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Background: The autonomic nervous system is frequently affected in some neurodegenerative diseases, including Parkinson's disease and Dementia with Lewy bodies. In vivo imaging methods to visualize and quantify the peripheral cholinergic nervous system are lacking. By using [18F]FEOBV PET, we here describe the peripheral distribution of the specific cholinergic marker, vesicular acetylcholine transporters (VAChT), in human subjects. We included 15 healthy subjects aged 53–86 years for 70 min dynamic PET protocol of peripheral organs. We performed kinetic modelling of the adrenal gland, pancreas, myocardium, renal cortex, spleen, colon, and muscle using an image-derived input function from the aorta. A metabolite correction model was generated from venous blood samples. Three non-linear compartment models were tested. Additional time-activity curves from 6 to 70 min post injection were generated for prostate, thyroid, submandibular-, parotid-, and lacrimal glands. Results: A one-tissue compartment model generated the most robust fits to the data. Total volume-of-distribution rank order was: adrenal gland > pancreas > myocardium > spleen > renal cortex > muscle > colon. We found significant linear correlations between total volumes-of-distribution and standard uptake values in most organs. Conclusion: High [18F]FEOBV PET signal was found in structures with known cholinergic activity. We conclude that [18F]FEOBV PET is a valid tool for estimating VAChT density in human peripheral organs. Simple static images may replace kinetic modeling in some organs and significantly shorten scan duration. Clinical Trial Registration Trial registration: NCT, NCT03554551. Registered 31 May 2018. https://clinicaltrials.gov/ct2/show/NCT03554551?term=NCT03554551&draw=2&rank=1. [ABSTRACT FROM AUTHOR]

One of the major discoveries of Hinode's Extreme-ultraviolet Imaging Spectrometer (EIS) is the presence of upflows at the edges of active regions. As active regions are magnetically connected to the large-scale field of the corona, these upflows are a likely contributor to the global mass cycle in the corona. Here we examine the driving mechanism(s) of the very strong upflows with velocities in excess of 70 km s−1, known as blue-wing asymmetries, observed during the eruption of a flux rope in AR 10977 (eruptive flare SOL2007-12-07T04:50). We use Hinode/EIS spectroscopic observations combined with magnetic-field modeling to investigate the possible link between the magnetic topology of the active region and the strong upflows. A Potential Field Source Surface (PFSS) extrapolation of the large-scale field shows a quadrupolar configuration with a separator lying above the flux rope. Field lines formed by induced reconnection along the separator before and during the flux-rope eruption are spatially linked to the strongest blue-wing asymmetries in the upflow regions. The flows are driven by the pressure gradient created when the dense and hot arcade loops of the active region reconnect with the extended and tenuous loops overlying it. In view of the fact that separator reconnection is a specific form of the more general quasi-separatrix (QSL) reconnection, we conclude that the mechanism driving the strongest upflows is, in fact, the same as the one driving the persistent upflows of ≈10 – 20 km s−1 observed in all active regions. [ABSTRACT FROM AUTHOR]

Spectroscopic observations at extreme- and far-ultraviolet wavelengths have revealed systematic upflows in the solar transition region and corona. These upflows are best seen in the network structures of the quiet Sun and coronal holes, boundaries of active regions, and dimming regions associated with coronal mass ejections. They have been intensively studied in the past two decades because they are likely to be closely related to the formation of the solar wind and heating of the upper solar atmosphere. We present an overview of the characteristics of these upflows, introduce their possible formation mechanisms, and discuss their potential roles in the mass and energy transport in the solar atmosphere. Although past investigations have greatly improved our understanding of these upflows, they have left us with several outstanding questions and unresolved issues that should be addressed in the future. New observations from the Solar Orbiter mission, the Daniel K. Inouye Solar Telescope, and the Parker Solar Probe will likely provide critical information to advance our understanding of the generation, propagation, and energization of these upflows. [ABSTRACT FROM AUTHOR]

