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Objective. Conventionally, if two metabolic processes are of interest for image analysis, two separate, sequential positron emission tomography (PET) scans are performed. However, sequential PET scans cannot simultaneously display the metabolic targets. The concurrent study of two simultaneous PET scans could provide new insights into the causes of diseases. Approach. In this work, we propose a reconstruction algorithm for the simultaneous injection of a β + -emitter emitting only annihilation photons and a β + - γ -emitter emitting annihilation photons and an additional prompt γ -photon. As in previous works, the γ -photon is used to identify events originating from the β + - γ -emitter. However, due to e.g. attenuation and down-scatter, the γ -photon is often not detected and not all events can correctly be associated with the β + - γ -emitter as they are detected as double coincidences. In contrast to previous works, we estimate this number of double coincidences with origin in the β + - γ, emitter including the attenuation of the prompt γ, and incorporate this estimation in the forward-projection of the maximum likelihood expectation maximization algorithm. For evaluation, we simulate different scenarios with varying objects and attenuation maps. The nuclide 18F serves as β + -emitter, while 44Sc functions as β + - γ emitter. The performance of the algorithm is assessed by calculating the residual error of the β + - γ -emitter in the reconstructed β + -emitter image. Additionally, the intensity values in the simulated cylinders of the ground truth (GT) and the reconstructed images are compared. Main results. The remaining activity in the β + -emitter image varied from 0.4% to 3.7%. The absolute percentage difference between GT and reconstructed intensity for the pure β + emitter images was found to be between 3.0% and 7.4% for all cases. The absolute percentage difference between the GT and the reconstructed intensity for the β + - γ emitter images ranged from 8.7% to 10.4% for all simulated cases. Significance. These results demonstrate that our approach can reconstruct two separate images with a good quantitation accuracy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Morphological imaging using MRI is essential for brain tumour diagnostics. Dynamic susceptibility contrast (DSC) perfusion-weighted MRI (PWI), as well as amino acid PET, may provide additional information in ambiguous cases. Since PWI is often unavailable in patients referred for amino acid PET, we explored whether maps of relative cerebral blood volume (rCBV) in brain tumours can be extracted from the early phase of PET using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET). Procedure: Using a hybrid brain PET/MRI scanner, PWI and dynamic 18F-FET PET were performed in 33 patients with cerebral glioma and four patients with highly vascularized meningioma. The time interval from 0 to 2 min p.i. was selected to best reflect the blood pool phase in 18F-FET PET. For each patient, maps of MR-rCBV, early 18F-FET PET (0–2 min p.i.) and late 18F-FET PET (20–40 min p.i.) were generated and coregistered. Volumes of interest were placed on the tumour (VOI-TU) and normal-appearing brain (VOI-REF). The correlation between tumour-to-brain ratios (TBR) of the different parameters was analysed. In addition, three independent observers evaluated MR-rCBV and early 18F-FET maps (18F-FET-rCBV) for concordance in signal intensity, tumour extent and intratumoural distribution. Results: TBRs calculated from MR-rCBV and 18F-FET-rCBV showed a significant correlation (r = 0.89, p < 0.001), while there was no correlation between late 18F-FET PET and MR-rCBV (r = 0.24, p = 0.16) and 18F-FET-rCBV (r = 0.27, p = 0.11). Visual rating yielded widely agreeing findings or only minor differences between MR-rCBV maps and 18F-FET-rCBV maps in 93 % of the tumours (range of three independent raters 91–94%, kappa among raters 0.78–1.0). Conclusion: Early 18F-FET maps (0–2 min p.i.) in gliomas provide similar information to MR-rCBV maps and may be helpful when PWI is not possible or available. Further studies in gliomas are needed to evaluate whether 18F-FET-rCBV provides the same clinical information as MR-rCBV. [ABSTRACT FROM AUTHOR]

