Clinical Magnetic Resonance Spectroscopy Clinical Magnetic Resonance Spectroscopy Ernest B. Cady University College Hospital London, United Kingdom Plenum Press • New York and London Library of Congress Cataloging-in-Publication Data Cady, Ernest B. Clinical magnetic resonance spectroscopy I Ernest B. Cady. p. em. Includes bibliographical references. Inc I udes index. ISBN-13: 978-1-4684-1335-9 e-ISBN-13: 978-1-4684-1333-5 DOl: 10_1007/978-1-4684-1333-5 1. Nuclear magnetic resonance spectroscopy--Oiagnostic use. r. Title. [ONLM: 1. Nuclear Magnetic Resonance. 00 96.NS C126cl RC7S.7.N83C33 1990 616.07·548--dc20 DNLM/OLC for Library of Congress 90-7400 CIP © 1990 Plenum Press, New York Softcover reprint of the hardcover 1s t edition 1990 A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Foreword Nobody can know everything. For the successful application of techniques based on nuclear magnetic resonance to clinical problems, it is a vital necessity that individuals with widely different skills should learn a little of each others' trades by co-operation and communication. Ernest Cady has long proved himself a master of these arts to his colleagues at University College London, and by writing this excellent book he extends his experience to a wide circle of readers. Although the nuclear magnetic resonance (NMR) phenomenon had been predicted theoretically (and to some degree demonstrated experimentally) appreciably earlier, it required the advances in electronics that took place during World War II to turn NMR into a practical technique, as demonstrated independently in 1946 by Bloch and Purcell. Since then, NMR has been used extensively and increasingly by chemists and physicists. In the 1970s the first applications of NMR to animal organs yielded important advances in our knowledge of the biochemical and physiological processes as they occur in genuinely intact tissues. They showed incidentally that some conventional techniques introduce significant artifacts. More importantly, when combined with massive technical advances in the design of superconducting magnets and in radiofrequency technology, this work laid the foundations for the explosive expansion of human clinical applications that has occurred within the past decade. One casualty of this expansion has been in terminology. The very word "nuclear" sent shudders down the spines of many patients even though the energy per quantum of the radiofrequencies employed is some 1010 times less than that of ionizing radia tions. Nevertheless for clinical purposes the "N" has been dropped from the name; "MR" is used instead throughout this book. This may seem trivial but v vi Foreword it is not; the mental equanimity of patients is just as important as their physical condition. The change is distinctly confusing to other scientists, who wonder whether the clinicians are employing a totally different technique, especially since in some new developments they are! Another loss is that the name NMR is succinctly descriptive-Nuclear because the fundamental phenomenon arises from the spin of those atomic nuclei that have it (all those containing uneven numbers of protons and/or neutrons ); Magnetic because the spin and positive charge make the nucleus behave like a tiny magnet which will interact with externally applied magnetic fields; and Resonance because the use of the technique depends on first exciting and then detecting resonant frequencies. This book deals almost exclusively with MR spectroscopy (MRS), one of whose main uses is the noninvasive chemical analysis of tissues. MRS has had some success in solving clinical problems, notably in assessing the condition of the brain and the prognosis in new-born human babies. Enzyme defects in muscle, which are easily detected by MRS, tum out on survey to be rare. The real and well-justified clinical success of the decade has been in MR imaging (MRI). In this technique, the resonances from the IH nuclei, so plentiful in the body, and also intrinsically the most sensitive, are manipulated in such a way that they produce pictures of high quality of sections in any plane within the body. Because radio-frequency technique is so versatile, these sections can be "stained" in different ways so as to show up contrasts that are impossible when using X-ray tomography. Nevertheless, the appearance of a book on clinical MRS now is singularly well timed. MRS is increasingly being combined with MRI in the same wide bore, high-field spectrometer. In this way a certain volume of tissue can be located using MRI and its chemical composition determined by MRS. The possibilities seem endless and the excellent reference listings not only describe the past but also put up many pointers to the future. Since clinical MR is such a multifaceted subject, it is hard to know how to begin to present it optimally to readers whose own knowledge will also be very variable. My advice to them is that they need not necessarily start at the beginning of the book but should start from topics that they already know something about and are especially interested in. They can then work outward, colloquially