Paul Lauterbur and the Invention of MRI
Page 1
Paul Lauterbur and the Invention of MRI
Paul Lauterbur, 1996.
Paul Lauterbur and the Invention of MRI
M. Joan Dawson
The MIT Press
Cambridge, Massachusetts
London, England
© 2013 Massachusetts Institute of Technology
All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means (including photocopying, recording, or information storage and retrieval) without permission in writing from the publisher.
Unless noted otherwise, all illustrations are drawn from the Paul C. Lauterbur collection, Chemical Heritage Foundation Archives, Philadelphia PA.
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Library of Congress Cataloging-in-Publication Data
Dawson, M. Joan, 1944–
Paul Lauterbur and the invention of MRI / M. Joan Dawson.
p. cm.
Includes bibliographical references and index.
ISBN 978-0-262-01921-7 (hardcover : alk. paper)
I. Title.
[DNLM: 1. Lauterbur, Paul C., 1929–2007. 2. Magnetic Resonance Imaging—history—Biography. 3. Magnetic Resonance Spectroscopy—instrumentation—Biography. 4. Nobel Prize—Biography. WZ 100]
616.07′548092—dc23
[B]
2012046012
10 9 8 7 6 5 4 3 2 1
Contents
Foreword by Edwin D. Becker
Acknowledgments
Prologue
1 Epiphany in a Hamburger
2 Portrait of a Scientist as a Young Man
3 Study, Work, and War
4 Early Breakthroughs
5 The 1960s: Stony Brook, Stanford, and Spectrometers
6 The First Fruitful Weeks
7 The Worldwide Laboratory
8 Baby Grows Up
9 Among the Corn Fields
10 The End and the Beginning
Epilogue
Appendix A: The Notebook, September 1971
Appendix B: Magnetography, October 1971
Appendix C: Draft Disclosure, August 1972
Notes
Index
Foreword
Edwin D. Becker
I first heard about the concept of NMR imaging from Paul Lauterbur one evening in December 1972 in midtown Manhattan. We were attending a biological MR meeting and, as a number of attendees returned to our hotel from a reception, I happened to be walking with Paul. “Ted,” he said, “you would be interested in this experiment I did with an A-60.” He explained that he had deliberately mis-set the homogeneity control to create a linear field gradient and found two separate NMR signals from two identical tubes of water in the probe. Of course—once he pointed it out!—that is just what one would expect. As he further made clear, he had done this in various directions and put the data together to create a two-dimensional image. So here was a lovely, simple way to look inside materials and animals. At that stage, it had to be a very small animal to fit inside an NMR probe, but, as Paul said, scale-up was mostly engineering.
This was only the latest in Paul’s record of innovative accomplishments. Fifteen years earlier he had published the first systematic study of 13C NMR, which in later years became extremely important in chemical NMR. He also was a pioneer in investigating several other nuclei, such as 29Si, 27Al, 119Sn, 59Co and 207Pb. He had done many other clever NMR experiments. So, long before imaging, Paul was well known and widely respected in the worldwide chemical NMR community. In 1972–1973, we all appreciated his new idea, but most of us certainly did not realize then just how much effort Paul had already devoted to working out in detail the potential for more efficient techniques and the immense range of possibilities for medical application. As time went on, I had the opportunity to deal peripherally with some aspects of MR imaging and to write at some length about the history of NMR, where Paul’s many contributions are amply recorded.
Now, in this biography we have a marvelous account of Paul Lauterbur as a person and as a scientist. Joan Dawson’s well-written account gives us the “inside story,” as only she could write it. She describes Paul’s journey from childhood to Nobel Laureate in the personal terms of a loving wife. Her description of the science involved draws on her own scientific credentials but is written in clear language that nonscientists can readily understand. She does not hesitate to “name names” as she recounts the rocky path that Paul encountered during his efforts over many years to develop his ideas for further advances in imaging in an academic environment. She includes an enormous amount of documentation from Paul’s extensive files.
The Nobel Prize for MR imaging was awarded in 2003—long after the method had generated a multibillion dollar industry and revolutionized diagnostic radiology. It was clear to just about everyone that Paul Lauterbur had initiated this whole field and deserved the Nobel Prize, but year after year passed with no prize for these great advancements in science. The question that held up a decision was: Who else—if anyone—might deservedly share the prize? Several early workers—particularly Waldo Hinshaw and Raymond Damadian—provided demonstrations of NMR images by building up the image one point at a time, but these proved to be too slow to be of practical importance. Several groups, notably at Aberdeen and Nottingham, showed important but rather primitive clinical applications. Richard Ernst advanced the initial Lauterbur technique by showing that the methods he and his coworkers developed for two-dimensional NMR spectroscopy could create two-dimensional images very efficiently, but this aspect of his work was already recognized in the Nobel Prize in Chemistry, which had been awarded to Ernst in 1991. Peter Mansfield conceived an idea for imaging in solids about the same time as Lauterbur’s initial experiments in 1972, and later he developed widely used methods for slice selection and rapid echo-planar imaging in animals and humans. In the end, the Nobel Committee appropriately selected Lauterbur and Mansfield as co-recipients of the Nobel Prize in Physiology or Medicine.
