kth royal institute of technology Doctoral Thesis in Physics Phase-Contrast X-Ray Imaging of Complex Objects ILIAN HÄGGMARK Stockholm, Sweden 2021 Phase-Contrast X-Ray Imaging of Complex Objects ILIAN HÄGGMARK Academic Dissertation which, with due permission of the KTH Royal Institute of Technology, is submitted for public defence for the Degree of Doctor of Philosophy on Friday the 28th May 2021, at 1:00 p.m. in Zoom and the BioX Library, AlbaNova University Center, Roslagstullsbacken 21, Stockholm. Doctoral Thesis in Physics KTH Royal Institute of Technology Stockholm, Sweden 2021 © Ilian Häggmark ISBN 978-91-7873-847-2 TRITA-SCI-FOU 2021:03 Printed by: Universitetsservice US-AB, Sweden 2021 iii Preface The doctoral work on phase-contrast X-ray imaging presented in this Thesis was carried out between 2016 and 2021 in the Biomedical and X-ray physics group at the Department of Applied Physics, KTH Royal Institute of Tech- nology, under the supervision of Prof. Hans Hertz and Assoc. Prof. Anna Burvall. iv v Abstract X-ray imaging is a group of techniques using electromagnetic radiation of high energy. The ability to quickly visualize internal structures in thick opaque objects has made it an indispensable tool in research, medicine, and industry. Contrast is generally achieved by differential absorption, however, this mechanism has a strong dependence on atomic number. This results in low contrast within materials consisting of mainly elements of low atomic number, such as hydrogen, carbon and oxygen, e.g., soft organic matter. The problem with low contrast is further complicated by limitations in radiation dose. To improve contrast the phase shift of the X-rays can be measured without increasing the dose. This Thesis concerns one method to harness this phase signal – propagation- based phase-contrast X-ray imaging (PBI). Three aspects on how to image complex objects are addressed: multi-material phase retrieval, simulations of clinical imaging, and small-animal imaging on compact systems. First, the derivation of a previously published method for multi-material phase retrieval is shown. A comparison between this method and another fur- ther reveals important differences. Secondly, a strategy to use large digital voxel-based phantoms for clinical imaging is developed. The method is demonstrated on a mammography phantom and in a reader study on clini- cal lung imaging. Finally, a compact X-ray system is used to demonstrate imaging of vascular canals in rat bone and high-resolution lung imaging on free-breathing mice, i.e., without mechanical ventilation. vi Sammanfattning Röntgenavbildning är en samling tekniker som använder elektromagnetisk strålning av hög energi. Förmågan att snabbt åskådliggöra inre strukturer i tjocka ogenomskinliga objekt har gjort den till ett oumbärligt redskap inom forskning, medicin och industri. Kontrast åstadkoms generellt genom skillnader i absorption av röntgenstrålningen, men denna mekanism är starkt beroende av atomnummer. Detta resulterar i låg kontrast för material som huvudsakligen består av grundämnen med lågt atomnummer som väte, kol, och syre – typiskt mjuk biologisk vävnad. Begränsningar i stråldos försvårar ytterligare problemet med låg kontrast. För att förbättra kontrasten kan röntgenstrålningens fasskift mätas utan att dosen ökas. Denna avhandling behandlar en metod som nyttjar denna fassignal – pro- pagationsbaserad faskontrast (PBI). Tre aspekter av hur komplexa objekt kan avbildas behandlas: fasåterhämtning av objekt med flera material, si- muleringar av klinisk avbildning och smådjursavbildning med kompakta röntgensystem. Först görs en härledning av en tidigare publicerad metod för fasåterhämtning av objekt med flera material. Viktiga skillnader visas i en jämförelse mellan denna metod och en annan. Sedan utvecklas en strategi för hur stora digitala voxelbaserade fantomer kan användas för klinisk av- bildning. Den förevisas på en mammografifantom och tillämpas i en studie med radiologer om klinisk lungavbildning. Slutligen demonstreras hur kom- pakta röntgensystem kan användas för att avbilda nätverket av vaskulära kanaler i råttben och hur lungavbildning kan utföras med hög upplösning på möss som andas naturligt, d.v.s. utan mekanisk ventilering. vii List of papers This Thesis is based on the following papers: Paper A I. Häggmark, W. Vågberg, H. M. Hertz, and A. Burvall, ”Comparison of quantitative multi-material phase-retrieval algorithms in propagation-based phase-contrast X-ray tomography”, Opt. Express 25(26), 33543–33558 (2017). Paper B I. Häggmark, K. Shaker, and H. M. Hertz, ”In Silico Phase-Contrast X- Ray Imaging of Anthropomorphic Voxel-Based Phantoms”, IEEE T. Med. Imaging 40(2), 539–548 (2021). Paper C I. Häggmark*, K. Shaker*, S. Nyrén, B. Al-Amiry, E. Abadi, W. Segars, E. Samei, and H. M. Hertz, ”Propagation-based phase-contrast CXR: a virtual clinical study”, manuscript in preparation. Paper D I. Häggmark, J. Romell, S. Lewin, C. Öhman, and H. M. Hertz, ”Cellular-Resolution Imaging of Microstructures in Rat Bone using Laboratory Propagation-Based Phase-Contrast X-ray Tomography”, Microsc. Microanal. 