Abstract

Background: Parkinsonisms are neurodegenerative disorders characterized pathologically by α-synuclein-positive (e.g., PD, diffuse Lewy body disease, and MSA) and/or tau-positive (e.g., PSP, cortical basal degeneration) pathology. Using R2* and quantitative susceptibility mapping, susceptibility changes have been reported in the midbrain of living parkinsonian patients, although the exact underlying pathology of these alterations is unknown. Objective: The current study investigated the pathological correlates of these susceptibility MRI measures. Methods: In vivo MRIs (T1- and T2-weighted, and T2*) and pathology were obtained from 14 subjects enrolled in an NINDS PD Biomarker Program (PDBP). We assessed R2* and quantitative susceptibility mapping values in the SN, semiquantitative α-synuclein, tau, and iron values, as well as neuronal and glial counts. Data were analyzed using age-adjusted Spearman correlations. Results: R2* was associated significantly with nigral α-synuclein (r = 0.746; P = 0.003). Quantitative susceptibility mapping correlated significantly with Perls' (r = 0.758; P = 0.003), but not with other pathological measurements. Neither measurement correlated with tau or glial cell counts (r ≤ 0.11; P ≥ 0.129). Conclusions: Susceptibility MRI measurements capture nigral pathologies associated with parkinsonian syndromes. Whereas quantitative susceptibility mapping is more sensitive to iron, R2* may reflect pathological aspects of the disorders beyond iron such as α-synuclein. They may be invaluable tools in diagnosing differential parkinsonian syndromes, and tracking in living patients the dynamic changes associated with the pathological progression of these disorders.

Original languageEnglish (US)
Pages (from-to)1432-1439
Number of pages8
JournalMovement Disorders
Volume33
Issue number9
DOIs
StatePublished - Sep 1 2018

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Synucleins
Parkinsonian Disorders
Substantia Nigra
Pathology
Iron
Neuroglia
National Institute of Neurological Disorders and Stroke
Lewy Body Disease
Mesencephalon
Neurodegenerative Diseases
Cell Count
Biomarkers

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

@article{bfbae89f527f4dcd94b14166818b766d,
title = "Susceptibility MRI captures nigral pathology in patients with parkinsonian syndromes",
abstract = "Background: Parkinsonisms are neurodegenerative disorders characterized pathologically by α-synuclein-positive (e.g., PD, diffuse Lewy body disease, and MSA) and/or tau-positive (e.g., PSP, cortical basal degeneration) pathology. Using R2* and quantitative susceptibility mapping, susceptibility changes have been reported in the midbrain of living parkinsonian patients, although the exact underlying pathology of these alterations is unknown. Objective: The current study investigated the pathological correlates of these susceptibility MRI measures. Methods: In vivo MRIs (T1- and T2-weighted, and T2*) and pathology were obtained from 14 subjects enrolled in an NINDS PD Biomarker Program (PDBP). We assessed R2* and quantitative susceptibility mapping values in the SN, semiquantitative α-synuclein, tau, and iron values, as well as neuronal and glial counts. Data were analyzed using age-adjusted Spearman correlations. Results: R2* was associated significantly with nigral α-synuclein (r = 0.746; P = 0.003). Quantitative susceptibility mapping correlated significantly with Perls' (r = 0.758; P = 0.003), but not with other pathological measurements. Neither measurement correlated with tau or glial cell counts (r ≤ 0.11; P ≥ 0.129). Conclusions: Susceptibility MRI measurements capture nigral pathologies associated with parkinsonian syndromes. Whereas quantitative susceptibility mapping is more sensitive to iron, R2* may reflect pathological aspects of the disorders beyond iron such as α-synuclein. They may be invaluable tools in diagnosing differential parkinsonian syndromes, and tracking in living patients the dynamic changes associated with the pathological progression of these disorders.",
author = "Mechelle Lewis and Guangwei Du and Jennifer Baccon and Amanda Snyder and Ben Murie and Felicia Cooper and Christy Stetter and Lan Kong and Christopher Sica and Richard Mailman and James Connor and Xuemei Huang",
year = "2018",
month = "9",
day = "1",
doi = "10.1002/mds.27381",
language = "English (US)",
volume = "33",
pages = "1432--1439",
journal = "Movement Disorders",
issn = "0885-3185",
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}

Susceptibility MRI captures nigral pathology in patients with parkinsonian syndromes. / Lewis, Mechelle; Du, Guangwei; Baccon, Jennifer; Snyder, Amanda; Murie, Ben; Cooper, Felicia; Stetter, Christy; Kong, Lan; Sica, Christopher; Mailman, Richard; Connor, James; Huang, Xuemei.

