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Purpose: Motor function and recovery after stroke likely rely directly on the residual anatomical connections in the brain and its resting-state functional connectivity. Both structural and functional properties of cortical networks after stroke are revealed using multimodal magnetic resonance imaging (MRI). Specifically, functional connectivity MRI (fcMRI) can extract functional networks of the brain at rest, while structural connectivity can be estimated from white matter fiber orientations measured with high angular-resolution diffusion imaging (HARDI). A model that marries these two techniques may be the key to understanding functional recovery after stroke. In this study, a novel set of voxel-level measures of structurofunctional correlations (SFC) was developed and tested in a group of chronic stroke subjects., Methods: A fully automated method is presented for modeling the structure-function relationship of brain connectivity in individuals with stroke. Brains from ten chronic stroke subjects and nine age-matched controls were imaged with a structural T1-weighted scan, resting-state fMRI, and HARDI. Each subject's T1-weighted image was nonlinearly registered to a T1-weighted 152-brain MNI template using a local histogram-matching technique that alleviates distortions caused by brain lesions. Fractional anisotropy maps and mean BOLD images of each subject were separately registered to the individual's T1-weighted image using affine transformations. White matter fiber orientations within each voxel were estimated with the q-ball model, which approximates the orientation distribution function (ODF) from the diffusion-weighted measurements. Deterministic q-ball tractography was performed in order to obtain a set of fiber trajectories. The new structurofunctional correlation method assigns each voxel a new BOLD time course based on a summation of its structural connections with a common fiber length interval. Then, the voxel's original time-course was correlated with this fiber-distance BOLD signal to derive a novel structurofunctional correlation coefficient. These steps were repeated for eight fiber distance intervals, and the maximum of these correlations was used to define an intrinsic structurofunctional correlation (iSFC) index. A network-based SFC map (nSFC) was also developed in order to enhance resting-state functional networks derived from conventional functional connectivity analyses. iSFC and nSFC maps were individually compared between stroke subjects and controls using a voxel-based two-tailed Student's t-test (alpha = 0.01). A linear regression was also performed between the SFC metrics and the Box and Blocks Score, a clinical measure of arm motor function., Results: Significant decreases (p < 0.01) in iSFC were found in stroke subjects within functional hubs of the brain, including the precuneus, prefrontal cortex, posterior parietal cortex, and cingulate gyrus. Many of these differences were significantly correlated with the Box and Blocks Score. The nSFC maps of prefrontal networks in control subjects revealed localized increases within the cerebellum, and these enhancements were diminished in stroke subjects. This finding was further supported by a reduction in functional connectivity between the prefrontal cortex and cerebellum. Default-mode network nSFC maps were higher in the contralesional hemisphere of lower-functioning stroke subjects., Conclusion: The results demonstrate that changes after a stroke in both intrinsic and network-based structurofunctional correlations at rest are correlated with motor function, underscoring the importance of residual structural connectivity in cortical networks.

Purpose: 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)., Conclusion: 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.