Title: A novel Deep Raman spectroscopy platform for non-invasive in situ molecular analysis of disease specific tissue compositional changes.
Funder: Engineering and Physical Sciences Research Council

Abstract: Recently, we have pioneered a portfolio of revolutionary optical technologies in the area of laser spectroscopy, namely deep Raman spectroscopy, for non-invasive molecular probing of biological tissue. The developments have the potential of making a step-change in many fields of medicine including cancer diagnosis. The techniques comprise spatially offset Raman spectroscopy (SORS) and Transmission Raman (both patented by the applicants). The methods are described in detail in a tutorial review: http://www.rsc.org/Publishing/Journals/CS/article.asp?doi=b614777c . There is an urgent clinical need for early objective diagnosis and prediction of likely treatment outcomes for many types of subsurface cancers. This is not addressed by existing technologies. There are numerous steps along the cancer clinical pathway where real-time, in vivo, molecular specific disease analysis would have a major impact. This would allow for more accurate and immediate diagnosis at first presentation, by improving screening or surveillance techniques, leading to earlier diagnosis and better treatment outcomes. Secondly it would allow surgical margin assessment and treatment monitoring in real-time and thirdly identification of metastatic invasion in the lymphatic system during routine surgery. There are numerous other areas where a rapid molecular analysis of a tissue sample in the clinic or theatre environment would allow improved clinical decision-making. Clearly these approaches would be beneficial to the patient by reducing cancer recurrence rates; but also by minimising the numbers of invasive procedures required, thus reducing costs and patient anxiety. Raman spectroscopy is a highly molecular-specific method, which itself has proven to be a useful tool in early epithelial cancer diagnostics, although it has been restricted to sampling the tissue surface of less than 1 mm deep. Our new technology unlocks unique access to tissue abnormalities of up to several cm's deep, i.e. at depths one to two orders of magnitude higher than those previously possible with conventional Raman. We propose to make major breakthroughs in this area and advance diagnostics (including cancer margin assessment and staging) particularly focussed on breast cancer and lymph node metastasis initially as focused case studies and then potentially applied to prostate cancers (not included directly in this proposal). This will be explored as a joint cross-disciplinary venture between Profs Stone and Matousek, the two key researchers in this area, who between them have pioneered the concepts and have established a team of cross-disciplinary scientists and clinicians to advance this field. To fully capitalise on our international lead, we now seek funding to progress this work in a timely manner by developing a novel medical diagnostic platform. We propose to bring together key players from multidisciplinary areas covering physical sciences, spectroscopy, radiology, cancer diagnostic and therapeutic surgery, and histopathology to exploit all of the relevant skills and develop a critical mass of researchers. The principal collaborating teams at the heart of the programme will include: 1) Matousek group in Central Laser Facility at Rutherford Appleton Laboratory focussing on maximising the potential of the technique by implementing further technological developments. 2) Stone group with 17 years experience of applied clinical spectroscopy to develop and evaluate the technology applied to human tissues and undertake complex multivariate analysis to distil the data into relevant diagnostic outputs.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS