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Simultaneous MR-PET/-SPECT is an emerging technology that capitalises on the invaluable advantages of both modalities, allowing access to numerous sensitive tracers and superior soft-tissue contrast alongside versatile functional imaging capabilities. However, to optimise these capabilities, concurrent acquisitions require the MRI antenna located inside the PET/SPECT field-of-view to be operated without compromising any aspects of system performance or image quality compared to the stand-alone instrumentation. Here, we report a novel gamma-radiation-transparent antenna concept. The end-fed J-shape antenna is particularly adept for hybrid ultra-high field MR-PET/-SPECT applications as it enables all highly attenuating materials to be placed outside the imaging field-of-view. Furthermore, this unique configuration also provides advantages in stand-alone MR applications by reducing the amount of coupling between the cables and the antenna elements, and by lowering the potential specific absorption rate burden. The use of this new design was experimentally verified according to the important features for both ultra-high field MRI and the 511 keV transmission scan. The reconstructed attenuation maps evidently showed much lower attenuation ( ∼ 15 %) for the proposed array when compared to the conventional dipole antenna array since there were no high-density components. In MR, it was observed that the signal-to-noise ratio from the whole volume obtained using the proposed array was comparable to that acquired by the conventional array which was also in agreement with the simulation results. The unique feature, J-shape array, would enable simultaneous MR-PET/-SPECT experiments to be conducted without unduly compromising any aspects of system performance and image quality compared to the stand-alone instrumentation.

The glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR

Building on the success of positron emission tomography (PET)/CT scanners, a hybrid imaging technology, combining PET with the versatile attributes of magnetic resonance imaging (MRI), has been in use for over ten years. At the Forschungszentrum Julich, one of the four prototypes available worldwide, combining a commercial 3T MRI with a newly developed BrainPET insert, was installed in 2008, allowing simultaneous data acquisition with PET and MRI. Here, we report on our ten-year-long experience of the methods and technology developed through this paper with numerous patients and volunteers. In the course of our research, a number of different radiotracers, such as [18F]Fluoroethyltyrosine, [11C]Flumazenil, [11C]Raclopride, and [15O]H2O, have been applied while simultaneously measuring several different MR sequences. The PET data obtained with the BrainPET has demonstrated higher image quality and superior resolution capability compared to the stand-alone PET scanner, ECAT Exact HR+. Furthermore, the simultaneous acquisition of MR images alongside BrainPET scans, using different sequences, showed an excellent quality without any relevant artifacts and provided useful complementary information. Our experiences with the hybrid 3T MR-BrainPET indicate a promising basis for further developments of this unique technique, allowing simultaneous brain imaging in a clinical setting.

Currently, the metabotropic glutamate receptor 5 (mGluR5) is the subject of several lines of research in the context of neurology and is of high interest as a target for positron-emission tomography (PET). Here, we assessed the feasibility of using [11C]ABP688, a specific antagonist radiotracer for an allosteric site on the mGluR5, to evaluate changes in glutamatergic neurotransmission through a mismatch-negativity (MMN) task as a part of a simultaneous and synchronized multimodal PET/MR-EEG study. We analyzed the effect of MMN by comparing the changes in nondisplaceable binding potential (BPND) prior to (baseline) and during the task in 17 healthy subjects by applying a bolus/infusion protocol. Anatomical and functional regions were analyzed. A small change in BPND was observed in anatomical regions (posterior cingulate cortex and thalamus) and in a functional network (precuneus) after the start of the task. The effect size was quantified using Kendall’s W value and was 0.3. The motor cortex was used as a control region for the task and did not show any significant BPND changes. There was a significant ΔBPND between acquisition conditions. On average, the reductions in binding across the regions were - 8.6 ± 3.2% in anatomical and - 6.4 ± 0.5% in the functional network (p ≤ 0.001). Correlations between ΔBPND and EEG latency for both anatomical (p = 0.008) and functional (p = 0.022) regions were found. Exploratory analyses suggest that the MMN task played a role in the glutamatergic neurotransmission, and mGluR5 may be indirectly modulated by these changes.

