Science for Health
Ever since 1896 when X-rays were first used to display images of human skeletons and organs, doctors have realised the importance for diagnosis of being able to see inside the human body without the need for surgery. When in the mid 1970's, X-ray scanners were introduced which could provide cross-sectional pictures of any selected region of the body, a process known as computerised tomography, CT, there seemed little need for another imaging technique in addition to this excellent tool. It is not surprising that when the fledgling magnetic resonance imaging (MRI) technique entered this formidable arena its initial modest efforts were regarded with much scepticism by almost everyone except the few dedicated scientists who could foresee its potential. Developments over the last twenty-five years have fully justified the confidence of those early pioneers and the MRI method has emerged as a very powerful diagnostic imaging technique which has become the method of choice for many applications. Its ability to provide information about the state of health of organs and tissues in addition to details of their shape and appearance offers major advantages over other methods. MRI can detect differences between normal and diseased tissue in images showing exquisite detail. It is an excellent method for showing the differences between grey and white matter in brain scans for example and sometimes it can detect damage which is not observed in CT scans. In other cases it gives clear images for regions of organs that are inaccessible to X-rays because of their location within dense bone structures that absorb the X-rays and block their penetration. For the same reason it has proved to be the best imaging technique for detecting tumours within the brain stem and for characterising injuries to the spinal cord. It has become an important tool for detecting brain damage in multiple sclerosis patients and it is now the definitive method for diagnosing this disease. MRI is also an excellent method for studying heart function and blood flow, a procedure known as angiography. It has also been used in research to investigate the functions of the brain by observing changes in images of the brain caused for example by thought processes, opening up exciting possibilities for understanding the workings of the human brain. All this information is provided using procedures which have no known safety hazards. Neither ionising radiation nor radioactivity is involved. It is easy to see why the method has gained rapid acceptance and there are now several thousand MRI scanners installed for use in hospitals around the world. In fact, although there are many other uses of MRI, the rapid development of the technique has been largely driven by the needs of doctors and surgeons.
It is conceptually easy to see how X-rays can produce images. Within months of their discovery by Röntgen in 1895 they were being used to display images of skeletons and foreign objects such as bullets within the body. This was done simply by placing the part of the body between a source of X-rays and a photographic plate. The different parts of the sample absorbed the X-rays to different extents and cast a shadow or image of the object being examined. When the plate was developed the image was revealed.
But how does the MRI method work? The technique is based on a phenomenon called nuclear magnetic resonance which was discovered fifty years ago by two american scientists, Felix Bloch and Edward Purcell, who won the Nobel prize for their work in 1952. All atoms consist of outer shells of negatively charged particles called electrons buzzing around in diffuse clouds, and a dense central portion called the nucleus. Some of these nuclei behave like small bar magnets and when placed in a powerful magnetic field about half line up in the direction of the magnetic field and about half line up in the opposite direction. By providing energy in the form of radio waves these tiny magnets can be caused to change orientation, to resonate absorbing energy at a resonance frequency that depends directly on the strength of the magnetic field. When the magnetic field is changed slightly this resonance frequency also changes in a predictable fashion.
At first the magnetic resonance technique was used mainly as a research tool for determining the structures of molecules. It relied on using very uniform magnetic fields, so that every part of the sample was exposed to the same field. It was more than twenty-five years after the original discovery of the magnetic resonance phenomenon that the possibility of using non-uniform magnetic fields to produce images was first realised. This transformation into an imaging method required a brilliant piece of lateral thinking which considered the consequences of using a magnetic field which was not uniform but varied in a known way throughout the sample. This results in each distinct part of the sample experiencing its own unique magnetic field which is characteristic of its position. Nuclei at each different position will have different characteristic resonance frequencies. So, detecting the resonance frequencies of the nuclei becomes equivalent to detecting where they are in the sample, and detecting the size of the signal tells you how many nuclei there are at that position. With information relating number of atomic nuclei with position in the sample it is possible using computer programs to reconstruct a detailed three-dimensional image of the whole sample which can then be examined on a monitor screen as cross-sectional slices in any direction. The implementation of these ideas independently by Lauterbur in New York State University at Stonybrook and Mansfield and Grannell at Nottingham University signalled the beginning of a new imaging method.
