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Nucleation of cavitation in vivo
Prof Larry Crum (University of Washington, US)
email: lacuw@uw.edu

The presence of cavitation nuclei are normally required in order to induce cavitation in water-based materials, such as mammalian tissue, as the homogeneous nucleation threshold is beyond the range of most acoustic-pressure generation systems (a notable exception is the “intrinsic threshold” achieved by some histotripsy devices). There are a number of potential models for these nuclei, but one that continues to receive favor is the “crevice model”, in which a pocket of gas is contained in a crack or crevice in a contaminating particle and stabilized against diffusion by the geometry of the crevice. This presentation will present evidence that the crevice model also applies to cavitation nucleation in soft tissue.

Bubbles in front of a solid boundary
Prof Werner Lauterborn (University of Gottingen, GE)
email: Werner.Lauterborn@phys.uni-goettingen.de

Bubbles near solid boundaries are interesting objects because of their erosion and cleaning potential. The scientific approach to describe and build up an understanding for bubble action on solid surfaces is reviewed and discussed up to the latest developments. Experimentally, the highest-speed photographic instrumentation is needed to capture the fast dynamics of bubble shape—in particular liquid jet formation—and shock wave propagation. On the theoretical-numerical side, the respective bubble models have to be formulated and solved. Because of the complicated dynamics recourse has to be made to the Navier-Stokes equations with appropriate boundary conditions. Their numerical solution requires high-speed computation facilities and appropriate software. Results on bubble shape dynamics with jet formation and shock wave emission  obtained with the help of the open source software package OpenFOAM is reported for bubbles expanding and collapsing at different distances from a flat solid boundary.

Probing hidden interfaces of nanobubbles by elaborate optical and combined optical-force microscopy methods
Prof Holger Schonherr (University of Siegen, GE)
email: schoenherr@chemie.uni-siegen.de

In the past decades long-lived gas surface nanobubbles (SNBs) were shown to reside e.g. at the solid-water. The long controversy of SNB stability and the on-going discussion about bulk nanobubbles may have been fuelled by ill-defined experimental conditions. In particular the role of contaminations and the adequate analysis of nanobubble properties are of paramount importance. Here we discuss new rigorous experimental protocols and time-resolved optical as well as combined optical – atomic force microscopy (AFM) approaches that ascertain that (i) indeed nanobubbles are being studied, which provides that (ii) the boundary conditions for the development of adequate theories are established.

High fidelity simulations of compressible multiphase flows using front tracking
Prof Yiannis Ventikos (University College London, UK)
email: y.ventikos@ucl.ac.uk

Front tracking is among the earliest computational methodologies to be developed for the numerical simulation of multiphase flows. Despite providing with impressive results, it is not favoured by the research community due to the significant complexities that arise when treating three dimensional problems. In this talk, we will document detailed simulations of compressible liquid-gas flows using a high fidelity front tracking technique. The investigations include three dimensional configurations and provide a detailed look into the complex flow phenomena that develop following the interaction of shock waves with bubbles, drops, free and solid surfaces. By drawing inspiration from these physical phenomena, unique technological applications with immense potential can be developed.

High Performance Simulation of Multiphase Flow
Prof Stephane Zaleski (Sorbonne Université,CNRS,Institut Jean le Rond ∂’Alembert, FR)
email: stephane.zaleski@upmc.fr

Droplets, bubbles and interfaces offer fascinating physical and mathematical problems and are a key part of the microscopic modeling of multiphase flow in cavitation and other contexts. The talk will describe how to address these problems numerically, using tools such as the Volume of Fluid method with exactly mass and momentum conserving numerical methods and accurate, well balanced capillary forces. The issues arising from the upscaling of simulations to the most extreme HPC environments will also be discussed.

Research Highlights from the MSCA-ITN programme: ‘Development
and experimental validation of computational models for Cavitating Flows, surface Erosion damage and material loss ‘Dr Steffen

Dr Steffen Schmidt (Technical University of Munich, GE)
email: steffen.schmidt@tum.de

Vibrating microbubbles for Imaging and Therapy
Prof Nico Je Jong (Erasmus/TU Delft, NL)
email: n.dejong@erasmusmc.nl

