Search

Repeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild traumatic brain injury (rmTBI) and chronic variable stress mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [ 18 F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespread decreases in synaptic density coupled with an i ncrease in local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions with higher synapse density showed a greater increase in fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.

Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [ 11 C]UCB-J PET. Methods: Participants included 31 older adults with AD and 16 with normal cognition. The distribution volume ratio (DVR) using simplified reference tissue model 2 was compared with SUVR at short scan windows using a whole-cerebellum reference region. Results: Synaptic density was reduced in AD participants using DVR or SUVR. SUVR using later scan windows (60-90 or 70-90 min) was minimally biased, with the strongest correlation with DVR. Effect sizes using SUVR at these late time windows were minimally reduced compared with effect sizes with DVR. Conclusion: A simplified tissue-to-reference method may be useful for multicenter and longitudinal studies seeking to measure synaptic density in AD., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

The collaboration of Yale, the University of California, Davis, and United Imaging Healthcare has successfully developed the NeuroEXPLORER, a dedicated human brain PET imager with high spatial resolution, high sensitivity, and a built-in 3-dimensional camera for markerless continuous motion tracking. It has high depth-of-interaction and time-of-flight resolutions, along with a 52.4-cm transverse field of view (FOV) and an extended axial FOV (49.5 cm) to enhance sensitivity. Here, we present the physical characterization, performance evaluation, and first human images of the NeuroEXPLORER. Methods: Measurements of spatial resolution, sensitivity, count rate performance, energy and timing resolution, and image quality were performed adhering to the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. The system's performance was demonstrated through imaging studies of the Hoffman 3-dimensional brain phantom and the mini-Derenzo phantom. Initial 18 F-FDG images from a healthy volunteer are presented. Results: With filtered backprojection reconstruction, the radial and tangential spatial resolutions (full width at half maximum) averaged 1.64, 2.06, and 2.51 mm, with axial resolutions of 2.73, 2.89, and 2.93 mm for radial offsets of 1, 10, and 20 cm, respectively. The average time-of-flight resolution was 236 ps, and the energy resolution was 10.5%. NEMA sensitivities were 46.0 and 47.6 kcps/MBq at the center and 10-cm offset, respectively. A sensitivity of 11.8% was achieved at the FOV center. The peak noise-equivalent count rate was 1.31 Mcps at 58.0 kBq/mL, and the scatter fraction at 5.3 kBq/mL was 36.5%. The maximum count rate error at the peak noise-equivalent count rate was less than 5%. At 3 iterations, the NEMA image-quality contrast recovery coefficients varied from 74.5% (10-mm sphere) to 92.6% (37-mm sphere), and background variability ranged from 3.1% to 1.4% at a contrast of 4.0:1. An example human brain 18 F-FDG image exhibited very high resolution, capturing intricate details in the cortex and subcortical structures. Conclusion: The NeuroEXPLORER offers high sensitivity and high spatial resolution. With its long axial length, it also enables high-quality spinal cord imaging and image-derived input functions from the carotid arteries. These performance enhancements will substantially broaden the range of human brain PET paradigms, protocols, and thereby clinical research applications., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: While the amygdala receives early tau deposition in Alzheimer's disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms., Methods: We examined n=598 individuals (n=347 amyloid-positive (58% female), n=251 amyloid-negative (62% female); subset into tau PET and fMRI cohorts) from the A4 Study. In our tau PET cohort, we used amygdalar segmentations to examine representative nuclei from three functional divisions of the amygdala. We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the fMRI cohort. Finally, we conducted exploratory post-hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores., Results: Amyloid-positive individuals demonstrated increased tau binding in medial and lateral amygdala ( F (4,442)=14.61, p =0.00045; F( 4,442)=5.83, p =0.024, respectively). Across amygdalar divisions, amyloid-positive individuals had relatively increased regional connectivity from amygdala to other temporal regions, insula, and orbitofrontal cortex. There was an interaction by amyloid group between tau binding in the medial and lateral amygdala and anxiety. Medial amygdala to retrosplenial connectivity negatively correlated with anxiety symptoms (r s =-0.103, p =0.015)., Conclusions: Our findings suggest that preclinical tau deposition in the amygdala may result in meaningful changes in functional connectivity which may predispose patients to mood symptoms., Competing Interests: DISCLOSURES WX is currently employed in a fellowship role at Unlearn. AI Inc. JL, ST, BFT, SW, CH, TT, SN, CZ, YZ, AP, EB, and CF have no conflicts of interest or financial interests to declare.

Mycoplasma mobile is a parasitic bacterium that forms gliding machinery on the cell pole and glides on a solid surface in the direction of the cell pole. The gliding machinery consists of both internal and surface structures. The internal structure is divided into a bell at the front and chain structure extending from the bell. In this study, the internal structures prepared under several conditions were analyzed using negative-staining electron microscopy and electron tomography. The chains were constructed by linked motors containing two complexes similar to ATP synthase. A cylindrical spacer with a maximum diameter of 6 nm and a height of 13 nm, and anonymous linkers with a diameter of 0.9-8.3 nm and length of 14.7±6.9 nm were found between motors. The bell is bowl-shaped and features a honeycomb surface with a periodicity of 8.4 nm. The chains of the motor are connected to the rim of the bell through a wedge-shaped structure. These structures may play roles in the assembly and cooperation of gliding machinery units., Competing Interests: The authors declare that they have no conflict of interest., (2024 THE BIOPHYSICAL SOCIETY OF JAPAN.)

