Tremendous advancement has been made in biomarker assessment, molecular neuroimaging and disease modifying therapy in neurodegenerative cognitive disorders. China is lacking clinical cohorts that deeply profile patients from memory clinic that integrate both comprehensive clinical assessment and multi-modal biomarker examinations. The Shanghai Memory Study (SMS) is an ongoing prospective hospital-based cohort study. Participants underwent extensive clinical and neuropsychological assessments, genotyping, multimodal magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and various biospecimen collection. In this article, the rationale, aims, study design, data collection, and future directions of SMS were summarized. Preliminary analyses including plasma biomarker assay using the Simoa platform, molecular neuroimaging of Aβ PET and tau PET were performed across different diagnostic groups. A total of 2,001 participants with cognitive complaints were enrolled, including 115 with subjective cognitive decline (SCD), 938 with mild cognitive impairment (MCI), and 948 with dementia. The proportions of individuals with A+/T+ in PET scans were 15.8% in SCD cases, 51.2% in MCI cases, and 100% in AD dementia. And the proportions of individuals with A+/T- in PET scans were 5.3% in SCD cases and 3.3% in MCI cases. In the analysis with plasma biomarkers, as the CDR score increased, Aβ40, Aβ42, and Aβ42/Aβ40 ratio exhibited a decreasing trend, whereas t-tau, NfL, and p -tau181 showed an increasing trend. In a subcohort of 251 patients with amnestic MCI (aMCI), during a median follow-up of 4.7 years, 88 (35.1%) progressed to AD dementia, 8 developed non-AD dementia. Individuals with low Aβ42/Aβ40 and high p -tau181 at baseline demonstrated the highest risk of developing AD (hazard ratio = 4.83, 95% CI 2.37–9.86). By offering an integrated framework for investigating cognitive disorders, SMS will facilitate the exploration of AD pathogenesis and deepen the understanding of cognitive disorders.

BACKGROUND:Clinical-biological diagnosis of Alzheimer's disease (AD) is gaining increasing recognition. Beyond diagnosis, biological profiles can be of great benefit for disease monitoring and prognosis, although evidence from real-world memory clinics is still limited. METHOD:211 subjects with cognitive concerns and 31 cognitive unimpaired (CU) volunteers visiting our memory clinic with longitudinal follow-up were enrolled (mean (SD) interval: 1.89 (1.19) years). All participants received AD pathological evaluations (core 1: amyloid-PET or plasma p-tau 217; core 2: Florzolotau tau-PET) at baseline. Biomarkers were assessed by binary amyloid and tau status, and quantitative tau burden in key regions (medial temporal lobe (MTL), neocortical areas (NEO)). Clinical progression served as the primary outcome (increase in CDR or annual MMSE decline ≥ 6). The prognostic values of biomarkers were compared with basic demographic characteristics (a combination of significant risks in Cox Proportional Hazard Models) by receiver operating characteristic analysis. RESULT:91 (37.6%) participants were classified as clinical progression (0 CU (0%), 0 SCD (0%), 41 MCI (31.5%) and 50 (56.8%) AD dementia). Only age (older, HR = 1.03, 95%CI 1.01-1.07, P = 0.005) and sex (female, HR = 1.61, 95%CI 1.02-2.52, P = 0.039) showed the significant risks for clinical progression. In the entire cohort, incorporating any of the above biomarkers individually into the basic model (AUC = 0.57) significantly improved the prognostic value (AUC = 0.73-0.80, all P < 0.001), with quantitative tau burden in NEO showing the best added value. Combining both amyloid and tau biomarkers into the basic model further slightly improved the prognosis (AUC = 0.77-0.82), with the one with binary amyloid status plus quantitative tau burden in NEO showing the best added value. In the A+ subcohort, prognostic value was significantly increased by incorporating the quantitative tau burden (MTL: AUC = 0.71, P < 0.001; NEO: AUC = 0.73, P < 0.001) into the basic model (AUC = 0.50), while binary tau status didn't achieve significant improvement (AUC = 0.60, P = 0.125). CONCLUSION:AD core biomarkers are promising in improving clinical prognosis, among which quantitative tau burden is preferable to binary assessment, especially in the AD continuum.

