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Dopamine transporter (DAT) imaging is an important adjunct in the diagnostic workup of patients with Parkinsonism. 18F-FE-PE2I is a suitable PET radioligand for DAT quantification and imaging with good pharmacokinetics. The aim of this study was to determine a clinical optimal simplified reference tissue-based image acquisition protocol and to compare the discriminatory value and effect size for 18F-FE-PE2I to that for 123I-FP-CIT scan currently used in clinical practice. Nine patients with early Parkinson’s disease (PD, 64.3 ± 6.8 years, 3M), who had previously undergone a 123I-FP-CIT scan as part of their diagnostic workup, and 34 healthy volunteers (HV, 47.7 ± 16.8 years, 13M) underwent a 60-min dynamic 18F-FE-PE2I PET-MR scan on a GE Signa 3T PET-MR. Based on dynamic data and MR-based VOI delineation, BPND, semi-quantitative uptake ratio and SUVR[t1–t2] images were calculated using either occipital cortex or cerebellum as reference region. For start-and-end time of the SUVR interval, three time frames [t1–t2] were investigated: [15–40] min, [40–60] min, and [50–60] min postinjection. Data for putamen (PUT) and caudate nucleus-putamen ratio (CPR) were compared in terms of quantification bias versus BPND and discriminative power. Using occipital cortex as reference region resulted in smaller bias of SUVR with respect to BPND + 1 and higher correlation between SUVR and BPND + 1 compared with using cerebellum, irrespective of SUVR [t1–t2] interval. Smallest bias was observed with the [15–40]-min time window, in accordance with previous literature. The correlation between BPND + 1 and SUVR was slightly better for the late time windows. Discriminant analysis between PD and HV using both PUT and CPR SUVRs showed an accuracy of ≥ 90%, for both reference regions and all studied time windows. Semi-quantitative 123I-FP-CIT and 18F-FE-PE2I values and relative decrease in the striatum for patients were highly correlated, with a higher effect size for 18F-FE-PE2I for PUT and CPR SUVR. 18F-FE-PE2I is a suitable radioligand for in vivo DAT imaging with high discriminative power between early PD and healthy controls. Whereas a [15–40]-min window has lowest bias with respect to BPND, a [50–60]-min time window at pseudoequilibrium can be advocated in terms of clinical feasibility with optimal discriminative power. The occipital cortex may be slightly preferable as reference region because of the higher time stability, stronger correlation of SUVR with BPND + 1, and lower bias. Moreover, the data suggest that the diagnostic accuracy of a 10-min static 18F-FE-PE2I scan is non-inferior compared with 123I-FP-CIT scan used in standard clinical practice.

RATIONALE: 11C-UCB-J binds to synaptic vesicle glycoprotein 2A, a protein ubiquitously expressed in presynaptic nerve terminals, and can therefore serve as in vivo proxy of synaptic density. There are discrepancies in postmortem data on stability of synaptic density with healthy aging. In this study, healthy aging and sex as potential modifiers of 11C-UCB-J binding were investigated in healthy volunteers over 7 adult decades, assuming that the number of SV2A vesicles per synapse is not influenced by age or sex. METHODS: 80 healthy volunteers underwent 11C-UCB-J PET and structural T1 and T2 MR imaging. Grey matter changes with aging were firstly evaluated by voxel-based morphometry (VBM). Parametric 11C-UCB-J standardized uptake value ratio (SUVR) images were calculated using the centrum semiovale as reference tissue. To correct for atrophy-related partial volume effects, a region-based voxel-wise type partial volume correction (PVC) was applied in FreeSurfer. The correlations of 11C-UCB-J binding with age and with sex were investigated by a voxel-based and volume-of-interest (VOI)-based approach, and with and without PVC to assess the contribution of underlying morphology changes upon aging. RESULTS: Full results were available for 78 participants (19-85y; 33 M/45 F). VBM grey matter concentration changes with aging were most predominant in the perisylvian and frontal regions. After PVC, no significantly decreased 11C-UCB-J SUVR with aging was found in the voxel-based analysis, whereas the VOI-based analysis showed a slight decrease in the caudate nucleus (-1.7% decrease per decade, p= 0.0025) only. There was no association between sex and 11C-UCB-J SUVR, nor an interaction between aging and sex for this parameter. CONCLUSION: In vivo, PET using 11C-UCB-J does not support a cortical decrease of synaptic density with aging, whereas subcortically a small effect with aging in the caudate nucleus was observed. In addition, no association between synaptic density and sex was detected, which allows pooling of datasets of both sexes. ispartof: NEUROIMAGE vol:232 ispartof: location:United States status: published