Background: Sleep disorders can occur in early Parkinson's disease (PD). However, the relationship between different sleep disturbances and their longitudinal evolution has not been fully explored. Objective: To describe the frequency, coexistence, and longitudinal change in excessive daytime sleepiness (EDS), insomnia, and probable REM sleep behavior disorder (pRBD) in early PD. Methods: Data were obtained from the Parkinson's Progression Markers Initiative (PPMI). EDS, insomnia, and pRBD were defined using the Epworth Sleepiness Scale, MDS-UPDRS Part I sub-item 1.7, and RBD screening questionnaire. Results: 218 PD subjects and 102 controls completed 5 years of follow-up. At baseline, 69 (31.7%) PD subjects reported one type of sleep disturbance, 25 (11.5%) reported two types of sleep disturbances, and three (1.4%) reported all three types of sleep disturbances. At 5 years, the number of PD subjects reporting one, two, and three types of sleep disturbances was 85 (39.0%), 51 (23.4%), and 16 (7.3%), respectively. Only 41(18.8%) patients were taking sleep medications. The largest increase in frequency was seen in insomnia (44.5%), followed by EDS (32.1%) and pRBD (31.2%). Insomnia was the most common sleep problem at any time over the 5-year follow-up. The frequency of sleep disturbances in HCs remained stable. Conclusions: There is a progressive increase in the frequency of sleep disturbances in PD, with the number of subjects reporting multiple sleep disturbances increasing over time. Relatively a few patients reported multiple sleep disturbances, suggesting that they can have different pathogenesis. A large number of patients were not treated for their sleep disturbances. [ABSTRACT FROM AUTHOR]

Purpose: Loss of neuronal synapse function is associated with a number of brain disorders. The [11C]UCB-J positron emission tomography (PET) tracer allows for in vivo examination of synaptic density, as it binds to synaptic vesicle glycoprotein 2A (SV2A) expressed in presynaptic terminals. Here, we characterise [11C]UCB-J imaging in Göttingen minipigs.Procedures: Using PET imaging, we examined tracer specificity and compared kinetic models. We explored the use of a standard blood curve and centrum semiovale white matter as a reference region. We compared in vivo [11C]UCB-J PET imaging to in vitro autoradiography, Western blotting and real-time quantitative polymerase chain reaction.Results: The uptake kinetics of [11C]UCB-J could be described using a 1-tissue compartment model and blocking of SV2A availability with levetiracetam showed dose-dependent specific binding. Population-based blood curves resulted in reliable [11C]UCB-J binding estimates, while it was not possible to use centrum semiovale white matter as a non-specific reference region. Brain [11C]UCB-J PET signals correlated well with [3H]UCB-J autoradiography and SV2A protein levels.Conclusions: [11C]UCB-J PET is a valid in vivo marker of synaptic density in the minipig brain, with binding values close to those reported for humans. Minipig models of disease could be valuable for investigating the efficacy of putative neuroprotective agents for preserving synaptic function in future non-invasive, longitudinal studies. [ABSTRACT FROM AUTHOR]

Neuroinflammation (microglial activation) and subclinical nigrostriatal dysfunction have been reported in subjects at risk of Parkinsonism. Eight non-manifesting carriers (NMCs) of LRRK2 G2019S mutation had 11C-PK11195 and 18F-DOPA PET to assess microglial activation and striatal dopamine system integrity, respectively. Comparisons were made with healthy controls. Five LRRK2-NMCs had subclinical reductions of putaminal 18F-DOPA uptake. Three of them had significantly raised nigral 11C-PK11195 binding bilaterally. These findings indicate that nigrostriatal dysfunction and neuroinflammation occur in LRRK2-NMCs. Studies in larger cohorts with appropriate follow-up are needed to elucidate the significance of neuroinflammation in the premotor phase of LRRK2-PD. [ABSTRACT FROM AUTHOR]

