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S. Taheri

a

, S.H. Ong

b,

*

, V.F.H. Chong

c

a

Department of Electrical and Computer Engineering, National University of Singapore, Singapore

b

Department of Electrical and Computer Engineering and Division of Bioengineering, National University of Singapore, Singapore

c

Department of Diagnostic Radiology, National University Hospital, National University of Singapore, Singapore

a r t i c l e i n f o

Article history:

Received 27 June 2007

Received in revised form 20 January 2009

Accepted 3 April 2009

Keywords:

3D segmentation

Threshold

Level-set

a b s t r a c t

The level set approach can be used as a powerful tool for 3D segmentation of a tumor to achieve an accu-

rate estimation of its volume. A major challenge of such algorithms is to set the equation parameters,

especially the speed function. In this paper, we introduce a threshold-based scheme that uses level sets

for 3D tumor segmentation (TLS). In this scheme, the level set speed function is designed using a global

threshold. This threshold is dened based on the idea of condence interval and is iteratively updated

throughout the evolution process. We propose two threshold-updating schemes, search-based and adap-

tive, that require different degrees of user involvement. TLS does not require explicit knowledge about

the tumor and non-tumor density functions and can be implemented in an automatic or semi-automatic

form depending on the complexity of the tumor shape. The proposed algorithm has been tested on mag-

netic resonance images of the head for tumor segmentation and its performance evaluated visually and

quantitatively. The experimental results conrm the effectiveness of TLS and its superior performance

when compared with a region-competition based method.

2009 Elsevier B.V. All rights reserved.

1. Introduction

The accurate estimation of tumor size is important for clinical

reasons, e.g., for treatment planning and therapy evaluation.

Although maximum tumor diameter is widely used as an indica-

tion of tumor size, it may not reect a proper assessment of this tu-

mor attribute because of the 3D nature and irregular shape of the

tumor [1,2]. Tumor volume, on the other hand, may be an appro-

priate representation of tumor size. One way to obtain an estimate

of tumor volume is via segmentation. Such schemes implicitly ac-

quire the tumor volume by extracting the tumor surface. Surface

extraction has been obtained either directly by 3D tumor segmen-

tation or indirectly via a pseudo-3D approach, i.e., reconstruction

of the 3D surface from the extracted 2D contours [3]. Since the for-

mer approach generally achieves higher accuracy, it is the main fo-

cus of our research.

There are several proposed approaches in the literature for tu-

mor segmentation and volume estimation. Fuzzy-connectedness

is a useful method that has been adapted for measuring the tumor

volume in MR images [4,5]. Markov random elds (MRFs) are also

popular models for many medical image processing tasks such as

segmentation [6,7]. Lee et al. [8] evaluated the use of support vec-

tor machine (SVM) classication method and MRFs for brain tumor

segmentation and claimed the superiority of SVM-based approach.

Recently, Corso et al. [9] applied the extended graph-shifts algo-

rithm for image segmentation and showed its application in tumor

segmentation. Also, in a more recent publication [10] the Bayesian

generative model was incorporated into the graph-based image

segmentation and was applied to brain tumor segmentation.

Active surfaces/contours are other popular methods that are

widely used for the segmentation of 3D objects, implicitly in the

form of a level set function or explicitly as a snake function. In

the recent years, the level set method has become popular due to

its ability to handle complex geometries and topological changes.

The level set is in fact a shape-driven tool which, using a properly

dened speed function, can grow or shrink to take the shape of any

complex object of interest. Unlike the traditional deformable mod-

els, the level set method does not depend on the parameterizations

of the surface [11]. This makes it very attractive and exible in

shape modeling and image segmentation. Another attractive

advantage of the level set method is that, given an initial zero level

set (initial hypersurface), the entire segmentation procedure is

fully automatic. Moreover, unlike other methods, the extension

of the algorithm to 3D is straightforward and does not require

additional machinery. These properties make the level set one of

the state of the art methods for segmentation, especially 3D seg-

mentation. Therefore, the focus of the paper is on level set-based

approaches.

0262-8856/$ - see front matter 2009 Elsevier B.V. All rights reserved.

doi:10.1016/j.imavis.2009.04.005

* Corresponding author. Address: Department of Electrical and Computer Engi-

neering, National University of Singapore, E4-05-14, Singapore 117576, Singapore.

Tel.: +65 65162245; fax: +65 67773117.

E-mail addresses: sima.taheri@gmail.com (S. Taheri), eleongsh@nus.edu.sg (S.H.

Ong), dnrcfhv@nus.edu.sg (V.F.H. Chong).

Image and Vision Computing 28 (2010) 2637

Contents lists available at ScienceDirect

Image and Vision Computing

j our nal homepage: www. el sevi er . com/ l ocat e/ i mavi s

However, there are difculties in using level sets that make

them less desirable in some circumstances. One problem is that

the level set formulation entails the tuning of several parameters.

The difculty in adjusting such parameters for specic applications

has led to several approaches. In some methods, the interactive

rates for solving the level set partial differential equation give

the user immediate feedback on the parameter settings; the user

can therefore tune the parameters and control the shape of the le-

vel set in real time [1214]. The disadvantage of these methods is

that they increase user interaction and provide good segmentation

results only if the user is sufciently familiar with the level set for-

mulation and the object of interest. Another method, proposed by

Leventon et al. [15], provides a more generic and automated seg-

mentation of tumor through the combination of level set evolution

with statistical shape constraints. In this method, a priori shape

information is incorporated into a geodesic active contour so that

the model parameters are estimated, and the curve then evolves

based on that estimation. The problem with this approach is that

it may be difcult to obtain statistical prior knowledge in many

cases, especially for tumor segmentation.

