Kim Annink

120 Chapter 6 MRI – TBSS Image processing and analysis of the DWI were performed using tools from the FMRIB’s Software Library (FSL v6.0.3) (24), DTI-ToolKit (DTI-TK) (v.2.3.1) and tract- based spatial statistics (TBSS v1.2) (25). FSL was used to correct for susceptibility induced distortions, using the non-diffusion weighted images with opposite-phase directions. Next, the data were corrected for eddy-induced distortions and head movements followed by a brain extraction to remove non-brain tissue. Finally, the tensor was fitted, after which all data were normalized to a template. DTI-TK, which uses a tensor based registration, was used to create a population specific template and to normalize all data. A mean Fractional Anisotropy (FA) map was derived from this template to create a mean FA skeleton. Using TBSS, an FA threshold of ≥0.15 was used to limit the inclusion of non-white matter voxels and voxels with high-inter subject variability. The FA values of each subject were projected on this skeleton for further analysis. A generalized linear model was used to assess the relationship between FA and the clinical variables, hippocampal volume and mammillary body atrophy, corrected for sex and age at scan. Analyses were performed using Randomise and were subject to family-wise-error correction for multiple comparisons following threshold-free cluster enhancement and p-values <0.05 were considered significant. Statistical analysis Statistical analysis was performed using SPSS version 25 (IBM corp., Armonk NY, United States). Baseline characteristics were compared between the non-HT versus HT group and normal versus abnormal MB using the independent t-test or Mann-Whitney-U test for continuous variables. For categorical variables the Chi 2 - test was used. Outcome measures and volumes were also compared between the groups using the independent t-test or Mann-Whitney-U test depending on the Gaussian distribution. Univariate analysis was performed with the outcome measure as dependent variable and the brain volume or MB atrophy score as independent variable. Non-significant associations were excluded for the following analysis. Multivariable linear regression was performed including the outcome measure as dependent variable and the brain volume/MB atrophy, therapeutic hypothermia and their interaction term as independent variables. Variables with a p-value <0.05 were retained in the model and those with a p-value ≥0.1 deleted.