Computers in Biology and Medicine 53 (2014) 265–278

Contents lists available at ScienceDirect

Computers in Biology and Medicine

journal homepage: www.elsevier.com/locate/cbm

Fully automated liver segmentation from SPIR image series

Evgin Göçeri a,n, Metin N. Gürcan b, Oğuz Dicle c
a
Department of Computer Engineering, Pamukkale University, Denizli, Turkey
b
Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA
c
Department of Radiology, Faculty of Medicine, Dokuz Eylul University, Narlıdere, Izmir, Turkey

art ic l e i nf o a b s t r a c t

Article history: Accurate liver segmentation is an important component of surgery planning for liver transplantation,
Received 11 June 2014 which enables patients with liver disease a chance to survive. Spectral pre-saturation inversion recovery
Accepted 10 August 2014 (SPIR) image sequences are useful for liver vessel segmentation because vascular structures in the liver
are clearly visible in these sequences. Although level-set based segmentation techniques are frequently
Keywords: used in liver segmentation due to their flexibility to adapt to different problems by incorporating prior
Variational level set knowledge, the need to initialize the contours on each slice is a common drawback of such techniques. In
SPIR this paper, we present a fully automated variational level set approach for liver segmentation from SPIR
Liver segmentation image sequences. Our approach is designed to be efficient while achieving high accuracy. The efficiency
Signed pressure force function
is achieved by (1) automatically defining an initial contour for each slice, and (2) automatically
Active contour
computing weight values of each term in the applied energy functional at each iteration during
evolution. Automated detection and exclusion of spurious structures (e.g. cysts and other bright white
regions on the skin) in the pre-processing stage increases the accuracy and robustness. We also present
a novel approach to reduce computational cost by employing binary regularization of level set function.
A signed pressure force function controls the evolution of the active contour. The method was applied to
ten data sets. In each image, the performance of the algorithm was measured using the receiver
operating characteristics method in terms of accuracy, sensitivity and specificity. The accuracy of the
proposed method was 96%. Quantitative analyses of results indicate that the proposed method can
accurately, efficiently and consistently segment liver images.
& 2014 Elsevier Ltd. All rights reserved.

1. Introduction evaluation is needed to decide whether the donor and recipient is

Liver is an essential organ with several vital functions such as
protein synthesis and detoxification. Additionally, it regulates
biochemical reactions that include the synthesis or breakdown
of complex and small molecules and produces bile, which is an
alkaline compound aids in digestion. Yet, no technique or device
can compensate for the absence of the liver. The only available
option is liver transplantation, which is a major and risky surgery.
Although transplantation from cadavers utilized to be the first
choice, transplantation from living donors has become a choice of
treatment due to the shortage of cadaver donation in recent years
[1]. Before the surgical procedure, the livers that belong to the
living donor and the recipient are evaluated: to identify the liver
region, to determine the size mismatch, to measure liver volume,
and to analyze the vascular structure. Knowledge obtained by the
n
Corresponding author.
E-mail address: egoceri@pau.edu.tr (E. Göçeri).
a good match and when the transplantation should be performed.
The success of the surgical operation and reduction of complica-
tions (which may occur during or after the operation) to minimum
level depends on accuracy of anatomic information of the portal
and hepatic veins, compatibility of these vessels and liver volume.
Therefore, precise measurements and analysis of liver and vessels
that requires accurate liver segmentation from all image slices
have vital importance for liver transplantation at pre-evaluation
stage [2].
Several automatic and semi-automatic liver segmentation
methods from Computed Tomography (CT) [3] and from Magnetic
Resonance (MR) images [4–11] have been proposed to overcome
problems of manual liver segmentation. An important problem of
manual segmentation is that liver boundaries can be identified
differently by different radiologists and even by the same radi-
ologist at a different time (i.e. inter and intra-reader variability).
Thus, segmentation results depend on experience and skills of
radiologists. Also, it is very time consuming and tedious task
because of the high number of image slices and data sets.

