The 2003 Nobel Prize for MRI: Significance and impact

As this editorial was prepared on December 10, 2003, our colleagues, Paul C. Lauterbur, PhD, and Sir Peter Mansfield, both former Presidents of the International Society for Magnetic Resonance in Medicine (ISMRM), were recognized in Stockholm as co-recipients of the 2003 Nobel Prize in Physiology or Medicine. Their separate contributions in gradient imaging and echo-planar imaging are internationally recognized as seminal accomplishments in the field. In addition, each has made significant contributions to the scientific community, as evidenced by their presence as authors in the archival literature, their training of young investigators, and their support and voluntary contributions to organized medicine, including, in particular, our society. This event highlights the rapid development in the field and the truly significant impact on health care delivery that magnetic resonance imaging (MRI) and its correlative diagnostic imaging and associated therapeutic modalities have provided. In this issue, we have several invited editorial comments that focus on the excitement and energy that the Nobel Prize in Medicine for MRI has generated. First, we present laudatory remarks from Michael Moseley, PhD, President of the ISMRM, and Jörg F. Debatin, MD, Medical Director and Chief Executive Officer of the University Hospital, Hamburg, Germany, and a member of the Editorial Board of JMRI. These are followed by an editorial by Chris Boesch, MD, PhD, former President of ISMRM, in which he places the current award in a perspective of 13 Nobel Prizes directly and indirectly related to the development of MRI. Third, we have two observations on the disappointment of our colleague, Raymond Damadian, MD, in not being recognized with a share of the Nobel Prize. Presenting their views on this matter are William G. Bradley, MD, PhD, Chairman of the Department of Radiology, University of California at San Diego and JMRI Editorial Board member, and Jürgen Hennig, PhD, Universität Freiburg, Germany, past President of ISMRM and JMRI Editorial Board Member. Finally, we close with a discussion of the complex genesis of MRI that touches on all of the above issues by Ian Young, PhD, member of the Editorial Board of JMRI. It is noted that the editorial opinions expressed in the following articles are the personal opinions of the authors and not the official position of the ISMRM. Any discussion concerning the selection of Nobel Laureates could certainly benefit from the expertise of someone directly associated with that process. Hans G. Ringertz, MD, PhD, Professor and Chairman of the Department of Radiology at Karolinska Institute, is also the Chairman of the Nobel Academic Council and was kind enough to share some of the intricacies involved in awarding the Nobel Prize for Physiology or Medicine. The nomination procedure is an extensive, year-long process that invites a great number of universities and other organizations to recommend possible nominees. As has been discussed elsewhere during this year's debate, up to three individuals involved in the discovery and/or development of the specific entity being honored may receive a Nobel Prize; however, the contributions of each of the winners do not always have to correlate directly. In March, the top nominees from the previous year are re-examined, and preliminary international investigations are begun. The field is narrowed to 20-25 potential prizes by June, and experts in all of those areas are chosen to conduct more thorough investigations of the nominees. Further winnowing then occurs until the top three possibilities are chosen at the end of September. The final meeting of the Nobel Assembly occurs in October, and then that year's Nobel Laureate(s) are chosen and announced. The process then culminates in the actual awarding ceremony in Stockholm during the first half of December. This year, there is considerable debate regarding the Nobel Prize awards in Medicine for MRI, and I trust that the following editorials will contribute to that discussion. We certainly welcome editorial comments that would seek to disagree, be supportive, or correct any of the observations and conclusions mentioned in this introduction or the invited editorials that appear in this issue of JMRI. Recent editorial opinions by John Gore, PhD, Editor, Magnetic Resonance Imaging (1), and Felix W. Wehrli, PhD, Editor-in-Chief, Magnetic Resonance in Medicine (2), provide important historic perspectives describing the evolution of the science and technology of MRI. These are exciting days in our field, and it is indeed an honor to be a part of the process. Notice that I have provided brief descriptive comments, in italics, to separate sections of this collection of editorial opinions. C. Leon Partain, MD, PhD Editor-in-Chief Gore