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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Segmentation and Landmark Localization Based on Multiple Atlases</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Orcun Goksel</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Tobias Gass</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Gabor Szekely</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Computer Vision Lab</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>ETH Zurich</string-name>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Switzerland</string-name>
        </contrib>
      </contrib-group>
      <fpage>37</fpage>
      <lpage>43</lpage>
      <abstract>
        <p>In this work, we present multi-atlas based techniques for both segmentation and landmark detection. We focus on modality and anatomy independent techniques to be applied to a wide range of input images, in contrast to methods customized to a specific anatomy or image modality. For segmentation, we use label propagation from several atlases to a target image via a Markov random field (MRF) based registration method, followed by label fusion by majority voting weighted by local cross-correlations. For landmark localization, we use a consensus based fusion of location estimates from several atlases identified by a template-matching approach. Results in IEEE ISBI 2014 VISCERAL challenge as well as VISCERAL Anatomy1 challenge are presented herein.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>Introduction</title>
    </sec>
    <sec id="sec-2">
      <title>Segmentation</title>
      <p>For segmentation, a multi-atlas based technique is used by registering several atlases individually
to a target image using our implementation of the MRF-based deformable registration method
in [GKT+08]. These registrations are then used to propagate the anatomical labels (ground-truth
annotations) from each atlas image into the target coordinate frame. At voxel level, a majority
voting is held to decide the winning label where each label votes based on the locally-normalized
cross-correlation (LNCC) [CBD+03] of the registered atlas to the given target at that location.
2.1</p>
      <sec id="sec-2-1">
        <title>Atlas-based segmentation using registration via MRF</title>
        <p>Finding an optimal displacement vector field Tˆ can be defined as the minimization of a functional:
Tˆ = arg min E (T, X, An)</p>
        <p>T
SX,n = SAn (Tˆ).</p>
      </sec>
      <sec id="sec-2-2">
        <title>Label fusion via weighted majority voting</title>
        <p>Although MRF-based registration is a relatively robust method, it can only guarantee a locally
optimal solution and is therefore susceptible to poor initialization. Furthermore, for a grossly different
atlas, correspondences for registration may not be guaranteed. Accordingly, the segmentation from
where X is a target image and An is an atlas image and E is the registration energy. MRFs provide
an efficient means for the minimization of such energy, with the main advantage being that it does
not rely on the gradient of the criterion and therefore is less prone to poor local optima. In order
to use MRFs for solving the minimization problem, this energy is decomposed into unary (ψ) and
pairwise (Ψ) potentials over discrete labels as follows:
(1)
(2)
(3)
E (T, X, An) = X
p∈Ω

ψp (lp) +</p>
        <p>X
q∈N (p)</p>
        <p>
λ Ψpq (lp, lq) ,
where Ω is the discretized image space. The continuous displacement space is sampled discretely,
so that each registration label lp and lq in the set of all registration labels LR maps to a unique
displacement vector d~p. The unary potentials are then a local similarity metric, measuring the fit
between the deformed atlas image and the target image at a location i. The pairwise potentials
correspond to prior assumptions over the displacement, which is often implemented as a smoothing
over the neighborhood N as justified by a first-order Markov assumption. λ is the pairwise weight.</p>
        <p>For robust and smooth solution of (2), an efficient method was proposed in [GKT+08] that seeks
the displacements d~ of control points in a multi-resolution cubic B-spline framework. We use our
implementation of this method with four levels of detail, where the coarsest grid resolution has
three nodes along the shortest edge of an input image and a spacing as isotropic as possible given
that a control-point is required on each corner of the image. Each following level of the resolution
hierarchy has twice the resolution compared to the previous step. At each level of detail, we sample
four displacements in each cardinal direction, yielding 25 displacement samples in total. Within
each direction, samples are equidistant, with the largest displacement set to 0.4 times the control