The kinetic analysis of $^{{18}}\text{F}$ -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-to-peak and linear slope during the late uptake phase. Here, we derived and validated a linearized model for TACs of $^{{18}}\text{F}$ -FET in dynamic PET scans. Emphasis was put on the robustness of the numerical parameters and how reliably automatic voxel-wise analysis of TAC kinetics was 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 $\approx ~{1}$ 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).

Translational Psychiatry 11(1), 60 (2021). doi:10.1038/s41398-020-01160-2, Published by Nature Publishing Group, London

The PET data were acquired using a 3T hybrid MR-BrainPET insert system (SIEMENS, Erlangen, Germany) in list mode. The coincidences were corrected for random events using the delayed window technique with VRR, dead time, attenuation and scattered coincidences (single scatter simulation – SSS method), and physical decay. An adapted NEMA phantom, without lung insert and with six sphere inserts, was used. One insert was filled with 11C and the others contained cold (no activity) water contrasting in a warm background cylinder. Coincidence data were acquired during eight isotope half-lives, giving 163 minutes total acquisition time for 11C, which has a half-life of T1/2 = 20.35 minutes. The ratio of the activity concentration between the sphere (Hot with 28 mm of nominal internal diameter) and the background region (BG) was 1.85:1. This value is frequently found for the ratio of activity concentrations in the grey matter cortex (GM) and cerebellar grey matter (reference region) during the steady-state condition in [11C]ABP688 studies. A cold transmission scan of the adapted NEMA phantom using 68Ge sources was acquired in a Siemens ECAT Exact HR+ PET scanner. This acquisition (2 bed positions, 20 minutes of transmission, reconstructed with OSEM 2D – 6 iterations and 16 subsets and a 256 × 256 matrix) was used to create the attenuation map for the phantom used in the 11C decay study.

Background: Iterative image reconstruction algorithms are widely used in positron emission tomography (PET). However, they are known to contribute to quantitation bias, which is particularly pronounced during dynamic PET studies such as neuroreceptor binding studies with 11C-labelled radiotracers where count rates become low towards the end of the examination. This problem is relevant in case simultaneous PET/MR studies which apply a bolus-infusion protocol to allow the multimodal comparison between control or resting state and stimulation effects in a single session of e.g. 60 min, i.e. 3 half-lives of 11C. A quantitation bias may interfere with stimulation related changes. In this study, we evaluated the impact of the 3D ordinary Poisson OSEM (3D OP-OSEM) on quantitation accuracy reconstructions and the subsequent propagation into binding potential values using a decay study of a 11C filled phantom and a human brain data set. To evaluate the reconstruction bias, we tested different reconstruction framing schemes and propose a framing scheme that keeps the counts per time frame constant over the full acquisition time. We also compared the vendor’s 3D OP-OSEM image reconstruction method to an in-house developed reconstruction (PRESTO toolkit). Results: In general, a bias for low and high activity concentration regions was observed in the range of ± 3% and - 3% to 5%, respectively. Using the alternative proposed framing scheme, a lower bias was achieved for regions with low activity concentration using PRESTO, and a stabilization of the mean bias for the binding potential was achieved at around 5% with the vendor’s reconstruction throughout the relevant activity curve time interval. Conclusions: The bias in activity concentration propagated into the binding potential values leading to a mean bias of around 5%, thus allowing the detection of changes in binding values during equilibrium of > 5%.

Simultaneous trimodal positron emission tomography/magnetic resonance imaging/electroencephalography (PET/MRI/EEG) resting state (rs) brain data were acquired from 10 healthy male volunteers. The rs‐functional MRI (fMRI) metrics, such as regional homogeneity (ReHo), degree centrality (DC) and fractional amplitude of low‐frequency fluctuations (fALFFs), as well as 2‐[18F]fluoro‐2‐desoxy‐d‐glucose (FDG)‐PET standardised uptake value (SUV), were calculated and the measures were extracted from the default mode network (DMN) regions of the brain. Similarly, four microstates for each subject, showing the diverse functional states of the whole brain via topographical variations due to global field power (GFP), were estimated from artefact‐corrected EEG signals. In this exploratory analysis, the GFP of microstates was nonparametrically compared to rs‐fMRI metrics and FDG‐PET SUV measured in the DMN of the brain. The rs‐fMRI metrics (ReHO, fALFF) and FDG‐PET SUV did not show any significant correlations with any of the microstates. The DC metric showed a significant positive correlation with microstate C (r (s) = 0.73, p = .01). FDG‐PET SUVs indicate a trend for a negative correlation with microstates A, B and C. The positive correlation of microstate C with DC metrics suggests a functional relationship between cortical hubs in the frontal and occipital lobes. The results of this study suggest further exploration of this method in a larger sample and in patients with neuropsychiatric disorders. The aim of this exploratory pilot study is to lay the foundation for the development of such multimodal measures to be applied as biomarkers for diagnosis, disease staging, treatment response and monitoring of neuropsychiatric disorders.

