Title: Near infrared LED illumination and endoscopy for image guided cancer surgery
Funder: Department of Health and Social Care

Abstract: Current surgery is almost exclusively undertaken using visible light, either by the surgeon directly viewing the surgical site by eye, or by the recording of images using colour camera systems which are viewed on a colour monitor. Whilst these observations are sufficient to allow the surgeon to make precise cuts and dissect tissues, the surgical outcome would be improved if it was possible to visualise sub-surface structures or to detect subtle differences between healthy and cancerous tissues[Cleary10]. This is particularly important during minimally invasive procedures, where in addition to poor tissue visualisation, the lack of tactile feedback deprives the surgeon of additional diagnostic information about the tissue. It has long been an aim of the biophotonics and computer assisted surgery communities to bring the potential molecular sensitivity of optical methods into image guided surgery. Whilst there have been some clinical success stories such as optical coherence tomography[Fujimoto2003] and narrow band imaging[Gono2004], the lack of clinically approved contrast agents has hampered the application of large area imaging methods[Guo2014]. Partly as a result there is a renewed interest in imaging using an approved agent, indocyanine green (ICG), which emits light in the infrared spectral region and penetrates relatively deep into tissues due to low absorption at these wavelengths[Frangioni2003]. Recent applications of of serum albumin/globulin-bound ICG medical imaging include metastases identification[Kosaka2011], lymph vessel and sentinel node detection and tumour demarcation[Marshall2010]. These instruments have mainly been used for open surgery, and where endoscopic devices have been demonstrated they lack multispectral versatility and accuracy, or require sequential imaging of white light and fluorescence. A new LED/laser-based light source is proposed, together with a dual-head camera that can allow convenient and versatile multispectral open and endoscopic imaging. This will realise the advantages of NIR imaging in an affordable, compact device including the provision of a perfectly registered augmented reality image overlay showing the fluorescence signal on top of the standard white light images. The challenges include finding methods to deal with background non-specific fluorescence, indicate the depth from which the fluorescence originates, deal with blood absorption and optimise the spectral mix and control of the visible and NIR light sources. The unique approach will exploit the colour selectivity that is available with the multi-LED light box, and the interplay that these illumination spectra have with the spectral sensitivity of the camera head, achieving a limited narrow-band multispectral data set in real-time and allowing the blood and spectral shift in ICG to be detected. The clinical exemplar applications of this technology have been selected based on the experience of the investigators, and also to balance high volume procedures against those with previously demonstrated benefits to patient outcome and healthcare economies. The open/semi-endoscopic procedure of breast excision cavity imaging during breast conserving surgeries and limited fully endoscopic oesophageal imaging have been chosen, including peritoneal metastases imaging and imaging of reconstructed oesophageal blood supply, as described in more detail in subsequent sections. This product provides a mixture of near-market development with opportunities for more far-reaching research, providing different levels of risk and potential future benefits. We address the following five aims: Create an affordable and versatile LED/laser light source for light-guided illumination for colour and near-infrared fluorescence; Implement a dual camera head imaging system for simultaneous visible and near-infrared fluorescence imaging as well as a practical multispectral function; Design and test a tissue motion, background fluorescence and tissue chromophore removal method and combine optical images to provide the surgeon with an augmented reality view of the tissue; Conduct a clinical evaluation in breast tumour surgery and margin detection; Conduct a clinical evaluation in endoscopic oesophageal-related minimally invasive surgery.

Lay abstract: Surgeons currently rely on white light illumination of tissue during surgery and observe the colour and texture of tissue either by eye or using a video camera system. While this can provide convenient and high resolution viewing, only the exposed tissue surface can be seen and only with limited diagnostic cues. Additional information is typically used to improve the surgical accuracy, such as pre-operative images including MRI and CT, or tissue palpation. During image-guided surgery there are increased ergonomic and navigational challenges, and identification of target tissues is complex. This proposal will develop a new illumination and camera system, together with novel multispectral analysis methods to allow the presence of an exemplar near infrared (NIR) fluorescent marker, indocyanine green (ICG), to be detected. This molecule was clinically approved in the 1970 s but has recently been the subject of renewed interest as a means to detect lymph vessels and nodes, monitor tissue perfusion, as well as the location of tumourous tissues due to leaky blood vessels. The research and development work will include: the production of a new visible and near-infrared excitation source using LEDs; a dual-head multispectral camera that can record registered images of white light and NIR fluorescence; image analysis methods to remove artefacts caused by other tissue chromophores and background fluorescence; augmented reality display of the data overlaid on the white light image; clinical evaluation in breast and oesophageal surgeries. The potential for this image guided surgery instrument extends beyond the immediate use with ICG, since many other markers and procedures are currently in development[Guo2014]. The medical device can be easily adapted for open and endoscopic surgeries, representing a large and increasing market, and intellectual property protection is either already in place or will be sought for the individual components.

Research activity codes: 5.4 SURGERY;5.3 MEDICAL DEVICES
Health categories: CANCER AND NEOPLASMS