Tau PET is increasingly recognized for its prognostic and disease-monitoring value in Alzheimer’s disease (AD); however, real-world evidence in heterogeneous memory clinic populations remains limited, especially for novel tau positron emission tomography (PET) with 18F-Florzolotau. We prospectively enrolled 340 individuals (patients with cognitive complaints and community volunteers) undergoing baseline amyloid PET and tau PET with 18F-Florzolotau, with subsets for clinical follow-up (n = 260; median interval 1.45 [0.96–2.56] years) and repeat tau PET (n = 64; median interval 2.27 [1.47–2.88] years). The incremental prognostic role of tau PET beyond demographic and clinical characteristics was assessed using binary clinical outcomes and continuous cognitive declines. The monitoring utility of tau PET was evaluated through tau accumulation rates versus clinical outcomes, and cognition-tau correlations. Cross-sectionally, tau standardized uptake value ratios (SUVRs) increased with cognitive impairment severity and correlated with domain-specific deficits. Longitudinally, baseline tau SUVRs provided incremental prognostic value, with higher neocortical SUVR as the sole independent predictor beyond demographic and clinical characteristics, particularly in AD spectrum (HR = 1.62, p = 0.018). Accelerated tau deposition was observed in motor regions including the precentral gyrus (β = 0.07 SUVR/year, p = 0.007) and supplementary motor area (β = 0.08 SUVR/year, p = 0.017) in those clinically progressive individuals than stable counterparts. Critically, these motor regions showed stronger cognition-tau correlations than canonical tau-vulnerable regions (medial temporal lobe and neocortex), establishing them as superior monitoring biomarkers. 18F-Florzolotau PET provides significant prognostic value and enables AD progression tracking. Motor cortices offered enhanced sensitivity for monitoring clinical deterioration in symptomatic stages, supporting their integration into stage-specific frameworks.

BACKGROUND AND PURPOSE:Epilepsy, a globally prevalent neurologic disorder, necessitates precise identification of the epileptogenic zone (EZ) for effective surgical management. While the individual utilities of FDG-PET and flumazenil (FMZ)-PET have been demonstrated, their combined efficacy in localizing the epileptogenic zone remains underexplored. We aim to improve the noninvasive prediction of EZ in temporal lobe epilepsy (TLE) by combining FDG-PET and FMZ-PET with statistical feature extraction and machine learning. MATERIALS AND METHODS:This study included 20 drug-resistant patients with unilateral TLE (14 mesial TLE, 6 lateral TLE) and 2 control groups (n = 29 for FDG, n = 20 for FMZ). EZ of each patient was confirmed by postsurgical pathology and 1-year follow-up, while propagation zone (PZ) and noninvolved zone (NIZ) were derived from the epileptogenicity index based on presurgical stereo-encephalography (SEEG) monitoring. Whole brain PET scans were obtained with dual tracers [18F]FDG and [18F]FMZ on separate days, from which standard uptake value ratio (SUVR) was calculated by global mean scaling. Low-order statistical parameters of SUVRs and t-maps derived against control groups were extracted. Additionally, fused FDG and FMZ features were created by using arithmetic operations. Spearman correlation was used to investigate the associations between FDG and FMZ, while multiple linear regression analyses were used to explore the interaction effects of imaging features in predicting epileptogenicity. Crafted imaging features were used to train logistic regression models to predict EZ, whose performance was evaluated by using 10-fold cross-validation at ROI level, and leave-1-patient-out cross-validation at patient level. RESULTS:FDG SUVR significantly decreased in EZ and PZ compared with NIZ, while FMZ SUVR in EZ significantly differed from PZ. Interaction effects were found between FDG and FMZ in their prediction of epileptogenicity. Fusion of FDG and FMZ provided the best prediction model with an area under the curve (AUC) of 0.86 [0.84-0.87] for EZ versus NIZ and an AUC of 0.79 [0.77-0.81] for EZ versus PZ, eliminating 100% false-positives in 50% of patients, and ≥80% FPs in 90% of patients at patient level. CONCLUSIONS:Combined FDG and FMZ offer a promising avenue for noninvasive localization of the epileptogenic zone in TLE, potentially refining surgical planning.

