Non-invasive Markers of Neurodegeneration in Movement Disorders

运动障碍神经退行性变的非侵入性标志物

基本信息

批准号：
8661314
负责人：
David E Vaillancourt
金额：
$ 39.6万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-24 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8661314
关键词：
Affect Alzheimer&apos s Disease Basal Ganglia Behavioral Biological Markers Brain Cell Nucleus Cerebellum Clinical Corpus striatum structure Critiques Data Development Diagnosis Diagnostic Diffusion Magnetic Resonance Imaging Disease Disease Progression Essential Tremor Functional Imaging Functional Magnetic Resonance Imaging Functional disorder Goals Grant Head Image Imaging Techniques Individual Inferior Institutes Judgment Lead Lobule Location Magnetic Resonance Imaging Measures Modeling Motor Movement Movement Disorders Multiple System Atrophy Nerve Degeneration Neurodegenerative Disorders Neurons Parkinson Disease Parkinsonian Disorders Participant Patient Care Patients Pharmaceutical Preparations Phase Population Positioning Attribute Progressive Supranuclear Palsy Radioactive Recruitment Activity Research Sensitivity and Specificity Severities Statistical Methods Structure Substantia nigra structure Symptoms Synaptic Potentials Task Performances Techniques Testing Time United States Variant base clinically relevant density disability experience follow-up grasp gray matter imaging modality innovation neuroimaging neurorestoration outcome forecast patient population progression marker public health relevance putamen radiotracer relating to nervous system trait water diffusion white matter

项目摘要

DESCRIPTION (provided by applicant): Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Other movement disorders that commonly mimic symptoms of PD include the Parkinsonian variant of multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and essential tremor (ET). Taken together, these movement disorders affect over 10 million people in the United States alone. Current diagnostic approaches for PD, MSA, PSP, and ET are based on behavioral signs and clinical judgment, and this can often lead to the incorrect diagnosis, especially early in the course of the disease. In fact, it is estimated that 15% of patients in disease modifying drug trials for early PD do not have PD. Objective, valid, non- invasive, and biologically relevant markers of PD, MSA, PSP, and ET are pivotal for early and accurate diagnosis (trait), and for tracking disease progression (state). Our group has recently shown that diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) can be used to identify mechanisms for basal ganglia dysfunction in individuals with Parkinson's disease. Our preliminary data indicate that DTI and fMRI measures from the basal ganglia and cerebellum show excellent promise for differentiating PD, MSA, PSP, and ET, and for tracking longitudinal disease-specific changes in neurodegeneration. We will recruit 150 individuals for the study: 30 patients with PD, 30 patients with MSA, 30 patients with PSP, 30 patients with ET, and 30 control subjects. In Aim 1, we will use DTI and fMRI of the basal ganglia and cerebellum to focus on the development of a sensitive and specific trait marker for each movement disorder. In Aim 2, we will test the same individuals following 2 years using DTI and fMRI of the basal ganglia and cerebellum to develop state markers of neurodegeneration for each movement disorder. With the large and carefully diagnosed patient population at the Center for Movement Disorders and Neurorestoration and the state-of-the-art MRI facility at the McKnight Brain Institute, our group is uniquely positioned to complete the proposed study. The proposed research is innovative because it will utilize structural and functional imaging modalities with a 32-channel head coil performed on a state-of-the-art 3 Tesla MRI unit. The proposed research is significant because it will be the first stud to develop non-invasive trait and state markers of four debilitating movement disorders that affect over 10 million people in the United States.

描述（由申请人提供）：帕金森氏病（PD）是仅次于阿尔茨海默氏病的第二常见神经退行性疾病。通常模仿PD症状的其他运动障碍包括多种系统萎缩（MSA）的帕金森氏症变体，进行性核上麻痹（PSP）和Essenta Tremor（ET）。综上所述，仅在美国，这些运动障碍就会影响超过1000万人。 PD，MSA，PSP和ET的当前诊断方法基于行为体征和临床判断，这通常会导致诊断不正确，尤其是在疾病的早期。实际上，据估计，早期PD的药物试验中有15％的患者没有PD。 PD，MSA，PSP和ET的客观，有效，非侵入性和与生物学相关的标记对于早期和准确的诊断（性状）以及跟踪疾病进展（状态）至关重要。我们的小组最近表明，可以使用扩散张量成像（DTI）和功能性磁共振成像（fMRI）来识别帕金森氏病个体中基底神经节功能障碍的机制。我们的初步数据表明，来自基底神经节和小脑的DTI和FMRI测量对区分PD，MSA，PSP和ET和跟踪神经退行性变化的纵向疾病特异性变化表现出极好的希望。我们将招募150个人进行研究：30例PD患者，30例MSA患者，30例PSP患者，30例ET患者和30名对照组患者。在AIM 1中，我们将使用基底神经节和小脑的DTI和fMRI专注于为每种运动障碍的敏感和特定特征标记的发展。在AIM 2中，我们将使用基底神经节和小脑的DTI和fMRI在2年后测试相同的个体，以开发每种运动障碍的神经变性的状态标记。在运动障碍和神经修养中心的大量且精心诊断的患者人群以及McKnight Brain Institute的最先进的MRI设施中，我们的小组位于完成拟议的研究。拟议的研究具有创新性，因为它将利用在最先进的3特斯拉MRI单元上执行的32通道头线圈的结构和功能成像方式。拟议的研究之所以重要，是因为它将是第一个发展非侵入性特征和州标记的研究，这些标志是四种令人衰弱的运动障碍，这些运动障碍影响了美国超过1000万人。