J. Out of the shadows—MRI and the Nobel Prize. N Engl J Med 2003;349:2290–2292. Wehrli FW. On the 2003 Nobel Prize in medicine or physiology awarded to Paul C. Lauterbur and Sir Peter Mansfield. Magn Res Med 2004;51:1–3. The International Society of Magnetic Resonance in Medicine fosters scientific dialogue on pertinent MR related topics for discussion, education, and documentation through the publication of enduring scholarly material. The Society speaks through its selected officials, the annual meetings, and its journals with their duly-established and broad-based editorial boards, who are accountable to the Society Board of Directors through its Publications Committee. The journals consider both invited and submitted editorial comments on appropriate topics as one of the vehicles of scientific dialogue. In that spirit, and within those guidelines, the first two invited editorial comments (below) come from the current President of the ISMRM and from a former member of the Board of Trustees of the ISMRM, respectively. These remarks illustrate the international balance that is valued at the ISMRM, with one coming from the United States and the other from Germany. Further, the balance between basic science and clinical investigators is also valued, and these two voices are representative of those two fundamental disciplines. It is also gratifying to help focus on our moral responsibility of providing the human benefits of MRI to the underserved of the world, in addition to those of us who are blessed to have more than our share of opportunity and resources. Additional commentary is invited from the members of our Society and others who read these words. They will be seriously considered for publication as part of our commitment to moderating meaningful scientific discussion. As the President of ISMRM, I would like to speak for all of our members in conveying our sincere congratulations to Professors Paul Lauterbur and Peter Mansfield on winning the 2003 Nobel Prize in Physiology or Medicine. This is the occasion that many of us have been waiting years for: the well-deserved recognition of the pioneering efforts that these two have made that has affected everything that we all do within the sphere of magnetic resonance. We are very happy that their work has finally been acknowledged with this prize. It provides the public recognition that MRI has deserved in significantly improved diagnostic imaging in many diseases for many disciplines. This award builds on the earlier Nobel Prizes given to the fundamental discoveries of the magnetic moments [Rabi, 1944], the nuclear magnetic resonance (NMR) phenomenon [Purcell and Bloch, 1952], the implementation of two-dimensional MR spectroscopy [Ernst, 1991], the development of MR spectroscopy for three-dimensional macromolecular structures [Wüthrich, 2002], and now, deservingly, for MRI. Beyond the recognition of this fact by the Nobel Academy, we should also be aware and grateful for the contributions that Drs. Lauterbur and Mansfield have made to the Society: both are members of our Society, both are past Gold Medal Winners, and both are Society Past-Presidents. To pay tribute, the Scientific Program Committees for the 2004 and 2005 Annual Meetings will be planning several Nobel celebrations for the 2004 Kyoto meeting. The ISMRM Board of Trustees has bestowed the ISMRM Honorary Membership to Drs. Lauterbur, Mansfield, Ernst, and Wüthrich. Clearly, these are momentous times for MRI. We all take pride in congratulating Drs. Lauterbur and Mansfield for their recognition by the Nobel Academy! Michael Moseley, PhD Stanford University Stanford, California The accomplishments of Paul Lauterbur and Sir Peter Mansfield have been evident long before this year's Award of the Nobel Prize in Physiology or Medicine. Millions of patients have benefited from the use of magnetic resonance in medicine over the past two decades. Awarding the Nobel Prize to Paul Lauterbur and Sir Peter Mansfield now pays tribute to the significance of their scientific contributions as the founders of modern MRI. The Nobel Prize carries another equally important message, however: MRI has entered the world stage of medicine and is here to stay. While this recognition is obvious to all those working with MRI, the benefits of this technology have remained limited to only the most developed regions of the world. A vast number of countries lack all infrastructure for MRI; and many other countries are considerably underserved. Thus, we should interpret the awarding of the prestigious Nobel Prize to the developers of MRI also as a moral obligation to widen the access to MRI technology. This will require increased research into means to reduce the cost of MRI infrastructure and new efforts to accelerate the training of staff required for operating and interpreting MRI studies. In my