Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder with different metabolic patterns in parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes, but their longitudinal changes are not well understood. To characterize longitudinal changes of glucose metabolism and network connectivity in MSA using 18 F-FDG-PET for early diagnosis and disease progression tracking, we retrospectively analyzed 29 MSA patients (17 MSA-P, 12 MSA-C) and 28 healthy controls. Regional glucose uptake was assessed as standardized uptake value ratios (SUVR). We examined inter-regional connectivity via correlation analysis and modeled metabolic decline using nonlinear mixed-effects models. Clinical progression was measured using the Unified Multiple System Atrophy Rating Scale (UMSARS). MSA-P displayed progressive hypometabolism in the putamen, cerebellum, and frontal cortex, while MSA-C showed declines primarily in the cerebellum and frontal regions. Longitudinal modeling indicated a faster putaminal decline in MSA-P ( β = −0.015 ± 0.006) than in MSA-C ( β = 0 ± 0.011), whereas cerebellar metabolism declined over time in both groups with overlapping slopes in MSA-P ( β = −0.022 ± 0.006) and MSA-C ( β = −0.022 ± 0.011). Regional metabolic reductions correlated with UMSARS progression (putamen in MSA-P: r = −0.59, p < 0.001; cerebellum in MSA-C: r = −0.62, p < 0.001). Significant connectivity disruptions were noted in frontal, basal ganglia, and cerebellar-parietal circuits. Longitudinal FDG-PET reveals distinct metabolic decline patterns in MSA subtypes—putamen in MSA-P and cerebellum in MSA-C—linked to clinical severity. These findings may inform clinical practice and trial design, supporting the use of FDG-PET for biological staging, monitoring disease progression, and potentially evaluating treatment responses.

Background/Objectives: This study explored the heterogeneous distribution pattern of translocator protein 18kDa (TSPO)-PET/MRI using radioligand [18F] DPA-714 in temporal lobe epilepsy patients and identified clinical factors influencing imaging outcomes. Methods: The TSPO imaging in individual patient was evaluated with both visual reading and quantitative assessment using an asymmetry index based on cerebellum-normalized standardized uptake values. The association between clinical factors and TSPO imaging outcomes was assessed. Pathological evaluation was conducted in three patients. Results: Twenty-nine TLE patients and ten healthy controls were enrolled. Visual evaluation revealed increased [18F] DPA-714 uptake in twenty patients as compared to controls, predominantly in a unilateral regional brain, while the remaining nine patients showed visually undetectable uptake of [18F] DPA-714. Consistently, quantitative analysis revealed that 69% (20/29) patients exhibited at least one brain area with significant asymmetry index, notably in the temporal lobe (85%, 17/20). A high asymmetry index could also be observed in the parietal (13.8%, 4/29) and occipital lobe (17.2%, 5/29). Significant associations were identified between the asymmetry index and seizure frequency (p = 0.045, OR = 7.994), and the interval from last seizure to PET scan (p = 0.033, OR = 6.712). Moreover, we confirmed the pathology in three patients via immunohistochemistry, which underscored the potential of TSPO-PET in detecting minor lesion. Conclusions: TSPO-PET reveals patient-specific and network-level neuroinflammatory heterogeneity in MRI-negative TLE, supporting its potential role as a complementary tool for presurgical evaluation.

Parkinson's disease (PD) exhibits a characteristic posterior-to-anterior gradient of striatal dopamine loss, yet the underlying upstream mechanisms remain unclear. We combined in vivo ¹⁸F-FPCIT dopamine transporter (DaT) PET/MRI, quantitative susceptibility mapping, and diffusion MRI tractography in 48 PD patients and 10 healthy controls to test whether substantia nigra pars compacta (SNc) iron and microstructural disruption mediate posterior putaminal vulnerability. PD patients showed marked posterior putamen (pPut) DaT reduction (~60%) and elevated SNc iron. SNc iron negatively correlated with striatal DaT availability, and nigrostriatal pathways to the pPut exhibited higher axial diffusivity. Serial mediation analyses demonstrated that SNc iron indirectly impaired striatal DaT function via reduced SNc DaT binding. Putaminal DaT-SBR robustly discriminated PD from controls (AUC 0.93-0.96), exceeding caudate performance. Transgenic and α-synuclein preformed fibril mouse models provided qualitative anatomical support. These findings identify SNc iron-related degeneration as a key driver of posterior striatal vulnerability in PD.

