Summary In the last years conventional wild type and genetically altered mice are becoming interesting models for better understanding the pathogenesis and improvement in diagnosis, prevention, and therapy of ischemic heart disease in humans, since they are not expensive, easy to handle and to house, are easily prone to genetic manipulations and show anatomic similarity in developmental and post-natal heart compared with humans. The small size and rapid rate of the mouse heart pose significant challenges for cardiac imaging, requiring high spatial resolution, great sensitivity, expensive equipment and established expertise. Several imaging techniques are currently used for morphological and functional phenotyping of mouse cardiovascular system, including high-resolution ultrasound, X-ray computed tomography (CT), magnetic resonance, and nuclear medicine procedures. Positron emission tomography (PET) is currently used for cardiovascular imaging in mice, allowing to examine noninvasively, on a molecular level and with high sensitivity, regional changes in myocardial perfusion, metabolism, apoptosis, inflammation and gene expression or to measure changes in anatomical and functional parameters in heart diseases. Hybrid PET/CT scanners for small laboratory animals are available, where CT adds high-resolution anatomical information. Moreover, dedicated image reconstruction and quantification software are necessary to perform quantitative measures in rodent heart. F-18 fluorodeoxyglucose (FDG) is the most widely used PET tracer and its uptake provides an established method in clinical practice to measure tissue viability in patients with advanced CHD and impaired LV function. In preclinical cardiovascular research, FDG is useful to accurately evaluate myocardial glucose metabolism and infarct size. This study assessed the applications of 18F-FDG PET in a mouse model of myocardial infarction using a high-resolution animal PET/CT system and dedicated images post-processing technology. Materials and Methods Forty inbred C57BL/6J wild-type mice were used for this study. Twenty mice were studied after induction of myocardial infarction (MI group), obtained through ligation of the descendant anterior branch of the left coronary artery and 20 mice under control conditions. Imaging was performed 45 min after intravenous administration of 18F-FDG (7.4 MBq) (Figure 1) using a high-resolution dedicated PET/CT scanner (eXplore Vista, GE Healthcare) with a PET spatial resolution of 1.6 mm FWHM and a CT spatial resolution of 200 micron (Figure 2). PET data were reconstructed using a 2D-OSEM iterative algorithm including random and scatter corrections. Scanner proprietary software and automated program (MunichHeart) was used to images post-processing and quantitative analysis of PET dataset. Results 18F-FDG PET/CT allow a qualitative assessment of LV myocardial infarction (Figure 3). The regional distribution of radiotracer activity in LV myocardium can be expressed in MBq/ml or standard uptake value (SUV) (Figure 4). Polar maps are normalized for maximum activity value and scaled from 0 to maximum activity of 100%, and display all perfusion values below 50% as blackout pixels. The quantitative measurement of infarct size in mice can be expressed in percentage value or in cm2.and showed excellent intraobserver and interobserver interpretative reproducibility (Figure 5). PET can also be used to measure changes in anatomic and functional parameters, such as surface area (mm2) and volume (µl), occurring in post-infarction cardiac remodeling (Figure 6). Conclusions PET/CT studies of myocardial perfusion and viability are successful tools to perform a quantitative evaluation of myocardial metabolism and to measure infarct size in an accurate and repeatable way in rodent cardiovascular research, with the help of high resolution preclinical scanner, automated software and dedicated post-processing programs. Since the same animal can be imaged repeatedly and each animal can be its own control, the number of animals examined is significantly reduced and the variability caused by inter-individual differences is removed, according to the principle of "refinement, reduction, and replacement". Accurate and serial PET quantification may allow future applications in different knockout genetic models and to evaluate the efficacy of interventional, pharmacological, or molecular therapies. References Gargiulo S, Greco A, Gramanzini M, Petretta MP, Ferro A, Larobina M, Panico M, Brunetti A, Cuocolo A.PET/CT imaging in mouse models of myocardial ischemia.J Biomed Biotechnol. 2012;2012:541872. Epub 2012 Mar 13. 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 Jun;19(3):492-9. doi: 10.1007/s12350-012-9538-5. Epub 2012 Mar 7. Greco A, Fiumara G, Gargiulo S, Gramanzini M, Brunetti A, Cuocolo A.High-resolution PET/CT imaging of the mouse heart. Exp Physiol. 2012 Nov 1. [Epub ahead of print]
18F-FDG PET/CT Imaging in Mouse Models of Myocardial Ischemia.
