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ACTA UNIVERSITATIS UPSALIENSIS UPPSALA 2008 Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 386 Visualization and haptics for interactive medical image analysis ERIK VIDHOLM ISSN 1651-6214 ISBN 978-91-554-7067-8 urn:nbn:se:uu:diva-8409

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Page 1: Visualization and haptics for interactive medical image analysis171287/FULLTEXT01.pdf · 2009-02-14 · 1.2 Medical image analysis Digital image analysis is the field of extracting

ACTAUNIVERSITATISUPSALIENSISUPPSALA2008

Digital Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Science and Technology 386

Visualization and haptics forinteractive medical image analysis

ERIK VIDHOLM

ISSN 1651-6214ISBN 978-91-554-7067-8urn:nbn:se:uu:diva-8409

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Dissertation presented at Uppsala University to be publicly examined in Häggsalen,Ångströmlaboratoriet, Polacksbacken, Uppsala, Friday, February 8, 2008 at 10:15 for thedegree of Doctor of Philosophy. The examination will be conducted in English.

Abstract

Vidholm, E. 2008. Visualization and Haptics for Interactive Medical Image Analysis.(Visualisering och Haptik för Interaktiv Medicinsk Bildanalys). Acta UniversitatisUpsaliensis. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty ofScience and Technology 386. 83 pp. Uppsala. ISBN 978-91-554-7067-8.

Modern medical imaging techniques provide an increasing amount of high-dimensional andhigh-resolution image data that need to be visualized, analyzed, and interpreted for diagnosticand treatment planning purposes. As a consequence, efficient ways of exploring these imagesare needed. In order to work with specific patient cases, it is necessary to be able to workdirectly with the medical image volumes and to generate the relevant 3D structures directly asthey are needed for visualization and analysis. This requires efficient tools for segmentation,i.e., separation of objects from each other and from the background. Segmentation is hard toautomate due to, e.g., high shape variability of organs and limited contrast between tissues.Manual segmentation, on the other hand, is tedious and error-prone. An approach combiningthe merits from automatic and manual methods is semi-automatic segmentation, where theuser interactively provides input to the methods. For complex medical image volumes, theinteractive part can be highly 3D oriented and is therefore dependent on the user interface.This thesis presents methods for interactive segmentation and visualization where true 3D

interaction with haptic feedback and stereo graphics is used. Well-known segmentationmethods such as fast marching, fuzzy connectedness, live-wire, and deformable models, havebeen tailored and extended for implementation in a 3D environment where volumevisualization and haptics are used to guide the user. The visualization is accelerated withgraphics hardware and therefore allows for volume rendering in stereo at interactive rates. Thehaptic feedback is rendered with constraint-based direct volume haptics in order to conveyinformation about the data that is hard to visualize and thereby facilitate the interaction. Themethods have been applied to real medical images, e.g., 3D liver CT data and 4D breast MRdata with good results. To provide a tool for future work in this area, a software toolkitcontaining the implementations of the developed methods has been made publicly available.

Keywords: medical image analysis, haptic rendering, volume visualization, interactivesegmentation

Erik Vidholm, Centre for Image Analysis, Box 337, Uppsala University, SE-75105Uppsala, Sweden

© Erik Vidholm 2008

ISSN 1651-6214ISBN 978-91-554-7067-8urn:nbn:se:uu:diva-8409 (http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8409)

Distributor: Uppsala University Library, Box 510, SE-751 20 Uppsalawww.uu.se, [email protected]

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Till minne av min pappa

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List of enclosed papers

This thesis is based on the following papers, which are referred to in the text

by their Roman numerals.

I E. Vidholm, X. Tizon, I. Nyström, and E. Bengtsson. Hapticguided seeding of MRA images for semi-automatic segmentation.In Proceedings of IEEE International Symposium on Biomedical

Imaging (ISBI), pp. 288-291, IEEE, 2004.

II E. Vidholm and I. Nyström. A haptic interaction technique forvolume images based on gradient diffusion. In Proceedings of

WorldHaptics, pp. 336-341, IEEE, 2005.

III F. Malmberg, E. Vidholm, and I. Nyström. A 3D live-wiresegmentation method for volume images using haptic interaction.In Proceedings of Discrete Geometry for Computer Imagery

(DGCI), pp. 663-673, LNCS 4245, Springer Verlag, 2006.

IV E. Vidholm, S. Nilsson, and I. Nyström. Fast and robust semi-automatic liver segmentation with haptic interaction. In Proceed-

ings of Medical Image Computing and Computer-Assisted Inter-

vention (MICCAI), pp. 774-781, LNCS 4191, Springer Verlag,

2006.

V E. Vidholm and I. Nyström. Haptic interaction with deformablemodels for 3D liver segmentation. In Proceedings of MICCAI

Workshop: Interaction in Medical Image Analysis and Visualiza-

tion, pp. 41–48, 2007.

VI E. Vidholm, M. Golubovic, S. Nilsson, and I. Nyström. Accurateand reproducible semi-automatic liver segmentation using hapticinteraction. In Proceedings of SPIE Medical Imaging: Visualiza-

tion, Image-guided Procedures, and Modeling, 2008. In press.

VII E. Vidholm, A. Mehnert, E. Bengtsson, M. Wildermoth, K.

McMahon, S. Wilson, and S. Crozier. Hardware acceleratedvisualization of parametrically mapped dynamic breast MRIdata. In Proceedings of MICCAI Workshop: Interaction in

Medical Image Analysis and Visualization, pp. 33–40, 2007.

VIII E. Vidholm, F. Malmberg, I. Nyström, and E. Bengtsson. A toolkitfor interactive medical image visualization and segmentation withhaptics. Submitted for journal publication.

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Reprints of Paper I and Paper II was made with kind permissions from the IEEE.

Reprints of Paper III and Paper IV was made with kind permission of Springer Science

and Business Media.

The author has significantly contributed to the work performed in all the papers.

In Paper III, the contribution was mainly on the implementation and in Paper VII

the author designed and implemented the visualization part. For the other papers, the

author has had the major responsibility for method development, implementation, and

writing.

Faculty opponent is Professor Gábor Székely, ETH Zürich.

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Contents

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

1.1 Thesis outline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

1.2 Medical image analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

1.2.1 Computed tomography . . . . . . . . . . . . . . . . . . . . . . . . . . 10

1.2.2 Magnetic resonance imaging . . . . . . . . . . . . . . . . . . . . . . 11

1.3 Interactive segmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

1.4 Volume visualization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

1.5 Haptic interaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

1.6 Goals of this thesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

2 Image analysis tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.1 Digital images . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.2 Spatial filtering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

2.2.1 General smoothing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

2.2.2 Bilateral filtering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

2.2.3 Gradient extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

2.3 Gradient vector flow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

2.4 Digital distance transforms . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

3 Interactive segmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

3.2 Segmentation by region growing . . . . . . . . . . . . . . . . . . . . . . . 21

3.3 Live-wire segmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

3.4 Fast marching segmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

3.4.1 Formulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

3.4.2 Fast marching . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

3.5 Fuzzy connectedness segmentation . . . . . . . . . . . . . . . . . . . . . 26

3.5.1 Fuzzy set theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

3.5.2 Fuzzy connectedness . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

3.6 Segmentation by deformable models . . . . . . . . . . . . . . . . . . . . 29

3.6.1 Formulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

3.6.2 Simplex meshes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

3.6.3 Deformation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

3.7 Evaluation of segmentation methods . . . . . . . . . . . . . . . . . . . . 33

4 Visualization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

4.1 Multi-planar reformatting . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

4.2 Volume rendering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

4.3 Hardware accelerated direct volume rendering . . . . . . . . . . . . . 38

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4.4 Surface rendering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

4.5 Stereo graphics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

5 Computer haptics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

5.1 Haptic devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

5.2 Haptic displays and software . . . . . . . . . . . . . . . . . . . . . . . . . . 44

5.3 Haptic rendering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

5.3.1 Haptic surface rendering . . . . . . . . . . . . . . . . . . . . . . . . . 46

5.3.2 Haptic volume rendering . . . . . . . . . . . . . . . . . . . . . . . . . 47

5.3.3 Proxy-based volume haptics . . . . . . . . . . . . . . . . . . . . . . 47

5.4 Volume haptics for medical image segmentation . . . . . . . . . . . 50

6 Contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

6.1 Haptics for seeding of region growing algorithms . . . . . . . . . . 51

6.1.1 Seeding of vessels in MRA . . . . . . . . . . . . . . . . . . . . . . . 51

6.1.2 Volume haptics based on GVF . . . . . . . . . . . . . . . . . . . . . 52

6.2 An extension of live-wire to 3D . . . . . . . . . . . . . . . . . . . . . . . . 53

6.3 Interactive deformable models . . . . . . . . . . . . . . . . . . . . . . . . . 56

6.4 Accurate and reproducible liver segmentation . . . . . . . . . . . . . 58

6.5 Visualization of dynamic breast MRI . . . . . . . . . . . . . . . . . . . . 62

6.6 The WISH toolkit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64

7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

7.1 Summary of contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

7.2 Future work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

7.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

8 Summary in Swedish . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77

Related work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

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1. Introduction

The increasing capabilities of medical imaging devices has strongly facilitated

diagnosis and surgery planning. During the last decades, the technology has

evolved enormously, resulting in a never-ending flow of high-dimensional and

high-resolution data that need to be visualized, analyzed, and interpreted. The

development of computer hardware and software has given invaluable tools

for performing these tasks, but it is still very hard to exclude the human oper-

ator from the decision making. The process of stating a medical diagnosis or

to conduct a surgical planning is simply too complex to fully automate. There-

fore, interactive or semi-automatic methods for image analysis and visualiza-

tion are needed where the user can explore the data efficiently and provide

his or her expert knowledge as input to the methods. The work in this thesis

is about development and application of such methods with an emphasis on

visualization and haptics for improved interaction.

1.1 Thesis outline

The outline of the thesis is as follows. First, the key areas and the specific

goals are summarized in the following introductory sections. In Chapter 2,

the basic image analysis methods used in this work are described. Chapter 3

presents interactive segmentation. Volume visualization and volume haptics

are described in Chapter 4 and Chapter 5, respectively. The scientific contri-

butions of this work are summarized in Chapter 6, and Chapter 7 concludes

the thesis summary with conclusions and suggestions for future work. A sum-

mary in Swedish is given in Section 8.

1.2 Medical image analysis

Digital image analysis is the field of extracting relevant information from dig-

ital images [44, 15]. Besides medicine, which is the application area consid-

ered in this thesis, it is also used in many other different areas in science and

industry, e.g., astronomy, remote sensing, defense, and security. The image

material considered in this work consist of three-dimensional (3D) and four-

dimensional (4D) medical images obtained with either computed tomography

(CT) or magnetic resonance imaging (MRI).

9

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1.2.1 Computed tomography

CT is probably the most well-known 3D medical imaging technique

and builds on transmission measurements of X-rays for several different

angles around the object under examination. The X-ray source is located

on a ring that rotates around the object. On the other side of the ring,

opposite the source, there is a detector array. From the transmission

measurements, mathematical image reconstruction is performed to produce

a 2D cross-section image of the object. By repeating this procedure, a stack

of 2D slices that can be regarded as a 3D image is obtained. A common

slice-size is 512×512 pixels. Modern multi-slice CT-scanners are capable of

acquiring multiple slices at a time with the use of up to 64 detector rings.

CT is used for diagnosing a variety of diseases in the brain, chest, heart, and

abdomen. It is also commonly used for imaging of complex fractures. With the

use of contrast agents, the images can be optimized for different organs. CT is

unique in the way that the image values are defined in the absolute Hounsfield

scale. Here, the radiodensity of distilled water at standard pressure and tem-

perature (STP) is defined as zero Hounsfield units (HU) and the radiodensity

of air at STP is defined as -1000 HU. Figure 1.1 shows an example of a CT

image.

Figure 1.1: An axial slice (left) and a coronal slice (right) of an abdominal CT volume.

Dark pixels represent low density and bright pixels represent high density.

10

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1.2.2 Magnetic resonance imaging

MRI is a standard medical imaging technique for both anatomical and func-

tional studies. Medical MRI relies on the relaxation properties of excited hy-

drogen nuclei in water and lipids. The object that is about to be imaged is

placed in a static magnetic field (typical strength 1.5 Tesla), resulting in that

the magnetic moment of the atom nuclei aligns with the field direction. By

applying a perturbation with another magnetic field in the form of a radio

pulse, the spin of the nuclei is excited and causes the magnetic moments to

point in the direction of the perturbing field. When the radio pulse is switched

off, the spins will return to their equilibrium state. During this relaxation, ra-

dio frequency signals are emitted. From these signals, that are detected by the

MRI equipment, the time it takes for the magnetic moments to realign with

the static magnetic field can be calculated. Since the relaxation times vary

between tissues, contrast is obtained in the reconstructed images. Figure 1.2

shows examples of MR images1.

Figure 1.2: Left: An axial slice of an MR image of the abdomen. Right: A sagittal

slice of an MR image of the brain.

An important difference between MRI and CT is that MR images reflect

the chemical structure of tissue whilst CT images reflect the radiodensity of

tissue. Therefore, MRI can provide good contrast between soft tissues and is

suitable for brain imaging in order to, e.g., find tumors and detect the small

changes in the brain caused by a stroke. MRI is also commonly used for imag-

ing of the heart, abdomen, and joints. Contrast agents for enhancement of

specific organs are common, e.g., in MR angiography where blood vessels are

imaged. A modern technique for diagnosing breast cancer uses dynamic con-

trast enhanced MRI (DCE-MRI), where the enhancement pattern over time is

analyzed to differentiate between benign and malign tissue.

1The dataset in Figure 1.2 (right) is courtesy of Dirk Bartz, VCM, University of Tübingen,

Germany.