BACKGROUND:Corticobasal syndrome (CBS) may arise from heterogeneous neuropathological substrates, including corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD), and biomarker-based stratification has therefore become central to its characterization in vivo. In a large CBS cohort, we examined whether 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) metabolic patterns reflect underlying amyloid-β deposition and tau topography, and how these patterns relate to the clinical phenotype. METHODS:We conducted a cross-sectional study of consecutive patients with CBS and were enrolled at Huashan Hospital, Fudan University, between December 2019 and February 2025. Each patient underwent 18F-FDG PET for cerebral glucose metabolism, amyloid status assessment using amyloid PET or cerebrospinal fluid biomarkers, and florzolotau(18F) PET for tau topography. RESULTS:Among 113 patients, 18F-FDG PET identified five distinct metabolic subgroups: AD type (n = 20), CBD type I (n = 45), CBD type II (n = 18), PSP type (n = 26), and frontotemporal dementia type (n = 4). The AD metabolic pattern showed high specificity for amyloid-β positivity (98.5%) and for combined AD pathology (amyloid-β plus tau, 98.6%), with correspondingly lower sensitivity (54.2% and 72.2%). 18F-FDG PET patterns further showed high specificity for the PSP tau profile (96.2%) and high sensitivity for the CBD tau profile (97.7%). On spatial analysis, amyloid-β deposition significantly mediated the regional coupling between tau accumulation and cerebral glucose hypometabolism. CONCLUSIONS:18F-FDG PET identifies metabolic patterns that correspond to specific proteinopathies underlying CBS with high specificity but requires integration within multimodal biomarker frameworks for comprehensive patient stratification. © 2026 International Parkinson and Movement Disorder Society.

BACKGROUND:Behavioral variant of frontotemporal dementia (bvFTD) often presents with parkinsonism. Our study aimed to characterize the dopaminergic deficit pattern in bvFTD-parkinsonism (bvFTD-P) using dopamine transporter (DAT) positron emission tomography (PET) and to assess its potential value in differentiating bvFTD-P from progressive supranuclear palsy (PSP), multiple system atrophy-parkinsonism (MSA-P), and Parkinson disease (PD). METHODS:A total of 30 bvFTD-P patients underwent 11 C-CFT or 18 F-FP-CIT PET and were compared with 71 patients with PSP, 41 with MSA-P, 61 with PD, and 43 healthy controls (HC). DAT binding values in the caudate, anterior putamen, and posterior putamen, as well as caudate/anterior putamen (C/AP) and caudate/posterior putamen (C/PP) ratios, were analyzed with generalized linear models. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic accuracy of DAT binding values and ratios. RESULTS:BvFTD-P patients exhibited significantly reduced DAT binding in the caudate, anterior putamen, and posterior putamen compared with HC (all P <0.01), with a caudate-predominant deficit pattern (lower C/AP and C/PP ratios), contrasting with the putamen-predominant loss observed in PSP, MSA-P, and PD. This caudate-predominant pattern was replicated in the independent 18 F-FP-CIT cohort. ROC analysis demonstrated that the C/PP ratio provided superior discriminatory performance between bvFTD-P and HC or other parkinsonian syndromes than absolute binding values. Furthermore, lateralization of striatal DAT reduction corresponded to the side of predominant motor symptoms. CONCLUSIONS:The caudate-predominant pattern of striatal dopaminergic deficit in bvFTD-P may serve as a useful imaging biomarker for differentiating it from PSP, MSA-P, and PD.

