Towards disease diagnosis through spectrochemical imaging of tissue architecture.

This proposal brings together a critical mass of scientists from the Universities of Cardiff, Lancaster, Liverpool and Manchester and clinicians from the Christie, Lancaster and Liverpool NHS Hospital Trusts with the complementary experience and expertise to advance the understanding, diagnosis and treatment of cervical, oesophageal and prostate cancers. Cervical and prostate cancer are very common and the incidence of oesophageal is rising rapidly. There are cytology, biopsy and endoscopy techniques for extracting tissue from individuals who are at risk of developing these diseases. However the analysis of tissue by the standard techniques is problematic and subjective. There is clearly a national and international need to develop more accurate diagnostics for these diseases and that is a primary aim of this proposal. Experiments will be conducted on specimens from all three diseases using four different infrared based techniques which have complementary strengths and weaknesses: hyperspectral imaging, Raman spectroscopy, a new instrument to be developed by combining atomic force microscopy with infrared spectroscopy and a scanning near field microscope recently installed on the free electron laser on the ALICE accelerator at Daresbury. The latter instrument has recently been shown to have considerable potential for the study of oesophageal cancer yielding images which show the chemical composition with unprecedented spatial resolution (0.1 microns) while hyperspectral imaging and Raman spectroscopy have been shown by members of the team to provide high resolution spectra that provide insight into the nature of cervical and prostate cancers. The new instrument will be installed on the free electron laser at Daresbury and will yield images on the nanoscale. This combination of techniques will allow the team to probe the physical and chemical structure of these three cancers with unprecedented accuracy and this should reveal important information about their character and the chemical processes that underlie their malignant behavior. The results of the research will be of interest to the study of cancer generally particularly if it reveals feature common to all three cancers. The infrared techniques have considerable medical potential and to differing extents are on the verge of finding practical applications. Newer terahertz techniques also have significant potential in this field and may be cheaper to implement. Unfortunately the development of cheap portable terahertz diagnositic instruments is being impeded by the weakness of existing sources of terahertz radiation. By exploiting the terahertz radiation from the ALICE accelerator, which is seven orders of magnitude more intense that conventional sources, the team will advance the design of two different terahertz instruments and assess their performance against the more developed infrared techniques in cancer diagnosis. However before any of these techniques can be used by medical professionals it is essential that their strengths and limitations of are fully understood. This is one of the objectives of the proposal and it will be realised by comparing the results of each technique in studies of specimens from the three cancers that are the primary focus of the research. This will be accompanied by developing data basis and algorithms for the automated analysis of spectral and imaging data thus removing subjectivity from the diagnostic procedure. Finally the team will explore a new approach to monitoring the interactions between pathogens, pharmaceuticals and relevant cells or tissues at the cellular and subcellular level using the instruments deployed on the free electron laser at Daresbury together with Raman microscopy. If this is successful, it will be important in the longer term in developing new treatments for cancer and other diseases.