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 EMI) in Middlesex, where he began work on radar systems and Two imaging modalities that have had a significant impact on later on computer technology. His research on computers led to radiology practice are computed tomography (CT) and magnetic the development of the EMIDEC 1100, the first solid-state busi- resonance imaging (MRI). The development of these two modali- ness computer in Great Britain. ties dates back several decades; currently, technical and clinical In 1967, Hounsfield was investigating pattern recognition and innovations continue at a rapid rate with remarkable results that reconstruction techniques using the computer. From this work, enhance the diagnosis and management of a patient’s medical he deduced that if an x-ray beam were passed through an object problems. As an imaging technique, MRI offers the best contrast from all directions and measurements were made of all the x-ray resolution compared to any other imaging modality and therefore transmission, information about the internal structures of that it is effective in providing excellent anatomical and pathological body could be obtained. details. Additionally, MRI is capable of functional imaging, a With encouragement from the British Department of Health, tool that is gaining widespread attention in medicine. The impact an experimental apparatus was constructed to investigate the of these two imaging modalities has been so significant that the clinical feasibility of the technique. The radiation used was from pioneers of both CT and MRI have received the Nobel Prize in an americium gamma source coupled with a crystal detector. Medicine or Physiology, for their contributions to these technolo- Because of the low radiation output, the apparatus took about nine gies. days to scan the object. The computer needed 2.5 hours to process The purpose of this paper is to outline the contributions of the 28,000 measurements collected by the detector. Because this these pioneers to the evolution and application of CT and MRI to procedure was too long, various modifications were made and the solving clinical problems in diagnostic medicine. gamma radiation source was replaced by a powerful x-ray tube. The results of these experiments were more accurate, but it took Computed tomography one day to produce a picture. Hounsfield, together with a radiolo- gist, Dr Ambrose obtained readings from a specimen of human Essential steps in CT imaging brain. The findings were encouraging in that tumour tissue was The overall steps in the production of the CT image are illus- clearly differentiated from grey and white matter and controlled trated in Figure 1; namely, data acquisition, image reconstruction, experiments using fresh brains from bullocks showed details such and image display/storage/communication. as the ventricles and pineal gland. Experiments were also done In data acquisition, the x-ray beam passes through the patient using kidney sections from pigs. and it is attenuated according to Lambert-Beer’s law: In­ 971, the first clinical prototype CT brain scanner was I = I e-µx t o installed at Atkinson-Morley’s Hospital and clinical studies were Where I and I are the original and transmitted x-ray beam o t conducted under the direction of Dr. Ambrose. The processing intensities respectively, µ is the linear attenuation coefficient of time for the picture was reduced to about 20 min. Later, with the the tissues being imaged, and x is the section thickness. In CT, introduction of minicomputers, the processing time was reduced a reconstruction algorithm is used to create an image using the further to 4.5 min. attenuation data collected from the patient along a number of In­ 972, the first patient was scanned by this machine. The lines or paths of known locations. The algorithms developed for patient was a woman with a suspected brain lesion, and the pic- CT image reconstruction are many and basically fall into iterative ture showed clearly in detail a dark circular cyst in the brain. From and analytic methods. It is not within the scope of this paper to this moment on and as more patients were scanned, the machine’s describe these methods. ability to distinguish the difference between normal and diseased Nobel prizes for CT pioneers tissue was evident. Dr. Hounsfield’s research resulted in the In 1979, Godfrey Newbold Hounsfield in England and Allan development of a clinically useful CT scanner for imaging the MacLeod Cormack, a physics professor at Tufts University in brain. For this work, Hounsfield received the McRobert Award Medford, Massachusetts, won the Nobel Prize in Medicine or (akin to a Nobel Prize in engineering) in 1972. By developing the Physiology for their contributions to the development of CT. first practical CT scanner, Hounsfield opened up a new domain for technologists, radiologists, medical physicists, engineers, and Contribution of Godfrey Newbold Hounsfield other related scientists. Godfrey Newbold Hounsfield was born in­ 919 in For a photograph and more details of Dr Hounsfield’s contri- Nottinghamshire, England. He studied electronics and electri- bution and the Nobel lecture, readers should refer to the Nobel cal and mechanical engineering. In 1951, Hounsfield joined the website at http://www.nobelprize.org/medicine/laureates/1979/ staff at EMI Limited (Electric and Musical Industries, now Thorn 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 resonance (NMR) a phenomenon that describes atomic and nucle- remembered as the individual whose invention has a significant ar magnetism. This term was coined by one of the early workers impact on the practice of radiology. 