The loss of synaptic vesicle glycoprotein 2 A (SV2A) can lead to dysfunction of GABAergic neurons, but a direct comparison of SV2A and GABAA receptor densities in humans has not been assessed. This study evaluated SV2A and GABAA receptor abnormalities in patients with drug-resistant epilepsy (DRE) and compared the patterns to glucose hypometabolism. Eleven patients with DRE were retrospectively recruited and underwent PET imaging with [18F]fluorodeoxyglucose ([18F]FDG), [18F]Flumazenil (FMZ), and [18F]SynVesT-1. Visual assessments counted abnormal metabolic brain regions based on the Anatomical Automatic Labeling (AAL) atlas, while voxel-level analyses delineated the abnormal metabolic distributions. The relationship between hypo-metabolic distributions and the age of epilepsy onset was analyzed. The hypometabolic regions in [18F]FDG PET, identified in the AAL atlas, was significantly broader than in [18F]FMZ (p = 0.0005) and [18F]SynVesT-1 (p = 0.0010) PET, with no statistical difference observed between [18F]FMZ and [18F]SynVesT-1 PET (p > 0.05). The voxel number in [18F]FDG PET was significantly higher than that of the [18F]FMZ and [18F]SynVesT-1 PET in both hypo-intensity area and severe hypo-intensity area. The ratio of the voxel number between these two area was higher for [18F]SynVesT-1 PET compared to [18F]FDG PET (p = 0.0195) and [18F]FMZ PET (p = 0.0237), and positively correlated with the age of epilepsy onset (r = 0.7397, p = 0.0145). [18F]FMZ and [18F]SynVesT-1 PET images revealed a more restricted pattern of reduced uptake compared to [18F]FDG PET in DRE patients. The age of epilepsy onset correlated with a reduction in [18F]SynVesT-1 uptake but not in [18F]FMZ or [18F]FDG uptake.

Background Epilepsy affects approximately 70 million people worldwide, with a third of them being drug-resistant and requiring surgical intervention. Accurate localization of the seizure onset zone (SOZ) is crucial for effective surgery but remains challenging. New method We proposed a method using iterative independent component analysis (ICA) to map seizure propagation of drug-resistant temporal lobe epilepsy (TLE). For each assumed seizure origin, ICA was applied to the remaining contacts to identify propagation components, with the highest correlating component being the propagating signal. Iterative removal of nearby contacts revealed spatial propagation profiles. Machine learning models were applied to the propagation profiles to distinguish the SOZ. Results Seizure propagation features differed significantly between SOZ and non-SOZ contacts in seizure free patients (both local cohort N=21, and independent dataset N=13), but not in non-seizure free patients (N=11). Propagation-based classifiers achieved robust performance (AUC = 0.85), outperforming iEEG source imaging (AUC = 0.73). In mesial TLE, propagation maintained high accuracy (AUC = 0.84) while iEEG source imaging dropped markedly (AUC = 0.64).Comparison with existing methodsTraditional methods for SOZ localization, such as visual inspection of SEEG and source imaging techniques, rely heavily on expert interpretation. iEEG source imaging assumes linear forward models and can be susceptible to inaccuracies due to electrode placement and noise. In contrast, our proposed iterative ICA approach is purely data-driven and adaptively identifies the dominant propagation pathways across individual seizures. Conclusion This work introduces a data-driven strategy to characterize seizure propagation, potentially improving SOZ localization with deep brain origins.

Clinical‐biological diagnosis of Alzheimer's disease (AD) is gaining increasing recognition. Beyond diagnosis, biological profiles can be of great benefit for disease monitoring and prognosis, although evidence from real‐world memory clinics is still limited. 211 subjects with cognitive concerns and 31 cognitive unimpaired (CU) volunteers visiting our memory clinic with longitudinal follow‐up were enrolled (mean (SD) interval: 1.89 (1.19) years). All participants received AD pathological evaluations (core 1: amyloid‐PET or plasma p ‐tau 217; core 2: Florzolotau tau‐PET) at baseline. Biomarkers were assessed by binary amyloid and tau status, and quantitative tau burden in key regions (medial temporal lobe (MTL), neocortical areas (NEO)). Clinical progression served as the primary outcome (increase in CDR or annual MMSE decline ≥ 6). The prognostic values of biomarkers were compared with basic demographic characteristics (a combination of significant risks in Cox Proportional Hazard Models) by receiver operating characteristic analysis. 91 (37.6%) participants were classified as clinical progression (0 CU (0%), 0 SCD (0%), 41 MCI (31.5%) and 50 (56.8%) AD dementia). Only age (older, HR = 1.03, 95%CI 1.01‐1.07, P = 0.005) and sex (female, HR = 1.61, 95%CI 1.02‐2.52, P = 0.039) showed the significant risks for clinical progression. In the entire cohort, incorporating any of the above biomarkers individually into the basic model (AUC = 0.57) significantly improved the prognostic value (AUC = 0.73‐0.80, all P < 0.001), with quantitative tau burden in NEO showing the best added value. Combining both amyloid and tau biomarkers into the basic model further slightly improved the prognosis (AUC = 0.77‐0.82), with the one with binary amyloid status plus quantitative tau burden in NEO showing the best added value. In the A+ subcohort, prognostic value was significantly increased by incorporating the quantitative tau burden (MTL: AUC = 0.71, P < 0.001; NEO: AUC = 0.73, P < 0.001) into the basic model (AUC = 0.50), while binary tau status didn’t achieve significant improvement (AUC = 0.60, P = 0.125). AD core biomarkers are promising in improving clinical prognosis, among which quantitative tau burden is preferable to binary assessment, especially in the AD continuum.