Purpose: This joint practice guideline or procedure standard was developed collaboratively by the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). The goal of this guideline is to assist nuclear medicine practitioners in recommending, performing, interpreting, and reporting the results of dopaminergic imaging in parkinsonian syndromes. Methods: Currently nuclear medicine investigations can assess both presynaptic and postsynaptic function of dopaminergic synapses. To date both EANM and SNMMI have published procedural guidelines for dopamine transporter imaging with single photon emission computed tomography (SPECT) (in 2009 and 2011, respectively). An EANM guideline for D2 SPECT imaging is also available (2009). Since the publication of these previous guidelines, new lines of evidence have been made available on semiquantification, harmonization, comparison with normal datasets, and longitudinal analyses of dopamine transporter imaging with SPECT. Similarly, details on acquisition protocols and simplified quantification methods are now available for dopamine transporter imaging with PET, including recently developed fluorinated tracers. Finally, [18F]fluorodopa PET is now used in some centers for the differential diagnosis of parkinsonism, although procedural guidelines aiming to define standard procedures for [18F]fluorodopa imaging in this setting are still lacking. Conclusion: All these emerging issues are addressed in the present procedural guidelines for dopaminergic imaging in parkinsonian syndromes. [ABSTRACT FROM AUTHOR]

Background: Venous thrombosis (VT) is an ongoing problem for patients undergoing elective splenectomy. There is limited data evaluating risk factors for VTs. An increase in platelet counts is commonly seen after splenectomy; however, there is a paucity of literature evaluating post-operative platelet counts as a risk factor for VTs in this patient cohort. The objective of this study was to determine the incidence of VT events and to use the platelet count as a predictor for VT development.Methods: A retrospective review was undertaken at Brigham Women's Hospital, evaluating elective splenectomy patients between 1997 and 2018. Descriptive statistics were utilized to determine the incidence of VTs. Receiver operator characteristic (ROC) curves were utilized to identify platelet counts that could predict VTs.Results: Five hundred and twenty splenectomies were included in the study of which 344 were completed in an open manner and 176 were done laparoscopically. The overall incidence of VT events was 6.7% (35/520), 6.1% (21/344) for open, and 8.0% (14/176) for laparoscopic approaches (p = 0.43). ROC curves demonstrated platelet counts to be a good predictor for the development of VTs with an area under the curve (AUC) of 0.77 (95% CI 0.69-0.86; p < 0.001) for all splenectomy patients, 0.70 (95% CI 0.59-0.81; p < 0.001) for those completed in an open manner, and 0.88 (95% CI 0.77-0.99; p < 0.001) for those done laparoscopically. The optimal platelet cutoff was found to be 545 for the overall splenectomy cohort, 457 for the open, and 659 for the laparoscopic cohorts. These platelet counts had a diagnostic accuracy that ranged from 61 to 86% and a negative predictive value (NPV) that ranged from 97 to 99%.Conclusion: These results suggest platelet cutoffs that predict VTs. This information can be used to individualize prophylactic strategies. [ABSTRACT FROM AUTHOR]

The third flight of the High-Resolution Coronal Imager (Hi-C 2.1) occurred on May 29, 2018; the Sounding Rocket was launched from White Sands Missile Range in New Mexico. The instrument has been modified from its original configuration (Hi-C 1) to observe the solar corona in a passband that peaks near 172 Å, and uses a new, custom-built low-noise camera. The instrument targeted Active Region 12712, and captured 78 images at a cadence of 4.4 s (18:56:22 – 19:01:57 UT; 5 min and 35 s observing time). The image spatial resolution varies due to quasi-periodic motion blur from the rocket; sharp images contain resolved features of at least 0.47 arcsec. There are coordinated observations from multiple ground- and space-based telescopes providing an unprecedented opportunity to observe the mass and energy coupling between the chromosphere and the corona. Details of the instrument and the data set are presented in this paper. [ABSTRACT FROM AUTHOR]

