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Australian Institute of Radiography The Radiographer 2006: 53 (1): 4–7 History Nobel Prize for CT and MRI pioneers Historical article Euclid Seeram British Columbia Institute of Technology, Burnaby, British Columbia, Canada Correspondence email [email protected] Introduction Two imaging modalities that have had a significant impact on radiology practice are computed tomography (CT) and magnetic resonance imaging (MRI). The development of these two modalities dates back several decades; currently, technical and clinical innovations continue at a rapid rate with remarkable results that enhance the diagnosis and management of a patient’s medical problems. As an imaging technique, MRI offers the best contrast resolution compared to any other imaging modality and therefore it is effective in providing excellent anatomical and pathological details. Additionally, MRI is capable of functional imaging, a tool that is gaining widespread attention in medicine. The impact of these two imaging modalities has been so significant that the pioneers of both CT and MRI have received the Nobel Prize in Medicine or Physiology, for their contributions to these technologies. The purpose of this paper is to outline the contributions of these pioneers to the evolution and application of CT and MRI to solving clinical problems in diagnostic medicine. Computed tomography Essential steps in CT imaging The overall steps in the production of the CT image are illustrated in Figure 1; namely, data acquisition, image reconstruction, and image display/storage/communication. In data acquisition, the x-ray beam passes through the patient and it is attenuated according to Lambert-Beer’s law: It = Io e-µx Where Io and It are the original and transmitted x-ray beam intensities respectively, µ is the linear attenuation coefficient of the tissues being imaged, and x is the section thickness. In CT, a reconstruction algorithm is used to create an image using the attenuation data collected from the patient along a number of lines or paths of known locations. The algorithms developed for CT image reconstruction are many and basically fall into iterative and analytic methods. It is not within the scope of this paper to describe these methods. Nobel prizes for CT pioneers In 1979, Godfrey Newbold Hounsfield in England and Allan MacLeod Cormack, a physics professor at Tufts University in Medford, Massachusetts, won the Nobel Prize in Medicine or Physiology for their contributions to the development of CT. Contribution of Godfrey Newbold Hounsfield Godfrey Newbold Hounsfield was born in 1919 in Nottinghamshire, England. He studied electronics and electrical and mechanical engineering. In 1951, Hounsfield joined the staff at EMI Limited (Electric and Musical Industries, now Thorn EMI) in Middlesex, where he began work on radar systems and later on computer technology. His research on computers led to the development of the EMIDEC 1100, the first solid-state business computer in Great Britain. In 1967, Hounsfield was investigating pattern recognition and reconstruction techniques using the computer. From this work, he deduced that if an x-ray beam were passed through an object from all directions and measurements were made of all the x-ray transmission, information about the internal structures of that body could be obtained. With encouragement from the British Department of Health, an experimental apparatus was constructed to investigate the clinical feasibility of the technique. The radiation used was from an americium gamma source coupled with a crystal detector. Because of the low radiation output, the apparatus took about nine days to scan the object. The computer needed 2.5 hours to process the 28,000 measurements collected by the detector. Because this procedure was too long, various modifications were made and the gamma radiation source was replaced by a powerful x-ray tube. The results of these experiments were more accurate, but it took one day to produce a picture. Hounsfield, together with a radiologist, Dr Ambrose obtained readings from a specimen of human brain. The findings were encouraging in that tumour tissue was clearly differentiated from grey and white matter and controlled experiments using fresh brains from bullocks showed details such as the ventricles and pineal gland. Experiments were also done using kidney sections from pigs. In 1971, the first clinical prototype CT brain scanner was installed at Atkinson-Morley’s Hospital and clinical studies were conducted under the direction of Dr. Ambrose. The processing time for the picture was reduced to about 20 min. Later, with the introduction of minicomputers, the processing time was reduced further to 4.5 min. In 1972, the first patient was scanned by this machine. The patient was a woman with a suspected brain lesion, and the picture showed clearly in detail a dark circular cyst in the brain. From this moment on and as more patients were scanned, the machine’s ability to distinguish the difference between normal and diseased tissue was evident. Dr. Hounsfield’s research resulted in the