Novel MRI Methods for Neuronal Loss and Iron Quantification in Parkinsons Disease

University Of Minnesota, Minneapolis MN

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Abstract

DESCRIPTION (provided by applicant): Parkinson's disease (PD) is a neurodegenerative disorder characterized by slowness, stiffness and often tremor. Over 1 million Americans have PD and globally 9 million people are projected to have PD by the year 2030. To date, there is no accepted objective biological measure, i.e, biomarker, that is reflective of disease pathogenesis or of pharmacological responses to treatment. Absence of a reliable biomarker severely limits early diagnosis, research on neuroprotective therapies and appreciation of disease pathogenesis. Current radiotracing imaging techniques such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) lack the ability to ascertain dopamine neuronal counts as well as density. Additionally, there is insufficient supportive data to allow their use as diagnostic tools or as surrogate endpoints in clinical trials. Likewise, magnetic resonance imaging (MRI) in its present state is not useful as a biomarker for PD. Therefore, there remains a need for a PD neuroimaging technique that provides a means to measure neuronal viability and density as well as address other issues of which present imaging techniques are unable to do. A method which could ascertain neuronal status as well as possible pathogenic factors such as iron would be potentially useful. This proposal is a step in the process of evaluating the research utility of two novel magnetic resonance imaging (MRI) techniques T1A and T2A, which may reflect the quantities of neurons and iron, respectively. T2A is sensitive to diffusion of water protons in environments with different local magnetic susceptibilities and likely reflects iron content;whileT1A reflects predominantly water-protein interactions, and, therefore might provide an indication of neuronal loss that could be used to assess PD nigral degeneration. At this time, it is not our intent to establish T1A and T2A as biomarkers or to determine their sensitivity/specificity as diagnostic tools. Our objective is to validate several aspects of T1A and T2A. We will perform a cross-sectional study of PD and control subjects using a 4 Tesla scanner and obtain SN T1A and T2A MRI measurements. Our goals are to validate T1A and T2A in their ability to separate individuals with PD from control subjects, and to determine the ability of T1A and T2A to evaluate disease severity of PD. PUBLIC HEALTH RELEVANCE This proposal is a step in the process of evaluating the research utility of two novel magnetic resonance imaging (MRI) techniques T1A and T2A, which may reflect the quantities of neurons and iron, respectively. T2A is sensitive to diffusion of water protons in environments with different local magnetic susceptibilities and likely reflects iron content;whileT1A reflects predominantly water-protein interactions, and, therefore might provide an indication of neuronal loss that could be used to assess PD nigral degeneration.