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The kinetic analysis of F-18-FET time-activity curves (TAC) can provide valuable diagnostic information in glioma patients. The analysis is most often limited to the average TAC over a large tissue volume and is normally assessed by visual inspection or by evaluating the time-topeak and linear slope during the late uptake phase. Here, we derived and validated a linearized model for TACs of F-18-FET in dynamic PET scans. Emphasis was put on the robustness of the numerical parameters and how reliably automatic voxel-wise analysis of TAC kineticswas possible. The diagnostic performance of the extracted shape parameters for the discrimination between isocitrate dehydrogenase (IDH) wildtype (wt) and IDH-mutant (mut) glioma was assessed by receiver-operating characteristic in a group of 33 adult glioma patients. A high agreement between the adjusted model and measured TACs could be obtained and relative, estimated parameter uncertainties were small. The best differentiation between IDH-wt and IDH-mut gliomas was achieved with the linearized model fitted to the averaged TAC values from dynamic FET PET data in the time interval 4-50 min p.i.. When limiting the acquisition time to 20-40 min p.i., classification accuracy was only slightly lower (-3%) and was comparable to classification based on linear fits in this time interval. Voxel-wise fitting was possible within a computation time similar to 1 min per image slice. Parameter uncertainties smaller than 80% for all fits with the linearized model were achieved. The agreement of best-fit parameters when comparing voxel-wise fits and fits of averaged TACs was very high (p < 0.001).

Accurate scatter correction is essential for qualitative and quantitative PET imaging. Until now, scatter correction based on Monte Carlo simulation (MCS) has been recognized as the most accurate method of scatter correction for PET. However, the major disadvantage of MCS is its long computational time, which makes it unfeasible for clinical usage. Meanwhile, single scatter simulation (SSS) is the most widely used method for scatter correction. Nevertheless, SSS has the disadvantage of limited robustness for dynamic measurements and for the measurement of large objects. In this work, a newly developed implementation of MCS using graphics processing unit (GPU) acceleration is employed, allowing full MCS-based scatter correction in clinical 3D brain PET imaging. Starting from the generation of annihilation photons to their detection in the simulated PET scanner, all relevant physical interactions and transport phenomena of the photons were simulated on GPUs. This resulted in an expected distribution of scattered events, which was subsequently used to correct the measured emission data. The accuracy of the approach was validated with simulations using GATE (Geant4 Application for Tomography Emission), and its performance was compared to SSS. The comparison of the computation time between a GPU and a single-threaded CPU showed an acceleration factor of 776 for a voxelized brain phantom study. The speedup of the MCS implemented on the GPU represents a major step toward the application of the more accurate MCS-based scatter correction for PET imaging in clinical routine.

Consistent findings postulate disturbed glutamatergic function (more specifically a hypofunction of the ionotropic NMDA receptors) as an important pathophysiologic mechanism in schizophrenia. However, the role of the metabotropic glutamatergic receptors type 5 (mGluR5) in this disease remains unclear. In this study, we investigated their significance (using [11 C]ABP688) for psychopathology and cognition in male patients with chronic schizophrenia and healthy controls. In the patient group, lower mGluR5 binding potential (BPND ) values in the left temporal cortex and caudate were associated with higher general symptom levels (negative and depressive symptoms), lower levels of global functioning and worse cognitive performance. At the same time, in both groups, mGluR5 BPND were significantly lower in smokers (F[27,1] = 15.500; p = .001), but without significant differences between the groups. Our findings provide support for the concept that the impaired function of mGluR5 underlies the symptoms of schizophrenia. They further supply a new perspective on the complex relationship between tobacco addiction and schizophrenia by identifying glutamatergic neurotransmission-in particularly mGluR5-as a possible connection to a shared vulnerability. Keywords: chronic schizophrenia; cognition; mGluR5 receptor; negative symptoms; positron emission tomography.

