TLEMsafe project aims to develop, validate, and clinically implement an ICT-based patient-specific surgical navigation system, using image-based models able to reproduce the adaptive capabilities of patients affected by musculoskeletal pathologies. TLEMsafe will help the surgeon to reach the optimal functional result for patients that require complex operations, improving safety and predictability of the surgical operation. TLEMsafe will represent also a user-friendly training facility for surgeons. Co-developing the interactive system with clinicians and companies eases the successful introduction to (future) surgeons.

The starting point of TLEMsafe project is the recently developed Twente Lower Extremity Model (TLEM) which undergoes rigid validation using functional data (e.g. glucose metabolism, oxygen consumption) measured on 10 healthy subjects. Since individual musculoskeletal characteristics differ considerably between subjects, state of the art 3-D image analysis techniques are developed to extract important parameters to create patient-specific models.

The patient-specific model predictions, different for each individual, are validated against extensive measurements (simulation of multiple daily living activities, such as walking at various speeds, sitting down and getting up from a chair, stair climbing…) on the patients before and after surgery. This allows to exactly quantify the adaptive capacity of the patient to the altered musculoskeletal system (e.g. due to the removal of a muscle in a tumour patient or to the implant of a hip prosthesis). This adaptive capacity, implemented in the model, represents a unique and essential feature to predict the functional effect of surgical interventions.

Next, an interactive link is created between the musculoskeletal model and the surgeon. Using a 3D virtual reality system, the surgeon is able to simulate a surgical operative plan on the patient-specific model and to clinically interpret the predicted functional outcome of the surgery. Once the optimal surgery plan is selected, this is fed into a computer navigation system that guide the surgeon in a step-wise manner through the surgery, in order to exactly reproduce the selected surgical plan.

Challenges
The burden of musculoskeletal diseases and prosthetic revision operations is huge and increasing rapidly with the aging population. For patients that require a major surgical intervention, procedures are unsafe, uncertain in outcome and have a high complication rate.

Project partners
TLEMsafe consortium comprises two technical universities (University of Twente and Warsaw University of Technology), one university medical centre (Radboud University Nijmegen Medical Centre), two large industrial partners (Brainlab GmbH and Materialise NV) and one small-medium enterprise (AnyBody Technology A/S).

TLEMsafe consortium has been designed to capitalise on project partner skills, complementarity, and opportunities for collaboration and technology transfer. The expertise of the multi-disciplinary partners covers a wide scientific and technological range, including complex musculoskeletal surgery, modelling know-how, computer navigation, medical imaging and virtual reality. The selection of partners ensures adequate vertical integration starting from basic science to clinical implementation.

Policy Context

An extensive World Health Organization (WHO) report shows that 40 % of people over 70 suffer from osteoarthritis of the lower extremity; 80 % of osteoarthritis patients have some degree of limitation of movement, and 25 % cannot perform their major daily activities of life[1]. Due to the increasing number of hip and knee prostheses (over 1 million per type worldwide) that are implanted, the number of complex revision surgeries is likely to double by 2015[2]. Hence, the costs of musculoskeletal diseases and prosthetic revision operations to the healthcare system are enormous and are increasing rapidly among the ageing population.

Key EC policies not only improve the quality of life for Europeans, but also change the way healthcare is delivered and the way medical knowledge is managed and transferred to clinical practice. As standards of living rise, the need for personalised or individualised healthcare increases as well. European industry positioning well placed in high-tech applications for surgical systems but needs to innovate to keep up and improve this position. Personalisation of healthcare will give plenty of opportunities for innovation, thus allowing it to grow, create jobs and spin-offs and to commercialise new products.

TLEMsafe feeds in with the recent advances in basic ICT components and the convergence of ICT technologies which allow for the development of life saving applications with great business opportunities. In this project, the various ICT tools offer a useful capability to improve the health status and safety of care and facilitate active participation of patients for this treatment option, thus opening new opportunities in personalised (patient-specific) health and disease management.