Human ageing is associated with a regional reduction in cerebral neuronal activity as assessed by numerous studies on brain glucose metabolism and perfusion, grey matter (GM) density and white matter (WM) integrity. As glucose metabolism may impact energetics to maintain myelin integrity, but changes in functional connectivity may also alter regional metabolism, we conducted a cross-sectional simultaneous FDG PET/MR study in a large cohort of healthy volunteers with a wide age range, to directly assess the underlying associations between reduced glucose metabolism, GM atrophy and decreased WM integrity in a single ageing cohort. In 94 healthy subjects between 19.9 and 82.5 years (mean 50.1 ± 17.1; 47 M/47F, MMSE ≥ 28), simultaneous FDG-PET, structural MR and diffusion tensor imaging (DTI) were performed. Voxel-wise associations between age and grey matter (GM) density, RBV partial-volume corrected (PVC) glucose metabolism, white matter (WM) fractional anisotropy (FA) and mean diffusivity (MD), and age were assessed. Clusters representing changes in glucose metabolism correlating significantly with ageing were used as seed regions for tractography. Both linear and quadratic ageing models were investigated. An expected age-related reduction in GM density was observed bilaterally in the frontal, lateral and medial temporal cortex, striatum and cerebellum. After PVC, relative FDG uptake was negatively correlated with age in the inferior and midfrontal, cingulate and parietal cortex and subcortical regions, bilaterally. FA decreased with age throughout the entire brain WM. Four white matter tracts were identified connecting brain regions with declining glucose metabolism with age. Within these, relative FDG uptake in both origin and target clusters correlated positively with FA (0.32 ≤ r ≤ 0.71) and negatively with MD (− 0.75 ≤ r ≤ − 0.41). After appropriate PVC, we demonstrated that regional cerebral glucose metabolic declines with age and that these changes are related to microstructural changes in the interconnecting WM tracts. The temporal course and potential causality between ageing effects on glucose metabolism and WM integrity should be further investigated in longitudinal cohort PET/MR studies.

Preclinical and postmortem studies have suggested that regional synaptic density and glucose consumption (CMRGlc) are strongly related. However, the relation between synaptic density and cerebral glucose metabolism in the human brain has not directly been assessed in vivo. Using [11C]UCB-J binding to synaptic vesicle glycoprotein 2 A (SV2A) as indicator for synaptic density and [18F]FDG for measuring cerebral glucose consumption, we studied twenty healthy female subjects (age 29.6 ± 9.9 yrs) who underwent a single-day dual-tracer protocol (GE Signa PET-MR). Global measures of absolute and relative CMRGlc and specific binding of [11C]UCB-J were indeed highly significantly correlated ( r > 0.47, p 18F]FDG and [11C]UCB-J uptake were observed, with up to 19% higher [11C]UCB-J uptake in the medial temporal lobe (MTL) and up to 17% higher glucose metabolism in frontal and motor-related areas and thalamus. This pattern has a considerable overlap with the brain regions showing different levels of aerobic glycolysis. Regionally varying energy demands of inhibitory and excitatory synapses at rest may also contribute to this difference. Being unaffected by astroglial and/or microglial energy demands, changes in synaptic density in the MTL may therefore be more sensitive to early detection of pathological conditions compared to changes in glucose metabolism.

