Tract-Based Spatial Statistics of Diffusion Tensor Imaging in Adult Dyslexia
Todd Richards1, Jeff Stevenson1, James Crouch2, L. Clark Johnson3, Kenneth Maravilla1, Patricia Stock4, Virginia Berninger4
1Dept. of Radiology, University of Washington
2School of Medicine, Saint Louis University
3Psychosocial & Community Health, School of Nursing, University of Washington
4Educational Psychology, University of Washington
Results/Discussion:
The skeletonized TBSS group map statistical tests
showed that adult controls had greater fractional
anisotropy compared to adult dyslexic subjects in many
language-related white matter fiber tracts (See Figure
2). In Figure 2, The crosshair is positioned on a
significant cluster near the right inferior frontal gyrus
(Talairach coordinates, x=45, y=8, z=19) . Significant
group difference map clusters occurred in specific white
matter tracts within the frontal lobe, temporal lobe,
occipital lobe, parietal lobe. These results are consistent
with our functional connectivity results (Figure 3)
showing stronger connectivity in adult controls from
seed points in bilateral inferior frontal gyrus5 .
BACKGROUND AND PURPOSE:
During the first two decades of in vivo brain imaging,
differences between developmental dyslexics and good
readers have been well documented at many different
levels of neural substrate, ranging from structural
neuroanatomy to white matter tracts, to neurochemical
changes, to PET and rCBF , to spatially sensitive fMRI
BOLD activation, to temporally sensitive MEG/ERP
techniques. We tested the hypothesis that dyslexics have
both a functional and structural disconnection between
brain regions associated with phonological processing.
Diffusion tensor imaging is an elegant method for
measuring structural connectivity to test for abnormalities
in specific language pathways.
Methods:
Fiber-Tracking Analysis:
We also performed fiber-tracking analyses and
visualization using custom software MRDiffusion
developed by Dr. Robert Dougherty and coworkers6 .
Figures 4, 5, and 6 show an
example of the IFG-Angular Gyrus Highway (Fiber tracts)
that resulted from a seed point/fiber tracking analysis
stemming from the inferior frontal gyrus. This important
language highway is used in our analysis of connectivity
deficits in dyslexia.
DTI scans were acquired from 7 healthy adult normal
readers and from 14 adult dyslexics on a Philips Achieva
1.5T scanner. DTI was performed using a single shot
spin-echo diffusion-weighted echo_planar pulse
sequence with 64 slices covering the whole brain at 2.5
mm slice thickness (TR/TE 9500/74 milliseconds;
acquisition matrix 128x128). Diffusion MRI images were
obtained from 32 non-colinear directions with a b value of
1000 s/mm2 along with a b zero image with no diffusion
gradients on. Images were processed off-line using FSL
(FMRIB's Software Library, http://www.fmrib.ox.ac.uk/fsl)
which includes eddy-current compensation, dtifit to
reconstruct diffusion tensors, and fractional anisotropy
(FA). Voxelwise statistical analysis of the FA data was
carried out using TBSS (Tract-Based Spatial Statistics1),
part of FSL2. First, FA images are created by fitting the
diffusion tensor to the raw diffusion data using FDT, and
then brain-extracted using BET3. All subjects' FA data are
then aligned into a common space using the nonlinear
registration IRTK4, www.doc.ic.ac.uk/~dr/software. The
mean FA image is then created and thinned to create a
mean FA skeleton which represents the centers of all
tracts common to the group. Each subject's aligned FA
data is then projected onto this skeleton (Figure 1) and
the resulting data are fed into voxelwise cross-subject
statistics. A randomization procedure (FSL's randomise,
Monte Carlo permutation test) was used to perform the
group analysis statistics. Tractography based spatial
statistical (TBSS) group maps were generated for the
case: controls > dyslexics and for the case- dyslexics >
controls.
Figure 1.
Overlay of skeletonized averaged FA map (orange) onto
standardized FA map from diffusion tensor images.
5
6
References:
1. Smith, SM et al.,. Neuroimage 31, 1487-1505 (2006).
2. Smith SM, et al, NeuroImage 23(S1), 208-219 (2004).
3. Smith SM, et al, Human Brain Mapping 17, 143-155
(2002).
4. Rueckert D, et al., IEEE Transactions on Medical
Imaging 18, 712-721 (1999) .
5. Stanberry et al., Magnetic Resonance Imaging 24,
217-229 (2006).
6. Dougherty, R,F., et al., Proceedings National Academy
Sciences U S A, 102(20), 7350-7355 (2005)
Acknowledgements: The authors gratefully
acknowledge funding from the National Institute of Child
Health and Human Development (grants P50 33812 and
HD25858). For tractography software, the authors thank
Dr. Robert Dougherty and Dr. Mark Eckert
for use of MR diffusion software from Stanford.
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2
1
4
Figure 2.
Group difference map for controls > dyslexics for skeletonized
diffusion fractional anisotropy using TBSS software. Orange-red
areas show significant clusters for group difference.
Figure 3.
Functional Connectivity result from Stanberry et al. 2006
showing abnormally low connectivy in dyslexics compared to
controls.