Coronary artery disease is the leading cause of death in the United States. It is estimated that in excess of 16 million people are living with coronary artery disease (CAD) and more than 1 in three deaths are due to CAD in the US. In addition, more than 1 million people are hospitalized each year in the US because of CAD. The most common form of CAD leads to the narrowing of the coronary arteries (stenosis) resulting in reduced blood flow and oxygen supplied to the heart muscle, results in myocardial ischemia - a condition where the oxygen demand of the myocardium is far in excess of the available supply. The presence of myocardial ischemia is an important risk factor for major adverse cardiac events (MACE: death, myocardial infarction, and stroke). Appropriate early interventions (coronary bypass, angioplasty, pharmacological, or medical therapy) that are guided by the extent and severity of ischemic burden associated with stable CAD may be instrumental in reducing the risk of MACE. Hence a reliable, non-invasive, and repeatable method for determining the extent and severity of ischemia is invaluable in managing patients with CAD. The broad, long-term objective of this proposal is to improve the prognosis of patients with coronary artery disease. An ideal strategy for assessing clinically significant myocardial ischemia would be completely non-invasive; that is, in addition to avoiding the risks of cardiac catheterization, it would be free of ionizing radiation, exogenous contrast media, and pharmacological stress-agents with both risks and side effects. Although the current clinical standards do not provide many of these benefits, a number of these requirements can be met by myocardial Blood-Oxygen-Level-Dependent (BOLD) MRI. However, the widespread use of this approach is currently limited by inadequate sensitivity, specificity, and the need for intravenous pharmacological (adenosine) stress, all of which pose considerable limitations in clinical practice. In the proposed project, we wish to significantly improve the reliability of myocardial BOLD MRI so that is becomes powerful enough to accurately quantify the ischemic volume associated with clinically significant CAD without intravenous pharmacological stress or exogenous contrast media. The proposed method utilizes (i) an individualized targeted change in arterial partial pressure of CO2 (PaCO2) as the non-invasive vasoactive stimulus, (ii) fast, high-resolution, 4D BOLD MRI at 3T and (iii) the generalized linear model (GLM) theory to derive statistical parametric maps (SPM) to reliably detect and quantify the clinically significant ischemic myocardial volume in a data-driven fashion. These studies are expected to provide the fundamental scientific basis for a non-invasive and reliable imaging strategy for evaluating prognosis of patients with coronary artery disease.

Public Health Relevance

Reliable detection of myocardial ischemia associated with significant coronary artery disease (CAD) is critical in the management of disease. Failing to accurately and non-invasively assess the progression of CAD exposes a vulnerable patient population to major cardiovascular events (stroke, myocardial infarction, or death). This proposal outlines an imaging strategy that is free of ionizing radiation, exogenous contrast media, and pharmacological stress agents to assess myocardial ischemia due to CAD; and has the potential to revolutionize ischemia testing in clinical settings.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL091989-07
Application #
8842175
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Evans, Frank
Project Start
2008-04-15
Project End
2016-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
7
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
Chartsias, Agisilaos; Joyce, Thomas; Giuffrida, Mario Valerio et al. (2018) Multimodal MR Synthesis via Modality-Invariant Latent Representation. IEEE Trans Med Imaging 37:803-814
Zhou, Zhengwei; Bi, Xiaoming; Wei, Janet et al. (2017) First-pass myocardial perfusion MRI with reduced subendocardial dark-rim artifact using optimized Cartesian sampling. J Magn Reson Imaging 45:542-555
Oksuz, Ilkay; Mukhopadhyay, Anirban; Dharmakumar, Rohan et al. (2017) Unsupervised Myocardial Segmentation for Cardiac BOLD. IEEE Trans Med Imaging 36:2228-2238
Yang, Hsin-Jung; Dey, Damini; Sykes, Jane et al. (2017) Arterial CO2as a Potent Coronary Vasodilator: A Preclinical PET/MR Validation Study with Implications for Cardiac Stress Testing. J Nucl Med 58:953-960
Kali, Avinash; Cokic, Ivan; Tang, Richard et al. (2016) Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse Remodeling. Circ Cardiovasc Imaging 9:
Bevilacqua, Marco; Dharmakumar, Rohan; Tsaftaris, Sotirios A (2016) Dictionary-Driven Ischemia Detection From Cardiac Phase-Resolved Myocardial BOLD MRI at Rest. IEEE Trans Med Imaging 35:282-93
Yang, Hsin-Jung; Sharif, Behzad; Pang, Jianing et al. (2016) Free-breathing, motion-corrected, highly efficient whole heart T2 mapping at 3T with hybrid radial-cartesian trajectory. Magn Reson Med 75:126-36
Rogatko, André; Cook-Wiens, Galen; Tighiouart, Mourad et al. (2015) Escalation with Overdose Control is More Efficient and Safer than Accelerated Titration for Dose Finding. Entropy (Basel) 17:5288-5303
Sharif, Behzad; Arsanjani, Reza; Dharmakumar, Rohan et al. (2015) All-systolic non-ECG-gated myocardial perfusion MRI: Feasibility of multi-slice continuous first-pass imaging. Magn Reson Med 74:1661-74
Cokic, Ivan; Kali, Avinash; Yang, Hsin-Jung et al. (2015) Iron-Sensitive Cardiac Magnetic Resonance Imaging for Prediction of Ventricular Arrhythmia Risk in Patients With Chronic Myocardial Infarction: Early Evidence. Circ Cardiovasc Imaging 8:

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