Contributions expérimentales et théoriques aux techniques de contraste de phase pour l'imagerie médicale par rayons X, Experimental and theoretical contributions to X-ray phase-contrast techniques for medical imaging

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Sous la direction de Jose Baruchel
Thèse soutenue le 28 février 2011: UNIVERSITE DE GRENOBLE, Grenoble
Différentes techniques d'imagerie par contraste de phase des rayons X ont été récemment développées. Contrairement aux méthodes conventionnelles, qui mesurent les propriétés d'absorption des tissus, ces techniques donnent aussi le contraste du déphasage introduit par l'échantillon. Puisque le changement dans la phase peut être important même quand les différences en atténuation sont faibles ou absentes, le contraste d'image obtenable peut être considérablement augmenté, notamment pour les tissus mous biologiques. Ces méthodes sont donc très prometteuses pour une application dans le domaine médical. Cette Thèse a le but de contribuer à une compréhension plus profonde de ces techniques, en particulier la propagation-based imaging (PBI), la analyzer-based imaging (ABI) et la grating interferometry (GIFM), et d'étudier leur potentiel et la meilleure implémentation pratique pour les applications médicales. Une partie importante de cette Thèse est dédiée à l'utilisation d'algorithmes mathématiques pour l'extraction, à partir des images acquises, d'informations quantitatives (absorption, réfraction et diffusion) concernant l'échantillon. En particulier, cinq parmi les algorithmes les plus connus pour la technique ABI sont analysés théoriquement et comparés expérimentalement, dans les modalités planaire et tomographique, en utilisant des fantômes et des échantillons de tissu mammaire et d'os-cartilage. Une méthode semi-quantitative pour l'acquisition et la reconstruction d'images tomographiques dans les techniques ABI et GIFM est aussi proposée. Les conditions de validité sont analysées en détail et la méthode, permettant une simplification considérable de l'implémentation pratique, est vérifiée expérimentalement sur des fantômes et des échantillons humains. Enfin, une comparaison théorique et expérimentale des techniques PBI, ABI et GIFM est présentée. Les avantages et les désavantages de chacune des techniques sont mis en évidence. Les résultats obtenus par cette analyse peuvent être très utiles pour déterminer quelle technique est la plus adaptée à une application donnée.
-Synchrotron
-Contraste de phase
-Imagerie
-Cartilage
-Tissu mammaire
-Tumeurs
Several X-ray phase-contrast techniques have recently been developed. Unlike conventional X-ray methods, which measure the absorption properties of the tissues, these techniques derive contrast also from the modulation of the phase produced by the sample. Since the phase shift can be significant even for small details characterized by weak or absent absorption, the achievable image contrast can be greatly increased, notably for the soft biological tissues. These methods are therefore very promising for applications in the medical domain. The aim of this Thesis is to contribute to a deeper understanding of these techniques, in particular propagation-based imaging (PBI), analyzer-based imaging (ABI) and grating interferometry (GIFM), and to study their potential and the best practical implementation for medical imaging applications. An important part of this Thesis is dedicated to the use of mathematical algorithms for the extraction, from the acquired images, of quantitative sample information (the absorption, refraction and scattering sample properties). In particular, five among the most known algorithms based on the geometrical optics approximation have been theoretically analysed and experimentally compared, in planar and tomographic modalities, by using geometrical phantoms and human bone-cartilage and breast samples. A semi-quantitative method for the acquisition and reconstruction of tomographic images in the ABI and GIFM techniques has also been proposed. The validity conditions are analyzed in detail and the method, enabling a considerable simplification of the imaging procedure, is experimentally verified on phantoms and human samples. Finally, a theoretical and experimental comparison of the PBI, ABI and GIFM techniques is presented. The advantages and drawbacks of each of these techniques are discussed. The results obtained from this analysis can be very useful for determining the most adapted technique for a given application.
-Synchrotron
-Phase contrast
-Imaging
-Cartilage
-Breast tissue
-Tumors
Source: http://www.theses.fr/2011GRENY009/document
Published : Saturday, October 29, 2011
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THÈSE
Pour obtenir le grade de
DOCTEUR DE L’UNIVERSITÉ DE GRENOBLE
Spécialité : Physique pour les sciences du vivant
Arrêté ministériel : 7 août 2006



