Download Nobel Prize for CT and MRI pioneers

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
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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
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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,
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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