Glutamate Signaling in Patients With Parkinson Disease With REM Sleep Behavior Disorder.

BACKGROUND AND OBJECTIVES: Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotransmitter systems remain elusive. METHODS: Combining magnetic resonance (MR) spectroscopy and [11C]ABP688 PET on a PET/MR hybrid system, we simultaneously investigated two different mechanisms of glutamate signaling in patients with PD. Patients were grouped according to their RBD status in overnight video-polysomnography and compared with age-matched and sex-matched healthy control (HC) participants. Total volumes of distribution (VT) of [11C]ABP688 were estimated with metabolite-corrected plasma concentrations during steady-state conditions between 45 and 60 minutes of the scan following a bolus-infusion protocol. Glutamate, glutamine, and glutathione levels were investigated with single-voxel stimulated echo acquisition mode MR spectroscopy of the left basal ganglia. RESULTS: We measured globally elevated VT of [11C]ABP688 in 16 patients with PD and RBD compared with 17 patients without RBD and 15 HC participants (F(2,45) = 5.579, p = 0.007). Conversely, glutamatergic metabolites did not differ between groups and did not correlate with the regional VT of [11C]ABP688. VT of [11C]ABP688 correlated with the amount of REM sleep without atonia (F(1,42) = 5.600, p = 0.023) and with dopaminergic treatment response in patients with PD (F(1,30) = 5.823, p = 0.022). DISCUSSION: Our results suggest that patients with PD and RBD exhibit altered glutamatergic signaling indicated by higher VT of [11C]ABP688 despite unaffected glutamate levels. The imbalance of glutamate receptors and MR spectroscopy glutamate metabolite levels indicates a novel mechanism contributing to the heterogeneity of PD and warrants further investigation of drugs targeting mGluR5.

Impact of improved dead time correction on the quantification accuracy of a dedicated BrainPET scanner.

OBJECTIVE: Quantitative values derived from PET brain images are of high interest for neuroscientific applications. Insufficient DT correction (DTC) can lead to a systematic bias of the output parameters obtained by a detailed analysis of the time activity curves (TACs). The DTC method currently used for the Siemens 3T MR BrainPET insert is global, i.e., differences in DT losses between detector blocks are not considered, leading to inaccurate DTC and, consequently, to inaccurate measurements masked by a bias. However, following careful evaluation with phantom measurements, a new block-pairwise DTC method has demonstrated a higher degree of accuracy compared to the global DTC method. APPROACH: Differences between the global and the block-pairwise DTC method were studied in this work by applying several radioactive tracers. We evaluated the impact on [11C]ABP688, O-(2-[18F]fluoroethyl)-L-tyrosine (FET), and [15O]H2O TACs. RESULTS: For [11C]ABP688, a relevant bias of between -0.0034 and -0.0053 ml/ (cm3 • min) was found in all studied brain regions for the volume of distribution (VT) when using the current global DTC method. For [18F]FET-PET, differences of up to 10% were observed in the tumor-to-brain ratio (TBRmax), these differences depend on the radial distance of the maximum from the PET isocenter. For [15O]H2O, differences between +4% and -7% were observed in the GM region. Average biases of -4.58%, -3.2%, and -1.2% for the regional cerebral blood flow (CBF (K1)), the rate constant k2, and the volume of distribution VT were observed, respectively. Conversely, in the white matter region, average biases of -4.9%, -7.0%, and 3.8% were observed for CBF (K1), k2, and VT, respectively. CONCLUSION: The bias introduced by the global DTC method leads to an overestimation in the studied quantitative parameters for all applications compared to the block-pairwise method. SIGNIFICANCE: The observed differences between the two DTC methods are particularly relevant for research applications in neuroscientific studies as they affect the accuracy of quantitative Brain PET images.

Hybrid PET/MRI in Cerebral Glioma: Current Status and Perspectives.

Advanced MRI methods and PET using radiolabelled amino acids provide valuable information, in addition to conventional MR imaging, for brain tumour diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumour progression from treatment-related changes, and the early assessment of responses to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing, and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other, leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods, but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumours. PET is only required in equivocal situations, and the spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumours compared with a single modality. This review focuses on studies investigating the diagnostic value of combined amino acid PET and 'advanced' MRI in patients with cerebral gliomas. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterisation of newly diagnosed tumours. Few data are available concerning the delineation of tumour extent. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumour recurrence from treatment-related changes. Here, the PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of cerebral gliomas, for which hybrid PET/MRI offers optimal conditions.

