NOVEL MRI METHODS FOR NEURONAL LOSS & IRON QUANTIFICATION IN PARKINSONS DISEASE

治疗神经元丢失的新 MRI 方法

• 批准号: 8362856
• 负责人: SHALOM MICHAELI
• 金额: $ 3.03万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362856
• 关键词: Address; American; Biological; Biological Markers; Clinical Trials; Cross-Sectional Studies; Data; Diagnostic; Disease; Dopamine; Early Diagnosis; Environment; Funding; Goals; Grant; Imaging Techniques; Individual; Iron; Magnetic Resonance Imaging; Magnetism; Measurement; Measures; Methods; NMR Spectroscopy; National Center for Research Resources; Neurodegenerative Disorders; Neurons; Parkinson Disease; Pathogenesis; Positron-Emission Tomography; Predisposition; Principal Investigator; Process; Proteins; Protons; Research; Research Infrastructure; Resources; Sensitivity and Specificity; Severity of illness; Source; Surrogate Endpoint; Techniques; Time; Tremor; United States National Institutes of Health; Water; cost; density; disorder control; neuroimaging; neuron loss; novel; response; single photon emission computed tomography; tool; water diffusion

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Parkinson's disease (PD) is a neurodegenerative disorder characterized by slowness, stiffness and often tremor. Over 1 million Americans have PD and globally 9 million people are projected to have PD by the year 2030. To date, there is no accepted objective biological measure, i.e, biomarker, that is reflective of disease pathogenesis or of pharmacological responses to treatment. Absence of a reliable biomarker severely limits early diagnosis, research on neuroprotective therapies and appreciation of disease pathogenesis. Current radiotracing imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) lack the ability to ascertain dopamine neuronal counts as well as density. Additionally, there is insufficient supportive data to allow their use as diagnostic tools or as surrogate endpoints in clinical trials. Likewise, magnetic resonance imaging (MRI) in its present state is not useful as a biomarker for PD. Therefore, there remains a need for a PD neuroimaging technique that provides a means to measure neuronal viability and density as well as address other issues of which present imaging techniques are unable to do. A method which could ascertain neuronal status as well as possible pathogenic factors such as iron would be potentially useful. This proposal is a step in the process of evaluating the research utility of two novel magnetic resonance imaging (MRI) techniques T1¿ and T2¿, which may reflect the quantities of neurons and iron, respectively. T2¿ is sensitive to diffusion of water protons in environments with different local magnetic susceptibilities and likely reflects iron content; whileT1¿ reflects predominantly water-protein interactions, and, therefore might provide an indication of neuronal loss that could be used to assess PD nigral degeneration. At this time, it is not our intent to establish T1¿ and T2¿ as biomarkers or to determine their sensitivity/specificity as diagnostic tools. Our objective is to validate several aspects of T1¿ and T2¿. We will perform a cross-sectional study of PD and control subjects using a 4 Tesla scanner and obtain SN T1¿ and T2¿ MRI measurements. Our goals are to validate T1¿ and T2¿ in their ability to separate individuals with PD from control subjects, and to determine the ability of T1¿ and T2¿ to evaluate disease severity of PD.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 帕金森氏病（PD）是一种神经退行性疾病，其特征是缓慢，僵硬和震颤。超过100万美国人的PD和全球900万人预计到2030年将具有PD。迄今为止，尚无公认的客观生物学测量，即生物标志物，反映了疾病发病机理或对治疗的药物反应。没有可靠的生物标志物严重限制了早期诊断，神经保护疗法的研究和疾病发病机理的欣赏。当前的辐射成像技术，例如正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）缺乏确定多巴胺神经元计数以及密度的能力。此外，在临床试验中，支持数据不足以允许其用作诊断工具或替代终点。同样，以当前状态的磁共振成像（MRI）作为PD的生物标志物也不有用。因此，仍然需要一种PD神经影像学技术，该技术提供了一种方法来衡量神经元的生存力和密度以及解决当前成像技术无法做到的其他问题。一种可以确定神经元状态以及可能的致病因素（例如铁）的方法将有可能有用。该建议是评估两种新型磁共振成像（MRI）技术T1和T2¿的研究实用程序的步骤，该技术可以分别反映神经元和铁的数量。对具有不同局部磁敏感性的环境中的水蛋白差异敏感，并且可能反映了铁含量。尽管1主要反映了水 - 蛋白质相互作用，因此可能提供了可用于评估PD ni骨变性的神经元丧失的指示。 目前，我们的目的不是将T1和T2¿建立为生物标志物或确定其敏感性/特异性作为诊断工具。我们的目标是验证T1和T2¿的几个方面。我们将使用4 Tesla扫描仪对PD和对照受试者进行横断面研究，并获得SNT1¿和T2¿MRI测量。我们的目标是验证t1¿和t2¿在他们将PD与对照受试者分开的能力，并确定T1¿和T2¿评估PD疾病严重程度的能力。