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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS095562-02
Application #
9250227
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Babcock, Debra J
Project Start
2016-04-01
Project End
2021-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
2
Fiscal Year
2017
Total Cost
$651,960
Indirect Cost
$224,468
Name
Weill Medical College of Cornell University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Cho, Junghun; Kee, Youngwook; Spincemaille, Pascal et al. (2018) Cerebral metabolic rate of oxygen (CMRO2 ) mapping by combining quantitative susceptibility mapping (QSM) and quantitative blood oxygenation level-dependent imaging (qBOLD). Magn Reson Med 80:1595-1604
Soman, S; Liu, Z; Kim, G et al. (2018) Brain Injury Lesion Imaging Using Preconditioned Quantitative Susceptibility Mapping without Skull Stripping. AJNR Am J Neuroradiol 39:648-653
Kee, Youngwook; Cho, Junghun; Deh, Kofi et al. (2018) Coherence enhancement in quantitative susceptibility mapping by means of anisotropic weighting in morphology enabled dipole inversion. Magn Reson Med 79:1172-1180
Jafari, Ramin; Chhabra, Shalini; Prince, Martin R et al. (2018) Vastly accelerated linear least-squares fitting with numerical optimization for dual-input delay-compensated quantitative liver perfusion mapping. Magn Reson Med 79:2415-2421
Ponath, Gerald; Park, Calvin; Pitt, David (2018) The Role of Astrocytes in Multiple Sclerosis. Front Immunol 9:217
Li, Jianqi; Lin, Huimin; Liu, Tian et al. (2018) Quantitative susceptibility mapping (QSM) minimizes interference from cellular pathology in R2* estimation of liver iron concentration. J Magn Reson Imaging 48:1069-1079
Liu, Zhe; Spincemaille, Pascal; Yao, Yihao et al. (2018) MEDI+0: Morphology enabled dipole inversion with automatic uniform cerebrospinal fluid zero reference for quantitative susceptibility mapping. Magn Reson Med 79:2795-2803
Wen, Yan; Nguyen, Thanh D; Liu, Zhe et al. (2018) Cardiac quantitative susceptibility mapping (QSM) for heart chamber oxygenation. Magn Reson Med 79:1545-1552
Gillen, Kelly M; Mubarak, Mayyan; Nguyen, Thanh D et al. (2018) Significance and In Vivo Detection of Iron-Laden Microglia in White Matter Multiple Sclerosis Lesions. Front Immunol 9:255
Wang, Yi; Spincemaille, Pascal; Liu, Zhe et al. (2017) Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care. J Magn Reson Imaging 46:951-971

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