To achieve the objectives of this project, state-of-the-art companies and research teams have been carefully selected and integrated. As a result, a consortium has been created which can address the multi-disciplinary nature of the various work packages in a most effective and innovative manner (imaging techniques, functional biomechanical modelling and assessment, biological adaptation, navigation for robotic systems, interfacing software development). The blend of the various fields of expertise of the different partners in this project makes it possible to develop this break-through technology, rather than developing incremental technology. The contribution to the European Research Area is significant, as the knowledge present within the companies as well as within the academic centres will increase in a sustainable fashion. This will have a long-term effect and will promote innovation within the companies and associated partners. Reinforcing the leadership of Europe's healthcare and medical imaging/devices industries and attracting back to Europe research activities of the pharmaceutical industry. TLEMsafe is funded under FP7.

Description of target users and groups

Patient selection
To develop and test the validity of TLEMsafe system, extensive tests are required that couple the predictions of musculoskeletal models to the actual results of the patients. It is clear that not all patient types can be included in this project, but that a focus is required on certain groups of patients. We have selected two types of patients that challenge the TLEM model and provide the opportunity to adapt and validate the model in different ways.

Expected users
It is expected that the project results in bridging the gap between bioengineers and clinicians. By putting emphasis on the musculoskeletal pathologies and the adaptive capabilities of the human musculoskeletal system, a unique system is obtained. By co-developing the software of the visual and interactive (surgical) parts with clinicians and companies, it is expected that it will be successfully introduced to (future) clinicians who perform surgical interventions to pathologies of the musculoskeletal system.

Description of the way to implement the initiative

In order to achieve the TLEMsafe objectives, five fields of expertise were identified:

1. Functional biomechanical modelling and assessment;
2. Biological adaptation;
3. Imaging techniques;
4. Navigation for robotic systems;
5. Interfacing software development.

The TLEMsafe consortium is comprised of two technical universities (University of Twente and Warsaw University of Technology), one university medical centre (Radboud University Nijmegen Medical Centre), two large industrial partners (Brainlab GmbH and Materialise NV) and one small-medium enterprise (AnyBody Technology A/S). This mix of world class research and academic institutes, together with highly focused industrial partners was designed to enable the achievement of TLEMsafe goals. The consortium was designed to capitalise on project partner skills, complementarity, and opportunities for collaboration and technology transfer. The expertise of the partners covers a wide scientific and technological range that is integrated in this project to reach the objectives. The selection of partners ensured adequate vertical integration starting from basic science to clinical implementation.

The TLEMsafe consortium was developed with the basic principle that all partners should have already at least one successful cooperation with another consortium partner. At the same time, new partnerships were introduced to stimulate innovation to the maximum.

The project management structure was defined in order to successfully accommodate the complexity and scale of this project. The management structure is based on rules and regulations described in the Consortium Agreement, including measures for the arrangement of confidentiality, IPR, exploitation rights, decision-making and change procedures, negotiation with third parties, as well as possible cooperation after the project’s end.

This management structure leads to:

• effective, transparent management of the TLEMsafe project;
• clear procedures for taking decisions and resolving conflicts effectively and quickly;
• quality control procedures with respect to all outputs and deliverables;
• proceeding of the project within the framework of the project budget and according to administrative, financial and legal principles defined by European and national regulations;
• conformation of the participants to their obligations under the contract and the consortium agreement;
• management of background and foreground intellectual property taking due account of the rights of the participants;
• appropriately addressed ethical issues.

The Hip Group
The first patient group consists of patients that have a dysplastic hip joint or require a revision of a failed hip prosthesis. In these patients, the centre of rotation of the hip is not placed in the correct anatomical position and needs to be restored (see image below). Often, bone grafts are needed to reconstruct the existing bone stock lost. Additionally, the muscle balancing is usually inadequate. Although the survival of these surgeries is satisfying[1], the functional results of these patients are not always satisfying: leg-length discrepancies up to about 25 % of the cases have been reported[2], and patients have sometimes an abnormal gait pattern.

The Tumour Group
The second patient group consists of patients with oncological musculoskeletal pathologies around the femur. The surgery usually involves removal of relatively large segments of bone and soft tissue. The bony segments are reconstructed with donor bone or a (massive) prosthesis (see image below). These prostheses often contain holes to which muscles can be attached. The optimal location for muscle attachment is often difficult to judge. Quite often, the extensor muscle group is partly resected: to restore its function, the surgeon may use an important knee-flexion muscle (for example the biceps femoris) and re-attach this muscle to the femur so that this muscle becomes an extensor.

