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IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 32, NO. 5, MAY 2013

Application of Radial Ray Based Segmentation


to Cervical Lymph Nodes in CT Images
Sebastian Steger*, Nazli Bozoglu, Arjan Kuijper, and Stefan Wesarg

AbstractThe 3D-segmentation of lymph nodes in computed


tomography images is required for staging and disease progression monitoring. Major challenges are shape and size variance, as
well as low contrast, image noise, and pathologies. In this paper,
radial ray based segmentation is applied to lymph nodes. From
a seed point, rays are cast into all directions and an optimization
technique determines a radius for each ray based on image appearance and shape knowledge. Lymph node specific appearance
cost functions are introduced and their optimal parameters are
determined. For the first time, the resulting segmentation accuracy
of different appearance cost functions and optimization strategies
is compared. Further contributions are extensions to reduce the
dependency on the seed point, to support a larger variety of
shapes, and to enable interaction. The best results are obtained
using graph-cut on a combination of the direction weighted image
gradient and accumulated intensities outside a predefined intensity
range. Evaluation on 100 lymph nodes shows that with an average
symmetric surface distance of 0.41 mm the segmentation accuracy
is close to manual segmentation and outperforms existing radial
ray and model based methods. The methods inter-observer-variability of 5.9% for volume assessment is lower than the 15.9%
obtained using manual segmentation.
Index TermsBelief propagation, computed tomography (CT),
graph cut, image segmentation, lymph nodes, radial rays.

I. INTRODUCTION

HE PRESENCE of regional lymph node (LN) metastasis


is the single most reliable prognostic factor for the progression of head&neck cancer [1]. Based on the size, shape and
texture of LNs in X-ray computed tomography (CT) or magnetic resonance imaging (MRI) scans or both, radiologists classify them as either benign or malign. This has many drawbacks.
The size is usually assessed in a single axial slice according to
the RECIST [2] criteria, which was shown in [3] to be inferior to
a 3D-assessment. Furthermore, most of the other properties are
qualitative only and therefore subject to a high inter-observer
variability. Computer aided diagnosis (CAD) may be able to improve this process. A prerequisite for such a CAD system is an

Manuscript received December 11, 2012; revised January 18, 2013; accepted
January 20, 2013. Date of publication January 25, 2013; date of current version
April 27, 2013. This work was supported within the NeoMark project (FP7ICT-2007-2-224483) by the European Commission. Asterisk indicates corresponding author.
*S. Steger is with Fraunhofer IGD, 64283 Darmstadt, Germany (e-mail:
sebastian.steger@igd.fraunhofer.de).
N. Bozoglu, A. Kuijper, and S. Wesarg are with Fraunhofer IGD, 64283
Darmstadt, Germany.
Color versions of one or more of the figures in this paper are available online
at http://ieeexplore.ieee.org.
Digital Object Identifier 10.1109/TMI.2013.2242901

Fig. 1. Radial ray based segmentation methods find a closed surface around a
seed point by assigning a radius to each radial ray.

accurate and robust segmentation of the region of interestthe


lymph nodein at least one imaging modality.
Since manual slice by slice delineation is very time consuming (up to 25 min for a single node [3]) and heavily
dependent on the operator, segmentation methods with the
least possible amount of user interaction are required. Over the
past years, several approaches with different amounts of user
interaction have been presented in the medical imaging literature. Many of them are equivalent to an energy minimization
problem, combining expected image characteristics with local
shape knowledge. Nevertheless, one key aspect has notoriously
been neglected: the cost function design including the selection
of optimal parameters.
The focus of this paper lies on the design of a cost function
specifically tailored to LN segmentation in CT images and the
selection of its parameters. The cost function is deployed in a
radial ray based 3D-segmentation framework: From a user defined seed point, rays are cast radially in all possible directions
and each ray is uniformly divided into bins. A segmentation
is expressed by assigning a bin index to each ray, resulting in
a closed surface around the seed point (see Fig. 1). Minimizing
a cost function consisting of 1) a data term depending on the
image and 2) a shape preserving term based on the bin assignment of neighboring rays eventually results in a segmentation.
We restrict our work to contrast-enhanced CT images because
of the smaller slice distance compared to MRI, the known intensities imposed by the Hounsfield scale, and because it is considered as the workhorse in head&neck imaging [4].
The segmentation of LNs imposes the following challenges,
which must be considered during cost function design.
The shape variability of LNs is high. Whereas benign LNs
are often somewhat elliptical or bean-shaped, enlarged
LNs tend to be more spherical. Other than those vague
statements, no further assumptions can be made.
The size of LNs varies considerably. The largest diameter
ranges between a few mm and 50 mm or even more.

0278-0062/$31.00 2013 IEEE

STEGER et al.: APPLICATION OF RADIAL RAY BASED SEGMENTATION TO CERVICAL LYMPH NODES IN CT IMAGES

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Fig. 2. Examples of LNs in CT images illustrating the challenges in LN segmentation. The gold standard segmentation is shown in green. (a) Typical healthy
bean shaped LN embedded in fat. (b) Enlarged LN with central necrotic tissue. (c) LN close to a bone in noisy CT image. (d) LN with surrounding tissue of similar
density.