mind, the ISMRM, with its two journals, MRM and JMRI, seems to be an excellent vehicle to accomplish this mission. Jörg Debatin, MD University Hospital Essen Essen, Germany The next invited editorial comes from the immediate past President of the ISMRM, Dr. Chris Boesch. His overview provides a special perspective on the rapid development and application of MRI over a relatively short period of time, involving the award of 13 Nobel Prizes, including one to his own major professor. His overview of this process from his perspective as a recognized, elected ISMRM officer and as a Swiss physician- investigator follows below. The article includes 31 references that help to focus on the history of the development of MRI. Additional commentary for supportive or conflicting views is invited for consideration for publication in JMRI. Multiplied many times by emails and phone calls, a press release went around the globe in a few hours: “The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine for 2003 jointly to Paul C. Lauterbur and Peter Mansfield for their discoveries concerning magnetic resonance imaging.” The MR community was speculating for years about a Nobel Prize that would be awarded to the developers of MRI. While it has been obvious that this discovery deserves recognition, it was a question of when and how the Nobel Prize Committee would select the laureates. While many contributed to the development of MRI in the early days, Paul C. Lauterbur and Sir Peter Mansfield unquestionably are the ones who had the fundamental ideas. While we celebrate happily these most recent laureates, their merits shall be put into a historic perspective of other Nobel Prizes in the field of NMR. In particular, I want to emphasize that four prizes were awarded for NMR in little more than a decade (Tables 1 and 2). Looking at the history of NMR (1-3) and at its applications in very different fields helps to recognize the enormous versatility of this physical effect and may explain why this field is so successful. It also gives an idea of how many applications are still hidden and waiting to be discovered in the future. In this respect, looking back may help to look forward. See Table 2, Norman F. Ramsey Toronto 2003: Lecture on I. Rabi (see Table 1) There is no question that Paul C. Lauterbur's 1973 publication in Nature represents a milestone in the development of MR in medicine (4). He suggested that magnetic field gradients could be used to define the spatial distribution of protons in water by different frequencies. In this seminal paper, he showed a two-dimensional image of two tubes filled with water based on a “projection reconstruction” algorithm that was closely related to image generation by computed tomography (CT). While Lauterbur's publication was the most explicit and clear-cut suggestion of how NMR could be used to obtain images in macroscopic dimensions, Mansfield considered the use of magnetic field gradients for a spatial separation of NMR signals in a more theoretical description about “NMR diffraction in solids” (5). This approach dealt with crystals and was so sophisticated that it was overlooked for almost a decade before the MR community realized that Mansfield, in fact, had also suggested the use of gradients for spatial encoding, i.e., for imaging. While gradients had been used in earlier years to destroy spurious signals from imperfect radiofrequency pulses or as diffusion and flow sensitizing elements in a pulse sequence, Lauterbur and Mansfield introduced the unique idea to use gradients for spatial encoding, i.e., to generate a spectrum of spatially distributed frequencies. Recently, Raymond Damadian claimed, in The Washington Post, his entitlement to the prize. It is unquestioned that he deserves recognition for his observation of relaxation time differences in malignant tissue (6). His suggestion motivated the application of MR in medicine, and, in that respect, it also fostered interest for the new imaging technology. However, his US patent on an “Apparatus and method for detecting cancer in tissue” (7) failed to show a feasible method to obtain spatially selected NMR signals. The described “beam of radiofrequency waves with a narrow cross-section, generated by helically moving transmitters” has, to the best of my knowledge, not been used so far to generate two-dimensional images. In particular, the later “Topical Magnetic Resonance” (8) and “FONAR” (9) are based on a spatial variation of the static magnetic field, not of the radiofrequency field. In contrast, two other ideas had a particular impact: “echo planar imaging,” proposed again by Sir Peter Mansfield (10), and the application of Fourier techniques (11), suggested by Richard R. Ernst's group (Nobel Laureate 1991). Tables 1 and 2 show nicely how NMR evolved from a physical tool (Prizes 1944 to 1989) to