Publications by authors named "Zhiwen You"

Introduction: To investigate the associations of metabotropic glutamate receptor 5 (mGluR5) with tau deposition and cognitive ability in patients with early Alzheimer's disease (AD).

Methods: Twenty-six cognitively impaired (CI) and 14 cognitively unimpaired (CU) individuals underwent mGluR5 positron emission tomography (PET) ([F]PSS232), amyloid PET ([F]florbetapir), and tau PET ([F]MK6240), and neuropsychological assessment. The relationships among mGluR5 availability, tau deposition, and neuropsychological assessment were analyzed using Spearman's correlation and mediation analyses.

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Background Synaptic loss is an important factor in Alzheimer disease (AD); however, blood assays that conveniently and rapidly reflect changes in synaptic density are lacking. Purpose To correlate multiple potential synaptic blood markers with synaptic density measured using F-SynVesT-1, a fluorine 18 (F)-labeled radiotracer, brain PET and to explore the independent associations between these markers and synaptic density. Materials and Methods This prospective study included 50 cognitively unimpaired (mean age, 65.

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A 57-year-old man with primary aldosteronism exhibited multiple nodules in the left adrenal, pancreatic tail, and splenic region. The left adrenal nodule showed positive 68 Ga-pentixafor and negative 68 Ga-FAPI-04 uptake, suggesting an aldosterone-producing adrenal adenoma. The nodule in the pancreatic tail exhibited high 68 Ga-pentixafor and low 68 Ga-FAPI-04 uptake, similarity with the nodule in splenic region, indicating accessory splenic nodule.

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Purpose: This study aims to explore the correlation between PET and CMR in integrated [Ga]Ga-FAPI-04 PET/CMR multimodal imaging and its value in the diagnosis and risk assessment of hypertrophic cardiomyopathy (HCM).

Methods: This study included 20 HCM patients and 11 age- and gender-matched controls. PET analysis evaluated left ventricular (LV) [Ga]Ga-FAPI-04 uptake, including SUV, TBR, cardiac fibroblast activity (CFA) and volume (CFV), and total SUV of the 16 segments.

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Article Synopsis
  • The nucleus basalis of Meynert (NBM) is crucial for understanding Alzheimer's Disease (AD) and its impact on the cholinergic system, yet the link between synaptic loss in the NBM and AD symptoms remains unclear.
  • A study involving 120 participants, including cognitively normal controls and those with cognitive impairment, used MRI and PET imaging to analyze synaptic density in the NBM and its correlation with cognitive performance and traditional AD biomarkers.
  • Findings revealed that lower synaptic density in the NBM was strongly associated with worse cognitive function and neurodegeneration, suggesting that neurite density in related white matter tracts may mediate this relationship.
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Radionuclide probes-targeted prostate-specific membrane antigen (PSMA) is used in diagnosis and treatment of prostate cancer (PCa). Recent studies have shown that PSMA is expressed in the tumor neovascular endothelium, such as in malignant liver tumors. We report a case of PCa with incidental intrahepatic cholangiocarcinoma (ICC) detection using F-PSMA-1007 and F-fluorodeoxyglucose (FDG) positron emission topography (PET)/MRI.

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A 43-year-old man with chronic hepatitis B and elevated alpha-fetoprotein levels showed no malignant evidence on 18 F-FDG PET/CT. However, subsequent assessment using 68 Ga-FAPI-04 PET/MR identified a lesion with increased FAPI uptake in the liver, coupled with detailed enhancement patterns on MRI, leading to a diagnosis of hepatocellular carcinoma, later confirmed by pathology. This case highlights the pivotal role of integrated 68 Ga-FAPI-04 PET and enhanced MRI in refining hepatocellular carcinoma diagnostics, advancing a more nuanced imaging approach over conventional modalities for comprehensive evaluation of hepatic lesions.

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The associations of synaptic loss with amyloid-β (Aβ) and tau pathology measured by positron emission tomography (PET) and plasma analysis in Alzheimer's disease (AD) patients are unknown. Seventy-five participants, including 26 AD patients, 19 mild cognitive impairment (MCI) patients, and 30 normal controls (NCs), underwent [F]SynVesT-1 PET/MR scans to assess synaptic density and [F]florbetapir and [F]MK6240 PET/CT scans to evaluate Aβ plaques and tau tangles. Among them, 19 AD patients, 12 MCI patients, and 29 NCs had plasma Aβ42/40 and p-tau181 levels measured by the Simoa platform.

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Introduction: We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants.

Methods: One hundred ten CI participants underwent amyloid positron emission tomography (PET) with F-florbetapir and synaptic density PET with F-SynVesT-1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers.

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Objectives: This study aimed to explore the potential of full dynamic PET kinetic analysis in assessing amyloid binding and perfusion in the cardiac region using F-Florbetapir PET, establishing a quantitative approach in the clinical assessment of cardiac amyloidosis disease.

Materials & Methods: The distribution volume ratios (DVRs) and the relative transport rate constant (R), were estimated by a pseudo-simplified reference tissue model (pSRTM2) and pseudo-Logan plot (pLogan plot) with kidney reference for the region of interest-based and voxel-wise-based analyses. The parametric images generated using the pSRTM2 and linear regression with spatially constrained (LRSC) algorithm were then evaluated.

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Background: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the initial pathophysiological mechanism of Alzheimer's disease (AD). The study aims to investigate the association between mGluR5 availability and AD's biomarkers and cognitive function.