Impact of framing scheme optimization and smoking status on binding potential analysis in dynamic PET with [11C]ABP688.

BACKGROUND: For positron emission tomography (PET) ligands, such as [11C]ABP688, to be able to provide more evidence about the glutamatergic hypothesis in schizophrenia (SZ), quantification bias during dynamic PET studies and its propagation into the estimated values of non-displaceable binding potential (BPND) must be addressed. This would enable more accurate quantification during bolus + infusion (BI) neuroreceptor studies and further our understanding of neurological diseases. Previous studies have shown BPND-related biases can often occur due to overestimated cerebellum activity (reference region). This work investigates whether an alternative framing scheme can minimize quantification biases propagated into BPND, whether confounders, such as smoking status, need to be controlled for during the study, and what the consequences for the data interpretation following analysis are. A group of healthy controls (HC) and a group of SZ patients (balanced and unbalanced number of smokers) were investigated with [11C]ABP688 and a BI protocol. Possible differences in BPND quantification as a function of smoking status were tested with constant 5 min ('Const 5 min') and constant true counts ('Const Trues') framing schemes. In order to find biomarkers for SZ, the differences in smoking effects were compared between groups. The normalized BPND and the balanced number of smokers and non-smokers for both framing schemes were evaluated. RESULTS: When applying F-tests to the 'Const 5 min' framing scheme, effect sizes (η2p) and brain regions which showed significant effects fluctuated considerably with F = 50.106 ± 54.948 (9.389 to 112.607), P-values 0.005 to < 0.001 and η2p = 0.514 ± 0.282 (0.238 to 0.801). Conversely, when the 'Const Trues' framing scheme was applied, the results showed much smaller fluctuations with F = 78.038 ± 8.975 (86.450 to 68.590), P < 0.001 for all conditions and η2p = 0.730 ± 0.017 (0.742 to 0.710), and regions with significant effects were more robustly reproduced. Further, differences, which would indicate false positive identifications between HC and SZ groups in five brain regions when using the 'Const 5 min' framing scheme, were not observed with the 'Const Trues' framing. CONCLUSIONS: Based on an [11C]ABP688 PET study in SZ patients, the results show that non-consistent BPND outcomes can be propagated by the framing scheme and that potential bias can be minimized using 'Const Trues' framing.

Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients.

Background: In glioma patients, multimodality therapy and recurrent tumor can lead to structural brain tissue damage characterized by pathologic findings in MR and PET imaging. However, little is known about the impact of different types of damage on the fiber architecture of the affected white matter. Patients and methods: This study included 121 pretreated patients (median age, 52 years; ECOG performance score, 0 in 48%, 1-2 in 51%) with histomolecularly characterized glioma (WHO grade IV glioblastoma, n=81; WHO grade III anaplastic astrocytoma, n=28; WHO grade III anaplastic oligodendroglioma, n=12), who had a resection, radiotherapy, alkylating chemotherapy, or combinations thereof. After a median follow-up time of 14 months (range, 1-214 months), anatomic MR and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET images were acquired on a 3T hybrid PET/MR scanner. Post-therapeutic findings comprised resection cavities, regions with contrast enhancement or increased FET uptake and T2/FLAIR hyperintensities. Local fiber density was determined from high angular-resolution diffusion-weighted imaging and advanced tractography methods. A cohort of 121 healthy subjects selected from the 1000BRAINS study matched for age, gender and education served as a control group. Results: Lesion types differed in both affected tissue volumes and relative fiber densities compared to control values (resection cavities: median volume 20.9 mL, fiber density 16% of controls; contrast-enhanced lesions: 7.9 mL, 43%; FET uptake areas: 30.3 mL, 49%; T2/FLAIR hyperintensities: 53.4 mL, 57%, p<0.001). In T2/FLAIR-hyperintense lesions caused by peritumoral edema due to recurrent glioma (n=27), relative fiber density was as low as in lesions associated with radiation-induced gliosis (n=13, 48% vs. 53%, p=0.17). In regions with pathologically increased FET uptake, local fiber density was inversely related (p=0.005) to the extent of uptake. Total fiber loss associated with contrast-enhanced lesions (p=0.006) and T2/FLAIR hyperintense lesions (p=0.013) had a significant impact on overall ECOG score. Conclusions: These results suggest that apart from resection cavities, reduction in local fiber density is greatest in contrast-enhancing recurrent tumors, but total fiber loss induced by edema or gliosis has an equal detrimental effect on the patients' performance status due to the larger volume affected.

