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Quantitative Mapping of Substantia Nigra Iron in Parkinson's Disease

帕金森病中黑质铁的定量图谱

基本信息

批准号：
10322082
负责人：
Alexander Shtilbans
金额：
$ 52.2万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10322082
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

项目摘要

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.