Introduction: EndoTrac is a line-attached sheath-type traction device that enables us to control the direction and the force of traction during endoscopic submucosal dissection (ESD). The efficacy of EndoTrac for gastric ESD has not been fully verified., Methods and Analysis: The G-Trac study is a multicentre (nine general hospitals and two university hospitals in Japan) collaborative trial assessing the efficacy of EndoTrac for gastric ESDs. Patients with superficial gastric neoplasms will be enrolled and randomly assigned to undergo either conventional ESD or EndoTrac ESD. Allocation will be stratified according to tumour location, operator experience and tumour diameter at an allocation rate of 1:1. The type of endoknife used will be confirmed before randomisation. The primary outcome, procedure time, will be compared between the groups in both intention-to-treat and per-protocol analyses using the Wilcoxon rank sum test. The efficacy-related, safety-related and device-related outcomes will be assessed in the secondary analysis. The planned sample size of the 142 patients in the two groups will enable us to detect a difference with a power of 80% by using the Wilcoxon rank sum test, assuming an effect size of 0.54, asymptotic relative efficiency of 0.864 and a two-sided type 1 error rate of 5%., Ethics and Dissemination: This trial was approved by the certified review board of Kobe University (22 December 2022). The results from this trial will be disseminated through peer-review journals, presentations at national and international conferences, and data sharing with other researchers., Trial Registration Number: jRCT1052220166., Competing Interests: Competing interests: Takashi Toyonaga has received royalties from Top for the development of the EndoTrac. The other authors declare no conflicts of interest regarding this article., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole ( 18 F-FMISO) and fluorine-18-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism., Methods: Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma ( n = 33) who underwent preoperative 18 F-FMISO and 18 F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort ( n = 17) and validated by The Cancer Genome Atlas (TCGA) database ( n = 167)., Results: Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 ( G6PC3 ) correlated with 18 F-FDG LNR ( P = 0.03). In addition, G6PC3 mRNA expression in 18 F-FMISO high-accumulated glioblastomas was significantly higher than that in 18 F-FMISO low-accumulated glioblastomas ( P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database., Conclusion: G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high 18 F-FDG and 18 F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma., Competing Interests: The authors have no relevant financial or nonfinancial interests to disclose., (Copyright © 2024 Michinari Okamoto et al.)

Parkinson's disease (PD) is the fastest growing neurodegenerative disease, but at present there is no cure, nor any disease-modifying treatments. Synaptic biomarkers from in vivo imaging have shown promise in imaging loss of synapses in PD and other neurodegenerative disorders. Here, we provide new clinical insights from a cross-sectional, high-resolution positron emission tomography (PET) study of 30 PD individuals and 30 age- and sex-matched healthy controls (HC) with the radiotracer [ 11 C]UCB-J, which binds to synaptic vesicle glycoprotein 2A (SV2A), and is therefore, a biomarker of synaptic density in the living brain. We also examined a measure of relative brain perfusion from the early part of the same PET scan. Our results provide evidence for synaptic density loss in the substantia nigra that had been previously reported, but also extend this to other early-Braak stage regions known to be affected in PD (brainstem, caudate, olfactory cortex). Importantly, we also found a direct association between synaptic density loss in the nigra and severity of symptoms in patients. A greater extent and wider distribution of synaptic density loss in PD patients with longer illness duration suggests that [ 11 C]UCB-J PET can be used to measure synapse loss with disease progression. We also demonstrate lower brain perfusion in PD vs. HC groups, with a greater extent of abnormalities in those with longer duration of illness, suggesting that [ 11 C]UCB-J PET can simultaneously provide information on changes in brain perfusion. These results implicate synaptic imaging as a useful PD biomarker for future disease-modifying interventions., (© 2024. The Author(s).)

Increasing number of patients with ulcerative colitis (UC) have received biologic treatment during the last decade. The association between endoscopic healing (EH) and biologic treatment failure remains understudied. Medical information of UC patients who started biologic treatment was retrospectively collected. EH was defined as Mayo endoscopic subscore of 0 or 1. Loss of response (LOR)-free drug continuation rate was compared between patients who achieved EH and those who did not using Kaplan-Meier estimator. Fifty-two patients received 53 biologic treatments and underwent follow-up colonoscopies within 2 years. Thirty-three patients achieved EH, all of which remained on the same treatment without LOR during the observational period. Twenty patients did not achieve EH, 8 of which ultimately discontinued the treatment due to LOR to biologic agents. Kaplan-Meier estimator found a significantly lower drug continuation rate in patients without EH (p < 0.001; log-rank test). A Cox regression analysis identified EH as an independent factor associated with a reduced risk of LOR-related biologic treatment failure irrespective of the types of biologic agents (Hazard Ratio = 0.0324, p < 0.001). EH within 2 years is associated with a reduced risk of LOR-related biologic treatment failure in patients with UC., (© 2024. The Author(s).)

Background: Progression of Alzheimer's disease leads to synapse loss, neural network dysfunction and cognitive failure. Accumulation of protein aggregates and brain immune activation have triggering roles in synaptic failure but the neuronal mechanisms underlying synapse loss are unclear. On the neuronal surface, cellular prion protein (PrP C ) is known to be a high-affinity binding site for Amyloid-β oligomers (Aβo). However, PrP C 's dependence in knock-in AD models for tau accumulation, transcriptomic alterations and imaging biomarkers is unknown., Methods: The necessity of PrP C was examined as a function of age in homozygous App NL-G-F /hMapt double knock-in mice (DKI). Phenotypes of App NL-G-F /hMapt mice with a deletion of Prnp expression (DKI; Prnp -/- ) were compared with DKI mice with intact Prnp, mice with a targeted deletion of Prnp (Prnp -/- ), and mice with intact Prnp (WT). Phenotypes examined included behavioral deficits, synapse loss by PET imaging, synapse loss by immunohistology, tau pathology, gliosis, inflammatory markers, and snRNA-seq transcriptomic profiling., Results: By 9 months age, DKI mice showed learning and memory impairment, but DKI; Prnp -/- and Prnp -/- groups were indistinguishable from WT. Synapse loss in DKI brain, measured by [18F]SynVesT-1 SV2A PET or anti-SV2A immunohistology, was prevented by Prnp deletion. Accumulation of Tau phosphorylated at aa 217 and 202/205, C1q tagging of synapses, and dystrophic neurites were all increased in DKI mice but each decreased to WT levels with Prnp deletion. In contrast, astrogliosis, microgliosis and Aβ levels were unchanged between DKI and DKI; Prnp -/- groups. Single-nuclei transcriptomics revealed differential expression in neurons and glia of DKI mice relative to WT. For DKI; Prnp -/- mice, the majority of neuronal genes differentially expressed in DKI mice were no longer significantly altered relative to WT, but most glial DKI-dependent gene expression changes persisted. The DKI-dependent neuronal genes corrected by Prnp deletion associated bioinformatically with synaptic function. Additional genes were uniquely altered only in the Prnp -/- or the DKI; Prnp -/- groups., Conclusions: Thus, PrP C -dependent synapse loss, phospho-tau accumulation and neuronal gene expression in AD mice can be reversed without clearing Aβ plaque or preventing gliotic reaction. This supports targeting the Aβo-PrP C interaction to prevent Aβo-neurotoxicity and pathologic tau accumulation in AD., (© 2023. The Author(s).)