11

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1.3 Interactive segmentation

One of the most important steps in medical image analysis is segmentation,

i.e., the process of partitioning the contents of an image into objects of interest

and background in order to facilitate further analysis and information extrac-

tion. Segmentation is needed in diagnostics, therapy monitoring, surgery plan-

ning, and several other medical applications. To manually segment the struc-

tures of interest in medical datasets is a very tedious and error-prone proce-

dure, while fully automatic segmentation is, despite decades of research, still

seen as an unsolved problem. Therefore, many methods are semi-automatic,

i.e., the segmentation algorithms are provided with high-level knowledge from

the user by some means of interaction. A successful semi-automatic method

combines the outstanding capabilities of the human to recognize and locate

objects in images with the computer’s ability to quickly perform tedious and

time-consuming tasks such as counting and exact object delineation. The in-

teractive part is highly dependent on the user interface. Interfaces that rely

on 2D interaction have many drawbacks when the data is 3D, since it is not

straight-forward how to map 2D interaction into 3D space.

1.4 Volume visualization

In order to visualize volume images on a computer screen, some sort of pro-

jection has to be performed. A common and simple way is to show 2D cross-

sections (slices) of the dataset. The slices can be orthogonal to the main axis

of the digitization grid, or arbitrarily positioned and oriented. If several slices

are viewed at once, this is called multi-planar reformatting. Another approach

is to extract and display surfaces representing certain intensity values in the

volumetric dataset. A more general, but also more complex approach, is to

use direct volume rendering (DVR). In this case, different colors and opaci-

ties are assigned to each voxel in the volume in order to visualize overlapping

objects. With modern graphics hardware, DVR can be performed in real-time

on standard workstations.

In order to provide a more realistic 3D visualization, stereo graphics can be

used where two renderings of the volume image are performed, one for the

left eye and one for the right eye. These images are then displayed to the user

by using, e.g., time-multiplexing or color-multiplexing.

12

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Figure 1.3: SenseGraphics 3D-IW haptic display with a PHANToM Omni haptic de-

vice. The haptic device is positioned beneath a semi-transparent mirror and the med-

ical image is visualized with time-multiplexed stereo graphics projected through the

mirror in order to obtain co-localization of haptics and graphics.

1.5 Haptic interaction

The word haptic stems from the greek word haptesthai which means “to

touch”. In psychology, haptics is the study of touching behavior and haptic

perception. Haptic perception can be divided into tactile perception and kines-thetic perception. Tactile perception involves the receptors in the skin that al-

low us to feel temperature and pressure in order to determine, e.g., the texture

and roughness of surfaces. The kinesthetic component involves the receptors

in muscles and joints which are used for body control and for determining

weights and friction.

In computer science, haptics refers to the use of tactile and kinesthetic feed-

back as a human-computer interface component, i.e., rendering of virtual ob-

jects with force feedback. The task here is to generate intuitive force feedback

when the user moves the haptic device so that it comes in contact with an

object. An advantage with haptic interaction is that it provides the unique pos-

sibility of simultaneous exploration and manipulation of data. In this work,

the focus is on haptic rendering of medical volume images in order to, e.g.,

feel boundaries between organs and provide input to segmentation algorithms.

The aim with the haptic feedback is to convey more information about the data

than can be obtained with only visual rendering.

13

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1.6 Goals of this thesis

The main goal of this thesis is to provide new intuitive ways of interaction for

efficient, accurate and high-precision medical image segmentation by using

a 3D user interface capable of haptic feedback and stereo visualization, see

Figure 1.3. The cover image illustrates two examples of interactive medical

image segmentation with haptic feedback performed in this work.

The use of haptic interaction for segmentation is a young research field with

few contributions. This means that there are no standard methods or widely

spread software packages available to start from. Therefore, to reach the main

goal stated above, the following tasks need to be accomplished:

• Development of new methods and tailoring of existing methods,

where visualization, haptic rendering, and interactive segmentation

are integrated.

• Application and evaluation of the methods on real medical image

data.

• Efficient implementations of the methods in a framework for research

and development. This framework should be possible to extend and

easy to integrate into other software packages.

The emphasis in this work lies on the development, implementation, appli-

cation, and evaluation of the methods. The author has not been involved in

the image acquisition and is not an expert in the medical field. However, the

applied parts of the work involve strong collaborations with research groups

at the Department of Oncology, Radiology, and Clinical Immunology at Upp-

sala University Hospital and the ITEE Biomedical Engineering group at The

University of Queensland, Brisbane, Australia.

14

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2. Image analysis tools

In this chapter, a presentation of digital images and the basic image analysis

tools used in this work is given.

2.1 Digital images

A general digital image may be regarded as a discrete integer-valued function

f (x, t,b), where x = (x,y,z) are the spatial coordinates, t is time, and b is the

spectral (color) component. In the work described here, mainly 3D gray-level

images are considered, which will be reflected in the notation and terminol-

ogy. A digital image consists of a finite number of elements, each with a

x

y

z

Δx

Δ

Δ

y

z

Figure 2.1: Left: A 3D image and the commonly used coordinate system. Right: A

voxel with size (Δx,Δy,Δz).

particular location and value. In a digitization grid of size M×N×P, thereare MNP elements and the spatial coordinates x belong to the range

[0,M− 1]× [0,N − 1]× [0,P− 1]. These elements are called pixels (picture

elements) in 2D and voxels (volume picture elements) in 3D, see Figure 2.1.

The gray-level value at each pixel or voxel is referred to as the intensity or

brightness. In computer memory, the intensity is most commonly represented

with signed or unsigned integer data types having a certain bit-depth N, mean-

ing that f ∈ [0,2N−1] (unsigned) or f ∈ [−2N−1,2N−1−1] (signed). Common

bit-depths are 8 and 16. A binary image has only two intensities representing

background and object, respectively.

15

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If a voxel has the same size in all spatial directions, i.e., Δx = Δy = Δz, thegrid is uniform (isotropic). In medical images it is common that the voxels are

elongated in the z-direction, i.e., the grid is non-uniform (anisotropic). This

has to be considered when implementing both image analysis and visualiza-

tion algorithms.

The connectivity of voxels is of importance for many image analysis algo-

rithms. In the standard digitization grid, a voxel has 26 neighbors consisting

of six face neighbors, twelve edge neighbors, and eight vertex neighbors, see

Figure 2.2.

Figure 2.2: In a 3×3×3 neighborhood in the standard digitization grid, each voxel has

six face neighbors (left), twelve edge neighbors (middle), and eight vertex neighbors

(right).

2.2 Spatial filtering

Filtering of images may be performed for purposes such as noise reduction

and edge enhancement. A spatial filtering method involves the use of a filter

mask or kernel that covers a certain neighborhood N of the center voxel that

is the origin of the mask, see Figure 2.3.

w(1,−1)w(0,−1)

w(0,0)w(−1,0) w(1,0)

w(−1,−1)

w(0,1)w(−1,1) w(1,1)

f(x,y−1)f(x−1,y−1)

f(x−1,y+1) f(x,y+1)

f(x+1,y)f(x,y)f(x−1,y)

f(x+1,y−1)

f(x+1,y+1)

Figure 2.3: 2D example of a 3×3 filter mask (left) and the corresponding image pixels

under the filter mask (right).

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The size of the filter mask is application dependent. For each voxel, a value

based on the neighbors are calculated and used as output. A linear filter con-

tains coefficients that are multiplied with the corresponding values in the input

image and the result is a weighted sum of the voxels covered by the mask, i.e.,

a convolution:

g(x) = ∑s∈N

w(s) f (x+ s),

where w is the filter mask, f the input image, and g is the output image. Non-

linear filters output values based on other criteria, e.g., the median value or the

maximum value.

2.2.1 General smoothing

Smoothing filters are used for blurring and noise reduction. There exist both

linear and non-linear versions. The output of a smoothing, linear spatial filter

is simply a weighted average of the voxels covered by the filter mask, i.e.,

g(x) = ∑s∈N w(s) f (x+ s)∑s∈N w(s)

.

The most basic linear smoothing operation is the averaging filter where all

filter coefficients w(s) = 1. This means that all voxels contribute equally much

to the output. A better approach is Gaussian smoothing, where the filter mask

is a discrete approximation of a Gaussian function with a certain standard

deviation σ :

w(s) = e−12 ||s||2/σ2

.

Here, the central voxel contributes most and the voxels distant from the center

contribute less. To obtain a good approximation, the size of the filter mask

should increase with the value of σ . A Gaussian smoothing filter is symmetric,

which means that it can be efficiently implemented as three consecutive one-

dimensional convolutions.

2.2.2 Bilateral filtering

A problem with smoothing filters is that they do not take image content into

account. In many applications, edges are important and hence should be pre-

served. By using a linear smoothing filter, an edge is blurred equally much

as a homogeneous region. In order to mitigate this problem, methods for

edge-preserving smoothing have been developed. One common method is

anisotropic diffusion [36] which is based on solving a partial differential equa-

tion (PDE).

Another approach is bilateral filtering [47]. The main idea here is to not only

use the spatial distance between voxels for calculating the filter coefficients,

but also the range distance, i.e., the intensity difference for gray-level images.

As an example, a filter kernel composed of two Gaussian functions can be

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used, one for the domain (σd) and one for the range (σr). The filter produces

the output

g(x) = ∑s∈N e−12 ||s||2/σ2

d · e− 12 ( f (x+s)− f (x))2/σ2

r · f (x+ s)

∑s∈N e−12 ||s||2/σ2

d · e− 12 ( f (x+s)− f (x))2/σ2

r.

When implementing this filter, a new filter mask is computed at each voxel po-

sition. In Figure 2.4, a 2D illustration of bilateral filtering compared to Gaus-

sian smoothing is shown. The Gaussian smoothing removes a lot of detail

while the bilateral filter smoothes only in more homogeneous regions.

Figure 2.4: Bilateral filtering compared to Gaussian smoothing. Left: Maximum in-

tensity projection (MIP) of an MR angiography image. Middle: Result of Gaussian

smoothing with σ = 3 voxels. Right: Result of bilateral filtering with σd = 3 voxels

and σr = 20.

We used bilateral filtering for pre-processing in Paper IV, Paper V, and

Paper VI. The implementation is also included in our toolkit described in Pa-

per VIII.

2.2.3 Gradient extraction

Many image analysis algorithms, particularly segmentation algorithms, are

dependent on high-quality edge information. The gradient magnitude ||∇ f ||is a good indicator of edges. A standard method for estimating the gradient of

an image is to use centered differences, i.e.,

∇ f ≈

⎛⎜⎝

f (x+1,y,z)− f (x−1,y,z)Δx

f (x,y+1,z)− f (x,y−1,z)Δy

f (x,y,z+1)− f (x,y,z−1)Δz

⎞⎟⎠ .

This approximation can easily be implemented with three spatial filters.

If the image data is noisy, the gradient extraction becomes more robust if

some smoothing is performed before computing the gradient, e.g., Gaussian

smoothing or bilateral filtering. Another option is to involve smoothing

directly in the design of the gradient filter by using, e.g., derivatives of

Gaussian functions.

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2.3 Gradient vector flow

As discussed in Section 2.2.3, the gradient and the gradient magnitude are

important for many algorithms. However, the gradient is a local property and

may not provide sufficient global information. An example is segmentation

with deformable models [21, 32]. Here, the gradient magnitude can serve as

an external image force that drives deformable contours or surfaces in order

to find a certain object in the image. If the initial model is initialized far away

from the object of interest, the model will probably fail or have very slow con-

vergence because the object edges are not found. This is because the capture

range of the gradient magnitude is very limited. This problem was addressed

by Xu and Prince [53] when they introduced gradient vector flow (GVF). The

basic idea behind GVF is to propagate edge information from strong bound-

aries into the inner part of homogeneous regions by gradient diffusion.

The 3D GVF vector field V(x) = (u(x),v(x),w(x)) minimizes the energy

functional

E =∫

R3μ||∇V||2 + ||∇g||2||V−∇g||2dx,

where g is an edge map computed from the original image by using, e.g., a

gradient magnitude filter. Note that the ∇ operator is applied to each com-

ponent of V separately. The first term, ||∇V||2, is called the smoothing term

since it alone will produce a smoothly varying vector field, while the second

term, ||∇g||2||V−∇g||2, forces the vector field to be close to ∇g in regions

where ||∇g|| is large. The regularization parameter μ controls the effect of the

smoothing term. Figure 2.5 shows an example of GVF.

Figure 2.5: Left: A slice of an edge map of an abdominal MR image. Right: Magnified

view of the GVF field computed from the edge map.

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By using calculus of variations, it can be shown that V must satisfy the

Euler-Lagrange equation

μ∇2V−||∇g||2(V−∇g) = 0, (2.1)

where ∇2 is also applied to each component of V separately. The solution

to Equation (2.1) can be obtained by treating V as a function of time, t, andfinding the steady-state solution of

Vt = μ∇2V−||∇g||2(V−∇g). (2.2)

Equation (2.2) comprises three decoupled scalar PDEs that can be discretized

with finite differences and solved using standard numerical PDE solvers. In

higher dimensions, more sophisticated numerical solvers must be considered

in order to reduce computation time.

In this thesis, GVF is used both for haptic rendering and for driving de-

formable models, see Papers II, V, VI, and VIII. In a related publication [51],

we implemented and evaluated a number of numerical techniques for GVF

computation. Our implementations allow for computation times 1–2 orders of

magnitude faster than straight-forward implementations.

2.4 Digital distance transforms

Methods for measuring distances are useful image analysis tools, e.g., for

shape description. A distance transform (DT) is applied to a binary image and

computes the distance from each object element to the closest background ele-

ment. By regarding the object as background and vice versa, the distance from

each background element to the closest object element is computed. The re-

sult of a DT is a distance map, i.e., a gray-level image containing the distance

values. A signed DT assigns to each element the minimum distance from that

element to the nearest border element of the object. In this case, the distance

values have different signs depending on whether the element belong to the

object or to the background.

The DTs can be computed in different ways. In this work, we have used

weighted (chamfer) DTs [4] and DTs computed with the fast marching

method, see Section 3.4. The DTs have been used for deformable model

segmentation and for haptic rendering, see Papers IV, V, VI, and VIII.

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3. Interactive segmentation

This chapter gives a brief introduction to interactive segmentation and descrip-

tions of the segmentation methods that have been used in this work.

3.1 Introduction

Image segmentation is the process of separating objects of interest from each

other and from the background and is one of the most important topics in

image analysis. Since segmentation often is an initial step, all further analysis

and information extraction will depend on the result of the segmentation.

