High-field Cardiac Magnetic Resonance Imaging in Small Animal Models of Cardiovascular Disease

Myocardial infarction (MI), pulmonary hypertension (PH), and cardiomyopathy belong to a class of diseases collectively described as cardiovascular disease, the leading cause of death worldwide. Assessment of the left and right ventricular (LV, RV) structural and functional changes concomitant with the aforementioned pathologies is vital, particularly when evaluating the efficacy of a potential cardiac therapy. High-field in vivo cardiac magnetic resonance imaging (CMRI) provides high-resolution anatomical images without use of ionizing radiation and is thus uniquely suited to accurately assess the LV and RV. This dissertation reports the use of CMRI at 9.4T in precisely monitoring the LV and RV structural and functional adaptations in murine models of heart disease, specifically, MI, PH, and diabetic cardiomyopathy.As the first application, CMRI was utilized to quantify LV structure and function in an ischemia-reperfusion (IR) model of rat MI following treatment with mesenchymal stem cells (MSC) and hyperbaric oxygen (Ox). MRI results were compared to data acquired using histology and echocardiography. Although echocardiography was able to establish significant improvements in cardiac structure and function following MSC, Ox, and MSC+Ox therapies, CMRI revealed little improvement in LV structure or function, relative to MI animals.CMRI was also used to assess the LV in rat model of MI following human induced pluripotent stem (hiPS) cell-derived cardiomyocyte therapy, in direct comparison to human MSC (hMSC) therapy. MI was induced by permanent ligation of the left anterior descending (LAD) coronary artery. CMRI structural and functional data were compared to echocardiographic findings. While CMRI revealed significant improvements, relative to MI, in LV structure and function for the hiPS group, but not the hMSC group, echocardiography revealed little difference between the cell-treated groups.The effects of hypoxia-induced pulmonary hypertension (PH) on LV and RV structure and function were also examined using CMRI. No differences between the LV structure and function of control rats and rats exposed to three weeks of hypoxia were observed utilizing CMRI. However, CMRI revealed significant increases in RV volume and mass, as well as a significant decrease in RV function, for PH animals, when compared to control animals.The effects of left heart failure (LHF)-induced PH on LV structure and function were also quantified using CMRI. CMRI functional results were compared with data acquired using echocardiography. A significant increase, relative to control, in the LV volume and mass of PH animals was determined using CMRI four weeks following MI. Likewise, CMRI and echocardiography indicated significant decreases in LV function for PH rats, relative to control rats.CMRI was further utilized to assess LV structural and functional changes in a murine model of diabetic cardiomyopathy following an eight-week exercise program. With the exception of average LV mass, CMRI quantified no significant differences in LV structure or function following exercise therapy. Thus, high-field cardiac MR imaging was capable of accurately assessing left and right ventricular structure and function in small animal models of heart disease. Additonally, CMRI was utilized to evaluate the potential efficacy of cell- and exercise-based therapies, as applied to several small animal models of cardiovascular disease.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Biophysics

Grantor dc:publisher

The Ohio State University

Year dc:date

2013

Author dc:creator

• Citro, Lucas Abraham

Contributors dc:contributor

• Kuppusamy, Periannan

• Biophysics
• Cardiac Magnetic Resonance Imaging
• Small Animal
• Cardiovascular Disease
• Stem Cells
• Pulmonary Hypertension
• Myocardial Infarction
• Diabetic Cardiomyopathy

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=osu1365082830

OAI identifier oai:identifier

oai:etd.ohiolink.edu:osu1365082830