title: White matter structural connectivity is associated with sensorimotor function in stroke survivors.
abstract: OBJECTIVE
  Diffusion tensor imaging (DTI) provides functionally relevant information about white matter structure. Local anatomical connectivity information combined with fractional anisotropy (FA) and mean diffusivity (MD) may predict functional outcomes in stroke survivors. Imaging methods for predicting functional outcomes in stroke survivors are not well established. This work uses DTI to objectively assess the effects of a stroke lesion on white matter structure and sensorimotor function.
  
  
  METHODS
  A voxel-based approach is introduced to assess a stroke lesion's global impact on motor function. Anatomical T1-weighted and diffusion tensor images of the brain were acquired for nineteen subjects (10 post-stroke and 9 age-matched controls). A manually selected volume of interest was used to alleviate the effects of stroke lesions on image registration. Images from all subjects were registered to the images of the control subject that was anatomically closest to Talairach space. Each subject's transformed image was uniformly seeded for DTI tractography. Each seed was inversely transformed into the individual subject space, where DTI tractography was conducted and then the results were transformed back to the reference space. A voxel-wise connectivity matrix was constructed from the fibers, which was then used to calculate the number of directly and indirectly connected neighbors of each voxel. A novel voxel-wise indirect structural connectivity (VISC) index was computed as the average number of direct connections to a voxel's indirect neighbors. Voxel-based analyses (VBA) were performed to compare VISC, FA, and MD for the detection of lesion-induced changes in sensorimotor function. For each voxel, a t-value was computed from the differences between each stroke brain and the 9 controls. A series of linear regressions was performed between Fugl-Meyer (FM) assessment scores of sensorimotor impairment and each DTI metric's log number of voxels that differed from the control group.
  
  
  RESULTS
  Correlation between the logarithm of the number of significant voxels in the ipsilesional hemisphere and total Fugl-Meyer score was moderate for MD (R2 = 0.512), and greater for VISC (R2 = 0.796) and FA (R2 = 0.674). The slopes of FA (p = 0.0036), VISC (p = 0.0005), and MD (p = 0.0199) versus the total FM score were significant. However, these correlations were driven by the upper extremity motor component of the FM score (VISC: R2 = 0.879) with little influence of the lower extremity motor component (FA: R2 = 0.177).
  
  
  CONCLUSIONS
  The results suggest that a voxel-wise metric based on DTI tractography can predict upper extremity sensorimotor function of stroke survivors, and that supraspinal intraconnectivity may have a less dominant role in lower extremity function.
authors.affiliation: Department of Biomedical Engineering, Marquette University, Milwaukee, WI, USA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Kalinosky
authors.forename: Sheila
authors.initials: S
authors.lastname: Schindler-Ivens
authors.forename: Brian D
authors.initials: BD
authors.lastname: Schmit
keywords: DTI, diffusion tensor imaging; Diffusion tensor imaging; FA, fractional anisotropy; FM, Fugl-Meyer; FOV, field of view; LDV, log difference volume; LE, lower extremity; Lesion analysis; MD, mean diffusivity; Sensorimotor function; Stroke; TE, echo time; TFIRE, Tactful Functional Imaging Research Environment; TR, repetition time; Tractography; UE, upper extremity; VISC, voxel-wise indirect structural connectivity; Voxel-wise structural connectivity