Nobel Prize for CT and MRI pioneers - Minnis Journals

Nobel Prize for CT and MRI pioneersThe Radiographer ­Figure 1Figure 2On 12th August, 2004, Dr Hounsfield passed away. He will beremembered as the individual whose invention has a significantimpact on the practice of radiology.Allan MacLeod CormackAllan MacLeod Cormack was born in Johannesburg, SouthAfrica, in 1924. He attended the University of Cape Town wherehe obtained a Bachelor of Science in Physics in 1944, and earneda Master of Science in Crystallography in 1945. He subsequentlystudied nuclear physics at Cambridge University beforereturning to the University of Cape Town as a physics lecturer.He later moved to the United States and was on sabbatical atHarvard University before joining the physics department at TuftsUniversity in 1958.Prof Cormack developed solutions to the mathematical problemsin CT. Later in 1963 and 1964 he published two papers theJournal of Applied Physics on the subject, but they received littleinterest in the scientific community at that time. It was not untilHounsfield began worked on the development of the first practicalCT scanner that Dr Cormack’s work was also viewed as the solutionsto 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 ofMapungubwe, 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 contributionand the Nobel lecture, readers should refer to the NobelWebsite at http://www.nobelprize.org/medicine/laureates/1979/index.html.Magnetic resonance imagingMagnetic resonance imaging is based on nuclear magnetic ­resonance (NMR) a phenomenon that describes atomic and nuclearmagnetism. This term was coined by one of the early workersin this area, Isador Rabi, who earned the Nobel Prize in Physics in1937, for developing a technique that he used to measure the spinassociated with the nuclei of certain atoms. This work resulted inthe use of these ideas to examine the structure of molecules usingthe technique of NMR spectroscopy. The NMR phenomenon canbe observed when certain atoms are placed in a strong magneticfield. First, the material becomes magnetised, hence the use of theterm ‘magnetic’ to describe this magnetism. The second majorobservation is that the material experiences a resonance characteristic,hence the use of the term ‘resonance’. This refers to the factthat the nuclei of the atoms of certain materials, when exposedto an external stimulus such as radiofrequency (RF) radiation,absorb and subsequently re-emit RF at the same frequency ofthe stimulating radiation, after termination of the RF exposure.Finally, the term ‘nuclear’ refers to the nucleus of the atom fromwhich a RF signal emanates.Later, two physicists, Edward Purcell at Harvard University,and Felix Bloch at Stanford University, demonstrated that nucleiwith an odd number of protons and neutrons, when placed in astrong magnetic field align parallel to the field. For this work theyshared the Nobel Prize in Physics in 1946. Additionally, Blochdescribed the motion of the nuclei in the magnetic field with a setof differential equations referred to as the Bloch equations.The phenomenon of NMR gained widespread acceptance asa tool in chemistry for examining the structure of various molecules.This technique is referred to as NMR spectroscopy thatwas performed with an NMR spectrometer.Essential steps in magnetic resonance imagingThe essential steps in magnetic resonance (MR) imaging are

­The RadiographerEuclid Seeramillustrated in Figure 2, and the following brief description is necessaryin order to appreciate the importance of the work of theNobel laureates:In MRI a patient is placed in a strong stationary magneticfield to magnetise the tissues for data acquisition, and the basisof imaging depends on the use of the Larmor equation ω = γΒ 0where γ is the gyromagnetic ratio and Β 0is the magnetic fieldstrength, and ω is the frequency of precession of the protons. AnRF pulse of the same frequency as the precessional frequency ofthe protons is used to excite the protons from their equilibriumstate. When the RF pulse is turned off, the protons relax back toequilibrium according to two time constants, T1 and T2. It is thedifferences in the T1 times and T2 times of the various tissuesthat account for tissue contrast from which MR images can beproduced using three orthogonal magnetic field gradients that areapplied to the patient during the imaging process; one for sliceselection (z gradient) and the other two for spatial localisationwithin the slice (x