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Brain organoids have been widely used to study diseases and the development of the nervous system. Many reports have investigated the application of brain organoids, but most of these models lack vascular structures, which play essential roles in brain development and neurological diseases. The brain and blood vessels originate from two different germ layers, making it difficult to induce vascularized brain organoids in vitro.

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Background: Radical prostatectomy with pelvic lymph node dissection for the treatment of high-risk localized prostate cancer (PCa) results in long-term benefits in selected patients. But insufficient sensitivity of conventional examinations which are pelvic MRI and bone scan, limits the diagnosis of bone and lymph node metastasis of PCa. This affects the surgical management strategy of a large number of patients.

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A fundamental interest in developmental neuroscience lies in the ability to map the complete single-cell lineages within the brain. To this end, we developed a CRISPR editing-based lineage-specific tracing (CREST) method for clonal tracing in Cre mice. We then used two complementary strategies based on CREST to map single-cell lineages in developing mouse ventral midbrain (vMB).

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The cell lineages across developmental stages remain to be elucidated. Here, we developed single-cell split barcoding (SISBAR) that allows clonal tracking of single-cell transcriptomes across stages in an in vitro model of human ventral midbrain-hindbrain differentiation. We developed "potential-spective" and "origin-spective" analyses to investigate the cross-stage lineage relationships and mapped a multi-level clonal lineage landscape depicting the whole differentiation process.

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Synapse loss has been considered as a major pathological change in Alzheimer's disease (AD). It remains unclear about whether and how synapse loss relates to functional and structural connectivity dysfunction in AD. We measured synaptic vesicle glycoprotein 2 A (SV2A) binding using F-SynVesT-1 PET to evaluate synaptic alterations in 33 participants with AD, 31 with mild cognitive impairment (MCI), and 30 controls.

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Objective: Fibroblast activation protein (FAP)-targeting radiopharmaceutical based on the FAP-specific inhibitor (FAPI) is considered as a potential alternative agent to FDG for tumor-specific imaging. However, FAP is also expressed in normal adult tissues. The aim of this study was to explore the image features of non-tumoral regions with high uptake of Ga-FAPI-04 in positron emission tomography (PET) imaging and to reveal the physiological mechanisms of these regions.

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Oligodendrocyte spheroids (OL-spheroids) containing oligodendrocytes and neurons provide an accessible system to dissect demyelinating diseases and test therapeutic treatment. However, generation of human OL-spheroids is still technically challenging and time-consuming until now. Here, we presented evidence that overexpression of SOX10 and OLIG2 (SO) in human embryonic stem cells (hESCs)-derived ventral forebrain neural progenitors is sufficient to produce forebrain pre-oligodendrocytes (pre-OLs) and mature oligodendrocytes (OLs) within 20-40 days.

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Human pluripotent stem cell-based (hPSC-based) replacement therapy holds great promise for the treatment of Parkinson's disease (PD). However, the heterogeneity of hPSC-derived donor cells and the low yield of midbrain dopaminergic (mDA) neurons after transplantation hinder its broad clinical application. Here, we have characterized the single-cell molecular landscape during mDA neuron differentiation.

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Purpose: Respiratory motion causes mismatches between PET images of the myocardium and the corresponding cardiac MR images in cardiac integrated PET/MR. The mismatch may affect the attenuation correction and the diagnosis of non-ischemic cardiomyopathies. In this study, we present a two-stage cardiac PET and MR late gadolinium enhancement (LGE) co-registration method, which seeks to improve diagnostic accuracy of non-ischemic cardiomyopathies via better image co-registration using an integrated whole-body PET/MR system.

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Introduction: The low sensitivity of [F]-fluorodeoxyglucose ([F]-FDG) for the diagnosis of gastric cancer limits its application. In this study, we aimed to investigate the potential advantage of [ Ga]Ga-FAPI-04 over [F]-FDG in the evaluation of gastric cancer.

Methods: This was a bicentric retrospective analysis of a prospective parent study (clinical trial: HS-KY-2020-826 (Huashan Hospital) and DF-2020-102 (Shanghai East Hospital)).

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Background: Quantitative bone SPECT/CT is useful for disease follow up and inter-patient comparison. For bone metastatic malignant lesions, spine is the most commonly invaded site. However, Quantitative studies with large sample size investigating all the segments of normal cervical, thoracic and lumbar vertebrae are seldom reported.

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Purpose: To systematically evaluate the consistency of various standardized uptake value (SUV) lean body mass (LBM) normalization methods in a clinical positron emission tomography/magnetic resonance imaging (PET/MR) setting.

Methods: SUV of brain, liver, prostate, parotid, blood, and muscle were measured in 90 F-FDG and 28 F-PSMA PET/MR scans and corrected for LBM using the James, Janma (short for Janmahasatian), and Dixon approaches. The prospective study was performed from December 2018 to August 2020 at Shanghai East Hospital.

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Although cell transplantation can rescue motor defects in Parkinson's disease (PD) models, whether and how grafts functionally repair damaged neural circuitry in the adult brain is not known. We transplanted hESC-derived midbrain dopamine (mDA) or cortical glutamate neurons into the substantia nigra or striatum of a mouse PD model and found extensive graft integration with host circuitry. Axonal pathfinding toward the dorsal striatum was determined by the identity of the grafted neurons, and anatomical presynaptic inputs were largely dependent on graft location, whereas inhibitory versus excitatory input was dictated by the identity of grafted neurons.

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