White matter (WM) signal on ¹⁸F-florbetapir positron emission tomography (PET) is often regarded as nonspecific, yet its biological significance remains unclear. This study aimed to characterize the trajectory, clinical significance, and biomarker correlates of normal-appearing white matter (NAWM) ¹⁸F-florbetapir retention across the Alzheimer’s disease (AD) continuum. We analyzed NAWM ¹⁸F-florbetapir retention in 672 participants across the AD continuum from the Alzheimer’s Disease Neuroimaging Initiative and two Chinese cohorts. Longitudinal PET, plasma, and cerebrospinal fluid (CSF) biomarkers, as well as lecanemab treatment effects, were evaluated. NAWM retention followed a distinct trajectory from cortical amyloid, increasing during preclinical stages and plateauing in symptomatic phases. Elevated NAWM ¹⁸F-florbetapir retention independently predicted cognitive decline, correlated with plasma p-tau217 and CSF p-tau/Aβ42 ratio, and showed significant reductions following lecanemab therapy. Combined assessment of cortical and NAWM PET improved diagnostic accuracy for amyloid positivity to 92

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 Asymmetry in motor dysfunction and associated dopaminergic deficit is a common characteristic of Parkinson's disease (PD), yet potential explanations remain mysterious. Hereby, we assessed whether asymmetry in the nasal cavity is related to dopaminergic dysfunction asymmetry in PD patients. Methods This cross-sectional, multi-center observational study included 761 PD patients from three cohorts. First, we analyzed data from the Huashan Parkinsonian PET Imaging Database (March 2011 to February 2020), which served as the primary cohort (n=333). Second, we collected de novo data from all PD inpatients in the Hongqiao Campus of Huashan Hospital as internal validation cohort (May 2023 to July 2024, n=77). Finally, we used data from the Parkinson's Progression Markers Initiative as an external validation cohort (n=351). All cohorts included imaging data of structural MRI or CT, as well as dopaminergic neuroimaging using 11C−CFT, 18F−FP−CIT, or 18F−DTBZ on PET or 123I−DaTscan on SPECT. Nasal cavity asymmetry was assessed by visually inspecting the position of nasal septum deviation in structural MRI or CT to determine the dominant side. Both qualitative and quantitative analyses were performed to evaluate the correlations between nasal cavity asymmetry and dopaminergic deficit asymmetry. Results In the primary cohort, 70.2% of patients exhibited consistency between the dominant side of the nasal cavity and the side with a more severe dopaminergic deficit in striatum (φ=0.40, p<0.001). The striatal−specific binding ratios of dopamine uptake were significantly lower on the side ipsilateral to the dominant nasal cavity, and a significantly inverse correlation was found between the asymmetry index of nasal cavity surface area and that of the dopaminergic deficit (r=−0.31, p<0.001). Similar patterns were observed in internal (78.6%, φ=0.57, p<0.001) and external validation cohorts (73.1%, φ=0.45, p<0.001). A stronger correlation was found in sporadic PD (φ=0.67, p<0.001) compared to genetic PD patients (φ=0.31, p=0.3). Conclusions We made a novel and robust observation that the nasal cavity asymmetry is correlated with asymmetry in striatal dopaminergic deficiency in PD patients. The finding may have significant implications for both the etiological and clinical research of PD, supporting the nasal pathway as a potential route for both environmental pathogens and PD treatment. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work received financial support from the Shanghai Municipal Science and Technology Major Project (grants No. 22JC1410402), National Natural Science Foundation of China (grants No. 82171421, 82371432, 92249302, 82272039, 82021002, 81971641, 81902282, 82171252, and 82371266), National Health Commission of China (grants No. Pro20211231084249000238), the Research project of Shanghai Health Commission (grants No. 2020YJZX0111), the Clinical Research Plan of SHDC (grants No. SHDC2020CR1038B), and the STI2030-Major Projects (grants No. 2022ZD0211600). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Institutional Review Boards of Huashan Hospital. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

