Health Sciences

Radiotherapy

In cancer biology, imaging and therapy are inextricably linked. In the case of the proposed Beamline 10 at the Australian Synchtrotron, the capabilities designed for excellent imaging are also ideally suited for the study and development of novel radiotherapy techniques.

The major problems with the radiotherapy lie in determining the extent of the spread of the disease and delivering sufficient radiation to the tumour without damaging surrounding healthy tissues. These problems are particularly acute in tumours where the surrounding tissue is extremely sensitive. Synchrotron radiation is able to deliver high doses only to the targetted areas significantly better than current clinical techniques. Three methods are currently under investigation at overseas synchrotrons: photon activation therapy (PAT), computed tomography (CT) therapy, and microbeam radiation therapy.

Photon activation and CT therapy both use specific X-ray energies that are preferentially absorbed by an element that has been delivered into the tumour. In PAT a chemical agent such as cis-platinum, which is also used in chemo-therapy, is introduced and concentrates in the tumour. By choosing the correct energy the X-ray beam interacts preferentially in the tumour and delivers a highly localized dose. CT therapy also uses a contrast agent such as iodine and that also concentrates in the tumour. It takes advantage of beam spreading effects and stereotactic methods to spare normal tissues.

Perhaps the most exciting possibility is MRT. Here, extremely large radiation doses are applied to tissues in an array of micrometre-thick highly collimated X-ray beams. The extraordinary aspect of microbeam radiation is that it spares healthy tissue far better than large-area beams of the same dose, and yet the tumour is still damaged. The method has been used with great effectiveness to deliver doses in excess of 1000 Gy to live animals; a dose of 10 Gy delivered using conventional methods is lethal. The reason for this effect is unknown but is a fertile area for further study

It is possible that therapies utilizing this effect may revolutionize the treatment of some kinds of cancers which are currently untreatable. A string programme of research into the nature of this effect, together with determining the most effective way of delivering the dose, is planned to be a significant activity on the Australian Synchrotron. However, it should be noted that much research will be required before MRT could be considered for clinical application.

Biomedical imaging

Despite being by far the most popular medical imaging modality, lack of soft tissue contrast is a significant problem in both medical and biomedical X-ray imaging. The relatively small variations in density and composition of soft tissues mean that their X-ray attenuation characteristics are very similar. Conventional radiaography produces images through the differential absorption of X-rays, and so provides very little soft tissue contrast unless high doses are employed, as in computed tomography. Synchrotron-based imaging techniques produce high resolution images using differences in the refraction and scatter of X-rays as they pass through tissue. Genuine soft tissue contrast with micrometre-scale resolution is possible.

Furthermore, the collimation and monochromaticity of an imaging beamline allows high resolution images to be recorded at far lower doses than required by conventional equipment. This capability permits longitudinal studies (series imaging) to be performed for investigations where the dose required by conventional imaging would confound the experiment.

The power of these imaging techniques is particularly suited to the study of living processes. It will be possible to exploit the proximity of the Australian Synchrotron to Monash University, The University of Melboure, CSIRO and Monash Medical Centre to bring together the expertise and facilities that will make the imaging beamline (beamline 10) one of only two beamlines in the world capable of work on live animals. The studies of live animals for medical research is an area that is impractical under overseas access programs, and so relates to an essentially new and numerous Australian user class that has not been served in the past.

One of the problems at present is that animals are often sacrified in order to obtain anatomical information at high resolution. The proposed imaging beamline will allow in vivo imaging of small animals and so provide the major advantage of allowing longitudinal studies to be conducted. This has the significant advantage of following the same animal through the process and also dramatically reducing the number of animals sacrificed in a study.

Mammography

Two major areas where soft tissue contrast is vital are breast and lung imaging. Both breast and lung cancer are major killers and better methods of imaging these diseases would have a major impact on health care.

Screening for breast cancer, which is the biggest killer of women in the 35 to 55 year old age group, is based entirely on soft tissue X-ray absorption contrast. As a result, mammography, while having been proven to reduce mortality, suffers from some major deficiencies. In particular, it is non-specific, resulting in a large number of unnecessary biopsies, and it does not work well in women below the age of 50. The potential benefits of phase contrast imaging to improving the success of mammography in detecting cancer are enormous. Work by others has shown that the contrast increases by as much as 25 times by employing phase contrast. The beamline to be constructed would be used as a 'gold standard' facility to develop improved techniques for breast imaging.

Lung imaging

Anyone who has had a chest X-ray knows that the lungs are largely invisible to all but the highly-trained eye of a radiologist. However, the air-tissue interfaces in the lung appear with startling clarity using phase contrast imaging. This is particularly applicable to human babies, and an Australian project at a SPring-8 beamline is planned to investigate the potential for developing technology to image lung clearance at birth.

Phase contrast techniques offer enormous opportunities for the study of lung function and disease in both humans and animals. Examples include:

• The detailed study of the development of respiratory function in marsupials that are born in an embryonic state and yet can still breathe
• Longitudinal studies of the effect of anti-cancer therapies on mice and other animal models.

In addition to the dramatic improvements offered by phase contrast, workers at the ESRF have demonstrated xenon contrast respiration-gated synchrotron radiation computed tomography (SRCT) with a spatial resolution at the level of the respiratory lobule (terminal bronchiole and alveoli). This technique allows direct quantification of xenon as an inhaled contrast agent based on K-edge subtraction imaging and hence the dynamics of xenon wash-in can be used to calculate regionally specific quantitative maps of lung ventilation. Examples of the use of this technique include:

• Identifying local variations in lung function cased by diseases such as asthma and chronic obstructive pulmonary disease.
• Testing the efficacy of pharmaceuticals on respiratory dysfunction.