Purpose: Measurements of non-displaceable binding (VND) of positron emission tomography (PET) ligands are not often made in vivo in humans because they require ligands to displace binding to target receptors and there are few readily available, safe ones to use. A technique to measure VND for ligands for the 18-kDa translocator protein (TSPO) has recently been developed which compares the total volume of distribution (VT) before and after administration of the TSPO ligand XBD173. Here, we used XBD173 with an occupancy plot to quantify VND for two TSPO radiotracers, [18F]GE-180 and [11C]PBR28, in cohorts of people with multiple sclerosis (MS). Additionally, we compared plots of subjects carrying high (HAB) or mixed binding (MAB) affinity polymorphisms of TSPO to estimate VND without receptor blockade.Procedures: Twelve people with MS underwent baseline MRI and 90-min dynamic [18F]GE-180 PET or [11C]PBR28 PET (n = 6; three HAB, three MAB each). Arterial blood sampling was used to generate plasma input functions for the two-tissue compartment model. VND was calculated using two independent methods: the occupancy plot (by modelling the differences in signal post XBD173) and the polymorphism plot (by modelling the differences in signal across presence and absence of rs6971 genotypes).Results: Whole brain VT (mean ± standard deviation) was 0.29 ± 0.17 ml/cm3 for [18F]GE-180 and 5.01 ± 1.88 ml/cm3 for [11C]PBR28. Using the occupancy and polymorphism plots respectively, VND for [18F]GE-180 was 0.11 ml/cm3 (95 % CI = 0.02, 0.16) and 0.20 ml/cm3 (0.16, 0.34), accounting for, on average, 55 % of VT in the whole brain. For [11C]PBR28, these values were 3.81 ml/cm3 (3.02, 4.21) and 3.49 ml/cm3 (1.38, 4.27), accounting for 67 % of average whole brain VT.Conclusions: Although VT for [18F]GE-180 is low, indicating low brain penetration, half the signal shown by MS subjects reflected specific TSPO binding. VT for [11C]PBR28 was higher and two thirds of the binding was non-specific. No brain ROIs were devoid of specific signal, further confirming that true reference tissue approaches are potentially problematic for estimating TSPO levels. [ABSTRACT FROM AUTHOR]

Background: Robotic-assisted surgery is used with increasing frequency in general surgery for a variety of applications. In spite of this increase in usage, the learning curve is not yet defined. This study reviews the literature on the learning curve in robotic general surgery to inform adopters of the technology.Methods: PubMed and EMBASE searches yielded 3690 abstracts published between July 1986 and March 2016. The abstracts were evaluated based on the following inclusion criteria: written in English, reporting original work, focus on general surgery operations, and with explicit statistical methods.Results: Twenty-six full-length articles were included in final analysis. The articles described the learning curves in colorectal (9 articles, 35%), foregut/bariatric (8, 31%), biliary (5, 19%), and solid organ (4, 15%) surgery. Eighteen of 26 (69%) articles report single-surgeon experiences. Time was used as a measure of the learning curve in all studies (100%); outcomes were examined in 10 (38%). In 12 studies (46%), the authors identified three phases of the learning curve. Numbers of cases needed to achieve plateau performance were wide-ranging but overlapping for different kinds of operations: 19-128 cases for colorectal, 8-95 for foregut/bariatric, 20-48 for biliary, and 10-80 for solid organ surgery.Conclusion: Although robotic surgery is increasingly utilized in general surgery, the literature provides few guidelines on the learning curve for adoption. In this heterogeneous sample of reviewed articles, the number of cases needed to achieve plateau performance varies by case type and the learning curve may have multiple phases as surgeons add more complex cases to their case mix with growing experience. Time is the most common determinant for the learning curve. The literature lacks a uniform assessment of outcomes and complications, which would arguably reflect expertise in a more meaningful way than time to perform the operation alone. [ABSTRACT FROM AUTHOR]