Microbubbles for diagnosis: The mechanism by which the microbubbles enhance the contrast is two- fold. First, acoustic waves are scattered by the bubbles due to the large difference in acoustic impedance between the gas and the surrounding liquid. Second, the large compressibility of the gas bubbles results in radial oscillations of the bubbles in response to the ultrasound pressure waves. The radial oscillations are highly non-linear and produce non-linear sound waves, which are exploited in contrast-enhanced ultrasound imaging. The strong scattering of the microbubbles allows for the visualization and quantification of blood perfusion in organs, e.g. heart, liver, or kidney. The sensitivity of the bubble detection, down to a single bubble in vivo, facilitates targeted molecular imaging applications for the diagnosis of disease at the molecular level. Targeting ligands that bind specifically to selective biomarkers on the blood vessel wall can be labelled to the micro-bubble shell. The approach here is to inject targeted bubbles intravenously, then to wait 5 to 10 minutes for the freely flowing bubbles to be washed out by the lungs and the liver and then to image the adherent bubbles using ultrasound. One other approach is to discriminate acoustically between freely flowing and adherent bubbles through spectral differences through a resonance shift of the adherent bubbles due to the interaction between the bubble and the vessel wall. This approach would require that all bubbles have the same response to the ultrasound driving signal, which is up to now not possible because of the large size distribution of the commercial agents. Recently microbubbles were targeted to stem cells to produce echogenic complexes, which can be directed towards diseased tissue using acoustic radiation forces to up-regulate the therapeutic targeting efficiency Microbubbles for Therapy: Contrast bubbles can themselves serve as therapeutic agents. Several configurations are possible here. First, a drug can be co-administered with the bubbles while ultrasound-induced bubble oscillations close to cells promote local drug uptake through mechanical stress to the adjacent cell membranes, a process called sonoporation. Second, UCAs can be loaded with drugs, e.g. for the local delivery of chemotherapeutic drugs with a narrow therapeutic index, or for the delivery of genes. The payload can be directly incorporated in the bubble coating, or in the core of the bubble, or in liposomes attached to the bubble shell. Drug-loaded microbubbles can be imaged at low acoustic pressures aiding the guidance and real-time monitoring of the therapy, then at higher acoustic pressures rupture of the bubble shell triggers drug release. Ideally, the release of such a payload follows a step response after passing an insonation pressure threshold for the controlled release of the payload in a confined and highly localized region determined by the position of the acoustic focus and the position of the bubbles. The prime focus of such a local delivery is to reduce the systemic exposure to toxic drugs and to increase the delivery efficacy by preventing early capture of the drugs or genes by the systemic system.

Microbubbles & Nanobubbles for Therapeutic Drug Delivery
Prof Steven Evans (Leeds University, UK)
email: s.d.evans@leeds.ac.uk

In the presence of a gas bubble in solution lipids spontaneously assemble at the air/gas boundary presenting a lipid monolayer with the zwitterionic head groups oriented to the aqueous phase. The lipids both stabilize the gas from dissolution and present a biocompatible interface to reduce identification by the immune system. The natural echogenicity of such bubbles combined with their biocompatibility makes them ideal theranostic agents for ultrasound aided drug delivery. Here we describe our recent approaches for the bubble formation, characterisation and the treatment of cancer. In particular the development of microfluidics for the optimised production of drug loaded micro- and nanobubbles.[1,2] I will describe the formation and subsequent invitro and in vivo optimisation of lifetime and ultrasound properties, including their sub-harmonic response as well as describe some of our novel microbubble architectures.[3-8] Finally, I will show that our microbubbles plus ultrasound display enhanced therapeutic benefit for the treatment of colorectal cancer.

Bubbles and droplets for nanotechnology and nanomedicine
Prof Michel Versluis (University of Twente, NL)
email: m.versluis@utwente.nl

The acoustic excitation of bubbles and droplets has widespread use in medical technology and nanotechnology applications. These applications include bulk and surface acoustic waves for bubble and droplet production, as well as bubble and droplet actuation to perform local drug delivery or local and well-controlled surface cleaning. Microbubbles and low-boiling point nanodroplets can also be decorated with a payload which carries great potential for their use as drug delivery agents in the context of personalized medical therapy. Key to all these emerging applications is a precise acoustic control of the interaction of ultrasound with the bubbles and droplets. The challenge here is the combined microscopic length scales and ultrashort time scales associated with the mechanisms controlling bubble and droplet formation and its activation processes, which we solve by high-resolution ultrafast microscopy, even down to the nanosecond. Together with theoretical modeling and numerical simulations these experiments assist in our in-depth fundamental understanding of bubble and droplet behavior, which then provides intriguing new prospects for innovative solutions in nanotechnology industry and in nanomedicine.

Cavitation bubble dynamics in soft biological material
Dr Ashfaq Adnan (University of Texas, Arlington, US)
email: aadnan@uta.edu

Dynamic cavitation in soft materials is gaining interests due to emerging medical implications such as the potential of cavitation-induced brain injury or cavitation created by therapeutic medical devices. Our current understanding of dynamic cavitation in soft materials is still limited primarily due to unavailability of robust constitutive relations of soft materials in dynamic environment. This talk will cover cavitation nucleation mechanisms in soft materials such as gelatin and simulated extra cellular matrix. Recent progress on the development of viscoelastic constitutive models for gels will be discussed.

