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      Utility of Multi-Modal MRI for Differentiating of Parkinson's Disease and Progressive Supranuclear Palsy Using Machine Learning

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          Abstract

          Background: Patients with Parkinson's disease (PD) and progressive supranuclear palsy Richardson's syndrome (PSP-RS) often show overlapping clinical features, leading to misdiagnoses. The objective of this study was to investigate the feasibility and utility of using multi-modal MRI datasets for an automatic differentiation of PD patients, PSP-RS patients, and healthy control (HC) subjects.

          Material and Methods: T1-weighted, T2-weighted, and diffusion-tensor (DTI) MRI datasets from 45 PD patients, 20 PSP-RS patients, and 38 HC subjects were available for this study. Using an atlas-based approach, regional values of brain morphology (T1-weighted), brain iron metabolism (T2-weighted), and microstructural integrity (DTI) were measured and employed for feature selection and subsequent classification using combinations of various established machine learning methods.

          Results: The optimal machine learning model using regional morphology features only achieved a classification accuracy of 65% (67/103 correct classifications) differentiating PD patients, PSP-RS patients, and HC subjects. The optimal machine learning model using only quantitative T2 values performed slightly better and achieved an accuracy of 75.7% (78/103). The optimal classifier using DTI features alone performed considerably better with 95.1% accuracy (98/103). The optimal multi-modal classifier using all features also achieved an accuracy of 95.1% but required more features and achieved a slightly lower F1-score compared to the optimal model using DTI features alone.

          Conclusion: Machine learning models using multi-modal MRI perform significantly better than uni-modal machine learning models using morphological parameters based on T1-weighted MRI datasets alone or brain iron metabolism markers based on T2-weighted MRI datasets alone. However, machine learnig models using regional brain microstructural integrity metrics computed from DTI datasets perform similar to the optimal multi-modal machine learning model. Thus, given the results from this study cohort, it appears that morphology and brain iron metabolism markers may not provide additional value for classification compared to using DTI metrics alone.

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          Most cited references43

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          MDS clinical diagnostic criteria for Parkinson's disease.

          This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.
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            Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain.

            One of the most challenging problems in modern neuroimaging is detailed characterization of neurodegeneration. Quantifying spatial and longitudinal atrophy patterns is an important component of this process. These spatiotemporal signals will aid in discriminating between related diseases, such as frontotemporal dementia (FTD) and Alzheimer's disease (AD), which manifest themselves in the same at-risk population. Here, we develop a novel symmetric image normalization method (SyN) for maximizing the cross-correlation within the space of diffeomorphic maps and provide the Euler-Lagrange equations necessary for this optimization. We then turn to a careful evaluation of our method. Our evaluation uses gold standard, human cortical segmentation to contrast SyN's performance with a related elastic method and with the standard ITK implementation of Thirion's Demons algorithm. The new method compares favorably with both approaches, in particular when the distance between the template brain and the target brain is large. We then report the correlation of volumes gained by algorithmic cortical labelings of FTD and control subjects with those gained by the manual rater. This comparison shows that, of the three methods tested, SyN's volume measurements are the most strongly correlated with volume measurements gained by expert labeling. This study indicates that SyN, with cross-correlation, is a reliable method for normalizing and making anatomical measurements in volumetric MRI of patients and at-risk elderly individuals.
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              Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria.

              PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome.
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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
                14 April 2021
                2021
                : 12
                : 648548
                Affiliations
                [1] 1Department of Radiology, University of Calgary , Calgary, AB, Canada
                [2] 2Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf , Hamburg, Germany
                [3] 3Department of Neurology, University Hospital Würzburg , Würzburg, Germany
                [4] 4Department of Neurology, Klinikum Bremerhaven-Reinkenheide , Bremerhaven, Germany
                Author notes

                Edited by: Maria Carmela Tartaglia, University of Toronto, Canada

                Reviewed by: Matteo Bologna, Sapienza University of Rome, Italy; Alexandru Hanganu, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Canada

                *Correspondence: Nils D. Forkert nils.forkert@ 123456ucalgary.ca

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

                Article
                10.3389/fneur.2021.648548
                8079721
                33935946
                b998c3ec-6380-4f90-8c63-ff8f1b52e453
                Copyright © 2021 Talai, Sedlacik, Boelmans and Forkert.

                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
                : 31 December 2020
                : 22 March 2021
                Page count
                Figures: 1, Tables: 7, Equations: 0, References: 44, Pages: 11, Words: 8679
                Funding
                Funded by: Canada Excellence Research Chairs, Government of Canada 10.13039/501100002784
                Funded by: Calgary Foundation 10.13039/100012260
                Categories
                Neurology
                Original Research

                Neurology
                machine learning,magnetic resonance imaging,computer-assisted image analysis,parkinson's disease,progressive supranuclear palsy

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