Magnetic Resonance Imaging of Diffusion and Perfusion: Techniques and Applications to Cerebral Ischaemia David Lee Thomas Department of Medical Physics and Bioengineering University College London Submitted for the Degree of Doctor of Philosophy University of London January 1999 ProQuest Number: U644089 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest U644089 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Abstract Stroke and other cerebrovascular diseases are among the most common causes of death and disease in the Western world. Over recent years, magnetic resonance imaging (MRI) has been shown to be a sensitive indicator of tissue damage caused by cerebral ischaemia. Several techniques have been developed using MRI methods which enable different aspects of tissue status to be monitored. The aim of the work presented in this thesis was to develop these techniques and apply them to the study of experimental cerebral ischaemia in animal models of stroke. The non-invasive method of perfusion imaging known as FAIR was implemented. The method was developed to enable accurate quantitation of perfusion with good time efficiency by incorporation of a global pre-saturation pulse into the sequence. Transit time effects were minimised by the use of high definition adiabatic RF pulses. Use of the sequence to follow a perfusion time course in a gerbil model of transient global ischaemia is demonstrated. New techniques were developed for T 2 * mapping, using an interleaved echo planar imaging (EPI) approach, and diffusion-weighted imaging (DWI), using a version of magnetisation prepared TurboFLASH. The use of both the T 2 * and DWI sequences is demonstrated on phantoms and in vivo. Finally, MRI was used in the investigation of cerebral pathophysiology following middle cerebral artery occlusion in the rat at 8.5T. Continuous arterial spin labelling was used to monitor levels of perfusion, and ADC, Ti and T2 were also measured for a period of several hours after occlusion. Immediate changes in all parameters were observed, and physiological mechanisms for these changes and the potential for their diagnostic use are discussed. _________________Contents_________________ 1 INTRODUCTION..........................................................................................................1 1.1 H ist o r ic a l B a c k g r o u n d .................................................................................................................. 3 1.2 T h e sis A im s ................................................................................................................................................ 7 2 NMR THEORY AND IMAGING TECHNIQUES...................................................9 2.1 P r in c ip l e s o f N u c l e a r M a g n e t ic R e s o n a n c e - T h e Q u a n t u m A p p r o a c h 9 2.1.1 Quantum mechanics and the nuclear magnetic moment .................................. 9 2.1.2 Nuclear energy levels in a static magnetic field ..............................................11 2.1.3 Transitions between nuclear energy levels ...................................................... 13 2.1.4 The population distribution of the nuclear energy states ............................... 14 2 .2 P r in c ipl e s o f N u c l e a r M a g n e t ic R e s o n a n c e - T h e C l a s s ic a l A p p r o a c h ... 15 2.2.1 Nuclear magnetism and the net magnetisation vector. ................................... 15 2.2.2 Spin excitation: the rotating frame of reference and the oscillating Bj field 15 2.2.3 Relaxation ..........................................................................................................17 2.2.4 The Free Induction Decay and Signal Detection ............................................18 2.2.5 The Hahn spin echo ...........................................................................................19 2.2.6 The Inversion Recovery sequence .....................................................................19 2.2.7 Adiabatic RF pulses .......................................................................................... 22 2.3 Im a g e F o r m a t io n u s in g N u c l e a r M a g n e t ic R e s o n a n c e T e c h n iq u e s ..............23 2 .3.1 Slice selection ....................................................................................................24 2.3.2 Frequency encoding .........................................................................................24 2.3.3 Phase encoding ................................................................................................. 26 2.3.4 The concept ofk-space ..................................................................................... 2 7 2.3.5 Fast Low Angle Shot (FLASH) imaging .......................................................... 28 2.3.6 Echo Planar Imaging (EPI) ..............................................................................2 9 2 .4 Im a g e W e ig h t in g in M a g n e t ic Re s o n a n c e Im a g in g .................................................... 31 2.4.1 Image weighting using NMR parameters ........................................................ 31 2.4.2 Image weighting using biological parameters ................................................33 111 3 INTRODUCTION TO PERFUSION AND DIFFUSION........................................35 3.1 T h e c o n c e p t o f p e r f u s io n .............................................................................................................35 3 .2 M e t h o d s o f m e a s u r in g c e r e b r a l p e r f u s io n ....................................................................35 3.2.1 Group I methods ................................................................................................ 37 3.2.2 Group II methods ............................................................................................... 38 3 .3 M a t h e m a t ic s o f in e r t g a s c l e a r a n c e m e t h o d s ............................................................43 3.3.1 Fick principle ..................................................................................................... 43 3.3.2 Kety-Schmidt method .........................................................................................43 3 .4 M e a s u r in g p e r f u sio n u s in g NMR........................................................................................... 4 4 3.4.1 Perfusion MR Imaging with Exogenous Contrast Agents .............................. 45 3.4.2 Assessment of Tissue Perfusion using an Endogenous Susceptibility Contrast Agent - BOLD imaging ................................................................................................. 49 3.4.3 Introduction to Non-invasive Perfusion MR Imaging using Spin Labelling of Arterial Water ................................................................................................................. 50 3.4.4 Continuous Arterial Spin Labelling techniques .............................................. 57 3.4.5 Pulsed Arterial Spin Labelling techniques ...................................................... 57 3 .5 D if f u sio n in b io l o g ic a l s y s t e m s ..............................................................................................62 3.5.1 Molecular Diffusion ...........................................................................................62 3.5.2 Random walk and Einstein’s equation .............................................................63 3.5.3 Boundaries and restriction ............................................................................... 63 3 .6 E ffe c t s o f d if f u s io n o n t h e sp in e c h o MR s i g n a l ........................................................64 3.6.1 Motion, gradient and MR signal ......................................................................64 3.6.2 Spin echo and constant gradient ...................................................................... 66 3.6.3 Pulsed gradients and Stejskal-Tanner sequence .............................................67 3.6.4 Diffusion imaging ..............................................................................................67 3.7 D if f u sio n MRI a n d c e r e b r a l is c h a e m ia ............................................................................ 7 0 3.7.1 Potential mechanism for DWI changes ............................................................70 3.7.2 Diffusion-weighted imaging and the therapeutic window .............................. 77 4 NON-INVASIVE QUANTITATION OF CEREBRAL PERFUSION USING FAIR MRI..............................................................................................................................72 4.1 Introduction ........................................................................................................................................ 7 2 4 .2 D emonstrating th e b a s ic f l o w sensitivity o f FAIR.................................................. 73 IV 4 .3