Enhanced Delivery Ecosystem for Neurosurgery in 2020

Due to an ageing population and the spiralling cost of brain disease in Europe and beyond, EDEN2020 aimed to develop the gold standard for one-stop diagnosis and minimally invasive treatment in neurosurgery. Supported by a clear business case, it exploited the unique track record of leading research institutions and key industrial players in the field of surgical robotics to overcome many of the technological barriers that stand in the way of real clinical impact. With an initial focus on cancer therapy, EDEN2020 provided a step-change in the modelling, planning, and delivery of diagnostic sensors and therapies to the brain via flexible surgical access. It engineered a family of steerable catheters for chronic disease management that can be robotically deployed and kept in situ for up to 28 days. The system features 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 is able to sense and perceive intraoperative, continuously deforming, brain anatomy via three-dimensional intraoperative ultrasound registered to patient-specific preoperative images, and deploy optical sensors for shape recognition, in situ diagnostics and vessel avoidance, which represent the state-of-the-art in the field. By modelling and predicting drug diffusion within the brain with unprecedented fidelity, EDEN2020 also contributed to the wider clinical challenge of extending and enhancing the quality of life of cancer patients – with the ability to plan therapies along preferential pathways and around delicate tissue structures by exploiting tissue anisotropy within the brain, as proven by the consortium, and with unparalleled delivery accuracy. EDEN2020 was strengthened by a significant industrial presence, which was 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, with spinout, licencing, and follow-on translational funding currently being considered.

During the five-and-a-half-year Action, which was affected by the COVID-19 pandemic in 2020 and 2021, the consortium produced an advanced system for use in convection-enhanced drug delivery. EDEN2020’s steerable catheter, which is inspired by the egg-laying channel of certain insects, was 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 was complemented by an ecosystem of technologies to support the agile delivery of pharmaceuticals to procedure-optimised targets within the brain. EDEN2020 resulted in 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, platform specifications and design considerations 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 Period 2, 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 target pose. Tests in vivo with rigid catheters were also carried out 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, verified, and validated both in vitro and ex vivo on the ovine model. In Period 4, the consortium came together to complete the in vivo clinical trials of the integrated EDEN2020, albeit with a significant reduction in ambition and scope compared to the original Annex. Owing to the ongoing global pandemic and extensive cost-neutral extension (18 months overall), which affected the consortium’s ability to retain key staff, travel, move key equipment and support the clinical team in Lodi during the trials, only two live robotic-assisted surgeries on sheep were performed over the summer of 2021. Additionally, a collection of benchmarking trials of the system, carried out by consortium partners in isolation, was performed to assess sub-system performance against the literature and competing systems for which performance metrics were available in the public domain.

Regardless of the significant deviations in P4, which were unavoidable, this Research and Innovation Action remains a success and a testament to the significant efforts behind this complex, integrated project, which holds the promise to enhance the quality of life of cancer patients in the not-too-distant future. The project supported by a comprehensive, user-led 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: 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.

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, has been produced with the smallest cross-sectional diameter ever (2.5 mm), and it now features two complete working channels per segment (eight in total). Only one working channel had been possible until now. On completion of the final, in vivo phase of the Action, which was carried out over the summer of 2021, significant interest was 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. Aside from commercial exploitation, the consortium contributed to the open sourcing of methods developed in this Action for ultrasound processing (https://github.com/IFL-CAMP/supra) and published a unique set of clinical and preclinical datasets open access (https://zenodo.org/communities/eden2020) to support future research into brain disease.

Periodic Reporting for period 4 - EDEN2020 (Enhanced Delivery Ecosystem for Neurosurgery in 2020)

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