More than half the human body is composed of water which as everyone knows has two atoms of hydrogen joined to one atom of oxygen - H2O. Fortunately, hydrogen has all the right properties to demonstrate the magnetic resonance effect. So your body contains more than one thousand billion billion water molecules, each acting as a sensitive radio transmitter capable of reporting on its location, its state and its surroundings. This scenario would surely be regarded as the stuff of science fiction if we did not know that this indeed is the very basis of the MRI technique.
By 1977, the first images of the human body were being reported, one of the earliest being an image of a wrist showing features as small as about half a millimetre in diameter. Since those early days developments in the method have resulted in instruments capable of producing images showing details of size and shape equal to those seen in actual anatomical sections. Although the pioneering work originated in academic laboratories the final success of the MRI method owes a great deal to the inventiveness and ingenuity of the leading instrument manufacturers.
Anyone who has been involved in fund raising for a hospital MRI scanner knows that such instruments are expensive and typical installations can cost around one-and-a-half million pounds. At the heart of every MRI scanner is a very large magnet which can have a field strength of more than eighty thousand times the strength of the earth's magnetic field. Often the magnet is a superconducting solenoid coil which requires cooling to the temperature of liquid helium. At this temperature of around minus two hundred and seventy degrees centigrade, the superconducting coil of wire, the magnet, loses its resistance to electricity. After initially charging it with electricity the power is switched off leaving a persistent electric current flowing which produces the magnetic field. The bore of the superconducting magnet is sufficiently large to contain an adult human body. There are also facilities to generate the non-uniform magnetic field, a radiofrequency transmitter and receiver and a probe device that surrounds the relevant part of the body and transmits and receives the radiofrequency signals. The equipment also needs associated computers for controlling the scanning process, acquiring and analysing the data and reconstituting and displaying the three-dimensional images.
One of the drawbacks of the MRI technique in the early days was the length of time it took to record images. This was particularly critical for organs which would move during examination such as the heart and abdomen. However, a new procedure has been developed which can produce a complete well-resolved image following application of a single pulse of radiowaves, thus leading to shorter examination times. This method, developed by Peter Mansfield at Nottingham University, is beginning to open up many new applications involving heart, abdomen, chest and brain imaging. For example, it allows moving images of the working heart to be recorded and these can be used to characterise abnormalities. It is also beginning to allow chest images to be recorded in the brief time for which a breath can be held.
One of the important advantages of the MRI method over X-ray CT scanning is that it is possible to vary the contrast in the images in a controlled manner. MRI examinations are usually carried out by applying a sequence of pulses of radiowaves repetitively. Each of these pulses causes the hydrogen nuclei to absorb energy and the nuclei then need time to lose this energy and return to their equilibrium state before they receive the next pulse. Their speed of recovery depends on their surroundings and their movement. This means that the persistence of the signals from hydrogen nuclei in water molecules in different tissues may be different and it is possible to take advantage of these differences to obtain images of soft tissues which have different image contrast characteristics. The ability to control the image contrast is also useful when detecting water molecules in flowing samples such as blood. Because the flow of the blood continuously replenishes regions under examination with 'fresh' water molecules these regions appear in such images as bright intense signals. This has been successfully applied to examination of the lungs, brain and major arteries. MRI imaging of the heart allows assessment of normal heart function and can also be used with other well-established procedures based on ultrasound to examine heart disease by providing reliable estimates of blood flow. In some MRI procedures contrast agents are injected to change the recovery characteristics of the blood: this is particularly useful for measuring blood perfusion in brain tissue and has become a powerful new method for investigating brain diseases such as stroke.
A great attraction of MRI is its ability to monitor the effects of medicines and treatments in a safe and acceptable manner. Attitudes towards the use of even small doses of radiation have changed drastically over the years. Only thirty years ago it was common practice for X-ray machines to be used for trivial purposes such as in shoe shops for checking the fitting of new shoes. Nowadays, a more cautious approach to radiation has led to such practices being discontinued. In medical applications, considerable efforts have been made to decrease the radiation levels used in X-ray scans. Radiation risks become very important in cases where multiple examinations are required, as for example in following the progress of treatment and MRI is an ideal method for such examinations. Good examples are recent studies on patients with multiple sclerosis (MS). The MRI images of such patients reveal characteristic damage in the brain and spine which is diagnostic of the disease and very easy to detect. In recent treatments, the response of MS patients to interferon, a protein produced by our immune systems, has been followed with MRI by taking brain scans every four to six weeks. These procedures are being conducted as part of controlled trials and often show a significant reduction in disease activity for interferon-treated patients as judged both clinically and by the absence of new or increasing damage in the brain as indicated by MRI.