http://dx.doi.org/10.1016/j.compbiomed.2014.08.009
0010-4825/& 2014 Elsevier Ltd. All rights reserved.
266 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278
However, automatic or semi-automatic liver segmentation is more
challenging problem than manual segmentation due to inhomo-
geneous intensities, similar intensity values and unclear edges
between liver and other abdominal organs (i.e. kidneys, heart,
stomach, spleen). Anatomical shape of the liver are varies in
different slices, which complicates the process further.
Although recently published good hybrid methods [12–14]
were shown to be effective in segmenting organs, because of the
imaging modality differences and the notion of individual organ
segmentation in our case using specific MR sequence for liver, full
evaluation and comparison to the methods in our work is outside
the scope of their paper. The use of images that are generated with
different imaging modalities affects accuracy of results obtained
from these segmentation methods. Since, appearance of liver
surfaces in different imaging modalities are different, as illustrated
in Fig. 1, which shows abdominal CT images [14] and Spectral Pre-
saturation Inversion Recovery (SPIR) images from our data set.
In SPIR image sequences, surface of the liver may appear different
even in the same data set, and even in succeeding slices (Fig. 1d
and e) because of clearly visible veins in the liver, gallbladders,
which are seem on SPIR unlike CT images, and different slice
thicknesses used for CT and SPIR image sequences. Also, the
authors identify in their papers [12–14] that the effectiveness of
object detection with the proposed multi-object recognition strat-
egy depends on the number and distribution of objects considered
in the model assembly.
Multi-organ segmentation based techniques [15,16] using CT
images in the state of the art have their own drawbacks. For
example, in [15], authors propose an atlas-based multi-organ
segmentation method. The first step is to select suitable atlases
for an image from a database by measuring image appearance in
this method. Second, registration is applied by using the selected
atlases and the target image. Then, a local atlas weighting is
performed on an organ-by-organ basis and atlas labels are
weighted for each voxel by a patch-based segmentation algorithm.
Finally, a graph-cut based coarse-to-fine weighting algorithm is
applied to incorporate topological information and smoothness
constraints. However, potential misregistrations may cause inac-
curate results with the segmentation method. In another multi-
object segmentation method [16], a transformation matrix is
produced by registration of PET and CT images from test data sets.
A probabilistic liver CT atlas is generated with affine registration of
the transformation matrix and a probabilistic multi-organ atlas,
which is obtained from training CT data sets. The liver CT atlas is
mapped onto low-contrast CT images to assign a prior probability
value for each pixel. Liver is segmented with Gaussian mixture
model by using the prior probabilities. Parameters for expectation
maximization are obtained from a region of the liver on the PET
image. However, this approach requires a large number of training
data sets and registration of images accurately. Also, correct
estimation of region of interest in PET images is required to
segment liver images accurately.
Fig. 1. (a), (b), (c) Abdominal CT images [14]; (d), (e) example SPIR images.
In the state of the art, there is a probabilistic approach [7] for
automated liver segmentation method from T1 weighted MR
images. The first step is manual segmentation of liver on training
data sets by experts in this study. The next step is to generate
probability maps by incorporating prior knowledge about tissue
properties and locations of the liver. Then, the position probabil-
ities, which are determined from the probability maps, and the
tissue probabilities, which are determined according to the inten-
sity distributions in the MR data sets, are calculated for liver,
kidney and stomach. The intensities in all different weighted MR
channels are combined to calculate tissue probabilities. Therefore,
dimensionality reduction with linear discriminant analysis is
applied by using training images. The four-dimensional data is
reduced to three-dimensional MR data. The last step is to apply
region growing algorithm [17] for liver segmentation. However,
accuracy of results mainly depends on probability maps. Therefore,
a large number of training data, which represent more variation, is
required to generate the optimal probabilistic map.
In a more recent study [18], authors apply a marker-controlled
watershed method with a classifier to obtain liver using para-
meters from a training data set. However, overlapping of coeffi-
cients may cause misclassification in some MR images. The
solution for the misclassification problem is to add more seed
points manually by users. Therefore, results may not always be
accurate with this method.
Level Set Methods (LSMs) [19] are based on the curve evolution
theory [20]. According to this theory, the deformation of a curve is
written by a Partial Differential Equation (PDE). The importance of
PDEs has been increased in segmentation area since the first
implementation of the LSMs as image segmentation at the begin-
ning of the 1990s. The main reason for this is that a segmentation
problem can be transformed into a PDE framework. Also, PDEs can
use regularizers with these segmentation models. Another reason
is that finite difference methods can be used to solve PDEs. Also,
PDEs can be extended from two dimensions to higher dimensions.
In addition to these advantages, the solutions from the PDEs are
fast and they are able to perform an image segmentation operation
interactively. The main idea behind the LSM is to represent an
active contour as the zero level set of a smooth function, which is
a higher dimensional and called as the Level Set Function (LSF),
and to evolve this contour to the edges of the desired objects.
An important advantage of the level set approach is that the
geometric properties of the contour can be obtained using a level
set of the surface. Since, the arc-length parameterization and the
curve derivatives according to it are geometric, intrinsic and also
invariant to Euclidean transformations [21]. Another advantage is
that, following of contour evolution in three dimensional spaces is
similar to following in two dimensional spaces because propagat-
ing surfaces are easily obtained by extending the arrays and
gradient operators. Also, LSFs are signed distance functions which
define the closest distance between each pixel and the zero level
set. Therefore, active contours can break or merge during evolution
 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278
and handle topological changes. In addition, the LSF remains as a
whole function on the fixed Cartesian grid that provides efficient
computations.
In our previous work [10], we present an overview on liver
segmentation methods in MR images and show comparative
results of seven different liver segmentation approaches chosen
from deterministic (K-means based), probabilistic (Gaussian model
based), supervised neural network (multilayer perceptron based)
and deformable model based (level set) segmentation methods.
The results of quantitative and qualitative analysis show that our
level set based approach is a reasonable method for liver segmen-
tation from SPIR images.
In this study, we propose a Full-automated Liver Segmentation
(FLS) from SPIR image series for pre-evaluation of liver transplan-
tation by using a variational level set approach. This work
improves our recently published semi-automatic method [10],
which uses a Signed Pressure Force (SPF) function based energy
functional and user defined initial contour on pre-processed SPIR
images that show liver vessels very clear.
The organization of the remaining parts of the paper is as
follows. Relevant level set based medical image segmentation
methods are presented in Section 2. Our previous semi-
automatic method, on which the work in this study is based, is
briefly reviewed in Section 3. Contributions of this study, which
are automated detection and exclusion of structures (e.g. cysts and
other bright white regions on the skin), automatic definition of
initial contours and computation of weight value for the length
term of the active contour, are given in Section 4. Experimental
results and comparative performance analysis for the proposed
method and the semi-automatic method are represented in
Section 5. Finally, conclusions and discussions are given in Section 6.
2. Level set based image segmentation
Level set [19] based medical image segmentation methods have
been more popular in the last fifteen years due to the flexibility of
the level set technique to adapt to different problems by incorpor-
ating several prior knowledge [22–28]. Two major challenges have
to be addressed while developing a level set based image seg-
mentation technique. The first one is stopping the evolution of the
curve efficiently at the desired boundaries without over (i.e.
leakage) or under segmentation. The second difficulty is repre-
sentation of level set functions by signed distance functions
because level set methods do not implicitly preserve level set
functions as signed distance functions in practice. Therefore, in
conventional level set approaches, the level set function causes
irregularities during curve evolution. These irregularities result in
unstable evolution due to numerical errors. Re-initialization is the
typical approach to keep the level set function as a signed distance
function. In re-initialization process, the degraded level set func-
tion is replaced with a signed distance function, whose gradient is
equal to a unit vector. However, re-initialization is a serious
problem since it is not clear how and when it should be applied
to restore the degraded level set function as a signed distance
function [29]. Therefore, various Variational Level Set Methods
(VLSMs) have been proposed to avoid re-initialization (re-distan-
cing) problem by regularizing the level set function as a signed
distance function (by handling topological changes).
VLSMs, which are based on an energy functional, provide
higher computational efficiency and easier implementation. Mini-
mization of the energy functional in VLSMs is similar to an edge
detection method. In these alternative approaches, the energy
functional is defined with the level set function. Then, a partial
differential equation is obtained by using this energy functional
instead of an Eulerian equation as in classical level set methods
267
[30,31]. Among different VLSMs, Li et al. [32] proposed to use a
distance regularization term in the Distance Regularized Level Set
Evolution (DRLSE) method.
The DRLSE approach is based on a potential function and forces
the gradient magnitude of the level set function to one of its
minimum points. It eliminates the computationally expensive re-
initialization process. However, this method uses constant coeffi-
cients and the traditional edge stopping function, which is
Gaussian filter based, to remove the effect of noise in the energy
formulation. The Gaussian filter results in blurred edges while
reducing the image noise. Also, this method is very sensitive to
position, shape and size of the initial contour on SPIR images. It is
observed that this approach causes unstable evolution and cannot
segment liver from SPIR datasets successfully [10].
3. The semi-automated liver segmentation method
To overcome all problems in the DRLSE, we have proposed a
novel semi-automated VLSM based liver segmentation from SPIR
image series in our previous work [10], which is called as SLS
(Semi-automated Liver Segmentation) method in this study.
Experimental results and quantitative performance analysis of
the SLS method show that pre-processing and binary regulariza-
tion and also an adaptive SPF function based edge indicator in the
energy functional provide efficiently segmented liver images.
We describe the pre-processing step, energy functional and also
the edge indicator briefly in this section.
3.1. Pre-processing to reduce the effects of irrelevant organs
The first step for liver segmentation is pre-processing, which
detects and removes kidney, spleen, heart, gallbladder and spine
automatically from abdominal images, to suppress their interfer-
ence in the liver segmentation process. These organs are first
detected using anatomical knowledge and morphological opera-
tions are applied on these detected structures. Binary morpholo-
gical image reconstruction [33] is applied with an appropriate
marker image (seed region) on the organ. The required mask for
image reconstruction is obtained by choosing the cluster that
shows the organ, after clustering of the original image with
Gaussian mixture model [34,35].
An example in Fig. 2 shows different steps of the SLS algorithm
and how irrelevant organs are extracted on an example slice
(Fig. 2a) with a mask image (Fig. 2b) and a marker image for
spleen and stomach. First, boundaries from the left and right hand
side (the first non-zero values) are detected, which are shown as
blue lines in Fig. 2c. The mid-line between these blue lines
corresponds to the position of the spine (shown with the yellow
line in Fig. 2c). For spleen extraction, the anatomical knowledge
that spleen is located at the bottom-left side of an abdominal
image is used. Besides, it is observed that spleen is always
clustered as the third cluster (Fig. 2d) when the original image
is clustered into four clusters by K-means clustering algorithm:
(1) background region, (2) dark gray tissues, (3) bright gray tissues
(corresponds to spleen) and (4) brightest tissues. A marker image
that includes some part of the spleen is obtained at the left side of
the spine by using the middle of the yellow and blue lines (shown
as red color in Fig. 2d). The spleen image (Fig. 2e) is obtained after
morphological image reconstruction with the marker, which is
shown as green frame (Fig. 2d) and the mask image. Similarly,
stomach extraction is performed with the knowledge that stomach
is located at the left hand side of the spine and above the spleen.
A seed region is selected by using the mid-point of the yellow line
and red line at the left side of the spine (Fig. 2f). In this case,
268 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278