development of a clinically useful CT scanner for imaging the brain. For this work, Hounsfield received the McRobert Award (akin to a Nobel Prize in engineering) in 1972. By developing the first practical CT scanner, Hounsfield opened up a new domain for technologists, radiologists, medical physicists, engineers, and other related scientists. For a photograph and more details of Dr Hounsfield’s contribution and the Nobel lecture, readers should refer to the Nobel website at http://www.nobelprize.org/medicine/laureates/1979/ index.html Nobel Prize for CT and MRI pioneers The Radiographer Figure 1 Figure 2 On 12th August, 2004, Dr Hounsfield passed away. He will be remembered as the individual whose invention has a significant impact on the practice of radiology. Allan MacLeod Cormack Allan MacLeod Cormack was born in Johannesburg, South Africa, in 1924. He attended the University of Cape Town where he obtained a Bachelor of Science in Physics in 1944, and earned a Master of Science in Crystallography in 1945. He subsequently studied nuclear physics at Cambridge University before returning to the University of Cape Town as a physics lecturer. He later moved to the United States and was on sabbatical at Harvard University before joining the physics department at Tufts University in 1958. Prof Cormack developed solutions to the mathematical problems in CT. Later in 1963 and 1964 he published two papers the Journal of Applied Physics on the subject, but they received little interest in the scientific community at that time. It was not until Hounsfield began worked on the development of the first practical CT scanner that Dr Cormack’s work was also viewed as the solutions to the mathematical problem in CT. Cormack died at age 74, in Massachuetts on 7th May, 1998. In South Africa, Dr Cormack was granted The Order of Mapungubwe, South Africa’s highest honour, in December 2002, for his contribution to the invention of the CT scanner. For a photograph and more details of Dr Cormack’s contribution and the Nobel lecture, readers should refer to the Nobel Website at http://www.nobelprize.org/medicine/laureates/1979/ index.html. resonance (NMR) a phenomenon that describes atomic and nuclear magnetism. This term was coined by one of the early workers in this area, Isador Rabi, who earned the Nobel Prize in Physics in 1937, for developing a technique that he used to measure the spin associated with the nuclei of certain atoms. This work resulted in the use of these ideas to examine the structure of molecules using the technique of NMR spectroscopy. The NMR phenomenon can be observed when certain atoms are placed in a strong magnetic field. First, the material becomes magnetised, hence the use of the term ‘magnetic’ to describe this magnetism. The second major observation is that the material experiences a resonance characteristic, hence the use of the term ‘resonance’. This refers to the fact that the nuclei of the atoms of certain materials, when exposed to an external stimulus such as radiofrequency (RF) radiation, absorb and subsequently re-emit RF at the same frequency of the stimulating radiation, after termination of the RF exposure. Finally, the term ‘nuclear’ refers to the nucleus of the atom from which a RF signal emanates. Later, two physicists, Edward Purcell at Harvard University, and Felix Bloch at Stanford University, demonstrated that nuclei with an odd number of protons and neutrons, when placed in a strong magnetic field align parallel to the field. For this work they shared the Nobel Prize in Physics in 1946. Additionally, Bloch described the motion of the nuclei in the magnetic field with a set of differential equations referred to as the Bloch equations. The phenomenon of NMR gained widespread acceptance as a tool in chemistry for examining the structure of various molecules. This technique is referred to as NMR spectroscopy that was performed with an NMR spectrometer. Magnetic resonance imaging Magnetic resonance imaging is based on nuclear magnetic Essential steps in magnetic resonance imaging The essential steps in magnetic resonance (MR) imaging are The Radiographer illustrated in Figure 2, and the following brief description is necessary in order to appreciate the importance of the work of the Nobel laureates: In MRI a patient is placed in a strong stationary magnetic field to magnetise the tissues for data acquisition, and the basis of imaging depends on the use of the Larmor equation ω = γΒ0 where γ is the gyromagnetic ratio and Β0 is the magnetic field strength, and ω is the frequency of precession of the protons. An RF pulse of the same frequency as the precessional frequency of the protons is used to excite the protons from their equilibrium state. When the RF pulse is turned off, the protons relax back to equilibrium according to two time constants, T1 and T2. It is the differences in the T1 times and T2 times of the various tissues that account for tissue contrast from which MR images can be produced using three orthogonal magnetic field gradients that are applied to the patient during the imaging process; one for slice selection (z gradient) and the other