Contact person: Sara Gargiulo,
Actors: Sara Gargiulo,
Cardiovascular diseases are common causes of morbidity and mortality in developed countries, and coronary heart disease is a relevant cause of congestive heart failure, which is frequently secondary to myocardial infarction (MI). Different species have been used to reproduce MI models, but in recent years mice have become the animals of choice, because of their short life cycle and the possibility of genetic manipulation. The small dimensions of the mouse heart represent a challenge for image acquisition and analysis that requires expensive equipment capable of obtaining high-resolution images and established expertise. Promising results have been achieved with positron emission tomography (PET), that allows imaging of myocardial metabolism and perfusion with a picomolar sensitivity. PET is an important non- invasive imaging technique for characterization of the ischaemic area and for measurement of changes in functional parameters. In particular, 18F-Fluorodeoxyglucose (FDG) traces myocyte glucose uptake and phosphorylation and can be used to quantify regional myocardial glucose metabolism. Although the quantification of infarct size has been well established in humans with PET, this approach is more challenging in small animals owing to their smaller size. We demonstrated that visualization and measurement of infarct size in mice with 18F-FDG PET is feasible, highly accurate and repeatable with the help of automated software owners or dedicated programs. We assessed the reproducibility and accuracy of 18F-FDG for non-invasive quantification of MI size in wild type and transgenic mice by a volumetric polar map calculation that express the extent of the infarct as a percentage value. In addition, three-dimensional images can be reconstructed from PET data sets. Moreover, we showed that UCP3 gene deletion has an adverse effect on remodeling of myocardium, and induces a metabolic shift that favored glycolytic metabolism. We demonstrated that after permanent coronary artery ligation in mice, UCP3 genetic deletion is associated with larger infarct size and remodeling and higher cardiac 18F-FDG uptake in remote areas as compared to wild type mice, confirming the cardioprotective role of the UCP3 protein. We concluded that murine models of MI are useful to highlight the mechanisms underlying coronary heart disease and to test new therapeutic approaches, such as gene or stem cell therapy. Moreover, with technological advances, dedicated small laboratory PET/CT imaging provides in vivo a non-invasive, serial and quantitative assessment of myocardial perfusion and metabolism at a molecular level.
[18F] FDG PET/CT in a mouse with myocardial infarction. It is evident an area of absent uptake in the anteroapical region of left ventricle.
[18F] FDG PET. Left ventricular polar map obtained in a normal mouse (top) and in a mouse with myocardial infarction (lower).
Papers
S. Gargiulo*, MP. Petretta*, A. Greco, MR. Panico, M. Larobina, M. Gramanzini, GG. Schiattarella, G. Esposito, M. Petretta, A. Brunetti, A. Cuocolo, “Genetic deletion in uncoupling protein 3 augments 18F-fluorodeoxyglucose cardiac uptake in the ischemic heart”, BMC Cardiovascular Disorders 2014 Aug 8; 14:98. * equal contribution
A. Greco, G. Fiumara, S. Gargiulo, M. Gramanzini, A. Brunetti, A. Cuocolo, “High-resolution positron emission tomography/computed tomography imaging of the mouse heart”, Experimental Physiology 2013 Mar; 98.3; pp 645-651
S. Gargiulo, A. Greco, M. Gramanzini, MP. Petretta, A. Ferro, M. Larobina, MR. Panico, A. Brunetti, A. Cuocolo, “PET/CT Imaging in Mouse Models of Myocardial Ischemia”, Journal of Biomedicine and Biotechnology 2012; doi:10.1155/2012/541872
Greco A, Petretta MP, Larobina M, Gargiulo S, Panico M, Nekolla SG, Esposito G, Petretta M, Brunetti A, Cuocolo A. Reproducibility and accuracy of non-invasive measurement of infarct size in mice with high-resolution PET/CT. J Nucl Cardiol. 2012;19:492-9.
Abstract
Gargiulo S, MP. Petretta, M. Gramanzini, A.Greco, G. Schiattarella, G. Esposito, A. Brunetti, A. Cuocolo, “FDG-uptake by PET/CT in an Uncoupling Protein 3 Transgenic Murine Model of Myocardial Infarction”, EANM '13 - Annual Congress of the European Association of Nuclear Medicine, October 19-23, 2013 Lyon, France. (European Journal of Nuclear Medicine and Molecular Imaging Volume 40, Supplement 2 DOI 10.1007/s00259-013-2535-3).
S. Gargiulo, MP. Petretta, M. Gramanzini, A. Greco, A. Cuocolo, A. Brunetti , M. Salvatore, “18F-FDG PET/CT in a transgenic murine model of myocardial infarction”, 10Th International Congress on Coronary Artery Disease. October 13-16, 2013, Florence, Italy.
A.Greco, A.Ferro, S.Gargiulo, M.Larobina, M.P.Petretta, G.Esposito, M.R.Panico, S.G.Nekolla, A. Brunetti, A.Cuocolo. Reproducibility of quantitative measurement of infarct size in mice with high resolution PET/CT imaging. AINM (10th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging), March 18-21, 2011, Rimini (Italy).
A. Greco, M.P.Petretta, M.Larobina, S.Gargiulo, A.Ferro, M.R.Panico, S.G.Nekolla, G.Esposito, M.P. Petretta, A.Brunetti, and A. Cuocolo. Accuracy and Reproducibility of Noninvasive Measurement of Infarct Size in Mice with High-Resolution PET/CT. European Molecular Imaging Meeting of the ESMI 19-21 June 2011, Leiden, The Netherlands.
A. Ferro, A. Greco, S. Gargiulo, M. Larobina, M. P. Petretta, G. Esposito, R. Panico, A. Brunetti, A. Cuocolo. Reproducibility of Quantitative Measurement of Infarct Size in Mice With High-Resolution PET/CT Imaging. EANM '10 - Annual Congress of the European Association of Nuclear Medicine, October 9-13, 2010 Vienna, Austria.
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