On contrast-enhanced CT images, the interior of a benign


LN is usually homogeneous and the gray value range is
between 50 and 150 Hounsfield Units (HU). Exceptions
are LNs with central necrotic tissue, which are depicted
with lower intensities [see Fig. 2(b)].
The surrounding tissue is heterogeneous. Adjacent objects
can be of lower density such as fatty tissue, of similar density such as muscles, glands and other LNs, or of higher
density such as contrast enhanced vessels and bones. Thus,
without further context about the LN location, no assumptions about the exterior can be incorporated into the segmentation process.
For neighboring structures of similar density, the contrast
at the boundary becomes low and the image gradient
strength is low or even zero [see Fig. 2(d)].
Other neighboring structures may have different image intensities and the image gradient strength at their boundaries may be high. Nevertheless, those boundaries must not
distract the segmentation algorithm [see Fig. 2(c)].
Beyond designing a cost function addressing these points, this
paper comprehensively assesses the applicability of radial ray
based segmentation to LNs. After reviewing the LN segmentation state of the art in Section II, we present a significantly
large data set containing 100 cervical LNs along with a similarity index used for validation in Section III. In Section IV, we
then describe the radial ray based segmentation framework and
present different local and global optimization strategies for determining the surface. After that, we introduce image gradient
and image intensity based cost functions. Suitable parameters
are found by optimizing the similarity index on a training set of
LNs. Section V presents extensions to reduce the dependency on
the seed point, to support a larger variety of shapes, and to enable interaction. Evaluation is described in Section VI: Initially,
we justify the general suitability of radial ray based segmentation for LNs. Then, we compare the segmentation accuracy of
the different cost functions and optimization schemes and compare the accuracy of the final segmentation method to the state
of the art. Finally, we measure the robustness by assessing the
dependency on the seed point.
II. STATE-OF-THE-ART
The segmentation of LNs in different imaging modalities has
been subject to research for almost two decades and is still on-

going. A small part of the existing methods target MRI [5], [6]
and Ultrasound [7] images, but the majority targets 2D CT slices
or CT volumes.
In 1996, Rogowska et al. compared in [8] state-of-the-art
methods including automatic thresholding, snakes and the watershed transform for the segmentation of LNs in 2D-CT slices
concluding that advanced image segmentation techniques are
required.
One year later, Honea et al. [9] presented a snake based
method tailored to LN segmentation in CT slices. The authors
concluded that a 3D active contour may overcome the issues
resulting from the slice by slice approach and, later on, presented such a method [10]. An initially small spheric model
is manually placed inside the LN. Simulated annealing with a
bias towards the LN exterior is used to accept/reject modified
contour points based on the combination of shape and appearance energy. The latter is based on the image gradient strength
weighted by the gradient direction. Unfortunately, the method
was only evaluated on artificial data.
Yan et al. [11] use level sets for the slice by slice segmentation of LNs in CT images. The external energy depends on the
image gradient and boundary leaking is prevented by a manually placed sphere serving as hard stopping criteria.
Lu et al. presented in [12] an interactive slice by slice segmentation approach based on live-wires. Alternatively, points
on the contour guiding the live-wire can be detected automatically by casting radial rays from a seed point and selecting the
points with the largest image gradient magnitude for each ray.
The LN detection and segmentation method of Feulner et al.
[13] uses graph cut on a voxel grid for the segmentation part.
The graphs edge weights are computed from (joint) histograms
of the LN interior (boundary) extracted from manually annotated data. Further efforts are made to prefer spherical cuts.
Instead of local shape knowledge (e.g., smoothness), other
methods use an ellipse as global shape knowledge. Examples are
the joint segmentation and registration framework of Unal et al.
[5] for LNs in MRI slices and the method of Zhang et al. [7],
which uses an ellipse as a global shape prior in a graph-cut based
approach for the segmentation of LNs in ultrasound slices. In
both algorithms, a user defined rectangle serves as initialization.
Furthermore, Moltz et al. [14] use an ellipse extracted from a region growing result for setting markers of a watershed transform
in a multi-step 3D LN segmentation method working on CT

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images. A manually drawn stroke across the node specifies the


ROI that the algorithm is restricted to. The CT LN segmentation
method of Maleike et al. [15] is based on an elliptical geometric
deformable model. The deployed appearance model prefers spatial locations with typical LN interior intensities, different LN
exterior intensities, and a strong image gradient strength. Apart
from this semi-automatic approach, the paper also presents an
interactive adaptation framework.
Dornheim et al. presented in [16], [17] a stable spheric mass
spring model for the segmentation of LNs in CT scans. External forces push the model surface in its normal direction towards locations with large image gradients while inner masses
are pushed towards areas with typical LN intensities. Spring and
torsion forces between the masses preserve distances and angles
respectively. Initially, a model of predefined size is manually
placed inside the LN. A drawback of this method is the small
range of LN sizes being supported. To overcome this, we presented in [18] extensions to initially expand the model, to relate
to relative instead of absolute distances between masses, and
to apply torsion forces more balanced. Parallel to that, Dornheim et al. improved their method in a different way [19], [20]:
Models of different sizes are applied concurrently to same LN
and a quality of fit function [21] selects the best among them.
Besides those model based approaches, radial ray based segmentation has been used for LNs. The LN detection and segmentation method of Barbu et al. [22], [23] uses a radial ray
based segmentation technique. A gradient descent optimization
technique ensures that the surface points along the rays are as
close as possible to the first location leaving the LN intensity
range while at the same time radii of adjacent rays should be
as similar as possible. Wang et al. [24] find the optimal surface
around the seed point using graph-cut in order to segment LNs
in CT images. The appearance cost depends on gray value homogeneity in the interior, the distance to local maximum in discontinuity (edge term), and a size term rewarding radii with a
consistently large edge term for all rays. In [25], an interactive
segmentation refinement extension to this method is described.
For the 2D-segmentation of LNs in CT slices, we presented a
radial ray based method in [26]. Dynamic programming is used
to find an optimal path around a seed point based on the image
gradient magnitude at the boundary and expected CT intensities
in the interior.
To conclude, the biggest challenges in LN segmentation in
CT images are the large size and shape variance, the unknown
type of surrounding tissue, low contrast to neighboring structures, as well as the potential presence of necrotic tissue. To cope
with those challenges, real 3D methods are better suited than
slice-by-slice techniques. Very few methods exist that explicitly
support LNs with pathologies in form of central necrotic tissue,
although those LNs are of particular clinical importance. To
support different sizes, methods with a local adaptation scheme
require a good initialization, which often involves user interaction. Radial ray based segmentation with a global optimization scheme appears to be promising to cope with all of the
described challenges. Both cost functions and optimization algorithms differ throughout current worksall focusing on different image features. To obtain an optimal segmentation, cost
functions and optimization strategies need to be compared.

IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 32, NO. 5, MAY 2013

Fig. 3. Distribution of CT-intensities of LNs with and without necrosis including and excluding a 1-mm margin at the boundary.

