Glia Imaging Differentiates Multiple System Atrophy from Parkinson's Disease: A Pet Study Using [ 11C ] PBR28 and Machine Learning Enhanced Analysis

2021 ◽  
Author(s):  
Aurelija Jucaite ◽  
Zsolt Cselényi ◽  
William C. Kreisl ◽  
Eugenii A. Rabiner ◽  
Andrea Varrone ◽  
...  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alexandra Abos ◽  
Hugo C. Baggio ◽  
Barbara Segura ◽  
Anna Campabadal ◽  
Carme Uribe ◽  
...  

Abstract Recent studies combining diffusion tensor-derived metrics and machine learning have shown promising results in the discrimination of multiple system atrophy (MSA) and Parkinson’s disease (PD) patients. This approach has not been tested using more complex methodologies such as probabilistic tractography. The aim of this work is assessing whether the strength of structural connectivity between subcortical structures, measured as the number of streamlines (NOS) derived from tractography, can be used to classify MSA and PD patients at the single-patient level. The classification performance of subcortical FA and MD was also evaluated to compare the discriminant ability between diffusion tensor-derived metrics and NOS. Using diffusion-weighted images acquired in a 3 T MRI scanner and probabilistic tractography, we reconstructed the white matter tracts between 18 subcortical structures from a sample of 54 healthy controls, 31 MSA patients and 65 PD patients. NOS between subcortical structures were compared between groups and entered as features into a machine learning algorithm. Reduced NOS in MSA compared with controls and PD were found in connections between the putamen, pallidum, ventral diencephalon, thalamus, and cerebellum, in both right and left hemispheres. The classification procedure achieved an overall accuracy of 78%, with 71% of the MSA subjects and 86% of the PD patients correctly classified. NOS features outperformed the discrimination performance obtained with FA and MD. Our findings suggest that structural connectivity derived from tractography has the potential to correctly distinguish between MSA and PD patients. Furthermore, NOS measures obtained from tractography might be more useful than diffusion tensor-derived metrics for the detection of MSA.


2004 ◽  
Vol 35 (03) ◽  
Author(s):  
G Wasner ◽  
P Remien ◽  
C Guballa ◽  
M Hirschner ◽  
A Binder ◽  
...  

2020 ◽  
Vol 13 (5) ◽  
pp. 508-523 ◽  
Author(s):  
Guan‐Hua Huang ◽  
Chih‐Hsuan Lin ◽  
Yu‐Ren Cai ◽  
Tai‐Been Chen ◽  
Shih‐Yen Hsu ◽  
...  

2021 ◽  
pp. 105332
Author(s):  
Joachim Brumberg ◽  
Anastasia Kuzkina ◽  
Constantin Lapa ◽  
Sona Mammadova ◽  
Andreas Buck ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Benedict Tanudjojo ◽  
Samiha S. Shaikh ◽  
Alexis Fenyi ◽  
Luc Bousset ◽  
Devika Agarwal ◽  
...  

Abstractα-Synuclein is critical in the pathogenesis of Parkinson’s disease and related disorders, yet it remains unclear how its aggregation causes degeneration of human dopaminergic neurons. In this study, we induced α-synuclein aggregation in human iPSC-derived dopaminergic neurons using fibrils generated de novo or amplified in the presence of brain homogenates from Parkinson’s disease or multiple system atrophy. Increased α-synuclein monomer levels promote seeded aggregation in a dose and time-dependent manner, which is associated with a further increase in α-synuclein gene expression. Progressive neuronal death is observed with brain-amplified fibrils and reversed by reduction of intraneuronal α-synuclein abundance. We identified 56 proteins differentially interacting with aggregates triggered by brain-amplified fibrils, including evasion of Parkinson’s disease-associated deglycase DJ-1. Knockout of DJ-1 in iPSC-derived dopaminergic neurons enhance fibril-induced aggregation and neuronal death. Taken together, our results show that the toxicity of α-synuclein strains depends on aggregate burden, which is determined by monomer levels and conformation which dictates differential interactomes. Our study demonstrates how Parkinson’s disease-associated genes influence the phenotypic manifestation of strains in human neurons.


Sign in / Sign up

Export Citation Format

Share Document