Competing Interests: Dr Toyonaga receives royalties from TOP and Fujifilm. The other authors did not disclose any financial relationships.

Video 1Endoscopic submucosal dissection of a large, laterally spreading-type granular mixed polyp in the ascending colon followed by closure of the ulcer bed using modified double-layered endoscopic suturing with endoscopic clips., Competing Interests: Dr Toyonaga receives royalties from Fujifilm. The other authors did not disclose any financial relationships., (© 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

Objective We explored the clinicopathological characteristics and disease frequency of oxyntic gland neoplasms (OGNs). Methods We retrospectively evaluated the data of patients pathologically diagnosed with OGN at an internal medicine clinic. Patients A total of 13,240 upper gastrointestinal endoscopies were performed on 7,488 patients between December 1, 2017, and March 31, 2021. Results We identified 27 patients with 30 histopathologically confirmed OGNs, yielding a disease frequency of 0.36% (27/7,488). Furthermore, multiple simultaneous lesions were found in 3 of 27 patients (11%). One (3.3%) of the 30 lesions was present in the antrum, whereas the remaining lesions occurred in the body of the stomach. Nine (33%) of the 27 patients had no history of Helicobacter pylori infection, whereas the remaining 18 (67%) were either currently or had been previously infected. Nevertheless, 27/30 lesions (90%) still occurred in non-atrophied regions. After endoscopic treatment, a histopathological examination of the resected specimens revealed submucosal infiltration in 8 (44%) of the 18 lesions; however, none of the lesions showed submucosal desmoplasia. For all patients with submucosal involvement, only observation was performed. There were no recurrent lesions found on follow-up. Conclusion The period prevalence of OGN was 0.36%, which is much higher than previously reported. The discovery of a small submucosal appearing lesion with a faded yellow or white color and dilated microvasculature, especially in a non-atrophic area of the stomach, should raise suspicion for an OGN, which can be endoscopically managed.

Background/aims: Endoscopic submucosal dissection (ESD) is currently considered the first-line treatment for the eradication of superficial neoplasms of the esophagus in Eastern countries. However, in the West, particularly in Latin America, the experience with esophageal ESD is still limited because of the high technical complexity required for its execution. This study aimed to present the results of the clinical application of ESD to manage superficial esophageal neoplasms in a Latin American center in over 100 consecutive cases., Methods: This retrospective study included consecutive patients who underwent endoscopic ESD for superficial esophageal neoplasms between 2009 and 2022. The following clinical outcomes were assessed: en bloc, complete, and curative resection rates, local recurrence, adverse events, and procedure-related mortality., Results: Esophageal ESD was performed mainly for squamous cell carcinoma (66.6%), high-grade intraepithelial neoplasia (17.1%), and adenocarcinoma (11.4%). En bloc and complete resection rates were 96.2% and 81.0%, respectively. The curative resection rate was 64.8%. Adverse events occurred in six cases (5.7%). Endoscopic follow-up was performed for an average period of 29.7 months., Conclusion: ESD performed by trained operators is feasible, safe, and clinically effective for managing superficial neoplastic lesions of the esophagus in Latin America.

Video 1Peroral endoscopic myotomy for a pediatric case of suspected congenital esophageal stenosis., Competing Interests: Dr Toyonaga has ownership interest in Fujifilm. The other authors did not disclose any financial relationships., (© 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

[Purpose] The Trail Making Test is a valuable tool for predicting the transition from mild cognitive impairment to dementia. This cross-sectional study aimed to investigate gender-specific factors associated with the Trail Making Test using body composition and motor function among Japanese workers. [Participants and Methods] Demographic data, body composition, motor function, and cognitive and attentional functions (Trail Making Test, Part B) were analyzed among 627 workers who underwent health assessments during the 2019 fiscal year. After conducting univariate analysis, multiple regression analysis was performed. [Results] The presence of metabolic syndrome risk factors was found to significantly prolonged the performance time of the Trail Making Test-B in male workers. In addition, low fat-free mass and the 30-second chair stand test also significantly prolonged the performance time of the Trail Making Test-B in male workers. Among female workers, the presence of metabolic syndrome risk factors affected the performance time of the Trail Making Test-B. Therefore, MetS risk factors affect the performance times of the Trail Making Test-B in both male and female workers. [Conclusion] As male and female workers exhibit different body composition and motor function items in the Trail Making Test-B, gender differences should be considered when formulating measures to prevent cognitive and attentional decline., Competing Interests: The authors declare that they have no conflicts of interest., (2023©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Introduction: Synapse loss is one of the hallmarks of Alzheimer's disease (AD) and is associated with cognitive decline. In this study, we tested [ 18 F]SDM-16, a novel metabolically stable SV2A PET imaging probe, in the transgenic APPswe/PS1dE9 (APP/PS1) mouse model of AD and age-matched wild-type (WT) mice at 12 months of age., Methods: Based on previous preclinical PET imaging studies using [ 11 C]UCB-J and [ 18 F]SynVesT-1 in the same strain animals, we used the simplified reference tissue model (SRTM), with brain stem as the pseudo reference region to calculate distribution volume ratios (DVRs)., Results: To simplify and streamline the quantitative analysis, we compared the standardized uptake value ratios (SUVRs) from different imaging windows to DVRs and found that the averaged SUVRs from 60-90 min post-injection ( p.i .) are most consistent with the DVRs. Thus, we used averaged SUVRs from 60-90 min for group comparisons and found statistically significant differences in the tracer uptake in different brain regions, e.g., hippocampus ( p = 0.001), striatum ( p = 0.002), thalamus ( p = 0.003), and cingulate cortex ( p = 0.0003)., Conclusions: In conclusion, [ 18 F]SDM-16 was used to detect decreased SV2A levels in the brain of APP/PS1 AD mouse model at one year old. Our data suggest that [ 18 F]SDM-16 has similar statistical power in detecting the synapse loss in APP/PS1 mice as [ 11 C]UCB-J and [ 18 F]SynVesT-1, albeit later imaging window (60-90 min p.i .) is needed when SUVR is used as a surrogate for DVR for [ 18 F]SDM-16 due to its slower brain kinetics., 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 Zheng, Toyonaga, Chen, Nicholson, Mennie, Liu, Spurrier, Deluca, Strittmatter, Carson, Huang and Cai.)

