User-Guided Level Set Segmentation of

Anatomical Structures with ITK-SNAP

Paul Yushkevich1 , Joseph Piven2 , Heather Cody2 , Sean Ho3 , James C. Gee1 ,
and Guido Gerig4
1
Department of Radiology, University of Pennsylvania
2
Neurodevelopmental Disorders Research Center, University of North Carolina
3
Departments of Computing Science and Mathematics, Trinity Western University
4
Departments of Computer Science and Psychiatry, University of North Carolina

Abstract. Active contour segmentation and its robust implementation

using level sets have been studied thoroughly in the medical image analy-
sis literature. Despite the availability of these powerful methods, clinical
research still largely relies on manual slice-by-slice outlining for anatom-
ical structure segmentation. To bridge the gap between methodological
advances and clinical routine, we developed ITK-SNAP: an open source
application intended to make level set segmentation easily accessible to
a wide range of users with various levels of mathematical expertise. We
briefly describe this new tool and report the results of a validation study
in which ITK-SNAP was compared to manual segmentation of the cau-
date in the context of an ongoing child neuroimaging autism study.

1 Introduction

Medical image segmentation is used to address a wide range of biomedical re-

search problems: cancer detection, brain morphology, treatment planning, robot-
guided surgery, etc. The spectrum of segmentation techniques available to the
clinical researcher is broad, ranging from manual slice-by-slice outlining to fully
automatic techniques that incorporate prior knowledge about the shape and
intensity of the structures of interest. Amid this spectrum lie semiautomatic ap-
proaches that combine high efficiency, accuracy and repeatability of automatic
methods with expertise and quality control that can only come from human
supervision. Active contour segmentation via level set methods [2, 7] is an es-
pecially elegant segmentation technique that requires the expert to provide an
initialization, set control parameters, and terminate the segmentation.
Despite the advances in automatic segmentation methodology, many bio-
medical research labs continue to rely on manual delineation. This reluctance to
accept automation may be due to insufficient reliability and high specificity of
fully automatic methods and the lack of inexpensive user-friendly tools imple-
menting semi-automatic methods. To address this shortage, ITK-SNAP 5 was
5
ITK-SNAP source code can be obtained from www.itk.org, and stand-alone exe-
cutables are available at www.cognitica.com/snap.
developed, first as a series of student projects at UNC Chapel Hill, and later as
a component of the Insight Toolkit (ITK) [4].
ITK-SNAP is an open-source application intended to bring level set active
contour segmentation to the fingertips of clinical users. It was designed to make
segmentation and parameter selection as easy as possible for users without a
mathematical background. ITK-SNAP is more than just an implementation of a
given computational method: in addition to the automatic segmentation work-
flow, it contains innovative tools for manual outlining and quality control. In
recent years, a large number of 3D image processing toolboxes have been de-
veloped, both commercially (e.g., Analyze [6]) and in the public domain (e.g.,
Slicer [3]). These toolboxes tend to provide a broad range of algorithms rather
than focus specifically on segmentation. In contrast, ITK-SNAP was developed
specifically for segmenting anatomical structures and is considerably easier to
master than the above packages due to its tightly focused functionality.
This paper gives a brief overview of the methods used in ITK-SNAP, touches
on the key points of its user interface, and presents the results of validation exper-
iments performed in the context of an ongoing child neuroimaging autism study,
where the accuracy, repeatability and efficiency of ITK-SNAP segmentation of
the caudate are compared to manual segmentation using multiple raters.

2 Methods
ITK-SNAP implements the 3D geodesic active contour method developed by
Caselles et al. [1, 2] as well as the region competition method by Zhu and Yuille
[13]. Both can be formulated in terms of contour evolution:

Ct (t, u) = Finternal + Fexternal , (1)

where C(t, u) is the contour at time t parameterized by u and F are forces acting
on the contour in the normal direction. The internal force modulates evolution
based on the contour’s geometry, while the external force incorporates informa-
tion from the image being segmented. In the Caselles method, the external force
is computed from the gradient magnitude of the image intensity, while in the
Zhu and Yuille method it is based on voxel probability maps.
Caselles’s formulation is written as

