Periodic Reporting for period 1 - UCOM (Ultrasound Cavitation in Soft Materials) Reporting period: 2018-10-01 to 2020-09-30 Summary of the context and overall objectives of the project UCOM is the acronym of the project “Ultrasound Cavitation in sOft Materials”. Ultrasound Cavitation (US) has extended use in bioengineering. Lithotripsy to treat kidney stones, ultrasonic imaging to view the inside of the body and root canal treatment to deal with infections at the centre of a tooth, are only a few of the already existing applications which use technology that is based on the physics of ultrasound cavitation.Nevertheless, there are still a lot of unanswered questions regarding cavitation and its effects and the related technology is not yet ready for wide adoption. Therefore, studying the science behind the physical phenomena of ultrasound cavitation may further define the future of many clinical applications. To that purpose, UCOM is investigating in depth how the bubbles interact with tissues, aiming to provide a safe way to use ultrasound cavitation in the existing medical applications. This is crucial, since cavitation may be harmful if not controlled properly. For example, in lithotripsy a wrong choice of the applied acoustic wave parameters can cause damage to the kidney. Additionally, the UCOM research results may contribute to the development of more medical applications, e.g. sonoporation and sonoprinting. The UCOM researchers develop, improve and validate new state-of-the-art cavitation models and interaction with soft materials (e.g. tissues) against both existing and new experimental data to reply to the long-lasting open questions: (1) Can fundamental experimental studies be designed to allow the temperatures developing during bubble collapse be quantified by measurement/simulation? (2) Can new state-of-the-art, experimentally validated, computational models which couple fluid dynamics, chemistry and soft material mechanics, simulate the interactions of shockwaves, cavitating bubbles and soft matter in the aforementioned applications? (3) What is the cavitation threshold of tissues and how can we control cavitation in Tissue Mimicking Materials (TMM) that will allow the relevant experiments to be conducted in vitro? Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far Until mid - term the UCOM consortium has trained the 15 recruited ESRs on a range of unique scientific modules, that have broadened their perspectives in both research and classical engineering skills. Equally important, the ESRs have been trained on a range of transferable skills, have started disseminating the work performed and have been engaged to outreach activities. With regards to the research conducted, the ESRs have started performing experiments to address the onset of cavitation in tissue mimicking materials (TMM), ultrasound assisted drug delivery techniques, bubble cleaning as well as experiments during single bubble collapse dynamics. At a theoretical/numerical level, the UCOM researchers have started developing and validating new state-of-the-art tools for US modelling in tissues/TMM, heterogeneous bubble nucleation at walls, shockwave/bubble interaction (including deformable surfaces/cell membranes) and chemical reactions inside collapsing bubbles. This can help in the understanding of the applications mentioned above, and thus be essential in improving their efficacy.More information about the research related work conducted so far can be found here:http://ucom-itn.eu/research Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Progress beyond the state of the art has already been noted in the following areas:1. Facility for temperature/species measurements of collapsing bubbles: A purpose-build experimental test rig is ready to study the microscopic phenomena occurring at the last stage of the bubble collapse and the changes in concentration of gas species. These studies will improve physical understanding and aim to be transferable in medical treatments. (Davide Bernardo Preso, EPFL) 2. Experimental report on multi-modality imaging setup for characterization of the influence of various parameters on enhanced acoustic absorption: This study could result in a small pilot trial for clinical translation. (Ryan Holman, UNIGE)3. A 3D numerical solver has been developed simulating the bubble collapse processes considering real-fluid thermodynamics. The model can predict the temperatures developing inside the collapsing bubbles, considering deviation from the ideal gas and the occurrence of chemical reactions. (Saeed Bidi, CITY)4. Test rig for tissue mimicking materials: TMM are required for experiments and simulations investigating the effects of US on cavitation threshold and further development. Values of acoustic and thermal parameters for PVA hydrogels were found to be comparable to those of soft tissue. (Lisa Braunstein, ICR)5. Simulation of crown formation from a laser generated bubble close to a free surface: Numerical simulations of tiny, cavitation bubbles were performed in the vicinity of various parameters. These simulations can be used as a cost-effective tool, to tune some devices in the biomedical field, which employ cavitation bubbles to damage unwanted tissues or bodily masses. (Youssef Saade, UT)6. Fluid-structure interaction (FSI) solver for modelling the US-induced deformation of TMM:A multi-material solver has been developed and validated against benchmark experiments showing good agreement; it is now applied to realistic cases of US in order to provide insight of the physical mechanisms taking place at conditions where experimentation is not possible. (Armand Shams, CITY)7. Experimental facility for producing tuneable microbubble populations: This project thrives to achieve a better understanding of bubble and tissue interaction, which is crucial to the next generation of contrast agents and to the emerging application of therapy with ultrasound and microbubbles. (Ali Rezae, UT)8. Experiment for controlling cavitation nucleation:The results of the performed experiments may enable a new way to diagnose the cause of acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD), a progressive illness that results in long-term breathing problems. With the current methods of diagnosing the cause of exacerbation around 30% of the occurrences remain unexplained. (Dawid Surdeko, UT)Expected results until the end of the project: The project’s results aim to help engineers design commercial solutions that will be used in the medical sector. One of the main UCOM research topics is to study the physics behind the application of drug delivery for cancer treatment, aiming to further develop the techniques of sonoporation and sonoprinting. By using these two methods, one could deliver the medicine in doses that would be lower but in higher concentration, targeting directly the desired spot; the cancerous tissue. This way the rest of the patient’s body is protected from the harmful effects of chemotherapy. As a result, millions of patients that receive chemotherapy treatment each year will benefit from the development of this technology. Additionally, the techniques that use ultrasound cavitation require little to no hospital stay. The safe use of those techniques more often in the future could reduce the demand on hospital beds.Finally, the UCOM project investigates the use of ultrasound cavitation to clean dirty objects in the medical and industrial sector, a technique that offers a sustainable solution to significantly decrease the use of chemicals. Formation of an axisymmetric crown around the central jet
