Can Nitrogen-13 Ammonia Kinetic Modeling Define Myocardial Viability Independent of Fluorine-18 Fluorodeoxyglucose?

AbstractObjectives. The hypothesis of this study was that evaluation of myocardial flow and metabolism using nitrogen-13 (N-13) ammonia kinetic modeling with dynamic positron emission tomographic (PET) imaging could identify regions of myocardial scar and viable myocardium as defined by fluorine-18 fluorodeoxyglucose (F-18 FDG) PET.Background. Uptake of most perfusion tracers depends on both perfusion and metabolic retention in tissue. This characteristic has limited their ability to differentiate myocardial scar from viable tissue. The kinetic modeling of N-13 ammonia permits quantification of blood flow and separation of the metabolic component of its uptake, which may permit differentiation of scar from viable tissue.Methods. Sixteen patients, >3 months after myocardial infarction, underwent dynamic N-13 ammonia and F-18 FDG PET imaging. Regions of reduced and normal perfusion were defined on static N-13 ammonia images. Patients were classified into two groups (group I [ischemic viable], n = 6; group II [scar], n = 10) on the basis of percent of maximal F-18 FDG uptake in hypoperfused segments. Nitrogen-13 ammonia kinetic modeling was applied to dynamic PET data, and rate constants were determined. Flow was defined by K1; volume of distribution (VD = K1/k2) of N-13 ammonia was used as an indirect indication of metabolic retention.Results. Fluorine-18 FDG uptake was reduced in patients with scar compared with normal patients with ischemic viable zones (ischemic viable 93 ± 27% [mean ± SD]; scar 37 ± 16%, p ≤ 0.01). Using N-13 ammonia kinetic modeling, flow and VD were reduced in the hypoperfused regions of patients with scar (ischemic viable flow: 0.65 ± 0.20 ml/min per g; scar: 0.36 ± 0.16 ml/min per g, p ≤ 0.01; VD: 3.9 ± 1.3 and 2.0 ± 1.07 ml/g, respectively, p ≤ 0.01). For detection of viable myocardium in these patients, the sensitivity and specificity were 100% and 80% for N-13 ammonia PET flow >0.45 ml/min per g; 100% and 70% for VD >2.0 ml/g; and 100% and 90% for both flow > 0.45 ml/min per g and VD > 2.0 ml/g, respectively. The positive and negative predictive values for the latter approach were 86% and 100%, respectively.Conclusions. In this cohort, patients having regions with flow ≤0.45 ml/min per g or VD ≤ 2.0 ml/g had scar. Viable myocardium had both flow >0.45 ml/min per g and VD > 2.0 ml/g. Nitrogen-13 ammonia kinetic modeling permits determination of blood flow and metabolic integrity in patients with previous myocardial infarction and can help differentiate between scar and ischemic but viable myocardium.(J Am Coll Cardiol 1997;29:537–43

Chronic AMPK activity dysregulation produces myocardial insulin resistance in the human Arg302Gln-PRKAG2 glycogen storage disease mouse model

BACKGROUND: The cardiac PRKAG2 mutation in the γ2-subunit of adenosine monophosphate activated kinase (AMPK) is characterized by excessive glycogen deposition, hypertrophy, frequent arrhythmias, and progressive conduction system disease. We investigated whether myocardial glucose uptake (MGU) was augmented following insulin stimulation in a mouse model of the PRKAG2 cardiac syndrome. METHODS: Myocardial and skeletal muscle glucose uptake was assessed with 2-[(18)F]fluoro-2-deoxyglucose positron emission tomography imaging in n = 3 transgenic wildtype (TGwt) vs n = 7 PRKAG2 mutant (TGmut) mice at baseline and 1 week later, 30 min following acute insulin. Systolic function, cardiac glycogen stores, phospho-AMPK α, and insulin-receptor expression levels were analyzed to corroborate to the in vivo findings. RESULTS: TGmut Patlak Ki was reduced 56% at baseline compared to TGwt (0.3 ± 0.2 vs 0.7 ± 0.1, t test p = 0.01). MGU was augmented 71% in TGwt mice following acute insulin from baseline (0.7 ± 0.1 to 1.2 ± 0.2, t test p < 0.05). No change was observed in TGmut mice. As expected for this cardiac specific transgene, skeletal muscle was unaffected at baseline with a 33% to 38% increase (standard uptake values) for both genotypes following insulin stimulation. TGmut mice had a 47% reduction in systolic function with a fourfold increase in cardiac glycogen stores correlated with a 29% reduction in phospho-AMPK α levels. There was no difference in cardiac insulin receptor expression between mouse genotypes. CONCLUSIONS: These results demonstrate a correlation between insulin resistance and AMPK activity and provide the basis for the use of this animal model for assessing metabolic therapy in the treatment of affected PRKAG2 patients

