Hongwei Wen

Combining tract- and atlas-based analysis reveals microstructural abnormalities in early Tourette syndrome children

Tourette syndrome (TS) is a neurological disorder that causes uncontrolled repetitive motor and vocal tics in children. Examining the neural basis of TS churned out different research studies that advanced our understanding of the brain pathways involved in its development. Particularly, growing evidence points to abnormalities within the fronto‐striato‐thalamic pathways. In this study, we combined Tract‐Based Spatial Statistics (TBSS) and Atlas‐based regions of interest (ROI) analysis approach, to investigate the microstructural diffusion changes in both deep and superficial white matter (SWM) in TS children. We then characterized the altered microstructure of white matter in 27 TS children in comparison with 27 age‐ and gender‐matched healthy controls. We found that fractional anisotropy (FA) decreases and radial diffusivity (RD) increases in deep white matter (DWM) tracts in cortico‐striato‐thalamo‐cortical (CSTC) circuit as well as SWM. Furthermore, we found that lower FA values and higher RD values in white matter regions are correlated with more severe tics, but not tics duration. Besides, we also found both axial diffusivity and mean diffusivity increase using Atlas‐based ROI analysis. Our work may suggest that microstructural diffusion changes in white matter is not only restricted to the gray matter of CSTC circuit but also affects SWM within the primary motor and somatosensory cortex, commissural and association fibers. Hum Brain Mapp 37:1903–1919, 2016.

Structural brain alterations in primary open angle glaucoma: a 3T MRI study

Glaucoma is not only an eye disease but is also associated with degeneration of brain structures. We now investigated the pattern of visual and non-visual brain structural changes in 25 primary open angle glaucoma (POAG) patients and 25 age-gender-matched normal controls using T1-weighted imaging. MRI images were subjected to volume-based analysis (VBA) and surface-based analysis (SBA) in the whole brain as well as ROI-based analysis of the lateral geniculate nucleus (LGN), visual cortex (V1/2), amygdala and hippocampus. While VBA showed no significant differences in the gray matter volumes of patients, SBA revealed significantly reduced cortical thickness in the right frontal pole and ROI-based analysis volume shrinkage in LGN bilaterally, right V1 and left amygdala. Structural abnormalities were correlated with clinical parameters in a subset of the patients revealing that the left LGN volume was negatively correlated with bilateral cup-to-disk ratio (CDR), the right LGN volume was positively correlated with the mean deviation of the right visual hemifield, and the right V1 cortical thickness was negatively correlated with the right CDR in glaucoma. These results demonstrate that POAG affects both vision-related structures and non-visual cortical regions. Moreover, alterations of the brain visual structures reflect the clinical severity of glaucoma.

Multi-modal multiple kernel learning for accurate identification of Tourette syndrome children

Abstract Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder characterized by the presence of multiple motor and vocal tics. To date, TS diagnosis remains somewhat limited and studies using advanced diagnostic methods are of great importance. In this paper, we introduce an automatic classification framework for accurate identification of TS children based on multi-modal and multi-type features, which is robust and easy to implement. We present in detail the feature extraction, feature selection, and classifier training methods. In addition, in order to exploit complementary information revealed by different feature modalities, we integrate multi-modal image features using multiple kernel learning (MKL). The performance of our framework has been validated in classifying 44 TS children and 48 age- and gender-matched healthy children. When combining features using MKL, the classification accuracy reached 94.24% using nested cross-validation. Most discriminative brain regions were mostly located in the cortico-basal ganglia, frontal cortico-cortical circuits, which are thought to be highly related to TS pathology. These results show that our method is reliable for early TS diagnosis, and promising for prognosis and treatment outcome.

Combining Disrupted and Discriminative Topological Properties of Functional Connectivity Networks as Neuroimaging Biomarkers for Accurate Diagnosis of Early Tourette Syndrome Children

Tourette syndrome (TS) is a childhood-onset neurological disorder. To date, accurate TS diagnosis remains challenging due to its varied clinical expressions and dependency on qualitative description of symptoms. Therefore, identifying accurate and objective neuroimaging biomarkers may help improve early TS diagnosis. As resting-state functional MRI (rs-fMRI) has been demonstrated as a promising neuroimaging tool for TS diagnosis, previous rs-fMRI studies on TS revealed functional connectivity (FC) changes in a few local brain networks or circuits. However, no study explored the disrupted topological organization of whole-brain FC networks in TS children. Meanwhile, very few studies have examined brain functional networks using machine-learning methods for diagnostics. In this study, we construct individual whole-brain, ROI-level FC networks for 29 drug-naive TS children and 37 healthy children. Then, we use graph theory analysis to investigate the topological disruptions between groups. The identified disrupted regions in FC networks not only involved the sensorimotor association regions but also the visual, default-mode and language areas, all highly related to TS. Furthermore, we propose a novel classification framework based on similarity network fusion (SNF) algorithm, to both diagnose an individual subject and explore the discriminative power of FC network topological properties in distinguishing between TS children and controls. We achieved a high accuracy of 88.79%, and the involved discriminative regions for classification were also highly related to TS. Together, both the disrupted topological properties between groups and the discriminative topological features for classification may be considered as comprehensive and helpful neuroimaging biomarkers for assisting the clinical TS diagnosis.