PurposeO-(2-[F-18]fluoroethyl)-l-tyrosine ([F-18]FET) is an established positron emission tomography (PET) tracer for brain tumor imaging. This study explores the influence of dexamethasone therapy on [F-18]FET uptake in the normal brain and its influence on the maximum and mean tumor-to-brain ratio (TBR).Procedures[F-18]FET PET scans of 160 brain tumor patients were evaluated (80 dexamethasone treated, 80 untreated; each group with 40 men/40 women). The standardized uptake value of [F-18]FET uptake in the normal brain (SUVbrain) in the different groups was compared. Nine patients were examined repeatedly with and without dexamethasone therapy.ResultsSUV(brain) of [F-18]FET uptake was significantly higher in dexamethasone-treated patients than in untreated patients (SUVbrain 1.330.1 versus 1.06 +/- 0.16 in male and 1.45 +/- 0.25 versus 1.31 +/- 0.28 in female patients). Similar results were observed in patients with serial PET scans. Furthermore, compared to men, a significantly higher SUVbrain was found in women, both with and without dexamethasone treatment. There were no significant differences between the different groups for TBRmax and TBRmean, which could have been masked by the high standard deviation. In a patient with a stable brain metastasis investigated twice with and without dexamethasone, the TBRmax and the biological tumor volume (BTV) decreased considerably after dexamethasone due to an increased SUVbrain.ConclusionDexamethasone treatment appears to increase the [F-18]FET uptake in the normal brain. An effect on TBRmax, TBRmean, and BTV cannot be excluded which should be considered especially for treatment monitoring and the estimation of BTV using [F-18]FET PET.

PET imaging of amino acid transport using O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) and proton MR spectroscopy (MRS) imaging of cell turnover measured by the ratio of choline to N-acetyl-aspartate (Cho/NAA) may provide additional information on tumor extent of cerebral gliomas compared with anatomic imaging; however, comparative studies are rare. Methods: In this prospective study, 41 patients (16 women, 25 men; mean age +/- SD, 48 +/- 14 y) with cerebral gliomas (World Health Organization [WHO] grade II: 10 [including 1 patient with 2 lesions], WHO III: 17, WHO IV: 13, without biopsy low-grade: 1, high-grade: 1) were investigated with a hybrid PET/MR scanner. Tumor extent, spatial overlap, and the distance between the corresponding centers of mass in F-18-FET PET and MRS imaging of Cho/NAA, determined by simultaneously acquired, 3-dimensional spatially resolved MRS imaging data, were compared. Results: The average tumor volumes for F-18-FET uptake and increased Cho/NAA were 19 +/- 20 cm(3) (mean +/- SD) and 22 +/- 24 cm(3), respectively, with an overlap of 40% +/- 25% and separation of the centers of mass by 9 +/- 8 mm. None of the parameters showed a significant correlation with tumor grade. Conclusion: F-18-FET uptake and increased Cho/NAA ratio are not always congruent and may represent different properties of glioma metabolism. The relationship to histologic tumor extent needs to be further analyzed.

OBJECTIVE: To compare the diagnostic performance of O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) positron emission tomography (PET) and perfusion-weighted magnetic resonance imaging (PWI) for the diagnosis of progressive or recurrent glioma. METHODS: Thirty-two pretreated gliomas (25 progressive or recurrent tumors, 7 treatment-related changes) were investigated with F-18-FET PET and PWI via a hybrid PET/magnetic resonance scanner. Volumes of interest with a diameter of 16 mm were centered on the maximum of abnormality in the tumor area in PET and PWI maps (relative cerebral blood volume, relative cerebral blood flow, mean transit time) and the contralateral unaffected hemisphere. Mean and maximum tumor-to-brain ratios as well as dynamic data for F-18-FET uptake were calculated. Diagnostic accuracies were evaluated by receiver operating characteristic analyses, calculating the area under the curve. RESULTS: F-18-FET PET showed a significant greater sensitivity to detect abnormalities in pretreated gliomas than PWI (76% vs. 52%, P = 0.03). The maximum tumorto-brain ratio of F-18-FET PET was the only parameter that discriminated treatment-related changes from progressive or recurrent gliomas (area under the curve, 0.78; P = 0.03, best cut-off 2.61; sensitivity 80%, specificity 86%, accuracy 81%). Among patients with signal abnormality in both modalities, 75% revealed spatially incongruent local hot spots. CONCLUSIONS: This pilot study suggests that F-18-FET PET is superior to PWI to diagnose progressive or recurrent glioma.

