Reporting Period 3 – 01 Oct 2018 – 31 Mar 2021

October 1, 2021

Summary of the context and overall objectives of the project

Due to an ageing population and the spiralling cost of brain disease in Europe and beyond, EDEN2020 aims to develop the gold standard for one-stop diagnosis and minimally invasive treatment in neurosurgery. Supported by a clear business case, it will exploit the unique track record of leading research institutions and key industrial players in the field of surgical robotics to overcome the current technological barriers that stand in the way of real clinical impact. With an initial focus on cancer therapy, EDEN2020 will provide a step-change in the modelling, planning, and delivery of diagnostic sensors and therapies to the brain via flexible surgical access. It will engineer a family of steerable catheters for chronic disease management that can be robotically deployed and kept in situ for extended periods. The system will feature enhanced autonomy, surgeon cooperation, targeting proficiency and fault tolerance with a suite of technologies that are commensurate to the unique challenges of neurosurgery. Amongst these, the system will be able to sense and perceive intraoperative, continuously deforming, brain anatomy at unmatched accuracy, precision and update rates, and deploy a range of diagnostic optical sensors with the potential to revolutionise today’s approach to brain disease management. By modelling and predicting drug diffusion within the brain with unprecedented fidelity, EDEN2020 will contribute to the wider clinical challenge of extending and enhancing the quality of life of cancer patients – with the ability to plan therapies around delicate tissue structures and with unparalleled delivery accuracy. EDEN2020 is strengthened by a significant industrial presence, which is embedded within the entire R&D process to enforce best practices and maximise translation and the exploitation of project outputs. As it aspires to impact the state of the art and consolidate the position of European industrial robotics, it will directly support the Europe 2020 Strategy.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Since the start of the project, the EDEN2020 consortium has devoted a significant amount of effort to produce a steerable catheter system for use in convection-enhanced drug delivery. As of the end of this reporting period, EDEN2020’s steerable catheter, which is inspired by the egg-laying channel of certain insects, is being produced at a size and with materials suitable for clinical use, featuring eight working channels for drug delivery, optical-based theranostic modalities and shape sensing. It is complemented by an ecosystem of technologies to support the agile delivery of pharmaceuticals to procedure-optimised targets within the brain. In this reporting period, work has been completed on all technical work packages, with advancements to the state of the art in three-dimensional intraoperative ultrasound imaging; catheter shape sensing based on fibre brag gratings technology; advanced preoperative imaging based on state of the art MRI sequences; and a commercial front end, coupled with a state of the art stereotactic robotic system, both of which have been upgraded for use within EDEN2020. In Period 1, the ethics behind the complex array of clinical trials on both human and ovine models starting in year 2 of the project was completed, and detailed experimental protocols were defined for each phase of the study. In Period 2, the consortium made significant progress on all fronts: platform development, pre- and intra-operative imaging, image processing and sensorisation, and human and ovine clinical trials. In P2, the consortium delivered a family of pre-production steerable catheters within a bespoke blister pack, produced a complete robotic catheter driver, and a functional intelligent planner able to identify optimal curvilinear paths between a desired entry point and diffusion-modelling-based target pose, tested in vivo with rigid catheters as to provide the gold standard for ecosystem validation. In Period 3, the consortium completed all technical deliverables, implemented all system modules to specification, and integrated these in a fully functional prototype system which was deployed and assessed both in vitro and ex vivo on the ovine model. The project, supported by a comprehensive, user lead specification, was meticulously put together borrowing from industrial R&D templates and practices, with a view to facilitating eventual commercial exploitation of EDEN2020’s outputs, which has already begun, with completion of a detailed customer discovery phase, the start of commercial spinout conversations with the coordinating institution, and early licensing discussions with potentially interested corporate partners.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The consortium has beaten the state of the art on several fronts, including intraoperative ultrasound, shape sensing, needle steering, brain tissue modelling and characterisation, and real-time path planning and re-planning for dynamic tissue navigation in minimally invasive neurosurgery. The flagship module centres around EDEN2020’s steerable catheter delivery system, which is able to steer within full three dimensions without the need for an axial twist, it has been produced with the smallest cross-sectional diameter ever, and it now features two complete working channels per segment (eight in total), when only one working channel had been possible until now. As the project enters its final, in vivo phase over the summer of 2021, it is expected that significant interest can be generated to make use of EDEN2020’s platform technology for precision neurosurgery to improve patient outcomes, notably within the context of convection-enhanced drug delivery for neurosurgical cancer therapy, ablative therapies to treat neurological disorders and in situ diagnostics for more efficient and faster patient care.