Background & Aims: We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study., Methods: We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative, >2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C)., Results: Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS., Conclusion: ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871)., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Clinical investigations suggest involvement of the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of fear learning that underlies trauma-related disorders. Here, we utilized a 4-day fear learning paradigm combined with positron emission tomography (PET) to examine the relationship between mGluR5 availability and differences in the response of rats to repeated footshock exposure (FE). Specifically, on day 1, male (n = 16) and female (n = 12) rats received 15 footshocks and were compared with control rats who did not receive footshocks (n = 7 male; n = 4 female). FE rats were classified as low responders (LR) or high responders (HR) based on freezing to the context the following day (day 2). PET with [ 18 F]FPEB was used to calculate regional mGluR5 binding potential (BP ND ) at two timepoints: prior to FE (i.e., baseline), and post-behavioral testing. Additionally, we used an unbiased proteomics approach to assess group and sex differences in prefrontal cortex (PFC) protein expression. Post-behavioral testing we observed decreased BP ND in LR females, but increased BP ND in HR males relative to baseline. Further, individuals displaying the greatest freezing during the FE context memory test had the largest increases in PFC BP ND . Males and females displayed unique post-test molecular profiles: in males, the greatest differences were between FE and CON, including upregulation of mGluR5 and related molecular networks in FE, whereas the greatest differences among females were between the LR and HR groups. These findings suggest greater mGluR5 availability increases following footshock exposure may be related to greater contextual fear memory. Results additionally reveal sex differences in the molecular response to footshock, including differential involvement of mGluR5-related molecular networks., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Objective Endoscopic reports are conventionally written at the end of each procedure, and the endoscopist must complete the report from memory. To make endoscopic reporting more efficient, we developed a new speech recognition (SR) system that generates highly accurate endoscopic reports based on structured data entry. We conducted a pilot study to examine the performance of this SR system in an actual endoscopy setting with various types of background noise. Methods In this prospective observational pilot study, participants who underwent upper endoscopy with our SR system were included. The primary outcome was the correct recognition rate of the system. We compared the findings generated by the SR system with the findings in the handwritten report prepared by the endoscopist. The initial correct recognition rate, number of revisions, finding registration time, and endoscopy time were also analyzed. Results Upper endoscopy was performed in 34 patients, generating 128 findings of 22 disease names. The correct recognition rate was 100%, and the median number of revisions was 0. The median finding registration time was 2.57 [interquartile range (IQR), 2.33-2.92] seconds, and the median endoscopy time was 234 (IQR, 194-227) seconds. Conclusion The SR system demonstrated high recognition accuracy in the clinical setting. The finding registration time was extremely short.

