Quantitative mapping of substantia nigra iron in Parkinson's Disease

帕金森病中黑质铁的定量图谱

• 批准号: 9705911
• 负责人: Alexander Shtilbans
• 金额: $ 53.11万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9705911
• 关键词: Autopsy; Basal Ganglia; Biophysics; Brain; Clinical Trials; Coupled; Data; Development; Diagnosis; Differential Diagnosis; Disease; Disease Progression; Financial compensation; Image; Imaging Techniques; Immunohistochemistry; Iron; Magnetic Resonance Imaging; Magnetism; Maps; Mass Spectrum Analysis; Measurement; Measures; Methods; Midbrain structure; Mitochondria; Modeling; Molecular; Monitor; Nerve Degeneration; Neurodegenerative Disorders; Outcome; Outcome Assessment; Oxidative Stress; Parkinson Disease; Patients; Pharmaceutical Preparations; Phase; Plasma; Predisposition; Problem Solving; Process; Protocols documentation; Publishing; Reference Standards; Reporting; Reproducibility; Research; Research Project Grants; Sample Size; Signal Transduction; Source; Specimen; Substantia nigra structure; Testing; Therapy trial; Time; Tissues; Water; base; brain tissue; calcification; cost; dopaminergic neuron; high resolution imaging; imaging biomarker; imaging modality; improved; iron chelation therapy; mitochondrial dysfunction; motor disorder; neuron loss; pars compacta; public health relevance; putamen; tool

 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.

 描述（由申请人提供）：该项目的长期目标是开发针对帕金森病的无创、稳健、灵敏且准确的中脑铁图谱，帕金森病是一种神经退行性疾病，其特征是黑质致密部（SNc）多巴胺能神经元缺失。虽然 PD 的神经退行性过程可能是多因素的，但 SNc 中促氧化铁的升高显然是 PD 的一个不变特征。散发性和家族性帕金森病均会导致氧化应激和线粒体功能障碍，因此，无创定量黑质铁图谱可用于诊断帕金森病、评估帕金森病进展和监测帕金森病磁疗。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灵敏方法，我们已经定量开发了磁化率图（QSM），可以进行定量分析。通过使用偶极核对相位数据进行解卷积从梯度回波 MRI 数据中提取组织磁化率 根据磁化率估计铁必须考虑钙化的贡献，钙化是基底节中的另一个主要磁化率源，也可以使用最近开发的超短回波进行估计。因此，我们建议使用 QSM 方法开发无创准确的中脑铁映射，其具体目标如下：开发基于无创且准确的中脑铁映射。目标 2：使用元素分析和免疫组织化学验证黑质铁的无创测量。目标 3：确定 QSM 在监测 PD 铁螯合疗法方面比 R2* 更敏感。