plane spatial resolution, long temporal acquisition windows, and sensitivity to cardiac and respiratory motion. We have been developing efficient high-resolution 2D spiral CMR perfusion pulse sequences to overcome these limitations while providing whole-heart coverage. The broad long-term objective of this project is to develop robust high-resolution quantitative CMR perfusion techniques with whole-heart coverage to understand the development of perfusion abnormalities in animal models of microvascular disease and obstructive CAD, and to utilize these CMR techniques to improve the non-invasive diagnosis and risk stratification of patients with CAD and MVD. Improved diagnostic techniques for assessing myocardial perfusion in CAD and MVD could significantly reduce the need for invasive coronary angiography among patients being evaluated for angina.
The specific aims for this project are: (1) To develop an efficient high-resolution 2D spiral-based perfusion technique for robust, motion-insensitive and accurate measurements of myocardial perfusion and endocardial to epicardial (endo:ep) perfusion ratio. (2) To test the hypothesis that CMR accurately measures endo:epi perfusion ratios and detects a lower endo:epi ratio in obstructive CAD as compared to MVD in a porcine model. (3) To develop an algorithm using CMR derived MPR and endo:epi perfusion ratios to differentiate CAD from MVD in patients presenting with angina and known or suspected CAD. Successful completion of this project will result in an efficient, robust, and well-validated technique for high- resolution whole-heart quantification of myocardial perfusion able to accurately detect endo:epi perfusion gradients, quantify MPR and myocardial ischemic burden, and differentiate obstructive CAD from MVD. The very short temporal footprint and motion-insensitive reconstruction will enable robust perfusion quantification in patients with increased heart rates and inability to perform breath-holding extending the applicability of CMR.

Public Health Relevance

This proposal seeks to create highly innovative whole-heart 2D quantitative stress cardiac magnetic resonance perfusion techniques with high-spatial resolution to improve the non-invasive diagnosis of coronary artery disease and microvascular disease which are highly prevalent among the greater than 8 million patients in the US that suffer from angina. The improved accuracy of these non-invasive tests could significantly reduce health care costs resulting from patients undergoing expensive and often unnecessary invasive procedures, and would reduce the number of incorrect diagnoses. Thus, this project has the potential to reduce health care expenditures while improving patient care.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL131919-02
Application #
9418092
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Danthi, Narasimhan
Project Start
2017-02-01
Project End
2022-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Lopez, David; Pan, Jonathan A; Pollak, Peter M et al. (2017) Multiparametric CMR imaging of infarct remodeling in a percutaneous reperfused Yucatan mini-pig model. NMR Biomed 30: