A NEW CAD SYSTEM FOR EARLY DIAGNOSIS OF DYSLEXIC BRAINS

A. El-Baz1 , M. Casanova2 , G. Gimelfarb3 , M. Mott2 , A. Switala2 , E. Vanbogaert 1 and R. McCracken 1

1

Bioimaging Laboratory, Bioengineering Dept., University of Louisville, Louisville, KY, USA.

2

Department of Psychiatry and Behavioral Science, University of Louisville, USA.

3
Computer Science Department, University of Auckland, New Zealand.

The importance of accurate early diagnosis of dyslexia, which severely

affects the learning abilities of children, cannot be overstated. Neuropathological studies have revealed an abnormal anatomy of the cerebral white matter (CWM) in dyslexic brains. We explore a possibility of
distinguishing between dyslexic and normal (control) brains by a quantitative shape analysis of CWM gyrifications on 3D Magnetic Resonance
(MR) images. Our approach consists of (i) segmentation of the CWM
on a 3D brain image using a deformable 3D boundary; (ii) extraction
of gyrifications from the segmented CWM, and (iii) shape analysis to
quantify thickness of the extracted gyrifications and classify dyslexic
and normal subjects. The boundary evolution is controlled by two probabilistic models of visual appearance of 3D CWM: the learned prior and
the current appearance model. Initial experimental results suggest that
the proposed 3D texture analysis is a promising supplement to the current techniques for diagnosing dyslexia.

combined axons and myelin diameter. The result is a bias in connectivity which favors longer connections at the expense of shorter ones. In
dyslexia this is manifested as increased size of the corpus callosum (long
commisural fibers) [8, 9] despite a smaller than average brain size [5, 6].
The overall increase in longer fibers comes at the expense of a diminution in short arcuate connections. Most of the latter fibers populate the
outer radiate compartment of white matter and are late myelinating [10].
Reading ability does not result from the expression of a single gene
or the activity of a given brain center; rather, reading is a postnatally
acquired process that varies according to cultural norms. Neuroimaging studies suggest that changes in reading patterns may be the result of
remodeling of exuberant corticocortical connections throughout the first
few years of life. The size of the gyral window biases connections for optimal conduction and metabolic efficiency based on the relative amounts
of short and long corticocortical fibers. As an example, the striate cortex
has a small gyral window and short connections, whereas by contrast,
the motor cortex has a large gyral window and long connections.

Index Terms Diagnosis, Dyslexia, MRI, Levy Distance, Cerebral

White Matter (CWM) segmentation, CWM Gyrifications.

2. CEREBRAL WHITE MATTER (CWM) SEGMENTATION

ABSTRACT

1. INTRODUCTION
Developmental brain disorders represent one of the most interesting and
challenging research areas in neuroscience. Dyslexia and autism are two
of the most complicated developmental brain disorders that affect the
behavior and learning abilities of children. Dyslexia is characterized by
the failure to develop age appropriate reading skills despite normal intelligence level and adequate reading instructions [1], whereas autism is
characterized by qualitative abnormalities in behavior and higher cognitive functions [2]. Below we will present the related studies in neuropathology of dyslexia, existing image analysis frameworks, and the
proposed approach for analyzing MR images of dyslexic and control
subjects.
Dyslexia is characterized by substandard reading achievement which
remains unaccounted for after considering an individuals age, intelligence and education (DSM-IV-TR). Perceptual problems in dyslexia
seemingly result from an inability to retrieve correct verbal labels for
phonemes [3]. Consistent with this observation educational interventions that teach phoneme awareness have shown better results at dealing with reading disorders than other programs [4]. Although considerable progress has been made towards the identification of effective instructional practices, our knowledge regarding underlying pathological
changes and pathophysiological mechanisms remains fragmentary.
The previous studies [5, 6] showing a reduction in the gyral index
(i.e., the ratio of the contour of the pial surface to the convex hull of the
brains surface) of dyslexic patients suggests that any given gyral abnormality resides in the folding of the cortex rather than its thickness. Since
absolute brain size has long been considered an important determinant
of gyrification [7], our results shown in this paper complement previous
studies suggesting that, on average, dyslexic patients have reduced brain
volume [5, 6].
A larger gyral window in dyslexia removes the space constraint for
longer corticocortical fibers which are themselves of bigger width, i.e.,