80 healthy volunteers underwentFull results were available for 78 participants (19-85y; 33 M/45 F). VBM grey matter concentration changes with aging were most predominant in the perisylvian and frontal regions. After PVC, no significantly decreasedIn vivo, PET using

Importance During a time with the potential for novel treatment strategies, early detection of disease manifestations at an individual level in presymptomatic carriers of a hexanucleotide repeat expansion in the C9orf72 gene (preSxC9) is becoming increasingly relevant. Objectives To evaluate changes in glucose metabolism before symptom onset of amyotrophic lateral sclerosis or frontotemporal dementia in preSxC9 using simultaneous fluorine 18–labeled fluorodeoxyglucose ([18F]FDG positron emission tomographic (PET) and magnetic resonance imaging as well as the mutation’s association with clinical and fluid biomarkers. Design, Setting, and Participants A prospective, case-control study enrolled 46 participants from November 30, 2015, until December 11, 2018. The study was conducted at the neuromuscular reference center of the University Hospitals Leuven, Leuven, Belgium. Main Outcomes and Measures Neuroimaging data were spatially normalized and analyzed at the voxel level at a height threshold of P

BACKGROUND: Yoga is increasingly popular worldwide with several physical and mental benefits, but the underlying neurobiology remains unclear. Whereas many studies have focused on pure meditational aspects, the triad of yoga includes meditation, postures, and breathing. We conducted a cross-sectional study comparing experienced yoga practitioners to yoga-naive healthy subjects using a multiparametric 2 × 2 design with simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging. METHODS: 18F-FDG PET, morphometric and diffusion tensor imaging, resting state fMRI, and MR spectroscopy were acquired in 10 experienced (4.8 ± 2.3 years of regular yoga experience) yoga practitioners and 15 matched controls in rest and after a single practice (yoga practice and physical exercise, respectively). RESULTS: In rest, decreased regional glucose metabolism in the medial temporal cortex, striatum, and brainstem was observed in yoga practitioners compared to controls (p < 0.0001), with a significant inverse correlation of resting parahippocampal and brainstem metabolism with years of regular yoga practice (ρ < - 0.63, p < 0.05). A single yoga practice resulted in significant hypermetabolism in the cerebellum (p < 0.0001). None of the MR measures differed, both at rest and after intervention. CONCLUSIONS: Experienced yoga practitioners show regional long-term decreases in glucose metabolism related to years of practice. To elucidate a potential causality, a prospective longitudinal study in yoga-naive individuals is warranted. ispartof: EJNMMI RESEARCH vol:10 issue:1 ispartof: location:Germany status: published

Dopamine transporter (DAT) imaging is an important adjunct in the diagnostic workup of patients with Parkinsonism.Nine patients with early Parkinson's disease (PD, 64.3 ± 6.8 years, 3M), who had previously undergone aUsing occipital cortex as reference region resulted in smaller bias of SUVR with respect to BP

PURPOSE: A [11C]UCB-J blocking study was performed in healthy volunteers to validate simplified, non-invasive measures for quantifying presynaptic SV2A expression using subcortical white matter as reference tissue. METHODS: Ninety minutes dynamic [11C]UCB-J PET scanning with arterial blood sampling was performed in 10 healthy volunteers (8 M/2F; age 27.6 ± 10.0 yrs), before and after administration of a novel chemical entity with selective affinity for SV2A. The centrum semi-ovale (SO) was validated as reference region by comparing baseline and post treatment distribution volume (VT). Using SO as reference tissue, Binding Potential (BPSO) using a Simplified Reference Tissue Model (SRTM, down to 60 min acquisition) and Standardized Uptake Value Ratios (60-90 min post injection - SUVRSO,60-90min) were compared with regional distribution volume ratios (DVR). Next, SV2A occupancy values based on SRTM BPSO and SUVRSO,60-90min were compared to occupancy estimates using regional VT values and a Lassen plot. RESULTS: After pretreatment, regional VT values were reduced significantly except for SO. Highly significant correlations were found between DVR, SRTM BPSO and SUVRSO,60-90min. Compared to DVR, baseline SRTM BPSO showed a small bias (≤ 6.1%) with lower precision for shorter acquisition times, while SUVRSO,60-90min showed 3.5% bias with similar precision. Differences between SV2A occupancy values based on SUVRSO,60-90min and occupancy estimates using VT and a Lassen plot were small but significant, while negligible bias was found for SRTM based occupancy estimates (at least 70 min acquisition). CONCLUSION: This [11C]UCB-J blocking study validated SO as a suitable reference region for non-invasive quantification of SV2A availability and drug occupancy in the human brain. Accurate quantification can be achieved by using either SUVRSO,60-90min with a 60-90 min PET acquisition or SRTM BPSOwith at least 70 min dynamic PET acquisition. ispartof: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING vol:46 issue:2 pages:396-406 ispartof: location:Germany status: published

