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Recent studies have reported the usefulness of 18 F-FDG PET in aiding with the diagnosis and management of patients with cardiac sarcoidosis (CS). However, image interpretation of 18 F-FDG PET for CS is sometimes challenging. We sought to investigate the inter- and intraobserver agreement and explore factors that led to important discrepancies between readers. Methods: We studied consecutive patients with no significant coronary artery disease who were referred for assessment of CS. Two experienced readers masked to clinical information, imaging reports, independently reviewed 18 F-FDG PET/CT images. 18 F-FDG PET/CT images were interpreted according to a predefined standard operating procedure, with cardiac 18 F-FDG uptake patterns categorized into 5 patterns: none, focal, focal on diffuse, diffuse, and isolated lateral wall or basal uptake. Overall image assessment was classified as either consistent with active CS or not. Results: One hundred scans were included from 71 patients. Of these, 46 underwent 18 F-FDG PET/CT with a no-restriction diet (no-restriction group), and 54 underwent 18 F-FDG PET/CT with a low-carbohydrate, high-fat and protein-permitted diet (low-carb group). There was agreement of the interpretation category in 74 of 100 scans. The κ-value of agreement among all 5 categories was 0.64, indicating moderate agreement. For overall clinical interpretation, there was agreement in 93 of 100 scans (κ = 0.85). When scans were divided into the preparation groups, there was a trend toward higher agreement in the low-carb group versus the no-restriction group (80% vs. 67%, P = 0.08). Regarding the overall clinical interpretation, there was also a trend toward greater agreement in the low-carb group versus the no-restriction group (96% vs. 89%, P = 0.08). Conclusion : The interobserver agreement of cardiac 18 F-FDG uptake image patterns was moderate. However, agreement was better regarding overall interpretation of CS. Detailed prescan dietary preparation seemed to improve interobserver agreement., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Unlabelled: In patients with non-insulin-dependent diabetes mellitus (NIDDM), FDG PET imaging is often problematic because of poor uptake of FDG. Different protocols have been used; however, these have not been directly compared in patients with NIDDM who have both coronary artery disease (CAD) and severe left ventricular (LV) dysfunction, for which defining viability is most relevant. The aim of this study was to better define the optimal means of FDG PET imaging, assessed by image quality and myocardial glucose utilization rate (rMGU), among 3 imaging protocols in patients with NIDDM, CAD, and severe LV dysfunction., Methods: Ten patients with NIDDM, CAD, and severe LV dysfunction (mean ejection fraction, 29.8% +/- 7.1%) underwent dynamic FDG PET scanning using 3 different protocols: the standard protocol, consisting of oral glucose loading or a supplemental insulin bolus based on fasting glucose; the niacin protocol, consisting of pretreatment with niacin to lower free fatty acids; and the insulin clamp protocol, consisting of hyperinsulinemic euglycemic clamp. Image quality was satisfactory with at least 1 approach in 8 patients, who formed the primary analysis group., Results: Myocardium-to-blood-pool ratios were significantly higher with the insulin clamp (standard, 1.7 +/- 1.2; niacin, 1.6 +/- 1.0; insulin clamp, 3.4 +/- 2.5 [P < 0.05 vs. standard and niacin]). Values for rMGU were higher with the insulin clamp (standard, 0.11 +/- 0.07 micromol/g/min; niacin, 0.12 +/- 0.11 micromol/g/min; insulin clamping, 0.22 +/- 0.12 micromol/g/min [P = 0.004 vs. standard and 0.07 vs. niacin])., Conclusion: The hyperinsulinemic euglycemic clamp yielded the highest FDG PET image quality and the highest rMGU in a comparison with the standard and niacin protocols in this difficult group of patients with NIDDM, CAD, and severe LV dysfunction. The hyperinsulinemic euglycemic clamp may be the preferred method for FDG PET viability imaging in this population. Larger clinical trials are needed to assess whether accuracy is greater with this approach.

Unlabelled: Serial changes in myocardial perfusion may represent an important marker of disease progression or regression or the effects of therapy for patients with coronary artery disease (CAD). Quantitative methods have not been developed for the assessment of serial changes in perfusion. The objective of this study was to use receiver operator characteristic (ROC) analysis to determine the sensitivity and specificity of direct paired comparisons (DPCs) to detect changes in absolute myocardial perfusion measured with 82Rb PET., Methods: Repeated dynamic 82Rb PET scans were obtained on 8 dogs at rest and during hyperemia induced with dobutamine (n = 4) or atrial pacing (n = 4). Radiolabeled microspheres were used to verify perfusion changes. Polar maps of absolute 82Rb retention and associated SD were estimated from the dynamic images. Paired comparisons were then performed using a t test on each of the 532 polar map sectors. Rest-rest and stress-stress differences were used to assess specificity and reproducibility, and stress-rest differences were used to assess sensitivity., Results: 82Rb retention differences of 20% over baseline were detected with 85%-90% sensitivity and specificity, using the optimal DPC probability value and image smoothness. The average 82Rb retention differences correlated well with microspheres (r = 0.74; P = 0.001). Reproducibility of the mean retention values was 4.7% +/- 2.1%. As reproducibility varies, the DPC probability value can be adjusted to maintain specificity. These ROC results are directly applicable to other image modalities that produce measurements with similar SEs (3.7% +/- 0.9%)., Conclusion: The developed method of DPCs is sensitive and specific for the detection of changes in absolute myocardial perfusion measured with 82Rb PET.