Nowadays, presynaptic dopaminergic positron emission tomography, which assesses deficiencies in dopamine synthesis, storage, and transport, is widely utilized for early diagnosis and differential diagnosis of parkinsonism. This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism. We conducted a thorough literature search using reputable databases such as PubMed and Web of Science. Selection criteria involved identifying peer-reviewed articles published within the last 5 years, with emphasis on their relevance to clinical applications. The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis. Moreover, when employed in conjunction with other imaging modalities and advanced analytical methods, presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker. This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion. In summary, the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials, ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

BackgroundWhile the correlation between tau deposition and metabolism in Alzheimer's disease (AD) has been observed, the relationship between asymmetric tau deposition and metabolic asymmetry has not been thoroughly studied.ObjectiveTo analyze the asymmetry of tau deposition in AD and explore its correlation with cerebral metabolic asymmetry.MethodsWe retrospectively enrolled 304 AD patients who underwent 18F-Florzolotau PET imaging, with 238 also receiving 18F-FDG PET. Standardized uptake value ratios (SUVRs) were obtained, and asymmetry indices (AIs) of tau deposition and metabolism were calculated. AD patients were classified into subgroups of left/right-dominant or bilateral symmetric tau deposition and hypometabolism based on AI thresholds. Clinical differences and correlations between tau and metabolic asymmetry were assessed.ResultsAmong 304 AD patients, 21.7%, 23.3%, and 4.8% exhibited left-dominant, right-dominant, and bilateral symmetric tau deposition, respectively. For the 238 patients with 18F-FDG PET, 19.3%, 26.9%, and 8.0% had left-dominant, right-dominant, and bilateral symmetric hypometabolism. Longitudinally, tau and 18F-FDG metabolic asymmetries exhibited different trends. Tau deposition subgroups did not differ significantly in age, disease duration, sex, or MMSE scores. Significant negative correlations between tau and metabolic asymmetry were found in 16 ROI pairs (ρ = -0.639 to -0.192, p < 0.05), while no significant correlations were seen in 4 other ROIs (p > 0.05).ConclusionsNearly half of AD patients showed asymmetric tau deposition. Although tau asymmetry negatively correlated with metabolic asymmetry, differences in the proportions of asymmetry, variation trends, and clinical characteristics suggest that other factors influence metabolic heterogeneity in AD.

Considerable evidence suggests that midbrain-based magnetic resonance Parkinsonism index (MRPI) measurements are reliable biomarkers for the diagnosis of progressive supranuclear palsy (PSP). However, the longitudinal atrophy pattern of PSP and potential differences in change rates among PSP phenotypic spectrum remain unclear. This study aims to investigate the longitudinal changes of MRPI measurements and explore their potential role in PSP phenotype progression monitoring. Thirty-six patients with PSP-Richardson’s syndrome (PSP-RS), 21 patients with variant PSP (vPSP), and 21 healthy controls (HCs) with longitudinal MRI and clinical follow-up were enrolled. Midbrain-based morphometric measurements and the corresponding annual percentage changes (APCs) were measured and further used to evaluate the associations with disease progression. Significant differences in midbrain-based morphometric biomarkers were observed both at baseline and longitudinal trajectories between PSP and HC groups, but no significant differences were found between PSP-RS and vPSP subgroups. Baseline comprehensive measurements were significantly associated with the baseline PSP rating scale (PSPrs) in all PSP and PSP phenotypes. The APC of MRPI was significantly associated with the APC of PSPrs in all PSP (r = 0.267, p = 0.046) and the PSP-RS subgroup (r = 0.386, p = 0.020). This study characterizes the longitudinal atrophy trajectory of PSP phenotypes and the significant associations between morphometric measurements and disease severity. Dissecting the causal associations among core 4R-tau, dopamine, and subsequent atrophy trajectories may enhance the application of these biomarkers for phenotype attribution. Questions The use of midbrain-based MRPI measurements to assess the longitudinal prognosis of the PSP phenotype remains uncertain. Findings Significant differences in midbrain-based morphometric biomarkers were observed both at baseline and longitudinal trajectories between PSP and health control groups. Clinical relevance Midbrain-based morphometric measurements hold promise as potential radiological biomarkers for monitoring PSP disease progression and assessment.

