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In vivo MRI of mouse heart at 11.7 t: monitoring of stem-cell therapy for myocardial infarction and evaluation of cardiac hypertrophy

Kulkarni, Aditi C.

Abstract Details

2008, Doctor of Philosophy, Ohio State University, Biophysics.
Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality in the western world. Early detection and diagnosis of CVD by visualization of the heart may help reduce the mortality associated with it. Among the noninvasive techniques use for cardiac imaging, MRI stands out due to its advantages such as high spatial and temporal resolution, repeatability and reproducibility of the measurements, and capability of obtaining functional data from anatomical images.This dissertation reports the development of a cardiac MR imaging method and its application to cardiac disease models at high magnetic field (11.7 T). Optimization of hardware and software parameters was performed to obtain images of the mouse heart, which is characterized by its small size and very fast motion. Methods for data analysis were developed to obtain functional data (ejection fraction, stroke volume, cardiac output etc) from cine-images of the mouse heart. M-mode echocardiography (ECHO) is one of the most widely used methods for functional analysis of the heart. Therefore, CMRI was compared to ECHO for functional analysis of healthy and infarcted mouse heart. Although the absolute values of functional parameters obtained from the ECHO and CMRI were different, they showed similar trends over time. In general, there was agreement in the ejection fraction measurements made obtained from the two methods. After development and validation of the method, CMRI was employed for structural and functional evaluation of mouse heart after myocardial infarction (MI). MI was induced in the mice by permanent ligation of the left coronary artery. CMRI was able to detect the structural changes in the MI heart. It also showed a significant decrease in the function of mouse heart after MI.Another application of CMRI was to assess the cardiac hypertrophy in a transgenic mouse model of chronic hypertension. The hypothesis was that chronic hypertension, created by the transgenic model, leads to cardiac hypertrophy. Previous studies using ECHO were not able to substantially support this hypothesis. However, CMRI of these transgenic mice detected the decrease in the cardiac function and increase in the wall of the left ventricle, thus validating the model itself.Cardiomyoplasty, or implantation of stem cells into the infarcted heart muscle, is emerging as a promising approach for cardiac therapy. but very few studies have investigated the fate of transplanted stem cells. In this study, CMRI was used to monitor labeled stem cells that were transplanted in the mouse heart after MI. Mouse mesenchymal stem cells were labeled with superparamagnetic iron oxide particles (SPIO), before transplantation in the mouse heart. An optimized CMRI method was developed and tested in vitro, as well as, ex vivo. CMRI enabled the detection of the cells in vivo and their visualization for up to 4 weeks. In conclusion, in this dissertation the development and validation of cardiac MRI methods for imaging mouse heart at high magnetic field (11.7 T) have been performed successfully. These methods were applied to the evaluation of myocardial infarction and cardiac hypertrophy in mouse and the monitoring of labeled stem cells after their transplantation in the infarcted heart.
Periannan Kuppusamy, PhD (Advisor)
Petra Schmalbrock, PhD (Committee Member)
Hiranmoy Das, PhD (Committee Member)

Recommended Citations

Citations

  • Kulkarni, A. C. (2008). In vivo MRI of mouse heart at 11.7 t: monitoring of stem-cell therapy for myocardial infarction and evaluation of cardiac hypertrophy [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1228100866

    APA Style (7th edition)

  • Kulkarni, Aditi. In vivo MRI of mouse heart at 11.7 t: monitoring of stem-cell therapy for myocardial infarction and evaluation of cardiac hypertrophy. 2008. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1228100866.

    MLA Style (8th edition)

  • Kulkarni, Aditi. "In vivo MRI of mouse heart at 11.7 t: monitoring of stem-cell therapy for myocardial infarction and evaluation of cardiac hypertrophy." Doctoral dissertation, Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1228100866

    Chicago Manual of Style (17th edition)