Paul Lauterbur and the Invention of MRI

by M. Joan Dawson

  Paul never saw any documentation of the stupendous offers the press reported, and his attitude, having long worked in the New York State University System, was that such a big technical effort could never materialize. To reporters he said that one of his reasons for leaving Stony Brook was that it was difficult to secure funding for “operations from getting the snow plowed to getting a new program approved.”15 To me he said he had been thoroughly immersed in “the clueless penny pinching culture that was the State University System of New York” for too long. Would he be able to modify the proposed new MRI system sometimes to test his new ideas? In the “Retain Paul” committee formed to negotiate a joint NMR/MRI facility with access by basic scientists as well as radiologists, Mort Meyers, chairman of Radiology, was always listed as a participant, and his chair was always empty.

  Courtship

  Paul was considering not just a move but a new life altogether. He was separated from Rose Mary and hoped for some new kind of marital happiness.

  I met Paul at a conference at Oxford University in 1977. He had explained that spatial information could be encoded in magnetic gradients to form a three-dimensional image. This he illustrated with the renowned MR image of two water-filled capillary tubes, followed by many other examples, including Sharyn’s celebrated clam and various segmented vegetables. He showed images of red peppers, colored various intensities of red, and of green peppers colored green. There was a question after the lecture about the medical implications of the work. Paul said of course he was aware of, and hopeful for, using MRI for the noninvasive diagnosis of disease, but that he did not want to be premature about touting this possibility.

  I didn’t see Paul again until the spring of 1978 when we both attended, along with thousands of other people, the meeting of the International Society for Pure and Applied Biophysics, which took place in the International Conference Hall in Kyoto, Japan. The setting is extraordinary, backdropped by the beautiful hills over Kyoto. The entrance plaza is filled with fountains and koi ponds, all in a very beautiful Japanese style. The building itself is a large, then very new, cement structure of curving design containing many conference and meeting halls, as well as tiny sitting nooks for quiet conversation. Paul and I spent a long afternoon tucked into one of these little spaces, talking about science and getting to know one another. I sent him a note from London after returning, written on the back of a meeting schedule, which featured pictures of the koi in the plaza ponds. I hoped he would think this gesture to be very poetic and personal. (The truth is that, on my lecturer’s income, I couldn’t afford fancy stationery!)

  My strongest impressions of the meeting in Kyoto concerned not the science presented, or the gardens, or even Paul, but the food. There was a reception on the plaza following the opening remarks. Food and drinks were slow in coming, and we had all fanned out like a thousand hungry pigeons. When the waiters finally appeared, there was a feeding frenzy very similar to what one sees among pigeons or during feeding times at the zoo. Only the strongest were satisfied; the rest of us went away hungry. All my ideals of what a scientist should be were dashed by this beastly behavior. For me it was a double disaster. I lived on a small stipend, and these free handouts were dinner!

  Nineteen seventy-nine was the year of the London meeting of the Royal Society on Magnetic Resonance Imaging, where I was to meet, or at least hear presentations by, the leading figures in the field of MRI, which I had just entered. The Royal Society was housed in a lovely regency building overlooking the Strand: white, with beautiful columns at the entrance and elegant, high-ceilinged rooms displaying great, historical, and imposing artwork. My favorite piece was the portrait of Sir Isaac Newton, the founding president of the society, which hung to the left as one entered. The floors were marble, and I loved the sound of my high heels clickety-clicking across them. Approximately two hundred people from all over the world were in attendance.

  Paul gave his talk in a style he had perfected, full of anecdotes, whimsy, and exciting science. He spoke on advances in MRI and showed many series of two-dimensional renderings of three-dimensional images. At this stage he was exploring the use of paramagnetic ions (ions that bend the magnetic field) to increase the image contrast. He was using the somewhat toxic manganese ion, which caused Jack Leigh of the University of Pennsylvania to sniff, “And he calls that noninvasive!” I understood that the work was meant to show proof of principle, but after Jack’s cutting remark I was at a loss as to whether it was a good idea or not. (It is now a billion-dollar industry.)