two for spatial localisation within the slice (x and y gradients). The spatial characteristics of the MR image are a result of the imaging procedure, where a selected slice of the patient is first obtained. The slice is subsequently divided up into rows and columns to define a matrix of voxels or volume elements and MR signals arise from each of the individual voxels and these are converted into image data. The image is made up of a matrix of pixels (digital matrix) and the brightness of each pixel in the matrix reflects the signal strength coming from its corresponding voxel in the slice. During imaging, the MR signals (time domain) received from the patient from specific locations in the slice are digitised and sent into a frequency domain space referred to as a k-space. The MR reconstruction algorithm, the 2D or 3D Fourier Transform, uses the data in k-space to build up the image (Figure 2). For a comprehensive description of the basic physics of MRI, readers should refer to the work of Bushong.1 Nobel Prize for MRI pioneers Other significant discoveries related to MRI, are attributed to several individuals such as the work of Richard Ernst who worked on 2D NMR, particularly high resolution NMR spectroscopy. Additionally, Kurt Wüthrich developed NMR spectroscopy for examining 3D biomacromolecules. Both of these individuals earned the Nobel Prize in Chemistry (Ernst in 1991 and Wüthrich in 2003). For a detailed and comprehensive coverage of the work of these scientists as well as others, the interested reader should refer to a book entitled ‘The Pioneers of NMR and Magnetic Resonance in Medicine: The Story of MRI’ by Mattson and Simon (1996). For the development of a clinically useful MRI scanner, however, it is important to mention the work of other individuals such as Paul Lauterbur, in the United States, and Peter Mansfield in England. In addition, one other individual who made a contribution to MRI is Raymond Damadian in the United States. Contributions of Paul Lauterbur, PhD Paul Lauterbur obtained his PhD in Chemistry from the University of Pittsburg, Pennsylvania and is now professor and director of the Biomedical MR Lab at the University of Illinois at Urbana. Lauterbur’s contribution to the development of MRI focussed on the use of magnetic field gradients for spatial localisation purposes, a significant notion responsible for slice selection and subsequent pixel localisation within the slice. He labelled this technique ‘zeumatography’ from the Greek meaning ‘joining together’. He was describing the superimposition of weak mag- Euclid Seeram netic field gradients on the very strong stationary magnetic field of the main magnet (along the x, y, and z axis of the slice) together with the use of RF radiation during the imaging process. He later published a paper in Nature (1973; 242: 190–191) with the title ‘Image formation by induced local interactions: Examples employing magnetic resonance’. Paul Lauterbur shared the Nobel Prize for Physiology or Medicine with Sir Peter Mansfield in 2003. For more details on Dr Lauterbur, such as a photograph, education, appointments, honours and awards and research, the interested reader should refer to web sites which were active at the time of writing this article: www.nobel.se/medicine/laureates/2003/ lauterbur-cv.html; www.scs.uiuc.edu/chem/lauterb.htm and; www.beckman.uiuc.edu/faculty/lauterbu.html. Contributions of Sir Peter Mansfield Peter Mansfield was born in 1933 in Nottingham, England. In 1962, he obtained his PhD in Physics from the University of London. In 1993 Peter Mansfield was knighted. In 2003, he shared the Nobel Prize in Physiology or Medicine with Paul Lauterbur, for his significant contributions to the development of MRI. As noted by Mansfield, ‘most of the major developments that led to modern MRI machines came from Nottingham.’ In particular, Mansfield’s work focussed on spatial localisation to create 2D slices of an object. This task is accomplished by using weak magnetic field gradients superimposed on the main magnetic field of the scanner. But this took about 20 minutes to produce an image. He was able to reduce this time to about 20 mins by using ‘echo-planar imaging’, the technique that is still used today.2 The echo-planar technique allows MR operators to do extremely fast imaging and opens up new applications in functional MR imaging. Peter Mansfield now works at the Magnetic Resonance Centre School of Physics and Astronomy at the University of Nottingham. For further details, such as a photograph, education, appointments, research, honours and awards, the interested reader should visit the following web sites which were active at the time of writing this paper: www.nobel.se/medicine/laureates/2003/ mansfield-cv.html; www.nottingham.ac.uk/~ppzwww/staff/ Mansfield_P_t.html and; www.magres.nottingham.ac.uk/~mansfield/. Raymond Damadian – Nobel Prize controversy As a result of the recognition paid to Lauterbur and Mansfield, several articles appeared in the literature with the goal of addressing what has been popularly called a Nobel Prize Controversy. For example, in December 2003, the journal Diagnostic Imaging featured an article titled ‘Nobel Mistake?’ The views are wide and varied in describing Dr Damadian’s contribution to the development of MRI. Therefore, an attempt will be made here to quote relevant extracts from several articles to shed some light on the nature of the controversy. To begin, Cartlidge2 provides us with a small insight into the nature of the controversy. He states: ‘In particular, Raymond Damadian, a physician showed how NMR could be used to distinguish between cancerous and healthy tissue, took the unusual step of making his claim for the prize in full-page advertisements in the The Washington Post, The New York Times, and the Los Nobel Prize for CT and MRI pioneers Angeles Times, a few days after the awards were announced.’ ‘It had been clear for some time that there would be a prize for MRI, because of the impact that it has had, but it was not clear who would be included’ says Stephen Keevil of Guy’s Hospital in London. ‘I am sure however, that Lauterbur and Mansfield deserve the prize.’ Keevil says that he has some sympathy for Damadian but points out that the prize appears to have been awarded specifically for Lauterbur’s and Mansfield’s work on the use of magnetic field gradients saying: ‘Damadian has made major contributions to MRI but not in this specific area.’ In particular, Damadian’s work was centred on establishing T1 and T2 relaxation times for healthy and diseased tissues. In March 1972, he applied for a patent for an ‘Apparatus and Method for Detecting Cancer Tissue’. Subsequently, Damadian built an NMR imaging scanner that he called the ‘Indomitable’. In 1974, he received the patent and started a company called FONAR (Field Focused Nuclear Magnetic Resonance). For this contribution to MRI, Damadian received the National Medal of Technology Award in 1988 from President Reagan. This award is the highest honour bestowed by the President of the United States to notable innovators in the US, see www.technology.gov/Medal/default.htm. Dr Damadian was inducted into the National Inventors Hall of Fame in 1989, for his pioneering work. For more information on his work, the interested reader should refer to an article in Scientific American3 as well as the following web sites that were active at the time of writing this article: www.fonar.com/nobel.htm and; www.invent.org/hall_of_fame/36.html. In 1993, an article that appeared in Diagnostic Imaging4 entitled ‘Is there a Nobel Prize in MRI’s Future?’ included various opinions from several expert scientists and radiologists including Lauterbur, Ernst, Young, and Smith. From the perspective of the author of this brief paper, the opinion of Dr Francis Smith, professor and consultant in nuclear imaging in Scotland, provides a reasonable framework for awarding the prize. Dr Smith stated that: ‘If the prize were given on the basis of who was first, this would make a mockery of what came afterwards. There are about nine key players, but I think that it would be fair if the prize were shared in three ways: Damadian for his ideas, Lauterbur for showing that they were possible, and Mansfield for further developing the concept’.4 Conclusion It is interesting to note that the Nobel Prize for Physiology or Medicine has been awarded to physicists, chemists, and engineers, The Radiographer for their work that help physicians diagnose, treat and manage a wide range of patients’ medical problems. This article serves to impress upon us there is significant value in the study of not only the physics of imaging but the engineering aspects as well. These are the many tools we use to produce diagnostic images, so that our patients can benefit from our wisdom. Acknowledgment The author would like to express his sincere thanks to Anthony Chan, M.Eng., M.Sc., P.Eng., C.Eng., C.C.E ; Program Head and Faculty of the Biomedical Engineering Department at the British Columbia Institute of Technology, Burnaby, Canada; for his careful review of the manuscript. References 1 Bushong S. MRI: Physical and Biological Principles. Third Edition. 2003; Mosby, Inc. 2 Cartlidge E. MRI pioneers share medicine prize. Physics World 2003; 16 (6). 3 Profile of Raymond Damadian. Scientific American 1997; 32–4. 4 Nobel Mistake? Controversy overshadows recognition of MRI’s scientific prominence. Diagnos Imaging 2003; 42–9. Further reading Dallessio KM. RSNA Preview; Nobel Prize awarded for discoveries leading to MR imaging. Appl Radiol 2003; 66. Gore J. Out of the Shadows-MRI and the Nobel Prize. New Engl J Med 2003; 349 (24): 2290–2292. Mattson J and Simon M. The Pioneers of NMR and Magnetic Resonance in Medicine: The Story of MRI. Bar-Ilan University Press 1996. Ritter M. Doctors win Nobel Prize for MRI discoveries. Vancouver Sun. 2003; October 7th: A7. www.nobel.se/medicine/laureates/2003/lauterbur-cv.html www.scs.uiuc.edu/chem/lauterb.htm www.beckman.uiuc.edu/faculty/lauterbu.html www.nobel.se/medicine/laureates/2003/mansfield-cv.html www.nottingham.ac.uk/~ppzwww/staff/Mansfield_P_t.html www.magres.nottingham.ac.uk/~mansfield/ www.technology.gov/Medal/default.htm www.fonar.com/nobel.htm www.invent.org/hall_of_fame/36.html