A detector block-pairwise dead time correction method for improved quantitation with a dedicated BrainPET scanner.

'Objective. Dead time correction (DTC) is an important factor in ensuring accurate quantification in PET measurements. This is currently often achieved using a global DTC method, i.e., an average DTC factor is computed. For PET scanners designed to image dedicated organs, e.g., those used in brain imaging or positron emission mammography (PEM), a substantial amount of the administered radioactivity is located outside of the PET field-of-view (FOV). This activity contributes to the dead time (DT) of the scintillation detectors. Moreover, the count rates of the individual scintillation detectors are potentially very inhomogeneous due to the specific irradiation of each detector, especially for combined MR/PET systems, where radiation shields cannot be applied. Approach: We have developed a block-pairwise DTC method for our Siemens 3T MR BrainPET insert by extending a previously published method that uses the delayed random coincidence count rate to estimate the DT in the individual scans and planes (i.e., scintillation pixel rings). The method was validated in decay experiments using phantoms with a homogenous activity concentration and with and without out-of-FOV activity. Based on a three-compartment phantom, we compared the accuracy and noise properties of the block-pairwise DTC and the global DTC method.Main results. The currently used global DTC led to a substantial positive bias in regions with high activity; the block-pairwise DTC resulted in substantially less bias. The noise level for the block-pairwise DTC was comparable to the global DTC and image reconstructions without any DTC. Finally, we tested the block-pairwise DTC with a data set obtained from volunteer measurements using the mGluR5 (metabotropic glutamate receptor subtype 5) antagonist [11C]ABP688. When the relative differences in activity concentrations obtained with global DTC and block-pairwise DTC for the ACC and the cerebellum GM were compared, the ratios differed by a factor of up to 1.4 at the beginning-when the first injection is administered as a bolus with high radioactivity.Significance. In this work, global DTC was shown to have the potential to introduce quantification bias, while better quantitation accuracy was achieved with the presented block-pairwise DTC method. The method can be implemented in all systems that use the delayed window technique and is particulary expected to improve the quantiation accuracy of dedicated brain PET scanners due to their geometry.'

Two Decades of Brain Tumour Imaging with O-(2-[18F]fluoroethyl)-L-tyrosine PET: The Forschungszentrum Jülich Experience.

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Static FET PET radiomics for the differentiation of treatment-related changes from glioma progression.

PURPOSE: To investigate the potential of radiomics applied to static clinical PET data using the tracer O-(2-[18F]fluoroethyl)-L-tyrosine (FET) to differentiate treatment-related changes (TRC) from tumor progression (TP) in patients with gliomas. PATIENTS AND METHODS: One hundred fifty-one (151) patients with histologically confirmed gliomas and post-therapeutic progressive MRI findings according to the response assessment in neuro-oncology criteria underwent a dynamic amino acid PET scan using the tracer O-(2-[18F]fluoroethyl)-L-tyrosine (FET). Thereof, 124 patients were investigated on a stand-alone PET scanner (data used for model development and validation), and 27 patients on a hybrid PET/MRI scanner (data used for model testing). Mean and maximum tumor to brain ratios (TBRmean, TBRmax) were calculated using the PET data from 20 to 40 min after tracer injection. Logistic regression models were evaluated for the FET PET parameters TBRmean, TBRmax, and for radiomics features of the tumor areas as well as combinations thereof to differentiate between TP and TRC. The best performing models in the validation dataset were finally applied to the test dataset. The diagnostic performance was assessed by receiver operating characteristic analysis. RESULTS: Thirty-seven patients (25%) were diagnosed with TRC, and 114 (75%) with TP. The logistic regression model comprising the conventional FET PET parameters TBRmean and TBRmax resulted in an AUC of 0.78 in both the validation (sensitivity, 64%; specificity, 80%) and the test dataset (sensitivity, 64%; specificity, 80%). The model combining the conventional FET PET parameters and two radiomics features yielded the best diagnostic performance in the validation dataset (AUC, 0.92; sensitivity, 91%; specificity, 80%) and demonstrated its generalizability in the independent test dataset (AUC, 0.85; sensitivity, 81%; specificity, 70%). CONCLUSION: The developed radiomics classifier allows the differentiation between TRC and TP in pretreated gliomas based on routinely acquired static FET PET scans with a high diagnostic accuracy.

