Investigating white matter fibre density and morphology using fixel-based analysis.

“For the FC and FDC analysis, we included intracranial volume (as computed using FreeSurfer from T1-weighted images (Dale et al., 1999)) as a nuisance covariate.”

“Furthermore, as in TBSS (Smith et al., 2006), this approach is likely to suffer from inaccurate FA-based projection in regions of crossing fibres (Bach et al., 2014; De Groot et al., 2013; Schwarz et al., 2014), and lack of fibre-specific inference when investigating voxel-wise measures such as FA.”

“By far the most popular approach to VBA of diffusion MRI is the analysis of diffusion tensor-derived fractional anisotropy (FA) (Basser and Pierpaoli, 1996), with voxel- or clusterlevel statistical inference using packages such as SPM (http://www. fil.ion.ucl.ac.uk/spm/) or FSL…”

“Family-wise error corrected p-values were assigned to each fixel using non-parametric permutation testing (Holmes et al., 1996; Winkler et al., 2014) with 5000 permutations.”

“In the context of voxel-averaged DWI measures (e.g. Alexander et al., 2010; Zhang et al., 2012), the ‘density’ of a voxel will also be influenced by partial volume with cerebral spinal fluid.”

“, 2012), individual differences and brain-behaviour correlations (Johansen-Berg, 2010), genetics (Meyer-Lindenberg, 2009), structural plasticity (Scholz et al., 2009), treatment response (Szeszko et al.”

“(Jeurissen et al., 2014)) instead of tissue segmentations from T1-weighted images.”

“However, most white matter voxels contain contributions from multiple fibre populations (often referred to as crossing fibres), and therefore voxel-averaged quantitative measures (e.g. fractional anisotropy) are not fibre-specific and have poor interpretability.”

“8] 82 [75-87] Kawahara 2016(48) 168 18 Bayley III 146 (87%) 22 (13%) n.”

“Numerous models based on diffusion weighted imaging have been proposed to estimate parameters related to the restricted, intra-axonal compartment, commonly referred to as fiber density [57, 58].”