Présentée par
Paul Claude DIEMOZ


Thèse dirigée par José BARUCHEL et Paola COAN
codirigée par Alberto BRAVIN

préparée au sein du European Synchrotron Radiation Facility (ESRF)
dans l'École Doctorale de Physique

en cotutelle avec la Ludwig-Maximilians Universität Munich (Allemagne)


Contributions expérimentales et théoriques
aux techniques de contraste de phase pour
l’imagerie médicale par rayons X


Thèse soutenue publiquement le 28 février 2011,
devant le jury composé de :
Prof. Serge PEREZ
ESRF Grenoble, Président du jury
Prof. Timur E. GUREYEV
CSIRO Materials Science and Engineering (Australie), Rapporteur
Prof. Pekka SUORTTI
University of Helsinki (Finlande), Rapporteur
Dr. José BARUCHEL
ESRF Grenoble, Directeur de Thèse Université de Grenoble
PROF. Paola COAN
LMU University Munich (Allemagne), Directeur de Thèse LMU University Munich
Dr. Alberto BRAVIN
ESRF Grenoble, Co-directeur de Thèse
Prof. Ralf H. MENK
Elettra Synchrotron Light Source (Italie), Examinateur
Prof. Alessandro OLIVO
University College London (Royaume-Uni), Examinateur

tel-00602998, version 1 - 24 Jun 2011
tel-00602998, version 1 - 24 Jun 2011Acknowledgements

I would like here to thank all the people whoh ehlapveed me during these long three
years and contributed, in a way or in the oth ethr,e tsouccessful completion of this
Thesis.
First of all, I wish to express my gratitude etroto ABlbravin for introducing me to the
world of synchrotron and phase contrast, for heicsi oupsr teachings during beamtimes
and for always being open to new ideas, and Poaaonla foCr her guidance, the daily
discussions and unflagging help. Thanks Paola anlbde rtAo for having taught me the
difficult but rewarding job of the researcher! uIl d waolso like to acknowledge José
Baruchel, for his kind supervision and encouragetm. en
I am grateful to Timur Gureyev and Pekka Suwohrtot i,a ccepted to review this Thesis
and gave me valuable comments and suggestions own hto improve the manuscript. I
would also like to thank Serge Perez, who actPerde siadse nt of the Thesis panel, and the
examiners Alessandro Olivo and Ralph Menk.
I am particularly indebted to the ESRF and alpl etohpele of ID17 for providing me with
an excellent work environment and constantly hegl pmine with my work. A big thanks to
Christian Nemoz for the informatics support, fos r gohiod spirit and the ever-present
Pastis, and to Herwig Requardt and Thierry Broc hfaorrd their helpfulness and the
technical assistance during experiments. I also h wtios thank Géraldine Le duc and
Dominique Dallery for having taken care of our aalsn.im Merci aussi à mon nouveau
collègue Emmanuel Brun pour avoir corrigé les epsa rtein français de cette Thèse, et à
mes collègues de bureau, dans l’ordre chronolog iqAuneka, Sukhena, Charlène et Fanny,
pour m’avoir si gentiment supporté!
I want to extend my thanks to the ESRF scienotfitfwica rse group, and in particular to
Claudio Ferrero, for his continuous helpfulnesss, ehnithusiasm and the many
suggestions on how to perform the parallel calicounlas ton the ESRF cluster.
I am grateful to the Institute of Forensic Med iocifn ethe Ludwig-Maximilians University
(Munich, Germany) for providing the biological lesasm tphat I imaged in this work.
This Thesis would not have been possible withouet ftihnancial support from the
German Cluster of Excellence “Munich Centre for anAdcevd Photonics”, which is
gratefully acknowledged.

I am very happy now to thank the people that hemlpee dindirectly in this Thesis by
supporting and encouraging me during these threaer sy.e A special thanks to my friend
Francesco, with whom I shared many good momenet s,jo ktehs, the music, the food and,
not last, the difficult months of the Thesis rioend ac(tFrancesco, grazie per la tua
“agreabile” compagnia!). I want to thank also iemndy fCrarlo, for the continuous