Background: Overweight and obese patients are often asked to lose weight prior to ventral hernia repair (VHR). Improved outcomes are the reasons behind this strategy. Data regarding weight loss targets are scant, and it is not known at what body mass index (BMI) threshold postoperative complications increase. This study aimed to determine the threshold to allow proper patient counseling.Methods: All patients who underwent open VHR at our institution between 2002 and 2015 captured in the NSQIP database were included. The primary outcome was defined as any (≥1) of 18 captured postoperative complications. Patients were divided into five groups based on BMI: group 1 (<25 kg/m2); 2 (25-29.99 kg/m2); 3 (30-34.99 kg/m2); 4 (35-39.99 kg/m2); and 5 (≥40 kg/m2). Multivariable, adjusted logistic regression was performed to evaluate the association between BMI categories and postoperative complications.Results: Sixty seven of 922 patients (7.3 %) had at least one postoperative complication following VHR. The adjusted odds of complications in group 5 was 2.89 times greater compared to group 1 (OR 2.89; 95 % CI = 1.22-6.84), while there was no significant differences in odds of postoperative complications for groups 2, 3, or 4 compared to group 1. BMI category was also significantly associated with undergoing recurrent VHR, with 28.7 % of patients in group 5 having a recurrent repair compared to 14 % in patients in group 1 (p = 0.03).Conclusions: After VHR, complications are most likely to occur in patients with BMI ≥ 40 kg/m2. This subset of patients also had a significantly higher risk of undergoing surgery for a recurrent hernia, suggesting that this group of patients is likely to experience adverse outcomes after VHR and should be counseled to consider bariatric surgery prior to attempts at VHR. VHR at lower BMIs appears appropriate, and delaying therapy to achieve preoperative weight loss will likely offer no advantage. [ABSTRACT FROM AUTHOR]

Background: The benefits of laparoscopic splenectomy (LS) over open splenectomy (OS) for normal-sized spleens have been well documented. However, the role of laparoscopy for moderate and massive splenomegaly is debated.Methods: A retrospective review of patients undergoing elective splenectomy at one institution from 1997 to 2017 was conducted. Moderate and massive splenomegaly was defined as splenic weight of 500-1000 g and greater than 1000 g, respectively. We performed a 1:2 matching of laparoscopic to open splenectomy to control for differences in splenic weight. Differences in perioperative morbidity (infection, thromboembolism, reoperation, readmission), intraoperative factors (blood loss, operative time), length of stay, and mortality were examined.Results: A total of 491 elective splenectomies were identified. 268 cases were for splenic weights greater than 500 g. After a 1:2 matching of LS:OS, we identified 22 LS and 44 matched OS for moderate splenomegaly. The LS group had longer mean operative times (178 vs. 107 min, p < 0.01), with similar length of stay and blood loss. For massive splenomegaly, 26 LS were identified and matched to 52 OS. LS had longer mean operative times (171 vs. 112 min, p < 0.01) and higher readmission rates (27% vs. 6%, p < 0.05). Other factors and outcomes did not differ between LS and OS for moderate or massive splenomegaly. The conversion rate for LS was higher for massive versus moderate splenomegaly, but was not statistically significant (35% vs. 14%, p = 0.09).Conclusions: LS for moderate and massive splenomegaly is associated with longer operative times. Other perioperative outcomes were comparable to OS, with no demonstrated benefits for LS. Although LS may be a feasible approach to moderate and massive splenomegaly, its benefits require further clarification in this patient population. [ABSTRACT FROM AUTHOR]