III. MATERIALS
The data set used in this work was built from 25 clinically
acquired contrast enhanced head&neck CT-scans with a slice
thickness between 0.5 and 1.2 mm from 25 patients suffering
from oral cancer. A total of 100 lymph nodes was selected and
a gold standard segmentation was created for each of them. This
set is divided into two subsets (set 1 and set 2).
The 49 LNs in set 1 were selected from 13 of the 25 CT-scans
by an experienced radiologist. Five more radiologists independently delineated each LN in each CT slice. Based on that,
the STAPLE-algorithm [27] was used to create a consensus
segmentation which serves as the gold standard segmentation
for this set. In this set, the minor axis ranges between 5.2 and
32.5 mm with an average standard deviation of
whereas the major axis ranges between 9.2 and 47.6 mm with an
average standard deviation of
mm. Fig. 3 shows
CT-intensity histograms separately for LNs with and without
necrotic tissue. For non-necrotic LNs, 95% of all intensities in
the LN interior (1 mm minimum distance to the boundary) are
within an interval of 43 and 119 HU. The average is at 80 HU.
For set 2, a trained image analyst selected and manually delineated 51 LNs in the remaining 12 CT-scans. This manual segmentation serves as the gold standard for this set.
The algorithm design and most of the evaluation was carried
out solely on set 1 because 1) its gold standard is more reliable
and 2) during LN selection particular attention has been paid
to include cases reflecting the previously described challenges
(28.57% of the LNs contain central necrotic tissue, 10.2% show
very low contrast at the boundary and in another 10.2% of the
cases the CT images are very noisy). The purpose of set 2 is to
independently support the results achieved on set 1.
To compare two segmentations, we use a single quality index
[28], which is based on the voxel set based measures dice similarity coefficient (DSC) and volumetric overlap
error (VOE) as well as the surface distance based methods
average symmetric surface distance (ASD) and maximum symmetric surface distance (MSD). Whereas
indicates
perfect segmentation, a value of 75 corresponds to average
manual expert segmentation quality which has been computed
based on the five candidate segmentations for each LN in set 1
using leave-one-out cross-validation.

STEGER et al.: APPLICATION OF RADIAL RAY BASED SEGMENTATION TO CERVICAL LYMPH NODES IN CT IMAGES

Since set 1 is used for both training and evaluation, three-fold


cross-validation is carried out throughout this work. For this
purpose, the set is partitioned into three subsets with similar
properties. Each two subsets are combined to a training set.
Whenever in this paper parameters are determined based on
such a training set, evaluation is carried out on the subset not
used for the creation of the training set.
IV. RADIAL RAY BASED LYMPH NODE SEGMENTATION
From a user defined seed point , a radial ray based segmentation framework casts rays uniformly in all possible directions
so that they are uniformly distributed
on a surrounding sphere. Up to a maximal radius
each ray
is uniformly partitioned into
bins. A label is assigned to
each bin. A point
on a ray can be denoted by
and a closed surface around the seed point
can be denoted by a label vector
. Since this
representation relies on a straight connection between the seed
point and all points on the object surface without intersecting the
surface elsewhere, the supported class of shapes is restricted to
the star domain. As our experiments will show, this restriction
has hardly an impact for LN shapes.
To determine the configuration
that resembles the
boundary of a LN best, an energy
considering both image
appearance and object shape is assigned to each possible label
configuration . The segmentation problem is transformed into
an energy minimization problem:
. The
energy is of the form

(1)

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pearance term. The initial configuration is given by searching


for the minimum appearance cost for each ray independently

(3)
With a specific appearance cost function, this approach has been
pursued by Barbu et al. in their LN segmentation framework
[22]. Since GD is a local optimization strategy, it is prone to
being trapped in a local minimum around the initialization.
2) Belief-Propagation (BP): Since the energy given by (1)
depends on a unary term and pairwise connections between direct neighbors only, the energy minimization problem is suited
to be minimized by the belief-propagation algorithm [29]. Messages are iteratively passed from nodes to neighboring nodes,
thereby globally inferring the most likely assignment. Although
optimal solutions are not guaranteed for loopy graphs, it has empirically shown good results for loopy graphs [30] and has ever
since been successfully applied to inference problems in many
different application scenarios. In our case, we use the algorithm
to jointly infer the most likely label for each ray . Messages
are passed between neighboring rays. Like in the GD based algorithm, shape knowledge is incorporated by demanding similar
labels for neighboring rays using (2).
3) Graph-Cut (GC): Another optimization scheme that is
suitable to find an optimal closed surface around a seed point
is graph-cut. The approach was described in [31] for general
surfaces and later applied in a radial ray based segmentation
framework for the segmentation of LNs [24] and gliomas [32].
The underlying vertex weighted directed graph consists of
one vertex
for each node on each ray . The weights
of the vertices are given by differences of the appearance costs
(4)

where
assigns costs to a specific point based on the appearance in the image ,
is the set of all rays adjacent to
ray ,
assigns costs to the labels of an adjacent pair of rays
based on local shape knowledge (e.g., smoothness) and balances the appearance and shape terms.
A. Optimization Techniques and Shape Knowledge
1) Gradient Descent (GD): Demanding that neighboring
rays
have as similar labels as possible is commonly used to
incorporate shape knowledge into a radial ray based segmentation framework. This can be expressed by
(2)
where the parameter controls the stiffness. This shape cost
prefers spherical structures.
Minimizing (1) with a gradient descent optimization scheme
is simple and fast. Starting from an initial configuration , the
optimizer iterates into the direction given by the energy gradient
until convergence is reached. Whereas the partial derivatives of the shape term are determined analytically, finite differences are used to approximate the partial derivatives of the ap-

Intracolumn arcs connect the subsequent vertices


within each ray. Shape knowledge is incorporated by intercolumn arcs connecting the th vertex on ray with the
th
vertex of all neighboring rays
. The parameter defines
the maximum change of the label for adjacent rays, thereby
controlling the stiffness. Note that this type of shape prior does
not require an appearance term weight . Based on this graph,
the optimal surface is determined using a Min-Cut/Max-Flow
algorithm. Details can be found in [31].
B. Image Gradient and Image Intensity Based Cost Functions
Compared to the optimization strategy, the formulation of the
energy to be minimized has a larger impact on the segmentation accuracy [33]. Despite its importance, this aspect has notoriously been neglected for LN segmentation. All known LN
segmentation algorithms motivate different kinds of appearance
based cost functions, but spare a comparison to others. Moreover, the parameters are typically set rather ad-hoc. In this section we motivate and describe three different image gradient
based and three further cost functions depending on the intensities in the LN interior.