Simultaneous PET/MR/EEG (Positron Emission Tomography – Magnetic Resonance – Electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here within the framework of the European Union Project TRIMAGE. The trimodal, cost-effective PET/MR/EEG imaging tool makes use of cutting edge technology both in PET and in MR fields. A novel type of magnet (1.5T, non-cryogenic) has been built together with a PET scanner that makes use of the most advanced photodetectors (i.e., SiPM matrices), scintillators matrices (LYSO) and digital electronics. The combined PET/MR/EEG system is dedicated to brain imaging and has an inner diameter of 260 mm and an axial Field-of-View of 160 mm.It enables the acquisition and assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. The dopaminergic system and the glutamatergic system in schizophrenic patients are investigated via PET, the same physiological/pathophysiological conditions with regard to functional connectivity, via fMRI, and its electrophysiological signature via EEG. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.The preliminary performances of two components of the imaging tool (PET and MR) are discussed. Initial results of the search of possible candidates for suitable schizophrenia biomarkers are also presented as obtained with PET/MR systems available to the collaboration.

PET imaging of amino acid transport using O-(2-18F-fluoroethyl)-l-tyrosine (18F-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 18F-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 18F-FET uptake and increased Cho/NAA were 19 ± 20 cm3 (mean ± SD) and 22 ± 24 cm3, 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: 18F-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.

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.

PurposeO-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) is an established positron emission tomography (PET) tracer for brain tumor imaging. This study explores the influence of dexamethasone therapy on [18F]FET uptake in the normal brain and its influence on the maximum and mean tumor-to-brain ratio (TBR).Procedures[18F]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 [18F]FET uptake in the normal brain (SUVbrain) in the different groups was compared. Nine patients were examined repeatedly with and without dexamethasone therapy.ResultsSUVbrain of [18F]FET uptake was significantly higher in dexamethasone-treated patients than in untreated patients (SUVbrain 1.33 ± 0.1 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 [18F]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 [18F]FET PET.

O-(2-[[SUVDexamethasone treatment appears to increase the [

Objective To compare the diagnostic performance of O-(2-18F-fluoroethyl)-L-tyrosine (18F-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 18F-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 18F-FET uptake were calculated. Diagnostic accuracies were evaluated by receiver operating characteristic analyses, calculating the area under the curve. Results 18F-FET PET showed a significant greater sensitivity to detect abnormalities in pretreated gliomas than PWI (76% vs. 52%, P = 0.03). The maximum tumor-to-brain ratio of 18F-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 18F-FET PET is superior to PWI to diagnose progressive or recurrent glioma.

One challenge for PET-MR hybrid imaging is the correction for attenuation of the 511 keV annihilation radiation by the required RF transmit and/or RF receive coils. Although there are strategies for building PET transparent Tx/Rx coils, such optimised coils still cause significant attenuation of the annihilation radiation leading to artefacts and biases in the reconstructed activity concentrations. We present a straightforward method to measure the attenuation of Tx/Rx coils in simultaneous MR-PET imaging based on the natural 176Lu background contained in the scintillator of the PET detector without the requirement of an external CT scanner or PET scanner with transmission source. The method was evaluated on a prototype 3T MR-BrainPET produced by Siemens Healthcare GmbH, both with phantom studies and with true emission images from patient/volunteer examinations. Furthermore, the count rate stability of the PET scanner and the x-ray properties of the Tx/Rx head coil were investigated. Even without energy extrapolation from the two dominant γ energies of 176Lu to 511 keV, the presented method for attenuation correction, based on the measurement of 176Lu background attenuation, shows slightly better performance than the coil attenuation correction currently used. The coil attenuation correction currently used is based on an external transmission scan with rotating 68Ge sources acquired on a Siemens ECAT HR + PET scanner. However, the main advantage of the presented approach is its straightforwardness and ready availability without the need for additional accessories.

