Preklinische SPECT-beeldvorming gebaseerd op compacte collimatoren en hogeresolutiescintillatiedetectoren Preclinical SPECT Imaging Based on Compact Collimators and High Resolution Scintillation Detectors Karel Deprez Promotoren: prof. dr. S. Vandenberghe, prof. dr. R. Van Holen Proefschrift ingediend tot het behalen van de graad van Doctor in de Ingenieurswetenschappen Vakgroep Elektronica en Informatiesystemen Voorzitter: prof. dr. ir. J. Van Campenhout Faculteit Ingenieurswetenschappen en Architectuur Academiejaar 2013 - 2014 ISBN 978-90-8578-672-6 NUR 954, 959 Wettelijk depot: D/2014/10.500/18 Department of Electronics and Information Systems Medical Image and Signal Processing (MEDISIP) Faculty of Engineering and Architecture Ghent University MEDISIP IBiTech Campus Heymans, Blok B De Pintelaan 185 9000 Ghent Belgium Promotors Prof. dr. Stefaan Vandenberghe Prof. dr. Roel Van Holen Board of examiners Prof. dr. ir. Patrick De Baets, Ghent University, chairman Dr. Michael Tytgat, Ghent University / CERN, secretary Prof. dr. Luc Van Hoorebeke, Ghent University Prof. dr. Dennis Schaart, Delft University of Technology, The Netherlands Prof. dr. Carlo Fiorini, Politecnico di Milano, Italy Dr. Samuel Espana˜ Palomares, Advanced Imaging Unit, Centro Nacional de Inves- tigaciones Cardiovasculares (CNIC), Spain Dr. Peter Bruyndonckx, Bruker MicroCT, Belgium This work was supported by the 7th Framework Programme (FP7) of the European Union through the SUBLIMA project (Grant Agreement No 241711) Acknowledgements The work presented in this dissertation started in 2008, shortly after the birth of my daughter, and was finished in early 2014. Before I started at the university I had been working for several years as a electronics design engineer at Barco and Gemidis. The first thing that struck me when I started at the university was the content of my work. My new job involved a lot of different aspects, from that time on I would, besides designing electronics, also design mechanics, collimators, software and a lot of other things (such as adapting the architectural plans of the lab and mounting pegs in the corridor). This diversity was refreshing for me and it surely has boosted my creativity. This work would not have been possible without the help of a lot of people. First, I would like to thank prof. dr. Stefaan Vandenberghe, prof. dr. Roel Van Holen and prof. dr. ir. Steven Staelens. When I started at MEDISIP I was the first hardware designer; at that time most researchers at MEDISIP were performing simulation and image re- construction studies. In order to develop innovative imaging hardware, one has to do substantial investments because the measurement devices and hardware components are very expensive. Stefaan, Roel and Steven made funding available to buy these components and gave me the free- dom and time to develop MEDISIP’s first hardware. Additionally, they allowed me to present my research at numerous conferences abroad. I have to thank Stefaan for guiding me and for helping me to focus on the most innovative parts of my research. Roel convinced me at the start of my employment that I was doing innovative research by inviting me to Harry Barrett’s laboratory at the university of Arizona. It is Roel who, especially during the last two years, indicated how my research should evolve. Steven was a professor at the MEDISIP department during the first years of my employment. I want to thank him for the confidence he had in me. I want to thank prof. dr. Christian Vanhove for the fruitful discussions 4 and for allowing me to develop hardware in the Infinity lab. The people of the nuclear medicine division of the university hospital Ghent have helped me a lot by providing me 99mTc to perform measure- ments. I would especially like to thank Ingeborg Goethals, Lieselotte Moerman, Michel Ravier, Tamara Blanken and Carine Wartel. I would like to thank prof. dr. Romain Lefebvre for allowing me to use the tools in the mechanical workshop. Tom Vanthuyne, Sam Tshitengé and Diego De Baere have helped me a lot by learning me how to operate the various tools in the workshop. Also Bart Blanckaert and Cyriel Mabilde helped me a lot with practical machining issues during the first years of my employment. In this dissertation I developed an electronics board to perform the readout of a photodetector. This board is rather complex and I would not have been able to layout it without the help of Lieven Degrendele (CMST, Ghent university). Additive manufacturing is presented here as a new production method for tungsten collimators. Layerwise is the first company in the world that was able to produce these tungsten parts. I would like to thank Tom De Bruyne and Jonas Van Vaerenbergh for the successful collaboration. The first