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IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 32, NO. 5, MAY 2013

Fig. 4. Original/filtered CT image showing a typical lymph node. (a) Original


CT image. LN is next to a contrast enhanced vessel (bright structure), soft tissue
of similar density (left) and fat (dark). (b) Image gradient magnitude. Boundaries of surrounding structures have significantly larger gradient magnitudes.
(c) Plateau filtered. LN tissue has the highest intensities. Gradient magnitudes
in relevant HU range are preserved.

The following observations about LN appearance in


head&neck CT images motivate the cost function design.
The neighboring objects boundaries may have a higher
gradient strength than the object boundary itself [see
Fig. 4(b)].
The gradient direction is in the normal direction of the object surface. The orientation can be inwards or outwards,
depending on the surrounding tissue.
The interior is homogeneous with the exception of central
necrotic tissue, which has lower intensities and is often
present in enlarged, malign lymph nodes.
The exterior is heterogeneous and unpredictable because
of the different surrounding tissue.
Whereas the image gradient based cost functions reflect the
former two points, the intensity based cost functions reflect the
latter two points. More generic cost functions, such as learning
gray value profiles using machine learning, are not feasible for
lymph nodes because of the unknown exterior and the large variation in size.
To correct a potential systematic bias of a cost functions minimum location compared to a gold standard segmentation, a correction parameter is introduced for each cost function. Such
a bias can, for example, stem from the partial volume effect.
moves a point along the radial ray given by and the seed
point
(5)
For the computation of the appearance cost at a specific point ,
the image is accessed at the corrected version instead of at
itself.
To ensure that all image gradients at the LN boundary have
the same orientation and that only gradients in a relevant gray
value range are considered, a plateau filter similar to the one
described in [19] is applied to the original image for all image
gradient based costs

otherwise

(6)
The interval
is set to
. It is centered
at the mean of typical LN intensities and generously includes

the entire LN intensity range. Now, LNs are the objects with the
highest image intensity and image gradients at their boundary
always point inwards [see Fig. 4(c)].
In the following, we will describe three image gradient and
three image intensity based cost functions suitable for the segmentation of LNs (Fig. 5).
1) Logarithmic Absolute Gradient Strength (LAG): The first
and simplest image gradient based cost function solely depends
on its magnitude
(7)
where
is the gradient operator, the convolution operator,
and
is a Gaussian kernel of the variance . The maximum
cost of
is chosen so that
is always
true. The logarithm ensures that strong gradients of surrounding
objects do not result in significant lower costs than weak gradients at the LN boundary.
2) Direction Weighted Gradient (DWG): Besides the magnitude, the direction of the image gradient has an impact on the
likelihood of a position belonging to the boundary. It always
points towards the interior of the LN. Gradients that are tangential to the LN boundary or even point outwards (e.g., the
transition from central necrotic tissue to LN tissue) do likely
not belong to the LN boundary and therefore will be rejected.
The cost function given by (7) is not able to consider this. Assuming somewhat spherical objects around the seed point, the
approximate inward direction is given by the radial ray and (7)
is extended

(8)
otherwise
is the image gradient and
is the direction of the radial ray. Since the direction of the surface normal is only approximately given by ,
the parameter is introduced to model this uncertainty as it has
already been done in [10].
3) Local Gradient Maxima (LGM): Despite the logarithmic
scaling, both image gradient based cost functions given by (7)
and (8) still assign lower costs to locations with a higher image
gradient magnitude although there is no justification for that. In
[24], an interesting solution to this is presented: Gradient costs
depend on the distance to the local image gradient maxima. At
those local maxima, the cost is independent from the gradient
magnitude. We adopt this idea and express the third image gradient based cost function by

where

(9)
contains all
where models a spatial uncertainty. The set
local maxima of the direction weighted image gradient along
the radial ray through
(10)

STEGER et al.: APPLICATION OF RADIAL RAY BASED SEGMENTATION TO CERVICAL LYMPH NODES IN CT IMAGES

893

Fig. 5. Different image gradient (the three on the left) and image intensity (the three on the right) based appearance costs for a specific lymph node. (a) Log. absolute gradient strength (LAG). (b) Direction weighted gradient (DWG). (c) Local gradient maxima (LGM). (d) Homogeneity (HOM). (e) Distance from estimated
boundary (DST). (f) Accumulated intensities (ACI).

where
is the radius of the th bin and
is the
weighted image gradient at the th point of the radial ray with
the direction
. The weights are set based on the direction
of the image gradient analogously to (8).
4) Homogeneity (HOM): All previously described cost
functions only depend on the discontinuity at the LN boundary.
Properties of the LN interior, however, are not considered.
One exploitable property is the gray value homogeneity in the
interior, as it has for example been done in [24]. We express the
homogeneity for the th point on a ray by

6) Accumulated Intensities (ACI): Using the distance to an


estimated boundary highly depends on the estimation accuracy.
Image noise, low contrast at the LN boundary, and inhomogeneities may, however, inhibit an accurate estimation based on
a known intensity interval. A cost function based on accumulated intensity differences to that intensity interval reduces the
dependency on the estimated boundary

(14)
otherwise

(11)
where
is the average intensity and
is a Gaussian kernel suppressing negligible inhomogeneities
possibly resulting from noise. Low costs are assigned to points
that show a homogeneous gray value profile between them and
the seed point. The logarithm ensures high granularity for small
inhomogeneities while, at the same time, covering a large range
of homogeneities. This cost function does not explicitly consider central necrotic tissue.
5) Distance From Estimated Boundary (DST): Alternatively, gray value intensities in the LN interior can be considered
based on the known absolute intensities on the Hounsfield scale.
Along the radial ray, we first search for the closest bin to
the center that does not fulfill a certain image intensity based
criterion
(12)
where is the index of the first bin whose intensity
is
within the interval
. In case of the presence of
central necrotic tissue around the seed point, corresponds to
the first bin outside the central necrotic and inside the regular
LN tissue. This property enables the support of central necrotic
tissue. The cost at a point on that ray depends on its distance to
the estimated boundary given by
(13)
This cost function is almost identical to the one presented in
[23]. The main difference is the determination of the estimated
boundary , where only the gray value difference to the intensity
at the seed point is considered.

