Context Each year, about 400 000 patients in Europe and 500 000 in the USA have a Total Hip Athroplasty (THA). 13% of these surgeries lead each year to a hip revision surgery, with an average cost 35% superior to the primary procedure, and with a higher level of morbidity. Multiplying surgical procedures also reduces functional capacities of the patient and significantly increases the risk of infection. One of the main causes of failure is the surgical technique itself, based on statistical criteria defined by retrospective analysis of clinical series. As those criteria present a large variability, they are not always appropriate for a given patient. The goal of arthroplasty procedure is to restore kinematic capabilities close to the original hip joint. However, the planning of such procedure is only based on static criteria. In addition, it is already proven that the kinematic behaviour of the lombopelvic area, specific for each patient, also influences the final stability of the hip implant. Several solutions already exist to guide the surgeon for the placement of hip implants, but those solutions are all based on statistical and static criteria. Solution The goal of this program is to develop a new concept of surgical navigation for total hip arthroplasty that includes a preoperative planning step taking into account dynamic information specifically for each patient. First, a preoperative step measures the pelvic kinematics of the patient and integrates those specific data into the model of a decision support tool. Second, an intraoperative step helps the surgeon to reach the desired position of the implant, thanks to an innovative instrumentation, which secures the surgical procedure and save time. The optimization of the femoral implant is performed with a trial modular neck that can be adjusted thanks to the Smart Screw Driver of Blue Ortho. Objective of this program The goal of this program is to develop an integrated solution comprising (1) an innovative system to measure preoperative dynamic parameters of the patient, (2) an intraoperative guidance software integrating those parameters, (3) an innovative instrumentation and (4) an adjustable implant. A preclinical validation will be performed in order to validate the proof-of-concept. The ratio risk/benefit will be evaluated in a clinical study that is not part of this program in order to determine the delivered medical service. The commercialization will be managed by the industrial partner of this project through an international network already in place.

Context The project EMERGE fits into the overall problem of postoperative complications following the total knee arthroplasty (the implantation of a total knee replacement). These complications resulting from various surgical and non-surgical factors may shorten the lifespan of this implant and consequently lead to revision surgery. Given that the current designs of total knee replacement compensate for the absence of the anterior and posterior cruciate ligaments by their shapes more or less congruent, the stabilization functionality of the collateral ligaments can be ensured by the surgical technique. However, despite the fact that the cutting guides allow the surgeon to properly align the prosthetic components of total knee replacement with respect to the mechanical axis, there is no computerized system allowing him to perfectly balance the collateral ligaments as has been reported in several postoperative studies. Moreover, even if the collateral ligaments are perfectly balanced at the time of surgery, it is not necessary that the balance will remain perfect in the years following this surgery. This is due to the fact that the morphology of the patient including age, weight, and lifestyle will considerably change with time. Therefore, the functionality of total knee replacement becomes suboptimal; which may sometimes lead to a revision surgery (9% at 10 years, 16% at 15 years, and 22% at 20 years). These proportions will result in a considerable number of revision surgeries considering the increase in life expectancy on one hand, and the growing demand for this type of surgery from younger and active patients on the other hand. Solution To meet this issue, a new generation of knee implant, able to compensate for the variations of functionalities by its adjustable and adaptive shape, will be proposed. Developing such a self-powered implantable device involves ensuring its power supply and its control using embedded sensors. Innovative and multidisciplinary project aims to minimize the significant number of revision surgeries by implementing the first generation of dynamic implants. Objective of this program The goal of this program is to develop a new generation of instrumented knee implant comprising (1) an integrated power generator, (2) a power conditioning system (3) a telemetry system, and (4) an actuator for fin-tuning the implant shape in the postoperative period. A preclinical validation will be performed in order to validate the proof-of-concept. The ratio risk/benefit will be evaluated in a clinical study that is not part of this program in order to determine the delivered medical service.