One of the main parameters in the level set equation is the

speed function, whose design is perhaps the most important step

in the level set approach. The speed function can be dened based

on the results of various clustering algorithms such as K-means

clustering and fuzzy classication [1618]. In these approaches a

clustering step is performed and the deformable model then grows

on top of the clustered pixels. However, in some other approaches

classication and level set growing are performed simultaneously.

Ho et al. [19] proposed region competition in the evolution of the

level set, in which the difference between pre- and post-contrast

enhanced magnetic resonance (MR) images is used to adjust the

speed function. In their method, the histogram of the difference

image is tted by parametric distributions for both the enhanced

parts and the noisy background. Using this tted distribution, the

difference image is mapped to the tumor posterior probability for

use in the speed function. This idea can be extended based on

non-parametric density estimation by kernel expansion or Parzen

windowing [20]. The main drawback of such algorithms is their

dependency on the accurate estimation of tumor and non-tumor

probability density functions. On one hand, the parametric estima-

tion of density functions may not provide sufcient accuracy be-

cause tumors do not generally have uniform intensities. On the

other hand, non-parametric density estimation methods such as

Parzen windowing require sufcient training samples for both re-

gions. The additional complexity of estimation due to such algo-

rithms motivates us to use density-independent schemes.

Many level set algorithms may be distinguished on the basis of

their speed functions. Some approaches, for example, require user

interaction while others rely on prior estimation of the tumor den-

sity function. We propose a level set method for 3D brain tumor

segmentation which employs a speed function that does not re-

quire density function estimation and is obtained by minimal user

interaction [21]. The basic idea is to use a global threshold to form

the speed function. The initial threshold is calculated using the le-

vel set initialization and is then iteratively updated throughout the

process of segmentation. Upon reaching the tumor boundary, the

variation of the threshold declines because of the contrast between

tumor and non-tumor intensities, and the process stops. This algo-

rithmcan be implemented in an automatic or semi-automatic form

depending on the complexity of the tumor shape. A further advan-

tage is that it can be applied to either pre- or post-contrast T1 MR

images and does not require both these images at the same time.

The challenge of our scheme lies in the trade-off between the

rate of convergence and the accuracy of segmentation. A high con-

vergence rate is achieved when the variation of threshold with re-

spect to the iteration number is large. This, however, may lead to

low accuracy in segmentation or even destabilization of the algo-

rithm. On the other hand, a small variation of the threshold can

guarantee convergence, although at a reduced rate. In this paper,

we study this trade-off and propose an appropriate threshold cal-

culation algorithm.

The key contributions of this paper are:

We introduce the TLS method, which calculates a global thresh-

old for tumor segmentation, thereby making density estimation

of the tumor and non-tumor unnecessary.

We propose an algorithm to update the threshold iteratively.

The rest of the paper is organized as follows. Section 2 intro-

duces the TLS algorithm, an iterative approach for nding and

updating the threshold, and the stopping criterion. The initializa-

tion of the level set and the design of the speed function are also

presented. In Section 3, a detailed discussion of threshold updating

is provided in addition to the presentation of a modied TLS for

non-homogeneous tumors. The simulation results in Section 4

demonstrate the effectiveness of our algorithm. Section 5 con-

cludes the paper.

2. Threshold-based segmentation using level set

We assume that the histograms of the tumor and adjacent non-

tumor

1

regions slightly overlap. Such an assumption often holds in

MR images. Without loss of generality, we assume that the tumor re-

gion has mean intensity value greater than that of the background. In

such a situation, it is very likely that there exists a threshold which

discriminates between tumor and non-tumor voxels. Using the level

set, TLS species an algorithm to nd a proper threshold and a meth-

od to update it on an iterative basis. The initial value of the threshold

is based on the level set initialization performed by the user inside

the tumor region. TLS species a speed function on the basis of such

a threshold. An important feature of our approach is that explicit

knowledge of the density functions of tumor and non-tumor regions

is not required.

Fig. 1 shows two real instances in which appropriate thresholds

can be chosen from the shaded intensity ranges, which are where

the nal (converged) thresholds are very likely to lie. Intuitively,

when the densities of the tumor and non-tumor regions are more

widely separated, this range is expected to be wider, as can be seen

in Fig. 1(b). In the gures, the tumor and non-tumor regions are se-

lected based on the manual segmentations and are inside the vol-

ume of interest.

A brief description of the TLS approach is presented in Fig. 2. To

speed up the algorithm, we propose the use of narrow band [22,23]

in the level set evolution process and restrict processing to the vol-

ume of interest. TLS requires an appropriate estimate of the thresh-

old to segment the tumor properly, and this is obtained via the

concepts of condence interval and condence level. In the follow-

ing sections, we explain these ideas and their application to thresh-

old estimation. The level set evolution equation is presented and

its speed function designed on the basis of our threshold updating

approach. Level set initialization and the TLS stopping criterion are

also discussed.

2.1. Condence interval

The condence interval (CI) can be dened for any distribution

as an interval in which a certain percentage, the condence level

(CL), of observations is located. For a symmetric distribution such

1

The area around the tumor boundary and inside the cuboid that encompasses the

volume of interest.