Diffusion enters into hydrodynamic cavitation
Prof Peter Pelz (Technische Universität Darmstadt, Chair of Fluid Systems, GE)
email: peter.pelz@fst.tu-darmstadt.de

Diffusion is said to be far too slow for being important in hydrodynamic cavitation. This general statement is wrong when it comes to the initial process of cavitation: nucleation. During nucleation there is a large velocity difference between the bulk flow and surface bounded nuclei resulting in thin diffusion layer and surprisingly high muss flux. Thus, a nucleation frequency in the order of 1 to 10 kHz is feasible. In fact, such high nucleation rate is needed for the evolution of a cavity sheet of realistic length. Diffusion cannot be ignored. It is has become the key in understanding streak, sheet and cloud cavitation

Simulations of cavitating flows in ship hydrodynamics with incompressible flow models
Prof Richard Bensow (Chalmers University, SE)
email: rickard.bensow@chalmers.se

Cavitation on ship propellers may lead to issues in terms of pressure pulses and vibrations on the hull, radiated noise, material erosion, and thrust loss. Due to the placement in the stern of the ship, viscous effects are important to consider, and due the large size compressible flow models are prohibitively expensive. However, depending on which type of cavitation nuisance one studies, either RANS or LES approaches may be used while in design situations one is even restricted to potential flow methods. This presentation will give an overview of current state of the art in research and engineering, respectively, with respect to numerical cavitation assessment in ship propulsion, ranging from more canonical cases and detailed studies, through advanced applications with RANS and LES, to optimisation utilising the limited information from potential flow cavitation
solvers.

Cavitation erosion in hydraulic turbines
Dr Magdalena Neuhauser (Andritz Hydro, CH)
email: magdalena.neuhauser@andritz.com

Cavitation can cause damages in all types of hydraulic turbines from turbines with low head and large discharge to turbines with high head and small discharge. If possible turbines are designed in order to avoid cavitation in the whole operating range. CFD and reduced scale model tests allow to assess the risk of appearance of cavitation for a specific design.Since it is not always possible to avoid cavitation for all operating points, it is important to understand the mechanisms of cavitation erosion in order to evaluate the risk of damages in a turbine even if cavitation occurs. There are two main axes of research within ANDRITZ Hydro aiming at minimizing the occurrence of damages due to cavitation erosion. On the one hand coupled fluid structure simulations, like Smoothed Particle Hydrodynamics (SPH-ALE) for the fluid coupled to finite element analysis (FEM) for the structural part, are carried out to understand erosion at the microscopic scale of a bubble collapse. On the other hand different materials are tested for their resistance to cavitation erosion in dedicated cavitation erosion test rigs. These cavitation test rigs also allow to check the influence of several parameters and geometries, to visualize cavitation by high speed videos and to develop procedures that might help assessing cavitation erosion at reduced scale model tests like for example paint tests.

A metrological view on in-nozzle flow and primary atomization of modern GDI injectors
Prof Michael Wensing (FAU Friedrich-Alexander Universität Erlangen-Nürnberg, GE)
email: michael.wensing@fau.de

Due to small scales, high velocities and high optical density and/or limited optical access the in-nozzle flow and the primary breakup of modern GDI sprays is still not fully understood. Comparable atomization to diesel injection processes is reached with significantly lower fuel pressures. This is possible by massive cavitation, which creates a very complex multiphase transient flow inside the injector – sac volume and nozzle holes. New optical measurement technologies and high speed cameras provide new insight to the flow and atomization processes. Three synchrotron X-ray techniques are applied at matching experimental conditions and for the same injectors to study the initial spray velocity field, the mass distribution and the spray structure in the primary spray region. Additionally, a newly developed Light Sheet Fluorescence Microscopic Imaging (LSFM) technique and injection mass rate measurements provide information on primary spray structures and the underlying breakup mechanisms in the first 2mm after nozzle exit. A completely different spray breakup is found for the tested GDI in comparison to diesel injectors. While diesel jets leave the nozzle as an intact jet and disintegrate then very fast from the surface, GDI spray leave the nozzle almost broken up due to the massive cavitation inside the nozzle. High speed films provide a very clear view for the audience into the processes in the primary atomization region for present injector designs. The findings are summarized in the degree of spray hole filling — around 65 % for the GDI injector (approximately 100 % for the diesel case) – and penetration velocities and velocity profiles across the nozzle-hole. Glass nozzle investigation with different measurements techniques show cavitation structures inside the nozzle hole and variations of these structures with important design and operating parameters. From a fundamental point of view the breakup of liquid fuel and spray initiation in automotive applications is driven by cavitation, turbulence, aerodynamic forces and relaxation of velocity profiles. High sophisticated optical diagnostics provide an insight into the dominating spray breakup mechanisms at different stages of gasoline direct injection processes.