Again, is the smallest bin index whose intensity is within the


given interval. This cost function prefers all points having
only typical LN intensities between the seed point and . Thus,
it is only suitable to rule out unlikely areas but it does not assign lower costs to LN boundaries compared to the interior. In
our 2D-LN-segmentation method [26] such a cost function has
successfully been used in combination with an image gradient
based cost function.
C. Parameter Estimation
The whole segmentation framework as well as all the presented cost functions depend on a set of parameters. Since they
have a significant impact on the segmentation result, their selection is of paramount importance. This section is dedicated to this
crucial, yet often neglected aspect. Table II gives an overview
of the parameters recommended for the use in a clinical setting
and their way of selection.
1) Cost Function Parameters: Some of the cost function
parameters can be selected based on prior knowledge: The
intensity interval
for DST and ACI is set to
for the different folds in order
to cover 95% of all intensities occurring in the LN interior (see
blue curve Fig. 3). For other parameters, denoted by the vector
consisting of the systematic bias , the amount of smoothing
, and the uncertainty of the surface normal if applicable,
such a knowledge based selection is not possible. Instead, we
exploit that a cost function should have a minimum at as many
locations of the LN boundary as possible. For a given gold
standard vector of radii
describing the desired radii of a LN
this can be expressed by a coefficient
(15)

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where is some tolerance and


contains the distance to the
seed point (radius) of all local minima of a cost function along
the ray in direction . The desired radius of a specific ray
is computed from the gold standard segmentation of a LN by
walking along the ray beginning at the seed point until the
boundary of the gold standard segmentation is reached. For a
specific set of LNs with corresponding seed points and gold
standard segmentations, the average coefficient
is expressed
as a function of the parameters
, which is maximized to
obtain the optimal parameters.
An exhaustive search suggests that the function actually depends on these parameters and is well behaved, i.e., has a distinct maximum and is convex. Thus, a local optimization technique can be used to find the optimal parameters . We use the
Nelders downhill simplex optimization technique [34] because
it does not depend on the gradient of the objective function. It
has been deployed for all three training sets (see Section III)
separately for all image gradient based cost functions. The tolerance was set to 0.5 mm and the start values were ad-hoc set
to
mm,
mm, and
.
Instead of locating the LN boundary exactly, the image intensity based cost functions have been designed to roughly globally
restrict the LN boundary. To find their optimal parameters, (15)
was altered to considering only the global minimum of the
cost function along a ray instead of the set of all local minima
. Furthermore, the tolerance was increased to
mm.
For all cost functions, the obtained parameters are consistent
for all training sets (6% deviation on the average). With the exception of the homogeneity cost ( between 2.16 and 2.20 mm),
very little smoothing is required ( between 0.08 and 0.26 mm
depending on the cost function). Positive values of between
0.21 and 0.87 mm throughout all cost functions and training
sets indicate that the gold standard LN boundary is systematically underestimated by the deployed image features.
2) Cost Function Selection and Framework Parameters:
Besides the parameters of the appearance cost function, other
parts of the segmentation framework have parameters as well.
Along with the selection of the appearance cost function, they,
too, have an impact on the segmentation results. These are
the number of rays , the number of bins for each ray , the
maximal possible radius
, the exponent of the shape cost
function , and the weight of appearance cost function . In
case a gradient based appearance cost function is combined
with an intensity based appearance cost function, an additional
weight is required. Again, some parameters can be chosen
based on prior knowledge. Assuming a reasonable maximum
LN size and knowledge about CT image resolution, we set
mm and
.
The selection of every other parameter cannot go back to prior
knowledge and thus, again, optimization based on a training
set is deployed. This time, the average obtained segmentation
quality of a certain training set compared to the gold standard segmentation is regarded as a function of the parameters
and to be maximized. We do this in a two step process.
Appearance Cost Function Selection: In a first step, the
focus is on the selection of the combination of image gradient
and image intensity based appearance cost functions resulting in
the best average segmentation quality . This is done separately

IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 32, NO. 5, MAY 2013

TABLE I
FOR ALL POSSIBLE
AVERAGE SEGMENTATION QUALITY
COMBINATION OF IMAGE GRADIENT AND IMAGE INTENSITY
BASED APPEARANCE COST FUNCTIONS

for all three methods (GD, BP, GC) reported in Section IV-A.
To reduce other influences, most parameters are kept constant
(
,
). The cost function combination is expressed
by
(16)
(or
for GC, which does not have the parameter
) is maximized using the downhill simplex optimizer for all
three training sets and for all nine possible combinations. Following the idea of cross-validation, the segmentation quality
has then been computed on the corresponding test sets. The resulting average segmentation quality is depicted in Table I. The
best result (
) is achieved when combining DWG with
ACI using GC, but also other combinations are suitable.
Overall Parameter Optimization: Based on the cost function selection of the previous step, we determine the optimal
parameters for the different segmentation techniques that have
previously been regarded as constants. This is again done by a
downhill simplex based optimization with
as the target
function for all three training sets and the three segmentation
methods. This time, the variable segmentation parameter vector
consists of the number of rays as well as the shape cost
parameters and for GD and BP or for GC, respectively.
A detailed analysis of the achieved segmentation quality can be
found in Section VI.
Since combining DWG with ACI using GC results in the
best segmentation accuracy, the whole parameter optimization
process was executed again for this configuration, this time on
the entire set 1, resulting in the final parameters recommended
in a clinical setting (see Table II).
V. EXTENSIONS
The presented method has the following undesired properties.
The segmentation result depends on the seed point and thus
on the operator.
The shape cost expressed by (2) is minimal for spheres.
LNs, however, are often not-that-spherical. A more suitable shape cost may increase segmentation accuracy.
Low image contrast, noise, and other effects may lead to a
segmentation not expected by the user. A convenient way
to interactively manipulate the result is desirable.
We now present three extensions to radial ray based segmentation to address these issues.