These types of reconstructions are very expensive (about €100 000)[3] and are associated with a relatively high complication rates and sometimes its functional outcome is quite disappointing. Therefore an amputation of the lower limb may sometimes be more effective.

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Technology solution

It is important that the data and knowledge gathered in TLEMsafe has impact on and can be shared by a large number of clinical teams, that it has long-term value, and is easy usable for a broad range of applications. A crucial factor in this is standardisation. Therefore, we pay special attention to select and adhere to data and knowledge standards that are available. The attitude in TLEMsafe towards standard limitations becoming prohibitive is to not only develop extensions to solve such prohibitive limitations, but to also put in the effort to seek contact with standard committees to discuss and help remove the limitations in a future version of the standard. Otherwise the power of standardisation for impact, sharing, longevity, and broad applicability would be compromised.

The partners of the consortium are well aware that when the TLEMsafe system is to be introduced in the clinic, the requirements in terms of validity, predictability, reliability, confidentiality are of utmost importance. These requirements are described in CE and FDA standards and guidelines. During the project we continuously monitor to what extent the research methods comply with these standards and guidelines.

Here are some standards used when developing new software or managing data:

• Unified Modelling Language for definition of whole structure of software modules used in project as well as communication and data exchange between them;
• DoxyGen compatible software modules documentation;
• XML language for common and standardised meta-data exchange;
• C3D: the format is a public domain, binary file format commonly used in Biomechanics;
• STL: basic file format used for geometry, the file are based on triangles;
• BVH: Biovision hierarchical data file format used for motion data;
• All models will comply with ISB standards on coordinate systems;
• Marker configurations used to measure human kinematics will comply with the so-called Plug-In-Gait standardised model (Plug-in Gait Product Guide, Oxford Metrics Ltd UK);
• Human diseases will be named according to the ICD-10 (International Classification of Diseases) of the WHO;
• EMG measurements are performed according to the SENIAM (Surface ElectroMyoGraphy for the Non-Invasive Assessment of Muscles) standard.

Technology choice: Proprietary technology, Standards-based technology

Main results, benefits and impacts

Main results achieved
All the different steps of the TLEMsafe patient workflow are now connected to each other and have been validated. Combining the new updated version of the Twente Lower Extremity Model with an MRI scan of a patient, it is possible to generate a patient-specific musculoskeletal model. Then, the surgeon can use the prototype VR system SPE3D (Surgery Planning Environment 3D) to perform a series of virtual surgeries and predict their functional effects on the patient. Finally the optimal plan can be imported into the integrated navigation system and accurately reproduced the selected operative plan in the surgery room.

Benefits for the partners
In this project industrial and academic partners collaborate to establish a breakthrough technology which covers the fields of medical devices and healthcare. This high scientific standard collaboration offers partners to profile themselves in the field as experts in human modelling, functional analyses and patient treatment.

The three academic centres will have similar benefits: large number of publications and presentations in the science community can be expected, which is important for the future of the researchers involved. In addition, fundamental knowledge will be created with respect to technical/scientific issues related to the project. This will strengthen their research lines and undoubtedly bring about new project proposals and funding opportunities.

Furthermore the network with the partners and associated companies support the academic centres in their internal financial status and in their efforts to attract international industrial sponsorship and academic research funding on related topics. Thirdly, it will initiate technology transfer and stimulate entrepreneurship with possibilities for new businesses and strengthening of the position of the participants.

Some of the TLEMsafe results will be quite near to commercial exploitation, especially the patient-specific imaging techniques, the functional modelling prediction and the virtual reality pre-planning tools,. In addition, this project feeds in a new field of computer assisted surgery (CAS). Currently CAS is gaining popularity amongst the (mostly younger) surgeons; the implementation of the new TLEMsafe system in the navigation industry makes the project unique.

For the other TLEMsafe results, which are not really near to market introduction, the exploitation activities will have a more scientific and generic character. Particularly the quantification of the adaptive capacity of patients after severe surgery is a new approach and has a lot of scientific merits.