Background: Synaptic loss is considered an early pathological event and major structural correlate of cognitive impairment in Alzheimer's disease (AD). We used principal component analysis (PCA) to identify regional patterns of covariance in synaptic density using [ 11 C]UCB-J PET and assessed the association between principal components (PC) subject scores with cognitive performance., Methods: [ 11 C]UCB-J binding was measured in 45 amyloid + participants with AD and 19 amyloid- cognitively normal participants aged 55-85. A validated neuropsychological battery assessed performance across five cognitive domains. PCA was applied to the pooled sample using distribution volume ratios (DVR) standardized (z-scored) by region from 42 bilateral regions of interest (ROI)., Results: Parallel analysis determined three significant PCs explaining 70.2% of the total variance. PC1 was characterized by positive loadings with similar contributions across the majority of ROIs. PC2 was characterized by positive and negative loadings with strongest contributions from subcortical and parietooccipital cortical regions, respectively, while PC3 was characterized by positive and negative loadings with strongest contributions from rostral and caudal cortical regions, respectively. Within the AD group, PC1 subject scores were positively correlated with performance across all cognitive domains (Pearson r = 0.24-0.40, P = 0.06-0.006), PC2 subject scores were inversely correlated with age (Pearson r = -0.45, P = 0.002) and PC3 subject scores were significantly correlated with CDR-sb (Pearson r = 0.46, P = 0.04). No significant correlations were observed between cognitive performance and PC subject scores in CN participants., Conclusions: This data-driven approach defined specific spatial patterns of synaptic density correlated with unique participant characteristics within the AD group. Our findings reinforce synaptic density as a robust biomarker of disease presence and severity in the early stages of AD., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: APM, REC, and CHvD report grants from National Institutes of Health for the conduct of the study. APM reports grants for clinical trials from Genentech, Eli Lilly, and Janssen Pharmaceuticals outside the submitted work. MKC reports research support from the Dana Foundation and Eli Lilly and clinical trials from Merck outside the submitted work. YH reports research grants from the UCB and Eli Lilly outside the submitted work. YH, NBN, and REC have a patent for a newer version of the tracer. REC is a consultant for Rodin Therapeutics and has received research funding from UCB. REC reports having received grants from AstraZeneca, Astellas, Eli Lilly, Pfizer, Taisho, and UCB, outside the submitted work. CHvD reports consulting fees from Kyowa Kirin, Roche, Merck, Eli Lilly, and Janssen and grants for clinical trials from Biogen, Novartis, Eli Lilly, Merck, Eisai, Janssen, Roche, Genentech, Toyama, and Biohaven, outside the submitted work. No other disclosures are reported. AHC has licensed technology to Elysium Health, Inc. and hasreceived consulting fees from FOXO Technologies, Inc., bothfor work unrelated to the present manuscript., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Head motion presents a continuing problem in brain PET studies. A wealth of motion correction (MC) algorithms had been proposed in the past, including both hardware-based methods and data-driven methods. However, in most real brain PET studies, in the absence of ground truth or gold standard of motion information, it is challenging to objectively evaluate MC quality. For MC evaluation, image-domain metrics, e.g., standardized uptake value (SUV) change before and after MC are commonly used, but this measure lacks objectivity because 1) other factors, e.g., attenuation correction, scatter correction and parameters used in the reconstruction, will confound MC effectiveness; 2) SUV only reflects final image quality, and it cannot precisely inform when an MC method performed well or poorly during the scan time period; 3) SUV is tracer-dependent and head motion may cause increases or decreases in SUV for different tracers, so evaluating MC effectiveness is complicated. Here, we present a new algorithm, i.e., motion corrected centroid-of-distribution (MCCOD) to perform objective quality control for measured or estimated rigid motion information. MCCOD is a three-dimensional surrogate trace of the center of tracer distribution after performing rigid MC using the existing motion information. MCCOD is used to inform whether the motion information is accurate, using the PET raw data only, i.e., without PET image reconstruction, where inaccurate motion information typically leads to abrupt changes in the MCCOD trace. MCCOD was validated using simulation studies and was tested on real studies acquired from both time-of-flight (TOF) and non-TOF scanners. A deep learning-based brain mask segmentation was implemented, which is shown to be necessary for non-TOF MCCOD generation. MCCOD is shown to be effective in detecting abrupt translation motion errors in slowly varying tracer distribution caused by the motion tracking hardware and can be used to compare different motion estimation methods as well as to improve existing motion information., Competing Interests: Declaration of Competing Interest The other authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Radioactive iodine (RAI) therapy is a useful treatment for Graves' disease (GD). Most RAI sessions administer ≤ 500 MBq of iodine (I)-131. Sometimes patients require repeated RAI, often for longer periods of remission. We investigated the characteristics of patients for whom high dose (mostly 1110 MBq of I-131) RAI was effective as RAI therapy for GD., Methods: We retrospectively analyzed the cases of 79 patients who underwent RAI for GD in a multicenter setting. We divided the patients into two groups based on the I-131 dose administered: the low dose (LD) group who received ≤ 500 MBq (n = 44) and the high dose (HD) group who received > 500 MBq (n = 35). The therapeutic effect was defined as achieving remission and reaching the point of participating in thyroid hormone replacement therapy within 1 year after RAI. We compared the LD and HD groups' remission rates and conducted a multivariate logistic regression analysis of predictive factors for remission. In a simulation, using the formula for predicting the probability of remission obtained from the analysis results, we estimated how much the remission rate would change if the I-131 dose is increased from 500 to 1110 MBq., Results: The mean ± standard deviation I-131 dose administered in the LD group was 480 ± 6 MBq, and that of the HD group was 1054 ± 265 MBq. Thirty-five patients (80%) in the LD group and 26 patients (74%) in the HD group achieved remission; this difference in the remission rate was not significant. The multivariate analysis results demonstrated that the absorbed dose and thyroid-stimulating antibody (TSAb) were independent predictors of remission. Seven patients (8.9%) showed an increased probability of remission from < 50% to > 50% when the higher RAI dose was applied (1110 MBq instead of 500 MBq). The thyroid volume and TSAb values in these patients were relatively large at 54.7 ± 34.2 mL and 1378.4 ± 586.3%, respectively., Conclusion: Although the overall remission rate was not significantly different between the patients who received high- or low-dose I-131, treatment with high-dose RAI may improve the probability of remission in patients with a massive thyroid volume and/or high-TSAb Graves' disease., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

PET technology has produced many radiopharmaceuticals that target specific brain proteins and other measures of brain function. Recently, a new approach has emerged to image synaptic density by targeting the synaptic vesicle protein 2A (SV2A), an integral glycoprotein in the membrane of synaptic vesicles and widely distributed throughout the brain. Multiple SV2A ligands have been developed and translated to human use. The most successful of these to date is 11 C-UCB-J, because of its high uptake, moderate metabolism, and effective quantification with a 1-tissue-compartment model. Further, since SV2A is the target of the antiepileptic drug levetiracetam, human blocking studies have characterized specific binding and potential reference regions. Regional brain SV2A levels were shown to correlate with those of synaptophysin, another commonly used marker of synaptic density, providing the basis for SV2A PET imaging to have broad utility across neuropathologic diseases. In this review, we highlight the development of SV2A tracers and the evaluation of quantification methods, including compartment modeling and simple tissue ratios. Mouse and rat models of neurodegenerative diseases have been studied with small-animal PET, providing validation by comparison to direct tissue measures. Next, we review human PET imaging results in multiple neurodegenerative disorders. Studies on Parkinson disease and Alzheimer disease have progressed most rapidly at multiple centers, with generally consistent results of patterns of SV2A or synaptic loss. In Alzheimer disease, the synaptic loss patterns differ from those of amyloid, tau, and 18 F-FDG, although intertracer and interregional correlations have been found. Smaller studies have been reported in other disorders, including Lewy body dementia, frontotemporal dementia, Huntington disease, progressive supranuclear palsy, and corticobasal degeneration. In conclusion, PET imaging of SV2A has rapidly developed, and qualified radioligands are available. PET studies on humans indicate that SV2A loss might be specific to disease-associated brain regions and consistent with synaptic density loss. The recent availability of new 18 F tracers, 18 F-SynVesT-1 and 18 F-SynVesT-2, will substantially broaden the application of SV2A PET. Future studies are needed in larger patient cohorts to establish the clinical value of SV2A PET and its potential for diagnosis and progression monitoring of neurodegenerative diseases, as well as efficacy assessment of disease-modifying therapies., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