Purpose: Neuroinflammation and microglial activation play an important role in amnestic mild cognitive impairment (MCI) and Alzheimer’s disease. In this study, we investigated the spatial distribution of neuroinflammation in MCI subjects, using spectral analysis (SA) to generate parametric maps and quantify 11C-PBR28 PET, and compared these with compartmental and other kinetic models of quantification.Methods: Thirteen MCI and nine healthy controls were enrolled in this study. Subjects underwent 11C-PBR28 PET scans with arterial cannulation. Spectral analysis with an arterial plasma input function was used to generate 11C-PBR28 parametric maps. These maps were then compared with regional 11C-PBR28 VT (volume of distribution) using a two-tissue compartment model and Logan graphic analysis. Amyloid load was also assessed with 18F-Flutemetamol PET.Results: With SA, three component peaks were identified in addition to blood volume. The 11C-PBR28 impulse response function (IRF) at 90 min produced the lowest coefficient of variation. Single-subject analysis using this IRF demonstrated microglial activation in five out of seven amyloid-positive MCI subjects. IRF parametric maps of 11C-PBR28 uptake revealed a group-wise significant increase in neuroinflammation in amyloid-positive MCI subjects versus HC in multiple cortical association areas, and particularly in the temporal lobe. Interestingly, compartmental analysis detected group-wise increase in 11C-PBR28 binding in the thalamus of amyloid-positive MCI subjects, while Logan parametric maps did not perform well.Conclusions: This study demonstrates for the first time that spectral analysis can be used to generate parametric maps of 11C-PBR28 uptake, and is able to detect microglial activation in amyloid-positive MCI subjects. IRF parametric maps of 11C-PBR28 uptake allow voxel-wise single-subject analysis and could be used to evaluate microglial activation in individual subjects. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether white matter microstructural changes can be used as a predictor of worsening of motor features or cognitive decline in patients with Parkinson’s disease and verify whether white matter microstructural longitudinal changes differ between patients with Parkinson’s disease with normal cognition and those with mild cognitive impairment.Methods: We enrolled 120 newly diagnosed patients with early stage Parkinson’s disease (27 with mild cognitive impairment and 93 with normal cognition) along with 48 controls. Participants were part of the incidence of cognitive impairment in cohorts with longitudinal evaluation in Parkinson’s disease study and were assessed at baseline and 18 months later with cognitive, motor tests and diffusion tensor imaging. The relationships between fractional anisotropy and mean diffusivity with disease status, cognitive and motor function were investigated.Results: At baseline, patients with early stage Parkinson’s disease had significantly higher widespread mean diffusivity relative to controls, regardless of cognitive status. In patients with Parkinson’s disease/mild cognitive impairment, higher mean diffusivity was significantly correlated with lower attention and executive function scores. At follow-up frontal mean diffusivity increased significantly when comparing patients with Parkinson’s disease/mild cognitive impairment with those with normal cognition. Baseline mean diffusivity was a significant predictor of worsening of motor features in Parkinson’s disease.Conclusions: Mean diffusivity represents an important correlate of cognitive function and predictor of motor impairment in Parkinson’s disease: DTI is potentially a useful tool in stratification of patients into clinical trials and to monitor the impact of treatment on motor function. [ABSTRACT FROM AUTHOR]

Purpose: Recent evidence suggests that the tau radiotracer [18F]THK-5351 displays high affinity for the monoamine oxidase type B (MAO-B) enzyme. Utilizing another tau-tracer, flortaucipir ([18F]AV-1451), we previously reported that non-demented Parkinson's disease patients show off-target binding in subcortical structures, but no appreciable cortical uptake. However, 59 % of these patients were receiving MAO-B inhibitors at the time of their scan. Here, we retrospectively investigated if MAO-B inhibitors in clinical doses affect flortaucipir binding.Procedures: We compared the standard uptake values of flortaucipir at regional and voxel levels in Parkinson's disease patients who received MAO-B inhibitors with those who did not.Results: Sixteen of 27 Parkinson's disease patients received MAO-B inhibitors at the time of scan. We found no significant flortaucipir uptake differences between the groups at voxel or regional levels.Conclusion: Use of MAO-B inhibitors at pharmaceutical levels did not significantly affect flortaucipir binding. Thus, MAO-B does not appear to be a significant binding target of flortaucipir. [ABSTRACT FROM AUTHOR]

