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. 2019 Dec 1;40(17):5094-5107.
doi: 10.1002/hbm.24760. Epub 2019 Aug 12.

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

Trina Mitchell  1 , Derek B Archer  1 , Winston T Chu  1   2 , Stephen A Coombes  1 , Song Lai  3 , Bradley J Wilkes  1 , Nikolaus R McFarland  4 , Michael S Okun  4 , Mieniecia L Black  1 , Ellen Herschel  5 , Tanya Simuni  6 , Cynthia Comella  7 , Tao Xie  8 , Hong Li  9 , Todd B Parrish  10 , Ajay S Kurani  10 , Daniel M Corcos  5 , David E Vaillancourt  1   2   4
Affiliations

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

Trina Mitchell et al. Hum Brain Mapp. .

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.

Keywords: Parkinsonism; diffusion MRI; free-water; isotropic volume; neurite density; orientation dispersion.

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Conflict of interest statement

Dr. Derek B. Archer reports grant support from the Parkinson's Foundation. Dr. Nikolaus R. McFarland reports grants from the NIH and the Michael J. Fox Foundation, and has received personal honoraria from the NIH and the American Academy of Neurology. 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 Syndrome Association, and UF Foundation. Dr. Okun is an associate editor for New England Journal of Medicine Journal Watch Neurology. 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 Comella recieves research support from the NIH, Parkinson's Foundation, Dystonia Medical Research Foundation, Merz Pharmaceutical, Revance Therapeutic, Retrophin and Acorda Therapeutic, and has served as a consultant or an advisory committee member for Acorda Therapeutics, Allergan Inc, Lundbeck Ltd., Medtronic Inc., Merz Pharmaceuticals, Acadia Pharmaceuticals, Jazz Pharmaceuticals, Neurocrine Biosciences Inc., Revance Therapeutic, Sunovion. Dr. Comella serves on the editorial board of Clinical Neuropharmacology and Sleep Medicine, and receives royalties from Cambridge, Wolters Kluwer. Dr. Tao Xie has been funded by the Parkinson's Foundation, NIH, Michael J Fox Foundation for Parkinson's Research, Abbvie, Bristol‐Myers Squibb, Biogen and the University of Chicago for research and clinical trials, and also served as consultant for Parkinson's Foundation, Abbvie, and CVS/Caremark. Dr. Daniel M. Corcos reports grants from NIH. Dr. David E. Vaillancourt reports grants from NIH, NSF, and Tyler's Hope Foundation during the conduct of the study, and personal honoraria from NIH and Parkinson's Foundation unrelated to the submitted work. All other authors report no disclosures.

Figures

Figure 1
Figure 1
Free‐water imaging and NODDI maps. Free‐water imaging (left two columns) and NODDI maps (right three columns) in a single healthy control subject (CON; top three rows) and individual with progressive supranuclear palsy (PSP; bottom three rows). ODI, orientation dispersion index; Viso, isotropic volume fraction; Vic, intracellular volume fraction [Color figure can be viewed at http://wileyonlinelibrary.com]
Figure 2
Figure 2
NODDI imaging in Parkinsonism. Between group differences between PD, MSAp, and PSP versus Controls at all regions of interest for each NODDI metric. ODI, orientation dispersion index; Viso, isotropic volume fraction; Vic, intracellular volume fraction; aSN, anterior substantia nigra; pSN, posterior substantia nigra; PUT, putamen; CN, caudate nucleus; GP, globus pallidus; STN, subthalamic nucleus; RN, red nucleus; THA, thalamus; PPN, pedunculopontine nucleus; DN, dentate nucleus; MCP, middle cerebellar peduncle; SCP, superior cerebellar peduncle; LB V, cerebellar lobule V; LB VI, cerebellar lobule VI; VER, the cerebellar vermis; CC1, prefrontal of corpus callosum; and CC2, premotor of the corpus callosum. *p < .05, FDR‐corrected [Color figure can be viewed at http://wileyonlinelibrary.com]
Figure 3
Figure 3
Free‐water imaging in Parkinsonism. Between group differences between PD, MSAp, and PSP versus Controls at all regions of interest for each single‐shell FW metric. aSN, anterior substantia nigra; pSN, posterior substantia nigra; PUT, putamen; CN, caudate nucleus; GP, globus pallidus; STN, subthalamic nucleus; RN, red nucleus; THA, thalamus; PPN, pedunculopontine nucleus; DN, dentate nucleus; MCP, middle cerebellar peduncle; SCP, superior cerebellar peduncle; LB V, cerebellar lobule V; LB VI, cerebellar lobule VI; VER, the cerebellar vermis; CC1, prefrontal of corpus callosum; and CC2, premotor of the corpus callosum. *p < .05, FDR‐corrected [Color figure can be viewed at http://wileyonlinelibrary.com]
Figure 4
Figure 4
Differentiating atypical Parkinsonism. ROC analyses and corresponding AUC for each diffusion imaging model for PD versus atypical Parkinsonism (MSAp and PSP). The variables selected in each model are listed below. Delong's test was conducted to determine between‐model differences. ODI, orientation dispersion index; Viso, isotropic volume fraction; Vic, intracellular volume fraction; FWms, free‐water derived from the multi‐shell scan; FAtms, free‐water corrected fractional anisotropy derived from the multi‐shell scan. FWss, free‐water derived from the single‐shell scan; FAtss, free‐water corrected fractional anisotropy derived from the single‐shell scan. n.s.; not significant; TPR, true positive rate; FPR, false positive rate; SCP, superior cerebellar peduncle; MCP, middle cerebellar peduncle; LB V, cerebellar lobule V; LB VI, cerebellar lobule VI; GP, globus pallidus; THA, thalamus; STN, subthalamic nucleus; CC1, corpus callosum prefrontal area; CN, caudate nucleus; DN, dentate nucleus [Color figure can be viewed at http://wileyonlinelibrary.com]
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References

    1. Agosta, F. , Pievani, M. , Svetel, M. , Jecmenica Lukic, M. , Copetti, M. , Tomic, A. , … Filippi, M. (2012). Diffusion tensor MRI contributes to differentiate Richardson's syndrome from PSP‐parkinsonism. Neurobiology of Aging, 33, 2817–2826. - PubMed
    1. Ahmed, Z. , Josephs, K. A. , Gonzalez, J. , DelleDonne, A. , & Dickson, D. W. (2008). Clinical and neuropathologic features of progressive supranuclear palsy with severe pallido‐nigro‐luysial degeneration and axonal dystrophy. Brain, 131, 460–472. - PubMed
    1. Andica, C. , Kamagata, K. , Hatano, T. , Okuzumi, A. , Saito, A. , Nakazawa, M. , … Aoki, S. (2018). Neurite orientation dispersion and density imaging of the nigrostriatal pathway in Parkinson's disease: Retrograde degeneration observed by tract‐profile analysis. Parkinsonism & Related Disorders, 51, 55–60. - PubMed
    1. Archer, D. B. , Coombes, S. A. , Chu, W. T. , Chung, J. W. , Burciu, R. G. , Okun, M. S. , … Vaillancourt, D. E. (2018). A widespread visually‐sensitive functional network relates to symptoms in essential tremor. Brain, 141, 472–485. - PMC - PubMed
    1. Avants, B. B. , Epstein, C. L. , Grossman, M. , & Gee, J. C. (2008). Symmetric diffeomorphic image registration with cross‐correlation: Evaluating automated labeling of elderly and neurodegenerative brain. Medical Image Analysis, 12, 26–41. - PMC - PubMed

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