tel-00602998, version 1 - 24 Jun 2011support during the good and bad moments and a ll wtohnederful days of skiing we
shared together!
I am glad I had the occasion to meet some veriayl speocple here in Grenoble, my
friends Amalia, Angelo, Carlo M., Davide, ErImimnia, Irene, Loredana, Maria, Neda,
Raffa, Seb, Sheeba, Silvia, Valentina. I will brerm ealml the nice moments and outings
together in Grenoble, the mountains, the dinnheers ,la utghs… And also all the lunches
at the canteen and the discussions at the cafe,t ear iaray of sunshine in my working day!
Thanks also to Carmen and Elena, whom I met or naly sfhoort period. I enjoyed your
company, your good mood and spirit. Espero qupeo dnaoms os encontrar pronto!
Infine un ringraziamento speciale alla mia fam,ig licahe nonostante la lontananza mi ha
sempre sostenuto nelle mie scelte e costantemenntceo riaggiato. Ringrazio di cuore in
particolare i miei genitori, i miei nonni e fir amteiellii Henri e André.


Grenoble, March 2011

tel-00602998, version 1 - 24 Jun 2011Index


Introduction 1
Introduction en français 5


1 Cartilage and breast tissues imaging 11
1.1 Cartilage and osteoarthritis ....................................................................................... 12
1.1.1 The joint anatomy and its modifications in osteoarthritis.............................. 12
1.1.2 Limitations of existing techniques for cartilage imaging .............................. 15
1.2 Breast ........................................................................................................................ 19
1.2.1 Breast anatomy and related cancers............................................................... 20
1.2.2 Limitations of existing techniques for breast imaging .................................. 22
1.3 Conclusions and perspectives ................................................................................... 24


2 Phase-contrast imaging 27
2.1 Introduction............................................................................................................... 28
2.2 The complex refractive index and the phase contrast ............................................... 29
2.3 X-ray partial coherence ............................................................................................. 32
2.4 Propagation-based imaging ....................................................................................... 34
2.4.1 General PBI formalism .................................................................................. 37
2.4.2 Phase retrieval in the mixed TIE-CTF approach ........................................... 39
2.4.3 PBI coherence requirements and spatial resolution ....................................... 40
2.5 Analyzer-based imaging ........................................................................................... 42
2.5.1 General ABI formalism ................................................................................. 43
2.5.2 Geometrical optics approximation ................................................................ 44
2.5.3 Image contrast and sensitivity in ABI ........................................................... 47
2.5.4 ABI coherence requirements and spatial resolution ...................................... 48
2.6 Grating interferometry .............................................................................................. 49
2.6.1 General GIFM formalism .............................................................................. 50
2.6.2 Phase stepping method .................................................................................. 52
2.6.3 Coherence requirements and spatial resolution ............................................. 54
2.7 Overview of the state of the art in cartilage and breast phase-contrast imaging ....... 55
2.7.1 Phase-contrast imaging of cartilage ............................................................... 55
2.7.2 Phase-contrast imaging of breast ................................................................... 57


3 Experimental implementation and methods 65
3.1 X-ray sources ............................................................................................................ 66
3.1.1 X-ray tubes .................................................................................................... 66
3.1.2 Synchrotron radiation facilities ..................................................................... 67
3.1.3 Inverse Compton scattering sources .............................................................. 70
3.2 The European Synchrotron Radiation Facility (ESRF) ............................................ 71
3.2.1 Overview of the optics and of the main X-ray properties at
the biomedical ID17 beamline .................................................................... 72
3.2.2 Overview of the topography & tomography ID19 beamline
and of the optics BM5 beamline ................................................................. 74
3.3 Experimental setup for the ABI and GIFM techniques............................................. 75
3.3.1 ABI instrumentation at ID17 ......................................................................... 75
3.3.2 Diffraction gratings for GIFM ....................................................................... 78
3.4 Image acquisition ...................................................................................................... 80
i

tel-00602998, version 1 - 24 Jun 20113.4.1 X-ray detectors ............................................................................................. 80
3.4.2 Modalities of image acquisition .................................................................... 81
3.5 Image processing...................................................................................................... 83
3.5.1 Correction of taper deformations .................................................................. 83
3.5.2 Image normalization ..................................................................................... 84
3.5.3 Correction of artefacts in CT imaging .......................................................... 85
3.5.4 Distributed computation for fast image reconstruction ................................. 87
3.6 Contrast, signal-to-noise ratio and figure of merit ................................................... 87
3.6.1 Area contrast case ......................................................................................... 87
3.6.2 Edge contrast case ........................................................................................ 88


