Diffusion tensor and restriction spectrum imaging reflect different aspects of neurodegeneration in Parkinson's disease.

Tuva R Hope,Anders Dale,Lubomira Anderkova,Zuzana Balážová,Tormod Fladby,Per Selnes,Irena Rektorová,Nela Nemcova-Elfmarkova,Atle Bjørnerud,Pew-Thian Yap

doi:10.1371/journal.pone.0217922

Abstract

To meet the need for Parkinson’s disease biomarkers and evidence for amount and distribution of pathological changes, MRI diffusion tensor imaging (DTI) has been explored in a number of previous studies. However, conflicting results warrant further investigations. As tissue microstructure, particularly of the grey matter, is heterogeneous, a more precise diffusion model may benefit tissue characterization. The purpose of this study was to analyze the diffusion-based imaging technique restriction spectrum imaging (RSI) and DTI, and their ability to detect microstructural changes within brain regions associated with motor function in Parkinson’s disease. Diffusion weighted (DW) MR images of a total of 100 individuals, (46 Parkinson’s disease patients and 54 healthy controls) were collected using b-values of 0–4000s/mm2. Output diffusion-based maps were estimated based on the RSI-model combining the full set of DW-images (Cellular Index (CI), Neurite Density (ND)) and DTI-model combining b = 0 and b = 1000 s/mm2 (fractional anisotropy (FA), Axial-, Mean- and Radial diffusivity (AD, MD, RD)). All parametric maps were analyzed in a voxel-wise group analysis, with focus on typical brain regions associated with Parkinson’s disease pathology. CI, ND and DTI diffusivity metrics (AD, MD, RD) demonstrated the ability to differentiate between groups, with strongest performance within the thalamus, prone to pathology in Parkinson’s disease. Our results indicate that RSI may improve the predictive power of diffusion-based MRI, and provide additional information when combined with the standard diffusivity measurements. In the absence of major atrophy, diffusion techniques may reveal microstructural pathology. Our results suggest that protocols for MRI diffusion imaging may be adapted to more sensitive detection of pathology at different sites of the central nervous system.

Highlights

Parkinson’s disease (PD) is a slowly progressing neurodegenerative disorder, affecting both motor function and cognition
We found that that both diffusion tensor imaging (DTI)-derived and restriction spectrum imaging (RSI)-derived metrics are sensitive to group effects with significant clusters (p < 0.05) in the thalamus, the hippocampus and the amygdala manifested as increased CI, mean diffusivity (MD), Radial Diffusivity (RD) and AD and decreased ND in the PD group
We found no evidence that fractional anisotropy (FA) significantly differed between groups, diffusivity (MD, RD and AD) was increased in the thalamus of the PD group

Summary

Introduction

Parkinson’s disease (PD) is a slowly progressing neurodegenerative disorder, affecting both motor function and cognition. PD is primarily diagnosed clinically after the pathology has reached an advanced stage, and confirmed post-mortem by loss of dopamine neurons in the substantia nigra and the presence of intracellular aggregates of α-synuclein called Lewy bodies [1]. Formation of Lewy bodies, loss of neurites, loss of dopamine-containing neurons and gliosis in substantia nigra is an early phenomenon in PD, whereas cortical pathology is thought to precede major subcortical affection on Dementia with Lewy Bodies [2, 3]. In addition to accumulation in Lewy-bodies, a major deposition site of central nervous system (CNS) oligomeric α-synuclein is in the presynapse, accompanied by transsynaptic dendritic spine loss [5, 6], suggesting widespread pathology. There is a second pattern with medial temporal lobe atrophy more closely coupled to cognitive decline [8], and we recently described cortical metabolic changes associated with biomarker changes in temporo-occipital and frontal regions [9]

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