applications in chemistry (Prizes 1991 and 2002) and in medicine (Prizes 2003). Following the observation of Stern and Gerlach (12) in 1921, who observed the “spin” of silver atoms, Isidor Isaac Rabi published a one-page report on “A New Method of Measuring Nuclear Magnetic Moment” (13). He used oscillating fields to re-orient the nuclear spins and was awarded the Nobel Prize in Physics in 1944. At least two scientists contributed significantly to the field but failed in one or another way. It seems that E. K. Zavoisky, a scientist in Kazan/Russia, observed an NMR effect in 1941 (2), yet was not able to reproduce it, mainly due to World War II in his home country, the USSR. He was more successful in a related field, i.e., electron spin resonance (14). Another scientist, C. J. Gorter, attempted to measure nuclear paramagnetism. However, while he failed several times with his own measurements (15), he inspired Rabi's group to conduct their successful experiment (13). In the Western hemisphere, WWII promoted the development of radar and subsequently improved radio-transmitters and amplifiers, which were necessary for the discovery of magnetic resonance. At the end of the war, in 1946, Purcell, Torrey, and Pound (16) published a report on NMR effects in solids. At the same time, Bloch, Hansen, and Packard (17, 18) made a similar and successful attempt to measure what they called “nuclear induction.” It seems that it was not immediately clear that the two independent groups described the same effect. These reports were crucial for modern applications of NMR in solution and human tissue because they transferred knowledge about Rabi's work in molecular beams into an effect that had been observed in bulk matter. Bloch and Purcell were awarded the 1952 Nobel Prize in Physics. So far, NMR contributed almost exclusively to the development of nuclear physics, and research in this field continued to concentrate on characterizing materials and measuring nuclear parameters. In his Nobel Lecture, Richard R. Ernst revealed an astonishing fact: quite a few scientists who contributed to the early development of NMR received a Noble Prize in Physics for their subsequent work in other areas. A. Kastler (Nobel Laureate 1966) was one of those who proposed the “double resonance method,” combining optical with magnetic resonance (19). J.H. Van Vleck (Nobel Laureate 1977) developed the theory of dia- and paramagnetism and also published together with C.J. Gorter (Nobel Laureate on relaxation effects and the of (Nobel Laureate contributed significantly to electron resonance (Nobel Laureate 1989) developed nuclear resonance Ramsey (Nobel Laureate 1989) was Rabi's first and introduced the of the and J In the early years of a spectrum was by with radiofrequency waves by and E. showed that the signals and could also be the of the spins with a radiofrequency Ernst and realized that these signals the of a spectrum and introduced Fourier techniques into NMR. In the following the two subsequent Nobel Richard R. Ernst and both at the in an two on the of the chemistry their had been They used a NMR and Richard R. Ernst was because it was for he had the more Fourier In the following an successful between the two in to the the NMR was always new and an by Richard Ernst developed two-dimensional NMR spectroscopy which is also the for modern imaging techniques in While the on Fourier imaging had enormous impact on the development of MRI, Richard R. Ernst received his Nobel Prize 1991 for his to Fourier techniques were and his group NMR techniques for the of three-dimensional structures of of NMR of in solution an tool in and the Nobel Committee awarded the to Ernst in it was not immediately clear that would also be awarded some years However, when the decided to the Prize again to the field of the was 1) was so in chemistry that it was appropriate to select this field again and the scientific work of Ernst and was closely both contributions were so unique that they deserved an independent As an fact, the of Tables 1 and 2 illustrate how the ISMRM has been in for the at the annual are the and impact of applications of magnetic in particular the physical and NMR. This overview and the historic of the 2003 Nobel Prizes in Medicine shall how and NMR has been for several decades. NMR and in MR the same physical I would that many applications still to be transferred and that the successful history of MR is the of an It is this will in Nobel Laureates in the field of MR in the however, the field is so and that it will be a for the coming decades. Chris Boesch, MD, PhD University and The next two authors who with invited editorial comments are William G. Bradley, MD, PhD, and Jürgen Hennig, PhD, international MRI at Universität Freiburg, Freiburg, Germany. Their comments have been prepared as vehicles to and issues related to