WP9 Medical Validation, Pre-Clinical & Clinical Studies
The key objective of WP9 is the FUTURA system validation to achieve the outlined obectives. The consortium will apply the techniques and procedures described here to achieve this goal. The general objectives are to generate thorough understanding of the FUTURA system and its components, focusing on the two robotic arms in the context of safety, efficacy and efficiency for clinical use, workflow, and suitability for the clinical environment in which it will be applied. Validation of functionality for therapy planning and therapy monitoring will be performed. Each component of USgFUS will be assessed on specially developed in-vitro, ex-vivo and if required in-vivo experimental setups. Particular attention will be paid to safety and ease of use. Along side with the validation of the model, its placement in the clinical workflow and the integration of user feedback will be investigated in an early phase of the design and development process. This is part of “human factors engineering”, which involves the application of principles about human behaviours, abilities and limitations to the design of environments, and training in order to optimize human performance and safety. The methodology will follow three stages of evaluation: technical experiments, preclincal experiments and validation for potential clinical procedures.
New medical systems such as FUTURA must first have a technical evaluation to assess reliability and safety and to test specific functions. These will be analysed in a laboratory setting at UNIVDUN. The technical evaluation will be followed by an experimental evaluation simulating the clinical setting. Only when the quality and safety of the FUTURA prototypes have been proven, will the instruments undergo evaluation in clinical practice.
The human machine interfaces (graphic and haptic) will be evaluated including human factor analysis using methods to assess mental and physical workload on the clinical technician or clinician using the focused ultrasound system. The possibility for design-related human errors will be identified and minimized through a continuous feedback loop including the validation team and the development team. Objective analysis of the work flow process and development of an optimized workflow through the use of the FUTURA will accompany the validation process. The workflow will be modelled using Delmia Quest sotware (Dassault Systems, France).
Modified MISIT Delft methodology will also be applied to describe and analyse the robotic assisted ultrasonography guided focused ultrasound surgery process. This methodology consists of seven steps that can be used to measure the correctness and efficiency of task performance, protocols and the instruments used.
The Tasks of validation at the different levels and stages of FUTURA development will include:
- defining parameters and quantitative measures to analyse correctness and efficiency of the planning/monitoring/outcome prediction of robotic assisted focused ultrasound therapy;
- determining factors (limitations, possible incidents) that influence the safety of the robotic positioning, ultrasonography guidance and Focused Ultrasound Surgery (FUS) sonication;
- performing evaluation during the whole design process (in three stages: technical experiment in the early phase, simulated preclinical experiments, and the clinical setting), by analysing processes and workflow;
- providing input to improve the design and function according to the outcome of the previous evaluation;
- repeating the process and feedback to the teams above until the safety and reliability of FUTURA has reached the required level;
- pre-clinical case-based assessment of sonication simulated immobile organ and kidney tumors under respiratory motion.
DESCRIPTION OF WORK
T9.1 Definition and set up of preclinical in-vitro and ex-vivo experiments - The experimental setup will be defined in collaboration with the partners and necessary materials will be acquired. Ethical approval of the preclinical trials will be acquired (Thiel pre-project approval and animal trial approval amendment to the existing protocol at University Frankfurt).The current strategy is to establish a solid tumor model both for mobile an immobile organs. As FUS has been widely used for kidney tumors the plan is to set up a static kidney tumor model both with freshly excised organ from farm pigs delivered by the local abattoir in Dundee and Thiel soft embalmed kidneys. The kidneys will be set up for respiratory motion model using a pneumatic replacement (machine ventilator) of the kidney, while embedded in argarose moveable under a segment of porcine abdominal wall including rib sections. In the third step the kidney will be perfused using a heart lung machine (Maquet) to mimic physiological blood flow. In the fourth step the perfused kidney will be set up for respiratory motion. The final experiments is the set up of the Thiel soft embalmed cadavers with respiratory motion and kidney partial perfusion for testing the complete FUTURA set up includes the development, modeling and simulation of the appropriate effective and safe potential clinical work flow.
T9.2 Preclinical in-vitro and ex-vivo validation experiments system components - The experimental set-up of perfused porcine kidney and Thiel cadaver with and without respiratory motion will be used for the validation of outcomes both of robotic positioning of FUS therapy and of robotic therapy. The validation of the sonication procedure in order to define the position and orientation of the principal FUTURA platform components with respect to a common reference frame and automated FUS therapy will be validated. The sonication efficacy and target precision will be assessed and the procedure evaluated for safety, efficacy and time saving if compared with current techniques and Magnetic Resonance guided FUS in particular. Furthermore, pre-clinical protocols will be explored using appropriate artificial phantoms and specific protocols will be validated on the Thiel soft-embalmed cadavers available in UNIVDUN. These cadavers are amenable to ultrasonography, magnetic resonance imaging and computed tomography scanning and FUS and can be ventilated to achieve tissue motion and partially perfused to simulate blood flow. Therefore, they are an ideal basis to test the developed protocols and will also underpin the work to improve therapy planning and lesioning
strategies, involving feedback from the results of tests on them.
T9.3 Validation of the hardware and software based Human Machine Interfaces - The objectives of this WP concerned with the validation of the
hardware and software interfaces to be embedded in the final platform in order to integrate all the components. The validation will be done using the Thiel cadaver model and any issues with interfaces regarding systems performance and usability will be analyzed and reported back to the WP7 team. Particular regard will be given to the newly be developed Medical Workstation of FUTURA with haptic and graphic user interface. It will be assessed whether the surgeon is enabled to remotely control and supervise the therapy appropriately in the context of a simulated kidney tumor treatment.
T9.4 Validation of the Robotic and FUS safety strategy - The safety concept according to the previously defined list of technical constraints for ultrasonography guided FUS therapy by robotic assistance: robotic system including issues such as weight, size and need for safe, effective ultrasonic coupling will be validated. Any kind of mal function such as collision, false positioning, lost acoustic coupling will be recorded and fed back to the respective WP3. The safety strategy also encompasses the therapy planning and therapy monitoring. Both are highly critical items from a clinical safety point of view. During the validation of FUTURA on the Thiel soft embalmed cadavers worse case scenarios will be applied such as inadvertent movement of the cadaver, manual disconnection on components, decoupling of the FUS and imaging probes during sonication, etc. Failure modes and effects analysis will be applied to meet the ISO 13485 standards.
T9.5 Final preclinical validation of the FUTURA platform as a whole - This Task will be active during the final stage of the project. As the FUTURA platform is a highly complex, innovative and complete robotic system with components e.g. robot arms, transducer, hardware connecting interfaces, drives, sensors, internal control mechanism, human communication interfaces the system as whole including the complete clinical work flow will be validated and assessed in via of clinical use. The validation will also include set up and set down procedures including clinical staff form the UNIVDUN hospital und the lead of Dr Ghulam Nabi, the lead Urological Surgeon at UNIVDUN. With these sessions the staff can be trained on the system and their final assessment will be fed back to the respective WP teams to assure the systems final modifications and improvements to become ready for first in human.