The successful development and translation of PET imaging agents targeting β-amyloid plaques and hyperphosphorylated tau tangles have allowed for in vivo detection of these hallmarks of Alzheimer's disease (AD) antemortem. Amyloid and tau PET have been incorporated into the A/T/N scheme for AD characterization and have become an integral part of ongoing clinical trials to screen patients for enrollment, prove drug action mechanisms, and monitor therapeutic effects. Meanwhile, preclinical PET imaging in animal models of AD can provide supportive information for mechanistic studies. With the recent advancement of gene editing technologies and AD animal model development, preclinical PET imaging in AD models will further facilitate our understanding of AD pathogenesis/progression and the development of novel treatments. In this study, we review the current state-of-the-art in preclinical PET imaging using animal models of AD and suggest future research directions., 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 © 2022 Chen, Marquez-Nostra, Belitzky, Toyonaga, Tong, Huang and Cai.)

Head motion during PET scans causes image quality degradation, decreased concentration in regions with high uptake and incorrect outcome measures from kinetic analysis of dynamic datasets. Previously, we proposed a data-driven method, center of tracer distribution (COD), to detect head motion without an external motion tracking device. There, motion was detected using one dimension of the COD trace with a semiautomatic detection algorithm, requiring multiple user defined parameters and manual intervention. In this study, we developed a new data-driven motion detection algorithm, which is automatic, self-adaptive to noise level, does not require user-defined parameters and uses all three dimensions of the COD trace (3DCOD). 3DCOD was first validated and tested using 30 simulation studies ( 18 F-FDG, N = 15; 11 C-raclopride (RAC), N = 15) with large motion. The proposed motion correction method was tested on 22 real human datasets, with 20 acquired from a high resolution research tomograph (HRRT) scanner ( 18 F-FDG, N = 10; 11 C-RAC, N = 10) and 2 acquired from the Siemens Biograph mCT scanner. Real-time hardware-based motion tracking information (Vicra) was available for all real studies and was used as the gold standard. 3DCOD was compared to Vicra, no motion correction (NMC), one-direction COD (our previous method called 1DCOD) and two conventional frame-based image registration (FIR) algorithms, i.e., FIR1 (based on predefined frames reconstructed with attenuation correction) and FIR2 (without attenuation correction) for both simulation and real studies. For the simulation studies, 3DCOD yielded -2.3 ± 1.4% (mean ± standard deviation across all subjects and 11 brain regions) error in region of interest (ROI) uptake for 18 F-FDG (-3.4 ± 1.7% for 11 C-RAC across all subjects and 2 regions) as compared to Vicra (perfect correction) while NMC, FIR1, FIR2 and 1DCOD yielded -25.4 ± 11.1% (-34.5 ± 16.1% for 11 C- RAC), -13.4 ± 3.5% (-16.1 ± 4.6%), -5.7 ± 3.6% (-8.0 ± 4.5%) and -2.6 ± 1.5% (-5.1 ± 2.7%), respectively. For real HRRT studies, 3DCOD yielded -0.3 ± 2.8% difference for 18 F-FDG (-0.4 ± 3.2% for 11 C-RAC) as compared to Vicra while NMC, FIR1, FIR2 and 1DCOD yielded -14.9 ± 9.0% (-24.5 ± 14.6%), -3.6 ± 4.9% (-13.4 ± 14.3%), -0.6 ± 3.4% (-6.7 ± 5.3%) and -1.5 ± 4.2% (-2.2 ± 4.1%), respectively. In summary, the proposed motion correction method yielded comparable performance to the hardware-based motion tracking method for multiple tracers, including very challenging cases with large frequent head motion, in studies performed on a non-TOF scanner., Competing Interests: Declaration of Competing Interest The other authors declare that they have no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Neuronal damage and synapse loss in the spinal cord (SC) have been implicated in spinal cord injury (SCI) and neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS). Current standards of diagnosis for SCI include CT or MRI imaging to evaluate injury severity. The current study explores the use of PET imaging with [ 11 C]UCB-J, which targets the synaptic vesicle protein 2A (SV2A), in the human spinal cord, as a way to visualize synaptic density and integrity in vivo., Results: First, simulations of baseline and blocking [ 11 C]UCB-J HRRT scans were performed, based on SC dimensions and SV2A distribution to predict V T , V ND , and V S values. Next, human baseline and blocking [ 11 C]UCB-J HRRT images were used to estimate these values in the cervical SC (cSC). Simulation results had excellent agreement with observed values of V T , V ND , and V S from the real human data, with baseline V T , V ND , and V S of 3.07, 2.15, and 0.92 mL/cm 3 , respectively, with a BP ND of 0.43. Lastly, we explored full SC imaging with whole-body images. Using automated SC regions of interest (ROIs) for the full SC, cSC, and thoracic SC (tSC), the distribution volume ratio (DVR) was estimated using the brain gray matter as a reference region to evaluate SC SV2A density relative to the brain. In full body imaging, DVR values of full SC, cSC, and tSC were 0.115, 0.145, and 0.112, respectively. Therefore, measured [ 11 C]UCB-J uptake, and thus SV2A density, is much lower in the SC than in the brain., Conclusions: The results presented here provide evidence for the feasibility of SV2A PET imaging in the human SC, however, specific binding of [ 11 C]UCB-J is low. Ongoing and future work include further classification of SV2A distribution in the SC as well as exploring higher-affinity PET radioligands for SC imaging., (© 2022. The Author(s).)