lofthole collimators were machined by VASKON. I especially would like to thank Patrick D’Haeyer for the swift service. I am grateful to Prof dr. Pieter Dorenbos for explaining the spectra obtained with the LYSO detector. The production and processing of scintillators can be considered as some sort of artform; a lot of parameters determine the quality of a scintillator. I owe many thanks to Paul Schotanus (Scionix) and Jim Telfer (Hilger Crystals) to provide us with scintillators and to share knowledge with us. I would like to thank Vicky Van Ooteghem and Gerwin Raes for proof- reading the Dutch parts of this dissertation. Ewout Vansteenkiste and Kris Bonnarens were very supportive for the patent applications and valorization issues. I especially have to thank Ewout for his extensive knowledge and advice on the different possibili- ties to obtain funding for research and valorization. I also want to express my gratitude to my colleagues at MEDISIP. Bert never hesitated to (re-)explain image reconstruction algorithms to me, to bring a sandwich for lunch and to help me solving software issues. Karen is always keen on a SPECT-related discussion. I will never forget our legendary Everglades kayaking trip and I would like to thank her for convincing me to go running during lunch break. Lara has developed 5 the lofthole sensitivity formulas that are presented in this book. Be- sides that, she has great knowledge on mathematics and she was always willing to help me with math problems. Carmen has helped me when I encountered a physics related problem, thanks for that. Gregor is an EEG-researcher and a great DJ, thanks for the good vibes on several parties. I have to thank Saskia, Inge, Anne-Marie and Ayfer for gener- ating all those order forms, for handling loads of administrative issues and for a talk once in a while. I would like to thank Vincent for his medical insights. Thanks to Pieter (Van Mierlo) and Pieter (Mollet) for the many interesting discussions during lunch break and for helping me with PhD related things (dissertation, defense and parties). Many thanks to Nathalie and Shandra for promoting kayaking at MEDISIP. Willeke recently started and is MEDISIP’s youngest researcher, I’m sure that she will perform great research and I thank her for being such a nice person. Faruk frequently helped me with simulations, thanks for your expertise! Victoria and Hendrik were two of MEDISIP’s most remark- able persons, thanks for being around. I also have to thank Benedicte, Scharon, Philippe and Steven (Deleye) for helping me with practical is- sues in the lab. Radek is building an innovative PET system, I thank him for sharing the lab with me and I hope that we can collaborate in the future. Also thanks to Roma, Aaike, Erwann, Sinem, Enrico and Long. Thanks to Tom Ghekiere for helping me to solve C++ pointer problems and to Hans Hallez for explaining me math-related things. Ik wens ook mijn ouders te bedanken voor de steun die ze mij steeds gegeven hebben. Zonder het doorzettingsvermogen dat ik van mijn moeder geërfd heb en de technische handigheid die ik van mijn vader geërfd heb zou dit doctoraat er niet gekomen zijn. Via deze weg wil ik hen ook het beste voor de toekomst wensen. Mijn vriendin Leen wil ik bedanken voor de liefde, de kinderen, de in- teresse in mijn onderzoek, de flexibiliteit, het begrip, het nalezen en nog heel wat andere zaken. Mijn schoonouders, Marie-Anne en Guido, dank ik voor de interesse en voor het helpen met de kinderen. Finaal wens ik ook mijn kinderen, Sky en Andreas, te danken voor hun jeugdige enthousiasme en om mij te leren om met een andere blik naar de wereld te kijken. Karel, 20 maart 2014 ”I do not seek. I find.” Pablo Picasso Table of Contents Table of Contents i List of Figures vii List of Tables xxiii List of acronyms xxvi English summary xxxi Nederlandstalige samenvatting xxxv 1 Introduction 1 1.1 Medical imaging . .1 1.2 Single photon emission computed tomography . .4 1.3 Outline . .5 2 Single photon emission computed tomography 7 2.1 Introduction . .7 2.2 Radioisotopes and tracers for SPECT . 10 2.3 SPECT physics - interactions of gamma rays . 11 2.3.1 Photoelectric absorption . 11 2.3.2 Compton scatter . 12 2.3.3 Attenuation . 13 2.4 Collimators . 17 2.4.1 Introduction . 17 2.4.2 The parallel hole collimator . 19 2.4.2.1 Introduction . 19 2.4.2.2 Sensitivity and resolution . 20 2.4.3 The pinhole collimator . 21 2.4.3.1 Introduction . 21 ii Table of Contents 2.4.3.2 Sensitivity . 22 2.4.3.3 Resolution . 25 2.4.3.4 Resolution-sensitivity trade-off . 27 2.4.3.5 Non-ideal pinholes . 27 2.4.3.6 Other pinhole geometries . 28 2.4.3.7 Multi-pinhole collimators . 28 2.4.4 Fanbeam and conebeam collimators . 30 2.4.4.1 Introduction . 30 2.4.4.2 Sensitivity and resolution .