Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Collaborative Specialization

Molecular Imaging

Supervisor

Prato, Frank S.

Affiliation

Lawson Health Research Institute and Western University

2nd Supervisor

Thiessen, Jonathan D.

Affiliation

Lawson Health Research Institute and Western University

Co-Supervisor

Abstract

Background: After myocardial infarction (MI), fibrosis and an ongoing dysregulated inflammatory response are associated with adverse cardiac remodeling. Fluorodeoxyglucose (FDG) positron emission tomography (PET) is sensitive to inflammation provided suppression protocols are implemented to restrict the uptake of glucose in myocytes. Magnetic resonance imaging can be used to determine extracellular volume, a surrogate measure of fibrosis. In some cases, patients present with markedly reduced flow in the setting of a large infarct, i.e. microvascular obstruction, restricting the delivery of FDG and contrast agents. To overcome this problem, a constant infusion was explored as an alternative to the clinical standard bolus injection. This led to three objectives: a) comparison of the constant infusion to the bolus injection in healthy canines, b) investigation of the potential of the constant infusion to discriminate post-MI tissue types, and c) determination of the efficacy of the suppression protocol and its effect on extracellular volume.

Methods: All imaging was done with a hybrid PET/MRI scanner. MRI images were used to determine the regions of interest: remote, injured and obstructed myocardium. PET images were used to determine inflammation. To compare the injection strategies, five healthy canines were examined with all three. Subsequently, eight animals were imaged at baseline and days 3, 7, 14, 21, and 42 post-MI using a 60-min infusion. Lastly, seven animals were imaged at baseline and day 5 post-MI using a 150-min infusion. Forty minutes into the infusion, suppression of glucose uptake in myocytes was started.

Results: No significant differences in terms of glucose metabolism and extracellular volume were seen in healthy myocardium between the three injection strategies: bolus injection, constant infusion and bolus followed by constant infusion, showing that a strategy involving the constant infusion produced similar results as to those obtained with a bolus injection. Following MI, a significant increase in extracellular volume was seen in remote tissue on days 14 and 21, suggesting an inflammatory response. During the 150-min infusion, suppression of myocardial glucose uptake had the unexpected result of reducing FDG uptake in inflammatory cells within the infarcted area.

Conclusion: This research showed the possibility of using a constant infusion of Gd-DTPA and FDG to investigate inflammation within the entire myocardium. The finding that suppression affected inflammatory cells highlights the need for tracers which do not rely on myocardial glucose suppression.

Summary for Lay Audience

After a myocardial infarction, commonly referred to as heart attack, scar tissue and inflammation develop within the injured area. The scar tissue can be imaged with MRI and the inflammation with PET, provided injected contrast agents can reach the heart tissue. Some patients present with an area of extremely low flow within the injured region, unreachable with a clinically used bolus injection. A goal of my research is to test whether a constant infusion can be used to get the PET tracer and contrast agent into the injured region which is critical for imaging patient after a heart attack: if the PET tracer does not enter, there is no way to measure inflammation. The first experiment compared bolus injection and constant infusion in the normal healthy heart to establish if the results from these injection strategies are the same. The second experiment applied this approach in a model of myocardial infarction to determine if a constant infusion can measure inflammation and scarring in the remote, injured and obstructed regions of the heart. Lastly, since the PET imaging technique requires an infusion of fats to block the uptake of the PET tracer in normal heart tissue, the efficacy of this approach was tested.

Methods: All imaging was done with a hybrid PET/MRI scanner. MRI images were used to determine the regions of interest: remote, injured and obstructed myocardium. PET images were used to determine inflammation. To visualize inflammation lipids were infused.

Results: No differences were seen between constant infusion and bolus injection in healthy tissue. Findings from the second experiment suggested damage due to inflammation in remote tissue at days 14 and 21 after the heart attack. The last experiment showed that the suppression approach affected the injured region, suggesting that suppression measurement of inflammation in infarcted tissue may be underestimated

Conclusion: This research demonstrated the ability to use hybrid PET/MRI with a dual contrast agent protocol to image inflammation in the myocardium. It also showed that remote tissue may be damaged from a myocardial infarction and that the current approach of suppression, necessary for inflammation imaging, may affect inflammatory cells, hindering accurate quantification of inflammation.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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