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Arterial Spin Labelling Magnetic Resonance Arterial Spin Labelling Magnetic Resonance Imaging of the Brain: Techniques and Development Ph.D Thesis Jack Anthony Wells1,2 1The Advanced Magnetic Resonance Imaging Group Department of Medical Physics and Bioengineering 2 Radiology and Physics Unit UCL Institute of Child Health University College London Supervisors Dr. David Thomas1,2 Prof. Roger Ordidge1 “Perhaps no other organ of the body is less adapted to an experimental study of its circulation other than the brain” - Carl Wiggers, the “American father of pulmonary circulatory physiology”, 1905. 1 Declaration I, Jack Anthony Wells, confirm that the work presented in this thesis is my own work except where acknowledged in the text. This work is based on research that was undertaken by myself at University College London during the period 26th September 2005 to 10th August 2008. Signed........................................ Publications Characterising the Origin of the Arterial Spin Labelling Signal in MRI using a Multi- Echo Acquisition Approach. J A Wells, M F Lythgoe, M Choy, D G Gadian, R J Ordidge, D L Thomas. (2009). Journal for Cerebral Blood Flow and Metabolism. In Press. doi:10.1038/jcbfm.2009.99. Reduction of Errors in ASL Cerebral Perfusion and Arterial Transit Time Maps using Image De-noising. J A Wells, D L Thomas, M D King, A Connelly, M F Lythgoe, F Calamante. Magnetic Resonance in Medicine. In Press. In-vivo Hadamard Encoded Continuous Arterial Spin Labelling (H-CASL). J A Wells, M F Lythgoe, D G Gadian, R J Ordidge, D L Thomas. Magnetic Resonance in Medicine. In Press. 2 Acknowledgements I would like to thank David Thomas for his enduring expertise and patience. His intellectual contribution to the projects described in this thesis cannot be understated. Though busy with numerous other studies, Dr. Thomas always found time for guidance and discussion. I have taken up a huge amount of his time and have been very fortunate to have him as my Ph.D supervisor. My thanks extend to Roger Ordidge who first taught me the principles of MRI and was always available for advice and discussion throughout my studies. Many thanks go to Mark Lythgoe for his enthusiasm and encouragement and particularly for helping me to minimise systematic errors in the experimental acquisitions, which was key to the success of the projects. I would also like to thank Mankin Choy for teaching me how to use the 2.35T scanner. Despite interrupting him on many occasions to ask questions, he was always kind and helpful. I am especially thankful to Martin King who has helped me continually over the course of this work. Dr. King has provided several moments of inspiration which really helped push the projects forward. I consider myself very lucky to have taken up so much of his time and hope to be able to work together on future projects! I am grateful for the help and support of the many people who I have had the pleasure to work with, in particular (and in no particular order!) Ken Cheung, Rachael Dobson, Panos Kyrtatos, Jon Cleary, Sally Dowsett, John Thornton, Aaron Oliver-Taylor, David Carmichael, Enrico De-Vita, Sati Sohota, Johannes Riegler, Robert Turner and Harry Parkes. I am also grateful to David Gadian and Fernando Calamante who both offered key guidance and advice over the course of this work. I would also like to thank Ted Proctor who sadly passed away last year. His stories always cheered me up when my experiments we not working as well as I had anticipated! I would like to thank the Wellcome trust for funding my Ph.D and supporting this research. Finally, I would like to thank my parents, to whom this thesis is dedicated. 3 Contents Page Abbreviations ....................................................................................................................7 List of Figures ...................................................................................................................8 Abstract ...........................................................................................................................10 Chapter 1: Introduction to Arterial Spin Labelling, Diffusion Imaging and Relaxation in MRI .................................................................................................................................11 1.1 Introduction and Aims ..........................................................................................11 1.2 Organisation of Ph.D Thesis .................................................................................12 1.3 The Basic Principles of ASL.................................................................................13 1.3.1 Introduction....................................................................................................13 1.3.2 “Perfusion Imaging”. The First ASL Experiment..........................................13 1.3.3 Continuous Arterial Spin Labelling (CASL): Principles ...............................18 1.3.4 Pulsed Arterial Spin Labelling (PASL): Principles .......................................20 1.4 The Development of ASL.....................................................................................22 1.4.1 CASL Techniques and Development.............................................................22 1.4.2 PASL Techniques and Development .............................................................24 1.5 Issues in Accurate, Efficient and Robust ASL CBF Quantification .....................26 1.5.1 Transit time ....................................................................................................26 1.5.2 Vascular Artefacts..........................................................................................32 1.5.3 CBF Quantification Models ...........................................................................34 1.5.4 Measuring CBF in White Matter ...................................................................35 1.6 General ASL Optimisation and Development ......................................................36 1.7 Applications ..........................................................................................................37 1.7.1 Cerebrovascular Disease ................................................................................37 1.7.2 Functional MRI..............................................................................................39 1.8 T2: The Transverse Relaxation Time....................................................................40 1.8.1 Introduction....................................................................................................40 1.8.2 NMR Phenomena: How we Generate a Signal..............................................40 1.8.3 Spin-Spin Relaxation and the Spin Echo Acquisition....................................44 1.9 T1: The Longitudinal Relaxation Constant...........................................................50 1.10 Principles of Diffusion MRI ...............................................................................51 1.11 Half-Fourier Acquisitions and the POCS Reconstruction ..................................57 1.12 MRI Apparatus....................................................................................................59 1.13 Conclusion and Closing Remarks .......................................................................61 Chapter 2: Characterising the Origin of the Arterial Spin Labelling Signal in MRI using a Multi-Echo Acquisition Approach ...............................................................................67 2.1 Abstract .................................................................................................................67 2.2 Introduction...........................................................................................................67 2.3 Dependence of the Power of the Spin Echo Imaging Pulses on the Delay between the end of Labelling and Image Acquisition...............................................................70 2.4 Removal of Image Artefacts using Spoiler Gradients and Phase Cycling............74 2. 5 Investigating the Possible Diffusion Weighting Introduced to the Measured Signal by the Imaging Gradients in the Multi-Echo Acquisitions ..............................77 2.6 Characterising the Origin of the Arterial Spin Labelling Signal in MRI using a Multi-Echo Acquisition Approach: Pilot Studies .......................................................84 2.7 Calibration of Vascular Crusher Gradients...........................................................90 2.7.1 Diffusion Gradient Calibration for Vascular Suppression.............................97 4 2.8 Characterising the Origin of the Arterial Spin Labelling Signal in MRI using a Multi-Echo Acquisition Approach: Final Experiments ............................................100 2.8.2 Methods............................................................................................................101 2.8.2.1 Animal Preparation ...................................................................................101 2.8.2.2 Continuous Arterial Spin Labelling ..........................................................101 2.8.2.3 Image Analyses .........................................................................................102 2.8.3 Results..............................................................................................................105 2.8.4 Discussion ........................................................................................................114 2.8.5 Summary ..........................................................................................................119
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