Sir Peter Mansfield of the University of Nottingham and Paul C. Lauterbur of the University of Illinois share the Nobel Prize for Medicine for their work on MRI.
MAGNETIC Resonance Imaging (MRI) is perhaps the most important non-invasive diagnostic tool in today's medicine. This year's Nobel Prize in Medicine has been awarded jointly to the 74-year-old Paul Lauterbur of the University of Illinois, United States, and the 70-year-old Sir Peter Mansfield of the University of Nottingham, United Kingdom, who made the technique of modern MRI possible with their seminal discoveries in the 1970s that have led to the use of `nuclear magnetic resonance (NMR)' for exact visualisation of the various internal body structures.
The phenomenon of NMR itself was discovered in 1946 by American scientists Felix Bloch and Edward Purcell who were awarded the Nobel Prize in Physics in 1952. Indeed, other fundamental discoveries arising from NMR have resulted in two Nobel Prizes in Chemistry. In 1991, Richard Ernst was honoured for the development of high resolution NMR spectroscopy, an important analytical tool in chemistry. Last year Kurt Wuthrich got the prize for his work using NMR spectroscopy to determine 3D structures of biological macromolecules in solution. The work of Lauterbur and Mansfield constitutes a breakthrough in the use of principles of physics in medical diagnostics and research.
What is NMR? Spinning atomic nuclei are tiny magnets. In a strong external magnetic field the nuclei get ordered along specific orientations and rotate with a frequency that is dependent on the strength of the magnetic field. Different atomic nuclei have different characteristic frequencies. The energy of the spinning nuclei can be increased if they are made to absorb radio waves of their characteristic frequency. This is the familiar phenomenon of resonance. When the nuclei return to the previous energy states, radio waves are emitted. The emitting nuclei can be characterised by analysing the frequency spectrum. In the early decades following the discovery, NMR was mainly used for characterising chemical substances. However, the technique only revealed information of the substance as a whole and nothing of the internal structure of the sample until the pioneering work of this year's Nobel laureates, which led to the application of NMR to medical imaging.
MEDICAL imaging exploits the simple fact that water constitutes two-thirds of the human body weight. Water is a molecule composed of hydrogen and oxygen atoms. The nuclei of hydrogen atoms act as the tiny magnets that can be oriented in a strong magnetic field. The energy of the hydrogen atoms changes when a pulse of radio waves of appropriate resonance frequency is applied. After the pulse, the nuclei emit the resonance radio wave and return to their original energy state.
There are differences in water content among tissues and organs. The pathology of many diseases involves changes in this water content and this is reflected in the MR image. The small differences in the oscillations of the nuclei are detected and by the use of advanced computer processing, a 3D image can be generated that reflects the chemical structure of the tissue, including differences in water content and in the movement of the water molecules. The pathological changes can be studied with the help of the detailed images of tissues and organs in the investigated area.
Lauterbur discovered that instead of a constant magnetic field over a given volume, introduction of gradients in the field - variation with position - 2D images of structures could be obtained, which was not possible earlier. In 1973, he described how using gradients it was possible to visualise a cross-section of tubes with ordinary water surrounded by heavy water. No other imaging technique can differentiate between ordinary water and heavy water.
Mansfield took the idea further and showed that one could use the gradients to detect the differences in resonance across a sample. He developed the technique of detecting the emitted signals rapidly, mathematically analysing them and turning them into an image - an important step in realising the technique as a practical tool. Mansfield also evolved what is known as Echo Planar Imaging (EPI), which is essentially an extremely rapid imaging technique using very fast field gradients. Traditional MRI works by scanning essentially one line at a time. In order to make up an image, a series of such lines have to be scanned and assembled into a picture. EPI is basically a snapshot type of MRI that allows an image to be scanned all at once. This makes the process a lot quicker and renders 3D imaging feasible since a series of 10 scans would generate 10 `slice' pictures.
Since the work of these two scientists, MRI has grown rapidly as a reliable technique for non-invasive diagnosis and is constantly being improved. The first MRI equipment for applications in medicine made their appearance in the 1980s. Today it is routinely used the world over. In 2002, about 22,000 MRI cameras were in use worldwide and more than 60 million MRI examinations were performed. Unlike X-ray (Nobel Prize in Physics in 1901) or computer tomography (Nobel Prize in Medicine in 1979), MRI does not use any ionizing radiation and is therefore safe. MRI has significantly improved diagnostics in many diseases and has replaced several invasive modes of investigation, thereby reducing the risk and discomfort of patients. (However, patients with magnetic metal in the body or a pacemaker cannot use MRI owing to the use of strong magnetic field in the technique).
MRI is particularly valuable for imaging the brain and the spinal cord. Nearly all brain disorders lead to changes in the water content and even 1 per cent difference can cause pathological change. MRI can pick up these changes. Multiple sclerosis arises from the local inflammation of the brain and the spinal cord. MRI can detect where the inflammation has occurred in the nervous system, how severe it is and the impact of treatment. Another example is its use in diagnosing prolonged lower back pain. MRI can make a distinction between muscular pain and pain arising from pressure on a nerve or on the spinal cord. It enables a decision on whether surgical intervention is necessary.
Since MRI yields detailed 3D images, it can detect lesions, that is, valuable pre-operative information. For example, in certain microsurgical brain operations, MR images can guide the surgical procedure. The images are detailed enough to allow placement of electrodes in certain brain nuclei in order to treat severe pain or to treat movement disorders in Parkinson's disease. MRI examinations have become very important in diagnosis, treatment and follow-up of cancer. The images can reveal the exact nature of the tumour, a valuable aid to surgery or radiation therapy.
MRI has over the years replaced several invasive diagnostic techniques. Investigation of the pancreas and bile duct earlier used the painful technique of contrast media injection via an endoscope often resulting in serious complications. Now MRI can provide the information. Similarly MRI angiography and MRI arthroscopy (examination by inserting an optical instrument) are being replaced by MRI. Since no invasive instrument is used, the risk of any infection is eliminated.
The societal impact of the contributions of Lauterbur and Mansfield has thus been truly immense.