A software-based approach for calculating spatially resolved radiation exposure for structural radiation protection in nuclear medical imaging.

The objective of the work described is the development of a software tool to provide the calculation routines for structural radiation protection from positron and gamma emitters, for example,18F. The calculation of the generated local annual dose in the vicinity of these radioactive sources supports the engineering of structural measures necessary to meet regulatory guidelines. In addition to accuracy and precision, a visual and intuitive presentation of the calculation results enables fast evaluation. Finally, the calculated results are presented in a contour plot for design, evaluation, and documentation purposes. A python program was used to provide the calculation routines for structural radiation protection. For simplicity, the radiating sources can be considered as point sources. The attenuation of structural elements can be specified or, in the case of lead, calculated by virtue of its thickness. The calculated attenuation for the lead shielding is always slightly underestimated, which leads to a marginally higher calculated local dose rate than would be physically present. With the conservatively determined value, the structural radiation protection can be optimised in accordance with the general rule of as low as reasonably achievable. The pointwise comparison between the software results and the standard procedure for calculating the dose of points in space leads to similar values. In comparison with the general approach of calculating single representative points in the radiation protection area, the visual and intuitive presentation of the results supports the design and documentation of the measures required for structural radiation protection. In the present version of the software, the local dose rate and local annual dose are overestimated by a maximum of 4.5% in the case of lead shields. The proposed software, termed RadSoft, was successfully used to develop the structural radiation protection of a controlled area for hybrid magnetic resonance - positron emission tomography imaging, with the focus herein being on the requirements for PET.

Case Report: Disruption of Resting-State Networks and Cognitive Deficits After Whole Brain Irradiation for Singular Brain Metastasis.

Introduction: Long-term survivors of whole brain radiation (WBRT) are at significant risk for developing cognitive deficits, but knowledge about the underlying pathophysiological mechanisms is limited. Therefore, we here report a rare case with a singular brain metastasis treated by resection and WBRT that survived for more than 10 years where we investigated the integrity of brain networks using resting-state functional MRI. Methods: A female patient with a left frontal non-small cell lung cancer (NSCLC) brain metastasis had resection and postoperative WBRT (30.0 in 3.0 Gy fractions) and stayed free from brain metastasis recurrence for a follow-up period of 11 years. Structural magnetic resonance imaging (MRI) and amino acid [O-(2-[18F]fluoroethyl)-L-tyrosine] positron emission tomography (FET PET) were repeatedly acquired. At the last follow up, neurocognitive functions and resting-state functional connectivity (RSFC) using resting-state fMRI were assessed. Within-network and inter-network connectivity of seven resting-state networks were computed from a connectivity matrix. All measures were compared to a matched group of 10 female healthy subjects. Results: At the 11-year follow-up, T2/FLAIR MR images of the patient showed extended regions of hyper-intensities covering mainly the white mater of the bilateral dorsal frontal and parietal lobes while sparing most of the temporal lobes. Compared to the healthy subjects, the patient performed significantly worse in all cognitive domains that included executive functions, attention and processing speed, while verbal working memory, verbal episodic memory, and visual working memory were left mostly unaffected. The connectivity matrix showed a heavily disturbed pattern with a widely distributed, scattered loss of RSFC. The within-network RSFC revealed a significant loss of connectivity within all seven networks where the dorsal attention and fronto-parietal control networks were affected most severely. The inter-network RSFC was significantly reduced for the visual, somato-motor, and dorsal and ventral attention networks. Conclusion: As demonstrated here in a patient with a metastatic NSCLC and long-term survival, WBRT may lead to extended white matter damage and cause severe disruption of the RSFC in multiple resting state networks. In consequence, executive functioning which is assumed to depend on the interaction of several networks may be severely impaired following WBRT apart from the well-recognized deficits in memory function.

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).

FET PET Radiomics for Differentiating Pseudoprogression from Early Tumor Progression in Glioma Patients Post-Chemoradiation.