The study undertook an examination of corporate security through the lens of the broader socio-organisational literature to understand its organisational stratum, seating, and function. The methodology applied a survey questionnaire to security practitioners, incorporating two measurement tools to assess work level and time-span of discretion. Findings identified work levels across the corporate security function. These work levels indicate that the corporate security function operates at the operational and tactical strata, with limited strategic executive impact. Furthermore, the corporate security function is positioned within the technostructure, providing analytical support to business operations. The study identified a significant disconnect between the corporate security literature—as written by security practitioners and academia—and the socio-organisational literature, with many points of divergence. These findings suggest the need for study replication and a review of the security literature in regards to executive influence. [ABSTRACT FROM AUTHOR]

The elemental composition in the coronae of low-activity solar-like stars appears to be related to fundamental stellar properties such as rotation, surface gravity, and spectral type. Here we use full-Sun observations from the Solar Dynamics Observatory, to show that when the Sun is observed as a star, the variation of coronal composition is highly correlated with a proxy for solar activity, the F10.7 cm radio flux, and therefore with the solar cycle phase. Similar cyclic variations should therefore be detectable spectroscopically in X-ray observations of solar analogs. The plasma composition in full-disk observations of the Sun is related to the evolution of coronal magnetic field activity. Our observations therefore introduce an uncertainty into the nature of any relationship between coronal composition and fixed stellar properties. The results highlight the importance of systematic full-cycle observations for understanding the elemental composition of solar-like stellar coronae. [ABSTRACT FROM AUTHOR]

Purpose: PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand [C]PK-11195 limits accurate quantification. [F]GE-180, a novel TSPO ligand, displays superior binding to [C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [F]GE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures. Methods: Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of [F]GE-180. Kinetic modelling of time-activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution ( V ) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region. Results: The two-tissue compartment model was the best model. The average regional delivery rate constant ( K ) was 0.01 mL cm min indicating low extraction across the blood-brain barrier (1 %). The estimated median V across all ROIs was also low, ranging from 0.16 mL cm in the striatum to 0.38 mL cm in the thalamus. There were no significant differences in V between HABs and MABs across all ROIs. Conclusion: A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low V estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of [F]GE-180 in populations with neuroinflammatory disease is needed to determine its suitability for quantitative assessment of TSPO expression. [ABSTRACT FROM AUTHOR]