978-1-4244-1764-3/08/$25.00 2008 IEEE

Accurate CWM segmentation from a 3D MRI image is a challenging

problem because intensities in the CWM and surrounding organs are
not clearly distinguishable. Thus, we segment the MRI image using a
conventional 3D parametric deformable boundary [11] but control its
evolution with two original probabilistic models of visual appearance,
namely, a learned CWM appearance prior accounting for translationand rotation-invariant pairwise voxel interaction and a mixed model of
voxel intensities in the current CWM and surrounding tissues.
The appearance prior is a Markov-Gibbs random field (MGRF) with
multiple pairwise interaction having analytical identification (parameter estimation) from training data. The voxel-wise model of the current
CWM appearance is extracted from the multi-modal mixed intensity distribution by its precise approximation with a linear combination of discrete Gaussians (LCDG) [12].
Let (x, y, z) be Cartesian coordinates of 3D points. A finite 3D
arithmetic lattice R = [(x, y, z) : x = 0, . . . , X 1; y = 0, . . . , Y
1, z = 1, . . . , Z 1] supports a 3D image g : R Q and its 3D region
map m : R L where Q = {0, 1, . . . , Q 1} and L = {cwm, bg}
are finite sets of intensities and region labels, respectively. Each label,
mx,y,z , indicates whether a voxel gx,y,z in the corresponding intensity
data set g belongs to CWM, or background.
We use a conventional deformable boundary [11] that evolves in the
direction minimizing its energy E depending on internal, int (b), and
external, ext (b), forces:

E = Eint + Eext =
(int (b) + ext (b)) db
(1)
b

where b = [Pk : k K = {1, . . . , K}] is a parametric surface with

K vertices Pk = (xk , yk , zk ). But we introduce a new type of the
external energy involving the learned and on-going (current) visual appearance of CWM. Each image is normalized by mapping the signal
range [qmin , qmax ] for each 3D data set to [0, 255] as in Fig. 1 in order
to account for global contrast and offset deviations of intensities due to
different sensors.

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ICIP 2008

(a)

(b)

Fig. 1. An initial (a) and normalized (b) MRI image.

(a)

(b)

Fig. 2. Central-symmetric 2D (a) and 3D (b) neighborhoods for the eight distance ranges [d,min = 0.5, d,max = + 0.5); N = {1, . . . , 8}.
The normalized images are considered as samples of a prior MGRF
model of the CWM appearance. To exclude any image alignment before
segmentation, we use a generic translation- and rotation-invariant MGRF
with only voxel-wise and central-symmetric pairwise voxel interaction.
The latter is specified by a set N of characteristic central-symmetric
voxel neighborhoods {n : N} on R and a corresponding set
V of Gibbs potentials, one per neighborhood.
A central-symmetric voxel neighborhood n embraces all voxel
pairs such that (x, y, z)-coordinate offsets between a voxel (x, y, z)
and its neighbor (x , y  , z  ) belong to an indexed semi-open interval
[d,min , d,max ); N {1, 2, 3, . . .} of the inter-voxel distances:
d,min ((x x )2 + (y y  )2 + (z z  )2 )0.5 < d,max . Figure 2 illustrates the neighborhoods n for the uniform distance ranges
[ 0.5, + 0.5); N = {1, . . . , 8}.
Learning the appearance prior. Let S = {(gt .mt ) : t = 1, . . . , T }
be a training set of 3D images with known region maps. Let Rt =
{(x, y, z) : (x, y, z) R mt;x,y,z = cwm} denote the part of
R supporting CWM in the t-th training pair (gt , mt ); t = 1, . . . , T .
Let C,t be a family of voxel pairs in R2t with the co-ordinate offset (, , ) n in a particular neighborhood. Let Fvox,t and F,t
be a joint empirical probability distribution of voxel intensities and of
intensity co-occurrences,
respectively, in the training CWM from gt :

|R
|
Fvox,t = fvox,t (q) = |Rt,q
: q Q and F,t = [f,t (q, q  ) =
t|
|C,t;q,q  |

: (q, q ) Q ] where Rt,q = {(x, y, z) : (x, y, z)

|C,t |
Rt gx,y,z = q} is a subset of voxels supporting the intensity q and
C,t;q,q is a subset of the voxel pairs c,, (x, y, z) = ((x, y, z), (x +
, y + , z + )) R2t supporting the intensity co-occurrence (q, q  )
in the training CWM from gt . Let Vvox = [Vvox (q) : q Q] be a
potential function of voxel intensities that describes the voxel-wise interaction. Let V = [V (q, q  ) : (q, q  ) Q2 ] be a potential function
of intensity co-occurrences in the neighboring voxel pairs that describes
the pairwise interaction in the neighborhood n ; N.
The MGRF prior model of the t-th training pair is specified by the
joint Gibbs probability distribution on the sublattice Rt :