Dr. Dawson gives a clear and objective summary of the developments in MR imaging around the world during the 1970s and early 1980s. She also describes the Nobel controversy but does not dwell on it. Indeed, Paul himself appreciated the many awards he received, but he was motivated by science and by a stream of innovative ideas, not by prizes. We are all richer for Paul Lauterbur’s inspiration and achievements in NMR and MRI, and now we can be grateful to Joan Dawson for telling us much more about his life and work.
National Institutes of Health
Bethesda, MD
Acknowledgments
I thank my editors, freelance editor Linda Carbone, for helping to turn my scribbles into a book, and acquisitions editor Susan Buckley and senior editor Deborah Cantor-Adams of the MIT Press for refining that book. So many wonderful people have helped with this project by talking to me about Paul and the early days of MRI, and reading sections of the various versions of the manuscript that it would not be helpful to try to name them all. Please know that your help is greatly appreciated. Special thanks go to Debbie McCall, Elise Lauterbur, Z. P. Liang, Vikas Gulani, and Jeff Tso. Ted Becker of the NIH and Francis Bonner of Stony Brook University have both given me excellent guidance. Thank you all.
Prologue
Thomas Huxley in his inaugural address on becoming president of the Royal Society in 1883 observed, “What an enormous revolution would be made in biology if physics or chemistry could supply the physiologist with a means of making out the molecular st
ructure of living tissues comparable to that which the spectroscope affords to the inquirer into the nature of heavenly bodies.”
Andrew Huxley, grandson of Thomas, noted in his own inaugural address in 1980 that his grandfather’s wishes had come true with the invention of zeugmatography—better known today as magnetic resonance imaging, or MRI—by Paul Lauterbur in 1972. MRI is the most significant medical diagnostic discovery since x-rays. MRI changed the course of medicine. It became a leading diagnostic tool because it images the soft tissues of the body anatomically, biochemically, and functionally. It is noninvasive and safe, and unlike radiography (with x-rays) or computed tomography it involves no ionizing radiation. This book is the story of the man behind the invention.
I met Paul Lauterbur when he was a professor at the State University of New York, Stony Brook (now Stony Brook University), and I was a lecturer at University College, London. I was a graduate of Columbia University’s School of General Studies in New York and had received a PhD in pharmacology from the University of Pennsylvania. I took a postdoctoral fellowship in the Department of Physiology at University College, London, under the mentorship of Douglas Wilkie, an eminent muscle physiologist. I later received the prestigious Sharpey Scholarship and became a lecturer in the department.
Paul had accomplished a great deal as a young man, including showing the possibility of obtaining nuclear magnetic resonance (NMR) spectra from 13C NMR, an early accomplishment that made him famous in the NMR community long before his work on MRI. When I met Paul, he was in the early stages of MRI research. My colleagues and I were doing some of the first metabolic measurements on living tissues by NMR. The year was 1977. The place was Oxford, England, and the occasion was a symposium on biochemistry. We met again in 1978 at the International Biophysics Symposium in Kyoto, and in 1979 at a meeting of the Royal Society in London. We met many times in the following years in a fairy-tale romance that took place at conferences and symposia all over the world. Then there was a conference in Liège, Belgium, and I knew I was in love. Paul started planning his frequent European trips with a stopover in London. We would take a few days off and vacation in the Cotswolds or the West Country. I thought this was lovely, and I hoped it would go on forever. Then I received a note from him, written on the train between Rome and Milan. He had just had a startling revelation: he wanted to marry me.
We were never a young married couple; I was forty and Paul fifty-five when we took those vows. But we were in love, we raised our adored daughter together, and we had a partnership in science. Each understood the other’s passion for science. Paul always read my scientific papers before I sent them out for publication. And I read his papers, grant applications, and important letters. Paul was a romantic. He gave me an anniversary card and three roses each and every month on the third, the date of our wedding. He gave our daughter a single rose.
We had been married twenty years when Paul grew ill. I started to write this book when he was dying of kidney disease, which finally took his life at age seventy-eight. Talking about his life, his philosophy and ideas, was a means for the two of us to be together rather than me simply being his caretaker. It drew us even closer. Many of the quotations from Paul in this book are from those final months, when we had a few long conversations and little question-and-answer sessions over the dinner table, at bedtime, or whenever. He was happy with the idea of the book and thought that I, as his wife and scientific partner, was the logical person to write it, although he was profoundly skeptical of what I might produce!
I have tried to show how MRI, Paul’s most famous achievement, is an expansion and transmogrification of the thinking and work he had already done by his senior year in college. And I have tried to show the man’s great strengths and weaknesses. Tom Budinger wrote a note about Paul: “The third part of Aristotle’s virtue is called Eudainomia, which translates to happiness or joy and that’s what Paul has.” I have tried to show this joy as well. Knowing Paul was a great privilege for me, and I am only one of many who have expressed this sentiment.