S. Taheri et al. / Image and Vision Computing 28 (2010) 2637 27

as the normal, the CI is within k standard deviations, i.e., kr around

the population mean l. A general relation between CI and CL can

be found based on Chebyshevs inequality. It should be noted that

Chebyshevs inequality holds without any assumption regarding

the shape of the distribution. For a random variable, n, with nite

mean and variance, we have

Pjn lj Pkr 6

1

k

2

k > 0 1

which shows that greater than 1

1

k

2

100 percent of the popu-

lation falls within k standard deviations from the population mean.

For a non-symmetric distribution, the one-tailed version of Cheby-

shevs inequality is appropriate:

Pn l Pkr 6

1

1 k

2

2

Table 1 shows the values of Chebyshevs inequality and its one-

tailed version for some values of k [24].

2.2. Threshold updating

According to the concept of CI, we dene an expression for

threshold updating by

T

i1

^ l

i

k^ r

i

i P0 3

where T

i1

is the threshold estimation for the i 1th iteration and

k is the factor which determines the condence level and must be

chosen properly. The effect of this parameter will be discussed in

detail later. The mean and standard deviation, denoted by ^ l

i

and

^ r

i

, respectively, are calculated by

^ l

i

1

n

X

n

j1

x

ij

4

^ r

2

i

1

n 1

X

n

j1

x

ij

^ l

i

2

where n is the number of accepted tumor samples, fx

ij

g, up to the

ith iteration. Based on (3), we dene the threshold in each iteration

as a one-tailed interval of the accepted samples up to that iteration.

We use the one-tailed interval in this denition according to our

assumption that the mean intensity of the tumor region is grater

than that of the non-tumor region. However, this threshold can be

dened generally based on the two-tailed interval. Fig. 3 shows an-

other example of tumor and non-tumor distributions along with the

distribution of accepted samples up to the ith iteration and T

i1

. As

can be seen, fx

ij

g is a subset of the tumor region.

Table 1

Chebyshevs inequality evaluation, (Pjn lj Pkr and Pn l Pkr).

k 0.1 0.5 0.9 1 1.64 1.96 2 3 4

Two-tailed (%) (10000) (400) (123) 100 37.0 26.0 25 11.11 6.25

One-tailed (%) 99 80 55 50 27.0 20.7 20 10 5.88

Fig. 1. Distribution of tumor and non-tumor regions based on the manual segmentations in two real MR images. Threshold can be chosen from the shaded area.

Fig. 2. TLS algorithm.

28 S. Taheri et al. / Image and Vision Computing 28 (2010) 2637

2.3. Level set presentation

Level set segmentation involves solving the active contour min-

imization problem by the computation of minimal distance sur-

faces [25,11] in one higher dimension. A surface, ct, is

embedded as a zero level set of a higher dimensional function,

/x; t : R

n

R

of the point x from ct. The entire function evolves to minimize

a metric dened by the curvature and image attributes. The evolu-

tion equation of the level set is dened as

@/x; t

@t

Fx; tkr/x; tk 0 5

where Fx; t denotes the speed function of the level set which gives

the speed of ct in the normal direction. The normal vector, n, to

ct can be easily determined from/ by n

r/

kr/k

. Fig. 4 shows a level

set function, /x; y; t : R

2

R

time t 0; 1.

2.4. Level set speed function

In this section, we discuss the challenge of determining the

speed function of the level set. The original formulation of the

speed function uses the image gradient [22,11]. However, such a

speed function does not work well when the image is noisy or

when the boundary of the desired object is not distinct. Unfortu-

nately, such characteristics are common in many MR images. To

improve the performance of the level set, the idea of integrating

the region information instead of the image gradient into the level

set speed function was proposed [19,20,26]. Motivated by this idea,

TLS uses a threshold-based speed function.

The level set speed function in the ith iteration is,

F

i

F

0

:F

i

I

j

/

, where F

0

is a constant of propagation deter-

mined by a positive number, and F

i

I

is dened based on the image

characteristics in the ith iteration and causes the level set to nally

be attracted to the tumor boundary. The parameter j

/

is the mean

curvature of the level set and is expressed as a function of /x; t

by

j

/

r:

r/

kr/k

P

i;j;k2C

/

ii

/

jj

/

2

k

2/

ij

/

i

/

j

2/

2

x

/

2

y

/

2

z

3=2

6

In fact, j

/

is a smoothness parameter that prevents the level set

leaking into many small noisy structures in the tumor region. The

strength of this smoothing is controlled by a positive constant fac-

tor, .

Intuitively, it is desirable that growing speed is greater in a re-

gion where the tumor likelihood is higher and vice versa. TLS uses a

speed function which takes this feature into account. In other

words, TLS determines F

i

I

for each sample proportional to its

intensity difference from the threshold, so that the greater the dif-

ference the higher the speed. Let T

i

be the threshold associated

with the ith iteration. F

i

I

is dened for each sample based on its

normalized intensity difference from T

i

by

F

i

I

x; y; z

D

i

2

1 sgnD

i

maxD

i

1 sgnD

i

minD

i

7

where D

i

Ix; y; z T

i

and sgn is the signum function:

sgnx

1 x > 0

0 x 0

1 x < 0

8

>

<

>

:

8

It should be noted that the sign of F

i

I

indicates whether the sample

is inside (+) or outside () the tumor region. In (7), the rst and

second terms give the normalized level set speed for tumor and

non-tumor voxels, respectively. Such a denition benets from

the correlation among voxels in the image. For a voxel inside the tu-

mor region with Ix; y; z PT

i

, the larger the distance from the

threshold, the higher the likelihood of being surrounded by the tu-

mor voxels. Therefore, the level set speed function in the location of

such voxels can be faster than at the other locations. For non-tumor

voxels the analysis is the same.