1
T
T
Pt =
(2)
exp |Rt | Vvox
Fvox,t + N ,t V,t
F,t
Zt
where ,t = |C,t |/|Rt | is the average cardinality of n with respect
to Rt .
To simplify notation, let the CWM volumes in the training images
be similar, so that |Rt | Rcwm and |C,t | C,cwm for t = 1, . . . , T .
Here, Rcwm and C,cwm are the average cardinalities over the training set
S = {(gt .mt ) : t = 1, . . . , T }. Assuming the independent samples,
the joint probability distribution of intensities for all the training CWM
images is as follows:




1
T
PS = exp T Rcwm Vvox
(3)
Fvox + N VT F
Z

where = C,cwm /Rcwm , and the marginal empirical distributions of

intensities Fvox,cwm and intensity co-occurrences F,cwm describe now
all the CWM images from the training set. To eliminate zero empirical
probabilities caused by a relatively small volume of the training data, the
empirical probabilities are defined in terms of the ratios of cardinalities
of the related sublattices or subfamilies as follows: (nominator +
)/(denominator + S). For the Bayesian quadratic loss estimate,
= 1 and S = Q for the first-order or S = Q2 for the second-order
interactions.
To identify the MGRF model described in Eq. (3), we have to estimate the Gibbs Potentials V. In this paper we introduce a new analytical
maximum likelihood estimation for the Gibbs potentials (the mathematical proof for this new estimator is shown in [12]).

1
Vvox,cwm (q) = log fvox,cwm (q) Q
Q log fvox,cwm ();


V,cwm (q, q ) = (f,cwm (q, q ) fvox,cwm (q)fvox,cwm (q  )) ;
where the common factor is also computed analytically. They
can be omitted (e.g. = 1) if only relative potential values are used
for computing relative energies E,rel of the central-symmetric pairwise
voxel interactions in the training data:



E,rel = q,q Q2 f,cwm (q, q  ) f,cwm (q, q  ) fvox,cwm (q)fvox,cwm (q  )
that allow us to rank all the neighborhoods n and select the most characteristic top-rank neighbors N N to include to the appearance prior.
Under such a prior, any intensity pattern within a deformable boundary
b in an image g is described by its Gibbs energy

T
T
E(g, b) = Vvox,cwm
Fvox,cwm (g, b) + N V,cwm
F,cwm (g, b)
(4)
where N is an index subset of the selected top-rank neighborhoods, and
the empirical probability distributions are collected within the boundary
b in g.
LCDG-models of current appearance. Non-linear intensity variations
in a data acquisition system due to a scanner type and scanning parameters affect visual appearance of CWM in each data set g to be segmented.
Thus in addition to the learned appearance prior, we describe an ongoing CWM appearance with a marginal intensity distribution within an
evolving boundary b in g. This distribution is considered as a dynamic
mixture of two probability distributions that characterize the CWM and
its background, respectively, and is partitioned into these two models
using the EM-based approach in [12].
Boundary evolution under the two appearance models. We guide the
boundary evolution in such a way that the following external energy term
in Eq. (1) combining the learned prior and current appearance models
within the boundary is minimized:
ext (Pk = (x, y, z)) = pvox,cwm (gx,y,z )p (gx,y,z |S)
(5)
where pvox,cwm (q) is the marginal probability of the intensity q in the
above LCDG-model for the CWM and p (q|S) is the prior conditional
probability of q, given the fixed current intensities in the characteristic
central-symmetric neighborhood of Pk for the MGRF prior model of
Eq. (3):
exp (EP (gx,y,z |S))
P (gx,y,z |S) = 
qQ exp (EP (q|S))
where EP (q|S) is the conditional Gibbs energy of pairwise interaction
for the voxel P provided that an intensity q is assigned to it but the current intensities in all its neighbors over the characteristic neighborhoods
n ; N, remain fixed:


