# MRI Signatures of Neuromelanin and Iron Pathology in Parkinsonism

> **NIH NIH K23** · EMORY UNIVERSITY · 2020 · $192,564

## Abstract

Parkinson’s disease (PD), multiple system atrophy parkinsonian type (MSA-P), and progressive supranuclear
palsy (PSP) are costly and devastating neurodegenerative diseases. They have overlapping clinical
manifestations and diagnosis remains challenging in many cases. Thus far no effective treatments have been
developed to meaningfully slow or stop their progression. This is due in part to a lack of tools to objectively
measure degeneration in the neural systems affected by each of these diseases. Availability of such tools would
assist clinical diagnosis, facilitate selection of appropriate patient groups for trial recruitment, and enable
objective measurement of treatment outcomes. Recent MRI studies suggest that disease-specific brain changes
can, indeed, be identified in these parkinsonian diseases. The objective of this research is to identify univariable
markers and multivariable MRI signatures that capture distinct patterns of neurodegenerative change across
neural systems to accurately distinguish these diseases.
 To accomplish this the investigators use 3 Tesla MRI contrasts sensitive to key features of
neurodegeneration to 1) identify structures damaged by PD, MSA-P and PSP and 2) to quantify the extent of
damage in each neural system in parkinsonian diseases. Specifically, the investigators use neuromelanin-
sensitive MRI to measure neuromelanin loss and quantitative susceptibility mapping (QSM) and R2* imaging to
measure iron accumulation in patients with PD, MSA-P, and PSP. Using these contrasts and an innovative region
of interest (ROI) selection approach, they reproducibly measure patterns of neurodegenerative change across
neural systems. In Aim 1 the investigators use neuromelanin-sensitive MRI to study neuromelanin loss in PD,
MSA-P and PSP in to identify univariable disease features that are differentially affected by parkinsonian
diseases and may assist distinguishing these conditions. In Aim 2 they use QSM and R2* MRI to study ROIs
differentially impacted by PD, MSA-P and PSP to identify iron accumulation biomarkers to help distinguish these
diseases. In Aim 3 the investigators apply machine learning classification algorithms to identify multivariable MRI
signatures of neurodegenerative change across neural systems to differentiate PD, MSA-P and PSP. Study
outputs will be candidate MRI biomarkers and disease signatures. The long term goal of this research is to further
develop these outputs for use as clinical diagnostic tools and as biomarkers for subject selection and outcome
measurement in clinical trials.
 Through this career award Dr. Huddleston will gain new skills in MRI methods, data science, and neural
systems imaging in parkinsonian diseases. These new skills will enable Dr. Huddleston to design and lead
interdisciplinary neuroimaging biomarker studies for Parkinson’s disease and related disorders. His mentor team
is comprised of leaders in their fields. This team and the dynamic research environment at Emory Univers...

## Key facts

- **NIH application ID:** 9999688
- **Project number:** 5K23NS105944-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Daniel Huddleston
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,564
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999688

## Citation

> US National Institutes of Health, RePORTER application 9999688, MRI Signatures of Neuromelanin and Iron Pathology in Parkinsonism (5K23NS105944-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9999688. Licensed CC0.

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