Analysis of Spect Brain Images Using Wilcoxon

and Relative Entropy Criteria and Quadratic

Multivariate Classifiers for the Diagnosis of
Alzheimers Disease

F. J. Martnez1 , D. Salas-Gonzalez1 , J. M. Gorriz1 , J.

Ramrez1 , C. G. Puntonet2 , M. G omez-Ro3

Dept. of Signal Theory, Networking and Communications, University of Granada,

Spain.

Dept. of Computers Architecture and Technology

Virgen Nieves Hospital, Deptartment Nuclear Medicine, Granada, Spain

April 7, 2015

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
Table of Contents

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 Alzheimers disease (AD) is one of the most common cause of
dementia in the elderly people. approximately 30 millions
individuals worldwide.
With a growing older population in developed nations, AD
affected people is expected to quadruple over the next 50
years.
AD early diagnosis remains being a difficult task. Furthermore,
in this stage, there are more opportunities to treat the disease.
Single Photon Emission Computed Tomography (SPECT) is a
widely used technique to study the functional properties of the
brain.

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 Clinicians usually evaluate SPECT images via visual
inspection, therefore an automatic computer aided diagnosis
(CAD) tool is desirable.
Many efforts have been done lately in this direction, using
different analysis and clustering methods.
In this work, we choose a different approach, based on two
different classifiers with two different feature selection criteria,
and involving Factor Analysis and Multivariate Normal
Classifiers.

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 To study and test the classification of SPECT brain images,
we use a set of 97 images (41 Normal Controls (NC) and 56
Alzheimers Disease (AD)) from the Virgen de las Nieves
Hospital in Granada.

#samples Sex(M/F)(%) [range/]

NC 43 32.95/12.19 71.51[46-85/7.99]
AD1 30 10.97/18.29 65.29[23-81/13.36]
AD2 20 13.41/9.76 65.73[46-86/8.25]
AD3 4 0/2.43 76[69-83/9.90]
Table : Demographic details of the dataset. NC = Normal Controls, AD
1 = possible AD, AD 2 = probable AD, AD 3 = certain AD. and
stands for population mean and standard deviation respectively.

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 In SPECT imaging, the dimension of the feature space
(number of voxels) is very large compared to the number of
available training samples (usually 100 images).
Small Sample Size Problem: the number of available samples
is greater than the number of images.
Therefore, a reduction in the dimension of the feature vector
is desirable before to perform classification:
Each SPECT image has 67, 200 voxels (48 40 35) with
intensity values ranging from 0 to 255. Some of them
corresponds to positions outside the brain.
We initially discard those voxels which present an intensity
value lower than 70 (positions outside the brain and very
low-intensity regions inside).

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 Voxels are ranked using the absolute value obtained from
Mann-Whitney-Wilcoxon test and Relative Entropy.
In this example, Normals and AD images were considered in
the calculation of the image I t .
Mann-Whitney-Wilcoxon test and Relative Entropy gives us
information about voxel class separability. Note that the
ranking criteria are different from Mann-Whitney to Relative
Entropy. This aspect would help making a decision when
building the classifiers.

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 We select first N voxels from the ordered data.
N is still too high (thousands of voxels). We need another
feature reduction algorithm.
A number of key features (K ) are extracted using Factor
Analysis technique.
These K factors will be used as input vector to the classifier.

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 Factor analysis estimates how much of the variability in the
data is due to common factors.
The K observed variables are modeled as linear combinations
of the factors, plus error.
Once the K factor loadings have been estimated, we rotate
them using a varimax approach which is a change of
coordinates that maximizes the sum of the variance of the
squared loadings, which attempts to maximize the variance on
the new axes.
We obtain a pattern of loadings on each factor that is as
diverse as possible.

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 In this work, we use the multivariate normal classifier which
was selected among others options because of its good
performance when number of features is small.
Then, the performance of the classification is tested using the
leave-one-out method.
All SPECT images are classified and accuracy, sensibility and
specificity parameters are calculated.
These measures are obtained from Eq. 1, 2 and 3.

TP
Sensibility = (1)
TP + FN
TN
Specificity = (2)
TN + FP
TP + TN
Accuracy = (3)
TP + FP + FN + TN

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 TN and TP means true negative and true positive
respectively (number of correctly classified negative and
positive samples), and FN and FP means false negative and
false positive respectively (number of wrong classified negative
and positive samples).
This cross-validation strategy has been used to assess the
discriminative accuracy of different multivariate analysis
methods applied to the early diagnosis of Alzheimers disease,
discrimination of frontotemporal dementia from AD and in
classifying atrophy patterns based on magnetic resonance
images.

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 We study the behavior of the two different voxel selection
criteria in function of the number of voxels selected, N.
Fig. 1 shows that the two methods used have almost the
same behavior in function of N, although Wilcoxon performs
better when number of selected voxels is less than 13000
voxels and Relative Entropy is the best when using more than
15000 selected voxels.

Figure : Values of accuracy (left), sensibility (center) and specificity

(right) versus N for each classifier

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 When we look at the behavior in function of the number of
factor loadings extracted in the Factor Analysis step, we found
the pattern on Fig. 2
We can see that the best values for accuracy are K = 6 for
Classifier B and K = 8 for Classifier A.
Best sensibility values are found at these values of K too.

Figure : Values of accuracy (left), sensibility (center) and specificity

(right) versus K for each classifier

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 The final chosen model is composed of two different
classifiers, with these variables:
Classifier A: Mann-Whitney-Wilcoxon criterion for ranking
and selecting the best 6000 voxels. Factor analysis to extract 8
factor loadings, used as input to a multivariate normal
classifier .
Classifier B: Relative Entropy for ranking and selecting the
best 16000 voxels. Factor analysis to extract 6 factor loadings,
used as input to a multivariate normal classifier.
Mean of these two results is taken as the final result.

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 In Table 2 we find the validation results for this classifier, as
well as a comparition with some other methods found on
Bibliography: Voxels-as-Features, Principal Component
Analysis or Gaussian Mixture Models.
This is probably due to the two different voxel selection
criteria, which selects different areas in the brain that can be
related to different patterns in AD patients.

Quadratic VAF-LSVM PCA-LSVM GMM-SVM

Accuracy 92.78% 83.51% 89.69% 89.28%
Sensibility 92.68% 83.93% 89.28% 89.29%
Specificity 92.86% 82.93% 90.24% 90.24%

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr
 In this work, an automatic procedure to classify SPECT brain
images for the diagnosis of Alzheimers Disease is presented.
The proposed methodology takes one normalized
three-dimensional SPECT brain image input.
Then, most discriminative voxels are selected by two different
criteria. As different patients may show different patterns of
AD, the use of these two different criteria let us to find
different areas in the brain that otherwise would not be
selected.
Then, after a feature extraction step, the result of two
different multivariate quadratic classifiers is combined to
obtain the final result.
The proposed methodology achieves better results than recent
published articles for SPECT images, with sensibility,
specificity and accuracy values greater than 90%.

F. J. Martnez, D. Salas-Gonz
alez, J. M. G
orriz, J. Ramrez, C. G. Puntonet,
Analysis of
M.Spect
G
omez-R
Brain
o Images Using Wilcoxon and Relative Entr