Fig. 2. Pre-processing: (a) original slice; (b) clustered image; (c) boundaries of the image from the left and right hand side shown with blue lines and also the middle (shown
with the yellow line) of the distance between these two blue lines; (d) marker image shown as the green frame for spleen; (e) extracted spleen image; (f) marker image
shown as the green frame for some part of stomach; (g) the marker image for stomach on the mask image; (h) pre-processed image. (For interpretation of the references to
color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3. (a) Example SPIR slice; (b) the spine, kidneys and the gallbladder.

the original image is clustered into four clusters after the spleen
extraction. The last cluster that includes stomach is chosen in
order to use as the mask image. Fig. 2g shows the mask and
marker image for stomach, which are used to apply binary
morphological image reconstruction. The pre-processed image
without the spleen and stomach is presented in Fig. 2h.
Kidneys, which have similar gray level values with the liver,
may cause over-segmentation. Similarly, the spine may affect
curve evolution due to its high intensity value. Fig. 3 demonstrates
an example SPIR slice (Fig. 3a) to show kidneys and the spine
(Fig. 3b), which also shows the gallbladder.
Kidneys and spine are extracted in the pre-processing stage
with an algorithm similar to those of the stomach and spleen
extraction and the details are given in [10]. The anatomical
knowledge that kidneys are inside the ribs and located in the
bottom-left and bottom-right side of abdominal images is used for
kidney extraction. A seed region that includes some part of the
right kidney is obtained at the right side of the spine. The third
 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278 269

cluster that includes the right kidney is chosen in order to use as selected seed region as the marker image. Similarly, the left kidney
the mask image. The segmented right kidney is obtained after is detected and extracted automatically by selecting the seed
morphological image reconstruction with the mask and the region at the left side of the spine.

Fig. 4. Flow-chart of the proposed method.

270 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278
3.2. Energy formulation
To explain the applied energy functional,

let us assume that the
active contour is defined as C ¼ ðx; yÞ A Ωjϕðx; yÞ ¼ 0 , where
ϕðx; yÞ ¼ 0 is the zero level set function, Ω  ℜ and the image I :
Ω-ℜ is defined onΩ. The energy functional to be minimized, which
consists of the length and area term with their coefficients is given as,
EðϕÞ ¼ λLg ðϕÞ þ αAg ðϕÞ; α A ℜ; λ40
 