My handyman, Tem Jones, gave one of my favorite epitaphs. On the six-month anniversary of Paul’s death, Tem burned to talk about Paul.
It tickled me to see sometimes how easy he was. All that he got goin’ on an’ he wanted the bird seed” (watching the cardinals in winter was one of Paul’s favorite pastimes). “He a student like a tree. It has bark on it; he in the tree but you couldn’ see it. Inside that tree it’s growin’ an’ changin’ and in spring it’s blossomin’. Paul, he the tree; he got like a computer goin’ on his head at all times but you couldn’ see it. He got his own deck a cards and he play it his way. He could still read his paper while a wall fall down. He aint never made hiself up big. He small cause he choose ta be. He alwus stay on the playing field like the rest a us. He like a man in the woods and his thoughts was bigger ’n’ society-type thoughts. He always been that kid unner a tree readin’ a book. Everything else ’round him don’ matter.
Finally, I write because, as Thomas Aubrey, the sixteenth-century chronicler of Elizabethans, said of his Brief Lives, “all this would be lost were it not for fools like me.”
1
Epiphany in a Hamburger
Before every big breakthrough, it is first a crazy idea.
—Paul Lauterbur
On September 2, 1971, Paul Lauterbur was at the site of NMR Specialties, a company he had helped to found, in New Kensington, Pennsylvania, when a potential customer showed up. In his attempt to save the floundering company, Paul had been flying to New Kensington at the beginning of each week and back to his family and students at Stony Brook for the weekend. To feed his kids, save his research program, and save the small company from instant bankruptcy, he had spent the summer trying to learn, under extreme pressure, how to manage a company that would soon disappear forever.
As a sales strategy, NMR Specialties made its equipment available to potential customers. It was for this reason that on that September day, Leon Saryan, then a postdoctoral fellow at Johns Hopkins, came to the New Kensington laboratories in an effort to confirm the research findings of Raymond Damadian, of the State University of New York’s Downstate Medical Center in Brooklyn. Damadian had published a paper in Science earlier that year titled “Tumor Detection by Nuclear Magnetic Resonance,”1 in which he announced that the time to decay (T2 relaxation time) and the time to recovery of magnetization (T1) for NMR signals, those “I am here” signals from atomic nuclei, could be used to detect and diagnose cancer.
As Paul observed Saryan’s measurements, he saw that the signals differed markedly between normal and malignant tissues. But Saryan was cutting the tissue samples out of rats, and Paul thought such measurements could never be very useful in research or medicine. “It didn’t seem right to kill the patient to diagnose the illness,” he said. “It was a bloody messy affair, not the sort of thing chemists are used to seeing.” He never liked the sight of blood. “Thinking of a way to do it without surgery took on a greater importance for me than it might for a doctor,” he admitted. “As a naive chemist, I couldn’t imagine cutting people up to see if they were sick or not.” He felt there had to be a better way. If you could find a way to localize the NMR signals to specific places in a patient without using harmful invasive procedures, well, that would be a different matter altogether. If physicians could do that, they could look into any part of the body remotely to see what the problem was, and the patient would be unaffected by the analysis.
“I believed that NMR relaxation time measurements on tissue specimens were unlikely to contribute much to the rich variety of information available from optical microscopy. All of this information about the tissues was apparently there, however, within the living organism. Was there any way that one could tell exactly which location an NMR signal was coming from within a complex object?”2 That same evening he figured it out. He had taken a dinner break with Don Vickers, a friend and company officer, at a fast-food place. “On the second bite of a Big Boy hamburger,
” just as he was explaining to Don that the physics of NMR precluded imaging, in midsentence, he found the principle of MRI.
“I realized that inhomogeneous magnetic fields labeled signals according to their spatial coordinates, and made a leap of faith to the conclusion that the information could be recovered in the form of images.”3 He sketched the general idea to Don. “Heck, you could make pictures with this thing!” Don was astonished by how completely different Paul’s ideas were from what all spectroscopists had previously been doing.
Paul ran out to buy a notebook at a nearby drugstore. He spent much of the night refining his thoughts and convincing himself that he was not just on a wild goose chase, and by morning the book was bursting with ideas. “The Notebook,” as I call it, not only describes the principle of MRI but also predicts a great deal of its development during the next twenty-five years, and on into the future. Its title is “Spatially Resolved Nuclear Magnetic Resonance Experiments.” It begins:
The distribution of magnetic nuclei such as protons, and their relaxation times and diffusion coefficients, may be obtained by imposing magnetic field gradients . . . on a sample, such as an organism or a manufactured object, and measuring the intensities and relaxation behavior of the resonance as a function of the applied magnetic field.
He then described his idea more fully (see appendix A of this book). Four days after the hamburger revelation, Paul listed on sheet of loose-leaf paper ten distinct methods by which MRI could be done. The next day he finished the seven-page scrawl in The Notebook by distilling these ten methods into two fundamental categories of MRI methods, time dependent and time independent.