grid spacing. This was shown to guarantee diffeomorphic deformations [RAH+06]. For each level
of detail, we re-run the MRF registration with the displacements being re-scaled by the golden
ratio 0.618. The resulting displacements are then composed onto the previous deformation. This
guarantees that the result is still diffeomorphic and sub-pixel accuracy can be achieved. For the
unary potentials we use normalized cross correlation (NCC) of patches centered around each control
point with their radius equivalent to control grid spacing. Euclidean distance between displacements
of neighboring control grids is used to penalize non-smooth deformations. Tree-reweighted message
passing (TRW-S) [Kol06] is employed to find a solution to each energy minimization instance.</p>
        <p>A segmentation candidate of the target image X based on the atlas An is then obtained by
applying the resulting displacement field Tˆ to the known segmentation SAn as follows:
a single atlas may not be satisfactory. It was shown in different research fields that combination
of multiple weak information sources can surpass average accuracy. Multiple segmentations from
different atlases were combined in [HHA+06].</p>
        <p>Assume that N segmentation candidates of a target image X are computed from N atlases via
(3). Let final target segmentation SX be an image of the same size as X, where pixels take on values
from the set LS={1, . . . , NS} such that each discrete value corresponds to an organ or anatomical
structure. An intuitive and straight-forward method to combine multiple segmentation estimates
is then to choose the most frequent segmentation label (majority voting, MV) at each location p:
SXMV(p) = arg max X δ (lS, SX,n(p)) .</p>
        <p>lS∈LS n
Such majority voting does not take into account the individual quality of each registration and
therefore the resulting segmentation. We assume that post-registration image similarity between
the deformed atlas and the target image is an indicator of segmentation reliabilty and can be used
to locally assign weights w to each individual segmentation. The resulting weighted majority vote
(wMV) can then be formalized as follows:</p>
        <p>SXwMV(p) = arg max X wn(p) δ (lS, SX,n(p)) .</p>
        <p>lS∈LS n
To obtain the weights w, we use local normalized cross correlation (LNCC,[CBD+03]) between
image X and deformed atlas An(Tn). The advantages of LNCC are its smoothness and fast
computation time due to convolution with Gaussian kernels:</p>
        <p>LNCC(X, Y, p) =</p>
        <p>hX, Y i(p)
σX (p) σY (p)
X = GσG ∗ X
hX, Y i(p) = X · Y (p) − X(p) · Y (p)
σX2 (p) = X2(p) − X2(p),
where ∗ is the convolution operator and GσG is a Gaussian kernel with standard deviation σG . From
the LNCC metric, we compute the weights:
wn(p) =
1 − LNCCσ(X, An(Tn), p) γ
2
(4)
(5)
(6)
(7)
which normalizes LNCC to the range [0, 1]. γ is used to scale the similarity such that contributions
from individual segmentations are well spread [IK09].
3</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>Landmark Detection</title>
      <p>For anatomical landmark detection, we use a template based approach from multiple atlases, the
location estimates from which are fused based on their consensus. We localize each landmark ℓ
separately from the others using the two stages below. To localize the unknown voxel coordinates
pℓ of landmark ℓ in the target image X, we perform the following template matching procedure
from each atlas An where n represents the atlas index.
3.1</p>
      <sec id="sec-3-1">
        <title>Determining template and search regions</title>
        <p>The template is set as a box-shaped image region Aℓn in the current atlas. Similarly, a box-shaped
search region Xℓ is defined in the target image. Both such regions are chosen targeting a physically
isotropic region of interest (ROI) in corresponding image, while limiting the maximum number of
ROI voxels to ensure efficient computation. Specifics of ROI selection are given in Table 1.
pℓAn · ||AXn||</p>
        <p>When setting the template size, the trade-off between it containing sufficient image features and
final localization precision was considered. Template half-width was set to 20 mm empirically via
cross-validation in multiple modalities using different template sizes (e.g., 10, 20, 30, ...). The
search region is centered around a gross estimate of the landmark location, which is the normalized
voxel coordinates of the landmark from the atlas; using the fact that both the atlas and the target
have similar fields of view (ie. both abdomen, thorax, or whole body). Note that our large search
region covers most or all of the image in many modalities (e.g. in MRce) or at least a quadrant
thereof (e.g. in CT), such that the searched landmark can be guaranteed to exist therein.