INTRODUCTION:Despite advances in biomarker assessment, molecular neuroimaging, and disease-modifying therapies for cognitive disorders, China lacks well-characterized clinical cohorts integrating comprehensive clinical assessments and multimodal biomarkers. METHODS:The Shanghai Memory Study (SMS), an ongoing hospital-based cohort, enrolled participants undergoing clinical/neuropsychological assessments, genotyping, multimodal imaging, and biospecimen collection. RESULTS:From 2012 to 2024, 2001 participants were enrolled: 115 cognitively unimpaired (CU), 938 with mild cognitive impairment (MCI), and 948 with dementia. Positron emission tomography (PET) scan revealed A+/T+ positivity rates of 15.8% in CU, 51.2% in MCI, and 100% in Alzheimer's disease dementia (ADD). Plasma tau phosphorylated at threonine 181 (p-tau181) level increased gradually across the AD continuum. Blood p-tau181 and 18F-Florzolotau PET showed comparable utility for amyloid status identification. In a subcohort of 251 amnestic MCI (aMCI) patients, low Aβ42/Aβ40 and elevated p-tau181 predicted 4.7-year ADD risk. DISCUSSION:By offering an integrated framework, SMS will facilitate the exploration of AD pathogenesis and the understanding of cognitive disorders. HIGHLIGHTS:The SMS is an ongoing prospective cohort study based on a memory clinic in China. The SMS has established a relatively large-scale dataset that includes clinical data, biofluid markers, MRI and PET imaging, and novel biomarkers. By offering an integrated framework, SMS aims to facilitate the exploration of AD pathogenesis and deepen our understanding of cognitive disorders.

Artificial intelligence (AI)-assisted PET imaging is emerging as a promising tool for the diagnosis of Parkinson’s disease (PD). We aim to systematically review the diagnostic accuracy of AI-assisted PET in detecting PD. The Ovid MEDLINE, Ovid Embase, Web of Science, and IEEE Xplore databases were systematically searched for related studies that developed an AI algorithm in PET imaging for diagnostic performance from PD and were published by August 17, 2023. Binary diagnostic accuracy data were extracted for meta-analysis to derive outcomes of interest: area under the curve (AUC). 23 eligible studies provided sufficient data to construct contingency tables that allowed the calculation of diagnostic accuracy. Specifically, 11 studies were identified that distinguished PD from normal control, with a pooled AUC of 0.96 (95% CI: 0.94–0.97) for presynaptic dopamine (DA) and 0.90 (95% CI: 0.87–0.93) for glucose metabolism ( 18 F-FDG). 13 studies were identified that distinguished PD from the atypical parkinsonism (AP), with a pooled AUC of 0.93 (95% CI: 0.91 − 0.95) for presynaptic DA, 0.79 (95% CI: 0.75–0.82) for postsynaptic DA, and 0.97 (95% CI: 0.96–0.99) for 18 F-FDG. Acceptable diagnostic performance of PD with AI algorithms-assisted PET imaging was highlighted across the subgroups. More rigorous reporting standards that take into account the unique challenges of AI research could improve future studies.

