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Background: Several factors may decrease the accuracy of quantitative PET myocardial perfusion imaging (MPI). It is therefore essential to ensure that myocardial blood flow (MBF) values are reproducible and accurate, and to design systematic protocols to achieve this. Until now, no systematic phantom protocols have been available to assess the technical factors affecting measurement accuracy and reproducibility in MPI. Materials and methods: We implemented a standard measurement protocol, which applies a flow phantom in order to compare image-derived flow values with respect to a ground truth flow value with [15O]H2O MPI performed on both a Discovery MI (DMI-20, GE Healthcare) and a Biograph Vision 600 (Vision-600, Siemens Healthineers) system. Both systems have automatic [15O]H2O radio water generators (Hidex Oy) individually installed, allowing us to also study the differences occurring due to two different bolus delivery systems. To investigate the technical factors contributing to the modelled flow values, we extracted the [15O]H2O bolus profiles, the flow values from the kinetic modeling (Qin and Qout), and finally calculated their differences between test-retest measurements on both systems. Results: The measurements performed on the DMI-20 system produced Qin and Qout values corresponging to each other as well as to the reference flow value across all test-retest measurements. The repeatability differences on DMI-20 were 2.1% ± 2.6% and 3.3% ± 4.1% for Qin and Qout, respectively. On Vision-600 they were 10% ± 8.4% and 11% ± 10% for Qin and Qout, respectively. The measurements performed on the Vision-600 system showed more variation between Qin and Qout values across test-retest measurements and exceeded 15% difference in 7/24 of the measurements. Conclusions: A preliminary protocol for measuring the accuracy and reproducibility of flow values in [15O]H2O MPI between digital PET/CT systems was assessed. The test-retest reproducibility falls below 15% in majority of the measurements conducted between two individual injector systems and two digital PET/CT systems. This study highlights the importance of implementing a standardized bolus injection and delivery protocol and importance of assessing technical factors affecting flow value reproducibility, which should be carefully investigated in a multi-center setting. [ABSTRACT FROM AUTHOR]

Aims To evaluate the incremental value of positron emission tomography (PET) myocardial perfusion imaging (MPI) over coronary computed tomography angiography (CCTA) in predicting short- and long-term outcome using machine learning (ML) approaches. Methods and results A total of 2411 patients with clinically suspected coronary artery disease (CAD) underwent CCTA, out of whom 891 patients were admitted to downstream PET MPI for haemodynamic evaluation of obstructive coronary stenosis. Two sets of Extreme Gradient Boosting (XGBoost) ML models were trained, one with all the clinical and imaging variables (including PET) and the other with only clinical and CCTA-based variables. Difference in the performance of the two sets was analysed by means of area under the receiver operating characteristic curve (AUC). After the removal of incomplete data entries, 2284 patients remained for further analysis. During the 8-year follow-up, 210 adverse events occurred including 59 myocardial infarctions, 35 unstable angina pectoris, and 116 deaths. The PET MPI data improved the outcome prediction over CCTA during the first 4 years of the observation time and the highest AUC was at the observation time of Year 1 (0.82, 95% confidence interval 0.804–0.827). After that, there was no significant incremental prognostic value by PET MPI. Conclusion PET MPI variables improve the prediction of adverse events beyond CCTA imaging alone for the first 4 years of follow-up. This illustrates the complementary nature of anatomic and functional information in predicting the outcome of patients with suspected CAD. [ABSTRACT FROM AUTHOR]