(V,cwm (gx,y,z , q)
EP (q|S) = Vvox,cwm (q) +
N (,,)n

V,cwm (q, gx+,y+,z+ ))

(6)
The evolution terminates after the total energy Er of the 3D region
r R inside b does not change:

Er =
EP (gx,y,z |S)
(7)

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P=(x,y,z)r

3. QUANTITATIVE ANALYSIS OF CWM GYRIFICATIONS

Our main hypothesis is that thickness of gyral CWM for dyslexic subjects is greater than for normal subjects. To quantify this feature, we need
first to automatically extract CWM gyrifications from the segmented
CWM and then analyze their differences in order to classify normal and
dyslexic persons.

0.02
0.015
0.01
0.005
0
0

(a)

(a)

(b)

(c)

(d)

pi(d)
po(d)
f(d)
Empirical density f(d)
inside cortex grification pi(d)
outside cortex grification po(d)

t=2.35

10

d (cm)

15

(b)

Fig. 3. Axial section (a) in the 3D distance map for the segmented CWM
(the boundary found by segmentation is shown in green) and the estimated class densities (b) obtained from the mixed empirical distance
density for the segmented CWM.

Fig. 4. The proposed steps to extract the CWM gyrifications: (a) voxels
that are located at a distance less than or equal to T from CWM boundary
which are shown in pink, (b) voxels that are located at a distance less
than or equal to T from the voxels that are located at distance T from
the boundary of CWM which are shown in green, and (c, d) extracted
CWM gyrifications.

To extract gyrifications, we calculate the distance map inside the

segmented 3D CWM by a fast marching level set method in [13]. The
map gives the minimum Euclidean distance from each inner point of the
segmented object to the object boundary (Fig. 3). Using the EM-based
approach in [12], the mixed empirical marginal distribution of these distances is partitioned into two probability models: of the CWM gyrifications (class 1) and all other CWM tissues (class 2), respectively, shown
in Fig. 3. Then the CWM gyrifications are extracted as follows:

(a)
(a)

1. Use Fast Marching level sets to propagate a wave to find the voxels that are located at a distance less than or equal to T from the
boundary of CWM as shown in Fig. 4(a).
2. Use Fast Marching level sets to propagate a wave to find the voxels that are located at a distance less than or equal to T from the
voxels that are located at distance T from the boundary of CWM
as shown in green in Fig. 4(b).
3. Remove the voxels that are visited by the second wave (shown
in green color) form the voxels that are visited by the first wave
(shown in pink color). The remaining part represents the extracted CWM gyrifications as shown Fig. 4(c,d).
We propose to use the cumulative distribution function (CDF) of
distances in a distance map inside the extracted CWM gyrifications as
a generalized shape feature of the CWM structure. Figure 5 shows the
CDFs for 14 subjects (7 dyslexic and 7 normal ones) selected randomly
from the matched data for training. It is evident that the two classes,
dyslexic and normal, are clearly separable using these CDFs.
To classify the CDFs, the Levy distances between a CDF F = [Fu :
u = 0, 1, . . . , dmax ] in question for the distance map inside the extracted CWM gyrifications and the average CDFs FD/N in Fig. 5 serving as the templates of dyslexic or normal subjects are calculated [14]:
(Fu , FD/N ) = min{ : FD/N (d ) Fu (d) FD/N (d +
>0

) + }.
4. EXPERIMENTAL RESULTS AND CONCLUSIONS
The proposed approach has been tested on in-vivo data collected from
sixteen right handed dyslexic men aged 18 to 40 years, and a group of
14 controls matched for gender, age, educational level, socioeconomic
background, handedness and general intelligence. All the subjects are

(b)
(b)

(c)

(d)

Fig. 5. Cumulative distance distributions (a) inside the segmented training distance maps for 14 (seven normal and seven dyslexic) subjects;
the average CDFs for dyslexic and normal subjects (b), and the proposed classification (c,d) of unknown subjects (shown by green) by using the Levy distance () to the average CDFs: (c) the normal and (d)
the dyslexic subject.

