Brain Structural Analysis In Adolescents With Vertically HIV-Infection And Construction Of Anatomical Image Template For Cynomolgus Monkeys Brain

Part ⅠWM development is potentially influenced in adolescents with vertically-transmitted HIV infections:A tract-based spatial statistics studyObjective Convergent evidence indicates that HIV is associated with abnormal WM microstructure in adults. However, little is known about whether HIV affects WM development in adolescents. In this study, we used DTI to investigate the integrity of WM microstructure in adolescents with vertically-transmitted HIV-infections.Methods Fifteen HIV-positive adolescents with vertically-transmitted infections and 26 HIV-negative controls participated in this study. Whole brain analysis of fractional anisotropy (FA) was performed by tract-based spatial statistics (TBSS) to localize abnormal WM regions between groups. VOI analysis was further performed to explore the changes in diffusivity indices in the regions with FA alterations. Correlation analyses were used to assess the relationship between FA alterations and clinical measures within the HIV-positive group.Rusults Relative to HIV-negative controls, HIV-positive adolescents demonstrated significantly reduced FA alterations in the corpus callosum, superior and posterior corona radiata, frontal and parietal WM, pre/pro central gyrus, and superior longitudinal fasciculus. In the affected regions, FA reductions were caused by an increase in radial diffusivity (Dr), and no changes were observed in axial diffusivity (Da). Moreover, FA values in the bilateral frontal WM were negatively correlated with the duration of HAART and positively associated with the age at onset of HAART.Conclusions These findings suggest that early HIV infections may affect WM development, especially in the frontal WM, corpus callosum and corona radiata in adolescents, which may be associated with hypo-myelination and demyelination. Moreover, WM integrity may serve as a potential new treatment target.Part Ⅱ White matter changes in adolescents with vertically-transmitted HIV infection revealed by voxel-based morphometryObjective Neuroimaging studies have focused mainly on adults or younger children showing abnormal brain structure. However, very little is known whether HIV affects white matter structure in adolescents. In this study, we used voxel-based morphometry (VBM) to investigate the white matter integrity in adolescents who were vertically-transmitted HIV-infected.Methods Fifteen HIV-positive adolescents with vertically-transmitted infection and 26 HIV-negative controls participated in this study. VBM analysis was performed by SPM8. MR images were first segmented into GM, WM and CSF using the unified segmentation method. Then population templates were derived from the entire image dataset using the DARTEL technique. Non-linear warping of the segmented images was performed to match the corresponding MNI space DARTEL templates. The smoothed, modulated, normalized white matter maps were compared using analysis of covariance with age, gender and total intracranial volume included as covariates. Significant effects were identified using an uncorrected threshold (P<0.001) and voxel size 200.Rusults Relative to HIV-negative controls, the HIV-positive adolescents demonstrated significantly reduced GMV were found in the bilateral cerebellum, right pallidum, right calcarine, left anterior cingulate cortex and right superior occipital lobe. HIV-positive adolescents also demonstrated significantly reduced WMV in the bilateral cerebellum posterior lobe, right brainstem, and left occipital lobe. Significantly increased WMV were found in the bilateral frontal lobe, left temporal lobe, and bilateral parietal lobe. In addition, the HIV-positive adolescents demonstrated significantly reduced WMD in the bilateral corpus callosum (including the genu, body and splenium), bilateral cerebellum posterior lobe, bilateral frontal WM, left cingulate gyrus, and left temporal lobe. There were no significantly increased WMD brain regions in HIV+ group. Whole brain volume between HIV+ group and the control group (including whole GMV, whole WMV and whole grey, white matter volume) did not demonstrated significantly difference (using analysis of covariance with age, gender). The volume of anterior cingulate cotex is positively correlated with the MMSE score and CD4 cell counts.Conclusions After HIV infection in vertically-transmitted adolescents, the structure of white matter, gray matter has lot of changes, including reduced WMD and GMV in HIV+ adolescents. Of which the former may be involved with damaged myelin sheaths or hypomyelination in the development