目的 观察深部脑电刺激(DBS)后帕金森病(PD)患者运动症状改善与黑质纹状体不同亚区的相关性.方法回顾性分析6例经丘脑底核(STN)-DBS后运动症状改善的PD患者,分别于STN-DBS前及后7个月采用PD统一评分量表第Ⅲ部分(UPDRS-Ⅲ)及Hoehn-Yahr(H-Y)分级进行评估,计算运动症状改善值;同时行多巴胺转运蛋白(DAT)PET脑显像,以SPM12软件于双侧尾状核、壳核前部、壳核后部及黑质勾画ROI,获得各ROI内平均放射性计数,并以小脑为参考,计算双侧尾状核、壳核前部、壳核后部及黑质的DAT摄取及DAT摄取改善率;采用Spearman相关分析观察运动症状改善值与STN-DBS后7个月DAT摄取显著增高脑区治疗前DAT摄取及DAT摄取改善率的相关性.结果STN-DBS前UPDRS-Ⅲ评分及H-Y分级与其后7个月差异均有统计学意义(P均＜0.05).STN-DBS后7个月双侧壳核后部部分区域及起病侧黑质致密部DAT摄取显著高于STN-DBS前(P均＜0.01),而双侧尾状核及壳核前部部分区域DAT摄取显著低于STN-DBS前(P均＜0.01).STN-DBS前起病对侧黑质致密部DAT摄取与运动症状改善值呈高度负相关(r=-1.0,P＜0.05);双侧壳核后部及起病侧黑质致密部DAT摄取、双侧壳核后部及双侧黑质致密部DAT摄取改善率与运动症状改善值均无明显相关(P均＞0.05).结论 PD患者STN-DBS后双侧壳核后部部分区域及起病侧黑质致密部DAT摄取增高;STN-DBS前起病对侧黑质致密部DAT摄取与运动症状改善值呈高度负相关.

Background Gaining more information about the reciprocal associations between different biomarkers within the ATN (Amyloid/Tau/Neurodegeneration) framework across the Alzheimer’s disease (AD) spectrum is clinically relevant. We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography (PET) ATN biomarkers in subjects with cognitive complaints. Methods A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging ( 18 F-florbetapir for A, 18 F-Florzolotau for T, and 18 F-fluorodeoxyglucose [ 18 F-FDG] for N) was enrolled ( n = 137). The β-amyloid (Aβ) status (positive versus negative) and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances. Results Plasma phosphorylated tau 181 (p-tau181) level was found to be associated with PET imaging of ATN biomarkers in the entire cohort. Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+ and Aβ− subjects. An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+ subjects. Additionally, glucose hypometabolism – along with elevated plasma neurofilament light chain level – was related to more severe cognitive impairment in Aβ− subjects. Conclusion Plasma p-tau181, as well as 18 F-florbetapir and 18 F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβ status in symptomatic stages of AD. 18 F-Florzolotau and 18 F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment. Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.

Quantification of tau accumulation using positron emission tomography (PET) is critical for the diagnosis of Alzheimer’s disease (AD). This study aimed to evaluate the feasibility of 18F-florzolotau quantification in patients with AD using a magnetic resonance imaging (MRI)–free tau PET template, since individual high-resolution MRI is costly and not always available in practice. 18F-florzolotau PET and MRI scans were obtained in a discovery cohort including (1) patients within the AD continuum (n = 87), (2) cognitively impaired patients with non-AD (n = 32), and (3) cognitively unimpaired subjects (n = 26). The validation cohort comprised 24 patients with AD. Following MRI-dependent spatial normalization (standard approach) in randomly selected subjects (n = 40) to cover the entire spectrum of cognitive function, selected PET images were averaged to create the 18F-florzolotau-specific template. Standardized uptake value ratios (SUVRs) were calculated in five predefined regions of interest (ROIs). MRI-free and MRI-dependent methods were compared in terms of continuous and dichotomous agreement, diagnostic performances, and associations with specific cognitive domains. MRI-free SUVRs had a high continuous and dichotomous agreement with MRI-dependent measures for all ROIs (intraclass correlation coefficient ≥ 0.980; agreement ≥ 94.5