BACKGROUND AND PURPOSE:Whether microglial activation plays an important role in the pathogenesis of autoimmune encephalitis (AE), such as anti-leucine-rich, glioma-inactivated-1 (LGI1) encephalitis, remains unknown. [18F]-DPA714 PET targeting the translocator protein (TSPO) is a novel method to detect neuroinflammation via visualizing activated microglia. In this study, we aimed to investigate the application of [18F]-DPA714 PET in anti-LGI1 encephalitis. METHODS:Patients with anti-LGI1 encephalitis and non-inflammatory controls (NIC) underwent [18F]-DPA714 PET scans were enrolled. Standardized uptake value ratios normalized to the cerebellum (SUVRc) in LGI1-AE patients were calculated for semi-quantitative analysis. The microglial activation marker, soluble triggering receptor expressed on myeloid cells 2 (sTREM2) was measured in cerebrospinal fluid (CSF) to demonstrate its correlation with [18F]-DPA714 PET imaging. Logistic regression analysis was used to identify potential predictors of prognosis. RESULTS:Forty-six patients with anti-LGI1 encephalitis were included in this study. Increased TSPO uptake was identified in the hippocampus, frontal cortex, and caudate nucleus. Montreal Cognitive Assessment (MoCA) score was significantly correlated with SUVRc in the hippocampus (R2 = 0.13, p = 0.034) and frontal cortex (R2 = 0.13, p = 0.017). Overexpressed sTREM2 in CSF was correlated with SUVRc in the hippocampus (R2 = 0.18, p = 0.04). SUVRc in the hippocampus significantly decreased after immunotherapy and was associated with improvement of MoCA score (R2 = 0.54, p = 0.023). Increased SUVRc in the frontal cortex and hippocampus was associated with unfavorable disability recovery (odds ratio [OR] = 7.1, 95% CI 1.67-29.9, p = 0.008) and persistent amnesia (OR = 5.4, 95% CI 1.3-22.2, p = 0.021) respectively. CONCLUSION:Microglial activation visualized by [18F]-DPA714 PET is associated with clinical features and may be used as a potential biomarker for therapeutic and prognostic evaluation.

Dopamine transporter [11C]CFT PET is highly effective for diagnosing Parkinson’s Disease (PD), whereas it is not widely available in most hospitals. To develop a deep learning framework to synthesize [11C]CFT PET images from real [18F]FDG PET images and leverage their cross-modal correlation to distinguish PD from normal control (NC). We developed a deep learning framework to synthesize [11C]CFT PET images from real [18F]FDG PET images, and leveraged their cross-modal correlation to distinguish PD from NC. A total of 604 participants (274 with PD and 330 with NC) who underwent [11C]CFT and [18F]FDG PET scans were included. The quality of the synthetic [11C]CFT PET images was evaluated through quantitative comparison with the ground-truth images and radiologist visual assessment. The evaluations of PD diagnosis performance were conducted using biomarker-based quantitative analyses (using striatal binding ratios from synthetic [11C]CFT PET images) and the proposed PD classifier (incorporating both real [18F]FDG and synthetic [11C]CFT PET images). Visualization result shows that the synthetic [11C]CFT PET images resemble the real ones with no significant differences visible in the error maps. Quantitative evaluation demonstrated that synthetic [11C]CFT PET images exhibited a high peak signal-to-noise ratio (PSNR: 25.0–28.0) and structural similarity (SSIM: 0.87–0.96) across different unilateral striatal subregions. The radiologists achieved a diagnostic accuracy of 91.9

