Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Dr. Maria Drangova

Abstract

Mouse models are an important tool in cardiovascular disease research and a non-invasive imaging method is an advantageous way of monitoring disease progression. Cardiac micro-CT is rapid imaging technique capable of quantifying changes in cardiac structure and function in mice. The goal of this thesis was to demonstrate the utility of this technique in monitoring disease progression in a longitudinal study, as well as its capability for evaluating other methods of measuring cardiac function in mice.

In a longitudinal study, a mouse model of myocardial infarction was scanned weekly for four weeks; left ventricular volume and ejection fraction were measured from the images. Cardiac micro-CT was capable of tracking small changes in cardiac structure and function, with the MI mice demonstrating a significant increase in volume and a significant decrease in ejection fraction. Both inter- and intra-variability was low, indicating the results were highly reproducible.

Contrast agents are essential to evaluating the heart in micro-CT images. A new blood-pool agent was evaluated to determine its suitability for use in cardiac micro-CT studies. The agent produced excellent enhancement for the first 30 minutes post-injection, and had a unique characteristic of enhancing the myocardium, which may prove useful in studies evaluating wall motion.

The effect of x-ray dose delivered during a longitudinal micro-CT study was also evaluated. C57BL/6 mice were scanned weekly for six weeks; the total entrance dose delivered over the study was 5.04 Gy. No significant changes to the heart or lungs were detectable on the micro-CT images at six weeks, and the histology performed on myocardial and pulmonary tissue showed no indication of early inflammation at a cellular level. Micro-CT can therefore be used in longitudinal studies without concern of adverse effects.

Cardiac micro-CT was used to evaluate conductance catheters, and found that the catheter volumes were drastically underestimated compared to the micro-CT volumes. It was also determined that catheterization has the potential for causing cardiac enlargement; 40% of the mice demonstrated enlarged hearts following the catheterization procedure. Overall, cardiac-gated micro-CT is a rapid and reproducible imaging technique, and is proving to be valuable tool in cardiovascular disease research.

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