A Short History of Magnetic Resonance Imaging

VOL. 20 NO. 1 (2008) AARTICLERTICLE

A short history of magnetic resonance imaging

Peter A. Rinck European Magnetic Resonance Forum (EMRF) Foundation, WTC, BP 255, F-06905 Sophia Antipolis Cedex, France

In 1946, two scientists in the United States, independently of each other, described a physicochemical phenome- non that was based upon the magnetic properties of certain nuclei in the periodic system. This was “nuclear magnetic reso- nance”, for short “NMR”. The two scien- tists, Felix Bloch and Edward M. Purcell, see Figure 1, were awarded the Nobel Prize in Physics in 1952. Purcell worked at the Massachusetts Institute of Technology, MIT, and later joined the faculty of Harvard University. Bloch, a Swiss national, taught at the University of Leipzig until 1933; he then moved to the United States and joined the faculty of Stanford University at Palo Alto in 1934. In 1962 he became the first director of CERN in Geneva. Bloch was a Figure 1. Left: Felix Bloch (1905–1983); right: Edward M. Purcell (1912–1997). protagonist for the interaction between Europe and the United States. NMR and magnetic resonance imaging (MRI) Isidor Isaac Rabi’s laboratory at Columbia Zavoisky towards the end of the war. would not exist without this interaction. University in New York became a major Zavoisky had first attempted to detect Bloch and Purcell were not the only centre for related studies. NMR in 1941, but like Gorter he had scientists working in the field. Already Rabi’s research was successful, but failed. in 1924, Wolfgang Pauli suggested the only the visit by Cornelis Jacobus Gorter After the final breakthrough by Bloch possibility of an intrinsic nuclear spin. The from the Netherlands in September and Purcell, NMR developed across a year after, George Eugene Uhlenbeck 1937 finally showed how to measure wide range of applications. Hardly any of and Samuel A. Goudsmit introduced the nuclear magnetic moment. Gorter them were medical, although in vivo NMR the concept of the spinning electron. had tried similar experiments and failed. already had been performed since the Two years later Pauli and Charles Galton Rabi accepted and realised Gorter’s early 1950s. In 1955/1956, Erik Odeblad Darwin developed a theoretical frame- suggestions concerning his experiments, and Gunnar Lindström from Stockholm work for grafting the concept of electron changed them, and was able to observe published their first NMR studies of living spin into the new quantum mechan- resonance experimentally. This led to cells and excised animal tissue, including ics developed the year before by Edwin the publication (in Physical Review) of relaxation time measurements. Odeblad Schrödinger and Werner Heisenberg. “A New Method of Measuring Nuclear continued working on tissues throughout This development continued in the Magnetic Moment” in 1938. Gorter first the 1950s and 1960s. He is the major 1930s. After their initial pace-making used the term “nuclear magnetic reso- early contributor to NMR in medicine. work at the University of Frankfurt’s nance” in a publication, which appeared Oleg Jardetzky and colleagues, at Institute for Theoretical Physics, Otto in the war-torn Netherlands in 1942, the Stanford University Medical Center, Stern and Walther Gerlach in 1933 were attributing the coining of the phrase to performed sodium NMR studies in blood, able to measure the effect of the nuclear Rabi. plasma and red blood cells in 1956. T1 spin by deflection of a beam of hydro- Electron spin resonance was discov- and T2 relaxation time measurements of gen molecules. During the early 1930s, ered at Kazan University by Yevgeni K. living frog skeletal muscle were published www.spectroscopyeurope.com SPECTROSCOPYEUROPE 7 VOL. 20 NO. 1 (2008) AARTICLERTICLE

