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Modeling short-term psychotic states with subanaesthetic doses of ketamine provides substantial experimental evidence in support of the glutamate hypothesis of schizophrenia. Ketamine exerts its pharmacological effects both directly via interactions with glutamate receptors and indirectly by stimulating presynaptic release of endogenous serotonin (5-HT). The aim of this feasibility study was to examine whether acute ketamine-induced 5-HT release interferes with the binding of the 5-HT2A receptor (5-HT2AR) radioligand [18F]altanserin and positron emission tomography (PET). Two subjects treated with ketamine and one subject treated with placebo underwent [18F]altanserin PET at distribution equilibrium conditions. Robust physiological, psychopathological and cognitive effects were present at ketamine plasma concentrations exceeding 100 µg/l during >70 min. Notwithstanding, we observed stable radioligand binding (changes ±95% CI of −1.0 ± 1.6% and +4.1 ± 1.8% versus −1.2 ± 2.6%) in large cortical regions presenting high basal uptake of both, [18F]altanserin and ketamine. Marginal decreases of 4% of radioligand binding were observed in the frontal lobe, and 8% in a posteriorily specified frontomesial subregion. This finding is not compatible with a specific radioligand displacement from 5-HT2AR which should occur proportionally throughout the whole brain. Instead, the spatial pattern of these minor reductions was congruent with ketamine-induced increases in cerebral blood flow observed in a previous study using [15O]butanol PET. This may caused by accelerated clearance of unspecifically bound [18F]altanserin from cerebral tissue with increased perfusion. In conclusion, this study suggests that [18F]altanserin PET is not sensitive to acute neurotransmitter fluctuations under ketamine. Advantageously, the stability of [18F]altanserin PET towards acute influences is a prerequisite for its future use to detect sub-acute and chronic effects of ketamine. [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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Issa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR 5 and GABA A 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 (BP ND ), and total distribution volume (V T ) based on simultaneously acquired bolus-infusion positron emission tomography (PET) and MR data. The pipeline was applied to [ 11 C]ABP688-PET/MR (13 healthy male non-smokers, 26.6 ± 7.0 years) and [ 11 C]Flumazenil-PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as V T and BP ND atlases of mGluR 5 and GABA A , 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 δ ABP  = 3.0 ± 1.0% and δ FMZ  = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σ ABP  = 4.0%-16.0%, σ FMZ  = 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 [ 15 O]H 2 O-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., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

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 [ 11 C]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 (BP ND ) 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 BP ND 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 BP ND changes. There was a significant ΔBP ND 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 ΔBP ND 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., (© 2021. The Author(s).)

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., (© 2018 Wiley Periodicals, Inc.)

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., Competing Interests: The authors have declared that no competing interests exist.

The symbiosis of neuronal activities and glucose energy metabolism is reflected in the generation of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) signals. However, their association with the balance between neuronal excitation and inhibition (E/I-B), which is closely related to the activities of glutamate and γ-aminobutyric acid (GABA) and the receptor availability (RA) of GABA A and mGluR5, remains unexplored. This research investigates these associations during the resting state (RS) condition using simultaneously recorded PET/MR/EEG (trimodal) data. The trimodal data were acquired from three studies using different radio-tracers such as, [ 11 C]ABP688 (ABP) (N = 9), [ 11 C]Flumazenil (FMZ) (N = 10) and 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) (N = 10) targeted to study the mGluR5, GABA A receptors and glucose metabolism respectively. Glucose metabolism and neuroreceptor binding availability (non-displaceable binding potential (BP ND )) of GABA A and mGluR5 were found to be significantly higher and closely linked within core resting-state networks (RSNs). The neuronal generators of EEG microstates and the fMRI measures were most tightly associated with the BP ND of GABA A relative to mGluR5 BP ND and the glucose metabolism, emphasising a predominance of inhibitory processes within in the core RSNs at rest. Changes in the neuroreceptors leading to an altered coupling with glucose metabolism may render the RSNs vulnerable to psychiatric conditions. The paradigm employed here will likely help identify the precise neurobiological mechanisms behind these alterations in fMRI functional connectivity and EEG oscillations, potentially benefitting individualised healthcare treatment measures.

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.

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.