Attenuation correction (AC) of cerebral PET data acquired in hybrid MR/PET scanners is still a challenge. To overcome this problem we previously proposed a correction method by obtaining template-based attenuation maps (AM) using MR and ECAT EXACT HR+ transmission scans. In the present study we investigated (a) the basic difference between template-based and CT-based AC methods and (b) their influence on reconstructed PET images. The data of 11 subjects undergoing $^{18}{\rm FDG}$ imaging in the Siemens 3T MR-BrainPET scanner were used. Additionally, from all participants a CT scan of the whole head was acquired at the same day. These CT images were transformed to CT-based AMs. They were filtered by a 3D Gaussian kernel with 3 mm (BrainPET resolution) filter width, which was considered as reference. Comparisons between both AMs (CT-based and template-based) were performed by estimating the Dice coefficients D and calculating the numbers of true positive, true negative and false negative voxels. The BrainPET emission data were reconstructed with both AMs ( ${\rm AM}_{{\rm CT}3{\rm mm}}$ and ${\rm AM}_{\rm Template}$ ). All reconstructed PET images were scaled to standardized uptake values (SUVs) and normalized to the MNI brain for using the AAL-VOI Atlas analysis. Correlation plots with regression equation, coefficients of determination ${{\rm R}^2}$ and relative differences (RD) between ${\rm AM}_{{\rm CT}3{\rm mm}}$ and the ${\rm AM}_{\rm Template}$ were derived. The fraction of the overall true positive voxels averaged over the 11 subjects was $80.4 \pm 7.5\% $ for ${\rm AM}_{\rm Template}$ compared to ${\rm AM}_{{\rm CT}3{\rm mm}}$ ( ${{\rm D}_{\rm bone}} = 0.63 \pm 0.08$ ; ${{\rm D}_{\rm soft - tissue}} = 0.85 \pm 0.08$ ; ${{\rm D}_{\rm air}} = 0.79 \pm 0.04$ ). A misclassification of bone as soft tissue and vice versa was evident in the comparison. The correlation plot of all VOIs considered (1,276 values) showed a mean ${{\rm R}^2}$ of 0.964 and a slope of 1.02. A mean RD of $1.33 \pm 0.95\%$ ( ${\min} = - 0.12\% $ , ${\max} = 2.85\% $ ) was found. The template-based AC method proposed by our group shows considerable differences in comparison to the higher resolution CT-based AM with respect to the Dice coefficients, in particular in the classification of bone and soft tissue. However, this has no major influence on the reconstructed $^{18}{\rm FDG}$ PET data.

Aim Partial volume correction (PVC) is an essential step for quantitative positron emission tomography (PET). In the present study, PVELab , a freely available software, is evaluated for PVC in 18 F-FDOPA brain-PET, with a special focus on the accuracy degradation introduced by various MR-based segmentation approaches. Methods Four PVC algorithms (M-PVC; MG-PVC; mMG-PVC; and R-PVC) were analyzed on simulated 18 F-FDOPA brain-PET images. MR image segmentation was carried out using FSL (FMRIB Software Library) and SPM (Statistical Parametric Mapping) packages, including additional adaptation for subcortical regions (SPM L ). Different PVC and segmentation combinations were compared with respect to deviations in regional activity values and time-activity curves (TACs) of the occipital cortex (OCC), caudate nucleus (CN), and putamen (PUT). Additionally, the PVC impact on the determination of the influx constant ( K i ) was assessed. Results Main differences between tissue-maps returned by three segmentation algorithms were found in the subcortical region, especially at PUT. Average misclassification errors in combination with volume reduction was found to be lowest for SPM L (PUT 70%). Accurate recovery of activity data at OCC is achieved by M-PVC (apparent recovery coefficient varies between 0.99 and 1.10). The other three evaluated PVC algorithms have demonstrated to be more suitable for subcortical regions with MG-PVC and mMG-PVC being less prone to the largest tissue misclassification error simulated in this study. Except for M-PVC, quantification accuracy of K i for CN and PUT was clearly improved by PVC. Conclusions The regional activity value of PUT was appreciably overcorrected by most of the PVC approaches employing FSL or SPM segmentation, revealing the importance of accurate MR image segmentation for the presented PVC framework. The selection of a PVC approach should be adapted to the anatomical structure of interest. Caution is recommended in subsequent interpretation of K i values. The possible different change of activity concentrations due to PVC in both target and reference regions tends to alter the corresponding TACs, introducing bias to K i determination. The accuracy of quantitative analysis was improved by PVC but at the expense of precision reduction, indicating the potential impropriety of applying the presented framework for group comparison studies.

