Robust fiber crossing invariant analysis of white matter microstructure in acute mild traumatic brain injury

Mehrbod Mohammadian^1,2, Timo Roine³, Jussi Hirvonen^2,4, Timo Kurki², and Olli Tenovuo^1,2

¹Department of Rehabilitation and Brain Trauma, Turku University Hospital, Turku, Finland, ²Department of Clinical Medicine, University of Turku, Turku, Finland, ³iMinds-Vision Lab, Department of Physics, University of Antwerp, Antwerp, Belgium, ⁴Department of Radiology, Turku University Hospital, Turku, Finland

Synopsis

We used a robust diffusion MRI approach to analyze global microstructural abnormalities in mild traumatic brain injury (mTBI) without confounding effects of complex fiber configurations. Microstructural properties of white matter skeleton were investigated, but only voxels with a single fiber orientation detected with constrained spherical deconvolution were included. In addition, whole-brain fiber tractograms were investigated. We studied 107 patients with mTBI and 28 age-matched control subjects. We found that fractional anisotropy was significantly decreased in mTBI, while mean diffusivity and radial diffusivity were increased. These differences were more significant when the analysis was restricted to single-fiber voxels.

Purpose

We sought to evaluate a robust approach to investigate global microstructural changes in white matter in patients with mild traumatic brain injury (mTBI) using high angular resolution diffusion imaging. As diffusion tensor imaging (DTI) is unable to correctly characterize complex fiber orientations, present in the majority of white matter¹, we chose to use constrained spherical deconvolution (CSD) ². With CSD, complex fiber configurations can be reliably detected and used for fiber tractography ^3, ⁴.

Methods

We studied 28 healthy controls (age=48.46±19.19 years) and 107 patients (age= 47.25±19.84 years) with acute mTBI. Diffusion-weighted magnetic resonance images were acquired with a b-value of 1000 s/mm2 in 64 gradient directions. Fiber orientation distributions were estimated from diffusion-weighted images with CSD in ExploreDTI ⁵, and white matter tract skeleton was reconstructed ⁶. As microstructural indices based on traditional diffusion tensor imaging are affected by the complexity of fiber configurations, we chose to also analyze only the voxels with a single fiber orientation detected by CSD. Moreover, we studied the microstructural indices within the whole-brain fiber tractogram generated with probabilistic CSD-based tractography ⁷. Averages of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were then calculated. In addition to these diffusion measurements, histogram of fractional anisotropy (FA) values was also calculated both for white matter skeleton and single-fiber voxels within the skeleton. General linear model was then used to test for between group differences in all measurements with age as a covariate.

Results

We found decreased FA and increased MD and RD in patients with mTBI compared to healthy controls (Tables 1 and 2). The difference was most significant for the skeleton with only single-fiber voxels. Results from whole-brain tractogram were also more significant than those from traditional skeleton approach. There is a large difference in histograms of FA values between the approach restricted to single-fiber voxels in contrast to the traditional approach.

Discussion

We measured global microstructural white matter properties without the confounding effects of complex fiber configurations by rejecting voxels with multiple fiber configurations. We found that FA was significantly decreased in mTBI, which was mainly caused by an increase in RD. We plan to repeat the analysis for mTBI patients in chronic phase. We will also investigate local microstructural changes using a traditional voxel-wise methodology and fiber tract specific analyses.

Acknowledgements

This project is partially funded by the EU Commission under the 7th Framework Programme (FP7 TBIcare) and T.R received support from the Instrumentarium Scientific Foundation, Finland.

References

1. Jeurissen B, Leemans A, Tournier JD, et al. Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging. Hum Brain Mapp. 2013;34(11):2747-66.

2. Tournier JD, Calamante F, Connelly A. Robust determination of the fibre orientation distribution in diffusion MRI: non-negativity constrained super-resolved spherical deconvolution. NeuroImage. 2007;35(4):1459-1472.

3. Farquharson S, Tournier JD, Calamante F, et al. White matter fiber tractography: why we need to move beyond DTI. J Neurosurg. 2013;118(6):1367-77.

4. Kristo G, Leemans A, Raemaekers M, et al. Reliability of two clinically relevant fiber pathways reconstructed with constrained spherical deconvolution. Magn Reson Med. 2013;70(6):1544-56.

5. Leemans A, Jeurissen B, Sijbers J, et al. ExploreDTI: a graphical toolbox for processing, analyzing, and visualizing diffusion MR data. In Proc Intl Soc Mag Reson Med. 2009;3536.

6. Smith, SM, Jenkinson M, Johansen-Berg H, et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage. 2006;31(4):1487-1505.

7. Jeurissen B, Leemans A, Jones DK, et al. Probabilistic fiber tracking using the residual bootstrap with constrained spherical deconvolution. Hum Brain Mapp. 2011;32(3):461-79.

Figures

Figure 1. FA skeleton overlaid over B0 image.

Figure 2. Histogram of the FA values of patients with mTBI and controls with traditional skeleton approach (a) Histogram of the FA values of patients with mTBI and controls with single-fiber skeleton approach (b).

Table 1. FA values using the three different approaches for the global white matter analysis.

Table 2. MD, RD, AD values using the white matter tract skeleton with only the single-fiber voxels included.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)

3360