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Abstract
The novel technique of 1H MRS at a high-field strength (3 Tesla) was demonstrated to be a reproducible method to assess hepatic lipid content.
This technique was then used with another novel MR sequence of T1 mapping (ShMOLLI) at 3T to evaluate liver steatosis and fibrosis in subjects
with early type 2 diabetes. It was found that these subjects with early diabetes already had marked liver steatosis, compared to a matched control
group. There was no evidence of increased T1 values, as a measure of fibrosis. These advanced MR and MRS techniques were then used at 3T
to evaluate the myocardium in subjects with early type 2 diabetes. It was demonstrated that cardiac lipid content was elevated and PCr/ATP was
reduced, but cardiac systolic and diastolic function remained normal in these subjects. There was also no significant difference in myocardial strain
between the group of diabetics and matched controls.
Most of the previous MR studies looking at subjects with diabetes include patients who have had the disease for a longer duration and are often on
multiple medications. The subjects in the MR studies in this thesis had been recently diagnosed with diabetes and had not developed symptoms of
end-organ disease. The work presented here shows that, even in the early stages of diabetes, the metabolic abnormalities occurring in diabetes
had already begun to produce sub-clinical end-organ changes.
Finally, an anti-fibrotic compound called Tranilast was investigated to assess its effect on the myocardial reperfusion-injury and fibrosis pathways
in the isolated rat heart model. At lower dose Tranilast (10uM), it was shown there was marginal improvement in several of the parameters to
assess recovery of cardiac function. There was also a reduction of LDH, a marker of cardiomyocyte injury.