Unlabelled: One of the unique aspects of PET is its ability to noninvasively quantify metabolic processes. Metabolic rate parameters are estimated by fitting the time-activity curves from regions of interest (ROIs) placed on dynamic PET images with a kinetic model. In many cases it is possible to couple these datasets with common parameters, such as the time delay between arrival of tracer in the ROIs and the sampling site., Methods: Data from eight ROIs placed about images of the myocardium were coupled by the parameters describing the metabolite concentration in the blood. The method was evaluated by comparing estimates of k2 made using the coupled region method and the standard process of fitting data from each region separately. In addition, comparisons were made between estimates of k2 and measured myocardial oxygen consumption., Results: Very little change in mean values of k2 was obtained. The variances, however, were reduced by an average of 37%, compared to the standard method, when the common parameters were not constrained. When the values of the common metabolite parameters were constrained to values previously measured, the average variance in estimates of k2 was reduced by 30%., Conclusion: We have demonstrated that the use of this technique can significantly increase the precision of estimates of myocardial oxygen consumption utilizing 11C-acetate PET images. More precise estimates of such quantities can facilitate detection of small regional and/or temporal physiological changes measured with PET. Furthermore, this method can be utilized whenever it is known a priori that one or more kinetic model parameters has the same value for every set of ROI data.

Positron emission tomography (PET), in combination with myocardial blood flow tracers, allows highly accurate diagnosis of coronary artery disease using visual data interpretation. To increase the objectivity of data analysis and to reduce interobserver variability, we developed an automated analysis method for the three-dimensional definition of myocardial activity, which includes true volumetric data extraction and mathematical constraints of activity sampling to the expected shape of the left ventricle. Data are displayed in a standardized polar map or three-dimensional format for comparison with a normal database. The first clinical evaluation of this method in 52 patients using receiver operating characteristics (ROC) curve analysis demonstrated high diagnostic accuracy for detection as well as localization of coronary artery stenosis in predefined vascular territories. The interobserver and intraobserver agreement for localization of disease was excellent, with correlation coefficients varying from 0.85 to 0.99 for individual vascular territories. Thus, this automated quantitative analysis program provides highly accurate and reproducible evaluation of cardiac PET flow studies. Definite determination of its diagnostic accuracy requires a prospective multicenter trial in a larger patient population employing the criteria for abnormality established in this initial clinical evaluation.

In combination with PET, the tracer 13N-ammonia can be employed for the noninvasive quantification of myocardial perfusion at rest and after pharmacological stress. The purpose of this study was to develop an analysis method for the quantification of regional myocardial blood flow in the clinical setting. The algorithm includes correction for patient motion, an automated definition of multiple regions and display of absolute flows in polar map format. The effects of partial volume and blood to tissue cross-contamination were accounted for by optimizing the radial position of regions to meet fundamental assumptions of the kinetic model. In order to correct for motion artifacts, the myocardial displacement was manually determined based on edge-enhanced images. The obtained results exhibit the capability of the presented algorithm to noninvasively assess regional myocardial perfusion in the clinical environment.

Positron emission tomography has been shown to provide quantitative estimates of myocardial blood flow using 13N-ammonia and 15O-water. In a validation study, myocardial blood flow was noninvasively determined in 11 open-chest anesthetized dogs using dynamic positron emission tomography. The radiopharmaceuticals 13N-ammonia and 15O-water were intravenously administered and measurements were carried out at rest and following pharmacological vasodilation to assess blood flow over a range from 53 to 580 ml/100 g/min. Quantification of blood flow based on tracer kinetic modeling of 13N-ammonia data correlated closely with myocardial blood flow determined by microspheres (y = 0.944 x +7.22, r = 0.986) and with the 15O-water injection technique y = 1.054 x -15.8 (r = 0.99). The use of 13N-ammonia with positron emission tomography enables the accurate quantification of myocardial blood flow. Using this technique, uncomplicated study protocols simplify the measurement procedures while providing excellent qualitative and quantitative information.

Copper-62-labeled pyruvaldehyde bis(N-4-methylthiosemicarbazone) copper(II) (PTSM) is a generator-produced myocardial perfusion tracer. Animal studies have shown high myocardial tissue extraction and prolonged retention. The aim of this study was to define myocardial kinetics of 62Cu-PTSM and to determine its suitability for evaluating myocardial perfusion at rest and during pharmacological vasodilation in human subjects. In six healthy volunteers, 62Cu-PTSM was administered at baseline and during a 6-min adenosine infusion (140 micrograms/kg/min). Dynamic PET imaging with high temporal resolution was performed over 20 min. Good image quality was observed at rest and following adenosine. Myocardial kinetics demonstrated prolonged tissue retention with a clearance half-life of 105 +/- 49 min at rest and 101 +/- 65 min following adenosine (p = ns). Copper-62-PTSM tissue retention was quantified and showed only a 1.97-fold increase from rest to adenosine studies. This suggests attenuation of tracer retention at high flow rates. Copper-62-PTSM represents a promising new radiopharmaceutical for the evaluation of myocardial perfusion in the human heart.