Project: Hybrid navigator for image-guided surgery in urologic cancer

Fluorescence based surgical guidance is a rapidly growing field of clinical research, that has been predominantly focused on the near-infrared (NIR) dye indocyanine green (ICG) [1]. However, even with a 1-1.5 cm penetration of the NIR emission of ICG in tissue, fluorescence guidance is suboptimal for the localization of deep lesions and ends up requiring an exploratory surgical approach [2]. Furthermore, fluorescence imaging does not enable the acquisition of preoperative images for surgical planning, which could help minimize the region of exploration. It is for this reason that to date, clinical fluorescence guidance has mostly been restricted to superficial sentinel lymph nodes (SNs) of e.g. the breast or to lesions on the surface of an organ [1]._x000D_To extend the use of currently available fluorophores for fluorescence guided surgery to deeper structures, the project Ps of LUMC introduced the use of the hybrid tracer ICG-99mTc-Nanocolloid that is both radioactive (99mTc human albumin colloids) and fluorescent (ICG) [3]. The radioactive signal emitted by this tracer allows for the identification and localization of the lesions in 3D prior to the intervention using imaging modalities such as Single Photon Emission Computed Tomography with X-ray computed tomography (SPECT/CT), thereby facilitating preoperative surgical planning. Intraoperatively, the radioactive label helps the surgeon to first identify the region of interest using conventional gamma probes and then visualize the exact location of the lesion and its margins during the excision using fluorescence cameras. This hybrid-guidance concept was clinically introduced for the visualization of deeply situated pelvic SNs [4] and SNs in the head and neck region [5]._x000D_Still, even when fluorescence imaging is combined with preoperative surgical planning based on SPECT/CT and intraoperative gamma ray detection, surgical orientation in particular in minimally invasive surgery can be difficult. In previous studies by the group of LUMC, the limited tissue penetration of the fluorescent emission of ICG prevented intraoperative visualization of deeper lying or tissue embedded SNs [4,5]. In addition, SN identification using gamma probes was sometimes hindered by background signals from the nearby injection site [4,5]. This practical experience suggests that more accurate intraoperative image navigation towards the areas of interest, e.g. based on the SPECT/CT, could help to further improve sentinel node identification in complex areas._x000D_The expertise of the team of SurgicEye in intraoperative 3D nuclear imaging [6] and navigation of SPECT/CT and PET/CT images, as well as, their experience in development, certification and production of surgical devices, fits here perfectly the know-how of LUMC and opens space for the developments of systems with a potential to become products and be available for a vast public._x000D_This project aims at the development of a navigation system that combines pre-operative SPECT/CT images with intraoperative gamma and fluorescent detection. The resulting integrated system will be a hybrid navigator designed to exploit the advantages of the hybrid tracers designed by LUMC for a minimal invasive and yet complete resection of hybrid marked structures like SNs and primary tumors._x000D_The development will start from the preliminary work by the teams at LUMC and SurgicEye. Within the last year the collaboration has already made technical developments to provide a proof-of-concept in phantom studies and even in one clinical pilot case to illustrate how navigation based on SPECT/CT combined with intraoperative fluorescence and gamma detection may help improve surgery [7]. In this conceptual study the fluorescence, the gamma detection and the navigation system all worked separately._x000D_Within this proposal we would like to: (1) optimize the technology developed for the proof of concept by integrating all data sources in one single system (hardware and software), (2) make the integrated solution suitable for integration in the clinical workflow, (3) extend it to open-surgery and finally (4) put it through clinical testing in phase I trials. The general aim herein is the development of a unique new technology which can result in a break through towards 3D hybrid image guided surgery._x000D__x000D_References:_x000D_1) Mieog JSD et al. Ann Surg Oncol. 2011; 2) Chin PTK et al. Biomaterials 2011; 3) Buckle et al, Nanotechnology 2011 and van Leeuwen et al. J Biomed Opt, 2010; 4) van der Poel et al. Eur Urol 2011 and Buckle et al. J Nucl Med 2012 accepted; 5) Brouwer et al. Ann Surg Oncol 2012 E-pub, Brouwer et al. J Nucl Med 2012 accepted with minor revisions, and van den Berg et al. Eur J Nucl Med Mol Imaging 2012 accepted with minor revisions; 6) Wendler et al. Eur J Nucl Med Mol Imaging 2010; 7) Brouwer et al. submitted for publication.

Acronym	Hybrid Navigator (Reference Number: 7555)
Duration	01/01/2013 - 30/06/2015
Project Topic	Within this project 3D navigation of a combined fluorescence and radioactive navigation system will be developed and clinically validated for the procedure of sentinel lymph node biopsy in selected urologic malignancies.
Project Results (after finalisation)	A demonstrator was build that could be used for pre-clinical and also under an IRB for clinical evaluation. The navigation system that was developed and realized as a clinical usable demonstrator could overlay the SPECT information reconstructed with a handheld gamma detector to navigate the handheld optical camera to the location where the ICG / optical image is.
Network	Eurostars
Call	Eurostars Cut-Off 8

Project partner

Number	Name	Role	Country
2	Leiden University Medical Center	Partner	Netherlands
2	SurgicEye GmbH	Coordinator	Germany