Ct (t, u) = (αgI + βκgI + γ∇gI · N) N , (2)

where α, β, and γ are modulating weights, κ is the mean curvature of the contour,
N is the contour normal, and gI is a function that decreases monotonically with
the gradient magnitude of the image I:
 
k∇ (Gσ ∗ I) k 1
gI = fmap , fmap (x) = , (3)
max k∇ (Gσ ∗ I) k 1 + (x/ν)λ
where Gσ ∗ I denotes convolution with a Gaussian kernel, and ν, λ, and σ are
user-supplied parameters. The first term in (2) is an outwards-acting external
force, the second term is an internal force modulated by gI , and the third is
the external advection force, which can act inwards when a contour approaches
edges in the image, thus counterbalancing the outward gI -proportional forces.
In our implementation of the Zhu and Yuille method, the external force is
proportional to difference of probabilities Pobj = P (voxel ∈ object) and Pbg =
P (voxel ∈ background):

Ct (t, u) = [α(Pobj − Pbg ) + βκ] N . (4)

In ITK-SNAP, these probabilities are estimated using fuzzy one-sided and two-
sided thresholds. The Zhu and Yuille approach is more appropriate when the
structure of interest has a well-defined intensity range with respect to the im-
age background. In contrast, the Caselles method is well suited for structures
bounded by strong image intensity edges.
To implement contour evolution, ITK-SNAP uses the level set method [5, 8],
which ensures numerical stability. The contour is represented as a level set of a
function φ defined on the ambient space, and the relationship N = ∇φ/k∇φk is
used to write (2) and (4) as partial differential equations in φ. The equations are
solved iteratively using the extreme narrow banding method by Whitaker [10].

3 Software Design and User Interface

ITK-SNAP provides an interactive image viewing/labelling UI on top of which
a wizard-like automatic segmentation workflow is constructed. The image view-
ing UI (Fig. 1) emphasizes the three-dimensional nature of images by displaying
three orthogonal views that intersect at the position identified by the 3D cur-
sor. Within each view, the cursor can be repositioned in and out of the view
plane by dragging the mouse and rolling the mouse wheel. To perform manual
segmentation, the user marks up the image in either of the three views. Each
voxel in the image can be assigned a numerical label that corresponds to an
anatomical structure. Thus, the result of manual or automatic segmentation is
represented as an image rather than as a set of contours (partial labeling of vox-
els is not supported). The UI supports 3D rendering of the labeled structures,
and a cut-plane tool allows users to relabel segmentations directly in 3D.
The challenge in developing a user-friendly level set segmentation tool lies in
devising a simple way for the user to specify the values of various parameters
that affect segmentation (α, β, γ, λ, ν, σ, etc.). To assist the user in setting these
parameters, ITK-SNAP employs a structured wizard-like segmentation workflow
(Fig. 1) and live feedback/preview mechanisms. In the first step of the workflow,
the user chooses whether to base the segmentation on regions of uniform intensity
(Zhu and Yuille method) or on image edges (Caselles method). Then, the user
is presented with an interface, shown in Fig. 2, in which she must “convert” the
input image into an image that is bright in the regions where the snake should
expand, dark in the regions where it should stay put, and bright blue in the
regions where it should retract (only in the Zhu and Yuille case). As the user
changes the parameters, she is presented both with the graph of the function
Fig. 1. Left. ITK-SNAP user interface shows three orthogonal views of a volumetric
image, linked by a common cursor (light blue crosshairs). A fourth panel is used to view
the segmented structures in three dimensions. Right. The automatic segmentation
workflow is organized as a wizard, shown here in the initialization stage.

gI or Pobj (I), depending on the method, and the resulting image. ITK’s flexible
filter architecture allowed us to apply the preprocessing only to the subset of the
image that the user sees in the three slice views, making it possible to respond to
parameter changes in real time. In the workflow’s second step, the user initializes
the segmentation by placing one or more bubbles in the structures of interest
(Fig. 1). Previously computed segmentations can also be used for initialization.
In the third step, the user oversees the actual segmentation process using a
VCR-like UI. The user can choose between “easy” and “expert” interfaces for
adjusting the values of parameters α, β and γ. The easy interface gives textual
descriptions of the parameters’ meanings, while the expert interface shows the
formula relating the parameters. In both cases, the user sees a graphical 2-D
preview of each of the internal and external forces modulated by α, β and γ, as
well as their weighted sum (Fig. 2).