0 50 100 150 200 250

0

0.005

0.01

0.015

0.02

0.025

0.03

0.035

0.04

0.045

0.05

Intensity

Distribution of accepted samples up to the ith iteration (Tumor 3 )

Tumor

NonTumor

{x

ij

}~(

i

,

i

)

T

i+1

Fig. 3. Distribution of accepted tumor samples up to the ith iteration which are a

subset of tumor region. T

i1

is the threshold associated with i 1th iteration.

x

z

y

Level Set Function

x

z

y

) 1 , , ( t y x z

) 0 , , ( t y x z

Fig. 4. The 3D surface (light gray) is the level set function. ct at time t 0 and t 1 is the intersection of /x; t with the xy plane (dark gray) which is called the zero level

set.

S. Taheri et al. / Image and Vision Computing 28 (2010) 2637 29

Consequently, F

i

I

has the following properties that make the

zero level set converge to the tumor boundary in an iterative

manner:

F

i

I

> 0: The zero level set is inside the tumor region and grows

with the positive speed of F

i

.

F

i

I

< 0: The zero level set is outside the tumor region and

shrinks with the negative speed of F

i

.

In short, this speed function helps the level set evolve and ac-

cept the voxels that are supposed to be inside the tumor while

rejecting the remaining voxels. Obviously, at the tumor boundary,

the speed of the level set becomes slow and the zero level set stops

there; however, if the level set extends beyond the boundary and

accepts non-tumor voxels, its negative speed will allow the zero le-

vel set to shrink so that it eventually coincides with the tumor

boundary. Therefore, the surface of the tumor can nally be

approximated by the zero level set.

2.5. Level set initialization

Initialization for TLS is done in the tumor region, from which we

obtain the rst estimate of the threshold, T

1

. We dene the refer-

ence slice as the one that includes a relatively large tumor cross-

sectional area compared to the other slices. It should be noted that

the choice of this reference slice will not affect the end result.

For convex tumor shapes, the initial zero level set is a spherical

surface whose center is at the center of the tumor region in the ref-

erence slice. (A body is convex if, for any pair of points inside the

body, the line segment which joins them lies entirely in it; other-

wise the body is concave [27].) For simple tumor shapes whose

cross-sections at the reference slice are in the central portion of

the image, the center of the sphere is placed automatically at the

center of the reference slice. Such an initialization ensures that

the area of intersection of this sphere with the reference slice lies

entirely within the tumor region. However, it is not necessary for

the other slices to satisfy this condition. T

1

is calculated (from

(3)) using the tumor voxels in the area of intersection.

The initialization for a concave tumor is slightly more compli-

cated and multiple spheres may be required for higher segmenta-

tion accuracy. The choice of the initial sphere positions would

affect the nal result more signicantly compared to the case of

convex tumors. Generally, the spheres should be evenly distributed

across the entire tumor region. Fig. 5 shows some examples of such

initializations for convex and concave tumors. The robustness of

the algorithm to initial sphere positions is discussed in Section 3.3.

2.6. Stopping criterion

TLS updates the threshold at each iteration based on the ac-

cepted tumor samples up to that point. At the tumor boundary,

the negative level set speed for non-tumor samples causes TLS to

reject them. Therefore, the rate of accepting new samples declines

and the variation of the threshold will become negligible per iter-

ation. Fig. 6 shows the plot of threshold versus iteration number for

a real image.

The stopping window of length W

s

is dened such that it con-

tains the thresholds associated with the last W

s

iterations. TLS

stops when, for t

s

consecutive iterations, the variance of the

threshold values in the stopping windowbecomes less than a small

number e. Therefore, the triple W

s

; t

s

; e determines when the

algorithm stops. For example, triple 5; 3; 0:02 indicates that the

algorithmstops where the variance of the last ve threshold values

becomes less than 0.02 for three consecutive iterations. Suitable

values of these three parameters are obtained experimentally.

3. Analysis

In this section, we describe the procedure for threshold updating

and the modied TLS for segmentation of non-homogeneous tu-

mors. The robustness of the algorithm with respect to initialization

is also discussed and the values of some user dened parameters

such as F

0

, , radius of the initial sphere, r, and narrow band width,

NB, are proposed.

3.1. Threshold updating parameter

The convergence rate of the algorithm and the accuracy of seg-

mentation are directly related to the choice of the threshold, which

is also determined by k. For a small value of k, the level set may

Fig. 5. Level set initialization on the reference slices, (left) concave tumors, (right) convex tumors.

0 5 10 15 20 25 30

130

132

134

136

138

140

142

144

146

148

150

Threshold vs. Iteration (Tumor 3)

Iteration number

T

h

r

e

s

h

o

l

d

Fig. 6. Plot of threshold vs. iteration number. The threshold remains almost

unchanged over the last few iterations.

30 S. Taheri et al. / Image and Vision Computing 28 (2010) 2637

never grow while for a relatively large value of k, convergence of

TLS may not be possible. We propose two different schemes for

choosing an appropriate value of k. In the rst, search-based,

scheme the value of k is kept xed during the level set evolution

process, while in the second, adaptive, scheme, it is chosen adap-

tively as the level set evolves. The latter scheme, though, requires

a slightly more complicated initialization to reduce the overall

complexity of the algorithm.