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TABLE II
OVERVIEW OF THE PARAMETERS OF THE RADIAL RAY BASED SEGMENTATION
FRAMEWORK RECOMMENDED FOR THE USE IN A CLINICAL SETTING AND
THEIR WAY OF SELECTION

Fig. 6. For a given point, the expected radius of a neighboring ray is defined
by the intersection of that ray with a plane through the point orthogonal to the
image gradient direction.

A. Seed Point Invariance (SPI)


The reason for the intra- and inter- observer variability is that
starting the algorithm from a different seed point generally results in a different segmentation. To reduce this dependency, we
propose the following.
1) Start the segmentation from the user-defined seed point.
2) Compute the centroid of the resulting segmentation.
3) Restart the segmentation process using the centroid.
Steps 2 and 3 are repeated until the distance between the centroids of subsequent iterations drops below a certain threshold.
The underlying assumptions are that a slight change in the seed
point results only in a slight change of the segmentation result
and that the centroid is well suited as a seed point for the radial
ray based segmentation method.
B. Image Gradient Based Shape Prior (IGSP)
Since LNs are often not-that-spherical, we modify the shape
prior described by (2) so that not spherical, but structures that
are present in the image result in low shape costs. Our extension
[35] depends on the image gradient direction and can be used in
the belief-propagation based segmentation approach. The key
observation is that the image gradient direction at a point on an
object surface is in normal direction of the surface. Assuming
smoothness, the surface can locally be approximated by a plane
orthogonal to the image gradient direction (see Fig. 6). Let
be the surface point on ray . Then, the expected radius
of an adjacent ray
is given by the intersection of the plane
through

otherwise

(17)

is the smoothed image grawhere


dient vector at location and
is a constant expressing
the minimum meaningful gradient magnitude. Equation (2) then
becomes
(18)

Fig. 7. The interactive extension allows the user to correct the boundary.

For image gradient magnitudes smaller than


, this is equivalent to the traditional sphere shape prior. All additional parameters have again been determined by maximizing
as
described earlier.
C. Interactive Segmentation (IS)
To optionally include hints about the LN boundary from an
expert in the segmentation process, our interactive approach
[36] is used as a further extension to the iterative belief-propagation based approach. The process is illustrated in Fig. 7. First,
the user clicks a seed point in the approximate center of the LN
as usual. Then, preliminary segmentation results of the currently
most likely object boundary are shown in a live preview. The
user inspects the boundary and may give hints about the desired
boundary location by clicking on the boundary in axial, coronal,
and sagittal plane simultaneously. The user stops the segmentation process as soon as he or she is satisfied with the result.
The live preview of the segmentation result is accomplished
by extracting the most likely configuration after each iteration of
message passing in the belief-propagation algorithm. The hints
are incorporated by modifying the appearance cost
of the
ray closest to the provided desired contour point
otherwise

(19)

This changes the messages in all subsequent BP iterations and


thus a contour through those predefined points is preferred.
VI. EVALUATION
Most of the experiments reported in this section were carried out on set 1 described in Section III consisting of 49 LNs
in total. Set 2 consisting of further 51 LNs was only used for

896

Fig. 8. Min, 0.25-quant, median, 0.75-quant and max of the segmentation


quality for different approaches and different types of LNs.

an independent verification and for the comparison to other approaches. The centroid of the gold standard segmentation was
used as the seed point if not stated otherwise.
A. Segmentation Accuracy
1) Theoretical Limit: The supported set of shapes of any radial ray based segmentation technique is theoretically limited to
all objects for which each point within the object can be directly
connected to the seed point without intersecting the object surface. This includes all convex shapes, but also all star convex
shapes if the seed point is within the set of points with direct
connection to the entire object surface.
The applicability of radial ray based segmentation to LNs
is assessed in our first experiment. The best possible segmentation is created by removing all voxels from the gold standard segmentation that cannot be connected to the seed point
without intersecting the LN surface. This segmentation is then
compared to the original gold standard segmentation. Typically,
only very few voxels close to the LN boundary do not satisfy
the required condition and the achieved average segmentation
quality is
. Further statistics are depicted in
Fig. 8. Only for one single outlier, a significant part of the object cannot be represented by any radial ray based method with
the seed point in the centroid (
). Fortunately, moving
the seed point is able to recover this bad result and the resulting
segmentation quality for this LN becomes
.
To conclude, the LN shape is very unlikely to be the bottleneck of a radial ray based segmentation technique.
2) Optimization Approaches: The radial ray based segmentation methods with the different optimization techniques, along
with the corresponding kind of shape knowledge and the most
suitable cost function combination with the final parameters
depicted in Table II have been applied to the test sets. Then,
the similarity/error measures described in Section III have been
used to compare the segmentation results to the gold standard.
Results are summarized in Table III. Statistics about the segmentation quality for different types of LNs are shown in Fig. 8.
The examples for different types of LNs shown in Fig. 9 have
been selected based on the achieved segmentation quality of the
GC based approach (minimum, 0.25-quant, median, 0.75-quant,
maximum).

IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 32, NO. 5, MAY 2013

The GC based approach slightly outperforms the BP based


approach. Still, both global approaches perform better than the
local GD based approach. In general, the results for LNs with
central necrotic tissue are similar to those without necroses.
Heavy noise only slightly affects the segmentation performance.
LNs with a low contrast at the boundary achieve the worst segmentation quality. This result is not surprising because for those
LNs even human experts can only guess the boundary location.
Then we assessed the impact of the shape on the segmentation
quality of the best, the GC based, approach. The aspect ratio of
the major and minor axis discriminates roundish from elongated
LNs and thus is used as an indicator for different LN shapes.
Fig. 10 shows the dependency of the segmentation quality on
this property on our test sets. Different shapes do not affect the
segmentation quality significantly.
3) Extensions: For the three extensions, the segmentation
accuracy has been assessed in the same way as described earlier
and the results are also presented in Table III and partly in Fig. 8.
The design goal of the seed point invariant (SPI) extension
was to increase robustness, which is evaluated later in this section. Unfortunately, the SPI extension results in a slight decrease
in average segmentation quality of roughly 3%. This decrease,
however, is only attributed to the 25% of the LNs with the lowest
segmentation quality. The reason for this is that the seed point
has already been placed at the best possible positionthe centroid. For difficult cases, the segmentation algorithm may overor undersegment the target and thus SPI results in a drift of the
seed point away from the centroid. This explains the segmentation quality loss of the SPI extension. Using a different initial
seed point, SPI results in a segmentation gain (see Fig. 12).
As intended, the image gradient based shape prior (IGSP)
is slightly more suitable than the traditional sphere shape prior
in the BP based setup (roughly 1% increase in segmentation
quality), but the achieved results are still worse than those of the
GC based approach. A segmentation quality gain compared to
the baseline approach is primarily achieved for LNs with large
aspect ratios, confirming our design goal to better cope with
not-that-spherical objects.
One of us (S.S.) used the BP based approach with the interactive extension (IS) to segment the 49 LNs with as little user
interaction as required. A significant increase in segmentation
quality was the result (9% and 5% gain compared to the semiautomatic BP and GC, respectively). As shown in Fig. 8, the gain
was particularily large for LNs with a low contrast boundary,
which previously resulted in bad segmentations. This gain in
segmentation quality comes at the expense of increased interaction time. In 39% of the cases no interaction at all was required,
in all other cases 2.13 hints were given on average. The average
duration of the segmentation of a single LN was 12.1 s, ranging
between 1.88 and 35.5 s. Only correcting obviously false segmentations combined with the consistent segmentation from the
trained algorithm enables the BP-IS to even outperform manual
segmentation.
4) Comparison to Other Approaches: To compare the segmentation results of our methods with the state of the art, we implemented the radial ray based segmentation methods of Wang
et al. [24] and Barbu et al. [23] and applied them to both sets.
Furthermore, we applied our modification [18] (MSM) of the

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AVERAGE

897

TABLE III
STANDARD DEVIATION OF THE SEGMENTATION QUALITY FOR DIFFERENT SEGMENTATION TECHNIQUES MEASURED ON 49 LNS

Fig. 9. Example results of the GD (yellow), BP (blue), and GC (red) based segmentation method, respectively, compared to gold standard (green) for different
types of LNs. Selection on the examples is based on the segmentation qualities of the GC approach.

mass spring model based LN segmentation method of Dornheim et al. [17], [20] to the sets to compare the method to a
different segmentation algorithm class. See Section II for a brief
description of those algorithms. The parameters given in the respective papers were used. The results depicted in Table III and
Fig. 11 show that the proposed methods outperform the state of
the art. While the approach of Wang et al. achieves good results
in most cases and especially for small rather spherical LNs, it is
not able to cope well with low contrast images and the enlarged
necrotic cases. The approach of Barbu et al. uses a very simple
cost function and has a very low complexity. The segmentation accuracy remains moderate. Our results suggest that radial
ray based segmentation using a global optimization technique
such as GC is more suitable than model based segmentation for
LNs. Although efforts have been made in [18] to reduce its size

dependency, the results of the MSM still highly depend on the


proper initialization of the model. On the other hand, for LNs
with low contrast at the boundary, the model based approach
does not produce considerably worse results than for other LNs.
5) Additional Test Set: Overfitting to a particular dataset
is a common pitfall for all data driven approaches such as the
parameter optimization strategy described in this paper. To
prevent this, three-fold cross-validation was carried out on the
set consisting of 49 LNs. This, however, reduces the effective
number of training instances and therefore the statistical validity. To independently assess the segmentation accuracy, we
first obtained parameters for GC-based approach using the parameter optimization strategy described in this paper. Then, we
applied this method and the state of the art methods described
in the previous section to the independent set 2 consisting of

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IEEE TRANSACTIONS ON MEDICAL IMAGING, VOL. 32, NO. 5, MAY 2013

TABLE IV
COMPARISON OF THE PROPOSED GC BASED METHOD TO THE
STATE-OF-THE-ART ON AN INDEPENDENT SET OF 51 LNS

B. Seed Point Dependency


Fig. 10. Segmentation quality of the GC based segmentation approach depending on the shape (aspect ratio) of the LN for different types of LNs.

Fig. 11. Comparison of the proposed GC based method to the state of the art
for different types of LNs.

Fig. 12. Average and standard deviation of the mean segmenation quality and
relative volume deviations for different relative distances of the seed point to
the LN centroid using a logarithmic scale. Up to a distance of 25% the proposed
method (GC-SPI) is more robust than manual segmentation.

51 LNs. The results can be found in Table IV and statistics


about the segmentation quality are included in Fig. 11. For all
methods, the segmentation accuracy is consistently slightly
better on this second set. This indicates that overfitting has not
occurred during the parameter optimization process. Averaging
the segmentation accuracy from set 1 and set 2 results in
average DSC/VOE/ASD/MSD of 0.82/29.91%/0.41 mm/3.04
mm for all 100 LNs using the GC based approach.