4 ITK-SNAP in Clinical Applications

The ITK-SNAP tool, with its combination of user-guided 3D active contour seg-
mentation, manual post-editing in 2-D orthogonal slices, and 3D cutting knife
capability, is increasingly replacing conventional 2-D slice editing for a variety
of image segmentation tasks. ITK-SNAP is used in several large neuroimaging
studies at UNC Chapel Hill, Duke University and University of Pennsylvania.
Segmentation either uses the fuzzy threshold option for the definition of object
and background probabilities, e.g. for the segmentation of the intracranial vol-
ume in head MRI, or makes use of existing tissue probability maps. This option
is used for the segmentation of ventricles based on a cerebrospinal fluid prob-
abilistic segmentations, or for the segmentation of caudate nucleus structures
using gray matter probability maps. Also, tests of hippocampus segmentation
Fig. 2. Live feedback in ITK-SNAP. Left. A fuzzy two-sided threshold is being used
to define object and background probability maps; the maps are displayed to the user
of the fly. Right. Parameter selection dialog for contour evolution. The effect of the
parameters on the forces acting on the contour is illustrated in a 2-D example.

from MRI driven by intensity edges are encouraging but not ready for use in
large-scale clinical studies. In thin-slice computer tomography imaging (CT) in
radiation oncology applications, ITK-SNAP proved to be useful to segment the
liver, kidneys, bony structures and tumors. ITK-SNAP has been used to segment
lung volumes in CT images and pulmonary vasculature in lung MR images. ITK-
SNAP is used alongside deformable registration in several applications, including
building a cortical atlas for template deformation morphology [11], automatic
mask generation for 3D reconstruction of a murine brain from histology slices
[12], and manual landmark definition. Other uses of ITK-SNAP include man-
ual post processing for automatic brain extraction tools and 3D smoothing of
slice-by-slice manual segmentations with large step-edge artifacts.

4.1 Improved Efficiency and Reliability for Caudate Segmentation

To validate ITK-SNAP against the standard of manual segmentation, we com-

pared the two approaches in the context of an ongoing child neuroimaging autism
study conducted in partnership with the UNC Chapel Hill Psychiatry Depart-
ment. Segmentation of the caudate from T1-weighted MRI was chosen as the
application for validation. The caudate is a gray matter structure that presents
challenges for segmentation because boundaries with the adjacent gray matter
structures (nucleus accumbens, putamen) are not visible in MRI (see Fig. 3).
The validation study was conducted on a set of 15 MR images acquired with
voxel size 0.782 × 1.5mm3 and resampled to have isotropic voxels of size 1mm3 .
Using the drawing tools in ITK-SNAP, we have developed a highly reliable
manually assisted caudate segmentation procedure using slice-by-slice boundary
drawing in all orthogonal orientations. Additionally to the boundary overlays,
the segmentation is supported by a 3D display of the segmented structure. Cou-
pled cursors between slices and 3D display provide additional help to significantly
reduce slice-by-slice jitter as often seen in this type of segmentations. The time
Fig. 3. The caudates viewed in 2-D and 3D: coronal MRI slice (left), overlay of seg-
mented structures (middle), and 3D view of the caudate and putamen relative to the
lateral ventricles (right). Right and left caudates are shown in green and red; left and
right putamen in yellow; and the outline of the nucleus accumbens is shown in red. Note
the lack of contrast at the boundary between the caudate and the nucleus accumbens,
and the fine-scale cell bridges between the caudate and the putamen.

for manual segmentation of the left and right caudate is approximately 1.5 hours
for experienced experts.
In the course of the autism study, we developed a new protocol for caudate
segmentation using the level set workflow in ITK-SNAP. The distributions of T1
intensity values in the caudate regions in infant MRI show significant differences
among subjects. In order to achieve optimal reliability, we estimate these distri-
butions by using ITK-SNAP to mark regions in four axial slices of the caudate
and compute the mean intensity and standard deviation in these regions. These
estimates are then used to set the upper and lower fuzzy thresholds that define
probability maps Pobj and Pbg . Parameters α and β, which determine the trade-
off between internal and external forces in contour evolution, were trained in a
pilot study and kept unchanged. The regions used to estimate intensity distribu-
tions were also used to initialize the contour. Contour evolution was terminated
manually once the contour started to bleed into the adjacent putamen.
In this protocol, optimal threshold selection and contour evolution require
only about 5 minutes for the left and right caudate combined. In some cases,
the expert may choose to apply a cut plane to correct the segmentation in 3D,
which only takes a few additional seconds. In our autism project, we decided
to add a precise a detailed separation from the putamen and a masking of the
left and right nucleus accumbens. This is a purely manual operation since there
are no visible boundaries between caudate and nucleus accumbens in MRI. This
step added another 30 minutes to the whole process. Still, the total segmentation
time was reduced from 1.5 hours for slice-by-slice contour drawing to 35 minutes,
with the option to be reduced to only 5 minutes if simple cut-planes for inferior
boundaries would be sufficient. The raters also reported that they felt much
more comfortable with ITK-SNAP since they could focus their effort on a small
part of the boundary that is most difficult to identify.
Table 1 reports intra-rater and inter-rater reliability scores for manual and
ITK-SNAP segmentations of the caudate nucleus. The reliability scores are com-
Table 1. Intra- and inter-rater reliability of caudate segmentation, measured by ana-
lyzing volumes of the segmented structures for 3 replications of 5 test datasets by two
raters. Reliability values for manual segmentation by two experts (top), manual con-
touring versus ITK-SNAP, and ITK-SNAP segmentation by two experts show excellent
reliability of both methods and excellent agreement between manual segmentation and
ITK-SNAP. However, training to establish reliability was several months for the man-
ual method and significantly shorter for ITK-SNAP. Also, ITK-SNAP reduced user
time from 1.5 hours to 35 minutes.

