PET/CT Imaging in Mouse Models of Myocardial Ischemia

Different species have been used to reproduce myocardial infarction models but in the last years mice became the animals of choice for the analysis of several diseases, due to their short life cycle and the possibility of genetic manipulation. Many techniques are currently used for cardiovascular imaging in mice, including X-ray computed tomography (CT), high-resolution ultrasound, magnetic resonance imaging, and nuclear medicine procedures. Cardiac positron emission tomography (PET) allows 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. Currently hybrid PET/CT scanners for small laboratory animals are available, where CT adds high-resolution anatomical information. This paper reviews mouse models of myocardial infarction and discusses the applications of dedicated PET/CT systems technology, including animal preparation, anesthesia, radiotracers, and images postprocessing

Imaging techniques for assessment of coronary flow reserve

The assessment of coronary flow reserve (CFR) may be useful for the functional evaluation of coronary artery disease (CAD). Invasive techniques, such as intracoronary Doppler ultrasound and pressure-derived method, directly assess CFR velocity and fractional flow reserve. Positron emission tomography (PET) has emerged as an accurate noninvasive technique to quantify CFR. Nevertheless, this approach has not been applied to routine studies because of its high cost and complexity. Recently, attempts to estimate CFR with single-photon emission computed tomography (SPECT) tracers have been made in order to obtain, with noninvasive methods, data for quantitative functional assessment of CAD. This review analyzes the relative merit and limitations of CFR measurements by cardiac imaging techniques and describes the potential clinical applications

Total occlusion of the abdominal aorta in a patient with renal failure and refractory hypertension: a case report.

Total occlusion of the abdominal aorta is unusual, and potentially catastrophic. It occurs in patients with advanced atherosclerotic occlusive disease, and can cause severe ischemic manifestations, depending on the site of obstruction. Prompt and appropriate diagnostic and therapeutic approaches are important whenever this condition is suspected, in order to avoid a fatal outcome. The development of a complex network of collaterals may prevent the manifestation of acute ischemic phenomena, and cause a delay in diagnosis and treatment. Here we report the clinical case of a 59-year-old man who was referred to our Department for evaluation of renal failure and refractory hypertension. Ultrasonography and 99mTc-DTPA scintigraphy showed a shrunken, non-functioning left kidney, while CT angiography and aortography showed the complete occlusion of the aorta from below the right renal artery down to the bifurcation of both common iliac arteries, with a critical stenosis of the origin of the right renal artery, an occlusion of the left renal artery as well as of the origin of the inferior mesenteric artery. The patient was referred to the surgery department for aorto-bifemoral bypass surgery and re-implantation of the right renal artery

Total occlusion of the abdominal aorta in a patient with renal failure and refractory hypertension: a case report

Total occlusion of the abdominal aorta is unusual, and potentially catastrophic. It occurs in patients with advanced atherosclerotic occlusive disease, and can cause severe ischemic manifestations, depending on the site of obstruction. Prompt and appropriate diagnostic and therapeutic approaches are important whenever this condition is suspected, in order to avoid a fatal outcome. The development of a complex network of collaterals may prevent the manifestation of acute ischemic phenomena, and cause a delay in diagnosis and treatment. Here we report the clinical case of a 59-year-old man who was referred to our Department for evaluation of renal failure and refractory hypertension. Ultrasonography and 99mTc-DTPA scintigraphy showed a shrunken, non-functioning left kidney, while CT angiography and aortography showed the complete occlusion of the aorta from below the right renal artery down to the bifurcation of both common iliac arteries, with a critical stenosis of the origin of the right renal artery, an occlusion of the left renal artery as well as of the origin of the inferior mesenteric artery. The patient was referred to the surgery department for aorto-bifemoral bypass surgery and re-implantation of the right renal artery

Genetic deletion in Uncoupling Protein 3 augments 18F-Fluorodeoxyglucose cardiac uptake in the ischemic heart

