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: 8170461
• 负责人: SHALOM MICHAELI
• 金额: $ 2.57万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170461
• 关键词: Address; American; Biological; Biological Markers; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Cross-Sectional Studies; Data; Diagnostic; Disease; Dopamine; Early Diagnosis; Emission-Computed Tomography; Environment; Funding; Goals; Grant; Imaging Techniques; Individual; Institution; Iron; Magnetic Resonance Imaging; Magnetism; Measurement; Measures; Methods; Neurodegenerative Disorders; Neurons; Parkinson Disease; Pathogenesis; Photons; Positron-Emission Tomography; Predisposition; Process; Proteins; Protons; Research; Research Personnel; Resources; Sensitivity and Specificity; Severity of illness; Source; Surrogate Endpoint; Techniques; Time; Tremor; United States National Institutes of Health; Water; density; disorder control; imaging modality; neuroimaging; neuron loss; novel; response; tool; water diffusion

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 帕金森病 (PD) 是一种神经退行性疾病，其特征是行动迟缓、僵硬且经常出现震颤。到 2030 年，超过 100 万美国人患有 PD，预计到 2030 年全球将有 900 万人患有 PD。迄今为止，还没有公认的客观生物学指标（即生物标志物）能够反映疾病发病机制或治疗的药理学反应。缺乏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制的认识。 当前的放射性追踪成像技术，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和密度的能力。此外，没有足够的支持数据来允许它们用作诊断工具或临床试验中的替代终点。同样，目前的磁共振成像 (MRI) 并不能作为 PD 的生物标志物。因此，仍然需要一种PD神经成像技术，其提供测量神经元活力和密度以及解决现有成像技术无法解决的其他问题的方法。 一种可以确定神经元状态以及铁等可能致病因素的方法可能会有用。该提案是评估两种新型磁共振成像（MRI）技术T1¿和T2¿的研究效用过程中的一个步骤，这两种技术可以分别反映神经元和铁的数量。 T2¿ 对具有不同局部磁化率的环境中的水质子扩散敏感，并且可能反映铁含量；而T1¿主要反映水-蛋白质相互作用，因此可能提供神经元损失的指示，可用于评估PD黑质变性。 目前，我们无意将 T1 和 T2 建立为生物标志物或确定其作为诊断工具的敏感性/特异性。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 SN T1¿ 和 T2¿ MRI 测量结果。我们的目标是验证 T1 和 T2 将 PD 个体与对照受试者区分开的能力，并确定 T1 和 T2 评估 PD 疾病严重程度的能力。