In medical applications, segmentation is needed for basic tasks such as vol-

ume and area measurements and more complex tasks such as 3Dmodel extrac-

tion for surgical planning and image-guided therapy. There are several things

that make medical image segmentation hard, e.g., similar intensity patterns

for different tissues (low contrast) and bad image quality due to noise from

the imaging system. Another problem is the high shape variability of organs

making it hard to incorporate a priori information.

Over the recent decades, huge research efforts have been put on developing

automatic algorithms for medical image segmentation. Despite these efforts,

a general automatic algorithm is still not developed. Manual segmentation, on

the other hand, is very tedious and error-prone due to inter- and intra-observer

variability. Therefore, many methods are semi-automatic, i.e., the segmenta-

tion algorithms make use of input from the user [34]. The interaction can

involve manual delineation of an organ in selected 2D slices, positioning of

differently labeled seed-regions in different organs, or simply post-processing

of the result of an automatic method [20].

3.2 Segmentation by region growing

The basic idea in region growing is to group voxels into larger regions based

on predefined criteria. Starting from a set of seed-voxels [1], regions are grown

by appending neighboring voxels that have similar properties as the seeds.

The selection of seeds can be performed manually or automatically. The def-

inition of similarity is the key issue and is dependent on the application. In

the simplest case, the similarity measure is based on the intensity difference

between the seed-voxels and the voxels that are candidates for being included

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in the region. An important issue in region growing is when to terminate the

growing. One possibility is to stop when no more voxels fulfill the similarity

criteria, but this often results in over-segmentation (leaking) due to low con-

trast. Therefore, it is common to use global measures based on the size and

shape of the region.

In Paper I, we use a simple region growing algorithm, where the similarity

criteria is based on a non-linear mapping of intensity values. To avoid leak-

ing, the maximum size of the grown region is controlled. More sophisticated

region-growing algorithms based on fast marching and fuzzy connectedness

were used in Paper IV and Paper V. These algorithms are described in Sec-

tion 3.4 and Section 3.5.

3.3 Live-wire segmentation

Live-wire [13, 12] is a semi-automatic segmentation method for 2D images

and slice-wise segmentation of 3D images. It is based on shortest path calcu-

lation in a graph representation of the image. For every edge in the graph, a

cost is assigned to represent the likelihood that the edge belongs to a desired

boundary in the image. To segment an object, the user places a seed-point on

the object boundary. All possible minimum-cost paths from the seed-point to

all other points in the image are computed via Dijkstra’s algorithm [8]. As

the user moves the cursor in the image, the minimum-cost path, referred to as

the live-wire, from the current position of the cursor back to the seed-point

is displayed in real-time, see Figure 3.1. The idea is to have low cost at the

desired boundary in order to make the live-wire snap onto it. When the user is

satisfied with a live-wire segment, he continues by placing a new seed-point.

In this way, the entire object boundary can be traced with a rather small num-

ber of live-wire segments. The design of the cost function is the crucial part

of the algorithm and how it should be chosen is discussed in, e.g., [13]. Com-

monly, a combination of intensity measures and gradient magnitude measures

are used.

Live-wire is a method for 2D segmentation, but it can be also be used for

3D segmentation. Most 3D extensions are based on using the standard live-

wire method on a subset of 2D slices in the 3D volume, and then reconstruct-

ing the entire object based on this information [40, 11, 16]. Even though the

reconstruction algorithms might take 3D information into account, all user in-

teraction is performed in 2D. This sometimes cause problems, e.g., when the

object topology changes between slices.

In Paper III, we suggest a more direct 3D approach where live-wire curves

are connected to form surfaces. For this, we use the Image Foresting Trans-

form (IFT) [10] which is an extension of Dijkstra’s algorithm that allows an

arbitrary number of seed-points and finding of the shortest path from all image

points to any of the seed-points.

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Figure 3.1: Liver segmentation in a CT image with the live-wire method. The user

interactively positions seed-points (blue) on the liver boundary. As the user moves the

cursor, the shortest path (yellow) from the last seed-point to the current cursor position

is displayed in real-time. When a new seed-point is set, the current live-wire segment

is fixed (red).

3.4 Fast marching segmentation

In the live-wire method, a discrete shortest-path problem is solved by using

Dijkstra’s algorithm. Similar algorithms have also been used successfully for

computing discrete approximate solutions to continuous problems. Examples

are fast marching methods and level set methods [43].

3.4.1 Formulation

Consider a closed surface Γ ∈ Rn propagating in its normal direction n with

speed F(x). The front only propagates outwards, i.e., F > 0. To character-

ize the position of the expanding front, the time of arrival u(x) of the front

can be computed as it crosses each point x. Basic relations between distance,

speed, and time, gives that the speed F(x) must be inversely proportional to

the gradient, i.e.,

∇u(x) = C(x)n,

where C(x) = 1/F(x) can be regarded as a slowness or cost function. This

leads to the boundary value problem

||∇u(x)||= C(x), u(x) = 0 on Γ, (3.1)

which is known as the Eikonal equation and is the underlying equation in fast

marching methods.

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The relation between fast marching methods and level set methods can be

seen through an alternative approach of derivation. If the initial position of

the front is embedded as the zero level set of a function φ ∈ Rn+1, the time

dependent initial-value problem

φt +F ||∇φ ||= 0, (3.2)

is obtained. This is the level set equation and it describes the time evolution

of the level set function φ in such a way that the zero level set φ = 0 is always

identified with the propagating surface. This formulation is more general than

fast marching since it allows the speed function F to be both positive and

negative. Hence, it is also more computationally demanding.

3.4.2 Fast marching

In the work described here, we have focused on fast marching methods which

essentially are numerical schemes for solving Equation (3.1).

The central idea behind the fast marching method is to systematically con-

struct the solution u in a downwind fashion, i.e., to propagate information out-

wards from the boundary condition, from smaller values of u to larger values.

This requires upwind difference schemes in place of classical approximations

such as centered differences. A commonly used upwind gradient approxima-

tion is the Godunov scheme

||∇u|| ≈

⎡⎢⎣

max(D−xi jku,−D+x

i jku,0)2+

max(D−yi jku,−D+y

i jku,0)2+

max(D−zi jku,−D+z

i jku,0)2

⎤⎥⎦

1/2

,

where i, j, k denotes the indices in the discretization and D+ and D− are stan-

dard forward and backward difference operators, e.g.,

D+xi jku =

ui+1, j,k−ui, j,k

Δx, and

D−xi jku =

ui, j,k−ui−1, j,k

Δx.

Using this scheme, the discrete approximation of Equation (3.1) becomes

C2i jk =max

(ui, j,k−ui−1, j,k

Δx,ui, j,k−ui+1, j,k

Δx,0

)2

+

max

(ui, j,k−ui, j−1,k

Δy,ui, j,k−ui, j+1,k

Δy,0

)2

+

max

(ui, j,k−ui, j,k−1

Δz,ui, j,k−ui, j,k+1

Δz,0

)2

.

(3.3)

This equation can be solved for u by using the procedure in [22].

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The fast marching algorithm is accelerated by limiting the computational

domain to an area in the proximity of the front, the so called narrow band.While this narrow band is marching forward, the values of existing points are

accepted and new points are brought into the narrow band structure. Because

of upwinding, no point can be affected by grid points with larger values of u.Therefore, the point where u is minimal will be accepted and its downwind

neighbors are updated. In the Dijkstra-like algorithm, the narrow band points

are labeled as Trial points and the accepted points as Accepted. Points that

have not been reached by the front yet are labeled Faraway, see Figure 3.2.

The Trial points in the narrow band are stored in a priority queue based on

Accepted

Trial (narrow band)

Faraway

Figure 3.2: Fast marching front propagation. The computational domain is limited

to a narrow band in the proximity of the front. The narrow band contains the Trialpoints and is represented by a minimum heap data structure. In each iteration, the Trialpoint with the smallest time of arrival value is labeled as Accepted and its Farawayneighbors are brought into the narrow band.

a minimum heap data structure, a binary tree where the node with minimum

value is always located at the root. Accessing the root has complexity O(1)and point insertion/update has complexity O(logn) if there are n points in the

heap. The overall complexity is O(N logN) for grids with N elements, see

Algorithm 1.

The common use of fast marching methods in image segmentation is to de-

sign a proper cost functionC, provide a set of seed-points representing the ini-

tial front, and then propagate the front until a certain arrival time is reached.

The cost image C should be designed to achieve low costs in homogeneous

parts and high costs at edges, see Figure 3.3. In order to find a proper arrival

time threshold to obtain the final segmentation, visual inspection can be used.

More automatic methods are based on, e.g., global measures of the voxels be-

longing to the front [54]. Note also that by using a constant cost function, e.g.,

C = 1, the fast marching algorithm can be used to compute an approximation

of the Euclidean distance map from the set of seed-points.

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Algorithm 1: Fast marching

begininitialization;

forall p in the domain doset u(p) = ∞;

tag p as Faraway;forall p in the initial condition do

set u(p) = 0;

tag p as Accepted;forall p that are Accepted do

forall p′ that is a neighbor of p doif p′ is Faraway then

tag p′ as Trial;compute u(p′);insert p′ in the heap;

main loop;

while heap is not empty dopop the root of the heap and store it in p;tag p as Accepted;forall p′ that is a neighbor of p do

if p′ is Faraway thentag p′ as Trial;compute u(p′);insert p′ in the heap;

else if p′ is Trial thenrecompute u(p′);update the heap;

end

Our fast marching implementation follows Algorithm 1 and utilizes the Go-

dunov scheme for upwind gradient approximation. To efficiently solve the dis-

cretized Eikonal equation (3.3) for u, we use the procedure in [22]. We used

our implementation for liver segmentation in Paper IV and Paper VI. It is also

part of the toolkit in Paper VIII.

3.5 Fuzzy connectedness segmentation

Most segmentation algorithms give a crisp output, i.e., a set of points that

either belong to the object or to its complement. In cases when the objects

of interest show intensity patterns distinctly different from those of other

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Figure 3.3: Fast marching segmentation of the liver. Left: Seed-regions placed inside

the liver in an CT image. Middle: The cost image. Right: The resulting time-of-arrival

map with overlaid contour obtained by thresholding.

objects, crisp segmentation is often a good option. This is seldom the case

though, especially not for medical images where artifacts such as blur, noise

and background variation are introduced by the imaging device. The image

points rather belong to an object to a certain degree, i.e., they are fuzzy. Fun-damental work on the fuzzy topology and geometry of image subsets was

made by Rosenfeld. In [38], he reviews work in this field and its application

in image processing. For the work described here, a couple of basic notions

are required to present fuzzy connectedness and the segmentation evaluation

in Section 3.7.

3.5.1 Fuzzy set theory

For any reference set X , a fuzzy subset A of X is a set of ordered pairs

A= {(x,μA(x))|x ∈ X},

where μA : X �→ [0,1] is the membership function of A in X . The value μArepresents the degree of belongingness for x inA. If μA(x) �= 0 for any x ∈ X ,

A is said to be non-empty. In the definition list below, A and B are fuzzy

subsets of the reference set X and x is any point in X .

Fuzzy set union A∪B:

μA∪B(x) = max(μA(x),μB(x)).

Fuzzy set intersection A∩B:

μA∩B(x) = min(μA(x),μB(x)).

Fuzzy set difference A−B:

μA−B(x) = max(μA(x)−μB(x),0).

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Fuzzy set complement A:

μA(x) = 1−μA(x).

Fuzzy set cardinality |A|:|A|= ∑

x∈XμA(x).

Finally, a fuzzy relation ρ in X is a fuzzy subset of X×X :

ρ = {((x,y),μρ(x,y))|(x,y) ∈ X×X}, where μρ : X×X �→ [0,1].

3.5.2 Fuzzy connectedness

Fuzzy connectedness [50] defines how image elements hang together in a

fuzzy setting. The aim of FC is to capture the global hanging togetherness

between grid points through local hanging togetherness defined by the fuzzy

relations adjacency μad j(x,y) and affinity μa f f (x,y). The adjacency depends

on the spatial distance between grid points. Hard adjacency relations are com-

monly used, e.g., μad j(x,y) = 1 if x and y are face neighbors and zero other-

wise. The affinity takes into account the adjacency of the grid points as well

as their similarity in intensity. The closer they are and the more similar in in-

tensity they are, the higher the affinity between them. The selection of fuzzy

adjacencies is essential and can be compared to the cost function selection in

fast marching.

In order to assign a strength of connectedness between any pair of grid

points (x,y), all possible paths of points between x and y are considered.

These paths are made up of links between successive neighboring grid

points (xi,xi+1) along the path where the strength of each link is the affinity

μa f f (xi,xi+1). The strength of a path is the strength of its weakest link. The

strength of connectivity between x and y is associated with the maximum

strength of all possible paths.

For image segmentation, FC can be applied and implemented in a way sim-

ilar to fast marching. The user specifies a proper adjacency, select a set of

seed-points inside the object of interest, and then compute an FC map by us-

ing a modification of Algorithm 1. The propagation of time in fast marching

is simply replaced by propagation of affinity in FC. Here, a maximum heap

is needed since the propagation will be from higher connectedness values to

smaller. The resulting connectedness map is a fuzzy segmentation where the

values between zero and one indicate the degree of belongingness to the object

of interest.

An extension to FC is relative FC [49], where extraction of objects is per-

formed by competing multiple initial regions against each other. In the work

by Nyúl et al. [33], various implementations of FC for interactive 3D segmen-

tation are reviewed.

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Our implementation of FC is based on small modifications of the fast

marching implementation and it is also included in the toolkit described in

Paper VIII. In Paper V, we used the FC algorithm to create external forces

for driving a deformable model.

3.6 Segmentation by deformable models

Deformable models for image segmentation were introduced in 1988 by Kass,

Witkin, and Terzopoulos [21]. They dealt with 2D active contours (snakes).

The concept has been extended to 3D deformable surfaces in various ways, an

overview can be found in [32].