here λ, α corresponds to weight values and C p  4 0; is the edge
indicator function. The term Lg ðϕÞ is the length of the active contour
R
and expressed as Lg ðϕÞ ¼ Ω g δðϕÞj∇ϕjdxdy, where δ(.) is the Dirac
delta function. The term Ag ðϕÞ is the area in the active contour and
R
computed with the Heaviside function H(.) as Ag ðϕÞ ¼ Ω gH
ð  ϕÞdxdy. The weight value of the area term is calculated by using
summation of absolute values of minimum and maximum curva-
ture terms to increase the speed of the motion [10].
To obtain a minimum value of a function, a study state solution of
the gradient of this function can be found. The gradient flow equation
of the energy functional E(ϕ) (3.1) is written as, ∂∂tϕ ¼  ∂∂Eϕ, where ∂∂Eϕ is
the Gateaux derivative of E(ϕ). This is an evolution equation of a time
dependent level set function ϕ(x,y,t) with a spatial variable x and y.
The evolution direction of ϕ(x,y,t) is opposite of the Gateaux derivative
(i.e.  ∂∂Eϕ), which is the direction of the steepest descent of the energy
functional E(ϕ). Therefore, the gradient flow is known as gradient
descent flow or steepest descent flow.
3.3. Integrated edge indicator function
Edge based level set methods [32,36,37] usually use a regular,
positive and decreasing edge indicator function g, such that
lim gðtÞ ¼ 0 to stop level set evolution at boundaries. The edge
t-1
indicator function is the absolute of the gradient of the convolved
image with Gaussian function to remove the effect of noise in the
energy formulation, and written as,
1 obtained from a chosen initial slice. The initial liver image is used
gðj∇IjÞ ¼
1 þ j∇Gσ  Ij2
The level set function stops when the value of the edge
indicator function approaches to zero, which means that the active
contour will be stopped where the gradient of the image is large
enough for g-0. However, it is never equal to zero for digital
images since the discrete gradients are bounded. It causes unstable
evolution due to noise and non-homogeneous intensities in
abdominal SPIR images. The Gaussian filter cannot preserve edge
information while removing the noise effect and causes blurring
especially at weak edges. Choosing a small sigma value for the
Gaussian kernel may lead to sensitivity to noise. In this case, the
curve evolution will not be stable. Choosing a big sigma value may
cause boundary leakage problem, which results inaccurately
segmented images. Therefore, determination of the optimal stan-
dard deviation is a dilemma for liver segmentation from SPIR
datasets due to unclear boundaries and noise. Different alternative
solutions have been proposed in the literature to overcome this
problem [38–40]. In the SLS method, an edge indicator is defined
with a novel SPF function and its gradient to take into account
edges for stable results as,
g ¼ SPFðIðxÞÞ þ ∇SPFðIðxÞÞ
The applied adaptive SPF function according to the intensity
values outside and inside the active contour is,
8 IðxÞ  ðC þ C Þ=2
< max IðxÞ  1ðC þ2C Þ=2 ; if ðC 1 4 10  C 2 Þ or ðmaxðI  avgÞ o 5  avgÞ
ðj 1 jÞ
2
SPFðIðxÞÞ ¼
: IðxÞ  minðC 1 ;C 2 Þ
maxðjIðxÞ  minðC 1 ;C 2 ÞjÞ; else
where the term avg corresponds to ðC 1 þ C 2 Þ=2, C 1 and C 2 are
average intensity values outside and inside the active contour,
respectively, which are defined as,
R R
IðxÞH ε ðϕÞdx IðxÞð1  H ε ðϕÞÞdx
C 1 ¼ ΩR C 2 ¼ ΩR ð3:5Þ
Ω H ε ðϕÞdx Ω ð1  H ε ðϕÞÞdx
The partitioned SPF function (3.4) means that if the average
intensity value in the active contour is greater than ten times of
ð3:1Þ
the average intensity value of outside the contour (i.e. the average
intensity values inside and outside the active contour are not
close) or the difference between intensity values of each pixel and
the mean intensity value of inside and outside average intensities
is greater than the five times of the mean intensity value then
select the first part. Otherwise, select the second part of the SPF
definition. Since, the initial contour is always defined inside the
liver in our application. Therefore, if values of C 1 and C 2 are close
on a pre-processed image then contrast of the image is very low.
Then, the difference between each pixel value and the minimum
average intensity value is efficient for curve evolution. The
adaptive SPF based edge indication function gives effective results
even at weak boundaries.
Although the SLS method provides successfully segmented
liver images with low computational complexity, it has the
following limitations: First, effects of cysts and other bright white
regions on the skin have not been properly handled. Second, the
method requires a user defined initial contour for each slice in a
data set. Third, some of the parameters used in the algorithms are
determined heuristically. In this study, we present an approach
that overcomes these limitations by detecting and excluding of
cysts (see Section 4.1) and bright white regions on the skin (see
Section 4.2) and also generating initial contours automatically (see
Section 4.3). Moreover, we propose a novel approach to compute
the weight value for the length term (Section 4.4) in the applied
energy functional (3.1).
Fig. 4 shows the overall structure of our segmentation algo-
rithm. As can be seen in this flowchart, first an initial liver image is
ð3:2Þ
to generate the initial contour for the succeeding slice. All slices
are segmented iteratively beginning from the initial liver image to
the last slice, and again from the initial liver image to the first slice
in the image sequence. The first step of the iterative segmentation
algorithm is pre-processing (Section 3.1). Our proposed approach
for detection and extraction of cysts and bright white regions on
the skin is integrated into this step. Second step is generation of
initial contour from previous segmented liver image (Section 4.3).
Afterwards, necessary parameters, which are SPF function, edge
indicator function, weight value of the area term and length term,
are computed (Section 3.2, Section 3.3 and Section 4.4). Finally,
gradient of the energy functional is calculated until its minimum
value is found by using the gradient descent flow equation. Once
the liver image is obtained, it is used to generate the necessary
initial contour for liver segmentation for the next slice. This
iterative process continues until all slices are segmented (Fig. 4).
4. Proposed method
This section explains the four important steps of the proposed
ð3:3Þ approach that are integrated to our previous method [10] to
overcome its limitations.
In this study, upper abdominal MR data sets have been used.
The data sets were obtained from ten different patients (four men
and six women; age range, 52–81 years) using a 1.5 T MR imaging
device (Gyroscan Intera, Philips, ACS-NT, Best, The Netherlands).
The examined 16 bit DICOM images are fat suppressed
ð3:4Þ T2-weighted (TR/TE, 1600/70 ms; flip angle, 901; slice thickness,
 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278 271

8 mm) SPIR images (0.63 pixel per mm and the pixel size is 1.58 
1.58 mm) in the axial plane with a resolution of 256  256. Also,
images with different resolutions (i.e., 288  288 and 320  320)
have been tested.
4.1. Cyst detection and extraction
A cyst on the liver seems as bright white in abdominal SPIR
images (Fig. 5a). Cyst detection and extraction is applied in the
pre-processing step after removing irrelevant organs. We observed
that existence of a cyst negatively affects curve evolution due to its
high intensity values. This leads to erroneous results when the
area under the cyst is larger than the area of a vessel on the liver.
Therefore, cyst detection and extraction is applied after getting the
number of slices that include the cyst as a user defined parameter.
Extraction of the cyst according to its intensity and size is easier if
we use the pre-processed image (Fig. 5b) of the slice because a cyst
is always clustered in the last cluster when the pre-processed
image is clustered into four clusters, (see Section 3.1). Therefore,
the image in the last cluster is chosen (Fig. 5c) and the largest
connected component is detected to use as a marker, which
includes some part of the cyst. The image in the third cluster
shows the appropriate mask (Fig. 5d). Binary morphological image
reconstruction algorithm is applied with the marker and mask
images. Then the cyst, i.e. the reconstructed image, (Fig. 5e) is
extracted. The pre-processed image (Fig. 5f) after cyst extraction is
used for liver segmentation. Gallbladder (Fig. 3b) extraction is
performed with the same algorithm since a gallbladder is similar
to a cyst in the liver and seems as bright white.
4.2. Detection and extraction of bright white regions on the skin
Fig. 6a shows two bright regions at the top side on the skin that
occurs as a result of insufficient presaturation band localization.
These parts may lead to inaccurate edge indicator (3.3) due to
inaccurate selection in the SPF function (3.4). We have also
removed these bright white regions that are seen on the skin in
some slices to reduce their potential undesired effects during

Fig. 5. Cyst extraction: (a) original slice; (b) pre-processed image (without adjacent organs and spine); (c) marker image that includes a small part of the cystic region;
(d) mask image; (e) extracted cyst; (f) pre-processed image without cyst.