Posterior cortical atrophy (PCA) is generally considered an atypical variant of Alzheimer's disease (AD) and is an important component of early-onset AD. Symptomatologic heterogeneity has led to a high rate of misdiagnosis or delayed diagnosis of early-onset AD. We sought to establish the phenotypic-specific metabolic patterns of PCA and early-onset typical AD (tAD) and to assess whether phenotype-specific neuroimaging biomarkers are more valuable for disease recognition. Patients accepting 18F-FDG PET with an onset age younger than 65 years (PCA, n = 40; early-onset tAD, n = 37; behavioral variant frontotemporal dementia (bv-FTD), n = 35) and healthy controls (HCs, n = 30) were enrolled and divided into two cohorts for pattern establishment and validation, respectively. Similarities and differences between patterns were assessed by pattern topography, expression, classification performance and correlation with clinical severity. PCA-related pattern (PCARP) was characterized by extensively relative hypometabolism in the parietal lobe, occipital lobe, temporal lobe, cingulate gyrus, and relative hypermetabolism mainly in vermis, thalamus. Early-onset tAD-related pattern (EOtADRP) was characterized by relative hypometabolism mainly in the middle frontal gyrus, angular gyrus, precuneus, middle temporal gyrus, cingulate gyrus, caudate, and relative hypermetabolism mainly in vermis, thalamus, postcentral gyrus. PCARP and EOtADRP were closely related in topography (r = 0.909, P < 0.001) and expression (r = 0.862, P < 0.001). High accuracies in distinguishing corresponding patient group from HC were found in both, while only PCARP was capable of phenotype discrimination (PCA versus early-onset tAD; area under the receiver operating characteristic curve [AUC] = 0.84–0.88 for PCARP, AUC = 0.57–0.62 for EOtADRP) and distinguishment between PCA/early-onset tAD and bv-FTD (AUC = 1.00/0.91 for PCARP, AUC = 0.73/0.62 for EOtADRP). PCARP showed great potential in detecting clinical severity in both phenotypes whereas EOtADRP only worked in early-onset tAD. PCARP outperformed EOtADRP in phenotype discrimination with better potential in severity assessment.

PURPOSE:Accurate differentiation of Parkinsonism subtypes-including Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP)-is essential for clinical prognosis and treatment planning. However, this remains a major challenge due to overlapping symptomatology and high inter-individual variability in cerebral glucose metabolism patterns observed on fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS:To address these challenges, we propose PETFormer-SCL, a clinically informed deep learning framework that integrates convolutional neural networks (CNNs) with a channel-wise Transformer module, guided by supervised contrastive learning (SCL). This architecture is designed to enhance disease-specific feature learning while mitigating individual variability. RESULTS:Trained on 945 patients and evaluated on an independent test cohort of 330 patients (1275 in total), PETFormer-SCL achieved AUCs of 0.9830, 0.9702, and 0.9565 for MSA, PD, and PSP, respectively. In addition, class activation maps (CAMs) highlighted key disease-related brain regions-including the cerebellum, midbrain, and basal ganglia-demonstrating strong alignment with known pathophysiological findings. CONCLUSIONS:PETFormer-SCL not only achieves high diagnostic accuracy, particularly for subtypes with overlapping phenotypes, but also enhances interpretability. These results support its potential as a reliable clinical decision-support tool for the early and differential diagnosis of Parkinsonism.