Background As pediatric ambulatory surgeries are rising and existing methods to reduce perioperative anxiety and pain are lacking in this population, a serious game for health (SGH), CliniPup, was developed to address this unmet need. CliniPup was generated using the SERES framework for serious game development. Objective The goal of the research was to clinically evaluate CliniPup as an adjunct therapy to existing pharmacological interventions aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. Methods CliniPup was evaluated in a prospective randomized controlled pilot trial in 20 children aged 6 to 10 years who underwent elective surgery and their parents. Study participants were randomly assigned to the test (n=12) or control group (n=8). Children in the test group played CliniPup 2 days prior to surgery, and children in the control group received standard of care. On the day of surgery, pediatric anxiety was measured with the modified Yale Preoperative Anxiety Scale and parental anxiety was assessed with the State-Trait Anxiety Inventory. Pediatric postoperative pain was assessed by the Wong-Baker Faces Pain Rating Scale. Child and parent user experience and satisfaction were also evaluated in the test group using structured questionnaires. Results Despite the small sample, preoperative anxiety scores were significantly lower (P=.01) in children who played CliniPup prior to surgery compared to controls. Parental preoperative anxiety scores were also lower in the test group (P=.10) but did not reach significance. No significant differences were observed in postoperative pain scores between groups (P=.54). The evaluation of user experience and satisfaction revealed that both children and parents were satisfied with CliniPup and would recommend the game to peers. Conclusions Results of the pilot trial introduce CliniPup as a potentially effective and attractive adjunct therapy to reduce preoperative anxiety in children undergoing ambulatory surgery with a trend toward positive impact on parental preoperative anxiety. These results support the use of the SERES framework to generate an evidence-based SGH that results in positive health outcomes for patients. Based on these preliminary findings, we propose a research agenda to further develop and investigate this tool. Trial Registration ClinicalTrials.gov NCT03874442; https://clinicaltrials.gov/ct2/show/NCT03874442 (Archived by WebCite at http://www.webcitation.org/78KZab8qc)

Background An increasing number of children undergo ambulatory surgery each year, and a significant proportion experience substantial preoperative anxiety and postoperative pain. The management of perioperative anxiety and pain remains challenging in children and is inadequate, which negatively impacts the physical, psychosocial, and economic outcomes. Existing nonpharmacological interventions are costly, time consuming, vary in availability, and lack benefits. Therefore, there is a need for an evidence-based, accessible, nonpharmacological intervention as an adjunct to existing pharmacological alternatives to reduce perioperative anxiety and pain in children undergoing ambulatory surgery. Technology-enabled interventions have been proposed as a method to address the unmet need in this setting. In particular, serious games hold a unique potential to change health beliefs and behaviors in children. Objective The objective of this research was to describe the rationale, scientific evidence, design aspects, and features of CliniPup, a serious game aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. Methods The SERES Framework for serious game development was used to create the serious game, CliniPup. In particular, we used a mixed methods approach that consisted of a structured literature review supplemented with ethnographic research, such as expert interviews and a time-motion exercise. The resulting scientific evidence base was leveraged to ensure that the resulting serious game was relevant, realistic, and theory driven. A participatory design approach was applied, wherein clinical experts qualitatively reviewed several versions of the serious game, and an iterative creative process was used to integrate the applicable feedback. Results CliniPup, a serious game, was developed to incorporate a scientific evidence base from a structured literature review, realistic content collected during ethnographic research such as expert interviews, explicit pedagogical objectives from scientific literature, and game mechanics and user interface design that address key aspects of the evidence. Conclusions This report details the systematic development of CliniPup, a serious game aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. Clinical experts validated CliniPup’s underlying scientific evidence base and design foundations, suggesting that it was well designed for preliminary evaluation in the target population. An evaluation plan is proposed and briefly described.