Background: New Block-Sequential-Regularized-Expectation-Maximization (BSREM) image reconstruction technique has been introduced for clinical use mainly for oncologic use. Accurate and quantitative image reconstruction is essential in myocardial perfusion imaging with positron emission tomography (PET) as it utilizes absolute quantitation of myocardial blood flow (MBF). The aim of the study was to evaluate BSREM reconstruction for quantitation in patients with suspected coronary artery disease (CAD). Methods and Results: We analyzed cardiac [15O]H2O PET studies of 177 patients evaluated for CAD. Differences between BSREM and Ordered-Subset-Expectation-Maximization with Time-Of-Flight (TOF) and Point-Spread-Function (PSF) modeling (OSEM-TOF-PSF) in terms of MBF, perfusable tissue fraction, and vascular volume fraction were measured. Classification of ischemia was assessed between the algorithms. OSEM-TOF-PSF and BSREM provided similar global stress MBF in patients with ischemia (1.84 ± 0.21 g⋅ml−1⋅min−1 vs 1.86 ± 0.21 g⋅ml−1⋅min−1) and no ischemia (3.26 ± 0.34 g⋅ml−1⋅min−1 vs 3.28 ± 0.34 g⋅ml−1⋅min−1). Global resting MBF was also similar (0.97 ± 0.12 g⋅ml−1⋅min−1 and 1.12 ± 0.06 g⋅ml−1⋅min−1). The largest mean relative difference in MBF values was 7%. Presence of myocardial ischemia was classified concordantly in 99% of patients using OSEM-TOF-PSF and BSREM reconstructions Conclusion: OSEM-TOF-PSF and BSREM image reconstructions produce similar MBF values and diagnosis of myocardial ischemia in patients undergoing [15O]H2O PET due to suspected obstructive coronary artery disease [ABSTRACT FROM AUTHOR]

We studied whether TOF reduces error propagation from attenuation correction to PET image reconstruction in PET/MR neuroimaging, by using imperfect attenuation maps in a clinical PET/MR system with 525 ps timing resolution. Ten subjects who had undergone 18F-FDG PET neuroimaging were included. Attenuation maps using a single value (0.100 cm−1) with and without air, and a 3-class attenuation map with soft tissue (0.096 cm−1), air and bone (0.151 cm−1) were used. CT-based attenuation correction was used as a reference. Volume-of-interest (VOI) analysis was conducted. Mean bias and standard deviation across the brain was studied. Regional correlations and concordance were evaluated. Statistical testing was conducted. Average bias and standard deviation were slightly reduced in the majority (23–26 out of 35) of the VOI with TOF. Bias was reduced near the cortex, nasal sinuses, and in the mid-brain with TOF. Bland–Altman and regression analysis showed small improvements with TOF. However, the overall effect of TOF to quantitative accuracy was small (3% at maximum) and significant only for two attenuation maps out of three at 525 ps timing resolution. In conclusion, TOF might reduce the quantitative errors due to attenuation correction in PET/MR neuroimaging, but this effect needs to be further investigated on systems with better timing resolution. [ABSTRACT FROM AUTHOR]

We implemented a two-dimensional convolutional neural network (CNN) for classification of polar maps extracted from Carimas (Turku PET Centre, Finland) software used for myocardial perfusion analysis. 138 polar maps from 15O–H2O stress perfusion study in JPEG format from patients classified as ischemic or non-ischemic based on finding obstructive coronary artery disease (CAD) on invasive coronary artery angiography were used. The CNN was evaluated against the clinical interpretation. The classification accuracy was evaluated with: accuracy (ACC), area under the receiver operating characteristic curve (AUC), F1 score (F1S), sensitivity (SEN), specificity (SPE) and precision (PRE). The CNN had a median ACC of 0.8261, AUC of 0.8058, F1S of 0.7647, SEN of 0.6500, SPE of 0.9615 and PRE of 0.9286. In comparison, clinical interpretation had ACC of 0.8696, AUC of 0.8558, F1S of 0.8333, SEN of 0.7500, SPE of 0.9615 and PRE of 0.9375. The CNN classified only 2 cases differently than the clinical interpretation. The clinical interpretation and CNN had similar accuracy in classifying false positives and true negatives. Classification of ischemia is feasible in 15O–H2O stress perfusion imaging using JPEG polar maps alone with a custom CNN and may be useful for the detection of obstructive CAD. [ABSTRACT FROM AUTHOR]