Purpose: 18F-Florzolotau is a novel second-generation tau radiotracer that shows higher binding affinity and selectivity and no off-target binding. The proportion loss of functional connectivity strength (PLFCS) is a new indicator for representing brain functional connectivity (FC) alteration. This study aims to estimate the relationship between the regional tau accumulation and brain FC abnormality in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) patients based on Florzolotau PET and fMRI. Methods: 22 NC (normal control), 31 MCI and 42 AD patients who have already been scanned with 18F-Florzolotau PET were recruited in this study. (We calculated the PLFCS and standardized uptake value ratio (SUVR) of each node based on the Brainnetome atlas (BNA) template. The SUVR of 246 brain regions was calculated with the cerebellum as the reference region. Further functional connection strength (FCs), PLFCS and SUVR of each brain region were obtained in three groups for comparison.) For each patient, PLFCS and standardized uptake value ratio (SUVR) were calculated based on the Brainnetome atlas (BNA) template. These results, as well as functional connection strength (FCs), were then compared between different groups. Multiple permutation tests were used to determine the target nodes between NC and cognitive impairment (CI) groups (MCI and AD). The relationship between PLFCS and neuropsychological scores or cortical tau deposit was investigated via Pearson correlation analysis. Results: Higher PLFCS and FCs in AD and MCI groups were found compared to the NC group. The PLFCS of 129 brain regions were found to be different between NC and CI groups, and 8 of them were correlated with tau SUVR, including superior parietal lobule (MCI: r = 0.4360, p = 0.0260, AD: r = −0.3663, p = 0.0280), middle frontal gyrus (AD: MFG_R_7_2: r = 0.4106, p = 0.0129; MFG_R_7_5: r = 0.4239, p = 0.0100), inferior frontal gyrus (AD: IFG_R_6_2: r = 0.3589, p = 0.0316), precentral gyrus (AD: PrG_R_6_6: r = 0.3493, p = 0.0368), insular gyrus (AD: INS_R_6_3: r = 0.3496, p = 0.0366) and lateral occipital cortex (AD: LOcC _L_4_3: r = −0.3433, p = 0.0404). Noteworthily, the opposing relationship was found in the superior parietal lobule in the MCI and AD groups. Conclusions: Brain functional connectivity abnormality is correlated with tau pathology in AD and MCI.

ABSTRACT:Pineal yolk sac tumors (YSTs) are a rare type of extragonadal YST. They make up a small fraction of all intracranial germ cell tumors and an even small fraction of pineal masses overall. This study reported a case of pineal YST with α-fetoprotein production revealed by 18F-FDG and 68Ga-FAPI PET/MRI. In the PET images, 68Ga-FAPI showed a far better tumor-to-background ratio than 18F-FDG in the pineal YST because there is little 68Ga-FAPI uptake in the brain. This case indicates that 68Ga-FAPI PET/MRI may be a useful tool for evaluating intracranial YST and other types of tumors in central nervous system.

Objective:To explore the abnormal brain metabolic pattern and connectivity in temporal lobe epilepsy (TLE) patients.Methods:18F-FDG PET images of 75 patients diagnosed as drug resistant unilateral TLE from January 2014 to December 2016 in Huashan Hospital of Fudan University were collected retrospectively, including 41 (22 males, 19 females, age (28.4±8.7) years) left TLE (LTLE) and 34 (13 males, 21 females, age (28.5±8.8) years) right TLE (RTLE). Forty-four healthy controls (24 males, 20 females, age (31.2±6.2) years) were also enrolled. The cerebral glucose metabolism in TLE patients and the controls were analyzed with statistical parametric mapping (SPM) 12. The brain connectivity based on glucose metabolism were analyzed with bilateral hippocampus and amygdala as seeds. Permutation test with 1 000 permutations was used to analyze data. Results:Compared to control group, in both LTLE and RTLE groups, hypometabolism was found in affected hippocampus, amygdala, insula and temporal gyrus and hypermetabolism was observed in health hippocampus, parahippocampal gyrus, amygdala, lenticular nucleus and thalamus. In addition, hypometabolism was also found in affected superior/middle frontal gyrus and hypermetabolism was also found in bilateral frontal-orbital gyrus, bilateral cerebellum, affected lenticular nucleus and thalamus in LTLE group. In both TLE groups, affected seeds exhibited increased connectivity with affected superior frontal gyrus, lingual gyrus, fusiform gyrus, superior/middle temporal gyrus and temporal pole (all P<0.05); affected seeds exhibited increased connectivity with health superior frontal gyrus ( P=0.005), lingual gyrus ( P=0.018) and transverse temporal gyrus ( P=0.016) in RTLE group in addition. Besides, affected seeds exhibited decreased connectivity with bilateral default mode network (DMN) (all P<0.05), affected caudate nucleus ( P=0.015) and health thalamus ( P=0.008), in a uniform distribution pattern in LTLE group, and with bilateral cerebral cortex in an irregular distribution pattern in RTLE group (all P<0.05). In LTLE group, health seeds exhibited more increased connections with superior ( P=0.005)/middle frontal gyrus ( P=0.042), health hippocampus ( P=0.038), parahippocampal gyrus ( P=0.019), amygdala ( P=0.038), posterior cingulate gyrus ( P=0.004), and bilateral fusiform gyrusand ( P=0.048) compared with RTLE group; while, in RTLE group, health seeds exhibited more decreased connections with health superior ( P=0.047), inferior frontal gyrus ( P<0.001), orbital frontal gyrus ( P<0.001) and rectus gyrus ( P=0.016) compared with LTLE group. Conclusion:Altered brain glucose metabolism and connectivity pattern are found and will elucidate the underlying metabolic pattern of TLE.

