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.

The research programme will benefit the UK and world wide human population through improvements in health care, specifically through the development of new approaches to the diagnosis, and fundamental understanding of oesophageal, cervical and prostate cancers and more generally by the development of new techniques for fundamental research into the interactions between pathogens exploited as vectors or novel pharmaceutical-directed therapeutic approaches with healthy and diseased tissue.

More immediately the beneficiaries include all health care professionals; physicians, surgeons, pathologists, radiologists, scientists, nurses and dieticians working with these cancers and instrument manufacturers developing innovative technology for patient benefit.

All three cancers at the focus of the research programme have either a very high incidence or a rapidly increasing incidence in the UK and world population and the key to treating them is to obtain an early diagnosis. Considerable effort and resources have been invested in identifying individuals who are at risk of developing these diseases and there are cytology, biopsy and endoscopy techniques for extracting tissue for analysis. However such screening programmes are expensive. Some £ 200 million a year is needed in the UK alone to maintain the infrastructure to screen for cervical cancer so it is critical to optimize and simplify the technologies involved. Unfortunately the analysis of tissues by standard cytology and histology techniques remains significantly limited for these diseases. Typically for prostate cancer two histologists will only agree on the classification of excised tissue based on the Gleeson scale 50% of the time or less and false positives can lead to serious but unnecessary costly treatment and false negatives can be fatal. There is clearly a need to develop more accurate diagnostics for these diseases and that is a primary aim of this proposal.

One result of this proposal is that the UK will benefit from more informed policy making in the health section and the clinical members of the team are well placed to facilitate this though their membership of appropriate national policy bodies.

There is a UK and world-wide market for instruments that will deliver improved and more cost effective health care. UK companies are well placed to exploit this market and will benefit from the critical assessment of the potential of infrared (IR) and terahertz (THz) techniques for medical applications, one of the objectives of the proposal. The research programme will advance the development of several low cost portable IR and THz instruments which are expected to be used first as auxiliary instruments in medical practice. Combined with biospectral database for these cancers, and linked with refined data processing algorithms, they will be used by the developers of the instrumentation and medical professionals in clinical trials and if successful will augment, and may eventually replace, existing diagnostic procedures.

The understanding of pathogen-cell and drug-cell interactions and the exploration of a novel means for their direct study have considerable potential for use in the pharmaceutical industry, a sector where the UK is strong, in high-throughput screening in drug development.

Improved IR and THz instruments will find applications across a wide range of fields including security, plasma diagnostics, forensics, quality control, pharmaceutical, medical, automotive and cultural heritage. The industrial exploitation of these technological advances will be facilitated by patent protection of the resulting IPR and the close links between the applicants and instrument companies notably Anasys Instruments, QMC Instruments and TeraView. It is anticipated that this will bring licensing revenue to the collaborating Universities in addition to improving the commercial success of UK industry.