The aim of CURE-OP is to develop the first commercially available high intensity focused ultrasound (HIFU) platform specifically designed for combinational cancer therapy. We will develop robotic device that can deliver a broad range of ultrasound regimes (hyperthermia, thermal ablation and cavitation) enabling different types of cancer polytherapy. In the scope of this project’s timeframe, the HIFU device will be used in combination with a radiotherapy (RT) machine and tested clinically.
Surgeons and oncologists have been showing a keen interest in using HIFU to treat cancer, especially in combination with existing treatments. HIFU is a non-ionizing radiation, which can enhance RT treatments, thus increasing the safety profile and efficacy with reduced ionizing radiation and lower costs of the overall treatment. It will be possible to explore other combinational therapies such as local drug delivery and immunotherapy with malignant tumour ablation.
Extracorporeal high-intensity focused ultrasound (HIFU) provides a noninvasive alternative to conventional therapies. It consists of targeting a specific tissue area using a focused acoustic wave. While it goes through the tissue, the wave will lose some energy that will be dissipated in heat leading to a rise of temperature in the tissue.
Cancer has a significant and increasing impact on society as it was the second leading cause of death worldwide in 2018 with 9.6 million deaths estimated.
Radiotherapy (RT) is one of the most used cancer therapies. However, this technique induces serious side effects. Furthermore, the ionizing radiation delivery cannot be repeated several times due to lifetime dose accumulation. Heat is a known radiation sensitizer.
Indeed, hyperthermia (HT) is a therapeutic procedure often used as a cancer adjuvant therapy. It generally refers to the raise of the tissue temperature between 40 and 45 °C for several minutes up to an hour. Through different mechanisms such as immune stimulation or increase of perfusion and oxygenation, HT improves tumor responses to radiation therapy.
Combining RT and moderate heat could then lead to a reduction of ionizing radiation delivery improving patient safety and treatment efficiency. Thus, the idea to use HIFU to generate moderate heat in combination with RT. Theraclion is a French company specialized in echotherapy.
CURE-OP has the aim to develop an ultrasound therapy prototype machine for combinational cancer therapy.
HIFU is focused ultrasound at intensities in the range of Isa = 100-10000W/cm2. Both mechanical and thermal effects can occur in most applications. The most common mechanical effect is cavitation and the classic thermal effect is heating, due to absorption. The geometry of the heated/ablated area is often described as cigar-shaped, matching the focal volume of the HIFU field. Depending on the transducer frequency-of-operation, the size can range from a few millimetres at higher frequencies, up to a couple of centimetres for low frequency treatments.
Hyperthermia (HT) is a therapeutic procedure that tends to raise the tissue temperature between 40 and 45 °C. This technique differs from thermal ablation as it doesn’t target direct necrosis through intense and rapid heat (> 60 °C) but rather maintain a mild heat for a longer time. It is mostly used in combination with other therapies like chemotherapy (CT) and radiotherapy (RT). It has for goal to improve clinical response and decrease oncological treatment toxicity by sensitizing tumors allowing the main treatment to treat radio resistant tumors and/or lower ionizing radiation delivered to patient. Moderate heat of tissue increases blood perfusion as well as tumor oxygenation. As hypoxia (oxygen deficit) is a major factor of radio resistance, those microenvironment changes could lead to better tumor responses.
Cancer has a significant and increasing impact on society as it was the second leading cause of death worldwide in 2018 with 9.6 million deaths estimated. Radiotherapy (RT) is one of the most used cancer therapies. However, this technique induces serious side effects. Furthermore, the ionizing radiation delivery cannot be repeated several times due to lifetime dose accumulation.
Theraclion is a French company specialising in high-tech therapeutic ultrasound equipment. We design and market Echopulse® and SONOVEIN®, two innovative echotherapy solutions.
ICCAS is part of the University of Leipzig in Germany. The Innovation Center Computer Assisted Surgery – ICCAS – is a pioneer in developing computer-aided, integrative technologies and intelligent assistance systems in medicine. It is the interface between clinical requirements and economic implementation of innovative medical products. The main goal is the improvement of therapy methods and work processes to increase patient safety and economic relevant technology.
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Embedded in a worldwide network of clinical and academic partners, Fraunhofer MEVIS develops real-world software solutions for image and data supported early detection, diagnosis, and therapy. Strong focus is placed on cancer as well as diseases of the circulatory system, brain, breast, liver, and lung. The goal is to detect diseases earlier and more reliably, tailor treatments to each individual, and make therapeutic success more measurable.
WORK PACKAGE 1
Project management and IPR management
The objective of this WP is to implement a project management framework to coordinate and monitor the project tasks, track budget vs. actual cost and follow-up achievements as well as to manage IPR issues.
WORK PACKAGE 2
This WP aims at providing the required specifications related to the development of the hardware (structure of the device, components …) and software (Structure design of the software, …). It will also be dedicated to the definition of the test and validation Plan.
WORK PACKAGE 3
In this WP Theraclion will design and develop the mechanical and electronic hardware of the device according to the specifications defined in WP2:
1. The cabinet (including electronics, cooling system, power supplies, mechanical design, ultrasound engine) Many components of the Echopulse system will be incorporated into the new device. Nevertheless, the firmware (embedded software to drive the hardware) and the user interface (UI) will be adapted to the modified hardware and 3D imaging software.
2. The interface to the Treatment Head (VTU)
3. Software interfaces (basic low-level software components for hardware control, therapy planning and treatment control)
The ultrasound engine (electronics for the ultrasound imaging subassembly) will be acquired from an OEM vendor.
WORK PACKAGE 7
HIFU PULSE DESIGN and validation
This work package is entirely dedicated to investigate new pulse parameters that can be used to achieve mild heating or mild mechanical stress in tissue. Traditionally HIFU has been used for thermal ablation using highly energetic pulse sequences to achieve tissue coagulation. Theraclion uses a calibration technique which allows to fine tune the delivered acoustic power in order to assure reliable thermal ablation. We are planning to use a similar technique enhanced by numerical real-time simulations that can take advantage of a probing in order to optimize the energy delivery. Task 7.1 will define the parameters space and allow to validate to calibrate and validate the simulations with in controlled experiments. This experiments will be executed in ex-vivo tissue and in vivo animal models, which are already validated for ablation pulses. Task 7.2 will bring extra information to the simulation which can be run in real-time during a treatment. This information will be based on the attitude of tissue to change acoustical properties when the temperature changes. With fast processing times nowadays easily achievable the temperature of each adjacent pulse can be better estimated. The input is a probing or backscatter signal, which will be used to regulate the delivered power. Task 7.3 will be used to validate temperature control and generally the HIFU pulse and an in vivo setting to assure good translation into to the clinical trails.
WORK PACKAGE 8
Integration and clinical validation
The software and the hardware developed in WP 3 and 4 will be integrated together, then tested and validated in vivo.
WORK PACKAGE 9
Dissemination, regulary activities and market deployment
The objectives of WP6 are to have the new technologies resulting from the project interfaced with the different targeted data users (medical practitioner, industrialization….) and the corresponding market opportunities. To achieve this goal, the related tasks aim at: • Promoting extensively the project works in the medical sector, establishing links with related on-going research and industrial initiatives in hospitals and training centers (including university);
• Setting the foundations for future commercial exploitation and opportunities.
• Prepare the regulatory files to obtain the CE marking
WORK PACKAGE 6
Robotics and RT workflow
RT workflow integration, Synchronization, Robotic movement
The main purpose of this work package is the integration of the ultrasound therapy hardware with the robotic arm, the treatment head and the electronic cart into the radiation therapy facility. The challenge is here, that neither the ultrasound system should influence or hamper radiation therapy nor that the RT system influences the proper US therapy. Final goal is to allow a simultaneous US-RT-therapy. However, an intermediate stage would be a consecutive application of US followed by RT.
The work package is structured in 5 tasks. In Task 6.1 the physical hardware integration of the CURE-OR system is addressed. The CURE-OR system has to be fixed near the patient table so that both therapy modalities reach the target volume. In Task 6.2 a produce will be developed to synchronize the coordinate system of both therapy systems. Task 6.4 ensures that the robotic arm does not shield the beam of the RT system. Aim of Task 6.4 is to ensure a permanent acoustic coupling of the US treatment head to the skin of the patient, even if the treatment head moves due to focal steering of the HIFU beam or during the acquisition of diagnostic US images. The fine steering of the robotic arm in order to perform US-therapy (heating, ablation) or US imaging is solved in Task 6.5.
WORK PACKAGE 5
US Therapy planning and advanced imaging
This work package concentrates on planning of the ultrasound therapy as supplement to the RT-therapy planning. For this several data and information gained during the RT planning should be used for the US treatment. E.g. such data are CT and MR images, segmentation information of the different target volumes and the RT organs at risk. US therapy base on ultrasound image data from the CURE-OP treatment head (comp. T 6.5 and T4.2). So a fast and precise registration of this 3D data with the CT/ MR planning images is necessary. In addition, this WP also include experiments to assess whether photoacoustic imaging may yield added value for therapy monitoring in our setup.
The WP is structure in 6 tasks. In Task 5.1 the RT plan is analyzed and all information useful for US therapy planning will be automatically extracted. This is followed by the US therapy planning in task 5.2. Task 5.3 focus on the registration of the US data with the CT/MR data. The optimization task 5.4 allows to improvement the different software modules of WP 5.
WORK PACKAGE 4
Therapy visualisation and motion control
The objective of this WP is to provide software modules to operate the US-RT therapy with the CURO-OP hardware.
This work package is structured into five tasks. The goal of the first task is to collect all data, mainly ultrasound images and position data, and to provide these data for all other components of the software. In the second task the software for the reconstruction and registration of 3D image (3D volumes) from the 2D ultrasound images will be designed. A graphical user interface and visualization of imaging data will be done in the third task. An advance motion detection module with automated feature detection for the compensation of target motion will be developed in task 4.4. The objective of the last task 4.5 is to optimize the software after first completion and integration of all software components. In this task bugs and shortcomings of the first implementation will be fixed and the software improved.