Fig. 6. Extraction of the bright white regions on skin: (a) original image; (b) pre-processed; (c) mask image; (d) marker image, which shows bright white regions in the last
cluster and outside of the previously segmented liver shape; (e) pre-processed image.
272 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278
curve evolution. Similar to the cyst extraction process, binary
image reconstruction algorithm is applied with a mask and marker
image. The necessary mask image is obtained by choosing the
image in the third cluster (Fig. 6c), which include bright gray level
tissues and bright white tissues. A marker is obtained by inter-
secting the image in the last cluster (includes bright white regions
and vessels) with the image that is outside of the previous
segmented liver image. This intersection produces the image that
shows only some part of the bright white regions on the skin while
excluding vessels (Fig. 6d). Then, the reconstructed image by the
morphological binary image reconstruction is removed and the
pre-processed image (Fig. 6e) is obtained for liver segmentation.
4.3. Automatic initialization of contours
Initialization of contours is a key challenge for level set based
segmentation methods [41]. When done manually, each user can
draw different initial contours at different locations and sizes. The
user defined initial contours can cause inaccurate or non-robust
segmentation results regardless of the number of iterations. Finding
the correct number of iterations for each initial contour is not easy
at each slice. Therefore, we need to apply level set approaches for
liver segmentation automatically to overcome these drawbacks and
obtain acceptable results from all slices in a dataset.
The liver shape in a slice is close to the liver shape of the
previous or next slices with respect to other slices in the dataset.
Therefore, the shape of an initial segmented liver image can be
used as the initial contour for all the slices in a data set. This
approach was used in our previous automatic liver segmentation
method, which is called as automatic DRLSE with the SPF method
[10]. There are some drawbacks of this approach, which are related
to both the applied energy functional and generated initial con-
tour. The first drawback is on how to choose the value of the
standard deviation of Gaussian kernel. This kernel is used both in
the traditional edge stopping function, which is integrated into the
Fig. 7. (a), (f) Segmented liver image; (b), (g) skeleton image of the previous segmented liver; (c), (h) image after filling holes on the image that is intersection of the skeleton
with the pre-processed image; (d), (i) after median filtering and dilation; (e), (j) generated initial contour on the next slice. (For interpretation of the references to color in
this figure legend, the reader is referred to the web version of this article.)
length and area terms of the active contour, and also in the SPF
function. The other drawback is that using a constant standard
deviation value for a data set does not always produce successful
results for liver segmentation for all slices in a given data set. The
constant weight values for the length and area term cause
undesired results due to the vascular structure of liver and non-
homogenous intensity values. Also, irregular shape of the liver
reduces usability of the shape of the segmented liver in the
previous slice as the initial contour for the next slice.
To overcome these drawbacks, we have defined a novel SPF
function based edge indicator without using Gaussian function in the
SLS method as explained in Section 3. The algorithm of the SLS
method requires a manually initialized contour on the liver at each
slice. However, manually drawing an initial contour on each slice in a
data set increases segmentation time and is also very tedious
because of increasing number of data set. The user defined initial
contour has to be drawn inside or outside of the liver without
leakage. Moreover, if the liver is partitioned then an initial contour
has to be drawn on each partition by the operator. Therefore, in this
study, to improve the semi-automatic SLS method, we have proposed
to generate the necessary initial contour automatically for each slice
without any user interaction, which increases the efficiency and
improves the accuracy and consistency of the method.
We observed that the shape of the segmented liver image in one
slice is not always useful as an initial contour for liver segmentation
for succeeding slices because liver shapes are not regular. Also,
differences in slice thickness of data sets make this problem more
challenging. These identified factors in addition to noise and inho-
mogeneous intensities lead to over/under segmented liver images.
Therefore, in this study, we have generated an initial contour
automatically from the shape of an initially segmented liver instead
of using its shape directly as an initial contour. For this purpose,
similar to the marker image in the iterative Gaussian mixture model
based method [10], first, we have used the initial liver image (Fig. 7a),
which is the segmentation result of a selected slice (generally the
 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278 273

mid-slice in a data set), where liver boundaries are usually well-

defined so that the liver can be segmented by simple (e.g. K-means)
clustering. Then, we have obtained the skeleton (Fig. 7b) of the initial
liver image. Second, we have filled all holes (Fig. 7c) after intersecting
the skeleton image and the succeeding pre-processed image with
binary ‘AND’ operation. Then, dilation operation is applied with a
disk shaped structuring element (radius is 1). After dilation, we have
applied median filtering to remove small spots from the image.
Fig. 7d shows the generated initial contour as binary that is also
shown on the succeeding slice, which will be the next processed
image, as red color (Fig. 7e). The effect of the filling holes and dilation
operations by using another segmented liver image (Fig. 7f) and
skeleton (Fig. 7g) is given in Fig. 7h after the intersection process.
After dilation and median filtering, the generated initial contour
(Fig. 7i) is shown in Fig. 7j as red color.
All slices are segmented iteratively by beginning from the
initial liver image to the last slice and from the initial liver image
to the first slice in the image sequence.

4.4. Computation of the weight value for the length term

Fig. 8. Liver regions, which are surrounded with yellow color and red color, are The applied energy functional (3.1) is composed of length and
provided by experts with manual segmentation and the proposed segmentation area of the active contour. All VLSMs based on the length and area
method. (For interpretation of the references to color in this figure legend, the terms use constant weight values, which are chosen according to
reader is referred to the web version of this article.)
the experience of authors, for these terms [42–44,32,36]. Segmen-
tation results are sensitive to chosen weight parameters. However,
each data set has a different contrast ratio. Further, liver has a
Table 1 vascular structure and non-uniform intensity values. Different
Quantitative analysis of a curve evolution using the image shown in Fig. 8 to intensity gray levels of an image require different weight values,
present changing of the isoperimetric ratio and related terms of the applied energy
which makes it a challenge to choose the optimal λ value. In
functional at each number of iterations.
addition, using the same constant weight value during curve
Number Gradient value Sum of Sum of Isoperimetric evolution will not always produce acceptable results for liver
of of the energy differentiation differentiation ratio segmentation from SPIR image data sets even the most optimal
iterations functional of the area of the length constant value is chosen. Therefore, we have used adaptive weight
     
∂ϕ ∂E ∂A ∂L
∂t ¼  ∂ϕ term ∑ ∂ϕg term ∑ ∂ϕg values by computing automatically according to the feature of the
curve for the length and area terms in the SLS method [10].
1 5068 1.7627000 73.122 3.106
Although the implemented formulation that is given for the λ
2 4397 1.7899000 12.1522 8.315
3 4132 1.7589000 12.7151 9.314 parameter seems efficient, we propose another computation for
4 4050 1.7261000 12.5359 9.192 this parameter, which also provides smoothness, in this study.
5 4018 1.7138000 12.4810 9.116 The isoperimetric ratio is the value of shape of compactness,
6 4162 1.7083000 12.0334 8.567 which is an intrinsic property of objects and used as a shape
7 4139 1.6976000 11.9133 8.480
descriptor in pattern recognition [45]. We have computed the
: : : : :
58
59
2908
2905
1.2981000
1.2963000
109.595
109.301
9.314
9.329
ð
L2 ðϕÞ
Þ
isoperimetric ratio, Ag ϕ , at each iteration during curve evolu-
gð Þ

60 2905 1.2955000 109.042 9.336 tion and assigned its value to λ in our energy functional (3.1), and
61 2905 1.2953000 108.963 9.167 obtained the following equation.
62 2905 1.2950000 108.878 9.167
63 2905 1.2950000 108.878 9.167 L2g ðϕÞ
64 2905 1.2950000 108.878 9.167 EðϕÞ ¼ Lg ðϕÞ þ αAg ðϕÞ
Ag ðϕÞ

