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      Early prediction of cognitive deficits in very preterm infants using functional connectome data in an artificial neural network framework

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          Abstract

          Investigation of the brain's functional connectome can improve our understanding of how an individual brain's organizational changes influence cognitive function and could result in improved individual risk stratification. Brain connectome studies in adults and older children have shown that abnormal network properties may be useful as discriminative features and have exploited machine learning models for early diagnosis in a variety of neurological conditions. However, analogous studies in neonates are rare and with limited significant findings. In this paper, we propose an artificial neural network (ANN) framework for early prediction of cognitive deficits in very preterm infants based on functional connectome data from resting state fMRI. Specifically, we conducted feature selection via stacked sparse autoencoder and outcome prediction via support vector machine (SVM). The proposed ANN model was unsupervised learned using brain connectome data from 884 subjects in autism brain imaging data exchange database and SVM was cross-validated on 28 very preterm infants (born at 23–31 weeks of gestation and without brain injury; scanned at term-equivalent postmenstrual age). Using 90 regions of interests, we found that the ANN model applied to functional connectome data from very premature infants can predict cognitive outcome at 2 years of corrected age with an accuracy of 70.6% and area under receiver operating characteristic curve of 0.76. We also noted that several frontal lobe and somatosensory regions, significantly contributed to prediction of cognitive deficits 2 years later. Our work can be considered as a proof of concept for utilizing ANN models on functional connectome data to capture the individual variability inherent in the developing brains of preterm infants. The full potential of ANN will be realized and more robust conclusions drawn when applied to much larger neuroimaging datasets, as we plan to do.

          Highlights

          • Stacked sparse autoencoder for high-level connectome feature learning

          • Artificial neural network on functional connectome data for outcome prediction

          • Prediction of cognitive deficits in very preterm infants

          • Exploration of functional brain connections that most contribute to prediction

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          Most cited references44

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          LIBSVM: A library for support vector machines

          LIBSVM is a library for Support Vector Machines (SVMs). We have been actively developing this package since the year 2000. The goal is to help users to easily apply SVM to their applications. LIBSVM has gained wide popularity in machine learning and many other areas. In this article, we present all implementation details of LIBSVM. Issues such as solving SVM optimization problems theoretical convergence multiclass classification probability estimates and parameter selection are discussed in detail.
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            Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization.

            Resting state functional connectivity MRI (fcMRI) is widely used to investigate brain networks that exhibit correlated fluctuations. While fcMRI does not provide direct measurement of anatomic connectivity, accumulating evidence suggests it is sufficiently constrained by anatomy to allow the architecture of distinct brain systems to be characterized. fcMRI is particularly useful for characterizing large-scale systems that span distributed areas (e.g., polysynaptic cortical pathways, cerebro-cerebellar circuits, cortical-thalamic circuits) and has complementary strengths when contrasted with the other major tool available for human connectomics-high angular resolution diffusion imaging (HARDI). We review what is known about fcMRI and then explore fcMRI data reliability, effects of preprocessing, analysis procedures, and effects of different acquisition parameters across six studies (n = 98) to provide recommendations for optimization. Run length (2-12 min), run structure (1 12-min run or 2 6-min runs), temporal resolution (2.5 or 5.0 s), spatial resolution (2 or 3 mm), and the task (fixation, eyes closed rest, eyes open rest, continuous word-classification) were varied. Results revealed moderate to high test-retest reliability. Run structure, temporal resolution, and spatial resolution minimally influenced fcMRI results while fixation and eyes open rest yielded stronger correlations as contrasted to other task conditions. Commonly used preprocessing steps involving regression of nuisance signals minimized nonspecific (noise) correlations including those associated with respiration. The most surprising finding was that estimates of correlation strengths stabilized with acquisition times as brief as 5 min. The brevity and robustness of fcMRI positions it as a powerful tool for large-scale explorations of genetic influences on brain architecture. We conclude by discussing the strengths and limitations of fcMRI and how it can be combined with HARDI techniques to support the emerging field of human connectomics.
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              Infant Brain Atlases from Neonates to 1- and 2-Year-Olds

              Background Studies for infants are usually hindered by the insufficient image contrast, especially for neonates. Prior knowledge, in the form of atlas, can provide additional guidance for the data processing such as spatial normalization, label propagation, and tissue segmentation. Although it is highly desired, there is currently no such infant atlas which caters for all these applications. The reason may be largely due to the dramatic early brain development, image processing difficulties, and the need of a large sample size. Methodology To this end, after several years of subject recruitment and data acquisition, we have collected a unique longitudinal dataset, involving 95 normal infants (56 males and 39 females) with MRI scanned at 3 ages, i.e., neonate, 1-year-old, and 2-year-old. State-of-the-art MR image segmentation and registration techniques were employed, to construct which include the templates (grayscale average images), tissue probability maps (TPMs), and brain parcellation maps (i.e., meaningful anatomical regions of interest) for each age group. In addition, the longitudinal correspondences between age-specific atlases were also obtained. Experiments of typical infant applications validated that the proposed atlas outperformed other atlases and is hence very useful for infant-related studies. Conclusions We expect that the proposed infant 0–1–2 brain atlases would be significantly conducive to structural and functional studies of the infant brains. These atlases are publicly available in our website, http://bric.unc.edu/ideagroup/free-softwares/.
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                Author and article information

                Contributors
                Journal
                Neuroimage Clin
                Neuroimage Clin
                NeuroImage : Clinical
                Elsevier
                2213-1582
                31 January 2018
                2018
                31 January 2018
                : 18
                : 290-297
                Affiliations
                [a ]Perinatal Institute, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
                [b ]Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States
                [c ]Pediatric Neuroimaging Research Consortium, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
                [d ]Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
                Author notes
                [* ]Corresponding author. lili.he@ 123456cchmc.org
                Article
                S2213-1582(18)30032-9
                10.1016/j.nicl.2018.01.032
                5987842
                29876249
                861db638-9db7-457c-bf35-f2def0c01102
                © 2018 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 9 October 2017
                : 22 January 2018
                : 24 January 2018
                Categories
                Regular Article

                artificial neural network,stacked sparse autoencoder,support vector machine,very preterm infants,functional mri,cognitive deficit

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