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      Diffusion Tensor Imaging in Parkinson's Disease and Parkinsonian Syndrome: A Systematic Review

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          Abstract

          Diffusion tensor imaging (DTI) allows measuring fractional anisotropy and similar microstructural indices of the brain white matter. Lower than normal fractional anisotropy as well as higher than normal diffusivity is associated with loss of microstructural integrity and neurodegeneration. Previous DTI studies in Parkinson's disease (PD) have demonstrated abnormal fractional anisotropy in multiple white matter regions, particularly in the dopaminergic nuclei and dopaminergic pathways. However, DTI is not considered a diagnostic marker for the earliest Parkinson's disease since anisotropic alterations present a temporally divergent pattern during the earliest Parkinson's course. This article reviews a majority of clinically employed DTI studies in PD, and it aims to prove the utilities of DTI as a marker of diagnosing PD, correlating clinical symptomatology, tracking disease progression, and treatment effects. To address the challenge of DTI being a diagnostic marker for early PD, this article also provides a comparison of the results from a longitudinal, early stage, multicenter clinical cohort of Parkinson's research with previous publications. This review provides evidences of DTI as a promising marker for monitoring PD progression and classifying atypical PD types, and it also interprets the possible pathophysiologic processes under the complex pattern of fractional anisotropic changes in the first few years of PD. Recent technical advantages, limitations, and further research strategies of clinical DTI in PD are additionally discussed.

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          Most cited references225

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          Staging of brain pathology related to sporadic Parkinson’s disease

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            Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data.

            There has been much recent interest in using magnetic resonance diffusion imaging to provide information about anatomical connectivity in the brain, by measuring the anisotropic diffusion of water in white matter tracts. One of the measures most commonly derived from diffusion data is fractional anisotropy (FA), which quantifies how strongly directional the local tract structure is. Many imaging studies are starting to use FA images in voxelwise statistical analyses, in order to localise brain changes related to development, degeneration and disease. However, optimal analysis is compromised by the use of standard registration algorithms; there has not to date been a satisfactory solution to the question of how to align FA images from multiple subjects in a way that allows for valid conclusions to be drawn from the subsequent voxelwise analysis. Furthermore, the arbitrariness of the choice of spatial smoothing extent has not yet been resolved. In this paper, we present a new method that aims to solve these issues via (a) carefully tuned non-linear registration, followed by (b) projection onto an alignment-invariant tract representation (the "mean FA skeleton"). We refer to this new approach as Tract-Based Spatial Statistics (TBSS). TBSS aims to improve the sensitivity, objectivity and interpretability of analysis of multi-subject diffusion imaging studies. We describe TBSS in detail and present example TBSS results from several diffusion imaging studies.
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              Stages in the development of Parkinson's disease-related pathology.

              The synucleinopathy, idiopathic Parkinson's disease, is a multisystem disorder that involves only a few predisposed nerve cell types in specific regions of the human nervous system. The intracerebral formation of abnormal proteinaceous Lewy bodies and Lewy neurites begins at defined induction sites and advances in a topographically predictable sequence. As the disease progresses, components of the autonomic, limbic, and somatomotor systems become particularly badly damaged. During presymptomatic stages 1-2, inclusion body pathology is confined to the medulla oblongata/pontine tegmentum and olfactory bulb/anterior olfactory nucleus. In stages 3-4, the substantia nigra and other nuclear grays of the midbrain and forebrain become the focus of initially slight and, then, severe pathological changes. At this point, most individuals probably cross the threshold to the symptomatic phase of the illness. In the end-stages 5-6, the process enters the mature neocortex, and the disease manifests itself in all of its clinical dimensions.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                25 September 2020
                2020
                : 11
                : 531993
                Affiliations
                [1] 1Department of Psychiatry, War Related Illness and Injury Study Center, Veterans Affairs Palo Alto Health Care System , Palo Alto, CA, United States
                [2] 2Department of Psychiatry, Mainline Health, Bryn Mawr Hospital , Bryn Mawr, PA, United States
                Author notes

                Edited by: Emily Keshner, Temple University, United States

                Reviewed by: Fred Sampedro, Sant Pau Institute for Biomedical Research, Spain; Shantanu Ghosh, Akal University, India

                This article was submitted to Movement Disorders, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2020.531993
                7546271
                33101169
                4fd1986f-c5c9-4e89-9342-c6222d94021d
                Copyright © 2020 Zhang and Burock.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 April 2020
                : 18 August 2020
                Page count
                Figures: 4, Tables: 5, Equations: 0, References: 227, Pages: 25, Words: 19542
                Categories
                Neurology
                Review

                Neurology
                diffusion tensor imaging (dti),fractional anisotropy (fa),parkinson's progression marker initiative (ppmi),diffusion tensor tractography (dtt),dopaminergic pathway,substantia nigra (sn),parkinsion's disease (pd)

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