Fig. 9. Graphics of quantitative values, which are presented in Table 1 for the image given in Fig. 8, for isoperimetric ratios (a) and gradient descent flow (b).
274 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278
L3g ðϕÞ
EðϕÞ ¼ þ αAg ðϕÞ
Ag ðϕÞ
Eq. (4.1) implies that we increase the compactness degree of
the closed curve by multiplying the isoperimetric ratio L2g ðϕÞ=Ag ðϕÞ
with the length term Lg ðϕÞ. Therefore, the advantage of using the
isoperimetric ratio as the weight value instead of the λ coefficient
is to increase smoothness of the curve. In addition, we assign
the minimum value of the ratio of the isoperimetric inequality,
L2g ðϕÞ
which is Ag ðϕÞ
Z4 π , for the λ parameter when the value of
the computed λ is greater than 4π during the curve evolution.
Since, we are trying to find the minimum value of the applied
energy functional (4.1), which means that all terms have their
minimum value.
Fig. 8 illustrates the liver region surrounded with red color that
is obtained by the proposed segmentation method. Also, it shows
the liver region surrounded with yellow color that is provided by
experts with manual segmentation as the ground truth data.
Table 1 presents computed gradient values of the applied
energy functional, summation of differentiation of the length and
Fig. 10. (a),(b),(c),(ç),(d),(e),(f),(g) Original slice;(ğ), (h), (ı), (i), (j), (k), (l), (m) obtained initial contour; (n),(o),(ö),(p),(q),(r),(s),(ş) final shape of the initial contour; (t),(u),(ü),
(v),(w),(y),(z1),(z2) segmented liver images.
area terms and also the isoperimetric ratio at each iteration for the
ð4:1Þ image shown in Fig. 8. As can be seen from the quantitative analysis,
the value of the isoperimetric ratio converges automatically to a
constant value while the value of the energy functional converges to
its minimum. Numerical values do not change after the algorithm
finds the minimum energy level (62th iteration in Table 1). The
proposed method stops the curve evolution efficiently at this energy
level even the iteration process does not reach the final number of
iterations.
Quantitative values in Table 1 have been plotted in Fig. 9 for
isoperimetric ratios (Fig. 9a) and gradient values of the energy
functional (Fig. 9b).
Fig. 9 shows that the evolution of the active contour stops
efficiently even the maximum iteration number is bigger than the
iteration number corresponding to the minimum energy value.
5. Experimental results and performance analysis
A fully automatic level set based liver segmentation approach
from SPIR data sets is proposed in this study. Example initial
 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278 275

Fig. 10. (continued)

contours that are automatically obtained by this method using derived by evolution of these initial contours are presented in
original images (Fig. 10a–g) are shown in Fig. 10ğ, h, ı, i, j, k, l Fig. 10n, o, ö, p, q, r, s and ş while segmented liver images are given
and m. Final level set functions, which show liver boundaries, in Fig. 10t, u, ü, v, w, y, z1 and z2.
276 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278

It is observed that when there is a cyst on the original slice
(Fig. 10d), the automatic segmentation procedure with the itera-
tively generated initial contour (Fig. 10j) finds liver boundaries
(Fig. 10q) successfully and results in correctly segmented liver
image (Fig. 10w) after removing the cyst in the pre-processing
step. Therefore, the proposed segmentation method is efficient in
terms of accuracy not only for a slice that show healthy liver but
also for a slice that show a cyst on the liver.
An experienced operator spends about 30–45 min for manual
segmentation from 50 images to segment liver. The total compu-
tational time and results can be different according to experience
of operators both on the liver and the tool used for manual
segmentation. The results of the proposed FLS approach and the
SLS method with the most optimal user defined initial contours
have been evaluated according to their required computational
cost, sensitivity, specificity and accuracy values. These measures
are generally used to evaluate methods [46–49] and defined as
TP
Sensitivity ¼
TP þ FN
TP
Specificty ¼
TP þ FN
TN þ TP
Accuracy ¼
TP þ TN þFP þ FN
where TP (True Positive) is the number of pixels that are classified
correctly as foreground in the foreground region, TN (True Nega-
tive) is the number of pixels that are classified correctly as
background in the background region, FP (False Positive) is the
number of pixels that are classified as foreground in the back-
ground and FN (False Negative) is the number of pixels that are
classified as background in the foreground region. Table 2 presents
quantitative results of these evaluation criteria for the images
shown in Fig. 10a, b, c, ç, d, e, f and g. The computational costs in
terms of time have been obtained by using 2 GB RAM and Intel
Core i7-3612QM CPU at 2.40 GHz.
Sensitivity measures success of a method about identification
of the TP and FP cases. Specificity indicates that how well the
method can identify the TN and FN cases. Therefore, accuracy is
low (high) when both specificity and sensitivity are low (high).
However, only accuracy is not a good measure for performance
evaluation. Because the value of accuracy is biased towards either
specificity or sensitivity when any one of specificity or sensitivity
has high value and the other has low value. Therefore, we have
presented images whose sensitivity and specificity values are
mostly close to each other.
Volumetric visualization of segmentation results presents more
information to users for further analysis of images [50]. Therefore,
an example volumetric visualization of segmented images that are
obtained by the proposed approach is given in Fig. 11, which
ð5:1Þ
shows results in three-dimensional (3D) coronal view (Fig. 11a),
axial view (Fig. 11b) and sagital view (Fig. 11c).

Table 2
Quantitatively comparative performance analysis of the FLS and SLS method in
6. Conclusion and discussion
terms of required time (in second), sensitivity, specificity and accuracy (in
percentage). In this study, we proposed a novel fully automated liver
segmentation method, which overcomes the major drawbacks of
Original image Method Sensitivity Specificity Accuracy Required time
the previous approaches and does not have to rely on neither a
(in second)
distance regularization term nor the traditional edge stopping
Fig. 10a FLS 70.94 99.53 97.20 10.40 function. Additionally, it controls and stops the evolution of the
SLS 66.16 94.29 92.00 25.67 active contour efficiently with the edge and region based adaptive
Fig. 10b FLS 83.59 98.67 96.80 41.04 SPF function. The major conclusions of this study are increased
SLS 83.49 98.72 96.83 48.80
Fig. 10c FLS 75.90 99.68 97.01 17.37
accuracy (96%) of the segmentation results and reduced processing
SLS 74.90 99.66 97.04 38.36 time. These conclusions are based on the following experimental
Fig. 10ç FLS 62.32 99.75 94.85 39.58 evidence: First, we applied a pre-processing step to suppress
SLS 60.01 99.00 94.47 40.86 interference effects, which are caused by similar intensity values
Fig. 10d FLS 64.74 99.71 95.04 110.06
between liver and irrelevant organs (such as stomach and spleen),
SLS 60.77 79.10 73.98 81.14
Fig. 10e FLS 95.39 98.30 97.90 45.44 in the liver segmentation. We also removed the effects of cysts and
SLS 93.27 96.49 96.05 50.91 other bright white regions on the skin in this stage. Next, we
Fig. 10f FLS 79.59 97.66 96.15 28.43 generated initial contours automatically for each slice instead of
SLS 79.01 96.17 94.74 51.71 drawing them manually. Finally, we computed all weight values in
Fig. 10g FLS 73.99 99.66 96.92 65.66
SLS 74.28 96.92 94.50 90.25
the energy functional automatically by using intrinsic properties of
the active contour. Another important feature should be noted