the and significance of the Nobel Prize related to fundamental in our field. We are of their to help the historic of the development of MRI during this particular It was their that the scientific community has a responsibility to provide the from which the history of the development of related to MRI, may be with and In that spirit, or views are invited for consideration of publication in JMRI. On 2003, the Nobel Committee on Physiology and Medicine awarded the Nobel Prize to Paul Lauterbur and Sir Peter Mansfield for MRI. from this was Raymond the three individuals to be for a given the of Dr. Damadian was I there are two possible for their of Dr. The first is that the focus of this was more on imaging than magnetic resonance. Raymond was the of in not MR imaging had the Nobel Prize for MRI been awarded years it is that Sir Peter would have At the time, his planar imaging was a because the gradients to it were only then being the the of diffusion been in the of of and diffusion it is that MR will over the next few years as the imaging used to patients for Thus, could have an enormous impact on the of which has enormous This could be one that Dr. Mansfield the award A more that Dr. Damadian not the award has to do with his over the past I have Raymond Damadian for years and consider a I have always why a scientist to to relatively to be While I do not the of Dr. Damadian before or the was it is also for to how the Nobel Committee could not these and their on the There is no my at that Dr. Damadian the with his discovery of in cancer and his of the first working human MRI which Sir the Nobel Prize for the Nobel Committee could not the significance of these discoveries and to their on and than William G. Bradley, MD, PhD University of California at San Diego San California The from the Nobel Assembly at Karolinska Institutet on 2003 to award the Nobel Prize in Physiology or Medicine for 2003 jointly to Paul Lauterbur and Peter Mansfield for their discoveries concerning MRI has been received by the MR community with great and The award was given to Paul Lauterbur for his discovery of to a two-dimensional by gradients in the magnetic This discovery is described in his in he the first MR image of two tubes in a NMR Sir Peter Mansfield the award for his development of the of gradients in the magnetic field. He showed how the signals could be which made it possible to a imaging Mansfield also showed how imaging could be It was in the that the of the resonance of protons on the magnetic field be used to their a magnetic field were described applications in his on flow by NMR. To the from a method for of spins to an imaging a one of the moments in In our current world with it is to of the of and it for Paul Lauterbur to take that NMR at that time, were measuring the resonance of protons as a at the of a complex and This could be on an and as a on was the around the at this time could do little more than basic It is to what should be more the of Paul Lauterbur to an in to and signals gradients with the to these signals into an or his and to the necessary to finally the Lauterbur is to that for image had been described early this and have been used by in his work on at around the same He however, of these techniques and had to the for his from based on his that this be Sir Peter Mansfield has been in the development of these basic of MRI as we it he has and introduced which is the of all imaging The of to of the magnetic field the of gradient of that in of and and the by the used to the signals made the early images not to look It great and a in the for Sir Peter to working at over two until MR technology was to us the image is used as the imaging in many applications like diffusion and many In fact, many of the new fields in MR development would be not feasible scientists that the Nobel Prize for magnetic resonance has been long As a of the long of the Nobel one may that the thorough has finally to the two individuals who are by the MR community as being of the It of a to a new field of science like MR to two individuals The selection at three to a field to the of the Nobel Prize always has about it and is to those who are not on the This is certainly for those we are this of selection however, certainly to the and that the award has far into the any the of MRI within the of a scientific who has been has used fields to protons E. R. Damadian, and others had prepared NMR of tissue and that this may be to look at in but not it the and of and like Bradley, and others to MRI into the the efforts of the group around John in particular, who the first human MR MR have remained a in the for a long Thus, in all and for the deserved award for Paul Lauterbur and Peter Mansfield, we should also be grateful to all of the individuals who have and

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