We aimed to evaluate the diagnostic potential of dual-time-point imaging with positron emission tomography (PET) using O-(2-[(18)F]fluoroethyl)-L-tyrosine ((18)F-FET) for non-invasive grading of cerebral gliomas compared with a dynamic approach.Thirty-six patients with histologically confirmed cerebral gliomas (21 primary, 15 recurrent; 24 high-grade, 12 low-grade) underwent dynamic PET from 0 to 50 min post-injection (p.i.) of (18)F-FET, and additionally from 70 to 90 min p.i. Mean tumour-to-brain ratios (TBRmean) of (18)F-FET uptake were determined in early (20-40 min p.i.) and late (70-90 min p.i.) examinations. Time-activity curves (TAC) of the tumours from 0 to 50 min after injection were assigned to different patterns. The diagnostic accuracy of changes of (18)F-FET uptake between early and late examinations for tumour grading was compared to that of curve pattern analysis from 0 to 50 min p.i. of (18)F-FET.The diagnostic accuracy of changes of the TBRmean of (18)F-FET PET uptake between early and late examinations for the identification of HGG was 81% (sensitivity 83%; specificity 75%; cutoff - 8%; p 0.001), and 83% for curve pattern analysis (sensitivity 88%; specificity 75%; p 0.001).Dual-time-point imaging of (18)F-FET uptake in gliomas achieves diagnostic accuracy for tumour grading that is similar to the more time-consuming dynamic data acquisition protocol.• Dual-time-point imaging is equivalent to dynamic FET PET for grading of gliomas. • Dual-time-point imaging is less time consuming than dynamic FET PET. • Costs can be reduced due to higher patient throughput. • Reduced imaging time increases patient comfort and sedation might be avoided. • Quicker image interpretation is possible, as no curve evaluation is necessary.

Both perfusion-weighted MR imaging (PWI) and O-(2-18F-fluoroethyl)-L-tyrosine PET (18F–FET) provide grading information in cerebral gliomas. The aim of this study was to compare the diagnostic value of 18F–FET PET and PWI for tumor grading in a series of patients with newly diagnosed, untreated gliomas using an integrated PET/MR scanner. Seventy-two patients with untreated gliomas [22 low-grade gliomas (LGG), and 50 high-grade gliomas (HGG)] were investigated with 18F–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 18F–FET PET. Diagnostic accuracies of 18F–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). The diagnostic accuracy of 18F–FET PET and PWI to discriminate LGG from HGG was similar with highest AUC values for TBRmean and TBRmax of 18F–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. Both 18F–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 18F–FET PET and PWI is based on different pathophysiological phenomena.

To compare the diagnostic performance of O-(2-Thirty-two pretreated gliomas (25 progressive or recurrent tumors, 7 treatment-related changes) were investigated withThis pilot study suggests that

Both perfusion-weighted MR imaging (PWI) and O-(2-Seventy-two patients with untreated gliomas [22 low-grade gliomas (LGG), and 50 high-grade gliomas (HGG)] were investigated withThe diagnostic accuracy ofBoth

OBJECTIVES O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) is an established tracer for brain tumour imaging. (18)F-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 (18)F-FET PET in cerebral gliomas. MATERIALS AND METHODS Twenty patients with cerebral gliomas were investigated using arterial spin labelling MRI and dynamic (18)F-FET PET. Time-activity curves (TACs) of (18)F-FET uptake were analysed in 33 different tumour regions. The slopes of TAC during the early (0-5 min; slopeup) and late phases of tracer uptake (17-50 min; slopedown) 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 (18)F-FET uptake. The relationship between (18)F-FET parameters and rCBF was determined. RESULTS (18)F-FET uptake in the early phase (slopeup) showed a significant correlation with rCBF (r=0.4; P=0.02). In contrast, both slopedown 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). CONCLUSION There is a relationship between rCBF and (18)F-FET uptake in cerebral gliomas in the initial uptake phase, but the kinetic behaviour of (18)F-FET uptake in the late phase is not significantly influenced by rCBF. Thus, the differential kinetic pattern of (18)F-FET uptake in high-grade and low-grade gliomas appears to be determined by factors other than rCBF.