Objective:To investigate characteristics and differences of cerebral glucose metabolism in patients with anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis from the perspective of different trigger factors of antibodies. Methods:A total of 15 patients (8 males, 7 females, age (30.5±17.7) years) with anti-NMDAR encephalitis between January 2016 and January 2019 in Huashan Hospital, Fudan University were recruited retrospectively. All patients underwent resting state cerebral 18F-FDG PET imaging. The characteristics of brain glucose metabolism were analyzed, and the SUV ratio (SUVR) was semi-quantitatively compared with that in 12 healthy subjects (HS; 7 males, 5 females, age (51.5±9.6) years). Independent-sample t test was used to analyze the data. Results:Among 15 patients, 5 patients were viral encephalitis-related anti-NMDAR encephalitis, showing focal decreased metabolism in unilateral temporal lobe or basal ganglia (SUVR: patients: 0.659±0.219; HS: 1.754±0.203; t=-9.58, P<0.001), with increased metabolism in contralateral temporal lobe or basal ganglia (SUVR: patients: 2.275±0.244; HS: 1.960±0.227; t=2.55, P=0.022) in 18F-FDG PET imaging. Six patients were cryptogenic anti-NMDAR encephalitis, showing asymmetric increased metabolism in frontal, temporal, parietal and basal ganglia (SUVR: patients: 2.482±0.395; HS: 1.754±0.203; t=5.23, P<0.001), with decreased metabolism in bilateral occipital lobes. The remaining 4 cases were paraneoplastic origin accompanied by teratoma, showing increased metabolism in bilateral temporal and basal ganglia (SUVR: patient: 2.359±0.181; HS: 1.960±0.227; t=3.16, P=0.007), with mild decreased metabolism in bilateral occipital lobe. Conclusions:The abnormal changes of cerebral glucose metabolism in patients with anti-NMDAR encephalitis can be divided into at least three patterns according to different trigger factors. A comprehensive understanding of these characteristic metabolic changes is helpful for detecting disease, and may provide potential value in indicating different causes.

AIMS:We aimed to explore the evidence of brain microglia activation in diabetic neuropathic pain (DNP) and the effect and mechanism of glucagon-like peptide-1 receptor agonist (GLP-RA) on DNP via brain microglia.METHODS:Brain microglia activation was observed in DNP rats by positron emission tomography/computed tomography. The behavior of neuropathic pain was assessed in DNP rats after intracerebroventricular administration of GLP-1RA or microglial inhibitor minocycline. RNA sequencing was performed to explore the target of GLP-1RA on brain microglia. NOD-like receptor protein 3 (NLRP3) expression in brain microglia was evaluated in mentioned-above DNP rats, and the activation of NLRP3 inflammasome was analyzed in microglia treated with GLP-1RA.RESULTS:Microglia were activated in the cortex and thalamus of DNP rats. The thermal and mechanical allodynia were alleviated in DNP rats via intracerebroventricular administration of GLP-1RA or minocycline. And the activation of brain microglia was attenuated in DNP rats by intracerebroventricular administration of GLP-1RA. The expression of NLRP3 in brain microglia, which was found by RNA sequencing, was reduced in DNP rats by administration of GLP-1RA. Furthermore, GLP-1RA attenuated NLRP3 inflammasome activation in microglia triggered by LPS.CONCLUSION:GLP-1RA could alleviate DNP, possibly mediated by the suppression of brain microglia NLRP3 inflammasome activation.