A diagnosis model for early Tourette syndrome children based on brain structural network characteristics

Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder characterized by the presence of multiple motor and vocal tics. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of action. The aim of our work is to select topological characteristics of structural network which were most efficient for estimating the classification models to identify early TS children. Here we employed the diffusion tensor imaging (DTI) and deterministic tractography to construct the structural networks of 44 TS children and 48 age and gender matched healthy children. We calculated four different connection matrices (fiber number, mean FA, averaged fiber length weighted and binary matrices) and then applied graph theoretical methods to extract the regional nodal characteristics of structural network. For each weighted or binary network, nodal degree, nodal efficiency and nodal betweenness were selected as features. Support Vector Machine Recursive Feature Extraction (SVM-RFE) algorithm was used to estimate the best feature subset for classification. The accuracy of 88.26% evaluated by a nested cross validation was achieved on combing best feature subset of each network characteristic. The identified discriminative brain nodes mostly located in the basal ganglia and frontal cortico-cortical networks involved in TS children which was associated with tic severity. Our study holds promise for early identification and predicting prognosis of TS children.

Computer-Aided Prognosis: Accurate Prediction of Patients with Neurologic and Psychiatric Diseases via Multi-modal MRI Analysis

Multi-modal magnetic resonance imaging (MRI) is increasingly used in neuroscience research, as it allowed the non-invasive investigation of structure and function of the human brain in health and pathology. One of the most important applications of multi-modal MRI is the provision of vital diagnostic data for neurologic and psychiatric disorders. As traditional MRI researches using univariate analyses can only reveal disease-related structural and functional alterations at group level which limited the clinical application, and recent attention has turned toward integrating multi-modal neuroimaging and computer-aided prognosis (CAD) technology, especially machine learning, to assist clinical disease diagnose. Research in this area is growing exponentially, and therefore it is meaningful to review the current and future development of this emerging area. Hence, in this paper, based on our own studies and contributions, we review the recent advances in multi-modal MRI and CAD technologies, and their applications to assist the clinical diagnosis of three common neurologic and psychiatric disorders, namely, Alzheimer’s disease, Attention deficit/hyperactivity disorder and Tourette syndrome. We extracted multi-modal features from structural, diffusion and resting-state functional MRI, then different feature selection methods and classifiers were applied. In addition, we applied different feature fusion schemes (e.g. multiple kernel learning) to combining multi-modal features for classification. Our experiments show that using feature fusion techniques to integrate multi-modal features can yield better classification results for diseases prediction, which may outline some future directions for multi-modal neuroimaging where researchers can design more advanced methods and models for neurologic and psychiatric research.

Disrupted topological organization of structural networks revealed by probabilistic diffusion tractography in Tourette syndrome children

Tourette syndrome (TS) is a childhood‐onset neurobehavioral disorder. Although previous TS studies revealed structural abnormalities in distinct corticobasal ganglia circuits, the topological alterations of the whole‐brain white matter (WM) structural networks remain poorly understood. Here, we used diffusion MRI probabilistic tractography and graph theoretical analysis to investigate the topological organization of WM networks in 44 drug‐naive TS children and 41 age‐ and gender‐matched healthy children. The WM networks were constructed by estimating inter‐regional connectivity probability and the topological properties were characterized using graph theory. We found that both TS and control groups showed an efficient small‐world organization in WM networks. However, compared to controls, TS children exhibited decreased global and local efficiency, increased shortest path length and small worldness, indicating a disrupted balance between local specialization and global integration in structural networks. Although both TS and control groups showed highly similar hub distributions, TS children exhibited significant decreased nodal efficiency, mainly distributed in the default mode, language, visual, and sensorimotor systems. Furthermore, two separate networks showing significantly decreased connectivity in TS group were identified using network‐based statistical (NBS) analysis, primarily composed of the parieto‐occipital cortex, precuneus, and paracentral lobule. Importantly, we combined support vector machine and multiple kernel learning frameworks to fuse multiple levels of network topological features for classification of individuals, achieving high accuracy of 86.47%. Together, our study revealed the disrupted topological organization of structural networks related to pathophysiology of TS, and the discriminative topological features for classification are potential quantitative neuroimaging biomarkers for clinical TS diagnosis. Hum Brain Mapp 38:3988–4008, 2017.