24(S2), 368–369 (2018). Paper E K. Shaker*, I. Häggmark*, J. Reichmann, M. Arsenian-Henriksson, and H. M. Hertz, ”Resolving the terminal bronchioles in free-breathing mice: propagation-based phase-contrast CT”, manuscript. * Shared first authorship. viii Other publications The author has contributed to the following publications, which are related to this Thesis but have not been included in it. I. Häggmark, W. Vågberg, H. M. Hertz, and A. Burvall, ”Biomedical Ap- plications of Multi-Material Phase Retrieval in Propagation-Based Phase- Contrast Imaging”, Microsc. Microanal. 24(S2), 370–371 (2018). J. Romell, I. Häggmark, W. Twengström, M. Romell, S. Häggman, S. Ikram, and H. M. Hertz, ”Virtual histology of dried and mummified biological samples by laboratory phase-contrast tomography”, Proc. SPIE 11112, 111120S (2019). ix List of Abbreviations CCD Charge-coupled device CMOS Complementary metal-oxide-semiconductor CT Computed tomography CTF Contrast transfer function CXR Chest X-ray FBP Filtered back projection FDK Feldkamp-Davis-Kress FOV Field of view FRC Fourier ring correlation FSC Fourier shell correlation FWHM Full width at half maximum ICS Inverse Compton scattering LMJ Liquid-metal-jet LWFA Laser wakefield acceleration MC Monte Carlo PBI Propagation-based imaging PCI Phase-contrast X-ray imaging PSF Point spread function SNR Signal-to-noise ratio TIE Transport-of-intensity equation VCT Virtual clinical trial WP Wave propagation x Contents Preface iii Abstract v Sammanfattning vi List of papers vii Other publications viii List of Abbreviations ix 0 Historical note 1 0.1 Discovery . 1 0.2 Development of X-ray imaging . 4 0.3 Imaging with phase . 5 1 Introduction 7 1.1 Image quality . 7 1.2 Phase-contrast X-ray imaging . 8 1.3 Complex objects . 9 2 X-ray matter interaction 11 2.1 Fundamental interactions . 12 2.1.1 Single-photon interactions . 12 2.1.2 Ionizing radiation and dose . 15 2.2 Complex refractive index . 16 3 Sources and detectors 19 3.1 X-ray sources . 19 3.1.1 X-ray tubes . 19 3.1.2 Liquid-metal-jet sources . 22 xi 3.1.3 Synchrotrons . 22 3.1.4 Laser-based sources . 23 3.1.5 Comparison of sources . 24 3.2 X-ray detectors . 25 4 X-ray image formation 31 4.1 Attenuation-based imaging . 31 4.2 Phase-contrast imaging . 33 4.2.1 Mathematical description . 34 4.2.2 Phase-contrast imaging methods . 36 4.3 Propagation-based imaging . 39 4.3.1 Basic phenomenon . 39 4.3.2 Parameters . 40 4.4 Tomography . 43 4.4.1 Fourier slice theorem . 43 4.4.2 Reconstruction . 44 4.4.3 Angular sampling . 46 5 Phase retrieval 49 5.1 The phase problem . 49 5.2 Single-material methods . 50 5.3 Multi-material methods . 51 6 X-ray imaging simulations 55 6.1 Methods . 55 6.2 Object models . 57 6.2.1 Sampling . 58 6.2.2 Upsampling . 59 6.3 Virtual clinical trials . 61 7 Small-animal imaging on compact systems 63 7.1 Visualizing vascular canals in bone . 63 7.2 In-vivo lung tomography . 64 8 Conclusions and outlook 69 A Fourier Transform 71 Summary of papers 75 Acknowledgements 77 References 79 HISTORICAL NOTE | 1 Chapter 0 Historical note Below follows a short and incomplete description of selected events in the development of X-ray imaging and phase imaging. 0.1 Discovery Wilhelm Conrad Röntgen’s discovery of X-rays 1895 was immediately recognized as a significant contribution to science. The speed with which the technique was adopted around the world remains to this day unparalleled. On November 8, Röntgen made the discovery of an unknown radiation. Before the end of the year, on December 28, he published a solid report on his findings [1]. On January 5, Die Presse in Vienna published an article about the discovery entitled “Eine sensationelle Entdeckung” [2]. On January 23, Nature published a translation of Röntgen’s original report [3]. The already widespread use of the key hardware components to perform imaging – the discharge tube and film or a fluorescent screen – enabled scientists and enthusiasts to quickly begin their own experiments. On February 14, Science published an article by Edwin B. Frost, who had imaged various objects including a broken arm [4]. The following day New York Times included a news item with the title “X Rays Find a Needle in a Foot” which described how surgeons in Toronto used an X-ray image to locate a needle for removal [5]. In March Walter König at Physikalischer Verein in Frankfurt am Main showed X-ray images of animals, human teeth, and even mummies [6]. In May the first military X-ray was performed in Naples by Guiseppe Alvaro [7]. In Sweden, the discovery was received with great interest. On January 9, newspapers described Röntgen’s work [8]. One month later, on February 9, Knut Ångström and Hjalmar Öhrvall at Uppsala University acquired 2 | HISTORICAL NOTE images of frogs and a rat [9, 10].