speaking, to less familiar but very important territory. Anyone who wants to learn about MRS but feels daunted by every part of this book can take heart from the fact that Ernest Cady's first degree was in astronomy! Prof. D. R. Wilkie MD FRCP FRS Department of Physiology University College London Preface I have found the production of this book an exhilarating and self-educative experience. The initial impetus for its production occurred during the production of a chapter on the same subject, which was coauthored with S. R. Williams. It was apparent that enough material was available and that the subject had reached a sufficient degree of maturity to proceed with a more substantial work. It is hoped not only that the reader will find the text interesting as a description of the medical applications of magnetic resonance spectroscopy (MRS) but also that those who are actively involved in clinical investigations will find the work useful for reference purposes. Furthermore, it is anticipated that clinicians and other researchers entering the field without prior experience will find that the text gives useful information about both the practical implementation of MRS systems and the physiological information which can be derived from the spectra. Over the last decade, the in vivo MRS field has always been exciting -from the first collections of the P spectra of in situ human muscle using 31 surface coils to the recent acquisition of highly resolved proton spectra with full three-dimensional 1H image-guided localization from the living human brain. The field is still developing rapidly, with continuous publication of technical advances in data collection, localization, spectral editing, and spectral-analysis methods. I have attempted to ensure that as many recent "state of the art" publications as possible have been cited in the text. My initial interest in the clinical aspects of MRS was aroused by D. R. Wilkie, E. O. R. Reynolds, and R. H. T. Edwards; for this, and for the leadership shown by these individuals, I am eternally thankful. I am also grateful for discussions with various colleagues concerning the application vii viii Preface of MRS in the clinic. These include P. L. Hope, P. A. Hamilton, J. S. Wyatt, A. D. Edwards, A. M. de L. Costello, R. M. Gardiner, P. S. Tofts, S. Wray, M. J. Dawson, and D. T. Delpy. I must express my thanks to D. J. Newham, R. Aldridge, D. A. Jones, and J. K. Nicholson for assistance with collecting some of the spectra used in the present work and to H. Greenwood for secretarial assistance. Finally, but by no means least, I must thank my wife, Lorna, and my sons, Henry and Douglas, for their tolerance and patience during my many periods of absence while preparing the manuscript. Ernest B. Cady Hornsey, London Contents 1. An Introduction to Medical Magnetic Resonance Spectroscopy . . . . . .. 1 1.1. The Magnetic Resonance Phenomenon. . . . . . . . . . . . . . . . . . . .. 1 1.2. Magnetic Resonance in a Clinical Context. . . . . . . . . . . . . . . . . .. 4 1.3. Nuclei with Potential Clinical Applications. . . . . . . . . . . . . . . . .. 6 1.3.1. Phosphorus e1p). .................................. 6 1.3.2. Hydrogen eH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 8 1.3.3. Carbon (l3C) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 9 1.3.4. Nitrogen eSN) ..................................... 10 1.3.5. Oxygen (170) ...................................... 10 1.3.6. Fluorine (19F) ..................................... 10 e 1.3.7. Sodium 3Na) ..................................... 11 1.4. The Development of Biological MRSI ....................... 11 1.4.1. Skeletal Muscle .................................... 12 1.4.2. Cardiac Muscle .................................... 15 1.4.3. Smooth Muscle .................................... 17 1.4.4. Brain ............................................ 19 1.4.5. Liver ............................................. 31 1.4.6. Kidney ........................................... 33 1.4.7. Adipose Tissue .................................... 34 1.4.8. Lung(s) .......................................... 35 1.4.9. Testes ............................................ 36 1.4.10. Ovaries ........................................... 37 1.4.11. Skin ............................................. 38 1.4.12. Neoplastic Tissues ................................. 39 References .................................................. 40 ix x Contents 2. Fundamentals of Clinical Magnetic Resonance. . . . . . . . . . . . . . . . . . .. 47 2.1. The Origin of the Magnetic Resonance Signal. . . . . . . . . . . . . . .. 47 2.1.1. The Behavior of Nuclear Spins in a Magnetic Field. . . . .. 47 2.1.2. The Rotating Frame of Reference ..................... 49 2.1.3. The Bloch Equations and Relaxation Phenomena ....... 51 2.2. The Magnetic Resonance Signal . . . . . . . . . . . . . . . . . . . . . . . . . .. 53 2.2.1. The Free Induction Decay. . . . . . . . . . . . . . . . . . . . . . . . . .. 54 2.2.2. The Spin Echo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 57 2.2.3. Fourier Transformation. