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On the 2003 Nobel Prize in medicine or physiology awarded to Paul C. Lauterbur and Sir Peter Mansfield

2003; Wiley; Volume: 51; Issue: 1 Linguagem: Inglês

10.1002/mrm.10717

1522-2594

Félix W. Wehrli,

NMR spectroscopy and applications

The awarding of this year's Nobel Prize in medicine or physiology to Professors Paul C. Lauterbur and Peter Mansfield, fills me, as editor of this journal, with great joy and pride—an excitement that I trust the overwhelming majority of Magnetic Resonance in Medicine's readership shares with me. Both of these Nobel laureates (Fig. 1) have been honorary members of this journal for many years, and this year's ultimate science prize was perceived by many of us as long overdue recognition for the ingenuity and dedication of two scientists whose work led to one of the greatest innovations in diagnostic medicine. Here I take the liberty of briefly recounting what I believe are the key historical events in the evolution of a field of science and technology that has revolutionized medical diagnostics, and without which neither this journal nor the society it serves would exist. Of course, this note is not meant to be an account of the early history of MRI per se (which is covered, for example, in Ref.1), and thus it falls far short of doing justice to the many early contributors whose work led to the creation of whole-body clinical MRI. As Becker et al. (2) so eloquently stated in the Encyclopedia of NMR: "The history of NMR, like any history, has no real beginning. Every development, every discovery, can be traced back to antecedents that provided basic theory or applicable technology ready to be exploited." Professors Paul C. Lauterbur (left) and Sir Peter Mansfield (right). In 1973, two papers on NMR were published. Neither of these works received a great deal of attention at that time, and perhaps the majority of those who read them considered them to be esoteric at best. One, authored by Dr. Paul Lauterbur, then Professor of Chemistry at the State University of New York at Stony Brook, appeared in Nature and was entitled "Image Formation by Induced Local Interactions: Examples Employing Nuclear Magnetic Resonance" (3). It introduced an NMR method that generated a series of spectra by exposing an object (in that particular case, two water-filled vials) to a magnetic field gradient during signal collection. The experiment was performed on a 60 MHz Varian A 60 spectrometer (the first mass-produced NMR spectrometer for structure analysis). Like the majority of NMR systems, the electromagnet-based spectrometer used continuous-wave excitation, achieved by sweeping the magnetic field across the spectral resonances. The magnetic field gradient was generated by the system's linear z-shim. Lauterbur recognized that the spectra obtained in this manner represented projections of the object's spin density distribution onto the gradient axis, and that by rotating the object in equal angular increments, one could obtain a series of angular projections. He was also aware of the mathematics of back projection used in computed tomography. Because the interaction can be regarded as a coupling of two fields (polarizing and gradient), Lauterbur dubbed the technique "zeugmatography" (derived from the Greek word ζϵυγμα—"that which is used for joining"). Lauterbur also understood the signal modulations induced by differences in relaxation times. In this particular case, this was achieved by doping one of the samples with Mn2+ ions and cranking up the power of the B1 field to achieve partial saturation of the sample with the longer relaxation time. a: Principle of Lauterbur's zeugmatographic experiment, schematically showing four angular projections of the object, perpendicular to the direction of the magnetic field gradients, represented by arrows. b: Proton NMR zeugmatogram of two water-containing tubes (adapted from Ref.3). a: Transient proton NMR signal from three layers of camphor obtained with a line-narrowing pulse NMR technique. b: Fourier transform of the transient response of the signal in part a (adapted from Ref.4). Subsequent work in the laboratories at Stony Brook and Nottingham focused on technological improvements, such as scaling the experiment to enable imaging of larger objects, including live animals. Only 1 year after Lauterbur's seminal article appeared in Nature, he published a paper showing a zeugmatogram of the chest cavity of a live mouse (6). The methodology used was analogous to the original zeugmatographic experiment, except that the experiment was conducted on a larger gap magnet operating at a field of about 0.2T. In 1975 Mansfield and Grannell (7) published an extensive paper in which they showed projection images of small objects, including one of the human finger (perhaps the first "image" of live human anatomy). Mansfield soon recognized that for the method to be practical, scan acquisition speed had to be dramatically increased. He recognized that the lifetime of the transverse magnetization typically far exceeds sampling time, and that additional data can be acquired by sinusoidally oscillating the spatial encoding gradient so as to generate a train of echoes (8, 9). This concept gave rise to what is now known as echo-planar imaging (EPI). These initial experiments spurred significant interest from other investigators. Waldo Hinshaw (10, 11) and Raymond Andrew and colleagues (12) in the Physics Department at Nottingham pursued new approaches to image 3D objects, including a demonstration of the applicability to humans with a cross-sectional image of the hand (13). In 1976, Damadian and coworkers (14), then at Downstate Medical Center at the State University of New York, presented a method of point localization that relied on an inhomogeneous field to produce a saddle-shaped profile. Like similar approaches, this idea was found to be impractical and was never practiced in any other laboratory. A significant milestone in the further evolution of modern MRI was the development of Fourier zeugmatography (15) by Richard R. Ernst (winner of the 1992 Nobel Prize in chemistry) at the Swiss Federal Institute of Technology, in Zurich, Switzerland. This method introduced Cartesian k-space sampling of Fourier space, and thus was a direct precursor of spin-warp imaging (16), which remains the mainstay of clinical MRI today.