Purpose: The three positron emission tomography (PET) imaging compounds: (2 S ,4 R)-4-[18F]Fluoroglutamine ([18F]FGln), L -[methyl-11C]Methionine ([11C]Met), and 2-deoxy-2-[18F]fluoro- D -glucose ([18F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for their tumor detection potential. Dynamic acquisition of [18F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison. Procedures: Up to four imaging studies were performed on each orthotopically grafted BT4C glioma-bearing BDIX rat subject (n = 16) on four consecutive days. First, a DOTAREM® contrast enhanced MRI followed by attenuation correction CT and dynamic PET imaging with each radiopharmaceutical (20 min [11C]Met, 60 min [18F]FDG, and 60 min [18F]FGln with either the Molecubes PET/CT (n = 5) or Inveon PET/CT cameras (n = 11). Ex vivo brain autoradiography was completed for each radiopharmaceutical and [18F]FGln pharmacokinetics were studied by injecting 40 MBq into healthy BDIX rats (n = 10) and collecting blood samples between 5 and 60 min. Erythrocyte uptake, plasma protein binding and plasma parent-fraction were combined to estimate the total blood bioavailability of [18F]FGln over time. The corrected PET-image blood data was then applied to multiple pharmacokinetic models. Results: Average BT4C tumor-to-healthy brain tissue uptake ratios (TBR) for PET images reached maxima of: [18F]FGln TBR: 1.99 ± 0.19 (n = 13), [18F]FDG TBR: 1.41 ± 0.11 (n = 6), and [11C]Met TBR: 1.08 ± 0.08, (n = 12) for the dynamic PET images. Pharmacokinetic modeling in dynamic [18F]FGln studies suggested both reversible and irreversible uptake play a similar role. Imaging with Inveon and Molecubes yielded similar end-result ratios with insignificant differences (p > 0.25). Conclusions: In orthotopic BT4C gliomas, [18F]FGln may offer improved imaging versus [11C]Met and [18F]FDG. No significant difference in normalized end-result data was found between the Inveon and Molecubes camera systems. Kinetic modelling of [18F]FGln uptake suggests that both reversible and irreversible uptake play an important role in BDIX rat pharmacokinetics. [ABSTRACT FROM AUTHOR]

Background: Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI). Methods and results: Pigs underwent resting [15O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery. MBF, PTF, and PTI were compared with volume fraction of MI in matched segments as assessed by triphenyl tetrazolium chloride staining of LV slices. MBF and PTF were lower in infarcted than non-infarcted segments. Segmental analysis of MBF showed similar area under the curve (AUC) of 0.85, 0.86, and 0.90 with relative MBF, PTF, and PTI for the detection of viable myocardium defined as infarct volume fraction of < 75%. Cut-off values of relative MBF of ≥ 67% and PTF of ≥ 66% resulted in accuracies of 90% and 81%, respectively. Conclusions: Our results indicate that resting MBF, PTF, and PTI based on [15O]water PET perfusion imaging are useful for the assessment of myocardial viability. [ABSTRACT FROM AUTHOR]

Background and Aims: Computed tomography (CT)-derived adipose tissue radiodensity represents a potential noninvasive surrogate marker for lipid deposition and obesity-related metabolic disease risk. We studied the effects of bariatric surgery on CT-derived adipose radiodensities in abdominal and femoral areas and their relationships to circulating metabolites in morbidly obese patients.Methods and Results: We examined 23 morbidly obese women who underwent CT imaging before and 6 months after bariatric surgery. Fifteen healthy non-obese women served as controls. Radiodensities of the abdominal subcutaneous (SAT) and visceral adipose tissue (VAT), and the femoral SAT, adipose tissue masses were measured in all participants. Circulating metabolites were measured by NMR. At baseline, radiodensities of abdominal fat depots were lower in the obese patients as compared to the controls. Surprisingly, radiodensity of femoral SAT was higher in the obese as compared to the controls. In the abdominal SAT depot, radiodensity strongly correlated with SAT mass (r = -0.72, p < 0.001). After surgery, the radiodensities of abdominal fat increased significantly (both p < 0.01), while femoral SAT radiodensity remained unchanged. Circulating ApoB/ApoA-I, leucine, valine, and GlycA decreased, while glycine levels significantly increased as compared to pre-surgical values (all p < 0.05). The increase in abdominal fat radiodensity correlated negatively with the decreased levels of ApoB/ApoA-I ratio, leucine and GlycA (all p < 0.05). The increase in abdominal SAT density was significantly correlated with the decrease in the fat depot mass (r = -0.66, p = 0.002).Conclusion: Higher lipid content in abdominal fat depots, and lower content in femoral subcutaneous fat, constitute prominent pathophysiological features in morbid obesity. Further studies are needed to clarify the role of non-abdominal subcutaneous fat in the pathogenesis of obesity.Clinical Trial Registration Number: NCT01373892. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa). Methods: Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUV) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (V). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455. Results: In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly ( p < 0.01) outperformed that of PET/CT while no differences were detected between PET/MRI and mpMRI. SUV and V of Gleason score (GS) >3 + 4 tumors were significantly ( p < 0.05) higher than those for GS 3 + 3 and benign hyperplasia. A total of 442 lymph nodes were evaluable for staging, and PET/CT and PET/MRI demonstrated true-positive findings in only 1/7 patients with metastatic lymph nodes. Conclusions: Quantitative F-FACBC imaging significantly correlated with GS but failed to outperform MRI in lesion detection. F-FACBC may assist in targeted biopsies in the setting of hybrid imaging with MRI. [ABSTRACT FROM AUTHOR]

