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73 Microstructures | Trigonocephaly x 1.8 x 3.0 mm3. Both groups underwent deep sedation or anesthesia during the MRI procedure using sevoflurane or propofol. White matter tracts of the frontal lobe Major white matter tracts coursing completely or partially through the frontal lobe were analyzed: the anterior thalamic radiation (ATR), cingulate gyrus part of the cingulum (CGC), unicate fasciculus (UNC), the forceps minor (FMI), and the inferior fronto-occipital fasciculus (IFO). Tracts of the left and right hemisphere were analyzed separately as previous studies have shown regional asymmetry between hemispheres.18 Assuming mechanical restriction of the frontal lobe would not affect the occipital lobe, we also assessed the forceps major (FMA). The FMA locates in the occipital region and therefore served as a subject-specific control tract. As an additional measure, we assessed the ratio of FMI/FMA between patients and controls. DTI metrics The white matter metrics derived from DTI, voxel by voxel, are mathematically estimated based on three mutually perpendicular eigenvectors, whose magnitude is given by three corresponding eigenvalues. These eigenvalues are used to generate quantitative maps of fractional anisotropy (FA), the derivation of mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). As the FA, MD, RD, and AD equations are mathematically coupled, we first investigated FA and MD before analyzing the impact of the radial and axial measures of diffusivity. FA represents the amount of diffusional asymmetry in a voxel, which is presented from 0 (infinite isotropy) to 1 (infinite anisotropy). The MD is measured in mm2/sec. Data processing The image processing was performed with the use of the FMRIB Software library (FSL), version 6.0.0, created by the Analysis Group, FMRIB, Oxford, UK (ref). 19 First, the images were modified in a preprocessing step to exclude nonbrain tissue and then to correct for artifacts induced by eddy currents and for translations and/or rotations resulted from head motion. The resulting transformation matrices were used to rotate the gradient direction table to account for rotations applied to the data. The diffusion tensor was fitted at each voxel, and common scalar metrics were subsequently computed. Second, fully automated probabilistic tractography was performed as described by de Groot et al. on each subject’s diffusion data set, using the FSL plugin AutoPtx.20 The results of the probabilistic tractography were normalized to a scale from 0 to 1 using the total number of successful seed-to-target attempts. Next, we thresholded each pathway, using previously established values (ATR: 0.002, CGC: 0.01, IFO: 0.01, FMA: 0.005, FMI: 0.01, UNC: 0.01; de Groot et al., 2015). Nonzero mean DTI scalar measures were computed within each tract. Average fractional anisotropy and mean diffusivity values were then computed for each fiber bundle.21 5

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