The search-based scheme nds the best possible value of k by

searching an interval of feasible values. From (2), the smallest va-

lue of k which still can provide an acceptable condence level of

50% for the samples, is k 1. Therefore, this value can be used

as the lower bound of k in the following analysis (k

0

1). Now,

take k to be a relatively large value so that the threshold becomes

very small. It is obvious that in such a case, TLS never converges be-

cause the samples of non-tumor region will be included in the level

set evolution process. Therefore, there must exist a critical value of

k

c

P1, beyond which TLS diverges. Since TLS achieves its best per-

formance at k

c

, the main goal of the search-based scheme is to nd

an approximation of it. For this reason, the values of k, such that

k P1, are swept with a reasonably small step of s

k

. It should be

noted that s

k

decides the trade-off between the accuracy and speed

of this search. Our simulations show that in most cases k

c

is smal-

ler than 2:5.

The search-based scheme performs as follows. For each value of k

the algorithmgoes throughall the steps of tumor segmentationandif

it does not diverge, the current results are savedand the next value of

k

i

k

0

i:s

k

will be tried. The convergence of the algorithm at each

step is veried if for a certain number of iterations the value of the

threshold remains almost unchanged. This process is continued until

ndingthe rst k

n

k

0

n:s

k

for whichthe algorithmdiverges. Then,

the k

n1

k

0

n 1s

k

is the optimal one and the segmentation re-

sults using this optimal k

c

k

n1

is already available.

The search-based scheme is simple, but an exhaustive search

must be performed in order to nd k

c

. The adaptive scheme re-

moves the search complexity by an additional sampling from the

non-tumor region in the initialization phase. Such a sampling,

although requiring more user involvement, greatly reduces the

complexity of the computation. The shape of the selected area in

the non-tumor region is not important but must not contain any tu-

mor voxels. Preferably, it should be selected close to the tumor

boundary where the tumor and non-tumor intensities are more

correlated (Fig. 7). In the adaptive scheme, the value of k is

modied adaptively as the algorithmprogresses. To dene a proper

value of k

i

in each iteration, the condence interval of tumor sam-

ples along with the condence interval of non-tumor samples is

used.

If we assume that the intensities of tumor and non-tumor re-

gions are separated, their condence intervals are also separated,

so that we have

^ l

0

k

0

^ r

0

6 ^ l

i

k

i

^ r

i

9

where ^ l

0

; ^ r

0

are the mean and standard deviation associated with

the non-tumor samples. The goal is to nd the largest possible value

of k

i

so that the condence intervals of tumor and non-tumor sam-

ples do not overlap, and in the worst case ^ l

0

k

0

^ r

0

^ l

i

k

i

^ r

i

.

Moreover, since our condence about the tumor and non-tumor

samples is similar, the same condence level is considered for both

tumor and non-tumor samples in each iteration (k

0

k

i

). Therefore,

a proper approximation of k

i

can be found by

^ l

0

k

i

^ r

0

^ l

i

k

i

^ r

i

) k

i

^ l

i

^ l

0

^ r

i

^ r

0

10

Based on Eq. (10), the values of k

i

are proportional to the intensity

level difference between the tumor and background. The higher the

difference in intensity levels, the greater the value of k

i

, which

means a higher condence level around the tumor samples.

3.2. Modied TLS

The algorithmthat we have introduced is appropriate for homo-

geneous tumors because in the threshold updating procedure, all

accepted tumor samples up to each iteration are used. We intro-

duce minor modications to the threshold updating procedure so

that TLS would be able to segment non-homogeneous tumors.

First, ^ l

i

; ^ r

i

in each iteration is calculated using only the accepted

tumor samples that are greater than the threshold value of the pre-

vious iteration, T

i

:

^ l

i

1

n

X

x

ij

>T

i

x

ij

11

^ r

2

i

1

n 1

X

x

ij

>T

i

x

ij

^ l

i

2

Second, the initial level set should not contain any sample from the

non-homogeneous region. These modications, along with the ef-

fect of the smoothness parameter in the level set speed function,

enables TLS to segment the non-homogeneous tumors. Fig. 8 shows

an example of the tumor that has been successfully segmented by

the modied TLS. We use this modied algorithm as the default

method for segmenting the tumors because the modied TLS can

handle both homogeneous and heterogeneous tumors and is also

robust to image noise.

3.3. Algorithm robustness

In this section, we demonstrate that TLS is robust with respect

to level set initialization. To determine the effects of initialization

on the nal algorithm results, we move the center of the initial

sphere inside the convex tumor in the reference slice, and for each

Fig. 7. Initialization inside the non-tumor region near the tumor boundary where

the intensities are closer to those for the tumor. Fig. 8. Result of modied TLS in the reference slice of non-homogeneous tumor.

S. Taheri et al. / Image and Vision Computing 28 (2010) 2637 31

center position, adaptive TLS extracts the tumor surface and a

threshold curve is obtained. Fig. 9 shows the mean threshold curve

and the threshold deviation at each iteration resulting from 40 dif-

ferent initializations in one convex tumor. It can be seen that as the

iteration number increases, the threshold deviation decreases so

that in the last few iterations the deviations are almost zero. Since

the segmentation results are dependent on the threshold value,

this is a demonstration of algorithm robustness to initialization

which can also imply the robustness across the users. For concave

tumors, the convergence rate of the algorithm is more affected by

initialization, but the nal results are also the same.

3.4. Parameter setting

In this section, we propose the values of the parameters in the

level set equation that should be set by the user. For solving the

level set equation, a discrete Cartesian grid is used to compute a

numerical approximation of the solution. The grid size is chosen

based on the voxel resolution of the corresponding MR image.

