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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Model-Based Quanti cation of Small Tubular Structures in 3D Vascular Images</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Stefan Wo¨rz</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Hendrik von Tengg-Kobligk</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Karl Rohr</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Dept. Bioinformatics and Functional Genomics, Biomedical Computer Vision Group, University of Heidelberg</institution>
          ,
          <addr-line>BIOQUANT, IPMB, and DKFZ Heidelberg</addr-line>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Dept. Diagnostic and Interventional Radiology, University of Heidelberg</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>Dept. Radiology, German Cancer Research Center (DKFZ) Heidelberg</institution>
        </aff>
      </contrib-group>
      <fpage>23</fpage>
      <lpage>27</lpage>
      <abstract>
        <p>We introduce a new 3D tubular intensity model in conjunction with a model fitting scheme for accurate segmentation and quantification of small tubular structures in 3D vascular images. The tubular model is formulated based on principles of the image formation process. Compared to previous straight models, the new model allows to accurately represent curved tubular structures, to directly estimate the local curvature, as well as to more accurately estimate the parameters of tubular structures. We have successfully applied our approach to 3D synthetic images and 3D CTA vascular images.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>Introduction</title>
      <p>In modern radiology, different angiographic imaging modalities such as CTA and
MRA are used to visualize the human vascular system. Accurate quantification
of human vessels is important in different applications (e.g., diagnosis of
pathologies). In addition to quantifying the contrast, radius, and centerline of vessels, a
number of applications (e.g., analysis of tumor vasculature) require to quantify
a vessel’s tortuosity, which is related to the (local) curvature of the centerline.</p>
      <p>
        In previous work on 3D vessel segmentation, different types of approaches
have been proposed, for example, approaches based on differential measures
(e.g., [
        <xref ref-type="bibr" rid="ref1 ref2">1, 2</xref>
        ]) and approaches based on deformable models (e.g., [
        <xref ref-type="bibr" rid="ref3 ref4">3, 4</xref>
        ]). While
being computationally efficient, a disadvantage of differential measures is their
sensitivity to noise. On the other hand, approaches based on deformable models
generally exploit contour information of anatomical structures. Alternatively,
deformable models using 3D parametric intensity models have been suggested
(e.g., [
        <xref ref-type="bibr" rid="ref5 ref6">5, 6</xref>
        ]). Parametric intensity models describe the image intensities of a
structure within a region-of-interest (ROI), and are generally defined by an
analytic function comprising a certain number of parameters. So far, different types
of tubular models have been proposed (e.g., [
        <xref ref-type="bibr" rid="ref5 ref6">5, 6</xref>
        ]). However, these approaches
utilize straight tubular models, i.e., the curvature of vessels is not explicitly
modeled.
      </p>
      <p>
        In this contribution, we introduce a new curved tubular intensity model in
conjunction with a model fitting scheme for accurate segmentation and
quantification of small vessels in 3D tomographic images. The model comprises
parameters for the local contrast, width, 3D position, and 3D orientation. Moreover, the
model includes a parameter for the local (extrinsic) curvature, which describes
the local radius of curvature of a tubular structure. In contrast to previous
intensity-based approaches, which utilize straight tubular models [
        <xref ref-type="bibr" rid="ref5 ref6">5, 6</xref>
        ], a curved
tubular model has three major advantages. First, using a curved model we can
more accurately represent the intensity profile of curved structures, thus the
model is more realistic for medical applications. Second, based on our model we
can directly estimate the local curvature of tubular structures by model fitting.
And third, using a curved model instead of a straight model also improves the
accuracy of estimating the remaining model parameters such as the radius and
centerline of the tube. In comparison to our approach, in previous work often
the local curvature is not computed at all [
        <xref ref-type="bibr" rid="ref5 ref6">5, 6</xref>
        ], or the curvature is computed in
a subsequent step based on the estimated centerline.
2
      </p>
    </sec>
    <sec id="sec-2">
      <title>Methods</title>
      <p>For our 3D intensity model of small tubular structures, we assume a physical
image formation process where the intensity structures are generated by blurring
of ideal step-shaped structures. For thin structures with sizes below image
resolution, the unsmoothed structures can be represented by Dirac delta functions
. The central idea of our new model is to model the unsmoothed structure by a
Dirac ring. By Gaussian smoothing of the Dirac ring we obtain a Gaussian ring.
A 3D ROI of the Gaussian ring represents a thin curved tubular structure, where
the radius of the ring determines the radius of curvature R . The curvature is
given by = R 1. More formally, we define a Dirac ring as a series of shifted 3D
Dirac delta functions along a circle of radius R in the xz -plane. The center of
the ring (center of curvature) is located at x = (R ; 0; 0). Using the Gaussian
function G (x) = (p2 ) 1 exp( x2=(2 2)), the Gaussian ring is obtained by
a 3D convolution
gGR(x; R ; ) = (G (x) G (y) G (z))
Ring(x; R )
We have derived an analytic solution of the multiple integral in (1)
gGR(x) = j</p>
      <p>p
R j 2 e
(x R )2+y2+z2+R2
2 2</p>
      <p>I0
( R
2
√(x</p>
      <p>R )2 + z2
)
(1)
(2)
where I0 is a modified Bessel function of the first kind. Including the intensity
levels a0 and a1 as well as a 3D rigid transform R with rotation parameters
= ( ; ; ) and translation parameters x0 = (x0; y0; z0), we obtain the final
parametric intensity model gM; GR(x; p) = a0 + (a1 a0) gGR(R(x; ; x0)) with
a total of 10 parameters.</p>
      <p>If we analyze (2) in detail, it turns out that the Bessel function I0 grows
exponentially with increasing argument whereas the exponential function exp
decays exponentially (approaching zero). In the continuous formula (2), these
effects cancel out each other in the product, yielding an overall moderate value.