4 Extraction of quantitative information from analyzer-based projection images 91
4.1 Introduction .............................................................................................................. 92
4.2 Algorithms for quantitative analysis of AB images ................................................. 94
4.2.1 Diffraction-enhanced imaging (DEI) ............................................................ 94
4.2.2 Extended DEI (E-DEI) ................................................................................. 95
4.2.3 Generalized DEI (G-DEI) ............................................................................. 96
4.2.4 Multiple image radiography (MIR) .............................................................. 98
4.2.5 Limitations of MIR ....................................................................................... 99
4.2.6 Gaussian curve fitting (GCF) ..................................................................... 101
4.2.7 Methods for phase image calculation ......................................................... 101
4.3 Experimental methods ............................................................................................ 104
4.3.1 Experimental parameters ............................................................................ 104
4.3.2 Plastics phantoms ....................................................................................... 104
4.3.3 Biological sample ....................................................................................... 105
4.3.4 Computational implementation................................................................... 106
4.4 Results and discussion ........................................................................................... 106
4.4.1 Plastics phantoms planar images ................................................................ 106
4.4.2 Bone-cartilage planar images ..................................................................... 115
4.5 Conclusions ............................................................................................................ 118


5 Quantitative analysis of analyzer-based computed tomography images 123
5.1 Introduction ............................................................................................................ 124
5.2 Application of extraction algorithms to CT ........................................................... 125
5.2.1 Calculation of the refractive index decrement ............................................ 126
5.3 CT direct reconstruction method ............................................................................ 127
5.4 Experimental methods ............................................................................................ 130
5.4.1 Experimental configuration ........................................................................ 130
5.4.2 Plastics phantoms for CT ............................................................................ 130
5.4.3 Bone-cartilage and breast samples .............................................................. 131
5.4.4 Computational implementation................................................................... 131
5.5 Results and discussion ........................................................................................... 132
5.5.1 CT reconstruction of plastics phantoms with ABI extraction
algorithms ................................................................................................. 132
5.5.2 CT reconstruction of bone-cartilage sample with ABI
extraction algorithms ................................................................................ 136
5.5.3 CT direct reconstruction of two biological samples ................................... 140
5.6 Conclusions ............................................................................................................ 143


6 CT reconstruction methods for GIFM images 147
6.1 Phase stepping method: application to CT ............................................................. 148
6.2 CT direct reconstruction method ............................................................................ 151
6.3 Experimental methods ............................................................................................ 153
6.4 Results and discussion ........................................................................................... 153
6.5 Conclusions ............................................................................................................ 157
ii

tel-00602998, version 1 - 24 Jun 20117 Comparison of three phase-contrast imaging techniques 159
7.1 Introduction............................................................................................................. 160
7.2 Signal-to-noise ratio (SNR) and figure of merit (FOM) ......................................... 160
7.2.1 SNR and FOM in absorption imaging ......................................................... 162
7.2.2 SNR and FOM in propagation-based imaging ............................................ 163
7.2.3 SNR and FOM in analyzer-based imaging .................................................. 164
7.2.4 SNR and FOM in grating interferometry .................................................... 169
7.2.5 Sensitivity in PBI, ABI and GIFM .............................................................. 173
7.3 Experimental methods ............................................................................................ 175
7.4 Results and discussion ............................................................................................ 177
7.4.1 Experimental images ................................................................................... 177
7.4.2 Extraction of quantitative images ................................................................ 185
7.5 Conclusions............................................................................................................. 190


Conclusions 193
Conclusions en français 199
List of the publications produced in the framework of this Thesis 205










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tel-00602998, version 1 - 24 Jun 2011Introduction