BACKGROUND Increasing numbers of children undergo ambulatory surgery each year and a significant proportion experiences substantial preoperative anxiety and postoperative pain. The management of perioperative anxiety and pain remains challenging in children and is inadequate, which negatively impacts physical, psychosocial, and economic outcomes. Existing non-pharmacological interventions are costly, time consuming, vary in availability, and lack benefits. Therefore, there is a need for an evidence-based, accessible, non-pharmacological intervention as an adjunct to existing pharmacological alternatives to reduce perioperative anxiety and pain in children undergoing ambulatory surgery. Technology-enabled interventions have been proposed as a method to address the unmet need in this setting. In particular, serious games for health (SGHs) hold unique potential to change health beliefs and behaviors in children. OBJECTIVE The objective of this research was to describe the rationale, scientific evidence, design aspects, and features of CliniPup, an SGH aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. METHODS The SERES framework for SGH development was used to create the SGH, CliniPup. In particular, a mixed-methods approach was applied that consisted of a structured literature review supplemented with ethnographic research, such as expert interviews and a time-motion exercise. The resulting scientific evidence base was leveraged to ensure that the resulting SGH was relevant, realistic, and theory-driven. A participatory design approach was applied wherein clinical experts qualitatively reviewed several versions of the SGH and an iterative creative process was used to integrate the applicable feedback. RESULTS CliniPup, an SGH, was developed to incorporate (1) scientific evidence base from a structured literature review, (2) realistic content collected during ethnographic research such as expert interviews, (3) explicit pedagogical objectives from scientific literature, and (4) game mechanics and user interface design that address key aspects of the evidence. CONCLUSIONS This report details the systematic development of CliniPup, an SGH aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. Clinical experts validated CliniPup’s underlying scientific evidence base and design foundations, suggesting that it was well designed for preliminary evaluation in the target population. An evaluation plan is proposed and briefly described.

BACKGROUND As pediatric ambulatory surgeries are rising and existing methods to reduce perioperative anxiety and pain are lacking in this population, a serious game for health (SGH), CliniPup, was developed to address this unmet need. CliniPup was generated using the SERES framework for serious game development. OBJECTIVE To clinically evaluate CliniPup, an SGH, as an adjunct therapy to existing pharmacological interventions aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. METHODS CliniPup was evaluated in a prospective, randomized, controlled pilot trial in 20 children aged 6-10 years who underwent elective surgery, and their parents. Study participants were randomly assigned to the test (n=12) or control group (n=8). Children in the test group played CliniPup 2-days prior to surgery and children in the control group received standard of care. On the day of surgery, pediatric anxiety was measured with the modified Yale Preoperative Anxiety Scale (mYPAS) and parental anxiety was assessed with the State-Trait Anxiety Inventory (STAI). Pediatric postoperative pain was assessed by the Wong-Baker Faces Pain Rating Scale (WBFPRS). Child and parent user experience and satisfaction was also evaluated in the test group using structured questionnaires. RESULTS Despite the small sample, preoperative anxiety scores were significantly lower (P = .01) in children who played CliniPup prior to surgery, compared to controls. Parental preoperative anxiety scores were also lower in the test group (P = .10), but did not reach significance. No significant differences were observed in postoperative pain scores between groups (P = .54). The evaluation of user experience and satisfaction revealed that both children and parents were satisfied with CliniPup and would recommend the game to peers. CONCLUSIONS Results of the pilot trial introduce CliniPup as a potentially effective and attractive adjunct therapy, to reduce preoperative anxiety in children undergoing ambulatory surgery, with a trend towards positive impact on parental preoperative anxiety. These results support the use of the SERES framework to generate an evidence-based SGH, which results in positive health outcomes for patients. Based on these preliminary findings, we propose a research agenda to further develop and investigate this tool.

A [Ninety minutes dynamic [After pretreatment, regional VThis [