Magnetic Resonance Imaging –
How it all began
n late 1972, a prospective contributor to the British scientific journal Nature received an apologizing letter from the editor of the journal that read as follows:
"With regret I am returning your manuscript which we feel is not of sufficiently wide significance for inclusion in Nature. This action should not in any way be regarded as an adverse criticism of your work, nor even an indication of editorial policies on studies in this field. A choice must inevitably be made from the many contributions received; it is not even possible to accommodate all those manuscripts which are recommended for publication by the referees."
The paper submitted was very short and described a new imaging technique dubbed zeugmatography. For those who did not study Greek at school, zeugma is the yoke, or as the author put it: "That what is used for joining."
The author did not mean that two horses were to be joined with a yoke; rather, he meant two magnetic fields were to be joined. His method was derived from an analytical technique that had been used in chemistry since the late 1940s, called nuclear magnetic resonance, or, for short, NMR.
The author of the paper was Paul C. Lauterbur, Professor of Chemistry at the State University of New York at Stony Brook. In early September 1971 he had the idea of how to create three-dimensional images using magnetic resonance and described a "Spatially Resolved Nuclear Magnetic Resonance Experiment."  A year later he had enough results to publish them. Lauterbur wanted this paper to be printed in Nature and wrote back to the editor proposing to change the style of the paper:
"Several of my colleagues have suggested that the style of the manuscript was too dry and spare, and that the more exuberant prose style of the grant application would have been more appropriate. If you should agree, after reconsideration, that the substance meets your standards, ... I would be willing to incorporate some of the material below in a revised manuscript ..."
The answer from the editor was short and positive: "Would it be possible to modify the manuscript so as to make the applications more clear?"  Finally, the paper was accepted and published in the 16 March 1973 issue of Nature under the title:
Image Formation by Induced Local Interaction:
Examples Employing Magnetic Resonance .
From reading this title, one would not think that a revolutionary idea in medical imaging was hidden behind it. However, this idea was the foundation of MR imaging, which has developed into one of the most outstanding medical innovations of the twentieth century, comparable with Wilhelm Conrad Roentgen’s invention of the medical application of x-rays.
Magnetic resonance, or nuclear magnetic resonance (NMR) as natural scientists still call it, is a phenomenon that was first mentioned in the scientific literature before World War II. In 1946, independently of each other, two scientists in the United States described a physico-chemical phenomenon that was based upon the magnetic properties of certain nuclei in the periodic system. They found that when these nuclei were placed in a magnetic field, they absorbed energy in the radiofrequency range and re-emitted this energy during the transition to their original orientation. Because the strength of the magnetic field and the radiofrequency must match each other, the phenomenon was called nuclear magnetic resonance: nuclear because it is only the nuclei of the atoms that react; magnetic because it happens in a magnetic field; and resonance because of the direct dependence of field strength and frequency.
The two scientists, Felix Bloch working at Stanford University and Edward M. Purcell working at Harvard, received the Nobel Prize in Physics in 1952 [4, 5]. In 1991, the Nobel Prize in Chemistry was awarded to Richard R. Ernst of Zurich for his contributions to the field of NMR spectroscopy.
The two most important scientists for the development of magnetic resonance in medicine and biology were Erik Odeblad who in the early 1950s first described the differences of relaxation times in human tissue  and Paul C. Lauterbur.
In 2003, the Nobel Committee conferred their Prize in Medicine on Lauterbur for the invention of magnetic resonance imaging. He shared it with Peter Mansfield, a British physicist, who was awarded for the further development of the technique.
Shortly after the introduction of NMR to clinical imaging, the adjective nuclear was dropped by marketing people and radiologists because it sounded like nuclear warfare or nuclear power plant, words that for some people have a negative connotation – with which NMR has nothing in common at all. It was thought that the general public would be unable to distinguish between one nuclear and the other. Thus, today we talk about MR imaging or MRI and, e.g., MR spectroscopy – and the commercial people had taken over.
However, it should always be kept in mind that it is the nucleus we talk about because there is another kind of resonance that also can be used for imaging: electron spin resonance (ESR). ESR involves the electrons of an atom.
NMR signals carry encoded information about the physical and chemical environment of the nuclei. Originally, NMR was used as an analytical method to study the composition of chemical compounds. Today, there are applications in a wide range of areas in chemistry, physics, biology, medicine, and food science.
However, before Lauterbur's discovery, nobody could determine from where within a sample the NMR signal stems. It could originate at the left or right end, at the top or at the bottom. Lauterbur’s zeugmatography changed this. He joined the strong magnetic field and a second weaker field, the gradient field. Because the strength of the magnetic field is proportional to the radiofrequency, the frequency of, for instance, a hydrogen nucleus of a water molecule at one end of a sample differs from the signal of another hydrogen nucleus at the other end of the sample. Thus, the location of these nuclei can be calculated. Once their location is known, an image can be created of a slice through a human body, for example. Basically, therefore, MR imaging requires a strong static magnetic field produced by a large magnet, a second weaker magnetic field that varies across the sample, a radio transmitter and receiver, and a powerful computer to calculate an image.
Compared to x-ray and radioisotope methods, MR imaging uses energy on the opposite end of the electromagnetic spectrum, and to date, no permanent harmful side effects of MR imaging have been reported. The energy of MR imaging is nine orders of magnitude lower than that of x-rays and radioisotope techniques.
Although Lauterbur did not suggest distinct applications of the new technique in his paper, he did refer to the fact that it had been shown that cancer tissue had different signal properties compared to normal tissue, and he believed that zeugmatography could be used for medical imaging. Thus, he urged his university to file a patent application, but because neither the university patent lawyer nor the university administration itself believed in his idea, no patent application was filed and Lauterbur never obtained a patent on his invention. Others did – relatively fast.
Despite the nonbelievers within the university, it only took eight years for the first whole-body MR machines to appear in clinical settings, although these machines were crude prototypes compared to today's equipment. Ten years after the first description approximately a dozen research groups worked with whole-body imagers. Today, nobody knows exactly how many MR machines operate worldwide; more than 25,000 machines are a good guess – the majority of them in the United States and Japan, a quarter in Europe.
The hope that MR imaging, or other adaptations of MR in medicine, would be able to characterize cancerous cells in the body has not come true, but many other important applications of MR imaging have been found during the last decade. Today, MR imaging influences decisions in most areas of medicine, from neurology to orthopedics, from pediatrics to radiation therapy. MR imaging is even more interdisciplinary than roentgenology, although it is also complex and sophisticated.
1. Lauterbur PC. "Spatially Resolved Nuclear Magnetic Resonance Experiments." Handwritten and countersigned manuscript; 2 September 1971. in: Rinck PA. Magnetic Resonance in Medicine. The Basic Textbook of the European Magnetic Resonance Forum. 8th edition; 2014. Electronic version 8.2. Chapter 20: An Excursion into the History of Magnetic Resonance Imaging.
2. Hollis DP. Abusing cancer science. Chehalis, WA; U.S.A.: The Strawberry Fields Press 1987.
3. Lauterbur PC. Image formation by induced local interactions: examples of employing nuclear magnetic resonance. Nature 1973; 242: 190-191.
4. Bloch F, Hanson WW, Packard M. Nuclear induction. Phys Rev 1946; 69: 127.
5. Purcell EM, Torrey HC, Pound RV. Resonance absorption by nuclear magnetic moments in a solid. Phys Rev 1946; 69: 37-38.
6. Odeblad E, Lindström G. Some preliminary observations on the proton magnetic resonance in biological samples. Acta Radiol 1955; 43: 469-476.