Trimodal simultaneous acquisition of positron emission tomography (PET), magnetic resonance imaging (MRI), and electroencephalography (EEG) has become feasible due to the development of hybrid PET-MR scanners. To capture the temporal dynamics of neuronal activation on a millisecond-by-millisecond basis, an EEG system is appended to the quantitative high resolution PET-MR imaging modality already established in our institute. One of the major difficulties associated with the development of simultaneous trimodal acquisition is that the components traditionally used in each modality can cause interferences in its counterpart. The mutual interferences of MRI components and PET components on PET and MR images, and the influence of EEG electrodes on functional MRI images have been studied and reported on. Building on this, this study aims to investigate the influence of the EEG cap on the quality and quantification of PET images acquired during simultaneous PET-MR measurements. A preliminary transmission scan study on the ECAT HR+ scanner, using an Iida phantom, showed visible attenuation effect due to the EEG cap. The BrainPET-MR emission images of the Iida phantom with [18F]Fluordeoxyglucose, as well as of human subjects with the EEG cap, did not show significant effects of the EEG cap, even though the applied attenuation correction did not take into account the attenuation of the EEG cap itself.

Introduction: 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 [ 18 F]-Fluorodeoxyglucose-PET/MRI neurodegenerative dementing disorders, which are known to exhibit reduced levels of glucose metabolism in certain brain regions., Methods: 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., Results: 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., Conclusion: 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.

Objective: 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., Methods: 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., Results: 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)., Conclusion: 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., Key Points: • 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.

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.

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.

Multi-modal MR-PET-EEG data acquisition in simultaneous mode confers a number of advantages at 3 T and 9.4 T. The three modalities complement each other well; structural-functional imaging being the domain of MRI, molecular imaging with specific tracers is the strength of PET, and EEG provides a temporal dimension where the other two modalities are weak. The utility of hybrid MR-PET at 3 T in a clinical setting is presented and critically discussed. The potential problems and the putative gains to be accrued from hybrid imaging at 9.4 T, with examples from the human brain, are outlined. Steps on the road to 9.4 T multi-modal MR-PET-EEG are also illustrated. From an MR perspective, the potential for ultra-high resolution structural imaging is discussed and example images of the cerebellum with an isotropic resolution of 320 μm are presented, setting the stage for hybrid imaging at ultra-high field. Further, metabolic imaging is discussed and high-resolution images of the sodium distribution are presented. Examples of tumour imaging on a 3 T MR-PET system are presented and discussed. Finally, the perspectives for multi-modal imaging are discussed based on two on-going studies, the first comparing MR and PET methods for the measurement of perfusion and the second which looks at tumour delineation based on MRI contrasts but the knowledge of tumour extent is based on simultaneously acquired PET data., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Positron Emission Tomography (PET) images are prone to motion artefacts due to the long acquisition time of PET measurements. Recently, simultaneous magnetic resonance imaging (MRI) and PET have become available in the first generation of Hybrid MR-PET scanners. In this work, the elimination of artefacts due to head motion in PET neuroimages is achieved by a new approach utilising MR-based motion tracking in combination with PET list mode data motion correction for simultaneous MR-PET acquisitions. The method comprises accurate MR-based motion measurements, an intra-frame motion minimising and reconstruction time reducing temporal framing algorithm, and a list mode based PET reconstruction which utilises the Ordinary Poisson Algorithm and avoids axial and transaxial compression. Compared to images uncorrected for motion, an increased image quality is shown in phantom as well as in vivo images. In vivo motion corrected images show an evident increase of contrast at the basal ganglia and a good visibility of uptake in tiny structures such as superior colliculi.

Unlabelled: PET studies of cerebral neuroreceptors are often recorded over periods ranging from 1 to 2 h, and head movements during the studies not only lead to blurred images but also may seriously disturb the kinetic analysis. We report the effect of motion on parametric images of the distribution volume ratio (DVR), as well as possible improvements if the dynamic PET data are corrected for head movements., Methods: The study was performed with the 5-hydroxytryptamine 2A receptor ligand (18)F-altanserin. During PET scanning, which was performed in list mode for 1 h, the position of the head was monitored by an infrared motion-tracking system. The list mode data were sorted into time frames of between 10 s and 2 min. Motion was corrected using the multiple-acquisition-frame (MAF) approach, which calculates individual attenuation files for each emission frame and its corresponding head position to avoid misalignment of transmission and emission data. After reconstruction of attenuation-corrected emission frames, each image frame was realigned to match the head position of the first frame of the emission scan. The resulting motion-corrected dynamic images were evaluated using the noninvasive Logan plot to obtain parametric images of DVR., Results: DVR images of motion-affected (18)F-altanserin scans showed artifacts whose extent depended on the amount of movement. The artifacts were mainly at the border between gray matter and white matter and at the outer border of gray matter. They were seen as discontinuities and small spots whose values exceeded the expected DVR values or were even negative and that disappeared when motion correction was applied. These effects in human data were also seen on simulated (18)F-altanserin images that contained no statistical noise., Conclusion: Whereas the native PET images looked just blurred if the patient moved during the PET scan, parametric images of the Logan DVR, which are calculated by pixelwise linear regression, contained severe discontinuities primarily at the cortical edge. MAF-based motion correction was able to avoid these errors.