However, numerically computing the values of exp and I0 separately can lead to
numerical instabilities because of computational over- or underflows. To avoid
these over- and underflows we use an approximation of I0 for larger arguments,
which is based on an exponential function.</p>
      <p>To segment a vessel, we apply an incremental approach. For each segment
along a vessel, we use a model fitting approach based on least-squares fitting of
the 3D curved tubular model gM; GR to the image intensities g(x) within a
spherical 3D ROI. For minimization we apply the method of Levenberg-Marquardt.
As fitting result we obtain estimates of the model parameters p. Based on the
estimated position x0, orientation , and curvature , we can directly compute the
center of curvature x . Initial parameters for the fitting process are determined
from the estimated parameters of the previous segment using a Kalman filter,
i.e., the incremental scheme adjusts for varying thickness, changing direction,
and changing curvature.
3</p>
    </sec>
    <sec id="sec-3">
      <title>Experimental Results</title>
      <p>We have applied our new approach to 3D synthetic images as well as 3D CTA
image data. For the synthetic experiments, we have used 3D images
containing different curved tubular structures such as tori and spirals with a range of
different parameter settings. For example, we have generated 3D spirals using
a cross-section radius of R = 1, a contrast of a = 100, a standard deviation of
the Gaussian smoothing of = 1, and different levels of additive Gaussian noise
with standard deviations of n = 0; 1; 3; 5; 10. Note that a spiral has a varying
curvature along the tubular structure. For example, Fig. 1(a) shows the
segmentation result for a 3D spiral. In addition, Fig. 1 displays a 2D section of the
segmentation results highlighting the inner part of the spiral ( n = 5) using (b) a
previous straight model and (c) our new curved model. Shown are the centerline
(black) and the inner and outer contours (white). The spiral has been quite
well segmented using the curved model. In contrast, the straight model yields a
worse result, i.e., the estimated centerline and contours are shifted inwards with
increasing curvature.</p>
      <p>To quantify the segmentation results, we have computed the mean error e¯
and the maximal error emax of the estimated centerline position x0, the radius
R = , and the curvature along the spiral. Table 1 shows the results for
five different noise levels ( n = 0; 1; 3; 5; 10). From the experiments we found
that our curved tubular model generally yields accurate results for the centerline
position, radius, and curvature. The maximal errors of the centerline position
(emax;x0 = 0:41 voxels) and of the radius (emax;R = 0:26 voxels) for a relatively
high level of noise ( n = 10) are well in the subvoxel range, and even lower for
less image noise. Also the error of the curvature is quite small, i.e., the maximal
error is only about 10% of the true value. In comparison, for the straight model
significantly larger maximal errors of the position (emax;x0 = 0:94 voxels) and
of the radius (emax;R = 0:35 voxels) are obtained. Moreover, Fig. 1(d) shows
the error ex0 of the centerline position along the spiral for the previous straight
model (grey) and our new curved model (black). For the previous model, the
error increases strongly along the spiral, whereas for the new model the error
remains relatively small.</p>
      <p>We have also applied the new approach to different 3D CTA vascular images
of the human. Figs. 2a,b show the segmentation result for a small vessel in a 3D
CTA image of a human brain. For two positions on the centerline the estimated
curvature is visualized by displaying the osculating circle as a torus (bright ring).
The tori are defined by the estimated radius of curvature R , center of curvature
x , and radius R = . In the figure, examples are shown for a high curvature
(a) and a low curvature (b) vessel segment. In addition, the segmentation result
of a curved small vessel feeding a liver tumor is presented in Fig. 2(c). It turned
out that vessels of varying curvatures have been well segmented.
We introduced a new curved tubular intensity model in conjunction with a model
fitting scheme for accurate segmentation and quantification of small tubular
structures in 3D vascular images. The tubular model includes a parameter for the
local (extrinsic) curvature of tubular structures. We have proposed to formulate
the curved tubular model as a 3D Gaussian smoothed Dirac ring, and we have
derived an analytic solution for the model function. In contrast to previous
straight models, the new model allows to represent curved tubular structures,
to directly estimate the local curvature by model fitting, as well as to more
accurately estimate the remaining model parameters such as the radius and
centerline of tubular structures. We have successfully applied our approach to
3D synthetic images as well as 3D CTA images of the human vascular system.
Acknowledgement. This work has been funded by the Deutsche
Forschungsgemeinschaft (DFG) within the project QuantVessel (RO 2471/6).</p>
    </sec>
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