Validation type Side Intra A Intra B Inter AB

Intra/inter-rater Manual Left 0.963 0.845 0.916
(A Manual, B Manual) Right 0.970 0.954 0.967
Manual vs. ITK-SNAP Left 0.963 0.967 0.964
(A Manual, B SNAP) Right 0.970 0.969 0.969
Intra/inter-rater ITK-SNAP Left 0.967 0.958 0.958
(A ITK-SNAP, B ITK-SNAP) Right 0.969 0.990 0.961

puted as the intra-class correlation coefficients [9] of the volumes of the seg-
mented structures produced by different raters. The results show not only the
excellent reliability of ITK-SNAP segmentation but also reflects the excellent
reliability of the manual experts trained over several months. Therefore, reli-
ability between methods is not different. The ITK-SNAP segmentation, which
requires much less training and is significantly more efficient, is shown equivalent
to the manual expert, both with respect to intra-method reliability and inter-
method validity. However, this is to be compared with the significantly reduced
segmentation time and short rater training time of ITK-SNAP.

5 Conclusions

ITK-SNAP is an open source medical image processing application that fills

a specific set of biomedical research needs: it provides a combination of man-
ual and expert-controlled automatic tools for segmentation of structures in 3D
anatomical images of varying modalities and anatomical regions. To minimize
the amount of training needed to use the tool, the UI is focused on the specific
task of segmentation, parameter selection is simplified using live feedback, and
the “creep” of features unrelated to segmentation is carefully managed.
The validation study demonstrates excellent reliability of ITK-SNAP for ef-
ficient 3D segmentation. The tool competes with highly trained raters, which
explains the similar range of intra-method reliability. Besides efficiency, our ex-
perts preferred ITK-SNAP over slice contouring due to its capability to segment
directly in 3D and the simple option to postprocess the segmentation results.
Acknowledgements
The integration of the SNAP tool with ITK was performed by Cognitica Corpo-
ration under NIH/NLM PO 467-MZ-202446-1. The validation study is supported
by the NIH/NIBIB P01 EB002779, NIH Conte Center MH064065, and UNC
Neurodevelopmental Disorders Research Center, Developmental Neuroimaging
Core. The MRI images of infants and expert manual segmentations are funded by
NIH RO1 MH61696 and NIMH MH 64580 (PI: Joseph Piven). Manual segmen-
tations for the caudate study were made by Michael Graves and Todd Mathews,
with protocol development in collaboration with Cody Hazlett. Rachel Smith
and Michael Graves were the raters for the ITK-SNAP segmentations.
Many people have contributed to the development of ITK-SNAP and its pre-
decessors: Silvio Turello, Joachim Schlegel, Gabor Szekely (ETH Zurich, Original
AVS Module), Chris Wynn, Arun Neelamkavil, David Gregg, Eric Larsen, San-
jay Sthapit, Ashraf Farrag, Amy Henderson, Robin Munesato, Ming Yu, Nathan
Moon, Thorsten Scheuermann, Konstantin Bobkov, Nathan Talbert, Yongjik
Kim, Pierre Fillard (UNC Chapel Hill student projects, 1999-2003, supervised
by Guido Gerig), Daniel S. Fritsch and Stephen R. Aylward (ITK Integration,
2003-2004). Special thanks are extended to the members of the ITK community,
including Terry S. Yoo, James C. Gee, Joshua Cates, Luis Ibáñez, Julian and
Matthieu Jomier.

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