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 58 2.3. The Spectrum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 59 2.3.1. Chemical Shifts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 60 2.3.2. The Shapes and Widths of Spectral Peaks. . . . . . . . . . . . .. 69 2.3.3. Metabolite Concentrations. . . . . . . . . . . . . . . . . . . . . . . . . .. 74 2.4. The Signal-to-Noise Ratio. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 74 2.4.1. The SNR from a Single 90° Pulse ..................... 75 2.4.2. The Effect of T, and T2 on SNR ...................... 76 References ................................................. 79 3. Clinical Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 83 3.1. Introduction............................................ 83 3.2. Studies ofthe Human Brain ............................... 84 3.2.1. Studies ofthe Neonatal Brain. . . . . . . . . . . . . . . . . . . . . . .. 85 3.2.2. Spectroscopic Studies of the Adult Brain. . . . . . . . . . . . . .. 95 3.3. Studies of Human Skeletal Muscle .......................... 109 3.3.1. 3'p Spectroscopy of Human Muscle ................... 109 3.3.2. 'H Spectroscopy of Human Muscle ................... 121 3.3.3. 13C Spectroscopy of Muscle .......................... 122 3.4. Studies of Human Cardiac Metabolism ..................... 124 3.4.1. 3'p Studies of Human Cardiac Metabolism ............. 124 3.4.2. 'H Studies of the Human Heart ...................... 126 3.5. Studies of the Human Liver ............................... 126 3.5.1. 3' P Studies of the Human Liver ....................... 126 3.5.2. 13C Studies of Human Liver Metabolism ............... 129 3.6. Studies of Human Kidneys ................................ 130 3.7. Studies of Human Testes .................................. 131 3.8. In Vitro Studies of Human Body Fluids ..................... 132 3.8.1. 'H Studies of Urine ................................. 132 3.8.2. 'H Studies of Amniotic Fluid ......................... 135 3.8.3. 'H Studies of Human Blood Plasma ................... 136 3.9. Studies of Human Red Blood Cells ......................... 136 3.9.1. Results from 3'p Spectroscopy ........................ 137 3.9.2. 'H Spectroscopy of Red Blood Cells ................... 138 3.9.3. 23Na Spectroscopy of Red Blood Cells ................. 139 References ................................................. 139 Contents xi 4. Practical Aspects of Clinical Magnetic Resonance Spectroscopy Systems ......................................... 149 4.1. An Overview of the System ................................ 149 4.2. The Magnet. ............................................ 151 4.2.1. Permanent Magnets ................................ 152 4.2.2. Resistive Electromagnets ............................ 153 4.2.3. The Liquid-Helium Superconducting Magnet. .......... 154 4.2.4. Shim, Gradient, and Profiling Coils ................... 159 4.3. The Spectrometer ........................................ 159 4.3.1. The RF Probe ..................................... 160 4.3.2. RF Coils .......................................... 160 4.3.3. The Preamplifier ................................... 176 4.3.4. The Receiver ....................................... 178 4.3.5. The Analog-to-Digital Converter ..................... 179 4.3.6. The Computer System .............................. 181 4.4. Safety Requirements. ..................................... 182 4.4.1. The Static Magnetic Field ........................... 183 4.4.2. Rapid Magnetic Field Changes ....................... 185 4.4.3. Radio-Frequency Fields ............................. 186 4.4.4. Other Hazards ..................................... 187 4.5. Patient Handling ........................................ 187 References ................................................. 188 5. Data Acquisition in Clinical Magnetic Resonance Spectroscopy ...... 193 5.1. Fundamental Considerations .............................. 193 5.1.1. Collecting Data Using Repeated Single Pulses .......... 193 5.1.2. Reduction of Spectrum-Baseline Artifacts .............. 196 5.2. Signal Localization ...................................... 196 5.2.1. Surface-Coil-Localization Methods .................... 197 5.2.2. Magnetic Field Gradient Techniques .................. 201 5.3. Spin-Echo Techniques .................................... 213 5.3.1. Simplification of Spectra ............................. 213 5.3.2. Spin Echoes with Surface Coils ....................... 214 5.4. Solvent Suppression ...................................... 216 5.4.1. Composite Pulses ................................... 216 5.4.2. Spin Echoes ....................................... 217 5.4.3. Saturation Methods ................................ 218 5.4.4. Binomial Pulses .................................... 218 5.5. Spectral Editing ......................................... 220 5.5.1. Reduction of Bone and Phospholipid Signals ........... 221 5.5.2. Spectral Editing in IH Spectroscopy ................... 222 5.6. Absolute Quantitation .................................... 225 5.6.1. External Concentration References .................... 226