Novel MRI Methods for Neuronal Loss and Iron Quantification in Parkinsons Disease

描述（由申请人提供）：帕金森病（PD）是一种神经退行性疾病，以缓慢、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。迄今为止，还没有公认的客观生物学测量，即生物标志物，可以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）目前的状态也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，以提供一种测量神经元活力和密度的手段，并解决现有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（如铁）的方法可能是有用的。该建议是评估两种新型磁共振成像（MRI）技术T1A和T2A研究效用的一个步骤，这两种技术可以分别反映神经元和铁的数量。T2A在局部磁化率不同的环境中对水质子的扩散敏感，可能反映铁含量；而et1a主要反映水蛋白相互作用，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，我们不打算将T1A和T2A作为生物标志物，也不打算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T1A和T2A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 T1A和T2A MRI测量值。我们的目标是验证T1A和T2A区分PD患者与对照组的能力，并确定T1A和T2A评估PD疾病严重程度的能力。

DESCRIPTION (provided by applicant): 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 T1A and T2A, which may reflect the quantities of neurons and iron, respectively. T2A is sensitive to diffusion of water protons in environments with different local magnetic susceptibilities and likely reflects iron content; whileT1A 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 T1A and T2A as biomarkers or to determine their sensitivity/specificity as diagnostic tools. Our objective is to validate several aspects of T1A and T2A. We will perform a cross-sectional study of PD and control subjects using a 4 Tesla scanner and obtain SN T1A and T2A MRI measurements. Our goals are to validate T1A and T2A in their ability to separate individuals with PD from control subjects, and to determine the ability of T1A and T2A to evaluate disease severity of PD. PUBLIC HEALTH RELEVANCE This proposal is a step in the process of evaluating the research utility of two novel magnetic resonance imaging (MRI) techniques T1A and T2A, which may reflect the quantities of neurons and iron, respectively. T2A is sensitive to diffusion of water protons in environments with different local magnetic susceptibilities and likely reflects iron content; whileT1A reflects predominantly water-protein interactions, and, therefore might provide an indication of neuronal loss that could be used to assess PD nigral degeneration.