Impact for healthcare community
The clinical community is increasingly successful in treating life threatening diseases (such as cancer), thereby putting more emphasis on the functional recovery of the patient. The TLEMsafe project largely improves the quality of healthcare for affected by severe musculoskeletal deformities. The integration of technologies developed during the project will produce a system that can assist the surgeon to optimise his operative plan and outcome, thus enhancing surgical safety standards and quality control.

The developed platform will also offer the possibility to train surgeons. The current virtual training modules are not very realistic and have therefore only a limited added value. With the technology developed in this project; virtual reality simulations with reliable predictions are produced which will enhance the potential to exploit the results for training purposes.

Once the TLEMsafe system is developed and validated, it can be used to improve the sustainability of the quality of healthcare at an affordable cost. Productivity of healthcare systems can be improved by facilitating better integrated care and management of chronic diseases and quicker transfer of knowledge to clinical practice. Optimal medical intervention and prediction of potential errors in the surgery room would result in improved patient safety and resources saving. Moreover, improved functional outcome for the patients will lead to shorter rehabilitation period, which complies with the reducing workforce, availability and accessibility of skilled nurses and medical specialists.

Impact for the society
The project accommodates the urge of more demanding citizens who require best-quality care and cover for the use of latest diagnostics and treatments; a patient-specific treatment based on 3-D images of the patient represents the ultimate patient-specific treatment:

• With more relevant patient specific data, the surgery can be better prepared and planned, decreasing the risk for complications. In future applications and for very complex interventions, it is even thinkable that the surgeon may be able to practice the procedure in a virtual reality environment on beforehand.
• The intervention is better adapted to the properties and possibilities of the patient, so the functional outcome of surgery will improve, especially on the long term. This will improve the quality of life for the patient.
• The improved knowledge of the patient will better facilitate the use of robotic manipulators during surgery. This opens possibilities for less invasive and more precise surgery, again with better functional outcome and shorter hospital stays.

The obvious benefits for the well-being of the patients also have clear economic benefits. In addition to direct costs savings for hospital stays alone, the better functional outcome will allow people to better participate in the working process again, which has positive effects on a macro-economic scale.

Return on investment

Return on investment: Not applicable / Not available

Track record of sharing

The social ethical responsibility for this project to raise public awareness of its research and foster better dialogue and relations with its stakeholders, is tackled by participant involvement in continued dissemination and educational activities. These activities are performed for the general exploitation and dissemination of the TLEMsafe results and to ensure maximum potential for technology transfer into commercial applications. This includes the dissemination of knowledge to both scientific and professional audiences and to general public.

Participation to other research programmes
All the partners are very active at the national and European level, reinforcing the opportunities for extra-collaboration with other academic and medical centres and companies outside the TLEMsafe circle.

Orthopaedic/biomechanical conferences/workshops
Several scientific publications are coming out of this project, which have been presented at various biomechanical/orthopaedic conferences. Moreover, several stands are organised at conferences, where the academic partners present their work and results, and the companies show the implementation of the project to potential customers (surgeons). An own symposium will be organised at the end-stage of the project which will largely help to disseminate the results.

Education
Academic partners provide to implement the TLEMsafe results in educational curricula, in order to attract the attention of young students and researchers. Moreover, industrial partners involve professional and surgeons during their course and workshops. This educational network is successful in further acquainting a larger audience with the developed technology.

Web-based dissemination tools
TLEMsafe website is used to present the vision and goals of the project, to show the results obtained, and to inform about the dissemination efforts, including information for non-expert readers. A world-wide webcast, together with ABT, was organised to keep the participants, many of them leading clinicians and surgeons, up-to date on the new technological developments. Project will be announced and followed in these newsletters.

All these dissemination activities ensure, among other things, to accelerate the readiness of TLEMsafe technology for commercial market acceptance by improving scientists’ understanding of current commercial offerings and needs, and obtaining regular and frequent feedback. Moreover, continuous exchanges with the scientific or industrial community permit to discover areas of potential interest outside the scope of the TLEMsafe project.

Lessons learnt

• Collaboration between academic and industrial partners, with expertise in a wide scientific and research range, can offer a multidisciplinary approach that is essential to face the new challenges of modern healthcare and to establish a breakthrough technology.
• Involvement of clinical community, in particular the ‘young’ audience, permits to listen to their problems and requests, and to show what technology can offer and how it can help them.

Scope: Pan-European