In such a case, the smallest unit of measure on the grid is the cell

size denoted by fDx; Dy; Dzg. Since the level set can only grow on

this grid, the radius of the initial sphere must be larger than

minDx; Dy; Dz. We set it to r 2minDx; Dy; Dz. Choosing this

value for the sphere radius leads the front curvature, j

/

, to be

of the order O1= minDx; Dy; Dz [11]. Moreover, in the level set

speed function, F

0

F

I

decides the level set speed while j

/

pre-

vents the level set from trapping into the noisy structures that

are inside the tumor region. Therefore, the parameter j

/

must

be smaller than F

0

F

I

so that it does not affect the level set evolving

direction; for example, we select 0:5minDx; Dy; Dz and

F

0

2. The length of the narrow band around the zero level set

is selected equal to the maximum dimension of a voxel, i.e.,

NB maxDx; Dy; Dz, and the stopping criterion parameters are

experimentally set as 5; 3; 0:02.

4. Experimental results and discussion

We compare the performance of search-based and adaptive TLS

and validate the segmentation results. The test dataset contains tu-

mors of different shapes, locations, sizes, intensity, and enhance-

ment, as shown in Fig. 15.

4.1. Image acquisition

The dataset contains the MR images of 16 patients that were ac-

quired at the Singapore National Cancer Center. All the patients

were imaged on a 1.5T MR scanner using a standard clinical imag-

ing protocol to obtain T1-weighted (T1) and contrast enhanced T1

(gadolinium enhanced) images. Each MR image has an in-plane

resolution of 256 256, eld of view of 160240 mm, and slice

thickness of 23 mm. For the 3 mm slices, linear interpolation is

used to obtain higher inter-slice resolution of 1.5 mm and decrease

the uncertainty between slices. Among these MR images, 6 tumors,

labeled from 1 to 6, are concave and the other tumors, labeled from

7 to 16, are convex. We uses different types of tumors such as ves-

tibular schwannoma and meningioma. An experienced radiologist

manually segmented the tumors to obtain the expert labeling.

We refer to these outlined tumors as manual segmentation, MS,

and use them for validating our results.

0 5 10 15 20 25 30 35

110

111

112

113

114

115

116

117

118

119

120

Iteration number

T

h

r

e

s

h

o

l

d

Threshold vs. Iteration for different initializations

Fig. 9. Deviation of threshold for different initializations inside the tumor region.

The deviations in the nal iterations are very small.

0 5 10 15 20 25 30 35 40

60

80

100

120

140

160

180

200

Iteration number

T

h

r

e

s

h

o

l

d

Threshold vs. Iteration for some k (Tumor 3)

k=1.5

k=1.8

k

c

=2

k=2.1

0 5 10 15 20 25 30

40

60

80

100

120

140

150

Iteration number

T

h

r

e

s

h

o

l

d

Threshold vs. Iteration for some k (Tumor 13)

k=1.5

k=1.6

k

c

=1.7

k=1.8

Fig. 10. Variations of threshold vs iteration number for some values of k in search-based scheme and for two different tumor types. (left) concave tumor, kc 2 (right) convex

tumor, kc 1:7.

32 S. Taheri et al. / Image and Vision Computing 28 (2010) 2637

4.2. Search-based scheme vs adaptive scheme

The performance of the search-based and adaptive algorithms

are compared for the concave (Tumor 3) and convex (Tumor 13)

tumors (Fig. 7). In the search-based scheme, parameter k sweeps

the feasible values with the step size of s

k

0:1 to estimate k

c

.

Fig. 10 shows the variation of threshold versus iteration number

for some values of k in the search-based TLS and for both convex

and concave tumors. In both gures, when k is larger than certain

values, the algorithm diverges, which enables us to obtain k

c

equal

to 1.7 and 2 for the convex and concave cases, respectively. The

greater value of k

c

for Tumor 3 is expected because of the higher

difference in intensity level between the tumor and non-tumor re-

gions. It should be noted that in these two cases, for small values of

k, the threshold rst starts to increase and, then, after several iter-

ations, decreases toward its nal value. This is due to the existence

of non-tumor voxels inside the initialized sphere which belong to

non-reference slices. Consequently, the level set shrinks to discard

such voxels before growing inside the tumor region. For smaller

values of k, the duration of this shrinking is longer.

For the adaptive TLS, the variations of k versus iteration number

for the same tumors are shown in Fig. 11. The values of parameter

k are also higher for Tumor 3, which is consistent with the search-

based results. Another observation is that the value of k

i

for both

cases decreases to an almost constant value. The reason is because,

by growing the level set and increasing the standard deviation of

accepted tumor samples, ^ r

i

, the value of k

i

from Eq. (10) decreases

until the level set reaches the tumor boundary. At this stage, the

mean and standard deviation of the tumor set remain unchanged,

which results in an almost constant k

i

in the last few iterations.

Interestingly, the nal values of k

i

in both cases are close to their

corresponding k

c

obtained from the search-based TLS.

Finally, comparing the threshold variation curves associated

with both search-based and adaptive schemes (Fig. 12), we may

conclude that the convergence rate of the adaptive scheme is high-

er than that of the search-based scheme. This is explained by the

additional knowledge extracted from the non-tumor samples in

the adaptive scheme.