of cerebral white matter integrity, while the latter may be the direct effect of HIV, also may be HAART, eventually make dysplasia of cerebral and the decrease of GMV. The change of the anterior cingulate cotex integrity may be as a reliable biomarker of understanding the level of cognitive function after the HIV infection and antiretroviral therapy. Our results help to understand the mechanism of change in gray matter, white matter structure in vertically-transmitted adolescents with HIV infection.Part III Brain Anatomical Integrity in HIV Vertically-infected AdolescentsObjective Use neuroimaging techniques to analysis the differences between HIV+ vertical-transmitted subjects and HIV- group in brain anatomical integrity, to seek the sensitivity characteristics of imaging, and to further explore the pathogenesis and process of HIV infection in brain.Methods 24 HIV-positive adolescents with vertically-transmitted infections and 33 HIV-negative controls participated in this study. To compare the difference of gray matter structure, we use VBM analysis method, then use graph theory to build the brain network to study the range of brain connections, including hubs. We also use the global and regional network quantitative parameters, such as small world properties, standard clustering, standard path length, betweenness, degree, random failure, targeted attack analysis and so on, to make clear the differences of brain structural network features between the two groups.Rusults The networks of both groups followed a small-world organization across a wide range of network densities; both the networks had a path length slightly higher than random networks while having a clustering coefficient that was much higher than that in random networks. Compared with NC, the HIV network showed no significant difference in small world properties, standard clustering and standard path length across the range of densities (p> 0.05). Several regions in the inferior temporal gyrus showed lower centrality (local efficiency, betweenness, and degree centrality) in the HIV-infected network compared to HIV-exposed-uninfected network. The resilience of the HIV+ network to random failure was not significant compared to HIV-(p>0.05). The HIV+ network was generally less robust to targeted attack and the difference reached significance at a few fractions of attacked nodes (p< 0.05). For networks thresholded at Dmin, the common hubs in both groups are left cuneus cortex and right rolandic operculum. The HIV+ group owns the insula as the one of the hubs.Conclusions The gray matter volume of HIV+ group across multiple cortex and subcortical areas decrease, and these areas have the functions of promoting the cognition, sensorimotor and comprehensive role. In the structural network, the node properties are destroyed and the distribution of hubs associated with HIV infection and antiretroviral therapy offset into the sensorimotor area.Part Ⅳ Construction of MRI Template of the Chinese Cynomolgus Monkeys BrainObjective To establish a T1 image template of the Chinese cynomolgus monkeys (Macaca fascicularis) brain and perform a analysis brain tissue by developing a digital multi-atlas of grey matter, whiter matter and cerebrospinal fluid. All of these are for the following-up brain structure VBM analysis research between cynomolgus monkey AIDS animal model group with sivs simian immunodeficiency virus infection and normal cynomolgus monkey group.Methods Sixteen healthy Chinese cynomolgus monkeys were scanned by high resolution 3.0T magnatic resonance imaging (MRI) to acquire 3D sagittal T1W1 images. To construct an individual brain template and tissue digital atlases of grey matter, white matter and cerebrospinal fluid; segmentation, interpolation, spatial normalization and image smoothing of the MRIs were carried out using the fuzzy c-means clustering method (FCM). When co-registration and an average on the reference images were performed, cynomolgus monkeys brain atlases was then constructed after voxel-based morphometry (VBM) process analysis and testing of the multi-atlas.Rusults The 3D MRI template of healthy Chinese cynomolgus monkeys was established three tissue digital atlases of grey matter, white matter and cerebrospinal fluid were developed, distinctly indicating the whole brain T1-weighted contrast structure.Conclusions Animal model is an indispensable tool in many diseases, and cynomolgus monkeys are most closely related to human beings in the evolutionary relationships. The construction of MRI template of the cynomolgus monkeys brain provides a foundation and convenience for brain functional orientation with fMRI and brain structure analysis with VBM.