Prostate cancer is by far the most common cancer for men. A vast variety of prostate cancer treatments are today performed in clinical routine. However, most of them act on the entire gland and are characterized by a high rate of side effects that considerably impact the quality of life of the patient. From an economic point of view, the high side-effect rates of these therapies lead to particularly expensive aftercare costs. The search for improved solutions for the treatment of prostate cancer remains a major societal challenge. This issue is emphasized by the fact that constant improvement of prostate cancer diagnostic tools allows detecting highly localized and small tumors at an early age. In such cases, whole-gland treatment approaches are highly controversial. The high risk of side effects often justifies the choice of an active monitoring of the patient rather than therapy. In recent years, a very attractive therapeutic alternative treatment is gaining in popularity among experts: focal therapy. This is a localized treatment, restricted to cancerous zones, with the objective of preserving healthy functional tissues inside and outside of the organ, and thus the quality of life of the patient. Finally, focal therapy has a high potential to reduce the intervention cost and duration, and the cost of aftercare. However, the current brachytherapy procedures are not fully exploiting the latest state of the art in dosimetry calculation, guidance and imaging capabilities, and thus do not yet meet the requirements for a robust focal treatment. The ambition of the FOCUS project is to provide an innovative focal brachytherapy system, less invasive, with fewer side effects, in rupture with current brachytherapy procedures, capable of accurately irradiating very localized areas, while significantly decreasing the time of the intervention. To achieve such innovative focal brachytherapy system, a new hardware platform dedicated to transperineal prostate punctures will be developed as a part of the project including the use of new 3D Lateral endocavitary ultrasound probe. An essential innovation will be the intraoperative ultrasound-based target guidance in order to control with accuracy the instrument placement during the intervention. This will include multimodal image-fusion algorithms and real time navigation methods. A specific challenge is also the accuracy of the dosimetry. This calculation, already critical in global brachytherapy, is even more important when it comes to targeting small areas. We propose to develop the first clinical treatment planning system integrating edema prostate model and a fast and personalized Monte Carlo dosimetry calculation on GPU. New automatic seed detection in ultrasound images will be used to calculate the real in vivo dosimetry at any moment of the procedure and would thus enable intra-interventional correction in case of deviation from the planned dose distribution. Finally, all developed hardware and software will be integrated into a unique system. This demonstrator and the new clinical protocol of the novel focal brachytherapy procedure will be assessing using realistic phantoms in a clinical context. The FOCUS project is ambitious since it aims at transferring its research developments to health care industry through the industrial partner. The proposed system appears as a solution for a quarter of a million men diagnosed with prostate cancer each year worldwide, for whose no treatment is applied because the risk-benefit is deemed unsatisfactory. Brachytherapy stands out as an approach with a particularly high potential in the focal therapy market. Some systems and methods that will be developed in this project may also be used for other focal therapy approaches, which leverage the economic potential of the project and reducing the investment risk. Finally, patents and scientific publications will be generated by the FOCUS project.

The theranostics concept, defined as a therapeutic strategy (e.g. chemotherapy, hyperthermia, radiation therapy) combined with one or more in-vivo imaging modalities (e.g. PET, SPECT, CT, MRI), is a current trend towards achieving personalized medicine. A growing number of techniques and protocols involve significant interactions and feedback between imaging and therapy, for example the use of imaging to guide and monitor response to therapy. There is currently no integrating software platform allowing for the in-silico simulation of such theranostic scenarios that could help in designing, optimizing, testing and validating such protocols targeting different clinical applications. The overall objective of this project is to provide solutions in rupture with current state-of-the-art, allowing for the development of such a unique simulation platform. The proposed developments will facilitate i) the creation of links between different types of simulation and modeling such as Monte Carlo (MC) and analytical ones, ii) covering a large range of theranostics applications across several imaging modalities and therapeutic regimes, iii) at different spatial and temporal resolution scales, iv) within a computationally efficient framework. Different major methodological challenges will be addressed during the course of this project. These include the capability to model truly multimodal imaging and therapy protocols and their interactions within the same modeling framework, accounting for the simulation of dynamic processes. The second challenge to be addressed is that of the different resolution associated with the imaging modalities used to guide therapy (mostly at the millimetric scale) and the effects of therapy (mostly at the level of micrometric and sub-micrometric scale). Finally, the proposed platform has to be computationally efficient which cannot only be based on hardware acceleration solutions but also on the development of hybrid modeling approaches combining MC and analytical simulations within the same platform. All these methodological developments will be validated through different theranostic protocol demonstrators which are either currently in clinical practice or under development and/or evaluation for future clinical use. The proposed integrative platform will be developed based on the already popular GATE MC simulation platform in order to benefit from the existing capabilities to simulate different imaging modalities, therapeutic regimes, and the large selection of the underlying Geant4 physics process libraries. The different teams involved have substantial experience in the development of simulations for multi-modality imaging and therapy applications and can lead with success this project, whose final aim is the development of the first ever theranostics in-silico modeling platform.