Background/aims: Endoscopic submucosal dissection (ESD) for diverticulum-associated colorectal lesions is generally contraindicated because of the high risk of perforation. Several studies on patients with such lesions treated with ESD have been reported recently. However, the feasibility and safety of ESD for lesions in proximity to a colonic diverticulum (D-ESD) have not been fully clarified. The aim of this study was to evaluate the feasibility and safety of D-ESD., Methods: D-ESD was defined as ESD for lesions within approximately 3 mm of a diverticulum. Twenty-six consecutive patients who underwent D-ESD were included. Two strategic approaches were used depending on whether submucosal dissection of the diverticulum-related part was required (strategy B) or not (strategy A). Treatment outcomes and adverse events associated with each strategy were analyzed., Results: The en bloc resection rate was 96.2%. The rates of R0 and curative resection in strategies A and B were 80.8%, 73.1%, 84.6%, and 70.6%, respectively. Two cases of intraoperative perforation and one case of delayed perforation occurred. The delayed perforation case required emergency surgery, but the other cases were managed conservatively., Conclusion: D-ESD may be a feasible treatment option. However, it should be performed in a high-volume center by expert hands because it requires highly skilled endoscopic techniques.

Combined use of fibrin glue and polyglycolic acid (PGA) sheets has attracted attention as a preventive measure for complications associated with endoscopic submucosal dissection. However, fibrin glue is a protein that may be dissolved by gastric acid. We evaluated the effect of artificial gastric acid on fibrin clot. The dissolution time of three layers of fibrin glue with PGA sheets was measured in five groups (pH 1.2, 2.0, 4.0, 5.5, and 6.0 with pepsin). Measurements of three samples per group were made. The mean number of the remaining layers at each measurement point was observed for 168 h. The time to complete dissolution of the three layers of fibrin gel in the three samples was 2.5 h at pH 1.2, 5 h at pH 2.0, 24 h at pH 4.0, and 48 h and 6 h at pH 5.5. In order to maintain fibrin glue in the stomach for a long period, there was a need to avoid pepsin activation secondary to acidification of gastric juice. The use of strong antacids is recommended., (© 2022. The Author(s).)

Background: There has been an ongoing need to compare and combine the results of new PET imaging studies conducted with [ 11 C]raclopride with older data. This typically means harmonizing data across different scanners. Previous harmonization studies have utilized either phantoms or human subjects, but the use of both phantoms and humans in one harmonization study is not common. The purpose herein was (1) to use phantom images to develop an inter-scanner harmonization technique and (2) to test the harmonization technique in human subjects., Methods: To develop the harmonization technique (Experiment 1), the Iida brain phantom was filled with F-18 solution and scanned on the two scanners in question (HRRT, HR+, Siemens/CTI). Phantom images were used to determine the optimal isotropic Gaussian filter to harmonize HRRT and HR+ images. To evaluate the harmonization on human images (Experiment 2), inter-scanner variability was calculated using [ 11 C]raclopride scans of 3 human subjects on both the HRRT and HR+ using percent difference (PD) in striatal non-displaceable binding potential (BP ND) between HR+ and HRRT (with and without Gaussian smoothing). Finally, (Experiment 3), PD T/RT was calculated for test-retest (T/RT) variability of striatal BP ND for 8 human subjects scanned twice on the HR+., Results: Experiment 1 identified the optimal filter as a Gaussian with a 4.5 mm FWHM. Experiment 2 resulted in 13.9% PD for unfiltered HRRT and 3.71% for HRRT filtered with 4.5 mm. Experiment 3 yielded 5.24% PD T/RT for HR+., Conclusions: The PD results show that the variability of harmonized HRRT is less than the T/RT variability of the HR+. The harmonization technique makes it possible for BP ND estimates from the HRRT to be compared to (and/or combined with) those from the HR+ without adding to overall variability. Our approach is applicable to all pairs of scanners still in service., (© 2022. The Author(s).)

The development of novel PET imaging agents for synaptic vesicle glycoprotein 2A (SV2A) allowed for the in vivo detection of synaptic density changes, which are correlated with the progression and severity of a variety of neuropsychiatric diseases. While multiple ongoing clinical investigations using SV2A PET are expanding its applications rapidly, preclinical SV2A PET imaging in animal models is an integral component of the translation research and provides supporting and complementary information. Herein, we overview preclinical SV2A PET studies in animal models of neurodegenerative disorders and discuss the opportunities and practical challenges in small animal SV2A PET imaging. At the Yale PET Center, we have conducted SV2A PET imaging studies in animal models of multiple diseases and longitudinal SV2A PET allowed us to evaluate synaptic density dynamics in the brains of disease animal models and to assess pharmacological effects of novel interventions. In this article, we discuss key considerations when designing preclinical SV2A PET imaging studies and strategies for data analysis. Specifically, we compare the brain imaging characteristics of available SV2A tracers, i.e., [ 11 C]UCB-J, [ 18 F]SynVesT-1, [ 18 F]SynVesT-2, and [ 18 F]SDM-16, in rodent brains. We also discuss the limited spatial resolution of PET scanners for small brains and challenges of kinetic modeling. We then compare different injection routes and estimate the maximum throughput (i.e., number of animals) per radiotracer synthesis by taking into account the injectable volume for each injection method, injected mass, and radioactivity half-lives. In summary, this article provides a perspective for designing and analyzing SV2A PET imaging studies in small animals., Competing Interests: ZC is an Archer Foundation Research Scientist. The radioligand [18F]SynVesT-1 is the subject of international patent application PCT/US2018/018388, “Radiolabeled Pharmaceuticals and Methods of Making and Using Same,” filed on February 15, 2018 (ZC and RC are 2 of the 5 co-inventors). The remaining 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 © 2022 Toyonaga, Fesharaki-Zadeh, Strittmatter, Carson and Cai.)

