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      Classification algorithms with multi-modal data fusion could accurately distinguish neuromyelitis optica from multiple sclerosis

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          Abstract

          Neuromyelitis optica (NMO) exhibits substantial similarities to multiple sclerosis (MS) in clinical manifestations and imaging results and has long been considered a variant of MS. With the advent of a specific biomarker in NMO, known as anti-aquaporin 4, this assumption has changed; however, the differential diagnosis remains challenging and it is still not clear whether a combination of neuroimaging and clinical data could be used to aid clinical decision-making. Computer-aided diagnosis is a rapidly evolving process that holds great promise to facilitate objective differential diagnoses of disorders that show similar presentations. In this study, we aimed to use a powerful method for multi-modal data fusion, known as a multi-kernel learning and performed automatic diagnosis of subjects. We included 30 patients with NMO, 25 patients with MS and 35 healthy volunteers and performed multi-modal imaging with T1-weighted high resolution scans, diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). In addition, subjects underwent clinical examinations and cognitive assessments. We included 18 a priori predictors from neuroimaging, clinical and cognitive measures in the initial model. We used 10-fold cross-validation to learn the importance of each modality, train and finally test the model performance. The mean accuracy in differentiating between MS and NMO was 88%, where visible white matter lesion load, normal appearing white matter (DTI) and functional connectivity had the most important contributions to the final classification. In a multi-class classification problem we distinguished between all of 3 groups (MS, NMO and healthy controls) with an average accuracy of 84%. In this classification, visible white matter lesion load, functional connectivity, and cognitive scores were the 3 most important modalities. Our work provides preliminary evidence that computational tools can be used to help make an objective differential diagnosis of NMO and MS.

          Highlights

          • We developed models for automatic differential diagnosis between multiple sclerosis and neuromyelitis optica.

          • Multimodal imaging may be integrated with clinical and cognitive data to develop multidimensional classification algorithms.

          • Classification algorithms could be used to aid in objective clinical decision making.

          • Future research should assess the generalizability of classification algorithms in independent cohorts.

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          Most cited references36

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          Declaration of Helsinki. Ethical principles for medical research involving human subjects.

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            AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance.

            Antibodies to aquaporin-4 (also known as AQP4-Ab or NMO-IgG) are sensitive and highly specific serum markers of autoimmune neuromyelitis optica (NMO). Second-generation recombinant diagnostic assays can detect AQP4-Ab in >or=80% of patients with NMO, and a role for AQP4-Ab in the pathophysiology of this condition was corroborated by a series of in vitro studies that demonstrated disruption of the blood-brain barrier, impairment of glutamate homeostasis and induction of necrotic cell death by AQP4-Ab-positive serum. Additional evidence for such a role has emerged from clinical observations, including the demonstration of a correlation between serum levels of AQP4-Ab and disease activity. The finding of NMO-like CNS lesions and clinical disease following passive transfer of AQP4-Ab-positive serum in several independent animal studies provided definitive proof for a pathogenic role of AQP4-Ab in vivo. Together, these findings provide a strong rationale for the use of therapies targeted against B cells or antibodies in the treatment of NMO. In this Review, we summarize the latest evidence in support of a direct involvement of AQP4-Ab in the immunopathogenesis of NMO, and critically appraise the diagnostic tests currently available for the detection of this serum reactivity.
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              Diagnostic neuroimaging across diseases

              Fully automated classification algorithms have been successfully applied to diagnose a wide range of neurological and psychiatric diseases. They are sufficiently robust to handle data from different scanners for many applications and in specific cases outperform radiologists. This article provides an overview of current applications taking structural imaging in Alzheimer's Disease and schizophrenia as well as functional imaging to diagnose depression as examples. In this context, we also report studies aiming to predict the future course of the disease and the response to treatment for the individual. This has obvious clinical relevance but is also important for the design of treatment studies that may aim to include a cohort with a predicted fast disease progression to be more sensitive to detect treatment effects. In the second part, we present our own opinions on i) the role these classification methods can play in the clinical setting; ii) where their limitations are at the moment and iii) how those can be overcome. Specifically, we discuss strategies to deal with disease heterogeneity, diagnostic uncertainties, a probabilistic framework for classification and multi-class classification approaches.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                9 January 2015
                9 January 2015
                2015
                : 7
                : 306-314
                Affiliations
                [a ]MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
                [b ]Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran
                [c ]Interdisciplinary Neuroscience Research Program, Tehran University of Medical Sciences, Tehran, Iran
                [d ]National Brain Mapping Center, Department of Neurology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [e ]Centre de Recherche de l'Institut du Cerveau et de la Moelle Pinire, Universitat Pierre et Marie Curie, Inserm, Paris U975, France
                [f ]Department of Radiology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
                [g ]Iranian Center of Neurological Research, Neuroscience Institute, University of Medical Sciences, Tehran, Iran
                Author notes
                [* ]Correspondence to: Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran 1136746911, Iran. Tel: +98 21 66348572; fax: +98 21 66348570. msahrai@ 123456sina.tums.ac.ir
                Article
                S2213-1582(15)00002-9
                10.1016/j.nicl.2015.01.001
                4297886
                25610795
                4070998f-005a-416b-b400-5269d66e9bed
                © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 28 October 2014
                : 13 December 2014
                : 3 January 2015
                Categories
                Article

                multiple sclerosis,neuromyelitis optica,differential diagnosis,computational diagnosis,multi-modal imaging

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