Background — Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier super-family of proteins expressed in the mitochondrial inner membrane that uncouple oxygen consumption by the respiratory chain from ATP synthesis. UCP3 plays a role in fatty acid metabolism and energy homeostasis and is required to maintain high rates of glucose aerobic metabolism, while deficiency in UCP3 might results in a metabolic shift that promotes anaerobic glycolytic metabolism. In this study, we investigated the effects of UCP3 genetic deletion on 18F-fluorodeoxyglucose (FDG) cardiac uptake by a high-resolution positron emission tomography (PET)/computed tomography (CT) dedicated animal system after permanent coronary artery ligation. Methods and Results — To test the effects of UCP3 genetic deletion in vivo, cardiac 18F-FDG PET/CT was performed in UCP3 knockout (UCP3-/-) and wild-type (WT) mice one week after induction of myocardial infarction or sham procedure. In sham-operated mice no difference in left ventricular (LV) volume was detectable between WT and UCP3-/-. After myocardial infarction, LV volume was higher in both WT and UCP3-/- compared to sham animals, with a significant interaction (P < 0.05) between genotype and myocardial infarction. In sham-operated animals no difference in FDG standardized uptake value (SUV) was detectable between WT (1.8 ± 0.6) and UCP3-/- (1.8 ± 0.6). After myocardial infarction, SUV was higher in both WT (2.2 ± 0.6) and UCP3-/- (4.0 ± 0.9) compared to sham animals, with a significant interaction (P < 0.005) between genotype and myocardial infarction. A significant relationship (r = 0.68, P < 0.001) between LV volume and SUV was found. Conclusions — In a mice model of permanent coronary occlusion, UCP3 is required to maintain high rates of glucose aerobic metabolism and its deficiency results in a metabolic shift that favored anaerobic glycolytic metabolism and increased FDG uptake

Assessing myocardial viability in patients with ischemic left ventricular dysfunction

Left ventricular (LV) function is one of the most powerful predictors of prognosis in the setting of heart failure (HF) or following myocardial infarction. It is important to differentiate patients in whom LV dysfunction is caused by necrosis and scar tissue formation from those with LV dysfunction because of ischemia or hibernating, but viable myocardium. Previous studies showed that identification of the latter group of patients predicts substantial survival benefit, symptomatic improvement, and improved LV function with revascularization. On the other hand, more recent investigations, such as the Surgical Treatment for Ischemic Heart Failure (STICH) trial [3], did not find a significant interaction between myocardial-viability status and medical versus surgical treatment with respect to the rates of death from any cause or from cardiovascular causes or the rate of death or hospitalization for cardiovascular causes

Prognostic Value of Stress Myocardial Perfusion Imaging in Asymptomatic Diabetic Patients

Although there has been a marked decline in mortality due to coronary artery disease (CAD) in the overall population in the past three decades, reducing CAD mortality in patients with diabetes has proven exceptionally difficult. Several epidemiological studies have shown that diabetes is associated with a marked increase in the risk of CAD. The symptoms are not a reliable means of identifying patients at higher risk considering that angina is threefold less common in diabetics than in nondiabetics. The increasing prevalence of diabetes and the associated high cardiac risk raised the question as to the need to develop approaches to identify the diabetic patients at the highest risk of CAD. Stress myocardial perfusion single-photon emission computed tomography has taken a central role in the diagnosis, evaluation, and management of CAD in diabetic patients. This review focuses on the prognostic value of cardiac radionuclide imaging in asymptomatic diabetic patients. {\textcopyright} 2014 Springer Science+Business Media New York

Stress cardiac single-photon emission computed tomographic imaging late after coronary artery bypass surgery for risk stratification and estimation of time to cardiac events

OBJECTIVE: We assessed predictors and temporal characteristics of cardiac risk in patients undergoing stress single-photon emission computed tomography after coronary artery bypass grafting. METHODS: Stress cardiac tomography was performed in 362 patients 5 years after coronary artery bypass grafting. Cardiac death and myocardial infarction were considered as events. Cox proportional hazards analysis was used to identify predictors of events and parametric survival analysis to predict time to events. RESULTS: During a median follow-up of 27 months, 22 cardiac events occurred (6.1% cumulative event rate). At multivariable Cox analysis, ischemia at cardiac tomography (hazards ratio 3.7, 95% confidence interval 1.5-9.1; P = .004), and diabetes (hazards ratio 3.6, 95% confidence interval 1.5-8.5; P = .006) resulted in independent predictors of events. Event-free survival was 96% in patients with normal cardiac tomography, 86% in those with abnormal tomography without ischemia, and 70% in those with (log-rank 10.6, P for trend = .008). The parametric survival model revealed that the cardiac risk was greater for all time intervals and accelerated more over time in patients with ischemia than in those without (chi(2) 21.4, P < .0001). Patients without diabetes and normal cardiac tomography remained below a defined risk level (5%) for the entire follow-up period. CONCLUSION: Stress cardiac tomography performed 5 years after coronary artery bypass grafting is useful to characterize the risk of cardiac events and its temporal variation. Parametric survival model estimates the predicted time to risk and the level of risk at specific time intervals after coronary artery bypass grafting