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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 帕金森病(PD)是一种神经退行性疾病，以迟钝、僵硬和经常震颤为特征。超过100万美国人患有帕金森病，预计到2030年，全球将有900万人患有帕金森病。到目前为止，还没有公认的客观生物学指标，即反映疾病发病机制或药物治疗反应的生物标记物。缺乏可靠的生物标志物严重限制了早期诊断、神经保护治疗的研究和对疾病发病机制的认识。目前的放射性示踪成像技术，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数量和密度的能力。此外，没有足够的支持性数据允许将其用作诊断工具或临床试验中的替代终点。同样，磁共振成像(MRI)目前的状态并不能作为帕金森病的生物标志物。因此，仍然需要一种PD神经成像技术，提供一种测量神经元活性和密度的方法，以及解决目前成像技术无法解决的其他问题。一种可以确定神经元状态以及可能的致病因素(如铁)的方法将是潜在的有用的。这项建议是评估两种新的磁共振成像(MRI)技术T1和T2的研究效用的过程中的一步，这两种技术可能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很敏感，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丢失的迹象，可用于评估PD黑质变性。 目前，我们不打算将T1和T2确定为生物标志物或确定它们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特斯拉扫描仪对PD和对照受试者进行横断面研究，并获得SNT1和T2的MRI测量结果。我们的目标是验证T1和T2区分帕金森病患者和对照组的能力，并确定T1和T2评估帕金森病疾病严重程度的能力。