3.6.1 Formulation

Common for most deformable model algorithms is that the models are driven

by minimization of an energy functional E . The energy functional usually

consists of several terms including at least one internal shape regularizing

term Eint and one external term Eext based on image data, i.e.,

E(S) = Eint(S)+Eext(S),

where S is the deformable surface. The key is to build the energy functional

in such a way that the desired solution S∗ coincides with the global minimum

of E , i.e., S∗ =minS E(S). For given internal and external terms, the minimiza-

tion equation does not in general have an analytical solution. Therefore, it is

necessary to discretize and solve it numerically. The most common method

is to rewrite the problem by using the Euler-Lagrange equation ∇E(S) = 0

in order to obtain a stationary equation that describes a force equilibrium be-

tween internal regularizing forces and external forces. The resulting problem

is then discretized by using finite differences, initialized with an approximate

solution, and solved iteratively. With a proper initialization, the model will

converge towards a minimum.

The two main characteristics of a deformable surface model are its geomet-

rical representation and its law of deformation. The geometrical representation

sets the degrees of freedom and the topological flexibility of the model while

the law of deformation tells how the model should be deformed in order to fit

the underlying image data. Among the continuous representations, there are

parametric models and implicit models. Common discrete representations are

unstructured meshes and polygonal meshes. In this work, Delingette’s discrete

simplex mesh representation [7] has been used.

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3.6.2 Simplex meshes

A k-simplex mesh is a discrete surface mesh where each vertex is linked to

k +1 neighboring vertices by an edge. In 3D, a surface model is realized as a

2-simplex mesh where each vertex has three neighbors. An important property

of the simplex mesh representation is the duality with triangulations. There

exists a dual triangle for each mesh vertex and a dual triangulation vertex for

each mesh face, see Figure 3.4. Each simplex vertex pi has three neighbor-

Figure 3.4: Left: Close-up of a 2-simplex mesh also showing the dual triangulation.

Right: A sphere represented by a 2-simplex mesh consisting of 320 vertices and 162

faces.

ing vertices (pN1(i),pN2(i),pN3(i)). These points define a triangle in the tangent

plane with normal vector ni:

ni =(pN2(i)−pN1(i))× (pN3(i)−pN1(i))||(pN2(i)−pN1(i))× (pN3(i)−pN1(i))||

.

The simplex mesh geometry involves the circle (Ci,ri) circumscribed to the

triangle (pN1(i),pN2(i),pN3(i)) and the sphere (Oi,Ri) circumscribed to the four

vertices (pi,pN1(i),pN2(i),pN3(i)), see Figure 3.5. The orthogonal projection Fi

of pi onto the tangent plane triangle can be represented with the barycentric

coordinates called the metric parameters, i.e.,

Fi = ε1ipN1(i) + ε2ipN2(i) + ε3ipN3(i), ε1i + ε2i + ε3i = 1.

The simplex angle φi ∈ [−π,π] is defined by

sin(φi) =ri

Ri· sign((pN1(i)−pi) ·ni),

cos(φi) =||Ci−Oi||

Ri· sign((Ci−Oi) ·ni).

By drawing the projection of the sphere in the plane (Fi,Ci,pi), the simplex

angle appears as the angle between the segments that join pi to the projection

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N1(i)p

pN2(i)

pN3(i)

ip

F

O

C

Ri

i i

i

i

d

φi

n i

L( i di, ), iφr

ir

Figure 3.5: Simplex mesh geometry. The circle that circumscribes the three neighbor-

ing vertices (pN1(i),pN2(i),pN3(i)) has center Ci and radius ri. The sphere that circum-

scribes the vertex pi and its neighbors has center Oi and radius Ri. Fi is the orthog-

onal projection of pi onto the tangent plane and di = ||Fi−Ci||. The elevation of piwith respect to the tangent plane is L(ri,di,φi). The red triangle represents the plane

(Fi,Ci,pi). In the projection onto this plane, the simplex angle appears as the angle

between the segments that join pi to the projection of the circle.

of the circle. The height of pi with respect to the tangent plane is defined

through the elevation function

L(ri,di,φi) =(r2i −d2

i ) tan(φi)

±√

r2i +(r2i −d2i ) tan2(φi)+ ri

,

where di = ||Fi−Ci||. This means that pi can be represented in terms of its

three neighbors:

pi = Fi +L(ri,di,φi)ni = ε1ipN1(i) + ε2ipN2(i) + ε3ipN3(i) +L(ri,di,φi)ni.

While the metric parameters control the projection of pi onto the tangent

plane, the simplex angle controls the local mean curvature Hi = 1/Ri through

the simple relationship

Hi =sinφi

ri.

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3.6.3 Deformation

Mesh deformation is dependent on which law of motion that is selected. For

discrete models, Newtonian evolution is commonly used, i.e., each vertex is

regarded as a point-mass influenced by internal forces, external forces, and

damping. The differential equation for a unit mass vertex is

d2pi

dt2=−γ

dpi

dt+(Fint)i +(Fext)i,

i.e., a force equilibrium equation where t is the time, γ is the damping factor,

Fint are the internal forces, and Fext are the external forces. By discretization

with central finite differences, the following iterative scheme is obtained:

pt+1i = pt

i +(1− γ)(pti−pt−1

i )+αi(Fint)ti +βi(Fext)t

i.

The weights αi and βi control the level of the internal and external force com-

ponents, respectively.

For the simplex mesh, the internal forces are decomposed into a tangential

force and a normal force:

Fint = Ftangent +Fnormal.

The tangential force is based on a set of reference metric parameters ε·i. Thesedefine a reference projection Fi in the tangent plane and the resulting force is

simply a spring force between Fi and Fi, i.e., Ftangent = Fi−Fi. If uniformly

spread vertices are desired, the reference projection should be the centroid of

the neighbor triangle: ε1i = ε2i = ε3i = 1/3. A curvature based tangential force

can be used in order to concentrate vertices in areas where a denser mesh is

needed. The reference metric parameters are then updated based on the mean

curvature deviation vector

δ |H|i =

⎛⎜⎜⎜⎝

|HN1(i)|−|Hi||Hi|

|HN2(i)|−|Hi||Hi|

|HN3(i)|−|Hi||Hi|

⎞⎟⎟⎟⎠ ,

where |Hi|= (|HN1(i)|+ |HN2(i)|+ |HN3(i)|)/3 is the absolute mean curvature.

The normal force component is based on a reference simplex angle φi that

gives the resulting force Fnormal = (L(ri,di, φi)− L(ri,di,φi))ni. Different

choices of φi give rise to different shape constraints. To obtain smooth

surfaces, a C2 continuity constraint can be used where φi is defined as the

average of the simplex angles at neighboring vertices. Another option is to

use a global shape constraint by setting φi = φ0, where φ0 is a constant.

In Paper V and Paper VIII we present our implementation of deformable

simplex meshes. It follows the theory and equations above with Newtonian

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evolution as the law of deformation. For the internal forces, we use a C2 con-

straint in the normal direction and a curvature-based force in the tangential

direction. Which external forces to use is dependent on the application. In our

implementation, the external forces are applied at vertex pi as

(Fext)i = ∑k

wki(fki ·ni)ni,

where fki are the forces computed from image data and wki are weights. To

avoid instabilities, the external forces are applied only in the normal direc-

tion [7]. The forces we use are:

Gradient magnitude force: Attracts the vertex to the

voxel gi with maximum gradient magnitude in a specified

neighborhood:

fi = gi−pi.

Inflation force: Makes the vertex propagate in its positive

or negative normal direction depending on if the intensity

value I(pi) is higher or lower than the constant I0:

fi = sign(I(pi)− I0).

Potential field force: A force proportional to the gradient

of a potential field P, e.g., a distance map:

fi = ∇P(pi).

Vector field force: A force based on the vector field V,

e.g., GVF:

fi = V(pi).

Our implementation also involves external forces based on haptic interaction,

see Section 6.3.

3.7 Evaluation of segmentation methods

An important step in the development of segmentation methods is the evalua-

tion. There are mainly two questions that need to be answered:

1. How accurate is the segmentation result?

2. With which precision can the segmentation result be repeated?

Udupa et al. [48] recently presented a framework for comparing and evalu-

ating segmentation methods with focus on medical applications. This frame-

work provides tools for evaluation of segmentation efficacy, i.e., precision, ac-curacy, and efficiency. It is also suggested how to perform statistical analysis

of the data. The framework is developed to be able to handle fuzzy segmenta-

tions where crisp segmentations become a particular case.

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A fuzzy segmentation of object O obtained with method M is denoted by

CMO = (C, fO), where C is a 3D grid and for any x ∈ C, fO(x) ∈ [0,1] is the

degree of belongingness to the object. In order to evaluate the accuracy of a

segmentation method, the results need to be compared against a ground truth.

Since it is uncommon to have completely true segmentations available, surro-

gates of truth are used instead, e.g., manual delineations. If multiple manual

delineations CmanOk

= (C, fOk) exist, a fuzzy surrogate of truth Ctrue = (C, ftrue)can be generated by averaging, i.e.,

ftrue(x) =1

N

N

∑k=1

fOk(x),

where N is the number of delineations. The segmentation accuracy is then

obtained by computing the sensitivity as the true positive volume fraction

T PV FMO (O) =

|CT P||Ctrue| =

|CMO ∩Ctrue||Ctrue| ,

and computing the specificity as one minus the false positive volume fraction:

1−FPV FMO (O) = 1− |CFP|

|Ctrue|= 1− |C

MO −Ctrue||Ctrue|

.

A completely accurate segmentation method will have both specificity and

sensitivity equal to one, see Figure 3.6 for an illustration of the accuracy com-

ponents in the crisp case. For the definitions of union, intersection, comple-

ment, and cardinality for fuzzy sets, see Section 3.5.

C

C

C

C

C

FN

FP

TP

true

OM

Figure 3.6: 2D illustration of the accuracy components in the crisp case. The sensitiv-

ity is computed as |CT P|/|Ctrue| and the specificity is computed as 1−CFP/|Ctrue|.

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Segmentation precision is a measure of repeatability, i.e., how sensitive the

result is to the operator input, e.g., seeding. Both inter- and intra-operator pre-

cision must be considered. A full evaluation of precision also considers how

the patient positioning in the scanner affects the result (inter-scan precision).

The suggested precision metric for two fuzzy segmentations CMO1

and CMO2

ob-

tained with method M at different occasions is

PRM(O) =|CM

O1∩CM

O2|

|CMO1∪CM

O2| .

PRM(O) represents the amount of tissue common to both CMO1

and CMO2, the

intersection of the sets, as a fraction to the total amount of tissue found in the

union of CMO1

and CMO2.

We used this framework for evaluation of our fast marching segmentation

and deformable model segmentation in Paper IV, V, and VI. It is also imple-

mented in the WISH toolkit described in Paper VIII.

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4. Visualization

Visualization is the process of creating images to convey information. In com-

puter science, this involves rendering images onto a computer screen by us-

ing computer graphics techniques and graphical user interfaces. The aim of

a visualization is to reduce the huge amount of information contained in a

multi-dimensional dataset in order to make it perceptible for the user. Inter-

active visualizations that can be manipulated and examined in real-time are

preferable.

In medical image visualization, 2D, 3D, and 4D images, and sometimes

images of even higher dimensionality need to be visualized. 2D images are

straight-forward to visualize by displaying the images on the screen together

with a user interface that allows the user to select a proper contrast/brightness

window and to magnify or minify the image. For 3D and 4D images, more

sophisticated visualization techniques are required in order to not overwhelm

the user with information. In this chapter, we describe the methods for medical

image visualization that have been used in this work.

4.1 Multi-planar reformatting

Multi-planar reformatting (MPR) is a classic visualization technique for view-

ing 3Dmedical images. Arbitrarily positioned and oriented 2D planes are used

to visualize multiple cross-sections of the 3D dataset. The common applica-

tion of MPR is to display the three principal planes (axial, coronal, and sagit-

tal) next to each other along with a user interface that allows for translation

of the planes. It is also possible to display the planes in their correct 3D posi-

tion and orientation, see Figure 4.1. The simplicity of this approach, and the

fact that it is so widely used make it a standard tool in most medical image

visualization applications. MPR is a standard tool and was used in all papers

included in this work. In the WISH toolkit described in Paper VIII, the MPR

viewer has support for rendering of overlays to, e.g., display segmentation

results.

4.2 Volume rendering

Volume rendering techniques [25, 9] is a family of rendering techniques where

the full 3D dataset is considered. The parts of the volume important to the

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Figure 4.1: A CT image of the abdomen visualized with multi-planar reformatting.

user are displayed while uninteresting parts are made transparent or semi-

transparent by tuning of application specific transfer functions. The most com-

mon approach to perform volume rendering is by using ray-casting. Through

each pixel in the image plane, a ray is cast from the view position into the

volume, see Figure 4.2. For all voxels along the ray, the scalar value is sam-

pled and used for lookup in a transfer function. The resulting color of the

image plane pixel is determined by the selected compositing technique. Com-

mon compositing techniques are alpha blending, maximum intensity projec-

tion (MIP), and iso-surface extraction. Because no geometric representation of

the data is needed, the term direct volume rendering (DVR) is commonly used.

To perform DVR in software is computationally demanding and not suitable

for interactive renderings. By using hardware accelerated DVR, described in

the next section, it is possible to speed up the rendering to interactive rates on

ordinary workstations.

4.3 Hardware accelerated direct volume rendering

In recent years there has been a great development of consumer graphics hard-

ware where the fixed-function pipeline in the graphics processing unit (GPU)

has been replaced by programmable vertex processors and fragment proces-

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(0,0,1)

(0,1,0)

(0,1,0)

(1,1,0)

(1,0,0)

(1,1,1)

(1,0,1)(τ )

c

(τ)

Image plane

dr0

(0,0,0)

rr e

Figure 4.2: Volumetric ray-casting. Through each pixel in the image plane, a ray is cast

from the camera position c into the volume. In the GPU implementation, the volume

is represented by a 3D texture. For each fragment generated in the rasterization of the

bounding box, the entry point r0 and direction d = r0− c of the ray are interpolated.

sors. These can be customized for the application by using shader programs.The vertex shader is responsible for vertex transformation, projection, and for

specifying which varying vertex attributes (e.g., colors, normals, and texture

coordinates) should be interpolated across the primitive we are drawing. The

fragment shader is active in the primitive rasterization stage and is responsible

for writing a color to the frame buffer based on interpolated attributes from the

vertex shader and additional uniform data, e.g., textures.