and y gradients).The spatial characteristics of the MR image are a result of theimaging procedure, where a selected slice of the patient is firstobtained. The slice is subsequently divided up into rows andcolumns to define a matrix of voxels or volume elements andMR signals arise from each of the individual voxels and theseare converted into image data. The image is made up of a matrixof pixels (digital matrix) and the brightness of each pixel in thematrix reflects the signal strength coming from its correspondingvoxel in the slice. During imaging, the MR signals (time domain)received from the patient from specific locations in the slice aredigitised and sent into a frequency domain space referred to asa k-space. The MR reconstruction algorithm, the 2D or 3D FourierTransform, 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. 1Nobel Prize for MRI pioneersOther significant discoveries related to MRI, are attributed toseveral individuals such as the work of Richard Ernst who workedon 2D NMR, particularly high resolution NMR spectroscopy.Additionally, Kurt Wüthrich developed NMR spectroscopy forexamining 3D biomacromolecules. Both of these individualsearned the Nobel Prize in Chemistry (Ernst in 1991 and Wüthrichin 2003). For a detailed and comprehensive coverage of the workof these scientists as well as others, the interested reader shouldrefer to a book entitled ‘The Pioneers of NMR and MagneticResonance 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 suchas Paul Lauterbur, in the United States, and Peter Mansfield inEngland. In addition, one other individual who made a contributionto MRI is Raymond Damadian in the United States.Contributions of Paul Lauterbur, PhDPaul Lauterbur obtained his PhD in Chemistry from theUniversity of Pittsburg, Pennsylvania and is now professor anddirector of the Biomedical MR Lab at the University of Illinoisat Urbana. Lauterbur’s contribution to the development of MRIfocussed on the use of magnetic field gradients for spatial localisationpurposes, a significant notion responsible for slice selectionand subsequent pixel localisation within the slice. He labelledthis technique ‘zeumatography’ from the Greek meaning ‘joiningtogether’. He was describing the superimposition of weak magneticfield gradients on the very strong stationary magnetic fieldof the main magnet (along the x, y, and z axis of the slice) togetherwith the use of RF radiation during the imaging process. Helater published a paper in Nature (1973; 242: 190–191) with thetitle ‘Image formation by induced local interactions: Examplesemploying magnetic resonance’. Paul Lauterbur shared the NobelPrize for Physiology or Medicine with Sir Peter Mansfield in2003.For more details on Dr Lauterbur, such as a photograph,education, appointments, honours and awards and research, theinterested reader should refer to web sites which were active atthe 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 MansfieldPeter Mansfield was born in 1933 in Nottingham, England.In 1962, he obtained his PhD in Physics from the Universityof London. In 1993 Peter Mansfield was knighted. In 2003, heshared the Nobel Prize in Physiology or Medicine with PaulLauterbur, for his significant contributions to the development ofMRI. As noted by Mansfield, ‘most of the major developmentsthat led to modern MRI machines came from Nottingham.’In particular, Mansfield’s work focussed on spatial localisationto create 2D slices of an object. This task is accomplished byusing weak magnetic field gradients superimposed on the mainmagnetic field of the scanner. But this took about 20 minutes toproduce an image. He was able to reduce this time to about 20mins by using ‘echo-planar imaging’, the technique that is stillused today. 2 The echo-planar technique allows MR operators todo extremely fast imaging and opens up new applications in functionalMR imaging.Peter Mansfield now works at the Magnetic ResonanceCentre School of Physics and Astronomy at the University ofNottingham. For further details, such as a photograph, education,appointments, research, honours and awards, the interested readershould visit the following web sites which were active at the timeof 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 controversyAs a result of the recognition paid to Lauterbur and Mansfield,several articles appeared in the literature with the goal of addressingwhat has been popularly called a Nobel Prize Controversy.For example, in December 2003, the journal Diagnostic Imagingfeatured an article titled ‘Nobel Mistake?’ The views are wide andvaried in describing Dr Damadian’s contribution to the developmentof MRI. Therefore, an attempt will be made here to quoterelevant extracts from several articles to shed some light on thenature of the controversy.To begin, Cartlidge 2 provides us with a small insight into thenature of the controversy. He states: ‘In particular, RaymondDamadian, a physician showed how NMR could be used to distinguishbetween cancerous and healthy tissue, took the unusualstep of making his claim for the prize in full-page advertisementsin the The Washington Post, The New York Times, and the Los

