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Validation of Diffusion Basis Spectrum Imaging of Neuroinflammation in Schizophrenia

精神分裂症神经炎症扩散基谱成像的验证

基本信息

批准号：
10573475
负责人：
DANIEL MAMAH
金额：
$ 23.5万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-12-01 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10573475
关键词：
Address Adolescence Alzheimer&apos s Disease Anterior Autopsy Axon Biological Brain Brain Diseases Cellularity Characteristics Child Complement Corpus Callosum Data Delusions Demyelinations Development Diffusion Encephalitis Etiology Future Genes Genetic Goals Hallucinations Hippocampus Imaging Techniques Inflammation Inflammatory Internal Capsule Investigation Limb structure Longitudinal Studies Magnetic Resonance Imaging Major Histocompatibility Complex Mediating Methods Microglia Multiple Sclerosis Nerve Degeneration Pathogenesis Patients Persons Phase Positron-Emission Tomography Prefrontal Cortex Psychoses Psychotic Disorders Quality of life Radiation Radiation exposure Risk Risk Marker Role Sampling Schizophrenia Serum Specificity Temporal Lobe Testing Tissues United States United States National Institutes of Health Validation Variant Water Work aged axon injury brain abnormalities comparison control complement system cost density drug development emerging adult extracellular functional decline genome wide association study genomic locus gray matter histological specimens imaging biomarker imaging modality improved improved outcome in vivo in vivo imaging neuroimaging neuroinflammation neuropathology new therapeutic target novel prevent recruit risk variant schizophrenia risk spectrograph synaptic pruning white matter

项目摘要

PROJECT SUMMARY Schizophrenia (SCZ) is a heterogeneous brain disorder typically characterized by delusions, hallucinations, and functional decline, with a typical first onset in late adolescence and early adulthood. Genetic, neuropathological, and neuroimaging studies have suggested a role of neuroinflammation in the etiology of SCZ, which is evident early in the course of illness. This suggests neuroinflammation may represent a SCZ risk marker and therefore facilitate early recognition and future drug development to improve outcomes. In vivo imaging methods for estimating neuroinflammation have been limited by radiation exposure, specificity, and cost. Our proposal aims to validate a novel non-invasive, new magnetic resonance imaging (MRI) technique called Diffusion Basis Spectrum Imaging (DBSI) to identify neuroinflammation in SCZ. DBSI can simultaneously detect and quantify neuroinflammation (increased cellularity) and white matter alterations (axonal injury/loss and demyelination) and has been previously validated in multiple sclerosis and Alzheimer's disease, but not in SCZ. We propose to test the overarching hypothesis that DBSI will identify neuroinflammation in histological samples from SCZ patients. To achieve this objective, we will obtain postmortem brain samples of 18–30-year-old SCZ patients and matched controls (n=20) from the NIH Neurobiobank and investigate the relationship of the DBSI cellularity subcomponent with tissue reactivity for the microglial marker, CD163, and the complement marker, C4 (Aim 1). We hypothesize a strong linear relationship between DBSI cellularity and selected gray and white matter regions. In addition, we will use DBSI in vivo to characterize the brains of 18–30-year-old SCZ patients and controls (n=30) and identify group differences in DBSI subcomponents (Aim 2). We hypothesize greater DBSI cellularity in SCZ brains compared to controls. In completing this work, we expect to identify non-invasive neuroinflammation and white matter integrity markers for SCZ. In the long term, this information would be used to improve the identification of those at risk for developing psychosis and facilitate the testing of new treatments.

项目总结