Sara Gargiulo;Matteo Gramanzini;
2012
Abstract
Summary In the last years conventional wild type and genetically altered mice are becoming interesting models for better understanding the pathogenesis and improvement in diagnosis, prevention, and therapy of ischemic heart disease in humans, since they are not expensive, easy to handle and to house, are easily prone to genetic manipulations and show anatomic similarity in developmental and post-natal heart compared with humans. The small size and rapid rate of the mouse heart pose significant challenges for cardiac imaging, requiring high spatial resolution, great sensitivity, expensive equipment and established expertise. Several imaging techniques are currently used for morphological and functional phenotyping of mouse cardiovascular system, including high-resolution ultrasound, X-ray computed tomography (CT), magnetic resonance, and nuclear medicine procedures. Positron emission tomography (PET) is currently used for cardiovascular imaging in mice, allowing to examine noninvasively, on a molecular level and with high sensitivity, regional changes in myocardial perfusion, metabolism, apoptosis, inflammation and gene expression or to measure changes in anatomical and functional parameters in heart diseases. Hybrid PET/CT scanners for small laboratory animals are available, where CT adds high-resolution anatomical information. Moreover, dedicated image reconstruction and quantification software are necessary to perform quantitative measures in rodent heart. F-18 fluorodeoxyglucose (FDG) is the most widely used PET tracer and its uptake provides an established method in clinical practice to measure tissue viability in patients with advanced CHD and impaired LV function. In preclinical cardiovascular research, FDG is useful to accurately evaluate myocardial glucose metabolism and infarct size. This study assessed the applications of 18F-FDG PET in a mouse model of myocardial infarction using a high-resolution animal PET/CT system and dedicated images post-processing technology. Materials and Methods Forty inbred C57BL/6J wild-type mice were used for this study. Twenty mice were studied after induction of myocardial infarction (MI group), obtained through ligation of the descendant anterior branch of the left coronary artery and 20 mice under control conditions. Imaging was performed 45 min after intravenous administration of 18F-FDG (7.4 MBq) (Figure 1) using a high-resolution dedicated PET/CT scanner (eXplore Vista, GE Healthcare) with a PET spatial resolution of 1.6 mm FWHM and a CT spatial resolution of 200 micron (Figure 2). PET data were reconstructed using a 2D-OSEM iterative algorithm including random and scatter corrections. Scanner proprietary software and automated program (MunichHeart) was used to images post-processing and quantitative analysis of PET dataset. Results 18F-FDG PET/CT allow a qualitative assessment of LV myocardial infarction (Figure 3). The regional distribution of radiotracer activity in LV myocardium can be expressed in MBq/ml or standard uptake value (SUV) (Figure 4). Polar maps are normalized for maximum activity value and scaled from 0 to maximum activity of 100%, and display all perfusion values below 50% as blackout pixels. The quantitative measurement of infarct size in mice can be expressed in percentage value or in cm2.and showed excellent intraobserver and interobserver interpretative reproducibility (Figure 5). PET can also be used to measure changes in anatomic and functional parameters, such as surface area (mm2) and volume (µl), occurring in post-infarction cardiac remodeling (Figure 6). Conclusions PET/CT studies of myocardial perfusion and viability are successful tools to perform a quantitative evaluation of myocardial metabolism and to measure infarct size in an accurate and repeatable way in rodent cardiovascular research, with the help of high resolution preclinical scanner, automated software and dedicated post-processing programs. Since the same animal can be imaged repeatedly and each animal can be its own control, the number of animals examined is significantly reduced and the variability caused by inter-individual differences is removed, according to the principle of "refinement, reduction, and replacement". Accurate and serial PET quantification may allow future applications in different knockout genetic models and to evaluate the efficacy of interventional, pharmacological, or molecular therapies. References Gargiulo S, Greco A, Gramanzini M, Petretta MP, Ferro A, Larobina M, Panico M, Brunetti A, Cuocolo A.PET/CT imaging in mouse models of myocardial ischemia.J Biomed Biotechnol. 2012;2012:541872. Epub 2012 Mar 13. 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 Jun;19(3):492-9. doi: 10.1007/s12350-012-9538-5. Epub 2012 Mar 7. Greco A, Fiumara G, Gargiulo S, Gramanzini M, Brunetti A, Cuocolo A.High-resolution PET/CT imaging of the mouse heart. Exp Physiol. 2012 Nov 1. [Epub ahead of print]I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