Discrepancies between PET/CT and PET/MRI scanners can affect the determination of amyloid beta (Aβ) deposition thresholds in patients with cognitive impairment. This study aimed to identify these differences and propose a calibration method to standardize Aβ quantification across imaging modalities. A total of 133 patients with cognitive impairment underwent Aβ PET imaging and were divided into four groups: a head-to-head PET/CT and PET/MRI cohort (group A, n = 6), an independent PET/CT cohort (group B, n = 48), an independent PET/MRI cohort (group C, n = 79), and another independent PET/MRI cohort (group D, n = 10). Standardized uptake value ratios (SUVR) of global cortical target (CTXsuvr) and centiloid (CL) values were compared within group A and between groups B and C. A whole cerebellum (WC)-referenced SUVR method was used to calibrate CL values in group C, with verification in group D. CTXsuvr values were significantly higher in PET/MRI than in PET/CT in both group A (P < 0.05) and group C versus group B (P < 0.001). Aβ-negative/positive cases showed mean ± variance of CTXsuvr as 1.023 ± 0.104/1.479 ± 0.203 in group B and 1.146 ± 0.100/1.743 ± 0.254 in group C, with cutoffs of 1.140 (CL = 20) and 1.401 (CL = 60), respectively. WC-referenced calibration adjusted PET/MRI cutoff to 1.132 (CL = 19) in group C, aligning it with PET/CT thresholds and validated in group D. WC-referenced SUVR calibration effectively mitigates differences in Aβ thresholds between PET/CT and PET/MRI, enhancing Aβ quantification standardization in multi-modal imaging.

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.

BACKGROUND:Dementia with Lewy bodies (DLB) commonly exhibits a complex neuropathology, sharing characteristics with Alzheimer's disease (AD), including tau aggregates. However, studies using the 18F-AV-1451 tau tracer have shown inconsistent findings regarding both the extent and topographical distribution of tau pathology in DLB. OBJECTIVES:Our aim was to elucidate the topographical patterns of tau deposition in DLB and to investigate the in vivo pathological distinction between DLB and AD in virtue of the 18F-Florzolotau positron emission tomography (PET) imaging. METHODS:This cross-sectional study enrolled patients with DLB (n = 24), AD (n = 43), and cognitively healthy controls (n = 18). Clinical assessments and 18F-Florzolotau PET imaging were performed. 18F-Florzolotau binding was quantitatively assessed on PET images using standardized uptake value ratios and voxel-wise analysis. RESULTS:18F-Florzolotau PET imaging revealed widespread tau deposition across various cortical regions in DLB, uncovering heterogeneous topographical patterns. Among patients, 54.17% showed patterns similar to AD, whereas 16.67% exhibited distinct patterns. Compared to AD, DLB exhibited a unique in vivo neuropathological profile, characterized by a lower tau protein burden, heterogeneous topographical distributions, and a specific role of the medial temporal lobe in tau pathology. CONCLUSIONS:18F-Florzolotau PET imaging elucidated tau pathology patterns in DLB, providing valuable insights for future in vivo pathological differentiation and potential disease-modifying therapies. © 2024 International Parkinson and Movement Disorder Society.

Dopamine transporter imaging is routinely used in Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS) diagnosis. While [11C]CFT PET is prevalent in Asia with a large APS database, Europe relies on [123I]FP-CIT SPECT with limited APS data. Our aim was to develop a deep learning-based method to convert [11C]CFT PET images to [123I]FP-CIT SPECT images, facilitating multicenter studies and overcoming data scarcity to promote Artificial Intelligence (AI) advancements. A CycleGAN was trained on [11C]CFT PET (n = 602, 72

Clinical overlap with multiple other neurological diseases makes the diagnosis of autoimmune encephalitis challenging; consequently, a broad range of neurological diseases are misdiagnosed as autoimmune encephalitis. A 58-year-old man presented with abnormal behavior, irritability for 3 years, oculomotor disturbance, unsteady walking, and dysphagia and was suspected as having anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis as the anti-DPPX antibody was positive in the serum. However, the therapeutic effect of immunotherapy was unsatisfactory. Subsequently, colocalization of increased midbrain signals was observed in neuroinflammation PET using [F-18]DPA-714 and in tau PET using [F-18]florzolotau, suggesting the diagnosis of progressive supranuclear palsy.