In: Movement Disorders, Vol. 33, No. 9, 01.09.2018, p. 1432-1439.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Susceptibility MRI captures nigral pathology in patients with parkinsonian syndromes

AU - Lewis, Mechelle

AU - Du, Guangwei

AU - Baccon, Jennifer

AU - Snyder, Amanda

AU - Murie, Ben

AU - Cooper, Felicia

AU - Stetter, Christy

AU - Kong, Lan

AU - Sica, Christopher

AU - Mailman, Richard

AU - Connor, James

AU - Huang, Xuemei

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Background: Parkinsonisms are neurodegenerative disorders characterized pathologically by α-synuclein-positive (e.g., PD, diffuse Lewy body disease, and MSA) and/or tau-positive (e.g., PSP, cortical basal degeneration) pathology. Using R2* and quantitative susceptibility mapping, susceptibility changes have been reported in the midbrain of living parkinsonian patients, although the exact underlying pathology of these alterations is unknown. Objective: The current study investigated the pathological correlates of these susceptibility MRI measures. Methods: In vivo MRIs (T1- and T2-weighted, and T2*) and pathology were obtained from 14 subjects enrolled in an NINDS PD Biomarker Program (PDBP). We assessed R2* and quantitative susceptibility mapping values in the SN, semiquantitative α-synuclein, tau, and iron values, as well as neuronal and glial counts. Data were analyzed using age-adjusted Spearman correlations. Results: R2* was associated significantly with nigral α-synuclein (r = 0.746; P = 0.003). Quantitative susceptibility mapping correlated significantly with Perls' (r = 0.758; P = 0.003), but not with other pathological measurements. Neither measurement correlated with tau or glial cell counts (r ≤ 0.11; P ≥ 0.129). Conclusions: Susceptibility MRI measurements capture nigral pathologies associated with parkinsonian syndromes. Whereas quantitative susceptibility mapping is more sensitive to iron, R2* may reflect pathological aspects of the disorders beyond iron such as α-synuclein. They may be invaluable tools in diagnosing differential parkinsonian syndromes, and tracking in living patients the dynamic changes associated with the pathological progression of these disorders.

AB - Background: Parkinsonisms are neurodegenerative disorders characterized pathologically by α-synuclein-positive (e.g., PD, diffuse Lewy body disease, and MSA) and/or tau-positive (e.g., PSP, cortical basal degeneration) pathology. Using R2* and quantitative susceptibility mapping, susceptibility changes have been reported in the midbrain of living parkinsonian patients, although the exact underlying pathology of these alterations is unknown. Objective: The current study investigated the pathological correlates of these susceptibility MRI measures. Methods: In vivo MRIs (T1- and T2-weighted, and T2*) and pathology were obtained from 14 subjects enrolled in an NINDS PD Biomarker Program (PDBP). We assessed R2* and quantitative susceptibility mapping values in the SN, semiquantitative α-synuclein, tau, and iron values, as well as neuronal and glial counts. Data were analyzed using age-adjusted Spearman correlations. Results: R2* was associated significantly with nigral α-synuclein (r = 0.746; P = 0.003). Quantitative susceptibility mapping correlated significantly with Perls' (r = 0.758; P = 0.003), but not with other pathological measurements. Neither measurement correlated with tau or glial cell counts (r ≤ 0.11; P ≥ 0.129). Conclusions: Susceptibility MRI measurements capture nigral pathologies associated with parkinsonian syndromes. Whereas quantitative susceptibility mapping is more sensitive to iron, R2* may reflect pathological aspects of the disorders beyond iron such as α-synuclein. They may be invaluable tools in diagnosing differential parkinsonian syndromes, and tracking in living patients the dynamic changes associated with the pathological progression of these disorders.

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U2 - 10.1002/mds.27381

DO - 10.1002/mds.27381

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C2 - 29756231

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VL - 33

SP - 1432

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JO - Movement Disorders

JF - Movement Disorders

SN - 0885-3185

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