Simulations and Inversions in Photoacoustic Tomography for High Resolution Quantitative Biomedical Imaging

One out of every three people in the UK develops cancer at some stage in their life, and one in four die from it, according to the Office for National Statistics.It is well known that the early detection of cancer improves the chances of survival. For instance, malignant melanoma is a type of skin cancer that causes five deaths per day in the UK, but patients diagnosed at an early stage, when the treatments are much more effective, have an excellent prognosis with a five-year survival rate greater than 95%. A practical and inexpensive technique that could easily be deployed in clinics and hospitals to detect cancers at an earlier stage than is currently possible would therefore immediately improve survival rates.In the longer term, a better understanding of the processes and pathways that lead to cancerous tumours would aid in the development of new treatments and drugs. One of the most successful approaches to understanding disease in the human body has been to study similar diseases in small animals such as mice. There is sufficient similarity between murine and human physiology, such as in the way the immune system works, that 'mouse models' have become a mainstay of medical research. In recent years, advances in the techniques used to identify genes and proteins involved in disease mechanisms, and the increased availability of transgenic mice, have led to a demand for high-resolution, in vivo, small animal imaging modalities that can reveal where, and at what level, specific genes or proteins are being expressed, or other biomolecules or drugs are accumulating.Photoacoustic tomography is a new, inexpensive imaging technique that can provide 3D images of biological soft tissue, and has the potential to resolve structures within the tissue as narrow as a human hair (< 100 microns). By detecting the presence of small capillaries within nascent tumours, it may be able to detect cancers at an earlier stage than is currently possible. Early skin and breast tumours, for example, may be detectable using this approach. Furthermore, by using contrast agents, molecular markers or 'reporter' genes, 3D in vivo images of small animals showing the concentrations of the biomolecules of interest to within a few cells could become a realistic possibility.Photoacoustic tomography can distinguish between different biomolecules or tissues because of differences in their optical absorption spectra, ie. their colour. Small ultrasonic pulses are generated when light is absorbed in the tissue by, for instance, blood or a molecular marker. By illuminating the tissue with a colour of light that is absorbed only by the desired target, then only that target will generate ultrasound. By recording the ultrasound over several detectors, its origin can be calculated, in much the same way as we determine the location of a car horn by the difference in the time of arrival of the sound at our two ears. In this way a 3D image of the target absorber can be formed.Photoacoustic tomography clearly has great promise and the benefits to patients, clinicians and researchers could be enormous. However, some remaining technical hurdles must be overcome before all the potential benefits can be fully realised. For example, the speed at which the ultrasound travels through the tissue is not the same everywhere and so results in blurred images. Perhaps the most important outstanding problem is that of producing separate images of two or more absorbing substances (blood and a contrast agent, say) when they are simultaneously present in the tissue.The research proposed here will investigate a number of different ways to overcome the remaining challenges and so realize the full potential of photoacoustic tomography as a tool both for clinical diagnosis and high resolution imaging in biomedicine and the life sciences.