Quantitative mapping of substantia nigra iron in Parkinson's Disease

 描述（由申请人提供）：本项目的长期目标是开发用于帕金森病的非侵入性、稳健、灵敏和准确的中脑铁映射。PD是一种神经退行性疾病，其特征在于黑质致密部（SNc）中多巴胺能神经元损失和随之发生的运动障碍。虽然PD中的神经退行性过程可能是多因素的，但SNc中的促氧化剂铁升高显然是散发性和家族性PD形式的不变特征，有助于氧化应激和线粒体功能障碍，并作为疾病改善治疗的易处理靶点。因此，无创性定量黑质铁标测将有助于诊断PD，评估PD进展和监测PD治疗。非侵入性磁共振成像（MRI）被认为是检测中脑组织中少量高顺磁性铁的最敏感方法。我们已经开发了定量磁化率映射（QSM），使组织磁化率的定量提取梯度回波MRI数据通过去卷积相位数据与偶极核。根据磁化率估计铁必须考虑钙化的贡献，钙化是基底神经节中的另一个主要磁化率来源，也可以使用最近开发的超短回波时间MRI技术进行估计。因此，我们建议使用QSM方法开发无创准确的中脑铁映射，具体目标如下。目的1：建立一种基于QSM方法的无创、准确的中脑铁图。目的2：应用元素分析和免疫组化技术对黑质铁进行无创检测。目的3：建立在监测PD铁螯合治疗中，QSM比R2* 更敏感的黑质铁图。

 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.