For template matching, the template is convolved over the search region by computing two
independent similarity metrics, sum of squared differences (SSD) and normalized cross-correlation
(NCC), at each template location i with respect to search image. Both values are then normalized
linearly to [0, 1] such that they are both 1 at the best match location. A combined similarity metric
SSDa·CORb is then computed, where the parameters a=2 and b=3 were determined empirically via
cross-validation with several powers. The maximum of this combined metric gives the best match
location estimate pℓn for landmark ℓ considered atlas An.
3.3</p>
      </sec>
      <sec id="sec-3-2">
        <title>Statistical fusion of estimate location from atlases</title>
        <p>From cross-validation trials with different techniques such as the mean and weighted average of
location estimates, the median operator was determined to be the best method for fusing location
estimates. Accordingly, each axis coordinate of the the target landmark location is found as the
median value of those axes from atlas estimates. The entire process can be summarized as:
• Repeat for each atlas An :
→ Crop landmark template Aℓn centered at given landmark location pℓAn in atlas image An
→ Crop a large search region Xℓ centered around a grossly approximated location in X
→ Compute SSD Aℓn, Xℓ and COR Aℓn, Xℓ
→ pℓn = arg max SSD[i]2 · COR[i]3</p>
        <p>i
• pℓ = median pℓn | ∀n
4</p>
      </sec>
    </sec>
    <sec id="sec-4">
      <title>Results and Discussion</title>
      <p>Throughout the results, the following abbreviations are used for the image modalities: whole-body
CT images (CT), thorax+abdomen contrast-agent CT images (CTce), abdominal T1-weighted
contrast-agent MR images (MRce), and whole-body T1-weighted MR images (MR).</p>
      <p>We treated each modality separately. We used the training images from Anatomy1 benchmark as
atlases, ie. depending on the modality of the test image, six atlases for CTce and seven for CT, MR,
MRce. For convenience, we combined all organ segmentations for each atlas into a single multi-label
segmentation image, which was then deformed using the atlas-to-target registration Tˆ described in
Sec. 2.1. In Tab. 2, Dice overlap metric results regarding our segmentation approach reported by
VISCERAL for the test images can be seen both for the VISCERAL Anatomy1 benchmark and
the ISBI challenge.</p>
      <p>In order to compare our technique to other participants’ in the ISBI challenge, we computed an
average rank per organ per participant. For given test image, we assigned a rank to each method,
ie. {1,2,...,P } where P is the number of participants submitted a (non-blank) output for that test
image. In Fig. 1 the average of such ranks for all given test images is seen per anatomy. Our
submission was the only entrant that aimed to segment all images in all modalities and it achieved
competitive results for many organs as seen in the given figure. We did not plot ranks for the MR
modalities, since we were the only participant to submit such results.</p>
      <p>It is notable that the multi-atlas fusion has significantly lower segmentation accuracy for organs
which has low volume, e.g. urinary, gall bladder, and the adrenal glands. One possible explanation
is that such small structures are difficult to register using full-body images. Due to such
misalignments, overlap between multiple deformed atlas segmentations for such label can be small, resulting
in the weighted majority voting not selecting that label.
participant2
participant3
participant4
our Approach
participant1
participant2
participant3
participant4
our Approach
does not require any customisation to a specific modality or organ competed in all categories and
ranked satisfactorily compared to the results of other participants.
[CBD+03] Pascal Cachier, Eric Bardinet, Didier Dormont, Xavier Pennec, and Nicholas Ayache.</p>
      <p>Iconic feature based nonrigid registration: the PASHA algorithm. Computer Vision and
Image Understanding, 89(2-3):272–298, February 2003.
[GKT+08] Ben Glocker, Nikos Komodakis, Georgios Tziritas, Nassir Navab, and Nikos Paragios.</p>
      <p>Image Analysis, 12(6):731–741, December 2008. Medical
Dense image registration through MRFs and efficient linear programming.
[HHA+06] Rolf a Heckemann, Joseph V Hajnal, Paul Aljabar, Daniel Rueckert, and Alexander
Hammers. Automatic anatomical brain MRI segmentation combining label propagation
and decision fusion. NeuroImage, 33(1):115–26, October 2006.
[IK09]
[Kol06]</p>
    </sec>
  </body>
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