Background: Radiolabeled RGD peptides detect αvβ3 integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [68Ga]NODAGA-RGD detects increased αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αvβ3 integrin is expressed in viable ischemic or injured myocardium.Methods: We studied 8 Finnish landrace pigs 13 ± 4 days after percutaneous implantation of a bottleneck stent in the proximal left anterior descending coronary artery. Antithrombotic therapy was used to prevent stent occlusion. Myocardial uptake of [68Ga]NODAGA-RGD (290 ± 31 MBq) was evaluated by a 62 min dynamic PET scan. The ischemic area was defined as the regional perfusion abnormality during adenosine-induced stress by [15O]water PET. Guided by triphenyltetrazolium chloride staining, tissue samples from viable and injured myocardial areas were obtained for autoradiography and histology.Results: Stent implantation resulted in a partly reversible myocardial perfusion abnormality. Compared with remote myocardium, [68Ga]NODAGA-RGD PET showed increased tracer uptake in the ischemic area (ischemic-to-remote ratio 1.3 ± 0.20, p = 0.0034). Tissue samples from the injured areas, but not from the viable ischemic areas, showed higher [68Ga]NODAGA-RGD uptake than the remote non-ischemic myocardium. Uptake of [68Ga]NODAGA-RGD correlated with immunohistochemical detection of αvβ3 integrin that was expressed in the injured myocardial areas.Conclusions: Cardiac [68Ga]NODAGA-RGD PET demonstrates increased myocardial αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [68Ga]NODAGA-RGD uptake indicates that it reflects αvβ3 integrin expression associated with repair of recent myocardial injury. [ABSTRACT FROM AUTHOR]

Bariatric surgery results in notable weight loss and alleviates hyperglycemia in patients with type 2 diabetes (T2D). We aimed to characterize the vascular effects of a mixed meal and infusion of exogenous glucose-dependent insulinotropic polypeptide (GIP) in the splanchnic region in 10 obese patients with T2D before and after bariatric surgery and in 10 lean control subjects. The experiments were carried out on two separate days. Pancreatic and intestinal blood flow (BF) were measured at baseline, 20 min, and 50 min with 15O-water by using positron emission tomography and MRI. Before surgery, pancreatic and intestinal BF responses to a mixed meal did not differ between obese and lean control subjects. Compared with presurgery, the mixed meal induced a greater increase in plasma glucose, insulin, and GIP concentrations after surgery, which was accompanied by a marked augmentation of pancreatic and intestinal BF responses. GIP infusion decreased pancreatic but increased small intestinal BF similarly in all groups both before and after surgery. Taken together, these results demonstrate that bariatric surgery leads to enhanced splanchnic vascular responses as a likely consequence of rapid glucose appearance and GIP hypersecretion. [ABSTRACT FROM AUTHOR]