Using support vector machines with tract-based spatial statistics for automated classification of Tourette syndrome children

Tourette syndrome (TS) is a developmental neuropsychiatric disorder with the cardinal symptoms of motor and vocal tics which emerges in early childhood and fluctuates in severity in later years. To date, the neural basis of TS is not fully understood yet and TS has a long-term prognosis that is difficult to accurately estimate. Few studies have looked at the potential of using diffusion tensor imaging (DTI) in conjunction with machine learning algorithms in order to automate the classification of healthy children and TS children. Here we apply Tract-Based Spatial Statistics (TBSS) method to 44 TS children and 48 age and gender matched healthy children in order to extract the diffusion values from each voxel in the white matter (WM) skeleton, and a feature selection algorithm (ReliefF) was used to select the most salient voxels for subsequent classification with support vector machine (SVM). We use a nested cross validation to yield an unbiased assessment of the classification method and prevent overestimation. The accuracy (88.04%), sensitivity (88.64%) and specificity (87.50%) were achieved in our method as peak performance of the SVM classifier was achieved using the axial diffusion (AD) metric, demonstrating the potential of a joint TBSS and SVM pipeline for fast, objective classification of healthy and TS children. These results support that our methods may be useful for the early identification of subjects with TS, and hold promise for predicting prognosis and treatment outcome for individuals with TS.

Altered structural-functional coupling of large-scale brain networks in early Tourette syndrome children

Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder and its pathophysiological mechanism remains elusive. At present, TS-related abnormalities in either structural connectivity (SC) or functional connectivity (FC) have extensively been described, and discrepancies were apparent between the SC and FC studies. However, abnormalities in the SC-FC correlation for early TS children remain poorly understood. In our study, we used probabilistic diffusion tractography and resting-state FC to construct large-scale structural and functional brain networks for 34 drug-naive TS children and 42 healthy children. Graph theoretical approaches were employed to divide the group-averaged FC networks into functional modules. The Pearson correlation between the entries of SC and FC were estimated as SC-FC coupling within whole-brain and each module. Although five common functional modules (including the sensorimotor, default-mode, fronto-parietal, temporo-occipital and subcortical modules) were identified in both groups, we found SC– FC coupling in TS exhibited increased at the whole-brain and functional modular level, especially within sensorimotor and subcortical modules. The increased SC-FC coupling may suggest that TS pathology leads to functional interactions that are more directly related to the underlying SC of the brain and may be indicative of more stringent and less dynamic brain function in TS children. Together, our study demonstrated that altered whole-brain and module-dependent SC-FC couplings may underlie abnormal brain function in TS, and highlighted the potential for using multimodal neuroimaging biomarkers for TS diagnosis as well as understanding the pathophysiologic mechanisms of TS.

Multi-threshold white matter structural networks fusion for accurate diagnosis of Tourette syndrome children

Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder. To date, TS is still misdiagnosed due to its varied presentation and lacking of obvious clinical symptoms. Therefore, studies of objective imaging biomarkers are of great importance for early TS diagnosis. As tic generation has been linked to disturbed structural networks, and many efforts have been made recently to investigate brain functional or structural networks using machine learning methods, for the purpose of disease diagnosis. However, few studies were related to TS and some drawbacks still existed in them. Therefore, we propose a novel classification framework integrating a multi-threshold strategy and a network fusion scheme to address the preexisting drawbacks. Here we used diffusion MRI probabilistic tractography to construct the structural networks of 44 TS children and 48 healthy children. We ameliorated the similarity network fusion algorithm specially to fuse the multi-threshold structural networks. Graph theoretical analysis was then implemented, and nodal degree, nodal efficiency and nodal betweenness centrality were selected as features. Finally, support vector machine recursive feature extraction (SVM-RFE) algorithm was used for feature selection, and then optimal features are fed into SVM to automatically discriminate TS children from controls. We achieved a high accuracy of 89.13% evaluated by a nested cross validation, demonstrated the superior performance of our framework over other comparison methods. The involved discriminative regions for classification primarily located in the basal ganglia and frontal cortico-cortical networks, all highly related to the pathology of TS. Together, our study may provide potential neuroimaging biomarkers for early-stage TS diagnosis.