  In a negative way, the highlight of the meeting was the talk by Raymond Damadian. Damadian presented himself as the misunderstood genius, thwarted in his every endeavor to bring succor to mankind. He showed slide after slide of rejection letters, rejected grant applications, and poor reviews of papers submitted to scientific journals. It seemed never to have occurred to him that some of the negative reaction might be well founded. I felt very sorry for him; most of the audience, who knew him and his contributions to the field much better than I, was simply angry at the trumped-up claims he was making for the importance of his work. Although I never personally met him, Raymond Damadian was to have a huge negative impact on my life.

  Then there was Liège, and I was in love. I’d been invited to a meeting organized by John Griffiths of Kings College, London, to be held in Liège, Belgium, in 1982. I had seen from the participant list that Paul Lauterbur would be there talking about his three-dimensional imaging of surgical specimens. I didn’t know what to expect when meeting Paul once again and was quite nervous. As I boarded the shuttle bus from the airport to town, who should be in the nearest seat, right behind the driver, but Paul. We chatted in a very formal and stilted manner. Paul admitted the next day that he always seemed to be reaching for profound or clever things to say in order to impress me. I did not admit that I had been doing the same.

  We were at the same hotel and had been assigned rooms three or four doors apart on the same floor. Paul dropped by my room one morning to accompany me to the meeting hall. I was brushing my teeth when he knocked, and I answered the door with toothbrush still in hand. That ended the icy formality; Paul said much later that he had found me much more human when carrying a toothbrush. From then on we couldn’t stop talking. We talked about our work, we talked about our lives, we talked about all of our likes and enthusiasms and our dislikes and dreads. We talked about our childhoods. Paul talked about his children, and I talked about my dog. We talked about food and about places we had been, and about science. When the scientific meeting ended Paul was to take a train to Italy several hours earlier than my flight back to London, so I accompanied him to the train station. He missed the first train, because we didn’t notice the time, and we continued our conversation for another few hours. I was pretty overwhelmed by what seemed to be developing.

  Paul and I met later that year in Bucharest, Romania, where I was invited to a conference on muscle physiology organized by Caius Traian Dragomir. Paul was in Europe at the time, aware that I was attending that conference, and came to visit me there, checking into the International Hotel. He wrote on his entry card “tourist,” which must have seemed very suspicious. No one went to communist Romania to be a tourist in those days. I am sure the police were following him and relaxed when they found a woman was involved.

  From then on, Paul insisted on a stopover in London whenever he traveled to Europe, and he stayed in small hotels on Russell Square near my flat. We dined at local Indian and Middle Eastern restaurants near my home. These were the restaurants I could afford, and so they were the only ones I knew to suggest to him. I cooked him a meal (talking together in the kitchen all the while) and he professed himself mighty pleased with it. He accompanied me on walks to Regents Park with my dog, and we talked and talked some more. When he had a few days, we would plan an excursion to the Cotswolds or the West Country. For these we would pack up my tiny ten-year-old Morris Mini with his humongous suitcase and my little one, eking out a tiny space for
the dog, and off we would go, at a rather slow speed because the Mini couldn’t handle all that weight.

  One time, the Mini carried us to Lyme Regis, in Dorset, a resort area that I enjoyed visiting out-of-season (much too crowded in-season). We walked on the beach admiring the fossils of giant ammonites, which were once native to the sea overlying the region before its geological uplift. There is an interesting natural phenomenon in that place. The cliffs are slowly eroding and falling into the sea, leaving the undercliff, on which there is a footpath about eight miles long. I loved this trail. My visits to the region were usually in the raw early spring when the undercliff, a sun trap, was a wonderful warm respite. Primroses were flowering, and I could imagine that the rest of the populated world had melted away.

  One such spring Paul agreed to accompany me on this walk. I warned him that he would not find it easy. He slipped down the muddy trail in formal shoes, keeping himself upright using his umbrella. I had to laugh. He was rather portly and not at all fit. But he walked the whole eight miles, chattering away about interesting and clever things. I loved that he did all of this for love of me.