In order to generate the fragments (pixels) needed for the ray-casting, a

proxy geometry is needed, e.g., the bounding box of the volume. Each vertex

of the box is assigned a texture coordinate in [0,1]× [0,1]× [0,1]. These val-

ues are interpolated across the box faces during rasterization in order to obtain

the entry position r0 of the ray. The ray direction is computed as d = r0− c,where c is the camera position in texture coordinates. The ray-casting is then

performed in the fragment shader on the GPU by sampling the 3D texture

representation of the volume along the parametric ray r(τ) = r0 + τ d||d|| by in-

crementing τ with a suitable step length Δτ until r(τ) is outside the volume,

see Figure 4.2. This technique is the most common today [24, 46]. In ear-

lier approaches, when the programmability of the GPUs were limited, it was

common to slice the dataset with back-to-front ordered, viewplane-aligned

polygons [52].

With this general ray-casting engine it is possible to use different sample

compositing techniques along the ray. In our implementation described in Pa-

per VII we use a specialized maximum intensity projection (MIP) for color-

correct visualization of 4D MR breast images. In our toolkit (Paper VIII) we

have implemented three additional compositing modes: standard MIP, front-

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Figure 4.3: Left: Volume rendering with alpha compositing of a CT scan of the head

and upper thorax. Right: Ray-casting in iso-surface mode of the fast marching seg-

mentation result of a liver.

to-back alpha blending, and iso-surface extraction with shading. Figure 4.3

shows some rendering examples1.

4.4 Surface rendering

In surface rendering, polygonal surfaces are extracted from the dataset and

displayed by using standard computer graphics techniques. Because of sim-

plicity and hardware issues, triangles are commonly used. The most well-

known algorithm for surface extraction from volumetric data is Marching

Cubes (MC) [27]. MC is designed for iso-surface extraction, i.e., surfaces with

the same scalar value, see Figure 4.4. Eight voxels at a time are examined. De-

pending on whether the voxels are inside or outside the selected iso-surface,

a configuration number is computed and the corresponding triangulation is

obtained through table lookup. Because eight voxels are examined for being

inside or outside, there are 28 = 256 possible configurations.

Surface normals are obtained by computing the gradient of the data. By

performing tri-linear interpolation of positions and gradients, smooth shaded

surfaces can be obtained. The MC algorithm is also useful for rendering of

binary images obtained through, e.g., segmentation.

1Anders Persson, CMIV, Linköping, is acknowledged for providing the dataset in Figure 4.3

(left). The same dataset is also used in Figure 4.4 and Figure 4.5.

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Figure 4.4: Left: Iso-surface extraction of the skin in a CT image performed with

marching cubes. Right: A close-up of the ear where the large amount of generated

triangles are visible.

4.5 Stereo graphics

The standard way of rendering images onto a computer screen only provides

212D information. Perspective projection, occlusion, and shading effects pro-

vide quite strong depth cues, but the image is still 2D. In order to provide a

more realistic 3D perspective, stereo graphics can be used where two images

are presented to the user, one for the left eye and one for the right eye. These

images show the same scene from a slightly different perspective based on the

horizontal distance between the eyes, the disparity. To present a correct stereo

effect to the user, the left image must be visible to the left eye only, and vice

versa. To obtain this, there are a number of techniques available [41].

In color-multiplexed (anaglyph) displays, the left and right images are fil-

tered with near complementary colors and the user wears corresponding filter

glasses. A drawback with this technique used to be the limited color render-

ing, but with modern notch filters this problem is mitigated. Another technique

is polarization-multiplexing where polarizing filters are used for rendering of

the image pairs and the user wears polarizing glasses. This technique requires

that the screen preserves the polarization.

With time-multiplexing, the image pairs are rendered rapidly in alternate

refresh cycles and the user wears active shutter glasses that are synchronized

to the rendering. In this stereo rendering technique, the frame rate must be

twice as high compared to mono rendering. It is also common with cross-talk

(ghosting) effects due to non-perfect shuttering and slow phosphor decay of

the cathode ray tube (CRT) monitor. Time-multiplexing has been used in this

work. It is part of the haptic displays described in Section 5.2.

Location-multiplexing means that the images are rendered at different loca-

tions and sent to the eyes in separate channels. An example is head-mounted

displays (HMDs). A more simple example of location-multiplexing is illus-

trated in Figure 4.5, where it is possible to obtain a stereoscopic view by

41

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crossing the eyes. In [41], a good overview of stereoscopic rendering and 3D

displays is given, including modern auto-stereoscopic display technology.

Figure 4.5: Stereo pair of an iso-surface rendering of a CT image. The stereo effect is

obtained by crossing the eyes.

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5. Computer haptics

In this chapter an introduction to computer haptics is given. First, some haptic

devices, display solutions, and softwares for haptics are reviewed. The follow-

ing sections is about haptic rendering techniques with focus on volume haptics

and its use in medical segmentation.

5.1 Haptic devices

A haptic device, according to its name, should be capable of both tactile and

kinesthetic feedback, but most commercially available devices today provide

only kinesthetic feedback. Well-known devices are the PHANToM series from

Sensable Technologies1, the Omega.X family from Force Dimension2, and the

recently released low-priced Falcon from Novint3, see Figures 5.1 and 5.2.

These devices are impedance driven, i.e., they follow the rule position in –

force out. An admittance driven device follow the rule force in – position out.

The number of dimensions the haptic device can monitor and control is re-

ferred to as the degrees of freedom (DoF). The DoF need not to be the same for

input and output. The PHANToM desktop device takes a 3D position and three

rotations for input (6DoF) and for output it provides a force vector (3DoF).

Devices that have six DoF in and six DoF out provide more complexity and

are hence more expensive. Examples of six DoF in and six DoF out devices

are the PHANToM Premium 1.5/6DoF and PHANToM Premium 3.0/6DoF.

The design of a haptic device varies, but in most cases they are constructed

with a stylus or a ball that the user holds in her hands. A single point, the

haptic probe, is located at the tip of the stylus or at the center of the ball and

serves as the interface to the haptic device.

The haptic devices that have been used in this work are the PHANToM

Desktop and the PHANToM Omni, see Figure 5.1. Some features of these

devices are summarized in Table 5.1.

1URL: http://www.sensable.com2URL: http://www.forcedimension.com3URL: http://home.novint.com

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Figure 5.1: The PHANToM Desktop device (left) and the PHANToM Omni device

(right).

Figure 5.2: The Omega.X device from Force Dimension (left) and the Falcon device

from Novint (right).

5.2 Haptic displays and software

A desktop haptic devices can simply be positioned next to the keyboard and

mouse and used as an additional advanced interaction device. This way of

usage is common in the test phase of application development when the pro-

grammer need to test, restart, and recompile the application frequently.

In our work we have used special haptic displays from the Swedish com-

panies Reachin4 and SenseGraphics5 where the 3D capabilities of the device

are used to a higher extent. Both companies provide display solutions where

the haptic device is positioned beneath a semi-transparent mirror. The graph-

ics is rendered with time-multiplexed stereo and projected through the mirror

4URL: http://www.reachin.se5URL: http://www.sensegraphics.com

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Table 5.1: Features of the PHANToM Desktop and the PHANToM Omni devices.

PHANToM Desktop PHANToM OmniWorkspace 160 × 120 × 120 mm 160 × 120 × 70 mm

Weight 2.86 kg 1.79 kg

Position resolution 0.023 mm 0.055 mm

Maximum force 7.9 N 3.3 N

Continuous force 1.75 N 0.88 N

Stiffness 1.86 N/mm (x-axis) 1.26 N/mm (x-axis)

2.35 N/mm (y-axis) 2.31 N/mm (y-axis)

1.48 N/mm (z-axis) 1.02 N/mm (z-axis)

Interface Parallel port IEEE-1394 Firewire� port

Platform Intel PC Intel PC

in order to obtain co-localization of haptics and graphics, see Figure 5.3 and

Figure 1.3.

Both display vendors also provide programming API:s for 3D visualization

applications with haptics. Reachin provide their Reachin API and SenseG-

raphics has their dual commercial and GPL (open source) licensed software

H3D API. Both API:s have been used in this work, but the WISH toolkit de-

scribed in Paper VIII has been implemented in the H3D API. For research

purposes, an open source solution is more convenient.

Figure 5.3: The Reachin desktop display with a PHANToM Desktop haptic device.

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A low-level API for programming haptic applications is OpenHaptics from

Sensable. OpenHaptics has similar syntax as OpenGL, making it familiar to

graphics programmers. The H3D API (up to version 1.5) uses OpenHaptics

for haptic rendering.

5.3 Haptic rendering

Haptic interaction with objects in a 3D computer graphics environment in-

volves the task of generating intuitive force feedback when the user moves

the haptic probe so that it comes in contact with an object. Depending on

the application, there are different object representations to interact with. We

can have explicit (polygonal) surfaces, implicit surfaces, and, as in this work,

volumetric data. In order to obtain perceptually convincing haptic feedback,

the haptic update rate should be approximately 1 kHz. The haptic rendering

techniques described in this chapter is point-based haptic feedback with three

DoF.

5.3.1 Haptic surface rendering

An algorithm for surface haptics should generate force feedback when the

haptic probe comes in contact with, or penetrates, a surface. The first algo-

rithm for haptic interaction with polygonal surfaces was the penalty method

described in [31]. Since an impedance controlled haptic device cannot explic-

itly control the position of the haptic probe, the rendering algorithms must

allow for penetration of surfaces. In the penalty method, the force feedback

generated is proportional to the distance from the haptic probe to the closest

point on the polygon that has been penetrated. This method is unstable and is

not commonly used today. By instead introducing a virtual probe that can be

completely controlled by the algorithm, the force feedback can be based on the

distance between the true probe and a virtual probe. This was first suggested

in [56], where a so-called god-object was constrained to stay on the rendered

surface. This algorithm was further refined in [39], where the god-object was

replaced by a finite-sized spherical proxy point. These techniques are referred

to as constraint-based since the surfaces constrain the movements of the god-

object and the proxy. In the proxy-method, the connection between the haptic

probe and the proxy consists of a spring-damper, i.e., a virtual coupling device

consisting of a spring and a damper, see Figure 5.4. The rendering equation

for proxy-based surface haptics is

f =−k(x−p)− γ(x− p), (5.1)

where x is the probe position, p the proxy position, k the stiffness of the spring-

coupler, γ the damping coefficient, and x and p the velocities of the probe and

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Figure 5.4: Proxy-based surface haptics. The haptic probe (white) is connected to a

virtual proxy (black) through a spring-damper. Note that the distance between the

probe and the proxy is exaggerated.

the proxy, respectively. In many applications, the damping term is set to zero

since it is hard to determine an optimal value [35].

The distance between the probe and the proxy is in general small. For in-

stance, if the user applies a force of 1 N and the spring-damper stiffness is

500 N/m, the probe–proxy distance is 1/500 m=2 mm. To reduce the feeling

of offset, the graphical representation of the haptic probe can be rendered at

the proxy position.

5.3.2 Haptic volume rendering

One option to perform haptic rendering of volumetric data is to locally es-

timate surfaces and use them as an intermediate representation for a surface

haptics technique [23]. For direct haptic rendering of volumetric data, one of

the first algorithms was suggested by Avila and Sobierajski [2]. They proposed

a direct force mapping based on the current position and velocity of the haptic

probe along with local data measures, e.g., density value and gradient:

f = �F (x, x,V (x),∇V (x)) ,

where V is the volumetric data. A similar six DoF haptic rendering scheme

for direct display of vector data was suggested by Iwata and Noma [19]. A

drawback with these techniques is that they add energy to the system [35], and

therefore are noise sensitive and tend to result in vibrations. However, they

constitute an important step in the development of haptic volume rendering

techniques.

5.3.3 Proxy-based volume haptics

State-of-the art in direct volume haptics is derived from the proxy-based meth-

ods for surface haptics [56, 39] and was introduced by Lundin [30]. Here, the

interpolated gradient direction at the proxy position is used as a surface normal

to define a surface to which the proxy is constrained. By using haptic transfer

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functions, the stiffness and friction of the surface can be modulated. Ikits [18]

describes a general framework for three DoF haptic rendering of volumetric

data based on a constrained proxy-point. The basic idea here is to choose an

appropriate local reference frame (LRF) and generate constraints for proxy-

movements in the LRF. The proposed method works for arbitrary LRFs, and

as an example it is shown how to haptically render diffusion tensor MRI data.

Common for these techniques is that they require the axes in the LRF to be or-

thogonal. In 2005, Lundin [29] presented a more general framework based on

four basic haptic primitives: point, line, plane, and directed force. This frame-

work allows for direct volume haptics in non-orthogonal LRFs and provides

an intuitive abstraction layer for proxy-based volume haptics. The primitive-

haptics framework was further developed in [28] and summarized in Lundin’s

PhD thesis [35].

The implementation of proxy-based direct volume haptics used in this work

has mainly been based on the framework in [18]. The fundamentals of this

framework is described below.

Let {e0,e1,e2} denote the LRF, pt the proxy position at time step t, xt the

probe position, and d = (xt − pt−1) the displacement of the probe relative to

the previous proxy position. In each iteration of the haptic loop, the proxy is

moved in small steps according to local data measures, haptic transfer func-

tions, and rendering parameters. Allowed proxy movements are defined by

motion rules for each axis in the LRF. The proxy position at time step t is

computed as

pt = pt−1 +2

∑i=0

Δpiei,

where Δpi is a motion rule function of the displacement di = d · ei. The re-

sulting force is computed as f t =−k(xt −pt), where k is the stiffness of the

spring-coupler. Figure 5.5 gives an illustration of the algorithm. The motion

rule function for a unilateral constraint along axis i is defined by

Δpi =

{di if di > 0

max(|di|− si/k,0) if di ≤ 0,

where si is the strength of the constraint, in this case the force threshold that

the user must apply to move in the direction −ei. Along +ei, there is free

motion. This is the motion rule commonly used for surface simulation with

axis i being the normal direction, see Figure 5.6. For a bilateral constraint,we have

Δpi = sign(di)max(|di|− si/k,0),

which is used, e.g., to simulate friction of a surface in the directions orthogonal

to the surface normal.