Fig. 11. 3D visualization of segmentation results; Coronal view (a), axial view (b), sagital view (c).
 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278
here that these computed weight values are not constant in
our implementation during curve evolution. Since, we updated
(re-computed) them and assigned their new values in the energy
functional at each iteration.
The computational cost in terms of time required to process a
particular dataset depends on total number of slices in the dataset
when the proposed FLS approach is used. It is clear that processing
all slices iteratively without any user interaction requires less
processing time than processing them with a user defined initial
contour. Drawing an initial contour manually leads to longer
computational time for segmentation of the liver. The SLS method
needs a user-defined initial contour for each slice. If the liver
seems as partitioned in an image then users have to define an
initial contour on each partition. Initial contours can be defined at
different size and location according to experience of users and
shape of the liver. Longer processing time is required for detection
of liver boundaries in case of the size of the user defined initial
contour is small. Therefore, initialization of the active contour
affects both accuracy of results and waiting time for segmentation
and also processing time.
The FLS approach is successful not only for slices that show
healthy liver but also for slices that contain a cyst or any superficial
structures in the images. Results in Fig. 10v and w shows that
removing the cyst and the brightest regions on the skin in the pre-
processing step gives successfully segmented liver images. Exis-
tence of a cyst in the liver increases the required time for
segmentation because of the cyst detection and extraction process
in the FLS method.
As the future work, we will test the proposed FLS method with
more data sets to address different cases and apply a vessel
segmentation approach on segmented SPIR images. Also, an algo-
rithm can be developed and integrated into the pre-processing stage
to extract skin. Since, its gray level values may affect accuracy of
results that are obtained from images in SPIR datasets.
Conflict of interest statement
None declared.
References
[1] V. Gunabushanam, A. Chaudhary, A. Humar, Living donor advocacy, Living
Donor Liver Transplantation, Publisher: Springer, New York, ISBN 978-1-4614-
9142-229–40 (Book Part-I, chapter 3).
[2] 〈http://www.cpmc.org/advanced/liver/patients/topics/liver-cancer-profile.
html〉, 2014. California Pacific Medical Center.
[3] A.M. Mharib, A.R. Ramli, S. Mashohor, R.B. Mahmood, Survey on liver CT image
segmentation methods, Artif. Intell. Rev. 37 (2) (2012) 83–95.
[4] G. Chen, L. Gu, L. Qian, J. Xu, An improved level set for liver segmentation and
perfusion analysis in MRIs, IEEE Trans. Inf. Technol. Biomed. 13 (1) (2009)
94–103.
[5] C. Dongxiang, L. Tiankun, Iterative quadtree decomposition segmentation of
liver MR Images, in: International Conference on Artificial Intelligence and
Computational Intelligence, AICI 3 (2009) 527–529.
[6] L. Ruskó, G. Bekes, Liver segmentation for contrast-enhanced MR images using
partitioned probabilistic model, Int. J. Comput. Assisted Radiol. Surg. (CARS) 5
(2010) 1861–6410.
[7] O. Gloger, J. Kühn, A. Stanski, H. Völzke, R. Puls, A fully automatic three-step
liver segmentation method on LDA-based probability maps for multiple
contrast MR images, Int. J. Magn. Reson. Imaging 28 (6) (2010) 882–897.
[8] K. Jha, J.J. Rodriguez, R.M. Stephen, A.T. Stopeck, A clustering algorithm for liver
lesion segmentation of diffusion weighted MR images, in: IEEE SSIAI (2010)
93–96.
[9] H. Masoum, A. Behrad, M.A. Pourmina, A. Roosta, Automatic liver segmenta-
tion in MRI images using aniterative watershed algorithm and artificial neural
network, Biomed. Signal Process. Control 7 (5) (2012) 429–437.
[10] Goceri E. 2013. A Comparative Evaluation for Liver Segmentation from SPIR
Images and a Novel Level Set Method Using Signed Pressure Force Function,
Ph.D. Thesis.
[11] H.T. Huynh, I. Karademir, A. Oto, K. Suzuki, Liver Volumetry in MRI by Using
Fast Marching Algorithm Coupled with 3D Geodesic Active Contour
277
Segmentation. Computational Intelligence in Biomedical Imaging, Publisher:
Springer, New York, ISBN 978-1-4614-7244-5141–157 (Book Part II, Print).
[12] X Chen, J. K Udupa, U Bagci, Y Zhuge, J. Yao, Medical image segmentation by
combining graph cut and oriented active appearance models, IEEE Trans.
Image Process. 21 (2012) 2035–2046.
[13] U Bagci, X Chen, J.K. Udupa, Hierarchical scale-based multi-object recognition
of 3D anatomical structures, IEEE Trans. Med. Imaging 31 (2012) 777–789.
[14] X Chen, U. Bagci, 3D Automatic anatomy segmentation based on iterative
graph cut ASM, Med. Phys. 38 (2011) 4610–4622.
[15] R. Wol, C. Chu, K. Misawa, M. Fujiwara, K. Mori, D. Rueckert, Automated
abdominal multi-organ segmentation with subject-specific atlas generation,
IEEE Trans. Med 32 (9) (2013) 1723–1730.
[16] C. Li, X. Wang, Y. Xia, S. Eberl, Y. Yin, D.D. Feng, Automated PET guided liver
segmentation from low-contrast CT volumes using probabilistic atlas, Comput.
Methods Programs Biomed. 107 (2) (2012) 164–174.
[17] R Pohle, K. Toennies, Segmentation of Medical Images Using Adaptive Region
Growing, SPIE, San Diego (USA) (2001) 1337–1346.
[18] F. López-Mir, V. Naranjo, J. Angulo, M. Alcaniz, L. Luna, Liver segmentation in
MRI: a fully automatic method based on stochastic partitions, Comput.
Methods Programs Biomed. 114 (1) (2014) 11–28.
[19] S. Osher, J.A. Sethian, Fronts propagating with curvature-dependent speed:
algorithms based on Hamilton–Jacobi formulation, J. Comput. Phys. 79 (1)
(1988) 12–49.
[20] B.B. Kimia, A. Tannenbaum, S.W. Zucker, Toward a computational theory of