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 Allan MacLeod Cormack associated with the nuclei of certain atoms. This work resulted in Allan MacLeod Cormack was born in Johannesburg, South the use of these ideas to examine the structure of molecules using Africa, in 1924. He attended the University of Cape Town where the technique of NMR spectroscopy. The NMR phenomenon can he obtained a Bachelor of Science in Physics in 1944, and earned be observed when certain atoms are placed in a strong magnetic a Master of Science in Crystallography in­ 945. He subse- field. First, the material becomes magnetised, hence the use of the quently studied nuclear physics at Cambridge University before term ‘magnetic’ to describe this magnetism. The second major returning to the University of Cape Town as a physics lecturer. observation is that the material experiences a resonance character- He later moved to the United States and was on sabbatical at istic, hence the use of the term ‘resonance’. This refers to the fact Harvard University before joining the physics department at Tufts that the nuclei of the atoms of certain materials, when exposed University in 1958. to an external stimulus such as radiofrequency (RF) radiation, Prof Cormack developed solutions to the mathematical prob- absorb and subsequently re-emit RF at the same frequency of lems in CT. Later in 1963 and 1964 he published two papers the the stimulating radiation, after termination of the RF exposure. Journal of Applied Physics on the subject, but they received little Finally, the term ‘nuclear’ refers to the nucleus of the atom from interest in the scientific community at that time. It was not until which a RF signal emanates. Hounsfield began worked on the development of the first practical Later, two physicists, Edward Purcell at Harvard University, CT scanner that Dr Cormack’s work was also viewed as the solu- and Felix Bloch at Stanford University, demonstrated that nuclei tions to the mathematical problem in CT. Cormack died at age 74, with an odd number of protons and neutrons, when placed in a in Massachuetts on 7th May, 1998. strong magnetic field align parallel to the field. For this work they In South Africa, Dr Cormack was granted The Order of shared the Nobel Prize in Physics in 1946. Additionally, Bloch Mapungubwe, South Africa’s highest honour, in December 2002, described the motion of the nuclei in the magnetic field with a set for his contribution to the invention of the CT scanner. of differential equations referred to as the Bloch equations. For a photograph and more details of Dr Cormack’s contri- The phenomenon of NMR gained widespread acceptance as bution and the Nobel lecture, readers should refer to the Nobel a tool in chemistry for examining the structure of various mol- Website at http://www.nobelprize.org/medicine/laureates/1979/ ecules. This technique is referred to as NMR spectroscopy that index.html. was performed with an NMR spectrometer. Magnetic resonance imaging Essential steps in magnetic resonance imaging Magnetic resonance imaging is based on nuclear magnetic ­ The essential steps in magnetic resonance (MR) imaging are ­ The Radiographer Euclid Seeram illustrated in Figure 2, and the following brief description is nec- netic field gradients on the very strong stationary magnetic field essary in order to appreciate the importance of the work of the of the main magnet (along the x, y, and z axis of the slice) together Nobel laureates: with the use of RF radiation during the imaging process. He In MRI a patient is placed in a strong stationary magnetic later published a paper in Nature (1973; 242: 190–191) with the field to magnetise the tissues for data acquisition, and the basis title ‘Image formation by induced local interactions: Examples of imaging depends on the use of the Larmor equation ω = γΒ0 employing magnetic resonance’. Paul Lauterbur shared the Nobel where γ is the gyromagnetic ratio and Β0 is the magnetic field Prize for Physiology or Medicine with Sir Peter Mansfield in strength, and ω is the frequency of precession of the protons. An 2003. RF pulse of the same frequency as the precessional frequency of For more details on Dr Lauterbur, such as a photograph, the protons is used to excite the protons from their equilibrium