Drug-resistant temporal lobe epilepsy (TLE) is a potential candidate for surgery; however, nearly one-third subjects had a poor surgical prognosis. We studied the underlying neuromechanism related to the surgical prognosis using graph theory based on metabolic brain network. Sixty-four unilateral TLE subjects with preoperative 18F-fluorodeoxyglucose (FDG) PET scanning were retrospectively enrolled and divided into Ia (Engel class Ia, n = 32) and non-Ia (Engel class Ib-IV, n = 32) groups according to more than 3-year follow-up after unilateral anterior temporal lobectomy (ATL). The metabolic brain network was constructed and the changed metabolic connectivity of Ia and non-Ia was detected compared with 15 matched healthy controls (HCs). Further, the network properties, including small-worldness and global efficiency, were calculated and hub nodes were also identified for the 3 groups respectively. Non-Ia group exhibited increased connectivity between contralateral fusiform gyrus and contralateral lingual gyrus; while Ia showed decreased connectivity mainly among bilateral frontal, temporal and parietal cortex. Graph theoretical analysis revealed that non-Ia group showed increased small-worldness (35%<s < 55%, P ≤ 0.05) compared to HCs; and elevated global efficiency (P = 0.05) and decreased Lp (P = 0.05) compared to Ia group. Ia group showed reduced Cp (55%<s < 63%, P < 0.05) and increased small-worldness (35%<s < 37%, P < 0.05) compared to HCs; Furthermore, disrupted hub nodes distribution pattern with the midcingulate gyrus disappeared, was also found in non-Ia group compared with the Ia group. All those results revealed that elevated network integration and metabolic connectivity, redistributed hub nodes pattern is associated with ongoing postoperative seizures in subjects with intractable TLE.

Alzheimer's Disease (AD), the leading cause of senile dementia, is a progressive neurodegenerative disorder affecting millions of people worldwide and exerting tremendous socioeconomic burden on all societies. Although definitive diagnosis of AD is often made in the presence of clinical manifestations in late stages, it is now universally believed that AD is a continuum of disease commencing from the preclinical stage with typical neuropathological alterations appearing decades prior to its first symptom, to the prodromal stage with slight symptoms of amnesia (amnestic mild cognitive impairment, aMCI), and then to the terminal stage with extensive loss of basic cognitive functions, i.e., AD-dementia. Positron emission tomography (PET) radiotracers have been developed in a search to meet the increasing clinical need of early detection and treatment monitoring for AD, with reference to the pathophysiological targets in Alzheimer's brain. These include the pathological aggregations of misfolded proteins such as β-amyloid (Aβ) plagues and neurofibrillary tangles (NFTs), impaired neurotransmitter system, neuroinflammation, as well as deficient synaptic vesicles and glucose utilization. In this article we survey the various PET radiotracers available for AD imaging and discuss their clinical applications especially in terms of early detection and cognitive relevance.

Aim: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a subgroup of treatable autoimmune encephalitis, characterized by rapid development of psychosis, cognitive impairments and seizures. Etiologically, anti-NMDAR encephalitis could be divided into three subgroups, which are paraneoplastic (especially associated with ovarian teratoma), viral encephalitis-related and cryptogenic. Each type is different in clinical course, treatment strategies and prognosis. In this study, we aim to investigate whether anti-NMDAR encephalitis patients with different trigger factors exhibit distinct cerebral metabolic patterns detected by 18F-fluorodeoxyglucose positron emission tomography imaging. Methods: 24 patients with anti-NMDAR encephalitis in acute phase from Huashan Hospital, Fudan University (Shanghai, China) were recruited in this study. Each patient was classified into one of etiological subgroups. Positron emission tomography images of individual patients were analyzed with both routine visual reading and computer-supported reading by comparison with those of the same 10 healthy controls using a voxel-wise statistical parametric mapping analysis. Results: Patients in both the cryptogenic (13 patients) and paraneoplastic (five patients) subgroups showed hypermetabolism in the frontal-temporal lobes and basal ganglia, covarying with hypometabolism in the occipital regions. Notably, the abnormal metabolism was usually asymmetric in the cryptogenic subgroup, but relatively symmetric in the paraneoplastic subgroup. Moreover, the other six patients secondary to viral encephalitis presented with significant hypometabolism in the bilateral occipital regions, as well as in the unilateral temporal lobes and part of basal ganglia (also is virus infection side), but hypermetabolism in the contralateral temporal areas. Conclusion: This study revealed that patients with anti-NMDAR encephalitis triggered by different factors presented distinct cerebral metabolic patterns. Awareness of these patterns may help to better understand the varying occurrence and development of anti-NMDAR encephalitis in each subgroup, and could offer valuable information to the early diagnosis, treatment and prognosis of this disorder. Trial registration number ChiCTR2000029115 (Chinese clinical trial registry site, http://www.chictr.org)