Introduction: The fMRI BOLD response to emotional stimuli highlighting the role of the medial prefrontal cortex (MPFC) has been thoroughly investigated. Recently, the relationship between emotion processing and GABA levels has been studied using MPFC proton magnetic resonance spectroscopy (1H-MRS). However, the role of GABAA receptors in the MPFC during emotion processing remains unexplored. Methods: Using [11C]flumazenil PET, we investigated the relationship between the binding potential of GABAA receptors and emotion processing as measured using simultaneous fMRI BOLD. We hypothesized a correlation between the percent signal change in the BOLD signal and the binding potential of GABAA receptors in the MPFC. In a combined simultaneous fMRI and [11C]flumazenil-PET study, we analyzed the data from 15 healthy subjects using visual emotional stimuli. Our task comprised two types of emotional processing: passive viewing and appraisal. Following the administration of a bolus plus infusion protocol, PET and fMRI data were simultaneously acquired in a hybrid 3 T MR-BrainPET. Results: We found a differential correlation of BOLD percent signal change with [11C]flumazenil binding potential in the MPFC. Specifically, [11C]flumazenil binding potential in the ventromedial prefrontal cortex (vMPFC) correlated with passive viewing of emotionally valenced pictures. In contrast, the [11C]flumazenil binding potential and the BOLD signal induced by picture appraisal did show a correlation in the paracingulate gyrus. Conclusion: Our data deliver first evidence for a relationship between MPFC GABAA receptors and emotion processing in the same region. Moreover, we observed that GABAA receptors appear to play different roles in emotion processing in the vMPFC (passive viewing) and paracingulate gyrus (appraisal). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The glutamate and γ‐aminobutyric acid neuroreceptor subtypes mGluR5 and GABAA are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non‐displaceable binding potential (BPND), and total distribution volume (VT) based on simultaneously acquired bolus‐infusion positron emission tomography (PET) and MR data. The pipeline was applied to [11C]ABP688‐PET/MR (13 healthy male non‐smokers, 26.6 ± 7.0 years) and [11C]Flumazenil‐PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as VT and BPND atlases of mGluR5 and GABAA, were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δABP = 3.0 ± 1.0% and δFMZ = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σABP = 4.0%–16.0%, σFMZ = 3.9%–9.5%). An evaluation of PET‐to‐PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [15O]H2O‐template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions. [ABSTRACT FROM AUTHOR]

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 (rs = 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. [ABSTRACT FROM AUTHOR]

Iterative image reconstruction is widely used in positron emission tomography. However, it is known to contribute to quantitation bias and is particularly pronounced during dynamic studies with 11C-labeled radiotracers where count rates become low towards the end of the acquisition. As the strength of the quantitation bias depends on the counts in the reconstructed frame, it can differ from frame to frame of the acquisition. This is especially relevant in the case of neuro-receptor studies with simultaneous PET/MR when a bolus-infusion protocol is applied to allow the comparison of pre- and post-task effects. Here, count dependent changes in quantitation bias may interfere with task changes. We evaluated the impact of different framing schemes on quantitation bias and its propagation into binding potential (BP) using a phantom decay study with 11C and 3D OP-OSEM. Further, we propose a framing scheme that keeps the true counts per frame constant over the acquisition time as constant framing schemes and conventional increasing framing schemes are unlikely to achieve stable bias values during the acquisition time range. For a constant framing scheme with 5 minutes frames, the BP bias was 7.13±2.01% (10.8% to 3.8%) compared to 5.63±2.85% (7.8% to 4.0%) for conventional increasing framing schemes. Using the proposed constant true counts framing scheme, a stabilization of the BP bias was achieved at 2.56±3.92% (3.5% to 1.7%). The change in BP bias was further studied by evaluating the linear slope during the acquisition time interval. The lowest slope values were observed in the constant true counts framing scheme. The constant true counts framing scheme was effective for BP bias stabilization at relevant activity and time ranges. The mean BP bias under these conditions was 2.56±3.92%, which represents the lower limit for the detection of changes in BP during equilibrium and is especially important in the case of cognitive tasks where the expected changes are low. [ABSTRACT FROM AUTHOR]

In hybrid magnetic resonance-positron emission tomography (MR-PET) studies with the Siemens 3T MR-BrainPET scanner an instantaneous reduction of the PET sensitivity was observed during execution of certain MR sequences. This interference was investigated in detail with custom-made as well as standard clinical MR sequences. The radio-frequency pulses, the switched gradient fields and the constant magnetic field were examined as the relevant parameters of the magnetic resonance imaging (MRI) system as well as the air temperature within the PET detectors. Our investigation comprised the analysis of the analog PET signals, the total count rates, the geometric distribution of the count rate reduction within the BrainPET detector as well as reconstructed images. The fast switching magnetic field gradients were identified to distort the analog PET detector signals. The measured count rate reduction was found to be less than 3%, but only up to 2% in the case of echo planar imaging sequences, as applied in functional MRI. For clinical sequences routinely used in hybrid MR-BrainPET measurements, a correction method has been designed, implemented, and evaluated . [ABSTRACT FROM AUTHOR]