Aim Attenuation correction of PET data acquired by hybrid MR/PET scanners remains a challenge, even if several methods for brain and whole-body measurements have been developed recently. A template-based attenuation correction for brain imaging proposed by our group is easy to handle and delivers reliable attenuation maps in a short time. However, some potential error sources are analyzed in this study. We investigated the choice of template reference head among all the available data (error A), and possible skull anomalies of the specific patient, such as discontinuities due to surgery (error B). Materials and methods An anatomical MR measurement and a 2-bed-position transmission scan covering the whole head and neck region were performed in eight normal subjects (4 females, 4 males). Error A: Taking alternatively one of the eight heads as reference, eight different templates were created by nonlinearly registering the images to the reference and calculating the average. Eight patients (4 females, 4 males; 4 with brain lesions, 4 w/o brain lesions) were measured in the Siemens BrainPET/MR scanner. The eight templates were used to generate the patients' attenuation maps required for reconstruction. ROI and VOI atlas-based comparisons were performed employing all the reconstructed images. Error B: CT-based attenuation maps of two volunteers were manipulated by manually inserting several skull lesions and filling a nasal cavity. The corresponding attenuation coefficients were substituted with the water's coefficient (0.096/cm). Results Error A: The mean SUVs over the eight templates pairs for all eight patients and all VOIs did not differ significantly one from each other. Standard deviations up to 1.24% were found. Error B: After reconstruction of the volunteers' BrainPET data with the CT-based attenuation maps without and with skull anomalies, a VOI-atlas analysis was performed revealing very little influence of the skull lesions (less than 3%), while the filled nasal cavity yielded an overestimation in cerebellum up to 5%. Conclusions The present error analysis confirms that our template-based attenuation method provides reliable attenuation corrections of PET brain imaging measured in PET/MR scanners.

Background Despite an increasing number of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET studies in supratentorial gliomas, studies regarding the usefulness of 18F-FET PET in brainstem and spinal cord gliomas to date remain scarce. Methods Thirty-six 18F-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 18F-FET uptake (20-40 min post injection) as well as kinetic 18F-FET uptake parameters were determined. Final diagnoses were confirmed histologically (54%) or by clinical follow-up (46%). Results In all newly diagnosed high-grade (n = 3 patients) and in 5 of 11 patients with low-grade gliomas, 18F-FET uptake was increased (TBRmax ≥2.5 and/or TBRmean ≥1.9). In 2 patients with newly diagnosed gliomas without MR contrast enhancement, 18F-FET PET nevertheless showed increased metabolism. At suspected progression, the combination of TBRs with kinetic 18F-FET parameters correctly identified presence or absence of progressive disease in 9 of 11 patients (82%). Conclusions This preliminary study suggests that 18F-FET PET adds valuable diagnostic information in brainstem and spinal cord glioma, particularly when the diagnostic information derived from MRI is equivocal.

Until recently, no direct comparison between [15O]water positron emission tomography (PET) and arterial spin labeling (ASL) for measuring cerebral blood flow (CBF) was possible. With the introduction of integrated, hybrid magnetic resonance (MR)-PET scanners, such a comparison becomes feasible. This study presents results of CBF measurements recorded simultaneously with [15O]water and ASL. A 3T MR-BrainPET scanner was used for the simultaneous acquisition of pseudo-continuous ASL (pCASL) magnetic resonance imaging (MRI) and [15O]water PET. Quantitative CBF values were compared in 10 young healthy male volunteers at baseline conditions. A statistically significant ( P15O]water PET became possible for the first time so that temporal, physiologic, and functional variations were avoided. Regional and individual differences were found despite the overall similarity between ASL and PET, requiring further detailed investigations.

