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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 帕金森病（Parkinson's disease，PD）是一种神经退行性疾病，以行动迟缓、僵硬和震颤为特征.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，反映疾病的发病机制或对治疗的药理学反应。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评价。 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计数以及密度的能力。此外，没有足够的支持性数据允许将其用作临床试验中的诊断工具或替代终点。同样，磁共振成像（MRI）在其目前的状态是没有用作为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目前成像技术无法解决的其他问题的手段。 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有用的。这项建议是评估两种新型磁共振成像（MRI）技术T1 <$和T2 <$的研究效用的过程中的一个步骤，这两种技术可以分别反映神经元和铁的数量。T2？在具有不同局部磁化率的环境中对水质子的扩散敏感，并可能反映铁含量;而T1？主要反映水-蛋白质相互作用，因此可能提供可用于评估PD黑质变性的神经元损失的指示。 目前，我们并不打算将T1 <$和T2 <$确定为生物标志物或确定其作为诊断工具的灵敏度/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SN T1 <$$>和T2 <$MRI测量值。我们的目标是验证T1 <$$>和T2 <$$>在区分PD患者和对照受试者方面的能力，并确定T1 <$和T2 <$评估PD疾病严重程度的能力。

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.