In addition to the constraints above, we also define the motion rule function

for a directed force:Δpi = si/k +di,

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e

p

e0

t−1

2

p t

f txt

e1d

Figure 5.5: Proxy-based haptic volume rendering. The proxy is moved from pt−1 to

pt according to motion rules specified for each axis in the LRF. The resulting force is

proportional to the displacement (xt −pt).

d

0

0e

ks /

0ds0/

0e

k0

dd

Figure 5.6: Proxy-based volume haptics with a unilateral constraint for surface simula-

tion. Here, the gradient is used to compute the normal direction, i.e., e0 =−∇ f /||∇ f ||.In order to move in the direction −e0, the user has to apply a force such that

|d0| > s0/k. To the left, |d0| < s0/k which gives Δp0 = 0, i.e., the proxy will not

move. To the right, |d0| > s0/k which gives Δp0 = |d0| − s0/k, i.e., the proxy will

move Δp0e0.

which can be used, e.g., to follow a vector field. In our implementation of this

framework, the strengths si of the involved constraints are controlled through

haptic transfer functions, e.g., sigmoid functions based on the image intensity

I(p) at the proxy position:

si = si(I(p)) =A

1+ e−(I(p)−β )/α ,

where A is the maximum strength, β controls the center of the function, and αcontrols the width of the function. In Paper V and Paper VIII, we combine mo-

tion rules into haptic modes for haptic volume rendering of surfaces, viscosity,

potential fields, and vector fields. See also Section 6.3 and Section 6.6.

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5.4 Volume haptics for medical image segmentation

Volume haptics for image segmentation is not yet widely used, but there has

been some work conducted in this field. Harders and Székely [17] showed

by conducting user studies how haptic feedback significantly improved man-

ual center-line extraction of tubular structures in MR images. The aim was

to initialize a deformable surface for segmenting the small intestines. They

performed an approximate segmentation through thresholding and computed

a distance map of the thresholded dataset. The haptic feedback was then com-

puted from the gradient of the distance map by using a direct force mapping

technique. Spuhler [45] presents methods for improved interactive centerline

extraction by using haptic guidance and snakelets for application in virtual en-

doscopy. Giess et al. [14] employed haptics for positioning of landmarks in a

3D segmentation application for liver surgery planning. Senger [42] describes

an immersive segmentation environment where proxy-based haptic feedback

is used to provide a sense of touch for segmented structures and to control a

seeded region-growing algorithm.

In this work, proxy-based volume haptics has been used in several different

ways for interactive segmentation. In Paper I, the method in [30] was used for

tracing of vessels in MR angiography images. The aim here was to facilitate

seeding of vessels for separation of arteries and veins. The same volume hap-

tics implementation was also used in Paper III for guiding the user to draw

live-wire curves in 3D. In Paper II, we made an implementation of the frame-

work in [18] in order to perform haptic rendering based on GVF fields. This

implementation was extended in Paper V where it was used for exploration of

external force image data for deformable model segmentation.

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6. Contributions

In this chapter, the methods and results described in detail in the appended pa-

pers are presented briefly. The theory behind the methods has been described

in the previous chapters, and therefore the focus in this chapter is on the ap-

plication of the methods and the results.

6.1 Haptics for seeding of region growing algorithms

As mentioned in the introduction, semi-automatic segmentation methods

should combine the outstanding capabilities of the human to recognize

objects with the capabilities of the computer to perform the tedious task of

exact delineation. An example of recognition is seeding, i.e., positioning of

seed-points and seed-regions inside the object of interest.

6.1.1 Seeding of vessels in MRA

In Paper I, we present a method for seeding of vessels in whole-body CE-

MRA images directly in 3D guided by a hardware accelerated MIP and vol-

ume haptics. We use an implementation of Lundin’s proxy-based direct vol-

ume haptics method [30] where frictional surfaces are simulated by using

the gradient as surface normal. Thereby we are able to render stable haptic

feedback based directly on the image data, which differs from previous at-

tempts to trace tubular structures where direct force mapping from segmented

data [3, 17] has been used. The resulting haptic feedback allows the user to

trace the vessels, place seed-points with different labels (colors), and expand

them to larger seed-regions with a region growing method. The goal is to use

the seeds as input to a gray-scale connectedness algorithm (similar to FC)

in order to separate the main arteries from each other and from other bright

objects.

Previously, the seeding was performed with mouse interaction in an MPR

view. An advantage of the haptic interface and interaction compared to the

previous method, is a large increase of the number of placed seed-points and

thereby faster convergence of the gray-scale connectedness segmentation. An-

other advantage is the possibility to trace vessels directly in 3D which facili-

tates seeding of vessels with complex orientation. Figure 6.1 shows a screen-

shot from the application and a vessel separation result.

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Figure 6.1: Left: A screenshot from the application. The user is seeding the vascular

tree in a head and upper thorax data set guided by volume haptics and a hardware

accelerated MIP. Right: Final gray-scale connectedness segmentation result.

During the work with this application we made the first implementations of

proxy-based volume haptics and hardware accelerated volume rendering that

became fundamental tools in coming projects.

6.1.2 Volume haptics based on GVF

In Paper II, we introduce proxy-based volume haptics rendering based on GVF

fields. The application here is again seeding, but now for interactive liver seg-

mentation from MR images. The aim is to initialize a seed-region inside the

liver and then perform segmentation with the fast marching method. A draw-

back with the fast marching method is that it is prone to leaking if the ini-

tialization is asymmetric and/or positioned too close to the object boundary.

Therefore we provide haptic feedback to guide the user to stay centered inside

the liver in order to facilitate a symmetric initialization. Existing methods,

including our gradient-based feedback used in Paper I, provides the desired

feedback only for narrow and elongated objects as vessels, but not for wider

objects as the liver since feedback is provided only immediately at the bound-

ary where the gradient is large enough.

To overcome this limitation, we suggest a rendering method based on GVF.

The initial idea with GVF was to increase the capture range of the gradient for

segmentation with deformable models by propagating the gradient informa-

tion of strong boundaries into the inner part of homogeneous regions. Here,

we use this property to provide haptic feedback that allows the user to stay in-

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side the object while still feeling its boundaries. In this work we use the proxy-

based volume haptics framework by Ikits [18] described in Section 5.3.3. The

first component in our LRF is determined by the direction of the GVF field

V at the proxy position, i.e., e0 = V(p)/|V(p)|. The orthogonal directions are

constructed so that e1 ·e0 = 0, |e1|= 1, and e2 = e0×e1. We apply a unilateral

constraint with strength s0 that obstructs proxy movements along the GVF

field. In the orthogonal directions we use low-strength bilateral constraints.

The idea is to provide feedback that allows the user to move freely inside

the object without getting out. Therefore, the strength s0 is modulated with a

sigmoid shaped transfer function based on the magnitude of the GVF field:

s0 = s0(|V(p)|) = Tmin +Tmax−Tmin

1+ e−(|V(p)|−β )/α ,

i.e., s0 ∈ [Tmin,Tmax]. The parameters α and β are interactively controlled by

the user. This way, we obtain a high strength close to object boundaries where

the GVFmagnitude is high and a lower strength far away from the boundaries.

The suggested haptic rendering was tested on both synthetic and real data,

see Figure 6.2. From the force magnitude graph we see that the feedback

behaves as desired. The magnitude of the rendered force increases when we

move the haptic probe from the middle of the object towards the border. This

is because the constraint strength s0 increases with GVF magnitude. When we

move along the border there are only small changes in magnitude and while

we move along the GVF field into the center the force magnitude is very small.

The peak to the right occurs when we move from the center and finally leave

the object.

A drawback with this method at the time of submission of Paper II was

the time-consuming computation of the GVF field. In our work [51], we use

more advanced numerical schemes in order to speed up the computations.

With these schemes, the GVF equation was solved 1–2 orders of magnitude

faster than with the commonly used straight-forward implementation.

6.2 An extension of live-wire to 3D

In Paper III, we present a new 3D extension of the live-wire method. In the

2D live-wire method, the user places seed-points that are connected by optimal

minimum-cost paths. Our idea for a 3D extension is to let the user draw live-

wire curves which are connected by discrete minimum-cost surfaces, a process

we call bridging. The aim is to segment entire objects by drawing a relatively

small number of live-wire curves on the boundary of the object.

The live-wire method involves Dijkstra’s algorithm to compute shortest

paths in a graph representation of the image. To convert a 3D image into a

graph, we have chosen to place a node at the center of each voxel and cre-

ate edges to all its 26 neighbors. This definition does not use oriented edges

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0 5 10 150

0.5

1

1.5

Time (s)

Fo

rce

mag

nit

ud

e (N

)

Figure 6.2: Top left: A slice of the test volume and the path traveled with the hap-

tic device. Top right: The magnitude of the rendered force along the path. Bottom:

Screenshot from the application where the user has seeded the liver in an MR image

guided by the GVF-based haptic feedback.

as in [13], but it has the advantage that the resulting graph has relatively few

nodes. This is important since the bottleneck of Dijkstra’s algorithm is main-

taining the heap containing the nodes.

For actually drawing the curves interactively in 3D, we have implemented

a user interface where the user has two options: (1) place seed-points freely

in the volume guided by volume haptics and volume rendering, and (2) draw

the curve onto an arbitrarily oriented slice of the volume, see Figure 6.3. The

haptic feedback in the first case is proxy-based volume haptics tuned to feel

the surface of the object, and in the second case the slice plane is a haptic

surface that the user can feel while drawing.

The bridging algorithm for connecting two curves is based on the image

foresting transform (IFT) [10]. The IFT is essentially Dijkstra’s algorithm for

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Figure 6.3: Illustration of the 3D live-wire method. Left: Placing seed-points freely in

the volume using volume rendering and volume haptics to locate the boundary of the

object. Right: Drawing a live-wire curve onto an arbitrarily oriented slice.

(a) (b) (c) (d)

Figure 6.4: Illustration of the bridging algorithm. (a) A synthetic spherical object. (b)

Two closed live-wire curves on the boundary of the object. (c) Result of connecting

the two curves with the IFT. (d) Result of our algorithm including rasterization.

shortest path calculation, modified to allow an arbitrary number of seed-points

in order to find the shortest path from all points in the image to any of the seed-

points. With the IFT, we compute the optimal curves from each voxel in one

of the curves, using all voxels of the other curve as seed-points. Since the

curves we compute are independent of each other, the result is generally not a

tunnel-free surface. To fill the gaps between the curves we define a polygonal

surface between adjacent curves. These polygons are then rasterized to obtain

a discrete surface, see Figure 6.4. Note that all points on the second curve are

not necessarily the closest point to a point on the first curve. Therefore we run

the bridging algorithm from both directions and use the union of the results.

In this way, we are guaranteed that the result always includes the two original

curves.

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6.3 Interactive deformable models

In Paper V we present our framework for interactive segmentation with de-

formable models. The framework involves a standard 2-simplex mesh data

structure and deformation engine, see Section 3.6.2. The main contribution

here is the new interaction possibilities. By using our 3D interface we can

perform initialization of the model close to the structure of interest. This is

an important property since the sensitivity to initialization is commonly re-

garded as the main drawback with deformable model segmentation. In addi-

tion to the enhanced initialization we have the possibility to interact with the

model by providing interaction forces during deformation in order to speed

up convergence and to obtain a more accurate segmentation. As described in

Section 3.6.3, a deformable model is typically driven by a number of image

based external forces. In general, it is not possible to visualize all of the un-

derlying data that drives the model. Therefore, we also use volume haptics as

an additional channel to convey information about the data. This facilitates

the parameter tuning, which is regarded as another drawback with deformable

model segmentation.

Deformation engine

In our implementation, the deformation engine is based on Newtonian evolu-

tion and the internal regularizing forces are based on curvature adaption in the

tangential direction and a C2 constraint in the normal direction. We use the

four external forces that are described in Section 3.6.3: gradient magnitude

force, inflation force, potential field force, and vector field force.

Mesh interaction

The most basic interaction with the mesh is for initialization where the haptic

device is used to grab and translate the initial mesh. In order to provide inter-

action forces during deformation, we allow the user to select parts of the mesh

with the haptic probe, see Figure 6.5. The selected vertices are then affected

by interaction forces computed in a similar way as the image based external

forces, i.e.,

(Finteraction)i = wi(fprobe ·ni)ni,

with

fprobe = (r−pi)/||r−pi||.

Here, wi is a weight, r is the position of the probe, pi is the position of the

current vertex, and ni is the normal direction at pi. The sign of wi controls the

direction of the force, i.e., if the user will pull or push the selected sub-mesh.

This interaction is performed with haptic feedback where the force rendered

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Figure 6.5: Left: Initialization of the model with a sphere consisting of 42 vertices and

80 faces. The fuzzy connectedness map is overlaid on the original CT image. Right:

Interaction forces are applied to selected vertices (yellow).

to the user is the reaction force averaged over all selected vertices, i.e.,

Freaction =− 1

Nselected∑i∈S

(Finteraction)i,

where the set S contains the indices for the Nselected selected vertices.

Volume haptics

For the purpose of rendering the different types of external force data, the

volume haptics framework described in Section 5.3.3 was used to implement

four haptic modes. Note that in Paper V, only three modes were implemented,

but here we also include the additional viscosity mode that was added in

Paper VIII. The modes are:

Surface mode: In surface mode, a unilateral constraint is used in the normal

direction e0 = ∇I(p)/||∇I(p)|| and bilateral frictional constraints are used in

the orthogonal directions. The user sets the strength of the normal constraint

s0 and the friction coefficient μ through haptic transfer functions, i.e.,

s0 = s0(I(p)) and μ = μ(I(p)). The strengths of the frictional constraints are

computed as s1 = s2 = |f · e0|μ , where f is the current force generated by the

spring-coupler.

Viscosity mode: The aim with this mode is to provide an intensity-modulated

resistance force. Three bilateral constraints with equal strength are used. The

strength is controlled with a transfer function based on the intensity at the

proxy position. This mode is orientation independent which means that we

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can choose an arbitrary LRF.

Potential mode: In the potential mode, the main direction is computed

as e0 = ∇P(p), where P is a potential field, e.g., a signed distance map.

The constraint is either unilateral or a directed force. The strength s0 is

controlled with a transfer function based on the gradient magnitude, i.e.,

s0 = s0(||∇P(p)||). For the orthogonal directions e1 and e2, bilateral frictionalconstraints are used.

