Quantitative Mapping of Substantia Nigra Iron in Parkinson's Disease

 描述(由申请者提供)：该项目的长期目标是为帕金森氏症开发无创的、健壮的、敏感的和准确的中脑铁图谱。帕金森病是一种神经退行性疾病，其特征是黑质致密部多巴胺能神经元丢失，从而导致运动障碍。虽然帕金森病的神经退变过程可能是多因素的，但SNC中的氧化原铁升高显然是散发性和家族性帕金森病的一个不变特征，导致氧化应激和线粒体功能障碍，是疾病修正治疗的一个易处理的靶点。因此，无创定量黑质铁图有助于帕金森病的诊断、病情评估和治疗监测。无创磁共振成像(MRI)被认为是检测中脑组织中少量高顺磁性铁的最敏感的方法。我们开发了定量磁化率图(QSM)，通过用偶极核去卷积相位数据，能够从梯度回波MRI数据中定量提取组织磁化率。根据磁化率估计铁必须考虑钙化的贡献，钙化是基底节的另一个主要易感性来源，也可以用最近发展的超短回波时间MRI技术来估计。因此，我们建议使用QSM方法开发无创准确的中脑铁定位图，具体目标如下。目的1：建立一种基于QSM方法的无创、准确的中脑铁质地形图。目的2：用元素分析和免疫组织化学方法验证黑质铁的无创性测量。目的3：建立QSM比R2*更敏感的黑质铁定位监测PD铁螯合治疗的方法。

 DESCRIPTION (provided by applicant): The long term objective of this project is to develop noninvasive, robust, sensitive and accurate midbrain iron mapping for Parkinson's disease. PD is a neurodegenerative disorder characterized by loss of dopaminergic neuron loss in substantia nigra pars compactor (SNc) and consequent motor disorders. While the neurodegenerative processes in PD may be multifactorial, prooxidant iron elevation in the SNc is evidently an invariable feature of both sporadic and familial PD forms, contributing to oxidative stress and mitochondrial dysfuction and presenting as a tractable target for a disease modifying therapy. Therefore, noninvasive quantitative nigral iron mapping would be useful for diagnosing PD, assessing PD progression and monitoring PD therapy. Noninvasive magnetic resonance imaging (MRI) is regarded to be the most sensitive method for detecting small amounts of highly paramagnetic iron in midbrain tissue. We have developed quantitative susceptibility mapping (QSM) that enables a quantitative extraction of tissue magnetic susceptibility from gradient echo MRI data by deconvolving phase data with a dipole kernel. Estimation of iron from magnetic susceptibility must account for contributions of calcification, the other major susceptibility soure in basal ganglia that can also be estimated using recently developed ultrashort echo time MRI technique. Accordingly, we propose to develop noninvasive accurate midbrain iron mapping using the QSM approach with the following specific aims. Aim 1: Develop a noninvasive and accurate midbrain iron mapping based on QSM approach. Aim 2: Validate noninvasive measurement of substantia nigra iron using elemental analysis and immunohistochemistry. Aim 3: Establish that QSM is more sensitive than R2* for nigral iron mapping in monitoring PD iron chelation therapy.