  About Me

  As I have just inserted myself into Paul’s life, I should tell you a little about myself. I grew up in Midland, Michigan, home of the Dow Chemical Company, where my father worked as an engineer. It was not my father but my maternal grandmother who encouraged a love of learning and science. Maude Pendock was born to farming and had to leave school after sixth grade. But she had a sense of wonder. When I was very little she explained to me our heliocentric Solar System. We were both in awe of this mighty knowledge. My mother was a housewife. I was the oldest of nine children, and so I too did a lot of mothering during my own childhood. A brother says that one of his memories of me was washing dishes with a book propped up on the sink. These were not schoolbooks. I read good literature but usually not what was assigned, so my grades were not stellar. In this I was like Paul. And because I was also extremely shy and quiet my teachers and parents were shocked, quite shocked, when I became a National Merit Finalist.

  I was also like Paul in being raised a Catholic and leaving the Church when I left home. I matriculated at the University of Michigan, intending to work my way through school. It didn’t go so well, and I dropped out of Michigan and found my way to New York (on a Greyhound bus with $20 in my pocket) and Columbia University’s School of General Studies. I took a job first as a temporary worker so I would be paid right away, and then as a technician. My boss later said he hired me despite my inexperience because of the questions I asked. So I worked full time and took classes either full-time or part-time and finally got a BS degree and co-authored a paper in Science when I was twenty-six. I went to Penn for graduate work in pharmacology because, as my mentors explained, I could always work in pharmacology no matter where my husband’s job might take me. I was experienced in the lab and able to get a PhD in three years.

  Who can write honestly about themselves? Certainly not me. So I quote. Paul said he was originally attracted to me by independence of mind. He got more of that than maybe he wanted. An early boyfriend when we broke up said he would never again find a woman so generous as me. Other people have said similar things, and I hope they are true. In another breakup another boyfriend said I was like tempered steel—I would bend but not break. My brother said I was a liberated woman before women’s lib. And he said I was wise! A friend appreciated my subtle sense of humor. There were plenty of negative things said, too, all well deserved, but I have forgotten them all.

  I went to University College, London, to do a postdoc with Doug Wilkie, a prominent muscle physiologist. One December day we heard a talk by George Radda about in vivo NMR. The experiments he showed were actually ex vivo. They stuffed rat muscle into an NMR tube and used 31P NMR to watch as the “high-energy” phosphates ATP and phosphocreatine declined and their hydrolysis product, inorganic phosphate, rose. Doug told me to drop everything and said we would now use NMR as a tool in muscle physiology. I hardly knew what NMR meant, but I was happily instructed by the famous book by Tom Farrer and Ted Becker. I could feel myself spinning in the rotating frame along with those magnetic nuclei. So Doug and I and David Gadian, then a student in the laboratory of Sir Rex Richards at Oxford University, did some work on muscle energetics and fatigue that created some buzz at the time. Sir Rex is reported to have said, “That’s the way this work should be done—but you are far too slow.”

  So that is the woman Paul met in 1977 and then married, for better or for worse. I felt extremely fortunate to have him as my life partner.

  MRI Safety

  Safety in MRI was still a hotly contested issue. Physicians quickly understood: “The method does not use ionizing radiation, in contrast to ordinary x-rays or computed tomography; it relies on the reaction of atomic nuclei in the body to a harmless magnetic field.”16 Multiple MRI scans could be acquired safely, allowing doctors to monitor the effects of treatment or chart the progress of a chronic ailment. But was it really safe? What about those high magnetic fields? What about those electromagnetic currents? Although calculations based on sound physics said these were safe as used in MRI, it had to be shown.

  Some early reports were discouraging. Rats left overnight in an MRI scanner showed signs of severe stress, interpreted as a stress response to the static or varying magnetic fields. But it turned out that the poor rats showed the same stress even when the magnet was turned off! Tom Budinger of Berkeley seriously studied the safety aspects of MRI and gave many talks on the subject. He showed that small animals and cultured cells that exhibited adverse effects suffered from inadequate temperature control or from other forms of stress unassociated with MRI itself. But by and large, the power-line electromagnetic field hysteria of the early 1980s was avoided.