education, appointments, honours and awards and research, the state. When the RF pulse is turned off, the protons relax back to interested reader should refer to web sites which were active at equilibrium according to two time constants, T1 and T2. It is the the time of writing this article: differences in the T1 times and T2 times of the various tissues www.nobel.se/medicine/laureates/2003/ that account for tissue contrast from which MR images can be lauterbur-cv.html; produced using three orthogonal magnetic field gradients that are www.scs.uiuc.edu/chem/lauterb.htm and; applied to the patient during the imaging process; one for slice www.beckman.uiuc.edu/faculty/lauterbu.html. selection (z gradient) and the other two for spatial localisation within the slice (x and y gradients). Contributions of Sir Peter Mansfield The spatial characteristics of the MR image are a result of the Peter Mansfield was born in­ 933 in Nottingham, England. imaging procedure, where a selected slice of the patient is first In­ 962, he obtained his PhD in Physics from the University obtained. The slice is subsequently divided up into rows and of London. In 1993 Peter Mansfield was knighted. In 2003, he columns to define a matrix of voxels or volume elements and shared the Nobel Prize in Physiology or Medicine with Paul MR signals arise from each of the individual voxels and these Lauterbur, for his significant contributions to the development of are converted into image data. The image is made up of a matrix MRI. As noted by Mansfield, ‘most of the major developments of pixels (digital matrix) and the brightness of each pixel in the that led to modern MRI machines came from Nottingham.’ matrix reflects the signal strength coming from its corresponding In particular, Mansfield’s work focussed on spatial localisation voxel in the slice. During imaging, the MR signals (time domain) to create 2D slices of an object. This task is accomplished by received from the patient from specific locations in the slice are using weak magnetic field gradients superimposed on the main digitised and sent into a frequency domain space referred to as magnetic field of the scanner. But this took about 20 minutes to a k-space. The MR reconstruction algorithm, the 2D or 3D Fourier produce an image. He was able to reduce this time to about 20 Transform, uses the data in k-space to build up the image (Figure 2). mins by using ‘echo-planar imaging’, the technique that is still For a comprehensive description of the basic physics of MRI, used today.2 The echo-planar technique allows MR operators to readers should refer to the work of Bushong.1 do extremely fast imaging and opens up new applications in func- tional MR imaging. Nobel Prize for MRI pioneers Peter Mansfield now works at the Magnetic Resonance Other significant discoveries related to MRI, are attributed to Centre School of Physics and Astronomy at the University of several individuals such as the work of Richard Ernst who worked Nottingham. For further details, such as a photograph, education, on 2D NMR, particularly high resolution NMR spectroscopy. appointments, research, honours and awards, the interested reader Additionally, Kurt Wüthrich developed NMR spectroscopy for should visit the following web sites which were active at the time examining 3D biomacromolecules. Both of these individuals of writing this paper: earned the Nobel Prize in Chemistry (Ernst in 1991 and Wüthrich www.nobel.se/medicine/laureates/2003/ in 2003). For a detailed and comprehensive coverage of the work mansfield-cv.html; of these scientists as well as others, the interested reader should www.nottingham.ac.uk/~ppzwww/staff/ refer to a book entitled ‘The Pioneers of NMR and Magnetic Mansfield_P_t.html and; Resonance in Medicine: The Story of MRI’ by Mattson and Simon www.magres.nottingham.ac.uk/~mansfield/. (1996). For the development of a clinically useful MRI scanner, how- Raymond Damadian – Nobel Prize controversy ever, it is important to mention the work of other individuals such As a result of the recognition paid to Lauterbur and Mansfield, as Paul Lauterbur, in the United States, and Peter Mansfield in several articles appeared in the literature with the goal of address- England. In addition, one other individual who made a contribu- ing what has been popularly called a Nobel Prize Controversy. tion to MRI is Raymond Damadian in the United States. For example, in December 2003, the journal Diagnostic Imaging featured an article titled ‘Nobel Mistake?’ The views are wide and Contributions of Paul Lauterbur, PhD varied in describing Dr Damadian’s contribution to the develop- Paul Lauterbur obtained his PhD in Chemistry from the ment of MRI. Therefore, an attempt will be made here to quote University of Pittsburg, Pennsylvania and is now professor and relevant extracts from several articles to shed some light on the director of the Biomedical MR Lab at the University of Illinois nature of the controversy. at Urbana. Lauterbur’s contribution to the development of MRI To begin, Cartlidge2 provides us with a small insight into the focussed on the use of magnetic field gradients for spatial locali- nature of the controversy. He states: ‘In particular, Raymond sation purposes, a significant notion responsible for slice selection Damadian, a physician showed how NMR could be used to dis- and subsequent pixel localisation within the slice. He labelled tinguish between cancerous and healthy tissue, took the unusual this technique ‘zeumatography’ from the Greek meaning ‘joining step of making his claim for the prize in full-page advertisements together’. He was describing the superimposition of weak mag- in the The Washington Post, The New York Times, and the Los Nobel Prize for CT and MRI pioneers The Radiographer ­

Angeles Times, a few days after the awards were announced.’ for their work that help physicians diagnose, treat and manage a ‘It had been clear for some time that there would be a prize for wide range of patients’ medical problems. MRI, because of the impact that it has had, but it was not clear This article serves to impress upon us there is significant value who would be included’ says Stephen Keevil of Guy’s Hospital in in the study of not only the physics of imaging but the engineering London. ‘I am sure however, that Lauterbur and Mansfield deserve aspects as well. These are the many tools we use to produce diag- the prize.’ Keevil says that he has some sympathy for Damadian nostic images, so that our patients can benefit from our wisdom. but points out that the prize appears to have been awarded specifi- Acknowledgment cally for Lauterbur’s and Mansfield’s work on the use of magnetic The author would like to express his sincere thanks to Anthony field gradients saying: ‘Damadian has made major contributions Chan, M.Eng., M.Sc., P.Eng., C.Eng., C.C.E ; Program Head and to MRI but not in this specific area.’ Faculty of the Biomedical Engineering Department at the British In particular, Damadian’s work was centred on establishing T1 Columbia Institute of Technology, Burnaby, Canada; for his care- and T2 relaxation times for healthy and diseased tissues. In March ful review of the manuscript. 1972, he applied for a patent for an ‘Apparatus and Method for Detecting Cancer Tissue’. Subsequently, Damadian built an NMR References imaging scanner that he called the ‘Indomitable’. In­ 974, he 1 Bushong S. MRI: Physical and Biological Principles. Third Edition. 2003; received the patent and started a company called FONAR (Field Mosby, Inc. Focused Nuclear Magnetic Resonance). For this contribution 2 Cartlidge E. MRI pioneers share medicine prize. Physics World 2003; 16 (6). to MRI, Damadian received the National Medal of Technology 3 Profile of Raymond Damadian. Scientific American 1997; 32–4. Award in 1988 from President Reagan. This award is the highest 4 Nobel Mistake? Controversy overshadows recognition of MRI’s scientific honour bestowed by the President of the United States to notable prominence. Diagnos Imaging 2003; 42–9. innovators in the US, see www.technology.gov/Medal/default.htm. Further reading Dr Damadian was inducted into the National Inventors Hall Dallessio KM. RSNA Preview; Nobel Prize awarded for discoveries leading to of Fame in 1989, for his pioneering work. For more information MR imaging. Appl Radiol 2003; 66. on his work, the interested reader should refer to an article in Gore J. Out of the Shadows-MRI and the Nobel Prize. New Engl J Med 2003; 3 Scientific American as well as the following web sites that were 349 (24): 2290–2292. active at the time of writing this article: Mattson J and Simon M. The Pioneers of NMR and Magnetic Resonance in www.fonar.com/nobel.htm and; Medicine: The Story of MRI. Bar-Ilan University Press 1996. www.invent.org/hall_of_fame/36.html. Ritter M. Doctors win Nobel Prize for MRI discoveries. Vancouver Sun. 2003; In 1993, an article that appeared in Diagnostic Imaging4 enti- October 7th: A7. tled ‘Is there a Nobel Prize in MRI’s Future?’ included various www.nobel.se/medicine/laureates/2003/lauterbur-cv.html opinions from several expert scientists and radiologists including www.scs.uiuc.edu/chem/lauterb.htm Lauterbur, Ernst, Young, and Smith. From the perspective of the www.beckman.uiuc.edu/faculty/lauterbu.html author of this brief paper, the opinion of Dr Francis Smith, pro- www.nobel.se/medicine/laureates/2003/mansfield-cv.html fessor and consultant in nuclear imaging in Scotland, provides www.nottingham.ac.uk/~ppzwww/staff/Mansfield_P_t.html a reasonable framework for awarding the prize. Dr Smith stated www.magres.nottingham.ac.uk/~mansfield/ 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 www.technology.gov/Medal/default.htm nine key players, but I think that it would be fair if the prize were www.fonar.com/nobel.htm shared in three ways: Damadian for his ideas, Lauterbur for show- www.invent.org/hall_of_fame/36.html ing 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,