| The 2003
Nobel Prize in Physiology or Medicine awarded for "magnetic
resonance imaging"
The
Nobel Prize in Physiology or Medicine for 2003 was awarded
jointly to
Paul C Lauterbur and Peter Mansfield
Imaging of human internal organs with exact and non-invasive
methods is very important for medical diagnosis, treatment
and follow-up. This year's Nobel Laureates in Physiology or
Medicine have made seminal discoveries concerning the use
of magnetic resonance to visualize different structures. These
discoveries have led to the development of modern magnetic
resonance imaging, MRI, which represents a breakthrough in
medical diagnostics and research.
Atomic nuclei in a strong magnetic field rotate with a frequency
that is dependent on the strength of the magnetic field. Their
energy can be increased if they absorb radio waves with the
same frequency (resonance). When the atomic nuclei return
to their previous energy level, radio waves are emitted. These
discoveries were awarded the Nobel Prize in Physics in 1952.
During the following decades, magnetic resonance was used
mainly for studies of the chemical structure of substances.
In the beginning of the 1970s, this year’s Nobel Laureates
made pioneering contributions, which later led to the applications
of magnetic resonance in medical imaging.
Paul Lauterbur (born 1929), Urbana, Illinois, USA, discovered
the possibility to create a two-dimensional picture by introducing
gradients in the magnetic field. By analysis of the characteristics
of the emitted radio waves, he could determine their origin.
This made it possible to build up two-dimensional pictures
of structures that could not be visualized with other methods.
Peter Mansfield (born 1933), Nottingham, England, further
developed the utilization of gradients in the magnetic field.
He showed how the signals could be mathematically analysed,
which made it possible to develop a useful imaging technique.
Mansfield also showed how extremely fast imaging could be
achievable. This became technically possible within medicine
a decade later.
Magnetic resonance imaging, MRI, is now a routine method
within medical diagnostics. Worldwide, more than 60 million
investigations with MRI are performed each year, and the method
is still in rapid development. MRI is often superior to other
imaging techniques and has significantly improved diagnostics
in many diseases. MRI has replaced several invasive modes
of examination and thereby reduced the risk and discomfort
for many patients.
Nuclei of hydrogen atoms
Water constitutes about two thirds of the human body weight,
and this high water content explains why magnetic resonance
imaging has become widely applicable to medicine. There are
differences in water content among tissues and organs. In
many diseases the pathological process results in changes
of the water content, and this is reflected in the MR image.
Water is a molecule composed of hydrogen and oxygen atoms.
The nuclei of the hydrogen atoms are able to act as microscopic
compass needles. When the body is exposed to a strong magnetic
field, the nuclei of the hydrogen atoms are directed into
order – stand "at attention". When submitted
to pulses of radio waves, the energy content of the nuclei
changes. After the pulse, a resonance wave is emitted when
the nuclei return to their previous state.
The small differences in the oscillations of the nuclei are
detected. By advanced computer processing, it is possible
to build up a three-dimensional image that reflects the chemical
structure of the tissue, including differences in the water
content and in movements of the water molecules. This results
in a very detailed image of tissues and organs in the investigated
area of the body. In this manner, pathological changes can
be documented.
Several Nobel Prizes
The resonance phenomenon is governed by a simple relation
between the strength of the magnetic field and the frequency
of the radio waves. For every type of atomic nucleus with
unpaired protons and/or neutrons, there is a mathematical
constant by which it is possible to determine the wavelength
as a function of the strength of the magnetic field. This
phenomenon was demonstrated in 1946 for protons (the smallest
of all atomic nuclei) by Felix Bloch and Edward Mills Purcell,
USA. They were awarded the Nobel Prize in Physics in 1952.
Other fundamental discoveries concerning magnetic resonance
have in recent years resulted in two Nobel Prizes in Chemistry.
In 1991, Richard Ernst, Switzerland, was awarded for his contributions
to the development of the methodology of high resolution nuclear
magnetic resonance spectroscopy. In 2002, Kurt Wüthrich,
also Switzerland, was awarded for his development of nuclear
magnetic resonance spectroscopy for determination of the three-dimensional
structure of biological macromolecules in solution.