shape: an overview. Computer Vision–ECCV 90. (Ed. O. Faugeras), Lect. Notes
Comput. Sci. 427 (1990) 402–407.
[21] R. Kimmel, Numerical Geometry of Images: Theory, Algorithms and Applica-
tions, Springer-Verlag New York, Inc, ISBN 0-387-95562-317–45.
[22] L He, Z Peng, B Everding, X Wang, C.Y Han, K.L Weiss, W.G. Wee, A
comparative study of deformable contour methods on medical image seg-
mentation, Image Vision Comput. 26 (2008) 141–163.
[23] L. Hadjiiski, H.P. Chan, M.E. Caoili, H.R. Cohan, J. Wei, C. Zhou, Auto-initialized
cascaded level set (AI-CALS) segmentation of bladder lesions on multidetector
row CT urography, Acad. Radiol., ISSN 1076-633220 (2) (2013) 148–155.
[24] P.H. Lim, U. Bagci, L. Bai, Introducing Willmore flow into level set segmenta-
tion of spinal vertebrae, IEEE Trans. Biomed. Eng. 60 (1) (2013) 115–122.
[25] N. Birkbeck, M. Sofka, T. Kohlberger, J. Zhang, J. Wetzl, J. Kaftan, S.K. Zhou,
Robust Segmentation of Challenging Lungs in CT Using Multi-stage Learning
and Level Set Optimization. Computational Intelligence in Biomedical Ima-
ging, Publisher: Springer, New York, ISBN 978-1-4614-7244-5185–208 (Book
Part II).
[26] L. Wang, C. Pan, Robust level set image segmentation via a local correntropy-
based K-means clustering, Pattern Recognit., ISSN 0031-320347 (5) (2014)
1917–1925.
[27] Q.Y. Zhao, X.H. Wang, X.F. Wang, Y.F. Shih, Retinal vessels segmentation based
on level set and region growing, Pattern Recognit., ISSN 0031-320347 (7)
(2014) 2437–2446.
[28] H.C. Kuo, M.L. Giger, I. Reiser, J.M. Boone, K.K. Lindfors, K. Yang, A. Edwards,
Level set segmentation of breast masses in contrast-enhanced dedicated
breast CT and evaluation of stopping criteria, J. Digit. Imaging 27 (2) (2014)
237–247.
[29] J. Gomes, O. Faugeras, Reconciling distance functions and level sets, J. Visual
Commun. Image Represent. 11 (2) (2000) 209–223.
[30] V. Casselles, R. Kimmel, G. Sapiro, Geodesic active contours, Int. J. Comput.
Vision 22 (1997) 61–79.
[31] S. Osher, R. Fedkiw, Level Set Methods and Dynamic Implicit Surfaces,
Springer Verlag, New York, 2002.
[32] C. Li, C. Xu, C. Gui, M.D. Fox, Distance regularized level set evolution and its
application to image segmentation, IEEE Trans. Image Process. 19 (12) (2010)
3243–3254.
[33] L. Vincent, Morphological grayscale reconstruction in image analysis: applica-
tions and efficient algorithms, IEEE Trans. Image Process 2 (2) (1993)
176–201.
[34] G. McLachlan, D. Peel, Finite Mixture Models, John Wiley & Sons, New York,
2000.
[35] C. Fraley, A.E. Raftery, Model-based clustering, discriminant analysis and
density estimation, J. Am. Stat. Assoc 97 (2002) 611–631.
[36] C. Li, C. Xu, C. Gui, M.D. Fox, Level set evolution without re-initialization: a
new variational formulation. in: Proc. IEEE Conf. Computer Vision and Pattern
Recognition, 1, 2005, 430–436.
[37] G. Sapiro, Geometric Partial Differential Equations and Image Analysis, Chp 2,
Cambridge University Press, Cambridge, UK, 2001.
[38] B. Liu, H.D. Cheng, J. Huang, J. Tian, X. Tang, J. Liu, Probability density
difference-based active contour for ultrasound image segmentation, Pattern
Recognit. 43 (6) (2010) 2028–2042.
[39] T. Chan, L. Vese, Active contours without edges, IEEE Trans. Image Process 10
(2) (2001) 266–277.
[40] E. Goceri, M.Z. Ünlü, C. Güzeliş, O. Dicle. A liver segmentation method based
on partial differential equation and signed pressure force function, in:
BIYOMUT: 17th National Biomedical Engineering Meeting Proceedings (IEEE
Biomedical Engineering), Turkey, 2012, 237-240.
[41] S.K. Weeratunga, C. Kamath, An Investigation of Implicit Active Contours for
Scientific Image Segmentation. San Jose, CA, USA, 2004 210-221.
[42] Y. Wang, S. Xiang, C. Pan, L. Wang, G. Meng, Level set evolution with locally
linear classification for image segmentation, Pattern Recognit., ISSN 0031-
320346 (6) (2013) 1734–1746.
278 E. Göçeri et al. / Computers in Biology and Medicine 53 (2014) 265–278
[43] K.N. Prakash, S. Zhou, T.C. Morgan, D.F. Hanley, W.L. Nowinski, Segmentation
and quantification of intra-ventricular/cerebral hemorrhage in CT scans by
modified distance regularized level set evolution technique, Int. J. Comput.
Assist. Radiol. Surg 7 (5) (2012) 785–798.
[44] F. Yang, W. Qin, Y. Xie, T. Wen, J. Gu, A shape-optimized framework for kidney
segmentation in ultrasound images using NLTV denoising and DRLSE, Biomed.
Eng. Online 11 (1) (2012) 82.
[45] R.S. Montero, E. Bribiesca, State of the art of compactness and circularity
measures, Int. Math. Forum 4 (27) (2009) 1305–1335.
[46] W. Chen, H. Zhuang, G. Cheng, D.A. Torigian, A. Alavi, Comparison of FDG-PET,
MRI and CT for post radiofrequency ablation evaluation of hepatic tumors,
Ann. Nucl. Med. 27 (2013) 58–64.
[47] J.H. Choi, K. Park, Y. Kim, Comparison of clinical utility between new and old
bleeding criteria: a prospective study of evaluation for the bleeding academic
research consortium definition of bleeding in patients with undergoing
percutaneous intervention, J. Am. Coll. Cardiol. (JACC), 61(10) (2013) 60142–-
60144. http://dx.doi.org/10.1016/S0735-1097(13).
[48] L. Biganzoli, L. Boni, D. Becheri, E. Zafarana, C. Biagioni, S. Cappadona,
E. Bianchini, C. Oakman, S.U. Magnolfi, D.A. Leo, G. Mottino, Evaluation of
the cardiovascular health study (CHS) instrument and the Vulnerable Elders
Survey-13 (VES-13) in elderly cancer patients. Are we still missing the right
screening tool?., Ann. Oncol. 24 (2013) 494–500.
[49] T. Bhowmick, S. Mirrett, L.B. Reller, C. Price, C. Qi, M.P. Weinstein, T.J. Kirn,
Controlled multicenter evaluation of a bacteriophage based method for the
rapid detection of Staphylococcus aureus in positive blood cultures, J. Clin.
Microbiol. (JCM. 02967-12) 51 (4) (2013) 1226–1230.
[50] J.J. Caban, A. Joshi, P. Nagy, Rapid development of medical imaging tools with
open-source libraries, J. Digit. Imaging 20 (2007) 83–93.