Cited by 118Advanced Neuroimaging Techniques and ApplicationsParkinson's Disease Mechanisms and TreatmentsAdvanced MRI Techniques and Applications

Neurite orientation dispersion and density imaging (NODDI) and free‐water imaging in Parkinsonism

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Mitchell, Trina, Archer, Derek B., Chu, Winston T., Coombes, Stephen A., Lai, Song, Wilkes, Bradley J., McFarland, Nikolaus R., Okun, Michael S. +10 more·2019·Human Brain Mapping

Abstract

Neurite orientation dispersion and density imaging (NODDI) uses a three‐compartment model to probe brain tissue microstructure, whereas free‐water (FW) imaging models two‐compartments. It is unknown if NODDI detects more disease‐specific effects related to neurodegeneration in Parkinson's disease (PD) and atypical Parkinsonism. We acquired multi‐ and single‐shell diffusion imaging at 3 Tesla across two sites. NODDI (using multi‐shell; isotropic volume [Viso]; intracellular volume [Vic]; orientation dispersion [ODI]) and FW imaging (using single‐shell; FW; free‐water corrected fractional anisotropy [FAt]) were compared with 44 PD, 21 multiple system atrophy Parkinsonian variant (MSAp), 26 progressive supranuclear palsy (PSP), and 24 healthy control subjects in the basal ganglia, midbrain/thalamus, cerebellum, and corpus callosum. There was elevated Viso in posterior substantia nigra across Parkinsonisms, and Viso, Vic, and ODI were altered in MSAp and PSP in the striatum, globus pallidus, midbrain, thalamus, cerebellum, and corpus callosum relative to controls. The mean effect size across regions for Viso was 0.163, ODI 0.131, Vic 0.122, FW 0.359, and FAt 0.125, with extracellular compartments having the greatest effect size. A key question addressed was if these techniques discriminate PD and atypical Parkinsonism. Both NODDI (AUC: 0.945) and FW imaging (AUC: 0.969) had high accuracy, with no significant difference between models. This study provides new evidence that NODDI and FW imaging offer similar discriminability between PD and atypical Parkinsonism, and FW had higher effect sizes for detecting Parkinsonism within regions across the basal ganglia and cerebellum.

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  • ODI decreases are thought to indicate loss of crossing fibers and decreased dendritic arborizations evident in various central nervous system disorders.

    “ODI decreases are thought to indicate loss of crossing fibers 50,51 and decreased dendritic arborizations evident in various central nervous system disorders.45,47”

    From White Matter Changes after Neurobehavioral Therapy for Functional Seizures (2023) · cites this paper as [45]

    The Introduction and §3.4 (pages unavailable) say that decreased ODI in gray matter could indicate dendritic thinning, and §3.4 reports decreased ODI in patients with Parkinsonian disorders. The source does not extend that interpretation to ODI decreases in all tissue types or establish it across central nervous system disorders generally. The crossing-fiber clause carries different citations and is not judged here. (LLM, conf=0.84)

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  • NODDI has potential usefulness for discriminating Parkinson's disease from other Parkinsonian disorders, with greater abnormalities in progressive supranuclear palsy and multiple system atrophy than in Parkinson's disease.

    “The potential usefulness of NODDI for discriminating Parkinson's disease from the other Parkinsonian disorders has also been suggested (Mitchell et al., 2019), with NODDI showing greater abnormalities in progressive supranuclear palsy and multiple system atrophy than in Parkinson's disease.”

    From NODDI in clinical research (2020) · cites this paper as Mitchell et al., 2019

  • Increased f_fw in the substantia nigra was observed by Mitchell et al. 2019 but not by Kamagata et al. 2016.

    “In addition, increased f fw in the substantia nigra, which is consistent with accumulated evidence (Burciu et al., 2017(Burciu et al., , 2016) ) from free water imaging (Pasternak et al., 2009), was observed by (Mitchell et al., 2019) but not by (Kamagata et al., 2016).”

    From NODDI in clinical research (2020) · cites this paper as Mitchell et al., 2019

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  1. Dr. Michael S. Okun serves as consultant for the National Parkinson's Foundation, and has received research grants from the National Institutes of Health, National Parkinson's Foundation, Michael J. Fox Foundation, Parkinson Alliance, Smallwood Foundation, Bachmann-Strauss Foundation, Tourette Syn- drome Association, and UF Foundation. Dr. Okun is an associate editor for New England Journal of Medicine Journal Watch Neurology.
  2. Dr. Tanya Simuni reports grants from NINDS, Michael J. Fox Foundation, Parkinson's Foundation, Biogen, Roche, Neuroderm, Sanofi, and Sun Pharma for research and clinical trials, and served as a consultant for Michael J. Fox Foundation, Parkinson's Foundation, Acadia, Abbvie, Adamas, Anavex, Allergan, Accorda, Denali, Neuroderm, Neurocrine, Revance, Sanofi, Sunovion, TEVA, Takeda, Voyager, and US World Meds. Dr. Simuni has received honorarium from Acadia, Adamas, and TEVA. Dr. Cynthia Come- lla recieves research support from the NIH, Parkinson's Foundation, Dys- tonia Medical Research Foundation, Merz Pharmaceutical, Revance Therapeutic, Retrophin and Acorda Therapeutic, and has served as a con- sultant or an advisory committee member for Acorda Therapeutics, Alle- rgan Inc, Lundbeck Ltd., Medtronic Inc., Merz Pharmaceuticals, Acadia Pharmaceuticals, Jazz Pharmaceuticals, Neurocrine Biosciences Inc., Rev- ance Therapeutic, Sunovion. Dr. Comella serves on the editorial board of Clinical Neuropharmacology and Sleep Medicine, and receives royalties from Cambridge, Wolters Kluwer.

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Authors
Mitchell, T., Archer, D. B., Chu, W. T., Coombes, S. A., Lai, S., Wilkes, B. J., McFarland, N. R., Okun, M. S., Black, M. L., Herschel, E., Simuni, T., Comella, C., Xie, T., Li, H., Parrish, T. B., Kurani, A. S., Corcos, D. M., & Vaillancourt, D. E.
Affiliations
  • University of Florida (US)
  • University of Florida Health (US)
  • Northwestern University (US)
  • Rush University Medical Center (US)
  • University of Chicago (US)
  • Medical University of South Carolina (US)
Venue
Human Brain Mapping
Publisher
Wiley
Published
2019-08-12
Volume
40
Issue
17
Pages
5094-5107
ISSN
  • 1065-9471 (ISSN-L)
  • 1097-0193
OpenAlex
W2968327236
Cited by
118
References
55
Citations by year
2026: 14 · 2025: 16 · 2024: 21 · 2023: 24 · 2022: 18 · 2021: 13 · 2020: 11 · 2019: 1
FWCI
7.11
Type
journal article
Language
en
Open access
Locations
  • Human Brain Mapping (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (U01 NS102038)
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords
NODDI, free-water imaging, Parkinson's disease, atypical parkinsonism, progressive supranuclear palsy, diffusion MRI, brain microstructure, substantia nigra, basal ganglia, cerebellum, corpus callosum, neurodegeneration, disease discrimination
MeSH terms
Aged, Brain, Female, Humans, Male, Middle Aged, Parkinson Disease, Neurites, Parkinsonian Disorders, Diffusion Magnetic Resonance Imaging

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