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FUNCTIONAL CHARACTERIZATION OF CARDIAC PHENOTYPES BY MRI: APPLICATIONS IN DISEASED MOUSE MODELS

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2015, Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering.
Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide. Early diagnosis of CVD needs robust and accurate measurement of cardiac alterations at both functional and cellular levels. At the cellular level, calcium (Ca2+) influx through the voltage-gated L-type Ca2+ channel (LTCC) is central in cardiac excitation-contraction coupling and is altered in various cardiovascular diseases. The emergence of manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) provides the possibility for in vivo assessment of Ca2+ uptake. In the current project, we first developed a rapid, multi-slice cardiac T1 mapping method to capture the dynamics of Mn2+-induced R1 changes in mouse myocardium. The sensitivity of MEMRI using T1 mapping in detecting subtle changes in altered Ca2+ channel activity was evaluated in a mouse model with dystrophin-glycoprotein complex disruption. In addition, a mathematical compartment model was developed for quantitative assessment of the LTCC activity by least-squares fitting of the model to experimental MEMRI data. At the functional level, the analysis of regional myocardial wall motion has emerged as more sensitive measures of early-stage functional alterations compared with global functional parameters. Displacement-encoding with stimulated echoes (DENSE) MRI provides an accurate tool for noninvasive measurement of regional myocardial function. In this project, DENSE MRI was used to investigate the impact of disruption of cystic fibrosis transmembrane conductance regulator (CFTR), which causes cystic fibrosis (CF), on cardiac function. Cardiomyocyte contractility and Ca2+ transients were also measured in vitro. Our results show that the disruption of CFTR caused a wide range of changes in heart, including left-ventricular structure, global function, regional mechanics, and stress response. In conclusion, our studies demonstrated the capability of MEMRI and DENSE MRI in detecting cardiac diseases at early stage.
Xin Yu (Advisor)
Chris Flask (Committee Member)
Craig Hodges (Committee Member)
Rebecca Darrah (Committee Member)
Nicole Seiberlich (Committee Member)
113 p.

Recommended Citations

Citations

  • Jiang, K. (2015). FUNCTIONAL CHARACTERIZATION OF CARDIAC PHENOTYPES BY MRI: APPLICATIONS IN DISEASED MOUSE MODELS [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1421754199

    APA Style (7th edition)

  • Jiang, Kai. FUNCTIONAL CHARACTERIZATION OF CARDIAC PHENOTYPES BY MRI: APPLICATIONS IN DISEASED MOUSE MODELS . 2015. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1421754199.

    MLA Style (8th edition)

  • Jiang, Kai. "FUNCTIONAL CHARACTERIZATION OF CARDIAC PHENOTYPES BY MRI: APPLICATIONS IN DISEASED MOUSE MODELS ." Doctoral dissertation, Case Western Reserve University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1421754199

    Chicago Manual of Style (17th edition)