Another area where MRI has rapidly gained popularity is in the safe diagnosis of sport-related injuries involving tendons and ligaments in the shoulder, elbow, wrist, hand, spine, pelvis, knee, ankle and foot. Tendons and ligaments appear as dark areas in MRI images and it is easy to monitor alterations in their size, shape and continuity by examining the images. Partial tears and complete tears of tendons and ligaments are readily detected. In some cases MRI can be used to replace more invasive procedures that are sometimes used for examining such injuries. A typical example is diagnostic knee arthroscopy which involves introducing a sharp probe into the knee joint to investigate exercise-induced damage to ligaments and menisci or cartilages, the shock-absorbing pads. Fragmentation of these structures can cause the knee to lock in position and prevent bending, or to give way. MRI is now used to detect meniscal tears and fragmentation within the knee and can often replace the need for diagnostic arthroscopy.
While many of the original MRI installations were in research and teaching hospitals, the technique is now being used more widely in general hospital environments. X-ray CT scanning is still the dominant imaging method used in general medical applications but there are many applications for which MRI images of soft tissues are now being requested. There are major neurological applications, such as brain scanning for suspected encephalitis and multiple sclerosis, and several important orthopaedic applications involving spines, knees and hips. It can usefully be applied to cases of suspected spinal cord compression which often results from spinal tumours or from slipped disks. In these cases, MRI images can give the precise location and nature of the compression and help in ensuring that appropriate treatment is quickly applied. Earlier investigative procedures involved injecting dyes into the spinal column and then monitoring their distribution using X-rays. Such invasive procedures can have undesirable side effects resulting in inflammation of neural tissues which causes shooting pains. Clearly the non-invasive MRI method is a much more attractive alternative technique for such investigations.
One of the most recent and exciting applications of MRI, called functional MRI, attempts to study the human mind. By stimulating the brain, either through the senses or by thought processes, changes in MRI images occur corresponding to specific places in the brain. This opens up the possibility of using MRI to study the underlying processes controlling the working of the brain and may help to elucidate the changes that occur in such processes as memory formation. For example, changes in brain MRI images have been detected in response to seeing various flashing light sequences, to performing certain actions, such as finger movements, or to undertaking various specific thought processes. Over a century ago, doctors discussed such brain activity in terms of local changes in blood flow within the brain. Recent MRI work indicates that these changes can be related to the amount of oxygen in the blood. This exciting new area of MRI promises to make important contributions to neuroscience studies in the future.
We have been concentrating on MRI images obtained by detecting hydrogen nuclei in water in the samples. However, other types of molecules containing hydrogen, such as fats, can also be examined. The hydrogen atoms in these molecules absorb energy at a different frequency from the hydrogen in water so it is possible to make a separate image viewing the fat content of a sample. Other atoms such as phosphorus, sodium, helium and xenon can also be used to obtain images. For example, phosphorus images provide valuable information about how different parts of the body are working under various conditions such as oxygen shortage resulting from reduced blood flow. Recently, excellent MRI images of the airways in human lungs have been obtained by detecting inert gases such as helium or xenon inhaled by the patient.
It is interesting to imagine what future improvements in MRI methodology might be possible. We have seen that the MRI technique has a lower detection sensitivity than X-ray CT scanning and continued efforts will be made to improve this to the point where complete body scans will be possible in a few minutes. As the detection sensitivity improves, MRI will be used increasingly to examine organs such as abdomen and chest which have previously been the domain of X-ray CT scanning. MRI will also be used more widely to provide real-time images to guide internal surgical procedures. Several imaging instruments for use in such interventional MRI operations have already been delivered to surgery departments. Another area of improvement will be in magnet design. The technology for making superconducting magnets is continuously improving and this will result in stronger magnets at lower cost becoming available in the future: these will improve detection sensitivity and assist in developing other areas of MRI which are still in their infancy. Improved open-magnet designs could eventually provide more versatile instruments which do not require the patient to enter the bore of the magnet. This will certainly be good news for patients with claustrophobic tendencies! The enormous scope and potential of MRI has already been demonstrated and its full benefits will be realised as MRI scanners become more widely available in general hospitals.
This essay was published in the Mill Hill Essays 1996
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