The broad, long-term objective of the proposed project is to improve the prognosis of patients with myocardial ischemia caused by coronary artery disease (CAD) or coronary microvascular dysfunction (CMD). Early diagnosis of myocardial ischemia caused by CAD is important as both coronary revascularization and medical therapies can significantly reduce morbidity and mortality. CMD is a major cause for myocardial ischemia in the absence of obstructive CAD, particularly in women, due to abnormalities in coronary microcirculation. First- pass myocardial perfusion cardiac magnetic resonance (CMR) is a highly promising technique for detecting regional blood flow deficits caused by ischemia. It does not require ionizing radiation and provides higher spatial resolution than nuclear imaging. Dynamic images acquired during intravenous vasodilator stress delineate regions associated with myocardial ischemia. Despite considerable technical improvements and clinical experience, a recent multicenter multivendor study (MR-IMPACT II) shows that while the sensitivity of CMR to detect ischemia caused by CAD is superior to SPECT (67% vs 59%), specificity is inferior (61% vs 72%). Both sensitivity and specificity of CMR remain relatively low indicating substantial false positive and false negative diagnoses. Several studies using MBF CMR have shown that abnormal MBF can be used to detect ischemia caused by CMD. However, these studies have shown only moderate diagnostic accuracy, indicating the need for major improvements. Major technical limitations of MBF CMR that contribute to inaccurate diagnoses of CAD and CMD include: (i) image artifacts, such as dark rim artifact (DRA) and cardiac and respiratory motion-induced artifacts, which reduce the image quality and diagnostic accuracy; (ii) incomplete coverage of the LV for evaluating total ischemic burden; (iii) inadequate spatial resolution for reliable detection of subendocardial perfusion deficits; and (iv) errors in AIF estimation for flow quantification due to saturation of blood signal intensity at pea enhancement. In the proposed project, we will develop novel techniques to address these limitations (Aim 1). The techniques will be rigorously validated in animals using microsphere measurements as the reference (Aim 2). Finally, the techniques will be tested in CAD and CMD patients using PET and invasive coronary reactivity testing as reference, respectively (Aim 3). The end point of the project is the development and rigorous validation of a new myocardial perfusion quantification CMR method with whole-heart coverage, high isotropic resolution, cardiac phase-resolved acquisition, accurate arterial input estimation while without the requirements of ECG triggering or breath-hold. It is expected that such a technique will significantly improve image quality, reduce technical failures, increase the diagnostic accuracy, and facilitate the eventual adoption of myocardial perfusion CMR as the method of choice for detecting myocardial ischemia. .

Public Health Relevance

Coronary artery disease is the single most common cause of death worldwide. We propose to develop a non-invasive magnetic resonance imaging method for the early diagnosis of coronary artery disease, which will permit early treatment of the disease and avoid heart attack of patients.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Danthi, Narasimhan
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Cedars-Sinai Medical Center
Los Angeles
United States
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Sharif, Behzad; Motwani, Manish; Arsanjani, Reza et al. (2018) Impact of incomplete ventricular coverage on diagnostic performance of myocardial perfusion imaging. Int J Cardiovasc Imaging 34:661-669
Christodoulou, Anthony G; Shaw, Jaime L; Nguyen, Christopher et al. (2018) Magnetic resonance multitasking for motion-resolved quantitative cardiovascular imaging. Nat Biomed Eng 2:215-226
Ma, Sen; Nguyen, Christopher T; Christodoulou, Anthony G et al. (2018) Accelerated Cardiac Diffusion Tensor Imaging Using Joint Low-Rank and Sparsity Constraints. IEEE Trans Biomed Eng 65:2219-2230
Shaw, Jaime L; Yang, Qi; Zhou, Zhengwei et al. (2018) Free-breathing, non-ECG, continuous myocardial T1 mapping with cardiovascular magnetic resonance Multitasking. Magn Reson Med :
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
Salerno, Michael; Sharif, Behzad; Arheden, HÃ¥kan et al. (2017) Recent Advances in Cardiovascular Magnetic Resonance: Techniques and Applications. Circ Cardiovasc Imaging 10:
Nguyen, Christopher T; Buckberg, Gerald; Li, Debiao (2016) Magnetic Resonance Diffusion Tensor Imaging Provides New Insights Into the Microstructural Alterations in Dilated Cardiomyopathy. Circ Cardiovasc Imaging 9:
Nguyen, Christopher; Fan, Zhaoyang; Xie, Yibin et al. (2016) In vivo diffusion-tensor MRI of the human heart on a 3 tesla clinical scanner: An optimized second order (M2) motion compensated diffusion-preparation approach. Magn Reson Med 76:1354-1363
Chen, David; Sharif, Behzad; Bi, Xiaoming et al. (2016) Quantification of myocardial blood flow using non-electrocardiogram-triggered MRI with three-slice coverage. Magn Reson Med 75:2112-20
Bakir, May; Wei, Janet; Nelson, Michael D et al. (2016) Cardiac magnetic resonance imaging for myocardial perfusion and diastolic function-reference control values for women. Cardiovasc Diagn Ther 6:78-86

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