A Novel J-Shape Antenna Array for Simultaneous MR-PET or MR-SPECT Imaging.

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 (  âˆ¼ 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.

A Linearized Fit Model for Robust Shape Parameterization of FET-PET TACs.

The kinetic analysis of [Formula: see text]-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 [Formula: see text]-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 ≈ 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).

mGluR5 receptor availability is associated with lower levels of negative symptoms and better cognition in male patients with chronic schizophrenia.

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.

Influence of Dexamethasone on O-(2-[18F]-Fluoroethyl)-L-Tyrosine Uptake in the Human Brain and Quantification of Tumor Uptake.

PURPOSE: O-(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. RESULTS: SUVbrain 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. CONCLUSION: Dexamethasone 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.

Comparison of O-(2-18F-Fluoroethyl)-L-Tyrosine Positron Emission Tomography and Perfusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Patients with Progressive and Recurrent Glioma: A Hybrid Positron Emission Tomography/Magnetic Resonance Study.

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.

TRIMAGE: A dedicated trimodality (PET/MR/EEG) imaging tool for schizophrenia.

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.

Spatial Relationship of Glioma Volume Derived from 18F-FET PET and Volumetric MR Spectroscopy Imaging: A Hybrid PET/MRI Study.

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.

O-(2-[18F]fluoroethyl)-L-tyrosine PET in gliomas: influence of data processing in different centres.

BACKGROUND: PET using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) is an established method for brain tumour diagnostics, but data processing varies in different centres. This study analyses the influence of methodological differences between two centres for tumour characterization with 18F-FET PET using the same PET scanner. Methodological differences between centres A and B in the evaluation of 18F-FET PET data were identified for (1) framing of PET dynamic data, (2) data reconstruction, (3) cut-off values for tumour delineation to determine tumour-to-brain ratios (TBR) and tumour volume (Tvol) and (4) ROI definition to determine time activity curves (TACs) in the tumour. Based on the 18F-FET PET data of 40 patients with untreated cerebral gliomas (20 WHO grade II, 10 WHO grade III, 10 WHO grade IV), the effect of different data processing in the two centres on TBRmean, TBRmax, Tvol, time-to-peak (TTP) and slope of the TAC was compared. Further, the effect on tumour grading was evaluated by ROC analysis. RESULTS: Significant differences between centres A and B were found especially for TBRmax (2.84 ± 0.99 versus 3.34 ± 1.13; p < 0.001), Tvol (1.14 ± 1.28 versus 1.51 ± 1.44; p < 0.001) and TTP (22.4 ± 8.3 min versus 30.8 ± 6.3 min; p < 0.001) and minor differences for TBRmean and slope. Tumour grading was not influenced by different data processing. CONCLUSIONS: Variable data processing of 18F-FET PET in different centres leads to significant differences especially for TBRmax and Tvol. A standardization of data processing and evaluation is needed to make 18F-FET PET comparable between different centres.

Comparison of 18F-FET PET and perfusion-weighted MRI for glioma grading: a hybrid PET/MR study.

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

The use of O-(2-18F-fluoroethyl)-L-tyrosine PET in the diagnosis of gliomas located in the brainstem and spinal cord.

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.

Simulation-based partial volume correction for dopaminergic PET imaging: Impact of segmentation accuracy.

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 (SPML). 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 (Ki) 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 SPML (PUT < 30%) and highest for FSL (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 Ki 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 Ki 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 Ki 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.

Comparison of cerebral blood flow acquired by simultaneous [15O]water positron emission tomography and arterial spin labeling magnetic resonance imaging.