physically healthy and free of history of neurological diseases, head injury. Briefly, all the subjects have exactly the same psychiatric conditions. All images were acquired with the same 1.5T MRI scanner (GE,
Milwaukee, Wisconsin) with voxel resolution 0.9375 0.9375 1.5
mm3 using a T1 weighted imaging sequence protocol. The ground
truth diagnosis to evaluate the classification accuracy for each patient
was given by the clinicians.
Figure 6 demonstrates results of the CWM segmentation. The Gibbs
energies for each CWM voxel are higher than for any other brain tissues.
This is why the proposed approach is very accurate. The boundary evolution terminates after 127 iterations due to close to zero changes in the
total energy. The error of our segmentation with respect to the radiologists ground truth is 1.49%. To highlight the advantages of our
approach, we compare it to the most popular level-sets-based segmentation by Vese and Chan [15] where the level set evolution is controlled

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the known diagnosing techniques that exploit only volumetric descriptions of different brain structures and thus are in principle more sensitive to the selection of ages and segmentation errors [1618]. Contrastingly, the proposed approach derives efficient quantitative classification
features from 3D shapes of different brain structures. Our experiments
demonstrate statistically significant differences in the proposed generalized geometric characteristics of CWM gyrifications for 30 normal and
dyslexic subjects under consideration.
In the future, we will investigate additional brain structures in order to quantitatively characterize the development and changes of an
dyslexic brain over time. Our investigation will not be limited to the
CWM but will include the gray matter. Also, to validate and possibly
modify the proposed approach, we will test it on larger data sets with
known ground truth (doctors diagnosis).

S
(a)

(b)

(c)

(d)

(e)

Fig. 6. Results of 3D CWM segmentation projected onto 2D axial (A), coronal (C), and saggital (S) planes for visualization: 2D profiles of the original MRI
images (a), pixel-wise Gibbs energies (b) for 8, our segmentation (c), the
segmentation with the algorithm in [15] (d), and (e) the radiologists segmentation.
Table 1. Accuracy and time performance of our segmentation on 9 data sets
(1116 slices) in comparison to our previous technique in [12] and the level sets
based segmentation in [15].
Algorithm
Our
[12]
[15]
Minimum error, %
0.51
5.9
3.4
Maximum error, %
4.79
10.3
13.6
Mean error, %
1.53
7.8
4.95
Standard deviation,% 1.25
2.27
3.7
Significance, P
< 104 < 104
Average time, sec
365
75
489
by region statistics, e.g. mean and variance. The segmentation error for
their approach, as applied in the experiment shown in Fig. 6, is 9.6%.
Table 1 and Fig. 6 show more comparative segmentation results. For
the nine data sets in Table 1 with the known ground truth the differences in the mean errors between the proposed segmentation, our previous approach in [12], and the level-set based approach of Vese and
Chan [15] are statistically significant according to the unpaired t-test (the
two-tailed value P is less than 0.0001). The main problem in Vese and
Chans segmentation is that the errors usually occur just at the CWM
gyrifications, which are the main features to discriminate between the
dyslexic and normal subjects. The motivation behind our segmentation
was to exclude such errors as far as possible.
The training subset for classification (14 persons shown in Fig. 5)
was arbitrarily selected among all the 30 subjects. The accuracy of classification of both the training and test subjects was evaluated using the
2 -test at the three confidence levels 85%, 90% and 95% in order
to examine significant differences in the Levy distances. As expected,
the 85% confidence level yielded the best results the correctly classified 16 out of 16 dyslexic subjects (a 100% accuracy), and 14 out of 14
control subjects (a 100% accuracy). At the 90% confidence level, 16 out
of 16 dyslexic subjects were still classified correctly, however, only 13
out of 14 control subjects were correct, bringing the accuracy rate for
the control group down to 92.86%. The 95% confidence level obviously
gives the smaller accuracy rates for both the groups, namely, 14 out of
16 correct answers for dyslexic subjects (87.5%) and still 13 out of 14
control subjects (92.86%). The classification based on traditional volumetric approach is 7 out of 16 dyslexic subjects (a 43.75% accuracy),
and 9 out of 14 control subjects (a 64.29% accuracy) at a 85 confidence
interval, these results highlight the advantage of the proposed diagnostic
approach.
In total, these preliminary results show that the 3D texture analysis
of the MRI brain images is able to accurately discriminate between the
dyslexic and normal subjects. Our proposal substantially differs from

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