White Matter Fiber Density Reductions Associated with Poor Outcomes in TBI: A Fixel-Based Analysis
Poster No:
1300
Submission Type:
Abstract Submission
Authors:
Akul Sharma1, Anand Joshi1, Dominique Duncan1, Richard Leahy1
Institutions:
1University of Southern California, Los Angeles, CA
First Author:
Co-Author(s):
Introduction:
Traumatic brain injury (TBI) is a major cause of death and disability worldwide, with considerable heterogeneity in long-term outcomes (Vespa et al., 2017). TBI leads to widespread damage in white matter (WM), characterized by complex pathophysiology involving neurodegeneration, tissue damage, and diffuse axonal injury, which is associated with poor clinical functional recovery (Pitkänen et al., 2019). However, the neural correlates underlying functional limitations after TBI are not fully understood (McCrea et al., 2021). Diffusion tensor imaging (DTI) provides information about WM microstructural properties but has several limitations, primarily in its ability to resolve complex crossing fiber bundles (Wright et al., 2016). To address these challenges, recent advances in neuroimaging have introduced fixel-based analysis (FBA) as a more robust method for characterizing WM changes (Dhollander et al., 2021). The term "fixel" refers to a specific fiber bundle within a given voxel, representing the smallest discrete component of a fiber bundle, the mean orientation of the fibers within that bundle, and associated metrics such as fiber density (FD), which quantify the intra-axonal volume attributed to that fixel (Raffelt et al., 2017). While FBA has been applied in various neurological conditions, its application in TBI remains limited. This study leverages FBA to explore the relationship between white matter microstructural changes and functional recovery, as assessed by the Glasgow Outcome Scale–Extended (GOSE) (McMillan et al., 2016) in TBI patients.
Methods:
This study analyzed a subset of TBI patients from the TRACK-TBI study database, selected based on the availability of high-angular resolution diffusion imaging (HARDI) data. GOSE scores at follow-up were used to assess functional recovery. A total of 39 participants (mean age: 41.5 ± 16.2 years) were stratified into low outcome (GOSE ≤ 6, indicating moderate to severe disability; n = 22) and high outcome (GOSE ≥ 7, indicating good recovery; n = 17) groups. FBA was performed using the MRtrix3 pipeline (https://mrtrix.readthedocs.io/en/latest/fixel_based_analysis/st_fibre_density_cross-section.html).DWI data were preprocessed for motion, eddy-current distortions, susceptibility artifacts, and intensity inhomogeneities, followed by global intensity normalization. Fiber response functions were estimated and averaged to create a group response function. Fiber orientation distributions (FODs) were computed using constrained spherical deconvolution, and a study-specific FOD template was generated from a subset of 20 participants (Figure 1). All FOD images were registered to this template. MRtrix3 was used for all fixel-based statistical analyses. Connectivity-based fixel enhancement, using probabilistic tractography, was employed to correct for multiple comparisons, with 5,000 permutations. FD values from each WM fixel for both groups were compared (Low GOSE < High GOSE) , and any fixels that showed group differences in terms of FD were color-coded by the corresponding t-statistic (thresholded at p < 0.05)
·Figure 1
Results:
As seen in Figure 2, TBI patients with low GOSE scores exhibited significant reductions in FD compared to those with high GOSE scores (p < 0.05). These reductions were predominantly localized to bilateral frontal white matter, including the forceps minor, superior longitudinal fasciculus, anterior thalamic radiation, and sagittal stratum, thresholded to display only the fixels that are significant at p < 0.05. The results reflect key WM pathways previously affected in TBI (Harris et al., 2016).
·Figure 2
Conclusions:
This study demonstrates the utility of FBA-derived FD as a sensitive biomarker for microstructural alterations in TBI. The observed reductions in FD in key white matter tracts correlate with poorer functional outcomes, as measured by GOSE. These findings underscore the potential of FD metrics for stratifying injury severity and guiding targeted interventions in TBI rehabilitation.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Diffusion MRI Modeling and Analysis 1
Image Registration and Computational Anatomy
Neuroinformatics and Data Sharing:
Workflows
Keywords:
Data analysis
Demyelinating
Design and Analysis
Informatics
MRI
Statistical Methods
Tractography
Trauma
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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Provide references using APA citation style.
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McMillan, T., Wilson, L., Ponsford, J., Levin, H., Teasdale, G., & Bond, M. (2016). The Glasgow Outcome Scale—40 years of application and refinement. Nature Reviews Neurology, 12(8), 477-485.
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Raffelt, D. A., Tournier, J. D., Smith, R. E., Vaughan, D. N., Jackson, G., Ridgway, G. R., & Connelly, A. (2017). Investigating white matter fibre density and morphology using fixel-based analysis. Neuroimage, 144, 58-73.
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