Computational protocol: Axonal chronic injury in treatment-naïve HIV+ adults with asymptomatic neurocognitive impairment and its relationship with clinical variables and cognitive status

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Protocol publication

[…] All MRI scans were performed on a Siemens Trio 3.0 Tesla imager. Standard structural images were acquired using axial T1WI (repetition time (TR) = 250 ms, echo time (TE) = 2.46 ms) and T2-FLAIR combined fat saturation (TR = 8000 ms, TE = 2370.9 ms, inversion time = 97 ms) sequences to check whether there were visible intracranial lesions. For DTI data, a single-shot echo-planar imaging sequence was used for acquisition. The parameters for DTI were: TR = 3300 ms, TE = 90 ms, slice thickness = 4 mm with 1.2 mm gap, number of slices = 63, matrix size = 128 × 128, field of view = 230 × 230 mm, number of excitations = 3, space resolution = 1.8 mm × 1.8 mm × 1.8 mm, total acquisition time = 3.39 min. Diffusion sensitizing gradients were applied along 20 non-collinear directions with b = 1000 s/mm2, and one b = 0 s/mm2.DTI datasets were performed and analysed using FSL5.0 (FMRIB Image Analysis Group, Oxford, UK, http://www.fmrib.ox.ac.uk/fsl) []. Details of the DTI processing steps, including pre-processing and TBSS processing, have been described previously [, ]. There were three steps for pre-processing. The raw DTI images were first corrected for the effects of eddy currents and head movements and deformations using eddy current correction within FDT. Then, brain mask extraction was performed on one of the no-diffusion-weighting (b = 0) images by running the Brain Extraction Tool in FSL. Finally, the diffusion tensor model was computed using DTIFIT within FDT for whole brain volumes to generate tensor-derived maps, including FA, MD, AD, and RD. TBSS-processing includes four steps. The first is image registration. Using the FA map as a target template for registration, more accurate results can be achieved, as FA is a normalized measure of eigenvalue standard deviation and represents the degree of diffusion directionality. A common registration target brain image template (FMRIB58_FA) was identified, and all subjects’ FA images were aligned to this target using FMRIB’s non-linear image registration tool, through which all the FA volumes were aligned to a 1.0 × 1.0 × 1.0 mm3 Montreal Neurological Institute standard space. Second, the mean of all aligned FA images was skeletonized, and a mean FA skeleton image (threshold = 0.2) was generated. Third, the aligned FA image for each subject was projected onto the mean FA skeleton by filling the skeleton with maximum FA values from the nearest relevant tract centre to generate a skeletonized FA map. Corresponding skeletonized maps for the other diffusion measures (MD, AD and RD) were also similarly generated. Lastly, voxelwise statistical analyses of DTI metrics were carried out on the skeleton space. [...] Demographic characteristics of the HIV+ participants and healthy controls were analysed with IBM SPSS Statistics (version 22.0). Chi-squared analysis was used to evaluate the sex distribution between HIV+ patients and healthy controls. Independent t-test analysis was used to calculate the differences in age and education level between the two groups. Significance was defined as p < 0.05.For TBSS analysis, voxel-wised statistics of the DTI parameters (FA, MD, AD, RD) for the two group differences were tested in the general linear model framework using the FSL randomize tool with a non-parametric permutation testing (5000 random permutations) []. The threshold-free cluster enhancement (TFCE) method with a threshold set at 0.95 was used to obtain correction for multiple comparisons [], and statistical maps were obtained with family-wise error (FWE) correction at the p < 0.05 level. The significant group differences in tracts were located with the Johns Hopkins University (JHU)-ICBM-DTI-81 WM Label Atlas.To investigate the relationships between DTI metrics and clinical variables and cognitive performance for HIV-positive patients, multiple linear regression analysis between DTI indices and age, CD4+ counts, CD4+/CD8+ ratio, plasma viral load, duration of HIV infection and scores of cognitive performance was performed. A significance level of 0.05 was obtained using IBM SPSS Statistics (version 22.0). […]

Pipeline specifications

Software tools BET, SPSS
Applications Miscellaneous, Magnetic resonance imaging
Organisms Human immunodeficiency virus 2, Human poliovirus 1 Mahoney