Vector mode: The vector mode is identical to the potential mode, except

that the direction of the vector field V is used as the main direction, i.e.,

e0 = V(p)/||V(p)||.

Results

To demonstrate the system, we made a small-scale experiment where we per-

formed interactive segmentations of the liver in 10 abdominal contrast en-

hanced venous phase CT images. For each image, we have a manual de-

lineation of the liver made by a radiologist using the routine software of a

Siemens Leonardo workstation. The time required for the manual delineation

was between 5 and 18 minutes per dataset

To drive the model, we chose an inflation force based on a fuzzy connect-

edness (FC) map that we compute prior to initialization of the model. Seeding

of the FC map is performed interactively by using manual seeding of interior

liver voxels using the haptic probe. The deformable model is interactively ini-

tialized by a sphere, see Figure 6.5. When the deformation engine is activated,

the initial model propagates in its normal direction based on the FC map and

the internal curvature based forces adapt the mesh resolution locally to the

object. Typically, the initial mesh is coarse, and therefore global mesh refine-

ments through subdivision are also needed. By applying interaction forces

during deformation and performing global mesh refinements, the segmenta-

tion result is obtained in 2–3 minutes. The resulting mesh is voxelized in or-

der to measure the accuracy against the manual segmentations. This is done

according to the framework described in Section 3.7. The results show that we

obtain an average sensitivity of 90% and an average specificity of 99% for the

10 datasets.

6.4 Accurate and reproducible liver segmentation

In Paper IV, we describe an interactive fast marching method for liver seg-

mentation. Four users independently performed segmentation of the liver in 52

abdominal contrast enhanced venous phase CT images from 26 patients with

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either carcinoid or endocrine pancreas tumor that underwent two CT exami-

nations with time interval 3–17 months. The aim was to measure the volume

of the liver because disease progress is correlated to liver enlargement.

The fast marching method performs well, but in some cases there are prob-

lems with leakage due to low contrast between the liver and surrounding tis-

sue, especially between the liver and the heart. In Paper VI, we combine the

fast marching segmentation with a subsequent deformable simplex mesh seg-

mentation in order to mitigate the leakage problem.

Fast marching segmentation

The fast marching method in Paper IV involves interactive initialization of

the method (seeding) with the haptic interface, computation of a cost image,

and fast marching propagation of seed-regions with automatic time-of-arrival

thresholding. In the initialization step, the user performs seeding of the liver in

an MPR view where a haptic spring-force guides the user to draw seeds in the

desired slice. The reason why we did not use the GVF-based volume haptics

here was because our efficient GVF solver [51] was not developed yet. With

the standard solver, the computation time required would simply be too long

for the large number of datasets.

The average seeding time for the four users was 40 seconds and the average

number of initialized seed-voxels per dataset was just below 3000. Based on

gray-level statistics from the seed-regions, the cost image was computed in

four steps: (1) edge-preserving smoothing using bilateral filtering (see Sec-

tion 2.2.2), (2) voxel-wise gray-level transformation based on statistics from

the seed-regions, (3) gradient magnitude extraction, and (4) weighted sum of

the result from (2) and (3). See Figure 6.6. The result from the fast marching

method, as described in Section 3.4, is a time-of-arrival map that need to be

thresholded to obtain a crisp segmentation. To automatically find a threshold

value, we examine the average cost of the front voxels during propagation

and choose the time value with maximum average cost as threshold. This is

illustrated in Figure 6.7 together with a segmentation result.

Deformable model segmentation

In Paper VI we use our deformable model framework to fit simplex meshes to

the fast marching results in order to mitigate the leakage problem and obtain

a more accurate segmentation. From the fast marching result, we compute

a signed distance map with positive values outside the contour and negative

values inside the contour. This distance map is regarded as a potential field

and is used as an external force to drive the deformable simplex mesh. The

aim is to fit the mesh to the fast marching segmentation and make use of

the built-in shape regularization of the mesh to avoid capturing the irregular

erroneous regions caused by leaking. In addition to the potential force, the

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Figure 6.6: Cost image generation. (a) Original CT image. (b) Result of bilateral fil-

tering. (c) Result of voxel-wise gray-level transformation. (d) Gradient magnitude of

(c). (e) The resulting cost image, a weighted sum of (c) and (d). (f) Gray-level profile

for the edge in (e).

Figure 6.7: Left: The average cost of the front voxels at each time instance. The time

of arrival at the maximum peak is used as a threshold to obtain the final segmentation.

Right: A slice of one of the 52 datasets with overlaid segmentation result (blue) and

the seed regions (red).

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Figure 6.8: Left: Surface rendering of the fast marching segmentation result for one of

the livers. Note the leakage problem between the liver and the heart. Right: Segmen-

tation result obtained with the deformable mesh. Here, the irregular region caused by

leaking is removed because of the built-in shape regularization of the mesh.

user also provides interaction forces during deformation. In this experiment,

one user performed liver segmentation with the deformable simplex mesh for

two of the four sets of fast marching segmentations.

Results

We quantitatively evaluate both segmentation precision and accuracy using the

framework described in Section 3.7. For 23 of the datasets, we have manual

delineations performed by two radiologists using the routine software of a

Siemens Leonardo workstation. From these delineations, we construct a fuzzy

ground truth per dataset by averaging the manual delineations as described in

Section 3.7. The simplex mesh segmentations were voxelized in order to be

compared with the true segmentations.

The mean interaction time for seeding of the fast marching method was 40

seconds per dataset with standard deviation (SD) 23 seconds. For the subse-

quent deformable mesh segmentation, we have a mean interaction time of 93

seconds (SD 16 seconds). The interaction time required for the manual delin-

eation was between 5 and 18 minutes. For the two sets of 23 manual segmenta-

tions performed by the radiologists, we obtain a mean precision of 88.9% with

coefficient of variation (CV) 1.9%. The mean precision of the fast marching

method is 96.9% (CV 3.8%), which is considerably higher. For the two sets

of simplex mesh segmentations, we obtain a mean precision of 97.8% (CV

0.5%) which indicates a high reproducibility. For the fast marching method,

the average sensitivity is 93% and the specificity is close to 100%, i.e., we

have very few false positive voxels. When we apply the deformable mesh seg-

mentation, we obtain an average sensitivity of 96%, i.e., an increase of three

percentage points while the high specificity is maintained. See Figure 6.8 for

illustrations of the results.

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6.5 Visualization of dynamic breast MRI

In Paper VII, we present a new approach for visualization of dynamic contrast-

enhanced MRI images of the breast. DCE-MRI is emerging as a useful clini-

cal tool in the diagnosis and staging of breast cancer. It involves acquisition of

T1-weighted images of the breast before and after the injection of a contrast

agent. The signal intensity over time turns out to be an important criterion for

differentiating benign lesions from malign lesions. The enhancement curves

for most cancers exhibit rapid initial uptake and then washout whilst benign

tissue have either no enhancement, or slowed continued enhancement with de-

layed washout. Methods for quantitative analysis of the enhancement curves

exist, but the most commonly adopted approach in routine clinical practice

is the qualitative approach. This involves the tedious and error-prone manual

review of the raw 4D data and derived subtraction images (post-contrast mi-

nus pre-contrast) to identify suspicious areas, and a qualitative evaluation of

the shape of the associated enhancement curves. The high dimensionality and

high resolution of the data overwhelms the user with information.

In our work, we reduce the dimensionality of the data by parameteriza-

tion of the voxel-wise enhancement curves. Intensity observations over sev-

eral time points are reduced to a smaller number of parameters that can be

color-coded in hue-saturation-value (HSV) color space [15] to permit a 3D vi-

sualization of the 4D data. The parameterization and subsequent HSV color-

coding, described in Paper VII, results in a color volume where voxels with

rapid initial enhancement appear brighter and more saturated whilst the na-

ture and degree of intermediate to late enhancement is reflected in the hue

channel. To visualize this color volume, we perform a maximum intensity

projection (MIP) in HSV space. Since we want the rendering to be fast, we

implement a ray-casting engine on the GPU, see Section 4.3. We store the

color-coded volumes using an RGBα representation where the RGB part con-

tains the converted HSV triple, and the α-component contains the intensity

V. This representation allows for quick access to the intensity and no HSV

to RGB conversions are needed during rendering. Since the color volume has

high intensity in regions with high contrast agent uptake and almost zero in-

tensity elsewhere, direct visualization of this image can be hard to interpret

due to the lack of geometric context. We mitigate this problem by blending

the color volume with the pre-contrast volume. Figure 6.9 shows a screen-

shot from our software which also includes a slice-based interface for contour

delineation of regions of interest (ROIs).

Results

We made an experiment based on DCE-MR image data from 14 subjects. The

data were chosen to include 9 subjects with enhancing lesions subsequently

confirmed by histopathology to be cancer, and 5 subjects with enhancing le-

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Figure 6.9: Screenshot from the DCE-MRI Viewer showing one of the color-coded

datasets. The uptake of contrast medium over time in each voxel of the volume is con-

verted to a HSV color encoded volume that is visualized with hardware accelerated,

color-correct maximum intensity projection (MIP). The MIP can be rotated and ex-

plored dynamically giving a direct overview the volume. It is also possible to browse

the slices of the volume and to draw contours defining regions of interest.

sions subsequently confirmed by histopathology to be benign. The data in-

cludes screensaves of the suspicious regions of interest originally traced by

a radiologist and the corresponding findings. One of the malignant data sets

was used to familiarize the operator with our software and the nature of the

visualization for benign and malignant tissue. The operator was asked to de-

lineate suspicious lesions for the remaining 13 subjects and to report an over-

all finding of either malignant or benign. Our software permitted the operator

to examine the color MIP interactively and to define ROIs within individual

2D slices. The results show that the operator correctly identified eight of the

ten malignant cases identified by the original interpreting radiologist, i.e. 80%

sensitivity for malignancy, and two of the three benign cases; i.e. 67% speci-

ficity. The results also show that with respect to the histopathology findings,

the operator had a sensitivity of 100% and a specificity of 80%, whilst the

original interpreting radiologist had a sensitivity of 100% and specificity of

only 60%.

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6.6 The WISH toolkit

During our work with research and development of methods for segmentation,

visualization, and haptic rendering we have assembled a fairly large code li-

brary. With the aim to make this code library more homogeneous, usable, and

maintainable we have created a toolkit called WISH—Interactive Segmen-

tation with Haptics. The design and contents of this toolkit is described in

Paper VIII.

The core of the WISH software consists of a stand-alone C++ class library

for image analysis, visualization, and volume haptics. This means that the al-

gorithms can be integrated into applications written in C++ or even used as

command-line tools. However, in order to realize the haptic-enabled interac-

tive tool we aim for, we have chosen to create an interface between the core

functionality of WISH and the open source H3D API from SenseGraphics,

see Section 5.2. H3D API is implemented in C++ and is based on the X3D1

scene-graph standard. It also supports Python2 scripting.

The interface between the WISH core and the H3D API is called

WISHH3D, and consists of H3D API scene graph nodes for the image

processing filters, segmentation algorithms, visualization algorithms,

and volume haptics algorithms in WISH. The nodes are compiled into a

separate dynamically linked library that is imported into the main H3D API

application at startup. In this way, the WISHH3D nodes can be used and

controlled through X3D or Python. For our graphical user interface (GUI),

we use the TkInter library in Python. See Figure 6.10 for an illustration of the

toolkit components and Figure 6.11 for the GUI.

The WISH toolkit is a research tool that is intended for quick development

and prototyping of new interactive segmentation methods with multi-sensory

feedback. WISH integrates volume haptics and volume visualization with in-

teractive segmentation methods such as fast marching, deformable simplex

meshes, and live-wire. It also includes efficient implementations of several

other image analysis tools. The WISH toolkit is publicly available and can be

downloaded from http://www.cb.uu.se/research/haptics.

1URL: http://www.web3d.org2URL: http://www.python.org

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wishH3DVolume

wishH3DVolumeSlicer

wishH3DVolumeRenderer

wishH3DVolumeHaptics

wishH3DFastMarchingFilter

C++

Python

X3D

TkInter

H3D API

WISHH3D

WISH

OpenHaptics

OpenGL

Hapticdevice

GUI

Hapticdevice

Graphicswindow

...

Figure 6.10: The relations between WISH and the H3D API. WISHH3D is compiled

into a dynamically linked library with nodes that is imported into the H3D API. The

main scene is set up with X3D. Python is used to set up and manage the connections

between the TkInter GUI and the nodes and also the connections between nodes. On

the user input side we have the GUI and the haptic device. On the output side we have

OpenGL graphics and haptic feedback.

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Figure 6.11: Part of the WISH TkInter GUI.

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7. Conclusions

In this chapter, the work in this thesis is concluded with a summary of the

contributions and suggestions for future work.

7.1 Summary of contributions

A number of segmentation methods have been developed and tailored for im-

plementation in an environment with support for haptic interaction. These are

fast marching, fuzzy connectedness, 3D live-wire, and deformable simplex

meshes. Some of them (fast marching, fuzzy connectedness) require basic in-

teraction for facilitating navigation and seeding, while others (live-wire, de-

formable meshes) require more complex interaction. The performance of the

deformable meshes and the fast marching method was evaluated on a fairly

large set of real image data with convincing results.

For visualization, a fast ray-casting engine was implemented on the GPU. It

was used to render parametrically mapped time sequences of breast MRI data

with a color-correct maximum intensity projection (MIP). The potential of

this novel visualization technique was verified with experiments on real data.

The ray-casting implementation is general and allows for complex volume

visualization at interactive rates.

Stable proxy-based haptic rendering for volumetric data was implemented

and specially designed for use in interactive segmentation. In a first appli-

cation, this type of volume haptics was used for tracing of vessels in MRA

images. The encouraging results from this work led to the development of

a new rendering mode based on gradient vector flow (GVF) for facilitating

segmentation initialization in generally shaped structures. For the deformable

model method, the volume haptics engine was extended with a number of

haptic modes designed for exploration of external force data.

Most of the methods developed in this work have been assembled in a soft-

ware toolkit for interactive segmentation with haptic interaction. The aim with

this software is to provide a development framework that in the future can be

used for implementation of new image analysis and visualization methods that

can benefit from multi-sensory interaction.

