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      The Utility of Independent Component Analysis and Machine Learning in the Identification of the Amyotrophic Lateral Sclerosis Diseased Brain

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          Abstract

          Amyotrophic lateral sclerosis (ALS) is a devastating disease with a lifetime risk of ∼1 in 2000. Presently, diagnosis of ALS relies on clinical assessments for upper motor neuron and lower motor neuron deficits in multiple body segments together with a history of progression of symptoms. In addition, it is common to evaluate lower motor neuron pathology in ALS by electromyography. However, upper motor neuron pathology is solely assessed on clinical grounds, thus hindering diagnosis. In the past decade magnetic resonance methods have been shown to be sensitive to the ALS disease process, namely: resting-state connectivity measured with functional MRI, cortical thickness measured by high-resolution imaging, diffusion tensor imaging (DTI) metrics such as fractional anisotropy and radial diffusivity, and more recently magnetic resonance spectroscopy (MRS) measures of gamma-aminobutyric acid concentration. In this present work we utilize independent component analysis to derive brain networks based on resting-state functional magnetic resonance imaging and use those derived networks to build a disease state classifier using machine learning (support-vector machine). We show that it is possible to achieve over 71% accuracy for disease state classification. These results are promising for the development of a clinically relevant disease state classifier. Future inclusion of other MR modalities such as high-resolution structural imaging, DTI and MRS should improve this overall accuracy.

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          FSL.

          FSL (the FMRIB Software Library) is a comprehensive library of analysis tools for functional, structural and diffusion MRI brain imaging data, written mainly by members of the Analysis Group, FMRIB, Oxford. For this NeuroImage special issue on "20 years of fMRI" we have been asked to write about the history, developments and current status of FSL. We also include some descriptions of parts of FSL that are not well covered in the existing literature. We hope that some of this content might be of interest to users of FSL, and also maybe to new research groups considering creating, releasing and supporting new software packages for brain image analysis. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations.

            A previous report of correlations in low-frequency resting-state fluctuations between right and left hemisphere motor cortices in rapidly sampled single-slice echoplanar data is confirmed using a whole-body echoplanar MRI scanner at 1.5 T. These correlations are extended to lower sampling rate multislice echoplanar acquisitions and other right/left hemisphere-symmetric functional cortices. The specificity of the correlations in the lower sampling-rate acquisitions is lower due to cardiac and respiratory-cycle effects which are aliased into the pass-band of the low-pass filter. Data are combined for three normal right-handed male subjects. Correlations to left hemisphere motor cortex, visual cortex, and amygdala are measured in long resting-state scans.
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              Frequencies contributing to functional connectivity in the cerebral cortex in "resting-state" data.

              In subjects performing no specific cognitive task ("resting state"), time courses of voxels within functionally connected regions of the brain have high cross-correlation coefficients ("functional connectivity"). The purpose of this study was to measure the contributions of low frequencies and physiological noise to cross-correlation maps. In four healthy volunteers, task-activation functional MR imaging and resting-state data were acquired. We obtained four contiguous slice locations in the "resting state" with a high sampling rate. Regions of interest consisting of four contiguous voxels were selected. The correlation coefficient for the averaged time course and every other voxel in the four slices was calculated and separated into its component frequency contributions. We calculated the relative amounts of the spectrum that were in the low-frequency (0 to 0.1 Hz), the respiratory-frequency (0.1 to 0.5 Hz), and cardiac-frequency range (0.6 to 1.2 Hz). For each volunteer, resting-state maps that resembled task-activation maps were obtained. For the auditory and visual cortices, the correlation coefficient depended almost exclusively on low frequencies (<0.1 Hz). For all cortical regions studied, low-frequency fluctuations contributed more than 90% of the correlation coefficient. Physiological (respiratory and cardiac) noise sources contributed less than 10% to any functional connectivity MR imaging map. In blood vessels and cerebrospinal fluid, physiological noise contributed more to the correlation coefficient. Functional connectivity in the auditory, visual, and sensorimotor cortices is characterized predominantly by frequencies slower than those in the cardiac and respiratory cycles. In functionally connected regions, these low frequencies are characterized by a high degree of temporal coherence.
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                Author and article information

                Journal
                Front Hum Neurosci
                Front Hum Neurosci
                Front. Hum. Neurosci.
                Frontiers in Human Neuroscience
                Frontiers Media S.A.
                1662-5161
                10 June 2013
                2013
                : 7
                : 251
                Affiliations
                [1] 1Department of Radiology, University of Michigan , Ann Arbor, MI, USA
                [2] 2Department of Psychiatry, University of Michigan , Ann Arbor, MI, USA
                [3] 3Ann Arbor VA Healthcare System , Ann Arbor, MI, USA
                Author notes

                Edited by: Veronika Schöpf, Medical University Vienna, Austria

                Reviewed by: Federica Agosta, Vita-Salute San Raffaele University, Italy; Christian Rummel, University Institute for Diagnostic and Interventional Neuroradiology, Switzerland

                *Correspondence: Robert C. Welsh, Department of Radiology, University of Michigan, Medical Science I, Room 3208C, 1301 Catherine Street, Ann Arbor, MI 48109, USA e-mail: rcwelsh@ 123456med.umich.edu
                Article
                10.3389/fnhum.2013.00251
                3677153
                23772210
                c99bebad-b2e9-45cc-aad3-0f284df67e2e
                Copyright © 2013 Welsh, Jelsone-Swain and Foerster.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 25 January 2013
                : 20 May 2013
                Page count
                Figures: 6, Tables: 0, Equations: 2, References: 71, Pages: 9, Words: 6676
                Categories
                Neuroscience
                Original Research

                Neurosciences
                independent component analysis,support vector machine,resting-state functional connectivity,amyotrophic lateral sclerosis,machine learning,disease-state classification

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