Imaging of post-infarction myocardial inflammation with hybrid FDG PET/MR: feasibilty and preliminary findings in a canine model
Journal of Cardiovascular Magnetic Resonance volume 17, Article number: Q19 (2015)
An understanding of inflammation following myocardial infarction may be of importance in the development of novel therapeutics to limit the development of heart failure following myocardial injury. However, the quantification of inflammation in this setting continues to be challenging. Hybrid FDG PET/MR may offer a non-invasive in vivo solution through intrinsic registration of these complementary modalities. This study sought to validate its use in a canine model of myocardial infarction (MI).
Twenty dogs underwent a left thorocotomy with permanent or transient 3 hour ligation of the left anterior descending to induce MI. Hybrid PET/MR was performed on day 7 in all animals and out to day 21 in a subset of animals following suppression of basal myocardial glucose metabolism with a lipid infusion. Blinded analysis of fused imaging quantified FDG activity within and beyond MR-defined infarct zones. A detailed serial imaging evaluation and histologic comparison was also performed. Nine of these animals, sacrificed at various time points from day 7 through 21, also were the subject of ex vivo tissue analysis to establish correlations between concentrations of FDG, Indium-111, which had been used to label white blood cells injected 24 hours prior to sacrifice, and Tc99mTc-DTPA, used to mirror the distribution of Gd-DTPA.
All animals survived and completed imaging. Infarction was achieved in 18/20 subjects. Fused PET/MR yielded an imaging correlation of elevated FDG tracer activity within regions of myocardial infarction but reduced activity in regions of microvascular obstruction. A modest elevation was also seen in remote non-infarcted tissue. Animals studied out to day 21 showed signficant associations between tracer activity and adverse remodeling based on MR-derived left ventricular volumes. Histopathology correlated tracer activity to inflammatory celular infiltrate. In the 9 animals subject to ex vivo tissue analysis, there was a good correlation between FDG vs. Indium concentrations across the range of Tc-DTPA values, except in regions of microvascular obstruction and low Tc-DTPA, where Indium levels were much higher than those of FDG.
Hybrid PET/MR visualizes inflammatory activity early following MI and provides intrinsic registration to MR tissue imaging, which defines regions of infarct and microvascular obstruction. Reduced FDG activity within regions of microvascular obstruction may be secondary to limited delivery of tracer to these regions following bolus injection of the tracer. Our preliminary findings suggest a potential for evaluating infarct related inflammation and to provide associations to downstream adverse remodeling. Future studies using this novel imaging platform are justifed to explore such relationships and to determine if a constant infusion of both MR and FDG tracers may allow more precise quantification of the degree of inflammation within regions of microvascular obstruction.
Ontario Research Fund: Imaging in Cardiovascular Therapeutics Grant
Canadian Institutes of Health Research grant; IMAGE-HF
Program of Experimental Medicine (POEM), Department of Medicine, University of Western Ontario
Canadian Foundation for Innovation and the Ministry of Research and Innovation of the Province of Ontario: Infrastructure grant.
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Wisenberg, G., Mikami, Y., White, J.A. et al. Imaging of post-infarction myocardial inflammation with hybrid FDG PET/MR: feasibilty and preliminary findings in a canine model. J Cardiovasc Magn Reson 17 (Suppl 1), Q19 (2015). https://doi.org/10.1186/1532-429X-17-S1-Q19