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

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.

Synaptic Loss in Primary Tauopathies Revealed by [11C]UCB‐J Positron Emission Tomography

“…The principal result of this study is a widespread reduction in synaptic density in PSP‐Richardson’s syndrome and amyloid‐negative CBS (which we define as CBD). This accords with postmortem estimates of synaptic loss in PSP and CBD, using synaptophysin immunohistochemistry, 6 imaging of neurite density in PSP, 41 and morphological studies of cortical dendrites in the closely related condition of frontotemporal lobe dementia 42 . Indirect evidence of synaptic loss, from consequential reduction in metabolism, comes from [ 18 F]FDG PET changes in frontal, temporal, and parietal lobes 43‐46 .…”

In vivo coupling of dendritic complexity with presynaptic density in primary tauopathies

“…This extends previous investigations of ODI microstructural change in PSP-RS and CBS/CBD (Mitchell et al, 2019), demonstrating the in vivo coupling of dendritic complexity to presynaptic density, in line with preclinical models of tauopathies (Hoffmann et al, 2014;Rocher et al, 2010).…”

Aberrant Fiber Coherence of Amygdala−Accumbens−Pallidum Pathway Is Associated With Disorganized Nigrostriatal−Nigropallidal Pathway in Parkinson's Disease

“…Accordingly, reduced FA partially points to axonal disorganization and degeneration. 16,34 A previous study also identified anatomical connectivity deficits in the basal ganglia−motor cortex pathway, which was consistent with our results and jointly illustrated the degeneration of the basal ganglia−motor cortex pathway. 35 The negative correlations between MD as well as AD in the left nigrostriatal−nigropallidal pathway and FA in the left basal ganglia−motor cortex pathway indicate that the higher diffusivity in the nigrostriatal−nigropallidal pathway, the lower the fiber coherence in the basal ganglia −motor cortex pathway.…”