Besides a reduction in image evaluation time by a radiologist, another advantage of automatic segmentation approaches
is its high robustness, i.e., the same input data always results
in the same segmentation result. This enables tracking object
properties (e.g., the volume) over time with high validity. The
methods presented in this work, however, are semi-automatic
because the seed point has to be set manually. For a fair comparison of all methods, all experiments have been conducted
with the seed point in the centroid of the gold standard segmentation up to now. In this section, we aim to assess the dependency of segmentation quality and robustness on the seed
point for the GC based method (baseline) and the seed point invariant extended GC based method (GC-SPI). To this end, we
used 66 equally distributed seed points with different relative
distances to the centroid for all 49 LNs. This relative distances
were 5%, 10%, 25%, 50%, 75%, and 100% of the LNs minor
axis. For a specific relative distance and LN, the segmentation
algorithm was applied for all 66 seed points and the segmentation quality was measured. The average of those values is an
indicator for the quality whereas the standard deviation is related to the robustness.
Up to a relative distance of 25% from the seed point to the
LN centroid, the segmentation quality is hardly affected for both
the GC (
) and the GC-SPI (
) approach. However, the
robustness decreases a lot faster for the former approach. For
GC-SPI, the median of the relative standard deviation of 0.56%,
0.55%, and 0.93% for 5%, 10%, and 25% distance from the centroid, respectively, stays below 1%. For the baseline approch
(GC), these values are 1.03%, 2.27%, and 5.54%. Larger relative distances result in bad results, both in terms of segmentation
quality and robustness. Nonetheless, GC-SPI performs significantly better (in the median case
,
, and
for
50%, 75%, and 100% distance from the centroid, respectively).
To measure the relevance for practical use, we asked a radiologist to click in the approximate center of each LN and then
measured the distance to the LN centroid. The obtained average
relative distance of 21.6% and a median of 15.7% stays well
below the soft 25% limit and indicates that the GC-SPI is ready
for clinical use.
A key application scenario is tracking of LN properties over
time. For this scenario with the volume as the LN property, we
now compare our semi-automatic approach with manual segmentation in terms of segmentation accuracy and robustness.
The relative standard deviation from all 66 segmentations, we
obtained for different relative distances for each LN, were computed. The same was done for the five manual segmentations
available for each LN. We set those values in relation with the

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TABLE V
RUNTIME PERFORMANCE OF THE DIFFERENT OPTIMIZATION STRATEGIES.
ALL DURATIONS ARE REPORTED IN SECONDS

segmentation accuracies reported earlier. Fig. 12 shows the average and the standard deviation of those values for the different
relative distances and for the manual segmentations.
Up to a relative distance of 25%, the segmentation quality of
both approaches is close to manual segmentation, but the robustness is significantly higher. Assuming that different observers
set the seed point within a 25% radius relative to the minor
axis, the GC-SPI achieves a volume inter-observer variability
of 5.9% on the average. For 10% relative distance, this value
decreases to 3.0%. Both values are considerably lower than the
15.9% achieved by the human experts.
C. Runtime Performance
To give a rough impression of the runtime, we measured the
duration of the segmentation process for our implementations
of the different optimization techniques. All experiments have
been conducted on an Intel Core i72600K processor with 3.40
GHz and eight cores. Belief-propagation was implemented optionally using multiple threads (BP-MT) and the implementation of Boykov et al. [37] of graph-cut was used. The results are
depicted in Table V.
As expected, the local GD based technique is a lot faster than
the global optimization techniques. Nonetheless, the global optimization techniques are able to terminate within very few seconds. Exploiting parallelism ensures that the BP based method
achieves a runtime similar to the GC based method.
VII. CONCLUSION
In this paper, we apply radial ray based segmentation to cervical LNs in CT images, thereby coping with high variance of
size, shape, and surrounding tissue, as well as low contrast on
the object boundary, heavy image noise, and central necrotic
tissue inside the LN. From a user-defined seed point, radial
rays are cast uniformly in all directions and an optimization
strategy is used to find the best radius for each ray, considering image appearance and local shape knowledge. A local
GD optimizer has been compared with the global BP and GC
based algorithms along with suitable shape knowledge. Different image gradient and image intensity based image appearance cost function have been motivated and described, their
optimal parameters have been determined by maximizing the
amount of gold standard surface being close to a cost functions
minimum, and finally their combinations have been compared.
Furthermore, we have presented extensions to increase the robustness, to better cope with not-that-spherical shapes, and to
enable interactive corrections.
Evaluation in terms of segmentation accuracy, seed point dependency, and runtime performance has been conducted on a
set of 49 LNs of different sizes and shapes, containing normal,

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noisy, low contrast, and necrotic LNs. Three-fold cross-validation and evaluation on an additional set of another 51 LNs has
ensured the validity.
The main results of this work are as follows.
1) Radial ray based segmentation supports virtually all occurring LN shapes.
2) The image based cost function and its parameters have a
large impact on the segmentation quality.
3) GC achieves the best results working on a combination
of the direction weighted image gradient and accumulated
intensities outside a predefined interval as the appearance
cost function.
4) The average segmentation accuracy (dice coefficient: 0.82,
average symmetric surface distance: 0.41 mm) is close to
manual segmentation and considerably higher than state of
the art radial ray based and model based LN segmentation
techniques.
5) Noisy images and especially surrounding tissue of similar
density result in a segmentation accuracy penalty.
6) The interactive correction enables a user to modify inaccurate segmentations, resulting in a higher segmentation
accuracy than manual segmentation while only requiring
an average interaction time of 12.1 s.
7) The typical variation of manually selected seed points does
not affect the segmentation accuracy.
8) Automatically iteratively adapting the seed point increases
the robustness by a factor of about 5.
9) Assessing the volume of LNs using the proposed method
instead of manual segmentation decreases the average
inter-observer variability from 15.9% to less than 5.9%.
10) Our algorithm usually terminates within 5 s.
We argue that the presented radial ray based segmentation techniques are mature enough to be used in clinical practice.
Future work includes the improvement of the segmentation
quality for LNs surrounded by tissue with similar density. Combining the radial ray based technique with model based segmentation is a promising direction. Furthermore, it will be applied
to LNs in other areas of the body and other imaging modalities
like MRI, as well as to other somewhat spherical objects such
as different types of tumors.
ACKNOWLEDGMENT
The authors like to thank Dr. G. Chiari and his colleagues
from the Department of Clinical Sciences, Section of Radiology,
Parma University Hospital, Italy, as well as Dr. I. Rodriguez
Jimenez and her colleagues from the Radio-Diagnosis Department, Centro Oncologico MD Anderson International Spain for
providing the test images, selecting the lymph nodes and, most
importantly, creating the manual segmentations.
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