Nobel Prize for CT and MRI pioneersThe Radiographer ­Angeles Times, a few days after the awards were announced.’‘It had been clear for some time that there would be a prize forMRI, because of the impact that it has had, but it was not clearwho would be included’ says Stephen Keevil of Guy’s Hospital inLondon. ‘I am sure however, that Lauterbur and Mansfield deservethe prize.’ Keevil says that he has some sympathy for Damadianbut points out that the prize appears to have been awarded specificallyfor Lauterbur’s and Mansfield’s work on the use of magneticfield gradients saying: ‘Damadian has made major contributionsto MRI but not in this specific area.’In particular, Damadian’s work was centred on establishing T1and T2 relaxation times for healthy and diseased tissues. In March1972, he applied for a patent for an ‘Apparatus and Method forDetecting Cancer Tissue’. Subsequently, Damadian built an NMRimaging scanner that he called the ‘Indomitable’. In 1974, hereceived the patent and started a company called FONAR (FieldFocused Nuclear Magnetic Resonance). For this contributionto MRI, Damadian received the National Medal of TechnologyAward in 1988 from President Reagan. This award is the highesthonour bestowed by the President of the United States to notableinnovators in the US, see www.technology.gov/Medal/default.htm.Dr Damadian was inducted into the National Inventors Hallof Fame in 1989, for his pioneering work. For more informationon his work, the interested reader should refer to an article inScientific American 3 as well as the following web sites that wereactive 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 Imaging 4 entitled‘Is there a Nobel Prize in MRI’s Future?’ included variousopinions from several expert scientists and radiologists includingLauterbur, Ernst, Young, and Smith. From the perspective of theauthor of this brief paper, the opinion of Dr Francis Smith, professorand consultant in nuclear imaging in Scotland, providesa reasonable framework for awarding the prize. Dr Smith statedthat: ‘If the prize were given on the basis of who was first, thiswould make a mockery of what came afterwards. There are aboutnine key players, but I think that it would be fair if the prize wereshared in three ways: Damadian for his ideas, Lauterbur for showingthat they were possible, and Mansfield for further developingthe concept’. 4for their work that help physicians diagnose, treat and manage awide range of patients’ medical problems.This article serves to impress upon us there is significant valuein the study of not only the physics of imaging but the engineeringaspects as well. These are the many tools we use to produce diagnosticimages, so that our patients can benefit from our wisdom.AcknowledgmentThe author would like to express his sincere thanks to AnthonyChan, M.Eng., M.Sc., P.Eng., C.Eng., C.C.E ; Program Head andFaculty of the Biomedical Engineering Department at the BritishColumbia Institute of Technology, Burnaby, Canada; for his carefulreview of the manuscript.References1 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 scientificprominence. Diagnos Imaging 2003; 42–9.Further readingDallessio KM. RSNA Preview; Nobel Prize awarded for discoveries leading toMR 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 inMedicine: 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.htmlwww.scs.uiuc.edu/chem/lauterb.htmwww.beckman.uiuc.edu/faculty/lauterbu.htmlwww.nobel.se/medicine/laureates/2003/mansfield-cv.htmlwww.nottingham.ac.uk/~ppzwww/staff/Mansfield_P_t.htmlwww.magres.nottingham.ac.uk/~mansfield/www.technology.gov/Medal/default.htmwww.fonar.com/nobel.htmwww.invent.org/hall_of_fame/36.htmlConclusionIt is interesting to note that the Nobel Prize for Physiology orMedicine has been awarded to physicists, chemists, and engineers,