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7.2 Future work

An important topic for future research is evaluation. The evaluation and val-

idation we have made of the segmentation results indicate that haptics has a

clear potential for interactive segmentation. However, this potential must also

be quantitatively evaluated. An issue for such an evaluation is to find ways

to perform fair comparisons between methods. Methods designed for user in-

teraction with haptic feedback are often very different from methods that use

standard interaction techniques.

Another concern for future work is the importance of collaboration. The

multi-disciplinary nature of this field means that there are many methods and

techniques to consider how to combine. In each discipline, we need to find the

methods that are most suitable for interactive medical image analysis and if

they do not exist they should be developed. Therefore, one main suggestion to

move this research forward is strong collaboration between groups specialized

in haptics, visualization, and image analysis. It should be emphasized that this

collaboration to a high degree also should involve the physicians who are the

potential demanding end-users.

Some specific ideas for future work concern improvement and further de-

velopment of the presented methods. It would be interesting to combine the

3D live-wire method with segmentation based on graph cuts [5]. Live-wire

could be used for marking the boundary between object and background and

use this as input to the graph cuts algorithm.

A desirable extension to the deformable mesh framework is to be able

to handle other topologies than spherical. It would also be interesting to

work with multiple coupled objects and to incorporate statistical shape

constraints [6]. Another idea is to include more haptic tools for local

refinement of the model. In the LiverPlanner [37], such tools are described,

but not with haptic interaction.

The GPU-accelerated ray-casting engine should be extended to handle large

datasets. Due to the high resolution of medical images acquired with the latest

imaging equipment it is not possible to store the full volumes in GPUmemory.

There are techniques that combines efficient data reduction and memory man-

agement in order to render very large datasets [26]. An improvement concern-

ing rendering quality is to implement pre-integrated volume rendering [55].

The volume haptics framework should be generalized to work with non-

orthogonal reference frames. Here, the plan is to use the Volume Haptics

Toolkit (VHTK) [28, 35] for primitives-based haptics available for the H3D

API.

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7.3 Conclusion

This work has contributed to research in three different fields: image analysis,

visualization, and haptics. In the application to interactive medical image seg-

mentation, methods in these fields have been closely integrated. To conclude,

we go back to the list of tasks in Section 1.6:

• New methods and improvements of existing methods for visualiza-

tion, haptic rendering, and interactive segmentation have been devel-

oped.

• The methods have been applied and evaluated on real medical image

data.

• A software framework with efficient and general implementations of

the methods has been made available for future research and develop-

ment. This framework is based on open source code and is therefore

easy to extend and integrate into other packages.

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8. Summary in Swedish

Dagens utrustning för att skapa tredimensionella (3D) bilder av

människokroppens inre är oumbärlig för att diagnostisera och planera

behandling av t. ex. cancer. Vanliga avbildningstekniker är datortomografi

(eng. computed tomography, CT) där kroppen avbildas med röntgenstrålar

från många olika vinklar runt kroppen och magnetresonanstomografi (MRT)

där väteatomers egenskaper i olika vävnader i kroppen avbildas med en

magnetkamera. Dessa tekniker har utvecklats i snabb takt de senaste åren och

varje dag genereras mycket stora mängder bilddata som ska analyseras och

tolkas. Figur 1.1 och Figur 1.2 visar exempel på CT- och MR-bilder.

Att utvinna information ur digitala bilder kallas för digital bildanalys. I

medicinska tillämpningar kan bildanalys hjälpa till med uppgifter som t. ex.

volymmätning av organ baserat på bildinformation eller att konstruera 3D-

modeller av organ för användning inom kirurgiplanering och behandling. Ett

centralt problem som ofta måste lösas är segmentering, dvs. att separera or-

gan från varandra och från bildbakgrunden. Segmentering är ofta ett tidigt steg

i bildanalysprocessen och ligger till grund för all fortsatt informationsutvin-

ning och beräkning. Att segmentera flera organ manuellt i högupplösta bilder

är mycket tidskrävande och tröttsamt vilket innebär att det är lätt att göra fel.

Tyvärr är det inte heller möjligt att låta datorer utföra segmenteringen helt au-

tomatiskt eftersom kontrasten mellan olika organ i bilderna kan vara väldigt

låg och formen på organ kan variera mycket mellan patienter.

För att underlätta arbetet kan man istället använda interaktiva eller semi-

automatiska metoder där datorn gör en stor del av jobbet, men där användaren

kan styra och övervaka datorns arbete. Denna doktorsavhandling handlar om

utvecklandet av sådana metoder där den klassiska typen av interaktion med

mus och tangentbord ersätts med direkt 3D-interaktion som låter användaren

känna på bilderna med hjälp av haptisk återkoppling (kraftåterkoppling). För

att visualisera bilderna på skärmen används stereografik som ger en förstärkt

djupupplevelse jämfört med vanlig visualisering. Figur 1.3 och Figur 5.3 visar

den typ av arbetsstation som har använts.

Forskningsarbetet bakom avhandlingen innefattar tre områden: bildanalys,

visualisering och haptik. Inom bildanalysen har ett antal välkända

segmenteringsmetoder anpassats och byggts ut för att kunna användas

tillsammans med den här typen av interaktion. I de enklaste fallen så

handlar det om att användaren snabbt och effektivt kan placera ett stort antal

markörer i bilden och utifrån dessa segmenterar datorn det organ man är

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intresserad av. Två mer avancerade metoder illustreras på omslagsbilden.

I den vänstra bilden jobbar användaren med en deformerbar ytmodell.

Modellen består av ett antal små ytelement som sitter ihop med varandra

enligt fördefinierade villkor. Genom att koppla bildinformation till varje

punkt på modellen kan man få den att anpassa sig till bilden. I detta exempel

försöker användaren få den att anpassa sig till levern i en CT-bild genom

att påverka den med det haptiska instrumentet. Bilden till höger illustrerar

en metod som heter live-wire. Här placerar användaren en punkt på konturen

av levern och när han sedan flyttar markören så försöker algoritmen hitta

den bästa vägen mellan den placerade punkten och markören. Med rätt

parameterinställningar så ligger den bästa vägen längs leverkonturen och

därmed kan hela konturen segmenteras med bara några få punktplaceringar.

Här känner också användaren organet med det haptiska instrumentet och kan

därför glida längs konturen.

Flera metoder för visualisering av volymdata har också utvecklats. Förutom

den klassiska tekniken att visa genomskärningsbilder så har också hårdvaru-

accelererad direkt volymrendrering (DVR) använts. Med direkt menas att in-

gen ytrepresentation av bilden behövs utan man jobbar direkt med bilddatat.

DVR är ett sätt att simulera genomlysning av den tredimensionella bilden för

att visa inre strukturer. Genom att ställa in s. k. överföringsfunktioner mel-

lan det verkliga bilddatat och den bilden som ska visas kan olika organ syn-

liggöras med olika genomskinlighet och färg. Denna metod är beräkningsin-

tensiv och lämpar sig i vanliga fall inte för interaktiv visualisering med hög

kvalitet. Men genom att utnyttja den höga beräkningskapacitet som finns i da-

gens grafikhårdvara (GPU) kan man utföra DVR i tillräckligt hög hastighet,

även med sterografik. Figur 4.3 och Figur 4.5 visar några exempel. Bland an-

nat så har DVR anpassats för att visualisera tidssekvenser av MR-bilder på

bröst som ett led i utvecklingen av en metod för att lättare upptäcka bröst-

cancer.

Den tredje delen är haptisk rendrering, dvs. metoder för att generera

kraftåterkoppling från de medicinska bilderna. Här har direkt volymhaptik

använts som i likhet med direkt volymrendrering arbetar direkt på

bilddatat. Det haptiska instrumentet har en interaktionspunkt, en pekare,

där kraftåterkopplingen ges. När användaren för pekaren genom datasetet

så kan man med en analys av pekarens omgivning avgöra om det finns en

yta eller en övergång mellan olika organ. Baserat på denna information

kombinerat med användarens rörelser genereras en kraft som användaren

känner. Haptiken har använts bland annat för att kunna följa blodkärl i bilder

och markera olika delar av kärlträdet för att senare kunna dela upp det i olika

delar för fortsatt analys. Ett annat exempel är utforskning av datat som driver

de deformerbara modellerna. Här har man ofta flera olika bilder som driver

modellen och det är svårt att visualisera dem samtidigt. Genom att istället

kunna känna på datat kan man underlätta parameterinställningarna och uppnå

ett bättre segmenteringsresultat.

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Alla dessa metoder har applicerats och testats på riktiga medicinska bilder

och de resultat som har uppnåtts är positiva. Till exempel så har snabb och

effektiv segmentering av levern i ett stort antal CT-bilder genomförts med hög

noggrannhet och precision. Metoderna har även implementerats och samlats i

ett mjukvarupaket som har gjorts tillgängligt för fri nedladdning. Metoderna

kan på detta sätt komma till användning för framtida forskning och utveckling

av förbättrade bildanalysmetoder med 3D-visualisering och haptik.

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Acknowledgments

This work was performed between February 2003 and January 2008. Five

years that have been very enriching. I have learned a lot about many different

things, I have seen interesting places, and most important, I have met so many

interesting persons. I have really enjoyed this time and this is because of you.

Special thanks to:

• My supervisor Ingela Nyström for friendship, support and good collabora-

tion. You have taught me so much and always been very encouraging and

helpful.

• My supervisor Ewert Bengtsson for giving me the opportunity to do this

work. You have given me a lot of invaluable advice and support.

• The reference group: Stefan Seipel, Gunnar Jansson, Lennart Thurfjell, and

Hans Frimmel for good advice and interesting discussions.

• Filip Malmberg for good collaboration and proofreading. Good luck with

your PhD! I will be happy to give help and advice if you need it.

• Stina Svensson and Bosse Nordin for helping me with the language and

formulations in the thesis.

• Sven Nilsson for good collaboration and for teaching me about the contents

of the images that I have been looking at every day.

• Andrew Mehnert and family in Brisbane for friendship, infinite hospitality,

and good collaboration.

• All other co-authors and collaborators: Xavier Tizon, Per Sundqvist, Milan

Golubovic, Michael Wildermoth, Kerry McMahon, Steven Wilson, Stuart

Crozier, Jonas Agmund, and Tomas Bjerner.

• Daniel Evestedt and the rest of the SenseGraphics team.

• Lena Wadelius for making CBA feel like home.

• The “CBA permanents”: Ewert Bengtsson, Gunilla Borgefors, Ingela Nys-

tröm, Lena Wadelius, Olle Eriksson, Tommy Lindell, and Bosse Nordin for

making CBA a wonderful working place.

• My friends and colleagues at (or related to) CBA that I have been traveling

with, playing golf with, having friday beer with, visiting in Australia,

watching football with, having lunch with, sharing office with, working

with, going to the movies with, skiing with, creating “Blaskan” with,

...: Ida-Maria Sintorn, Ola Weistrand, Kristin Norell, Magnus Gedda,

Robin Strand, Stina Svensson, Patrick Karlsson Edlund, Hamid Sarvé,

Filip Malmberg, Milan Gavrilovic, Khalid Niazi, Bettina Selig, Maria

75

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Axelsson, Amin Allalou, Amalka Pinidiyaarachchi, Joakim Lindblad,

Nataša Sladoje, Carolina Wählby, Petra Philipsson, Mats Erikson, Roger

Lundqvist, Felix Wehrmann, Xavier Tizon, Mattias Aronsson, Hamed

Hamid Muhammed, Pasha Razifar, Mathias Raspe, Joel Kullberg,

Suthakar Somaskandan, Anders Hast, Lars Pettersson, Catherine Östlund,

Gerhard Bax, Celine Fouard, Jocelyn Chanussot, Susana Mata, Julia

Åhlen, Roger Hult, Stefan Seipel, Lucia Ballerini, Ewert Bengtsson,

Gunilla Borgefors, Ingela Nyström, Lena Wadelius, Olle Eriksson,

Tommy Lindell, Bosse Nordin, and many others.

♥ Min familj och mina vänner. Speciellt tack till Mamma och Sven-Erik för

allt ert stöd och till Terese för att du är underbar och har fått mig att koppla

av och tänka på annat under dessa intensiva månader.

Uppsala, January 2008

Erik

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Related work

In addition to the papers included in this thesis, the author has also written or

contributed to the following publications:

Reviewed publications

• E. Vidholm, P. Sundqvist, and I. Nyström. Accelerating the computation of3D gradient vector flow fields. In Proceedings of International Conference

on Pattern Recognition (ICPR), pp. 667-680, IEEE, 2006.

• E. Vidholm and J. Agmund. Fast surface rendering for interactive medicalimage segmentation with haptic feedback. In Proceedings of SIGRAD, pp.

33-39, 2004.

Non-reviewed publications

• S. P. Nilsson, A. Bergman, B. Eriksson, I. Nyström, E. Vidholm. Semi-automatic liver volumetry in CT images from patients with neuroendocrinetumours. In Proceedings of European Congress Of Radiology (ECR), 2007.

• E. Vidholm. Haptic interaction with deformable simplex meshes for 3Dsegmentation. In Proceedings of Swedish symposium on image analysis

(SSBA), pp. 1-4, 2007.

• F. Malmberg, E. Vidholm, and I. Nyström. Live-wire based interactive seg-mentation of volume images using haptics. In Proceedings of Swedish sym-

posium on image analysis (SSBA), pp. 57-60, 2006.

• E. Vidholm and I. Nyström. Haptic volume rendering based on gradientvector flow. In Proceedings of Swedish symposium on image analysis

(SSBA), pp. 97-100, 2005.

• E. Vidholm and X. Tizon. Facilitating semi-automatic segmentation ofMRA volumes using haptics. In Proceedings of Swedish symposium on

image analysis (SSBA), pp. 162-165, 2004.

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Acta Universitatis UpsaliensisDigital Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Science and Technology 386

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A doctoral dissertation from the Faculty of Science andTechnology, Uppsala University, is usually a summary of anumber of papers. A few copies of the complete dissertationare kept at major Swedish research libraries, while thesummary alone is distributed internationally through theseries Digital Comprehensive Summaries of UppsalaDissertations from the Faculty of Science and Technology.(Prior to January, 2005, the series was published under thetitle “Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Science and Technology”.)

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