X-ray imaging techniques are an indispensable diagnostic tool, which has found widespread use in
the clinical practice. Since the first use of X-rays for medical imaging dating back to more than a
century ago, these techniques have been developed and optimized. Efforts have particularly
focused on technical developments concerning the radiation sources (X-ray tubes) and the
detectors. An important step forward was also represented by the introduction, in the 1970’s, of
computed tomography, which enabled the generation of three-dimensional images of the human
tissues. However, the main physical principles upon which these techniques are based have
remained the same: the image contrast is generated by variations of the X-ray absorption that arise
from density differences and from changes in thickness and composition of the sample. The
contrast that can be achieved based on simple differential absorption is in some cases intrinsically
limited. This occurs for instance when soft (low atomic number) biological tissues are imaged,
since the differences in attenuation are very tiny.
Two emblematic examples are represented by the imaging of articular cartilage and breast
tissues, for which the contrast obtained in conventional absorption radiography is limited. A good
depiction of these tissues would be very useful for the diagnosis of diseases like osteoarthritis and
breast cancers. The detection of early stages of osteoarthritis would enable the realization of
longitudinal studies aimed at investigating the progress of the disease and at testing its response to
pharmacological treatments; the early detection of breast cancers would dramatically improve the
prognosis for the women affected by this disease. An introduction to these subjects is presented in
the chapter 1 of the Thesis.
With the aim of overcoming the present limitations of the clinical X-ray diagnostics, in the
last 20 years a number of phase-contrast imaging techniques have been developed. Unlike
conventional X-ray methods, which measure the amplitude of the wave exiting the sample,
determined by the attenuation properties of the tissues, these techniques derive contrast also from
the modulation of the phase produced by the sample. The interest for phase sensitive techniques in
medical applications resides in the fact that the X-ray phase shift can be significant even for small
details characterized by weak or absent amplitude modulation; as a result, the achievable contrast
for soft biological tissues can be greatly increased.
Various techniques have been developed to exploit the phase contrast in the X-ray regime. In
this Thesis, the work has been focused on three among the most promising phase-sensitive
imaging techniques, namely the propagation-based imaging (PBI), the analyzer-based imaging
(ABI) and the grating interferometry (GIFM). The first method, PBI, simply uses free-space
propagation between the sample and the detector to convert, through Fresnel diffraction, the beam
phase modulations into measurable intensity variations on the detector. ABI employs a perfect
crystal placed between the sample and the detector to analyze the radiation refracted inside the
1

tel-00602998, version 1 - 24 Jun 20112 In tr o d u ct i o n

sample, while in GIFM the image contrast is obtained by exploiting the Talbot effect through the
use of two diffraction gratings set at an appropriate mutual distance before the detector. The
theoretical description of these techniques, as well as the needed experimental setup and their
requirements in terms of the spatial and temporal coherence of the radiation illuminating the
object, are presented in chapters 2 and 3.

The phase-contrast X-ray imaging techniques have been extensively studied in recent years
and it has been demonstrated that they are able to provide much improved contrast with respect to
conventional absorption imaging. The aim of this Thesis is to contribute, both theoretically and
experimentally, to a deeper understanding of these techniques and to study their potential and
the best practical implementation for medical imaging applications.

An important subject considered in this Thesis is the use of mathematical algorithms for
extraction of quantitative information from the images of a given sample. In particular, in the ABI
technique several extraction algorithms have been proposed and applied in the literature to
separate and quantify the absorption, refraction and ultrasmall-angle scattering (USAXS)
contributions to the image contrast. These different physical effects, in fact, mix up in the acquired
AB images, making the image interpretation sometimes difficult, especially in the case of complex
object geometries. An efficient separation of these contributions to the contrast would highlight the
different properties of the object and therefore facilitate the image interpretation. Furthermore, the
extraction of accurate quantitative information may be very useful for precisely characterizing the
sample.
Despite the large number of published works on this subject, however, a comprehensive
theoretical and experimental comparison of these mathematical methods was missing in the
literature. In particular, their ability to provide quantitatively accurate results in different
experimental conditions, which may be important for some biomedical applications, had not been
systematically assessed. In this Thesis, five among the most known and used algorithms based on
the geometrical optics approximation are considered: diffraction-enhanced imaging (DEI),
extended diffraction-enhanced imaging (E-DEI), generalized diffraction-enhanced imaging (G-
DEI), multiple image radiography (MIR) and Gaussian curve fitting (GCF). The validity
conditions upon which these algorithms are based and the types of images that can be calculated
by each of them are discussed. A quantitative comparison of the results obtained with these
different methods with those predicted by theory is performed, based on the analysis of
experimental images of phantoms with known shape and composition and providing different
amounts of absorption, refraction and scattering. These algorithms are also applied to biological
samples and the resulting images are compared and discussed. This analysis is reported in the
chapters 4 and 5, respectively in the case of planar and tomographic imaging.

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