Despite an increasing number of O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) PET studies in supratentorial gliomas, studies regarding the usefulness of F-18-FET PET in brainstem and spinal cord gliomas to date remain scarce. Thirty-six F-18-FET PET scans were performed in 29 patients with brainstem (n = 29 scans) or spinal cord glioma (n = 7 scans). In 32 of 36 PET scans, a dynamic acquisition was performed. Fifteen scans in 15 patients were performed to assess newly diagnosed lesions, and 21 scans were obtained during follow-up: for diagnosing tumor progression (n = 15 scans in 14 patients) as well as for treatment monitoring (n = 6 scans in 3 patients). Four patients underwent additional serial scans (range, 1-2), and 3 of these 4 patients were examined for more than one indication. Maximum and mean tumor/brain ratios (TBRmax/mean) of F-18-FET uptake (20-40 min post injection) as well as kinetic F-18-FET uptake parameters were determined. Final diagnoses were confirmed histologically (54%) or by clinical follow-up (46%). In all newly diagnosed high-grade (n = 3 patients) and in 5 of 11 patients with low-grade gliomas, F-18-FET uptake was increased (TBRmax a parts per thousand 2.5 and/or TBRmean a parts per thousand 1.9). In 2 patients with newly diagnosed gliomas without MR contrast enhancement, F-18-FET PET nevertheless showed increased metabolism. At suspected progression, the combination of TBRs with kinetic F-18-FET parameters correctly identified presence or absence of progressive disease in 9 of 11 patients (82%). This preliminary study suggests that F-18-FET PET adds valuable diagnostic information in brainstem and spinal cord glioma, particularly when the diagnostic information derived from MRI is equivocal.

Purpose Both perfusion-weighted MR imaging (PWI) and O-(2-F-18-fluoroethyl)-L-tyrosine PET (F-18-FET) provide grading information in cerebral gliomas. The aim of this study was to compare the diagnostic value of F-18-FET PET and PWI for tumor grading in a series of patients with newly diagnosed, untreated gliomas using an integrated PET/MR scanner. Methods Seventy-two patients with untreated gliomas [22 low-grade gliomas (LGG), and 50 high-grade gliomas (HGG)] were investigated with F-18-FET PET and PWI using a hybrid PET/MR scanner. After visual inspection of PET and PWI maps (rCBV, rCBF, MTT), volumes of interest (VOIs) with a diameter of 16 mm were centered upon the maximum of abnormality in the tumor area in each modality and the contralateral unaffected hemisphere. Mean and maximum tumor-to-brain ratios (TBRmean, TBRmax) were calculated. In addition, Time-to-Peak (TTP) and slopes of time-activity curves were calculated for F-18-FET PET. Diagnostic accuracies of F-18-FET PET and PWI for differentiating low-grade glioma (LGG) from high-grade glioma (HGG) were evaluated by receiver operating characteristic analyses (area under the curve; AUC). Results The diagnostic accuracy of F-18-FET PET and PWI to discriminate LGG from HGG was similar with highest AUC values for TBRmean and TBRmax of F-18-FET PET uptake (0.80, 0.83) and for TBRmean and TBRmax of rCBV (0.80, 0.81). In case of increased signal in the tumor area with both methods (n = 32), local hot-spots were incongruent in 25 patients (78%) with a mean distance of 10.6 +/- 9.5 mm. Dynamic FET PET and combination of different parameters did not further improve diagnostic accuracy. Conclusions Both F-18-FET PET and PWI discriminate LGG from HGG with similar diagnostic performance. Regional abnormalities in the tumor area are usually not congruent indicating that tumor grading by F-18-FET PET and PWI is based on different pathophysiological phenomena.

ObjectivesO-(2-F-18-fluoroethyl)-l-tyrosine (F-18-FET) is an established tracer for brain tumour imaging. F-18-FET kinetics in gliomas appear to have potential for tumour grading, but the mechanisms remain unclear. The aim of this study was to explore the relationship between regional cerebral blood flow (rCBF) as measured by arterial spin labelling MRI and the kinetic behaviour of F-18-FET PET in cerebral gliomas.Materials and methodsTwenty patients with cerebral gliomas were investigated using arterial spin labelling MRI and dynamic F-18-FET PET. Time-activity curves (TACs) of F-18-FET uptake were analysed in 33 different tumour regions. The slopes of TAC during the early (0-5 min; slope(up)) and late phases of tracer uptake (17-50 min; slope(down)) were fitted using linear regression lines. In addition, TACs of each lesion were assigned to different curve patterns. Furthermore, we calculated tumour-to-brain ratios of F-18-FET uptake. The relationship between F-18-FET parameters and rCBF was determined.Results(18)F-FET uptake in the early phase (slope(up)) showed a significant correlation with rCBF (r=0.4; P=0.02). In contrast, both slope(down) and TAC patterns showed no significant correlation with rCBF. Furthermore, a significant correlation was found between rCBF and tumour-to-brain ratio (r=0.53; P=0.002).ConclusionThere is a relationship between rCBF and F-18-FET uptake in cerebral gliomas in the initial uptake phase, but the kinetic behaviour of F-18-FET uptake in the late phase is not significantly influenced by rCBF. Thus, the differential kinetic pattern of F-18-FET uptake in high-grade and low-grade gliomas appears to be determined by factors other than rCBF. (C) 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.