4.3. Segmentation validation

The results of 3D tumor segmentation by TLS over 16 MR

images for both search-based and adaptive schemes are compared

with the manual segmentations. Fig. 15 shows the nal segmenta-

tion results by adaptive TLS on some test images. Let X

M

and X

T

de-

note the set of tumor voxels in the manual segmentation and the

corresponding set resulting from TLS, respectively. In this paper,

three validation metrics are used. Jaccards measure (JM) or

volume overlap metric is the normalized voxel intersection count

for the pair of segmentations X

M

and X

T

, JM

#X

M

\X

T

#X

M

[X

T

. This

measure is sensitive to the difference between two sets since both

denominator and numerator change with increase or decrease in

the overlap. The second metric is the Hausdorff distance (HD)

which denes the maximum surface distance. This measure is ex-

tremely sensitive to outliers and may not reect the overall degree

of matching. The third metric, mean absolute surface distance

(MASD), indicates how different two surfaces are on average and

does not depend on the tumor size [28].

0 5 10 15 20 25 30

1.4

1.6

1.8

2

2.2

2.4

2.6

2.8

Iteration number

k

k vs. Iteration

Tumor 3

Tumor 13

Fig. 11. Variation of k vs iteration number in adaptive scheme and for two different

tumor types.

0 5 10 15 20 25 30

130

135

140

145

150

155

160

165

Iteration number

T

h

r

e

s

h

o

l

d

Threshold vs. Iteration for both schemes (Tumor 3)

adaptive k

searchbased (k

c

=2)

0 5 10 15 20 25 30

104

106

108

110

112

114

116

118

120

122

124

126

Iteration number

T

h

r

e

s

h

o

l

d

Threshold vs. Iteration for both schemes (Tumor 13)

adaptive k

searchbased (k

c

=1.7)

Fig. 12. Comparison between threshold variation for search-based and adaptive schemes and for two different tumor types.

S. Taheri et al. / Image and Vision Computing 28 (2010) 2637 33

The quantitative validation of the TLS segmentation method is

presented in Table 2, which also shows the volumes of segmented

tumors. The results for the surface distance metrics (HD and

MASD) indicate that the segmentation is reliable. The values of

these metrics for various tumors are more similar compared to

JM. The variable JM values demonstrate that this metric is more

sensitive to the size and complexity of tumors. It should be noted

that the large values of HD in some cases is due to the presence of

outliers. In other words, since HD denes the maximum surface

distance and two surfaces which are fairly matched may still have

large HD due to some outliers in the matching distances between

them. Therefore, while low HD is indeed an indicator of good

matching between two surfaces, high value of HD does not neces-

sary imply poor matching.

Fig. 13 compares JM for the two TLS schemes. As we can see in

this gure and also in Table 2, the variation of JM in the search-

based scheme is from 72:8% to 92:9% with a mean of

84:8 6:2%, and in the adaptive scheme from 78% to 93% with a

mean of 87:5 3:9%. Thus, the adaptive scheme generally per-

forms better than the search-based scheme.

The rst six tumors, as mentioned, have concave bodies while the

other tumors are convex. We see in Fig. 13 that the segmentation

Table 2

Quantitative validation of TLS segmentation results.

Index Volume mm

3

Overlap (JM%) Hausdorff (mm) MASD (mm)

MS Search Adaptive Search Adaptive Search Adaptive Search Adaptive

1 12454 9220 10331 72.8 78 4.895 4.668 0.936 0.795

2 18252 16170 16676 80.5 83 10.32 9.12 1.15 0.96

3 13771 11313 12654 79.8 84.5 5.615 5.63 0.679 0.72

4 10619 8508 9655 75 84 3.941 3.938 0.75 0.756

5 14147 13818 14118 79.8 84.1 5.127 4.311 0.831 0.793

6 6600 5933 6280 80.7 88.5 1.771 2.013 0.553 0.576

7 28328 26013 27589 87 89 4.196 4.693 0.788 0.875

8 7532 7056 7538 83 87 11.5 11.34 0.91 0.895

9 15858 14424 16899 90.6 87.4 9.44 8.28 0.756 1.104

10 6944 6503 6362 89.6 88 10.78 10.8 0.804 0.802

11 13512 12928 12528 91.8 90.6 2.502 2.168 0.724 0.656

12 21227 22068 20033 86.4 90.6 6.174 7.332 0.952 0.76

13 50808 49008 48648 88.5 90.1 6.848 6.38 0.864 0.814

14 17793 16582 17434 92.9 93 6.076 2.246 0.637 0.642

15 14159 14153 14300 90.6 91 3.82 3.514 0.823 0.8

16 16485 14735 15882 88.5 91 5.19 3.95 0.667 0.646

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

70

75

80

85

90

95

100

Tumor index

P

e

r

c

e

n

t

(

%

)

Volume overlap measure (JM)

searchbased

adaptive

Fig. 13. Comparison between search-based and adaptive schemes in term of

volume overlap (JM) metric.

2 5 8 11

71

75

79

83

87

91

93

Volume overlap measure (JM)

Tumor index

P

e

r

c

e

n

t

(

%

)

RC method

searchbased

adaptive TLS

2 5 8 11

1

3

5

7

9

11

13 13

Hausdorff distance metric

Tumor index

D

i

s

t

a

n

c

e

(

m

m

)

RC method

searchbased

adaptive TLS

2 5 8 11

0.6

0.7

0.8

0.9

1

1.1

1.2

1.3

Absolute surface distance

Tumor index

D

i

s

t

a

n

c

e

(

m

m

)

RC method

searchbased

adaptive TLS

Fig. 14. Quantitative comparison of RC results with the results of adaptive and search-based TLS using three metrics.