  Cardiac pacemakers were and are an issue, since they are switched off with fields comparable to switching the MRI gradients. The FDA decided to require posted warnings at the “5 gauss line,” to keep people who had not been screened for pacemakers or metallic implants well outside the danger zone. Hospitals often placed decorative plants or other barriers at the line. But the biggest hazard with early MRI was flying objects—pens, paper clips, hairpins, or anything magnetic. Before practices became standardized there were even examples of carpenters losing their hammers and janitors losing their floor polishers! An MRI magnet with a floor polisher hanging off it is a very sorry sight. In MRI suites, people worried about scalpels or gas tanks being sucked into the magnet by ethereal forces. With today’s safety procedures, these incidents are rare.

  Moreover, the magnetic fringe field affects the operation of nearby electrical and electronic devices, even if they are not in the same room, and vice versa. Years before I met Paul, I witnessed a magnet putting out a sudden electrical noise, making the signal unintelligible; the laboratory next door had placed an electric motor against the adjoining wall. Another time, after much frustrating investigation of why we couldn’t get NMR signals, we found that the laboratory next door had begun storing highly magnetic gas cylinders on the opposite side of the wall from our magnet. And we had to be careful about where we placed the computer that sent and received the MRI signals. We often placed computers just enough outside the fringe field to enable them to function, but the magnetic field would then tilt the display on the monitor. You would see operators sitting with their heads tilted in the same way.

  The Big Old 10 T

  The 1980s saw a big hullabaloo about the technical direction of MRI. It now became possible to build superconducting magnets at higher field strengths. Should imaging fields be kept low, about a tenth of a tesla (the unit for measuring magnetic field strength), or should they be increased to 1 T and beyond? The higher the field strength, the bigger the signal and the better the resolution. But increasing field strength also increases several endemic problems that make the images hard to compute. And as field strengths go higher, costs go higher, making MRI systems unaffordable in many places. Those were the da
ys of the field-strength wars. Our meetings rang with arguments between the low-field people and the high-field people. Sometimes personal insults were shouted.

  During this chaos, Paul, together with Tom Budinger, proposed that a commitment be made to manufacture a 10 T magnet! This was an order of magnitude beyond the general discussion, and absolutely shocking. Maybe they wanted to shock. The first discussion of such a plan was at a meeting on magnet technology at the Fermi Lab. Russ Huson of the Texas Accelerator Center was there, talking about designs for the magnet for the Superconducting Super Collider (SCC)—the very large, expensive, controversial project that was big science politics for a few years. Russ’s designs featured an iron shield to pull the magnetic field inward, a feature that would make MRI magnets much more practical than unshielded ones. When Paul and Tom got together they sparked each other’s imaginations and enthusiasms for big ideas; add Russ, and the whole thing was combustible. They reasoned that more would be learned quicker about the limits of useful field strength by trying for 10 T immediately rather than pushing up the field strength of magnets a half tesla or so at a time. And Russ’s method of limiting the footprint of the magnetic field would make this possible.

  Figure 8.4

  The jolly professor. The Village Times (Setauket–Stony Brook, N.Y.), November 15, 1984. Photograph by Mike Chen. Reproduced by permission.

  Paul calculated that the resonance frequency for protons at the lower field strengths then used was roughly similar to those of other nuclei at high field strengths; this meant that the required radio-frequency technology was already understood. New magnet designs, such as those discussed by Russ, seemed to make the idea feasible. These three musketeers looked for a reasonable break point for the technology, the highest field strength attainable with existing knowledge, beyond which it would be difficult to go. Over years of studying this issue, the break point seemed at various times to be somewhere between 8 and 12 T, hence the 10 T. Paul and Tom were never able to get their 10 T magnet out of the planning stage, and some people thought they verged on being quacks. The general opinion was that a field strength of 10 T was never going to happen. And so development proceeded in the small stages Tom and Paul had wished to avoid. Today 1.5 T is used for everyday clinical examinations and 3 T is found in advanced radiology departments. A field strength of 9.4 T is the new frontier.