Diffusion Basis Spectrum Imaging for Measurement of Neuroinflammation in Parkinson Disease

弥散基光谱成像用于测量帕金森病的神经炎症

• 批准号: 10426279
• 负责人: ROBERT L WHITE
• 金额: --
• 依托单位: ST. LOUIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426279
• 关键词: Adaptive Immune System; Affect; Alzheimer' s Disease; Anatomy; Animal Model; Astrocytes; Autopsy; Binding; Biological Markers; Blood; Brain; Brain Diseases; Brain imaging; Brain region; Calcium Binding; Caring; Cell Fraction; Cells; Cellularity; Cerebrospinal Fluid; Clinical; Clinical Trials; Clonal Expansion; Cognition Disorders; Cognitive; Cyclotrons; Data; Dementia; Development; Diffusion; Disease; Disease Progression; Edema; Elderly; Encephalitis; Evaluation; Flow Cytometry; Formalin; Functional disorder; Genetic Transcription; Glial Fibrillary Acidic Protein; Gliosis; Goals; Histologic; Histopathology; Hospitals; Human; Imaging Techniques; Immune Targeting; Immune response; Immune system; Immunohistochemistry; Impaired cognition; Impairment; Inflammation; Inflammatory; Inflammatory Response; Innate Immune Response; Innate Immune System; Investigation; Life; Link; Magnetic Resonance Imaging; Measurement; Measures; Methods; Microglia; Monitor; Motor; Movement; Multiple Sclerosis; Nerve Degeneration; Outcome; Parkinson Disease; Parkinsonian Disorders; Participant; Pathogenesis; Pathologic; Pathologic Processes; Pathology; Persons; Phenotype; Play; Population; Positron-Emission Tomography; Proteins; Radiation exposure; Research; Role; Severity of illness; Source; Specimen; Staging; Stains; Standardization; Structure; Substantia nigra structure; Surrogate Markers; T cell response; T-Lymphocyte; Testing; Thinking; Tissues; Tremor; United States Department of Veterans Affairs; United States Food and Drug Administration; Variant; Veterans; adaptive immune response; age related neurodegeneration; alpha synuclein; axon injury; biomarker validation; brain tissue; catalyst; clinical application; clinical predictors; cognitive function; cognitive impairment in Parkinson' s; diagnostic biomarker; dopaminergic neuron; experience; glial activation; imaging biomarker; imaging modality; immunohistochemical markers; improved; in vivo; interest; ionization; motor disorder; motor symptom; nervous system disorder; neuroimaging; neuroinflammation; neuropathology; new therapeutic target; non-demented; non-motor symptom; novel; novel therapeutics; patient stratification; peripheral blood; progressive neurodegeneration; prospective; recruit; response; single-cell RNA sequencing; spectrograph; targeted agent; therapy development; tool

Project Summary/Abstract Parkinson disease (PD) is an age-related neurodegenerative disease affecting a large number of U.S. veterans that causes significant motor symptoms such as slow movement and tremor, as well as non-motor symptoms such as cognitive decline and dementia. Development of therapies to slow PD progression requires validated biomarkers of pathologic processes that predict progression. The brain’s inflammatory response is increasingly recognized as an important source of pathology in PD, and imaging biomarkers of neuroinflammation in PD are needed. A novel Magnetic Resonance Imaging (MRI) technique, Diffusion Basis Spectrum Imaging (DBSI), is sensitive to intermingled changes in brain microstructure, and has the capacity to measure the component of inflammatory cells within a volume of tissue, and distinguish this component from neurodegenerative pathology or anatomic variation. DBSI MRI has been recently shown to quantify neuroinflammation in multiple sclerosis and Alzheimer’s disease. Here, we will develop and validate this measure in PD. We will determine how the DBSI measure of neuroinflammation compares to quantitative immunohistochemistry in already-collected antemortem MRI data with corresponding postmortem fixed brain tissues from people with PD (Aim 1). Prospectively, in PD and control participants we will compare DBSI measures to the positron emission tomography (PET) marker of neuroinflammation, PBR28 (Aim 2), and to the activation profile of T cells in blood and cerebrospinal fluid (Aim 3). We will correlate cross-sectional and longitudinal DBSI measures with clinical features of motor and cognitive disease progression (Aim 4). In this manner, we will develop a strong mechanistic understanding of changes in both neuroimaging and T cell biomarkers of inflammation, and how these relate to motor and cognitive decline in PD. This project holds great promise for identifying and validating biomarkers of neuroinflammation for prediction of PD progression, patient stratification for trials, and evaluation of new treatments targeting the immune system in PD. Because DBSI MRI only requires sequences that are already Food and Drug Administration approved and available on existing clinical MRI scanners, it could be quickly scaled to clinical applications and clinical trials.

项目概要/摘要 帕金森病 (PD) 是一种与年龄相关的神经退行性疾病，影响着大量美国退伍军人 导致明显的运动症状，例如运动缓慢和震颤，以及非运动症状 例如认知能力下降和痴呆。开发减缓 PD 进展的疗法需要经过验证 预测进展的病理过程的生物标志物。大脑的炎症反应越来越严重 被认为是 PD 病理学的重要来源，PD 神经炎症的影像学生物标志物是 需要。一种新颖的磁共振成像 (MRI) 技术——扩散基谱成像 (DBSI) 对大脑微结构的混合变化敏感，并且能够测量大脑微结构的成分 一定体积组织内的炎症细胞，并将该成分与神经退行性病理学区分开来 或解剖变异。 DBSI MRI 最近被证明可以量化多发性硬化症的神经炎症 和阿尔茨海默病。在这里，我们将在 PD 中开发并验证这一措施。我们将确定如何 神经炎症的 DBSI 测量与已收集的定量免疫组织化学进行比较 死前 MRI 数据以及 PD 患者相应的死后固定脑组织（目标 1）。 未来，在 PD 和对照参与者中，我们将比较 DBSI 测量值和正电子发射 神经炎症的断层扫描 (PET) 标记、PBR28（目标 2）以及血液中 T 细胞的激活情况 和脑脊液（目标 3）。我们将横截面和纵向 DBSI 测量与临床相关联 运动和认知疾病进展的特征（目标 4）。通过这种方式，我们将发展出强大的 对炎症神经影像学和 T 细胞生物标志物变化的机制理解，以及如何 这些与帕金森病的运动和认知能力下降有关。该项目对于识别和验证有很大希望 用于预测 PD 进展、试验患者分层和评估的神经炎症生物标志物 针对 PD 免疫系统的新疗法。因为 DBSI MRI 仅需要以下序列 已经获得美国食品和药物管理局的批准并可用于现有的临床 MRI 扫描仪，它可能是 迅速扩展到临床应用和临床试验。