The OVERALL OBJECTIVE of this application is to develop a novel quantitative computed tomography (CT)-based method for precise identification of coronary artery lesions that cause ischemia. At present, no non-invasive test exists that determines both coronary artery disease (CAD) stenosis severity and whether a stenosis causes ischemia, or reduced myocardial perfusion. Physiologic stress testing by myocardial perfusion imaging (MPI) is the traditional method for evaluating CAD, and identifies ischemia but not stenoses. In contrast, coronary CT angiography (CCTA) enables direct anatomic visualization of CAD, but cannot discriminate whether a stenosis causes ischemia. By invasive methods, a combined anatomic-physiologic approach to CAD evaluation by invasive coronary angiography and fractional flow reserve (FFR), respectively, improves diagnosis of patients with stenoses that cause ischemia, reduces unnecessary revascularization, and improves clinical outcomes. Recently, a combined anatomic-physiologic approach by non-invasive methods has become possible by the addition of CT perfusion (CTP) to CCTA. Similar to MPI, CTP permits physiologic assessment of stenoses through measures of regional myocardial signal attenuation. Early studies of CTP have been constrained by several limitations, including: 1) shading artifacts;2) motion artifacts;3) lack of a quantitative method for assessing perfusion;4 excess radiation;and 5) an inability to pinpoint specific lesions that cause ischemia. Projection based dual-energy CT (DECT) is a novel CT technology that directly addresses many of these limitations, providing the potential for dramatic reduction in artifacts and quantitative measurement of myocardial perfusion. Coupled with improvements in temporal resolution that reduce motion artifacts, DECT holds the potential to improve the diagnostic accuracy of CTP, with an undoubtedly positive and significant impact on the current diagnostic approach to patients with suspected CAD. The OVERALL HYPOTHESIS of this proposal is that a novel quantitative projection-based DECT-based method will enable discrimination of individuals who suffer from myocardial ischemia as well as the identification of the specific coronary artery lesions that are the cause. For this study, there are 3 specific aims: 1) Develop a novel DECT method that accurately quantifies material density;2) Determine the in vitro diagnostic accuracy of novel DECT method to characterize myocardial perfusion;3) Evaluate the in vivo diagnostic accuracy of CTP by the novel DECT method to determine coronary lesion-specific ischemia, as compared to an invasive FFR """"""""gold"""""""" standard.

Public Health Relevance

Coronary artery disease (CAD), or blockages in the heart arteries, is the leading cause of death in the world for both men and women. Computed tomography (CT) scans can visualize these blockages but cannot determine whether the blockages cause ischemia, or reduced blood supply to the heart muscle. This study will develop and validate novel CT methods (that reduce artifact and improve blood supply measurements) for both identification of individuals who manifest ischemia and also the specific coronary artery blockages that are the cause.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL111141-01A1
Application #
8438146
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Danthi, Narasimhan
Project Start
2013-02-04
Project End
2017-01-31
Budget Start
2013-02-04
Budget End
2014-01-31
Support Year
1
Fiscal Year
2013
Total Cost
$855,879
Indirect Cost
$200,441
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
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Rizvi, Asim; Hartaigh, Bríain Ó; Danad, Ibrahim et al. (2017) Diffuse coronary artery disease among other atherosclerotic plaque characteristics by coronary computed tomography angiography for predicting coronary vessel-specific ischemia by fractional flow reserve. Atherosclerosis 258:145-151
Schulman-Marcus, Joshua; Hartaigh, Bríain Ó; Gransar, Heidi et al. (2016) Sex-Specific Associations Between Coronary Artery Plaque Extent and Risk of Major Adverse Cardiovascular Events: The CONFIRM Long-Term Registry. JACC Cardiovasc Imaging 9:364-372
Danad, Ibrahim; Szymonifka, Jackie; Schulman-Marcus, Joshua et al. (2016) Static and dynamic assessment of myocardial perfusion by computed tomography. Eur Heart J Cardiovasc Imaging 17:836-44

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