Progression marker of Parkinson’s disease: a 4-year multi-site imaging study

Burciu, Roxana G.; Ofori, Edward; Archer, Derek B.; Wu, Samuel S.; Pasternak, Ofer; McFarland, Nikolaus R.; Okun, Michael S.; Vaillancourt, David E.

doi:10.1093/brain/awx146

Cited by 149 publications

(185 citation statements)

References 35 publications

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“…Free water values were found to be stable in the control group but increase in the PD group and also predict changes in bradykinesia scores and cognitive status. These findings were further confirmed in a larger multi-site cohort that was followed over a 4 year period [26]. These results are consistent with our study since both the MD (average diffusion in the voxel) and free water (a measure of the extracellular isotropic volume fraction) are related measures, although free water content is a more sensitive measure.…”

Section: Discussionsupporting

confidence: 92%

Validation of diffusion tensor imaging measures of nigrostriatal neurons in macaques

et al. 2018

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ObjectiveInterpretation of diffusion MRI in the living brain requires validation against gold standard histological measures. We compared diffusion values of the nigrostriatal tract to PET and histological results in non-human primates (NHPs) with varying degrees of unilateral nigrostriatal injury induced by MPTP, a toxin selective for dopaminergic neurons.MethodsSixteen NHPs had MRI and PET scans of three different presynaptic radioligands and blinded video-based motor ratings before and after unilateral carotid artery infusion of variable doses of MPTP. Diffusion measures of connections between midbrain and striatum were calculated. Then animals were euthanized to quantify striatal dopamine concentration, stereologic measures of striatal tyrosine hydroxylase (TH) immunostained fiber density and unbiased stereologic counts of TH stained nigral cells.ResultsDiffusion measures correlated with MPTP dose, nigral TH-positive cell bodies and striatal TH-positive fiber density but did not correlate with in vitro nigrostriatal terminal field measures or in vivo PET measures of striatal uptake of presynaptic markers. Once nigral TH cell count loss exceeded 50% the stereologic terminal field measures reached a near zero floor effect but the diffusion measures continued to correlate with nigral cell counts.ConclusionDiffusion measures in the nigrostriatal tract correlate with nigral dopamine neurons and striatal fiber density, but have the same relationship to terminal field measures as a previous report of striatal PET measures of presynaptic neurons. These diffusion measures have the potential to act as non-invasive index of the severity of nigrostriatal injury. Diffusion imaging of the nigrostriatal tract could potentially have diagnostic value in humans with Parkinson disease or related disorders.

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Section: Discussionsupporting

confidence: 92%

Validation of diffusion tensor imaging measures of nigrostriatal neurons in macaques

et al. 2018

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“…Our DTI analysis of patients with de novo PD from the PPMI cohort revealed no differences of MD and FA values on a whole‐brain level. In contrast, previous studies from independent labs analyzing different groups of participants within the PPMI cohort found such structural differences including unequivocal abnormalities of the SN . The latter studies, however, used other techniques and focused on the SN or the SN and further regions of interest, which is clearly different from our approach.…”

Section: Discussioncontrasting

confidence: 59%

Neuroimaging abnormalities in individuals exhibiting Parkinson's disease risk markers

et al. 2018

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“…A multi‐shell acquisition was used to conduct the NODDI model and the single‐shell was extracted from this acquisition to conduct the FW imaging model (FW ms and FAt ms ). A more clinically feasible single‐shell acquisition was also acquired to compute FW imaging measures (FW ss and FAt ss ) as has been done in prior studies (Burciu et al, ; Pasternak et al, ; Planetta et al, ).…”

Section: Introductionmentioning

confidence: 99%

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

Mitchell

Archer

Chu

et al. 2019

Human Brain Mapping

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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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Progression marker of Parkinson’s disease: a 4-year multi-site imaging study

Cited by 149 publications

References 35 publications

Validation of diffusion tensor imaging measures of nigrostriatal neurons in macaques

Validation of diffusion tensor imaging measures of nigrostriatal neurons in macaques

Neuroimaging abnormalities in individuals exhibiting Parkinson's disease risk markers

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

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