Currently, a reliable diagnostic test for differentiating pseudoprogression from early tumor progression is lacking. We explored the potential of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) radiomics for this clinically important task. Thirty-four patients (isocitrate dehydrogenase (IDH)-wildtype glioblastoma, 94%) with progressive magnetic resonance imaging (MRI) changes according to the Response Assessment in Neuro-Oncology (RANO) criteria within the first 12 weeks after completing temozolomide chemoradiation underwent a dynamic FET PET scan. Static and dynamic FET PET parameters were calculated. For radiomics analysis, the number of datasets was increased to 102 using data augmentation. After randomly assigning patients to a training and test dataset, 944 features were calculated on unfiltered and filtered images. The number of features for model generation was limited to four to avoid data overfitting. Eighteen patients were diagnosed with early tumor progression, and 16 patients had pseudoprogression. The FET PET radiomics model correctly diagnosed pseudoprogression in all test cohort patients (sensitivity, 100%; negative predictive value, 100%). In contrast, the diagnostic performance of the best FET PET parameter (TBRmax) was lower (sensitivity, 81%; negative predictive value, 80%). The results suggest that FET PET radiomics helps diagnose patients with pseudoprogression with a high diagnostic performance. Given the clinical significance, further studies are warranted.

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.

Scatter Correction Based on GPU-Accelerated Full Monte Carlo Simulation for Brain PET/MRI.

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.

Predicting IDH genotype in gliomas using FET PET radiomics.

Mutations in the isocitrate dehydrogenase (IDH mut) gene have gained paramount importance for the prognosis of glioma patients. To date, reliable techniques for a preoperative evaluation of IDH genotype remain scarce. Therefore, we investigated the potential of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET radiomics using textural features combined with static and dynamic parameters of FET uptake for noninvasive prediction of IDH genotype. Prior to surgery, 84 patients with newly diagnosed and untreated gliomas underwent FET PET using a standard scanner (15 of 56 patients with IDH mut) or a dedicated high-resolution hybrid PET/MR scanner (11 of 28 patients with IDH mut). Static, dynamic and textural parameters of FET uptake in the tumor area were evaluated. Diagnostic accuracy of the parameters was evaluated using the neuropathological result as reference. Additionally, FET PET and textural parameters were combined to further increase the diagnostic accuracy. The resulting models were validated using cross-validation. Independent of scanner type, the combination of standard PET parameters with textural features increased significantly diagnostic accuracy. The highest diagnostic accuracy of 93% for prediction of IDH genotype was achieved with the hybrid PET/MR scanner. Our findings suggest that the combination of conventional FET PET parameters with textural features provides important diagnostic information for the non-invasive prediction of the IDH genotype.

A Digital Preclinical PET/MRI Insert and Initial Results.

Combining Positron Emission Tomography (PET) with Magnetic Resonance Imaging (MRI) results in a promising hybrid molecular imaging modality as it unifies the high sensitivity of PET for molecular and cellular processes with the functional and anatomical information from MRI. Digital Silicon Photomultipliers (dSiPMs) are the digital evolution in scintillation light detector technology and promise high PET SNR. DSiPMs from Philips Digital Photon Counting (PDPC) were used to develop a preclinical PET/RF gantry with 1-mm scintillation crystal pitch as an insert for clinical MRI scanners. With three exchangeable RF coils, the hybrid field of view has a maximum size of 160 mm × 96.6 mm (transaxial × axial). 0.1 ppm volume-root-mean-square B 0-homogeneity is kept within a spherical diameter of 96 mm (automatic volume shimming). Depending on the coil, MRI SNR is decreased by 13% or 5% by the PET system. PET count rates, energy resolution of 12.6% FWHM, and spatial resolution of 0.73 mm (3) (isometric volume resolution at isocenter) are not affected by applied MRI sequences. PET time resolution of 565 ps (FWHM) degraded by 6 ps during an EPI sequence. Timing-optimized settings yielded 260 ps time resolution. PET and MR images of a hot-rod phantom show no visible differences when the other modality was in operation and both resolve 0.8-mm rods. Versatility of the insert is shown by successfully combining multi-nuclei MRI ((1)H/(19)F) with simultaneously measured PET ((18)F-FDG). A longitudinal study of a tumor-bearing mouse verifies the operability, stability, and in vivo capabilities of the system. Cardiac- and respiratory-gated PET/MRI motion-capturing (CINE) images of the mouse heart demonstrate the advantage of simultaneous acquisition for temporal and spatial image registration.