Magnetic resonance imaging of tissue microcirculation in experimental studies.

Magnetic resonance images may be sensitised to tissue perfusion and oxygenation, providing functional information about organs in the body. These MR techniques are of great value for the assessment of ischaemic conditions, both for clinical diagnosis and to investigate disease processes in animal models. Perfusion may be studied completely non-invasively using arterial spin labelling (ASL) to magnetically label blood. The presence of deoxyhaemoglobin (dHb) influences spin-spin relaxation times, producing blood-oxygen-level-dependent (BOLD) contrast in images. ASL and BOLD MRI are investigated in this thesis in rat brain and liver. Theoretical and practical aspects of labelling blood by velocity driven adiabatic fast passage (AFP) for continuous ASL (CASL) are considered. A computer model of the modified Bloch equations facilitated optimisation of velocity driven AFP under various experimental and physiological conditions in humans and animals. The computer model was extended to investigate the amplitude modulated (AM) control pulse for multiple-slice CASL. The effect of the AM control on moving spins and some of the reasons for the non-ideal performance of the technique are explained. The AM control was implemented and results in rat brain in-vivo demonstrate that the technique is significantly less sensitive to perfusion than the standard control technique for single slice CASL imaging. BOLD was employed in an animal model of intestinal ischaemiareperfusion (FR). This is a devastating condition that affects remote organs, including the liver, lungs, heart, kidney and central nervous system, and may lead to multiple-organ-dysfunction-syndrome. BOLD MRI of the liver during intestinal FR showed that R%* increases throughout reperfusion. This suggests that dHb accumulates in the liver, consistent with the triggering of the failure of hepatic energy metabolism by intestinal reperfusion following ischaemia. Acknowledgements Many people have generously shared their scientific expertise and enthusiasm with me in the course of completing this work. I should like to thank my principle supervisor Roger Ordidge, who gave me the opportunity to be involved in this exciting field at UCL and my second supervisor David Gadian, who allowed me to work in his laboratory at the Institute of Child Health. I have been privileged to have such thoughtful and thought-provoking colleagues as David Thomas and Paisarn Vejchapipat, who have been of great assistance throughout. I also thank Gaby Pell, Robert Helliar, Martin King, Fernanado Calamante. Sue Williams, Mark Lythgoe, Edward Proctor, Quyen Nguyen, Enrico De Vita, Neil Harris and Dan West for their invaluable contributions. I am grateful for the support and encouragement of all my colleagues, especially Sally Dowsett, Sati Sahota, Jo Perthen, Donald Tournier, John Thornton and Marzena Arridge. Friends and family make everything possible and special thanks must go to my Mum for her support and genuine interest in everything I do, as well as to my Dad and Hugh. Thanks to all my friends, near and far, for all moral and practical support, and in particular to Anand Madhvani, Sue Williams and Faye Jones, who have enriched these years enormously.