Parkinson's disease is now widely recognized to be a multisystem disorder affecting the brain and peripheral autonomic nerves. Extensive pathology is present in both the sympathetic and parasympathetic nervous system and the intrinsic gastrointestinal plexuses in patients. Autonomic pathology and symptoms such as constipation can predate the clinical diagnosis by years or decades. Imaging studies have contributed greatly to our understanding of Parkinson's disease but focused primarily on imaging cerebral pathology. However, given the importance of understanding the nature, chronology, and functional consequences of peripheral pathology, there has been renewed interest in imaging peripheral organs in Parkinson's disease. Suitable imaging tools can be divided into two types: radiotracer studies that directly estimate loss of sympathetic or parasympathetic nerve terminals, and imaging modalities to quantitate dysphagia, gastric emptying, esophageal and intestinal transit times, and anorectal dyssynergia. In this review, we summarize current knowledge about peripheral imaging in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Objectives: The Phase I safety, biodistribution and internal radiation dosimetry study in adult healthy Japanese males of flutemetamol ((18)F) injection, an in vivo β-amyloid imaging agent, is reported and compared with previously obtained Caucasian data.Methods: Whole-body PET scans of 6 healthy volunteers (age 51.8-61.7 years) were acquired approximately 4 h post-injection (administered activity 102-160 MBq). Venous blood sampling determined (18)F activity concentrations in whole blood and plasma and high-performance liquid chromatography (HPLC) established the percentages of parent [(18)F]flutemetamol and its metabolites. Voided urine activity was recorded. The decay-corrected and normalised (18)F activity of 14 source organ regions as a function of time was entered into the OLINDA/EXM software to calculate the internal radiation dosimetry and effective dose of each subject following the MIRD schema. The pharmacokinetics, biodistribution and dosimetry profiles were compared to data obtained from a cohort of healthy Caucasian adult volunteers from a previous Phase I study of [(18)F]flutemetamol.Results: Flutemetamol ((18)F) injection was well tolerated. The highest mean initial uptakes were measured in the liver (15.2%), lungs (10.2%) and brain (6.6%). The highest mean radiation absorbed doses were received by the gallbladder wall (366 μGy/MBq), upper large intestine (138 μGy/MBq) and small intestine (121 μGy/MBq). The mean effective dose was 34.9 μSv/MBq. HPLC analysis demonstrated that at 5-min post-injection about 75% of plasma (18)F radioactivity was in the form of parent [(18)F]flutemetamol, reducing to 8 and 2% at 25 and 90 min, respectively, giving rise to less lipophilic (18)F-labelled metabolites. Comparisons with the Caucasian cohort showed no differences that could be regarded as clinically significant.Conclusion: The clinical safety of [(18)F]flutemetamol demonstrated no differences of clinical significance in the pharmacokinetics, biodistribution and internal radiation dosimetry profiles between Caucasian and Japanese adults. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study presented was to investigate the brain uptake properties of the amyloid PET agent [F]flutemetamol in Japanese healthy controls and clinically probable Alzheimer's disease (AD) patients, and to make a comparison with the results of a previously performed study on Caucasian subjects. [F]flutemetamol was recently approved by the American Food and Drug Administration and the European Medicines Agency for visualization of amyloid in vivo. Since the first clinical study of [F]flutemetamol-an F derivative of the PET tracer 11C-Pittsburgh Compound B targeting β-amyloid--took place, several clinical studies have been performed, but few focusing on a Japanese population. Methods: In the Step A, three elderly healthy volunteers and three AD subjects underwent dynamic PET scanning 0-30 and 60-150 min after injection of 185 MBq [F]flutemetamol. The brain volume of distribution (V) was quantified using Logan's linear graphical analysis and as standardized uptake value ratios (SUVR) with a cerebellar reference. The optimal acquisition window was determined from brain time activity curves for Step B. In the Step B, 5 AD and 5 elderly healthy volunteers were scanned from 80 to 140 min after intravenous injection of [F]flutemetamol. The data from the two parts were pooled for estimation of overall efficacy. Results: [F]Flutemetamol injection was shown to be safe-no serious adverse events were reported during this study. A simplified SUVR estimate of the uptake of [F]flutemetamol using a time window of 85-115 min post injection successfully discriminated AD cases from healthy volunteers. AD subjects showed an elevated tracer uptake in prefrontal cortex, the lateral temporal cortex and precuneus amongst other regions. No significant [F]flutemetamol PET differences could be seen between the Japanese AD cases in this study and those from an earlier Caucasian study, or between control subjects in Japanese and Caucasian studies. Conclusions: This study supports the use of [F]flutemetamol PET in Japanese population as a marker of the presence of fibrillar β-amyloid. The lack of differences between the Japanese cohort and those from a previous Caucasian cohort supports the extrapolation of results from other Caucasian [F]flutemetamol PET studies to the Japanese population. [ABSTRACT FROM AUTHOR]

The molecular mechanism of neuronal loss and synaptic damage in Alzheimer's disease (AD), Parkinson's disease dementia (PDD), frontotemporal dementia (FTD) and Lewy body dementia (LBD) is poorly understood and could differ among different types of neurodegenerative processes. However, the presence of neuroinflammation is a common feature of dementia. In this setting, reactive microgliosis, oxidative damage and mitochondrial dysfunction are associated with the pathogenesis of all types of neurodegenerative dementia. Moreover, an increased body of evidence suggests that microglia may play a central role in AD progression. In this paper, we review the scientific literature on neuroinflammation related to the most common neurodegenerative dementias (AD, PDD, FTD and LBD) focussing on the possible molecular mechanisms and the available clinical evidence. Furthermore, we discuss the neuroimaging techniques that are currently used for the study of neuroinflammation in human brain. [ABSTRACT FROM AUTHOR]