The long-term objective is to develop an innovative and clinically robust cardiac diffusion MRI sequence that is sensitive to changes to myocardial tissue microstructure. The ability to characterize myocardial tissue microstructure will allow for unique insight to the pathophysiological progression of cardiovascular diseases (CVD) such as acute coronary syndrome, myocarditis, and cardiomyopathy, which are among the leading causes of morbidity and mortality of the US. Conventional cardiac MRI (CMR) techniques have shown to be clinically valuable in revealing morphological changes in the myocardium while providing excellent soft tissue contrast. However, validated CMR techniques used for myocardial tissue characterization require the use contrast agents. For patients with compromised renal systems such as those with Chronic Kidney Disease (CKD), these patients cannot benefit from these contrast-based techniques. Furthermore, 25% of CKD patients have a severe form of CVD that results in left ventricular hypertrophy (LVH) and can directly benefit from characterization of myocardial tissue fibrosis. Therefore, there is a need for a novel MR technique capable of non- contrast quantification of myocardial fibrosis, which we believe can be achieved with cardiac diffusion MRI. In this proposed project, a clinically translatable cardiac diffusion MR technique capable of myocardial fibrosis characterization of the human myocardium will be applied in hypertrophic cardiomyopathy patients (HCM) who are known to have high degree of fibrosis validated with contrast-enhanced CMR.
Specific Aim 1 addresses the technical challenges of the clinical translation of a newly established cardiac diffusion MR technique developed by our lab, which requires better spatial coverage, spatial resolution, and shorter scan times.
Specific Aim 2 will apply the proposed technique developed in Specific Aim 1 to HCM patients to characterize the extent of myocardial fibrosis and compare it with validated contrast-enhanced CMR methods. Hypothesis: Clinical translation of cardiac diffusion MRI requires major technical innovation, and a key application to demonstrate the technique's clinical utility for CKD+LVH patients would be to characterize myocardial fibrosis in HCM patients without the use of contrast agents.

Public Health Relevance

Chronic kidney disease (CKD) affects 1 in 4 Americans over the age of 60 and 25% of these patients have left ventricular hypertrophy (LVH), which increases the risk of death by 5 times compared to those with CKD alone. Myocardial fibrosis quantification via contrast-enhanced cardiac MRI has shown to have great prognostic value in hypertrophic cardiomyopathy patients who also have LVH. Unfortunately, CKD+LVH patients are ineligible for such scans and therefore, developing a clinically translatable in vivo cardiac diffusion MRI technique capable of characterizing the extent of myocardial fibrosis without the use contrast agents may drastically improve the clinical point of care for CKD+LVH patients similar to HCM patients.

Agency
National Institute of Health (NIH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31EB018152-01A1
Application #
8784942
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Erim, Zeynep
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
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Nguyen, Christopher; Lu, Minjie; Fan, Zhaoyang et al. (2015) Contrast-free detection of myocardial fibrosis in hypertrophic cardiomyopathy patients with diffusion-weighted cardiovascular magnetic resonance. J Cardiovasc Magn Reson 17:107
Nguyen, Christopher; Fan, Zhaoyang; Xie, Yibin et al. (2014) In vivo contrast free chronic myocardial infarction characterization using diffusion-weighted cardiovascular magnetic resonance. J Cardiovasc Magn Reson 16:68