Discoveries of importance to medicine
This year's Nobel Laureates in Physiology or Medicine are
awarded for crucial achievements in the development of applications
of medical importance. In the beginning of the 1970s, they
made seminal discoveries concerning the development of the
technique to visualize different structures. These findings
provided the basis for the development of magnetic resonance
into a useful imaging method.
Paul Lauterbur discovered that introduction of gradients
in the magnetic field made it possible to create two-dimensional
images of structures that could not be visualized by other
techniques. In 1973, he described how addition of gradient
magnets to the main magnet made it possible to visualize a
cross section of tubes with ordinary water surrounded by heavy
water. No other imaging method can differentiate between ordinary
and heavy water.
Peter Mansfield utilized gradients in the magnetic field
in order to more precisely show differences in the resonance.
He showed how the detected signals rapidly and effectively
could be analysed and transformed to an image. This was an
essential step in order to obtain a practical method. Mansfield
also showed how extremely rapid imaging could be achieved
by very fast gradient variations (so called echo-planar scanning).
This technique became useful in clinical practice a decade
later.
Rapid development within medicine
The medical use of magnetic resonance imaging has developed
rapidly. The first MRI equipments in health were available
at the beginning of the 1980s. In 2002, approximately 22 000
MRI cameras were in use worldwide, and more than 60 million
MRI examinations were performed.
A great advantage with MRI is that it is harmless according
to all present knowledge. The method does not use ionizing
radiation, in contrast to ordinary X-ray (Nobel Prize in Physics
in 1901) or computer tomography (Nobel Prize in Physiology
or Medicine in 1979) examinations. However, patients with
magnetic metal in the body or a pacemaker cannot be examined
with MRI due to the strong magnetic field, and patients with
claustrophobia may have difficulties undergoing MRI.
Especially valuable for examination of the brain and the spinal
cord
Today, MRI is used to examine almost all organs of the body.
The technique is especially valuable for detailed imaging
of the brain and the spinal cord. Nearly all brain disorders
lead to alterations in water content, which is reflected in
the MRI picture. A difference in water content of less than
a percent is enough to detect a pathological change.
In multiple sclerosis, examination with MRI is superior for
diagnosis and follow-up of the disease. The symptoms associated
with multiple sclerosis are caused by local inflammation in
the brain and the spinal cord. With MRI, it is possible to
see where in the nervous system the inflammation is localized,
how intense it is, and also how it is influenced by treatment.
Another example is prolonged lower back pain, leading to
great suffering for the patient and to high costs for the
society. It is important to be able to differentiate between
muscle pain and pain caused by pressure on a nerve or the
spinal cord. MRI examinations have been able to replace previous
methods which were unpleasant for the patient. With MRI, it
is possible to see if a disc herniation is pressing on a nerve
and to determine if an operation is necessary.
Important preoperative tool
Since MRI yields detailed three-dimensional images, it is
possible to get distinct information on where a lesion is
localized. Such information is valuable before surgery. For
instance, in certain microsurgical brain operations, the surgeon
can operate with guidance from the MRI results. The images
are detailed enough to allow placement of electrodes in central
brain nuclei in order to treat severe pain or to treat movement
disorders in Parkinson's disease.
Improved diagnostics in cancer
MRI examinations are very important in diagnosis, treatment
and follow-up of cancer. The images can exactly reveal the
limits of a tumour, which contributes to more precise surgery
and radiation therapy. Before surgery, it is important to
know whether the tumour has infiltrated the surrounding tissue.
MRI can more exactly than other methods differentiate between
tissues and thereby contribute to improved surgery.
MRI has also improved the possibilities to ascertain the
stage of a tumour, and this is important for the choice of
treatment. For example, MRI can determine how deep in the
tissue a colon cancer has infiltrated and whether regional
lymph nodes have been affected.
Reduced suffering for patients
MRI can replace previously used invasive examinations and
thereby reduce the suffering for many patients. One example
is investigation of the pancreatic and bile ducts with contrast
media injection via an endoscope. This can in some cases lead
to serious complications. Today, corresponding information
can be obtained by MRI.
Diagnostic arthroscopy (examination with an optic instrument
inserted into the joint) can be replaced by MRI. In the knee,
it is possible to perform detailed MRI studies of the joint
cartilage and the cruciate ligaments. Since no invasive instrument
is needed in MRI, the risk of infection is eliminated.
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