A Novel Deep Raman Spectroscopy Platform for Non-Invasive In-Vivo Diagnosis of Breast Cancer

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://pubs.rsc.org/en/content/articlelanding/2016/cs/c5cs00466g. 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 significantly reduce needle biopsy, in around 80% of those recalled following mammographic screening this step is unnecessarily - ie leading to the diagnosis of benign lesions. Our novel approach would allow for more accurate and immediate diagnosis in conjunction with mammography 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, for example when pre- operatively staging the disease and particularly when non-invasively monitoring tumour response during chemo/radiotherapy. 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 in its conventional form it has been restricted to sampling the tissue surface of much less than 1 mm deep. The 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 Raman. Following on from our previous project, where we were able to demonstrate conceptually a ~100x improvement in signal recovery compared to our early feasibility work, we are now able to rapidly develop a platform for real-clinical tools using this approach. We propose to make major breakthroughs in this area and advance diagnostics particularly focussed on breast cancer and lymph node metastasis initially as focused case studies and then potentially applied to prostate cancers (outside the scope of this proposal). This will be explored as a joint cross-disciplinary research venture between Profs Stone and Matousek, the two key researchers in this area. We now seek funding to progress this work in a timely manner by developing a novel medical diagnostic platform of major societal impact. 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 expertise to tackle these challenging issues.