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.

PUBLIC HEALTH RELEVANCE: The long term objective of this proposed research is to reliable, sensitive and accurate quantitative midbrain iron mapping using noninvasive magnetic resonance imaging, which can be used as an imaging biomarker for assessing progression and monitoring therapy of Parkinson's disease.