by Bratton and colleagues in 1965. In the However, Lauterbur’s idea revolution- 1960s and 1970s a very large amount ised NMR because it opened the field of work was published on relaxation, to imaging. Many of today’s innova- diffusion and chemical exchange of tions were thought of and developed water in cells and tissues of all sorts. In in his laboratory in the late 1970s and 1967, Ligon at Oklahoma State University 1980s. When he presented his approach reported the measurement of NMR relax- to NMR imaging at the International ation of water in the arms of living human Society of Magnetic Resonance (ISMAR) subjects. In 1968, Jackson and Langham meeting in January 1974 in Bombay, of the University of California, Los Alamos Raymond Andrew, William Moore and Scientific Laboratory, Los Alamos, New Waldo Hinshaw from the University of Mexico, published the first NMR signals Nottingham, UK, were in the audience from a living animal. and took note. As a result, Hinshaw devel- In the late 1960s, Jim Hutchison at the oped his own approach to MR imaging University of Aberdeen in Scotland began with their sensitive point method. working with magnetic resonance on in In April 1974, Lauterbur gave a talk at vivo electron spin resonance studies in a conference in Raleigh, North Carolina. mice. Hazlewood from Baylor College of This conference was attended by Richard Medicine, Houston, Texas, added to the Ernst from Zurich, who realised that work on relaxation time measurements instead of Lauterbur’s back-projection by studying developing muscle tissue. one could use switched magnetic field Cooke and Wien from the University of gradients in the time domain. This led California at San Francisco and Stanford Figure 2. Paul C. Lauterbur (1929–2007). to the 1975 publication, NMR Fourier University worked on similar topics. Zeugmatography by Anil Kumar, Dieter Hansen from the Procter and Gamble Welti and Richard Ernst, and to the basic Company, Cincinnati, Ohio, added NMR Among others, David Hoult and David G. reconstruction method for MR imaging studies of brain tissue. Others joined in Gadian belonged to this group. today. this kind of research, among the better A second NMR group in Nottingham known being the research groups of Spatial encoding also got involved in MR imaging. Its Raymond Damadian at Downstate In September 1971, Paul Lauterbur (see leader, Peter Mansfield, worked on stud- Medical Center in Brooklyn and Donald Figure 2) of the State University of New ies of solid periodic objects, such as crys- P. Hollis at Johns Hopkins University in York at Stony Brook had the idea of tals. At a Colloque Ampère conference Baltimore. Damadian’s group measured applying magnetic field gradients in all in Cracow in September 1973, Mansfield

T1 and T2 relaxation times of excised three dimensions and a back-projection and his collaborator Peter K. Grannell normal and cancerous rat tissue and (= projection–reconstruction) technique presented a one-dimensional inter- stated that tumorous tissue had longer to create NMR images. He published ferogram to a resolution of better than relaxation times than normal tissue. the first images of two tubes of water in 1 mm. This, however, cannot be consid- Hollis and his collaborators achieved March 1973 in the journal Nature. This ered an MR image. However, one year similar results, but were more balanced was followed later in the year by the later, Alan Garroway and Mansfield filed and scientifically critical in their postula- picture of a living animal, a clam, and in a patent and published a paper on image tions and deductions. Damadian wrongly 1974 by the image of the thoracic cavity formation by NMR. By 1975, Mansfield thought that he had discovered the ulti- of a mouse. Lauterbur called his imaging and Andrew A. Maudsley proposed a mate technology to detect cancer and, method zeugmatography, a term which line technique, which, in 1977, led to in 1972, filed a patent claim for an was later replaced by (N)MR imaging. the first image of in vivo human anat- Apparatus and Method for Detecting Field gradients had been used before. omy, a cross-section through a finger. In Cancer in Tissue. The patent included the They are an essential feature of the study 1978, Mansfield presented his first image idea but no description of a method or of molecular diffusion in liquids by the through the abdomen. technique of using NMR to scan, but not spin-echo method developed by Erwin In 1977, Hinshaw, Paul Bottomley and to image, the human body. In February L. Hahn in 1950; his group at Berkeley Neil Holland succeeded with an image of 1973 Abe and his colleagues at the used a gradient approach also to create a the wrist. Human thoracic and abdomi- University Hokkaido in Sapporo applied storage memory. In 1951, Roger Gabillard nal images followed, and by 1978, Hugh for a patent on a targeted NMR scanner. from Lille in France had imposed one- Clow and Ian R. Young, working at the They published this technique in 1974. dimensional gradients on samples. Carr British company EMI, reported the first Actual in vivo NMR spectroscopy took and Purcell described the use of gradi- transverse NMR image through a human off in Oxford from 1974, with the group ents in the determination of diffusion in head. Two years later, William Moore and of Rex E. Richards and George K. Radda. 1954. colleagues presented the first coronal