Imaging atherosclerosis with hybrid [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography imaging: What Leonardo da Vinci could not see

Prodigious efforts and landmark discoveries have led toward significant advances in our understanding of atherosclerosis. Despite significant efforts, atherosclerosis continues globally to be a leading cause of mortality and reduced quality of life. With surges in the prevalence of obesity and diabetes, atherosclerosis is expected to have an even more pronounced impact upon the global burden of disease. It is imperative to develop strategies for the early detection of disease. Positron emission tomography (PET) imaging utilizing [18F]fluorodeoxyglucose (FDG) may provide a non-invasive means of characterizing inflammatory activity within atherosclerotic plaque, thus serving as a surrogate biomarker for detecting vulnerable plaque. The aim of this review is to explore the rationale for performing FDG imaging, provide an overview into the mechanism of action, and summarize findings from the early application of FDG PET imaging in the clinical setting to evaluate vascular disease. Alternative imaging biomarkers and approaches are briefly discussed. © 2012 The Author(s)

F-18-Fluorodeoxyglucose Positron Emission Tomography Imaging-Assisted Management of Patients With Severe Left Ventricular Dysfunction and Suspected Coronary Disease A Randomized, Controlled Trial (PARR-2)

ObjectivesWe conducted a randomized trial to assess the effectiveness of F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)-assisted management in patients with severe ventricular dysfunction and suspected coronary disease.BackgroundSuch patients may benefit from revascularization, but have significant perioperative morbidity and mortality. F-18-fluorodeoxyglucose PET can detect viable myocardium that might recover after revascularization.MethodsIncluded were patients with severe left ventricular (LV) dysfunction and suspected coronary disease being considered for revascularization, heart failure, or transplantation work-ups or in whom PET was considered potentially useful. Patients were stratified according to recent angiography or not, then randomized to management assisted by FDG PET (n = 218) or standard care (n = 212). The primary outcome was the composite of cardiac death, myocardial infarction, or recurrent hospital stay for cardiac cause, within 1 year.ResultsAt 1 year, the cumulative proportion of patients who had experienced the composite event was 30% (PET arm) versus 36% (standard arm) (relative risk 0.82, 95% confidence interval [CI] 0.59 to 1.14; p = 0.16). The hazard ratio (HR) for the composite outcome, PET versus standard care, was 0.78 (95% CI 0.58 to 1.1; p = 0.15); for patients that adhered to PET recommendations for revascularization, revascularization work-up, or neither, HR = 0.62 (95% CI 0.42 to 0.93; p = 0.019); in those without recent angiography, for cardiac death, HR = 0.4 (95% CI 0.17 to 0.96; p = 0.035).ConclusionsThis study did not demonstrate a significant reduction in cardiac events in patients with LV dysfunction and suspected coronary disease for FDG PET-assisted management versus standard care. In those who adhered to PET recommendations and in patients without recent angiography, significant benefits were observed. The utility of FDG PET is best realized in this subpopulation and when adherence to recommendations can be achieved

Optimally Repeatable Kinetic Model Variant for Myocardial Blood Flow Measurements with 82Rb PET

Purpose. Myocardial blood flow (MBF) quantification with R b 82 positron emission tomography (PET) is gaining clinical adoption, but improvements in precision are desired. This study aims to identify analysis variants producing the most repeatable MBF measures. Methods. 12 volunteers underwent same-day test-retest rest and dipyridamole stress imaging with dynamic R b 82 PET, from which MBF was quantified usin

A Clinical Tool to Identify Candidates for Stress-First Myocardial Perfusion Imaging

Objectives: This study sought to develop a clinical model that identifies a lower-risk population for coronary artery disease that could benefit from stress-first myocardial perfusion imaging (MPI) protocols and that can be used at point of care to risk stratify patients. Background: There is an increasing interest in stress-first and stress-only imaging to reduce patient radiation exposure and improve patient workflow and experience. Methods: A secondary analysis was conducted on a single-center cohort of patients undergoing single-photon emission computed tomography (SPECT) and positron emission tomography (PET) studies. Normal MPI was defined by the absence of perfusion abnormalities and other ischemic markers and the presence of normal left ventricular wall motion and left ventricular ejection fraction. A model was derived using a cohort of 18,389 consecutive patients who underwent SPECT and was validated in a separate cohort of patients who underwent SPECT (n = 5,819), 1 internal cohort of patients who underwent PET (n=4,631), and 1 external PET cohort (n = 7,028). Results: Final models were made for men and women and consisted of 9 variables including age, smoking, hypertension, diabetes, dyslipidemia, typical angina, prior percutaneous coronary intervention, prior coronary artery bypass graft, and prior myocardial infarction. Patients with a score ≤1 were stratified as low risk. The model was robust with areas under the curve of 0.684 (95% confidence interval [CI]: 0.674 to 0.694) and 0.681 (95% CI: 0.666 to 0.696) in the derivation cohort, 0.745 (95% CI: 0.728 to 0.762) and 0.701 (95% CI: 0.673 to 0.728) in the SPECT validation cohort, 0.672 (95% CI: 0.649 to 0.696) and 0.686 (95% CI: 0.663 to 0.710) in the internal PET validation cohort, and 0.756 (95% CI: 0.740 to 0.772) and 0.737 (95% CI: 0.716 to 0.757) in the external PET validation cohort in men and women, respectively. Men and women who scored ≤1 had negative likelihood ratios of 0.48 and 0.52, respectively. Conclusions: A novel model, based on easily obtained clinical variables, is proposed to identify patients with low probability of having abnormal MPI results. This point-of-care tool may be used to identify a population that might qualify for stress-first MPI protocols