34 S. Taheri et al. / Image and Vision Computing 28 (2010) 2637

error for concave tumors is generally higher than that for convex

ones. This observation can be explained by the complexity of the tu-

mor shapes and the effect of the smoothness parameter on the level

set speed function. In the case of concave tumors, adaptive TLS gives

better results, while for convex tumors, it is possible that search-

based TLS performs better because of the exhaustive search. In the

cases of Tumors 11, 14and15, theperformanceof bothsearch-based

and adaptive TLS are almost the same. Considering their respective

Fig. 15. The cross-sections of extracted tumor surfaces with some of their image slices in addition to the 3D view of corresponding surfaces.

S. Taheri et al. / Image and Vision Computing 28 (2010) 2637 35

images, the reason is because the intensity overlap between the tu-

mor and non-tumor regions in these cases are relatively small.

The segmentation results of TLS are also compared with the re-

sults of the method proposed in [19]. As mentioned in Section 1,

this method is based on region-competition and we call it the RC

method. In this algorithm, the speed function is dened using

the idea proposed in [19], while the other parameters in the level

set equation are the same as those in the TLS approach. We com-

pare TLS with RC for some tumors whose pre- and post-contrast

T1 images are available. Fig. 14 shows the quantitative comparison

of the RC segmentation results with the results of both TLS

schemes for four tumors (2, 5, 8 and 11).

As seen in Fig. 14(a), the JM score in RC is generally less than

the other approaches, but, for Tumor 11 their values are about

the same. Among these approaches, the adaptive TLS gives the

highest JM values except for Tumor 11, where search-based

TLS performs the best. This tumor has a simple convex shape

so that its surface can be simply extracted. Furthermore, as men-

tioned in [19], RC works better for simple and convex tumors

than for complex and concave ones. This can also be veried

in two other gures. In Fig. 14(b and c), the distance metrics

for concave tumors (8, 11) for RC are close to those of TLS. All

gures show that while adaptive TLS generally outperforms the

other methods, RC performs worse than other two schemes.

These results are interesting since RC uses extra knowledge

(the second image) to segment the tumor while TLS, especially

the search-based scheme, uses no extra knowledge although it

may be more complex, and the adaptive scheme only takes

advantage of non-tumor sampling.

To compare the speed and complexity of TLS and RC algorithms

it should be noted that both algorithms are based on the level set

method but with different speed functions. Therefore, the differ-

ence in their speed/complexity is due to the procedure of obtaining

proper speed functions. Since in the TLS, the speed function is de-

ned using a simple thresholding idea, it is simpler than the RC

algorithm that ts a mixture density to the tumor and non-tumor

histogram.

The speed of the two algorithms can be compared using the

number of iterations they need to acomplish the tumor segmenta-

tion. This approach of speed comparison is valid since the time to

complete an iteration in both algorithms is the same. In other

words, the main complexity of RC method is in obtaining the prop-

er speed function which is dened once and does not change iter-

atively. On the other hand, in TLS method, the speed function is

updated at each level set iteration, but the updating process is very

fast (just a simple threshold updating). Therefore, the process at

each iteration of both algorithms is performed with the same speed

and the number of iterations can be a criterion for comparing their

speeds. Based on this argument, the number of iterations reported

in the original paper [19] (20 iterations), shows that the speeds of

both algorithms are almost the same. But one other consideration

is that the level set initialization in the RC method is close to the

tumor boundary since the difference between pre- and post-con-

trast enhanced MR images gives a rough idea about the tumor

boundary. Therefore, the same number of iterations can indicate

that TLS is even faster than RC method.

The TLS method can segment a variety of tumors as long as the

intensity difference between tumor and non-tumor regions in each

case is sufciently large. This constraint is not overly restrictive

and different tumor types such as schwannomas, neurobromas,

and meningiomas satisfy it. But compared to the RC method, this

constraint can limit the TLS scope to a certain level of homogeneity

in the tumors (TLS will diverge if the constraint is not satised).

The RC method can be more efcient in such cases due to the

use of extra knowledge from images in different channels. As

Fig. 15 shows, TLS can handle there non-convex cases. But, again

there are also some restrictions that are mainly due to the level

set capabilities in taking complex shapes and therefore are the

same for both RC and TLS approaches.

5. Conclusion and future work

This paper presents a new threshold-based approach called TLS

for 3D tumor segmentation in brain MR images. TLS uses the level

set as a deformable model and denes its speed function based on

intensity thresholding so that no explicit knowledge about the

density functions of the tumor and non-tumor regions are re-

quired. The threshold is updated iteratively throughout the level

set growing process using either a search-based or adaptive

scheme. Our test with various initializations shows that this algo-

rithm is robust so that the level set can grow into the entire tumor

in all cases. The visualization and quantitative evaluations of the

segmentation results demonstrate the effectiveness of our pro-

posed approach. TLS performance is better where the level of

intensity difference between the tumor and non-tumor regions is

higher. It can segment both concave and convex tumors, although

its performance is better for convex ones. In the cases of concavity,

good initialization can result in better segmentation. Moreover, it

can segment non-homogenous tumors provided the non-homoge-

neity is within the tumor region.

The segmentation method presented in this paper determines a

global threshold to segment the entire tumor. Therefore, TLS can-

not segment the tumors when such a global threshold does not ex-

ist. However, this method can be extended to nd several local

thresholds instead of a single global one. Using both pre- and

post-contrast T1 MR images or other MR modalities such as T2 in

some cases may provide more helpful information and improve

the segmentation results. Furthermore, using some methods for

abnormality detection reduces the user interaction and makes

the algorithm completely automatic. For this purpose brain atlases

can be effectively used. Considering these issues will be part of our

future work.

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