At present, a new hybrid imaging technology combining PET and MRI is emerging. The construction of hybrid scanners that allow simultaneous MRI and PET required the development of a new type of MR-compatible PET detector, which was first realized for studying small animals. The first industrial prototypes of such integrated MR-PET scanners for human brain studies have been installed recently. In this article, the feasibility of this new approach is demonstrated by first studies in brain tumor patients. Beyond time saving in patient management and optimal spatial overlay of anatomic and functional information, this technique offers new perspectives with regard to the simultaneous observation of physiological and biochemical processes. Functional brain activation and interaction of receptor ligands during special activation tasks or pharmacological intervention may be explored in humans. Thus, MR-PET opens new horizons in multiparametric neuroimaging.

The combination of Positron Emission Tomography (PET) with magnetic resonance imaging (MRI) in hybrid PET/MRI scanners offers a number of advantages in investigating brain structure and function. A critical step of PET data reconstruction is attenuation correction (AC). Accounting for bone in attenuation maps (μ-map) was shown to be important in brain PET studies. While there are a number of MRI-based AC methods, no systematic comparison between them has been performed so far. The aim of this work was to study the different performance obtained by some of the recent methods presented in the literature. To perform such a comparison, we focused on [18F]-Fluorodeoxyglucose-PET/MRI neurodegenerative dementing disorders, which are known to exhibit reduced levels of glucose metabolism in certain brain regions. Four novel methods were used to calculate μ-maps from MRI data of 15 patients with Alzheimer’s dementia (AD). The methods cover two atlas-based methods, a segmentation method, and a hybrid template/segmentation method. Additionally, the Dixon-based and a UTE-based method, offered by a vendor, were included in the comparison. Performance was assessed at three levels: tissue identification accuracy in the μ-map, quantitative accuracy of reconstructed PET data in specific brain regions, and precision in diagnostic images at identifying hypometabolic areas. Quantitative regional errors of −20–−10 % were obtained using the vendor’s AC methods, whereas the novel methods produced errors in a margin of ±5 %. The obtained precision at identifying areas with abnormally low levels of glucose uptake, potentially regions affected by AD, were 62.9 and 79.5 % for the two vendor AC methods, the former ignoring bone and the latter including bone information. The precision increased to 87.5–93.3 % in average for the four new methods, exhibiting similar performances. We confirm that the AC methods based on the Dixon and UTE sequences provided by the vendor are inferior to alternative techniques. As a novel finding, there was no substantial difference between the recently proposed atlas-based, template-based and segmentation-based methods.

Background Antibodies (ABs) against the 65-kDa isoform of the intracellular enzyme glutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) and other neurological conditions. The direct significance of anti-GAD65-ABs for epilepsy is unclear. However, in histological preparations from biopsies of resective epilepsy surgeries, predominantly cytotoxic T-lymphocytes were detected making close contacts to neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeutic interleukin-2 receptor Abs, such as basiliximab. Case presentation We report of a 25-year-old male patient with epilepsy since the age of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebrospinal fluid (CSF) and serum. Monthly, repetitive, intravenous cortisone pulse therapies that were initially administered for 6 months failed to improve his condition. Subsequent flow-cytometry analysis of CSF showed especially an increased fraction of activated HLA-DR+ CD8+ T-lymphocytes (fCD8+TL) when compared to controls. Thus, a second, intravenous cortisone pulse therapy with an additional basiliximab dose of 20 mg/month was started. After 3 months, the fCD8+TL in the CSF normalized; after 6 months, the psychological impulse-control deficits normalized; and after 11 months the patient was seizure free. However, 7 weeks later, seizures and, later on, psychological deficits recurred and fCD8+TL was once again present in the CSF. Flumazenil PET, magnetic resonance imaging-volumetry, and neuropsychological changes during therapy are described. Conclusion The correlation of the fCD8+TL in the CSF with clinical and paraclinical measures of disease activity combined with the unambiguous response to basiliximab strongly argues in favor of the putative pathogenic role fCD8+TL in anti-GAD65 LE. The clinical relapse at the end of the observation period might be due to the formation of human anti-drug ABs, a well-known complication of therapy with chimeric ABs.