Measuring inflammation in the entire myocardium in a canine model of myocardial infarction with hybrid PET/MRI
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.