UNCORRECTED PROOF 1 Comparing a diffusion tensor and non-tensor approach to white matter 2 fiber tractography in chronic stroke 3 A.M. Auriat a , M.R. Borich b , N.J. Snow a , K.P. Wadden a , L.A. Boyd a, * 4 a Department of Physical Therapy, Faculty of Medicine, University of British Columbia, Vancouver, Canada 5 b Department of Rehabilitation Medicine, Division of Physical Therapy, Emory University School of Medicine, Atlanta, USA abstract 6 article info 7 Article history: 8 Received 5 November 2014 9 Received in revised form 21 February 2015 10 Accepted 11 March 2015 11 Available online xxxx 12 Keywords: 13 Diffusion weighted imaging 14 Constrained spherical deconvolution 15 Diffusion tensor imaging 16 Motor outcome 17 Stroke 18 Diffusion tensor imaging (DTI)-based tractography has been used to demonstrate functionally relevant differ- 19 ences in white matter pathway status after stroke. However, it is now known that the tensor model is insensitive 20 to the complex fiber architectures found in the vast majority of voxels in the human brain. The inability to resolve 21 intra-voxel fiber orientations may have important implications for the utility of standard DTI-based tract recon- 22 struction methods. Intra-voxel fiber orientations can now be identified using novel, tensor-free approaches. 23 Constrained spherical deconvolution (CSD) is one approach to characterize intra-voxel diffusion behavior. In 24 the current study, we performed DTI- and CSD-based tract reconstruction of the corticospinal tract (CST) and cor- 25 pus callosum (CC) to test the hypothesis that characterization of complex fiber orientations may improve the ro- 26 bustness of fiber tract reconstruction and increase the sensitivity to identify functionally relevant white matter 27 abnormalities in individuals with chronic stroke. Diffusion weighted magnetic resonance imaging was performed 28 in 27 chronic post-stroke participants and 12 healthy controls. Transcallosal pathways and the CST bilaterally 29 were reconstructed using DTI- and CSD-based tractography. Mean fractional anisotropy (FA), apparent diffusion 30 coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were calculated across the tracts of interest. 31 The total number and volume of reconstructed tracts was also determined. Diffusion measures were compared 32 between groups (Stroke, Control) and methods (CSD, DTI). The relationship between post-stroke motor behavior 33 and diffusion measures was evaluated. Overall, CSD methods identified more tracts than the DTI-based approach 34 for both CC and CST pathways. Mean FA, ADC, and RD differed between DTI and CSD for CC-mediated tracts. In 35 these tracts, we discovered a difference in FA for the CC between stroke and healthy control groups using CSD 36 but not DTI. CSD identified ipsilesional CST pathways in 9 stroke participants who did not have tracts identified 37 with DTI. Additionally, CSD differentiated between stroke ipsilesional and healthy control non-dominant CST for 38 several measures (number of tracts, tract volume, FA, ADC, and RD) whereas DTI only detected group differences 39 for number of tracts. In the stroke group, motor behavior correlated with fewer diffusion metrics derived from the 40 DTI as compared to CSD-reconstructed ipsilesional CST and CC. CSD is superior to DTI-based tractography in de- 41 tecting differences in diffusion characteristics between the nondominant healthy control and ipsilesional CST. 42 CSD measures of microstructure tissue properties related to more motor outcomes than DTI measures did. Our 43 results suggest the potential utility and functional relevance of characterizing complex fiber organization using 44 tensor-free diffusion modeling approaches to investigate white matter pathways in the brain after stroke. 45 © 2015 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license 46 (http://creativecommons.org/licenses/by-nc-nd/4.0/). 47 48 49 50 51 1. Introduction 52 Diffusion-weighted magnetic resonance imaging (DW-MRI) is 53 a non-invasive imaging technique commonly used to evaluate the mi- 54 crostructural tissue properties of white matter fiber pathways in the 55 human brain using tractography. DW-MRI has been extensively used 56 to relate changes in white matter microstructural properties 57 and motor function after stroke (Jang, 2010). Differences in DW- 58 MRI-based measures of corpus callosum (CC) (Borich et al., 2012a; 59 Lindenberg et al., 2012) and corticospinal tract (CST) (Borich et al., 60 2014, 2012a; Lindenberg et al., 2010; Stinear et al., 2007) microstructur- 61 al tissue properties are predictive of both motor function and motor 62 learning in individuals with chronic stroke (Borich et al., 2014; 63 Lindenberg et al., 2012; Stinear et al., 2007). Indeed, recent work has de- 64 scribed DW-MRI-derived measures of white matter microstructural 65 properties as a more valid predictor of motor function than the func- 66 tional MRI (fMRI)-derived blood oxygen level dependent (BOLD) signal NeuroImage: Clinical xxx (2015) xxx–xxx * Corresponding author at: University of British Columbia, 212-2177 Wesbrook Mall, Vancouver, British Columbia V6T 2B5, Canada. Tel.: +1 604 822 7392; fax: +1 604 822 1860. E-mail address: lara.boyd@ubc.ca (L.A. Boyd). YNICL-00464; No. of pages: 11; 4C: http://dx.doi.org/10.1016/j.nicl.2015.03.007 2213-1582/© 2015 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Contents lists available at ScienceDirect NeuroImage: Clinical journal homepage: www.elsevier.com/locate/ynicl Please cite this article as: Auriat, A.M., et al., Comparing a diffusion tensor and non-tensor approach to white matter fiber tractography in chronic stroke, NeuroImage: Clinical (2015), http://dx.doi.org/10.1016/j.nicl.2015.03.007