Studiengangspezifischer Anhang des Fachbereichs Neuerer Philologie der Johann Wolfgang Goethe-Universität Frankfurt am Main für den Masterstudiengang Comparative Dramaturgy and Performance Research (Double Degree) mit dem Abschluss "Master of Arts" (M.A.) vom 31.05.2017 zur Ordnung für die Masterstudiengänge des Fachbereichs Neuere Philologien vom 9. Dezember 2015 : genehmigt vom Präsidium am 27. Juni 2017

ACE inhibitors are considered first line of treatment in patients with many forms of chronic kidney disease (CKD). Other antihypertensives such as calcium channel blockers achieve similar therapeutic effectiveness in attenuating hypertension-related renal damage progression. Our objective was to explore the value of positron emission tomography (PET) imaging of renal AT1 receptor (AT1R) to guide therapy in the 5/6 subtotal-nephrectomy (Nx) rat model of CKD. Ten weeks after Nx, Sprague-Dawley rats were administered 10mg/kg/d enalapril (NxE), 30mg/kg/d diltiazem (NxD) or left untreated (Nx) for an additional 8-10 weeks. Kidney AT1R expression was assessed using in vivo [18F]fluoropyridine-losartan PET and in vitro autoradiography. Compared to shams, Nx rats exhibited higher systolic blood pressure that was reduced by both enalapril and diltiazem. At 18-20 weeks, plasma creatinine and albuminuria were significantly increased in Nx, reduced to sham levels in NxE, but enhanced in NxD rats. Enalapril treatment decreased kidney angiotensin II whereas diltiazem induced significant elevations in plasma and kidney levels. Reduced PET renal AT1R levels in Nx were normalized by enalapril but not diltiazem, and results were supported by autoradiography. Reduction of renal blood flow in Nx was restored by enalapril, while no difference was observed in myocardial blood flow amongst groups. Enhanced left ventricle mass in Nx was not reversed by enalapril but was augmented with diltiazem. Stroke volume was diminished in untreated Nx compared to shams and restored with both therapies. [18F]Fluoropyridine-Losartan PET allowed in vivo quantification of kidney AT1R changes associated with progression of CKD and with various pharmacotherapies

Quantitative analysis of coronary endothelial function with generator-produced 82Rb PET : comparison with 15O-labelled water PET

Purpose: Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. Rubidium-82 (82Rb) is a generator-produced positron emission tomography (PET) myocardial perfusion tracer that is becoming more widely used. We aimed to develop a method for quantitative assessment of coronary endothelial function using the myocardial blood flow (MBF) response during a cold pressor test (CPT) in smokers, measured using 82Rb PET and ii) compare the results with those measured using 15O-water PET. Methods: MBF was assessed at rest and during CPT with 82Rb and 15O-water in 9 controls and 10 smokers. A one-compartment model with tracer extraction correction was used to estimate MBF with both tracers. CPT response was calculated as the ratio of MBF during CPT to MBF at rest. Results: At rest, measurements of MBF for smokers vs. controls were not different using 15O-water (0.86 ± 0.18 vs. 0.70 ± 0.13, p = 0.426) than they were using 82Rb (0.83 ± 0.23 vs. 0.62 ± 0.20, p = 0.051). Both methods showed a reduced CPT response in smokers vs. controls (15O-water, 1.03 ± 0.21 vs. 1.42 ± 0.29, p = 0.006; 82Rb, 1.02 ± 0.28 vs. 1.70 ± 0.52, p < 0.001). There was high reliability [intra-class correlation coefficients: 0.48 (0.07, 0.75)] of MBF measurement between 82Rb and 15O-water during CPT. Conclusions: Using CPT, 82Rb MBF measurements detected coronary endothelial dysfunctions in smokers. 82Rb MBF measurements were comparable to those made using the 15O-water approach. Thus, 82Rb PET may be applicable for risk assessments or evaluation of risk factor modification in subjects with coronary risk factors