As in all other medical fields, artificial intelligence (AI) is increasingly being used in nuclear medicine for oncology. There are many articles that discuss AI from the viewpoint of nuclear medicine, but few focus on nuclear medicine from the viewpoint of AI. Nuclear medicine images are characterized by their low spatial resolution and high quantitativeness. It is noted that AI has been used since before the emergence of deep learning. AI can be divided into three categories by its purpose: (1) assisted interpretation, i.e., computer-aided detection (CADe) or computer-aided diagnosis (CADx). (2) Additional insight, i.e., AI provides information beyond the radiologist's eye, such as predicting genes and prognosis from images. It is also related to the field called radiomics/radiogenomics. (3) Augmented image, i.e., image generation tasks. To apply AI to practical use, harmonization between facilities and the possibility of black box explanations need to be resolved., (© 2021. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background/aims: The anastomotic site after distal gastrectomy is the area most affected by duodenogastric reflux. Different reconstruction methods may affect the lesion characteristics and treatment outcomes of remnant gastric cancers at the anastomotic site. We retrospectively investigated the clinicopathologic and endoscopic submucosal dissection outcomes of remnant gastric cancers at the anastomotic site., Methods: We recruited 34 consecutive patients who underwent endoscopic submucosal dissection for remnant gastric cancer at the anastomotic site after distal gastrectomy. Clinicopathology and treatment outcomes were compared between the Billroth II and non-Billroth II groups., Results: The tumor size in the Billroth II group was significantly larger than that in the non-Billroth II group (22 vs. 19 mm; p=0.048). More severe gastritis was detected endoscopically in the Billroth II group (2 vs. 1.33; p=0.0075). Moreover, operation time was longer (238 vs. 121 min; p=0.004) and the frequency of bleeding episodes was higher (7.5 vs. 3.1; p=0.014) in the Billroth II group., Conclusion: Compared to remnant gastric cancers in non-Billroth II patients, those in the Billroth II group had larger lesions with a background of severe remnant gastritis. Endoscopic submucosal dissection for remnant gastric cancers in Billroth II patients involved longer operative times and more frequent bleeding episodes than that in patients without Billroth II.

Purpose: 11 C-UCB-J PET imaging, targeting synaptic vesicle glycoprotein 2A (SV2A), has been shown to be a useful indicator of synaptic density in Alzheimer's disease (AD). For SV2A imaging, a decrease in apparent tracer uptake is often due to the combination of gray-matter (GM) atrophy and SV2A decrease in the remaining tissue. Our aim is to reveal the true SV2A change by performing partial volume correction (PVC)., Methods: We performed two PVC algorithms, Müller-Gärtner (MG) and 'iterative Yang' (IY), on 17 AD participants and 11 cognitive normal (CN) participants using the brain-dedicated HRRT scanner. Distribution volume V T , the rate constant K 1 , binding potential BP ND (centrum semiovale as reference region), and tissue volume were compared., Results: In most regions, both PVC algorithms reduced the between-group differences. Alternatively, in hippocampus, IY increased the significance of between-group differences while MG reduced it (V T , BP ND and K 1 group differences: uncorrected: 20%, 27%, 17%; MG: 18%, 22%, 14%; IY: 22%, 28%, 17%). The group difference in hippocampal volume (10%) was substantially smaller than any PET measures. MG increased GM binding values to a greater extent than IY due to differences in algorithm assumptions., Conclusion: 11 C-UCB-J binding is significantly reduced in AD hippocampus, but PVC is important to adjust for significant volume reduction. After correction, PET measures are substantially more sensitive to group differences than volumetric MRI measures. Assumptions of each PVC algorithm are important and should be carefully examined and validated. For 11 C-UCB-J, the less stringent assumptions of IY support its use as a PVC algorithm over MG., Competing Interests: Declaration of Competing Interest The other authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

[Purpose] No study has examined whether the determinants of longitudinal changes in brachial-ankle pulse wave velocity differ depending on the baseline brachial-ankle pulse wave velocity values. Therefore, this study aimed to extract these determinants in high- and low-value groups based on the FY2014 brachial-ankle pulse wave velocity values. [Participants and Methods] Participants were 97 male workers who underwent continuous health assessments from FY2014 to four years later. Their demographic, lifestyle, body-composition, and hemodynamic data were recorded. First-year data were subtracted from data obtained four years later for each continuous variable item, and the difference divided by the number of years was considered as the annual change. Based on the first-year median brachial-ankle pulse wave velocity, participants were classified into high- and low-brachial-ankle pulse wave velocity groups, i.e., high- and low-value groups, respectively. Multiple regression analysis was performed with the annual change in brachial-ankle pulse wave velocity serving as the dependent variable for both groups. [Results] In comparison with the values obtained in the first year, brachial-ankle pulse wave velocity obtained four years later increased significantly in the low-value group and tended to increase in the high-value group. Increased visceral fat area in the high-value group and increased diastolic blood pressure and heart rate in the low-value group were associated with worsening brachial-ankle pulse wave velocity. [Conclusion] The determinants of longitudinal changes in the brachial-ankle pulse wave velocity differed depending on the baseline brachial-ankle pulse wave velocity values., (2021©by the Society of Physical Therapy Science. Published by IPEC Inc.)

[ 11 C]UCB-J PET for synaptic vesicle glycoprotein 2 A (SV2A) has been proposed as a suitable marker for synaptic density in Alzheimer's disease (AD). We compared [ 11 C]UCB-J binding for synaptic density and [ 18 F]FDG uptake for metabolism (correlated with neuronal activity) in 14 AD and 11 cognitively normal (CN) participants. We assessed both absolute and relative outcome measures in brain regions of interest, i.e., K 1 or R 1 for [ 11 C]UCB-J perfusion, V T (volume of distribution) or DVR to cerebellum for [ 11 C]UCB-J binding to SV2A; and K i or K i R to cerebellum for [ 18 F]FDG metabolism. [ 11 C]UCB-J binding and [ 18 F]FDG metabolism showed a similar magnitude of reduction in the medial temporal lobe of AD -compared to CN participants. However, the magnitude of reduction of [ 11 C]UCB-J binding in neocortical regions was less than that observed with [ 18 F]FDG metabolism. Inter-tracer correlations were also higher in the medial temporal regions between synaptic density and metabolism, with lower correlations in neocortical regions. [ 11 C]UCB-J perfusion showed a similar pattern to [ 18 F]FDG metabolism, with high inter-tracer regional correlations. In summary, we conducted the first in vivo PET imaging of synaptic density and metabolism in the same AD participants and reported a concordant reduction in medial temporal regions but a discordant reduction in neocortical regions.