Until recently, no direct comparison between [(15)O]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 [(15)O]water and ASL. A 3T MR-BrainPET scanner was used for the simultaneous acquisition of pseudo-continuous ASL (pCASL) magnetic resonance imaging (MRI) and [(15)O]water PET. Quantitative CBF values were compared in 10 young healthy male volunteers at baseline conditions. A statistically significant (P<0.05) correlation was observed between the two modalities; the whole-brain CBF values determined with PET and pCASL were 43.3±6.1 mL and 51.9±7.1 mL per 100 g per minute, respectively. The gray/white matter (GM/WM) ratio of CBF was 3.0 for PET and 3.4 for pCASL. A paired t-test revealed differences in regional CBF between ASL and PET with higher ASL-CBF than PET-CBF values in cortical areas. Using an integrated, hybrid MR-PET a direct simultaneous comparison between ASL and [(15)O]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.

Effects of magnetic fields of up to 9.4 T on resolution and contrast of PET images as measured with an MR-BrainPET.

Simultaneous, hybrid MR-PET is expected to improve PET image resolution in the plane perpendicular to the static magnetic field of the scanner. Previous papers have reported this either by simulation or experiment with simple sources and detector arrangements. Here, we extend those studies using a realistic brain phantom in a recently installed MR-PET system comprising a 9.4 T MRI-scanner and an APD-based BrainPET insert in the magnet bore. Point and line sources and a 3D brain phantom were filled with 18F (low-energy positron emitter), 68Ga (medium energy positron emitter) or 120I, a non-standard positron emitter (high positron energies of up to 4.6 MeV). Using the BrainPET insert, emission scans of the phantoms were recorded at different positions inside and outside the magnet bore such that the magnetic field was 0 T, 3 T, 7 T or 9.4 T. Brain phantom images, with the 'grey matter' compartment filled with 18F, showed no obvious resolution improvement with increasing field. This is confirmed by practically unchanged transaxial FWHM and 'grey/white matter' ratio values between at 0T and 9.4T. Field-dependent improvements in the resolution and contrast of transaxial PET images were clearly evident when the brain phantom was filled with 68Ga or 120I. The grey/white matter ratio increased by 7.3% and 16.3%, respectively. The greater reduction of the FWTM compared to FWHM in 68Ga or 120I line-spread images was in agreement with the improved contrast of 68Ga or 120I images. Notwithstanding elongations seen in the z-direction of 68Ga or 120I point source images acquired in foam, brain phantom images show no comparable extension. Our experimental study confirms that integrated MR-PET delivers improved PET image resolution and contrast for medium- and high-energy positron emitters even though the positron range is reduced only in directions perpendicular to the magnetic field.

Multimodal imaging utilising integrated MR-PET for human brain tumour assessment.

OBJECTIVES: The development of integrated magnetic resonance (MR)-positron emission tomography (PET) hybrid imaging opens up new horizons for imaging in neuro-oncology. In cerebral gliomas the definition of tumour extent may be difficult to ascertain using standard MR imaging (MRI) only. The differentiation of post-therapeutic scar tissue, tumour rests and tumour recurrence is challenging. The relationship to structures such as the pyramidal tract to the tumour mass influences the therapeutic neurosurgical approach. METHODS: The diagnostic information may be enriched by sophisticated MR techniques such as diffusion tensor imaging (DTI), multiple-volume proton MR spectroscopic imaging (MRSI) and functional MRI (fMRI). Metabolic imaging with PET, especially using amino acid tracers such as (18)F-fluoroethyl-L-tyrosine (FET) or (11)C-L-methionine (MET) will indicate tumour extent and response to treatment. RESULTS: The new technologies comprising MR-PET hybrid systems have the advantage of providing comprehensive answers by a one-stop-job of 40-50 min. The combined approach provides data of different modalities using the same iso-centre, resulting in optimal spatial and temporal realignment. All images are acquired exactly under the same physiological conditions. CONCLUSIONS: We describe the imaging protocol in detail and provide patient examples for the different imaging modalities such as FET-PET, standard structural imaging (T1-weighted, T2-weighted, T1-weighted contrast agent enhanced), DTI, MRSI and fMRI. KEY POINTS: Hybrid MR-PET opens up new horizons in neuroimaging. Hybrid MR-PET allows brain tumour assessment in one stop. Hybrid MR-PET allows simultaneous acquisition of structural, functional and molecular images.