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and sagittal images through a human head. In the research group of John Mallard at the University of Aberdeen, Jim Hutchison, Bill Edelstein and colleagues developed the spin-warp technique. They published a first image through the body of a mouse in 1974. Margaret Foster contributed much to this work. Some of the pioneers had performed quite impressive research in the United States; among them was Robert N. Muller (see Figure 3), who, in 1982, described off-resonance imaging, a technique known today as “magnetisation-transfer” imaging. Rinck et al. described, while at the State University of New York at Stony Brook, the first fluorine lung images. Paul C. Lauterbur received the Nobel Figure 3. Early magnetic resonance imaging experiment at Paul C. Lauterbur’s Laboratory in Prize in Medicine or Physiology in 2003 Stony Brook, NY, around 1981: left Peter A. Rinck, right Robert N. Muller. for the invention of magnetic resonance imaging. Peter Mansfield shared the Nobel Prize for his further development pulse sequence development, presented even though, at some stage of their of MRI. by Pykett and Rzedzian in 1987. career, many European scientists contem- In the 1980s, Continental Europe plate emigration to the USA. Some started to contribute intensively to MR Clinical applications become trans-Atlantic travellers, and imaging. Rapid imaging originated in At about this time, MR imaging started some even stay for good; others return, European laboratories. Jürgen Hennig, being clinically evaluated. One of the while there is hardly any movement in together with A. Nauerth and Hartmut most admirable research groups worked the other direction. The historical reasons Friedburg, from the University of Freiburg at Hammersmith Hospital in London. were different prior to and after the introduced RARE (rapid acquisition with The head of the group was Robert E. Second World War. Before the war, plain relaxation enhancement) imaging in Steiner, but Ian R. Young and Graeme M. survival for many depended on emigra- 1986. This technique is probably better Bydder were the moving forces. Among tion, or it was at least guided by political known under the commercial names of others, Frank H. Doyle and Jacqueline M. necessity. After the war, research facilities fast or turbo spin-echo. Pennock supplemented this group. in the United States were more attrac- At about the same time, FLASH (fast Early clinical imaging was extremely tive than those in Europe because the low angle shot) appeared, opening the difficult, time-consuming and often academic system in the USA was more way to similar gradient-echo sequences. disappointing. Spin-echo imaging, for flexible than the university structures in This sequence was developed at the instance, was a bigger step than many Europe—and dollars were plentiful for Max-Planck-Institute, Göttingen, by Axel imagine. Today it is taken for granted, but research and for personal income! Haase, Jens Frahm, Dieter Matthaei, it has helped immensely to enable MR Yet, the majority of novel develop- Wolfgang Hänicke and Dietmar K. imaging to become a routine technique. ments in MR imaging originated at Merboldt. FLASH was very rapidly Early MR images were mainly based European research sites. Hardware, adopted commercially. Hennig’s RARE upon proton-density differences, later software, new imaging techniques and was slower, and echo-planar imaging upon differences in T1 weighting. By accessories such as contrast agents (EPI)—for technical reasons—took even 1982–1983, the Hammersmith and were all advanced in Europe, not only more time. Echo-planar imaging had Wiesbaden groups pointed out that at academic facilities, but also because been proposed by Mansfield’s group in long heavily T2-weighted SE (spin-echo) some of the major commercial players 1977, and the first crude images were sequences were better at highlighting in the field are European. shown by Mansfield and Ian Pykett in pathology. It took some years until this the same year. Roger Ordidge presented was generally accepted, mostly because References the first movie in 1981. Its breakthrough many companies claimed that long TE An extensive list of primary and secondary came with manifold improvements in (echo times) was neither possible nor references can be found at the European many aspects of the associated method- necessary. Magnetic Resonance Foundation web ology and instrumentation—from gradient The input and impact of European site at: http://emrf.org/New Site/FAQs/ power supply and gradient coil design to scientists to MRI has been enormous, FAQs History of MRI page05.htm www.spectroscopyeurope.com SPECTROSCOPYEUROPE 9