Use of iterative algorithms to reconstruct three-dimensional (3-D) positron emission tomography (PET) data requires the computation of the system probability matrix. The pure geometrical contribution can easily be approximated by the length-of-intersection (LOI) between lines-of-response (LOR) and individual voxels. However, more accurate geometrical projectors are desirable. Therefore, we have developed a fast method for the analytical calculation of the 3-D shape and volume of volumes-of-intersection (VOI). This method provides an alternative robust projector with a uniformly continuous sampling of the image space. The enhanced calculation effort is facilitated by using several speedup techniques. Exploiting intrinsic symmetry relations and the sparseness of the system matrix allows to create an efficiently compressed matrix which can be precomputed and completely stored in memory. In addition, a new voxel addressing scheme has been implemented. This scheme avoids time-consuming symmetry transformations of voxel addresses by using an octant-wise symmetrically ordered field of voxels. The above methods have been applied for a fully 3-D, iterative reconstruction of 3-D sinograms recorded with a Siemens/CTI ECAT HR+ PET scanner. A comparison of the performance of the reconstruction using LOI weighting and VOI weighting is presented. [ABSTRACT FROM AUTHOR]

Objective. The pheno PET system is a plant dedicated positron emission tomography (PET) scanner consisting of fully digital photo multipliers with lutetium-yttrium oxyorthosilicate crystals and located inside a custom climate chamber. Here, we present the setup of pheno PET, its data processing and image reconstruction together with its performance. Approach. The performance characterization follows the national electrical manufacturers association (NEMA) standard for small animal PET systems with a number of adoptions due to the vertical oriented bore of a PET for plant sciences. In addition temperature stability and spatial resolution with a hot rod phantom are addressed. Main results. The spatial resolution for a 22 Na point source at a radial distance of 5 mm to the center of the field-of-view (FOV) is 1.45 mm, 0.82 mm and 1.88 mm with filtered back projection in radial, tangential and axial direction, respectively. A hot rod phantom with 18 F gives a spatial resolution of up to 1.6 mm. The peak noise-equivalent count rates are 550 kcps @ 35.08 MBq, 308 kcps @ 33 MBq and 45 kcps @ 40.60 MBq for the mouse, rat and monkey size scatter phantoms, respectively. The scatter fractions for these phantoms are 12.63%, 22.64% and 55.90%. We observe a peak sensitivity of up to 3.6% and a total sensitivity of up to S A , tot = 2.17%. For the NEMA image quality phantom we observe a uniformity of % STD = 4.22% with ordinary Poisson maximum likelihood expectation-maximization with 52 iterations. Here, recovery coefficients of 0.12, 0.64, 0.89, 0.93 and 0.91 for 1 mm, 2 mm, 3 mm, 4 mm and 5 mm rods are obtained and spill-over ratios of 0.08 and 0.14 for the water-filled and air-filled inserts, respectively. Significance. The pheno PET and its laboratory are now in routine operation for the administration of [ 11 C]CO 2 and non-invasive measurement of transport and allocation of 11 C-labelled photoassimilates in plants., (Creative Commons Attribution license.)

Introduction: The fMRI BOLD response to emotional stimuli highlighting the role of the medial prefrontal cortex (MPFC) has been thoroughly investigated. Recently, the relationship between emotion processing and GABA levels has been studied using MPFC proton magnetic resonance spectroscopy (1H-MRS). However, the role of GABAA receptors in the MPFC during emotion processing remains unexplored., Methods: Using [11C]flumazenil PET, we investigated the relationship between the binding potential of GABAA receptors and emotion processing as measured using simultaneous fMRI BOLD. We hypothesized a correlation between the percent signal change in the BOLD signal and the binding potential of GABAA receptors in the MPFC. In a combined simultaneous fMRI and [11C]flumazenil-PET study, we analyzed the data from 15 healthy subjects using visual emotional stimuli. Our task comprised two types of emotional processing: passive viewing and appraisal. Following the administration of a bolus plus infusion protocol, PET and fMRI data were simultaneously acquired in a hybrid 3 T MR-BrainPET., Results: We found a differential correlation of BOLD percent signal change with [11C]flumazenil binding potential in the MPFC. Specifically, [11C]flumazenil binding potential in the ventromedial prefrontal cortex (vMPFC) correlated with passive viewing of emotionally valenced pictures. In contrast, the [11C]flumazenil binding potential and the BOLD signal induced by picture appraisal did show a correlation in the paracingulate gyrus., Conclusion: Our data deliver first evidence for a relationship between MPFC GABAA receptors and emotion processing in the same region. Moreover, we observed that GABAA receptors appear to play different roles in emotion processing in the vMPFC (passive viewing) and paracingulate gyrus (appraisal)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Heinzel, Mauler, Herzog, Boers, Mottaghy, Langen, Scheins, Lerche, Neumaier, Northoff and Shah.)

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 176 Lu 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 176 Lu to 511 keV, the presented method for attenuation correction, based on the measurement of 176 Lu 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 68 Ge 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.