The 178th Meeting of the Acoustical Society of America (ASA) was held December 2–6, 2019, in San Diego, California. Although ASA meetings cover scientific, medical, and industrial aspects of sound, several segments were of particular interest to the focused ultrasound community, including special sessions on quantitative ultrasound, phantom development, and the bioeffects of cavitation.
ASA holds two large meetings each year, and each diverse program attracts up to 2,000 invited and contributed papers and posters.
The following presentations addressed various applications of therapeutic ultrasound:
Brain
- Elisa Konofagou from Columbia University presented an invited paper that provided an overview of drug delivery and treatment of neurodegenerative disease using focused ultrasound. Invited paper #4aBAa3.
- The Columbia group described their experiments conducting real-time in vivo imaging of brain displacement during focused ultrasound-induced neuromodulation in rodents. The group seeks to understand the physical mechanism behind neuromodulation and use the data to provide effective targeting and improved treatment monitoring. Abstract #2aBAb4.
- Hong Chen, from Washington University in St. Louis, presented an invited paper on focused ultrasound–enhanced opening of the blood-brain barrier to increase brain tumor biomarker concentrations in the blood. Her results in small and large animal models elevated brain-specific biomarker content in the blood of treated subjects, which could lead to improved diagnostic outcomes of brain tumors when using liquid biopsy. Invited paper #4aBAa5.
- Steven Craig, from the Georgia Institute of Technology, presented an invited paper on acoustic metamaterials for imaging through skull. To remedy the acoustic energy dissipation found in previously designed materials, the team used non-Hermitian complimentary metamaterial with an active gain circuit to achieve high acoustic transmission at high frequencies. Their novel design reserved imaging information for objects inside the skull and enhanced focused ultrasound energy delivery. Invited paper #4aPA7.
- A University of Minnesota group characterized the transmission efficiency of broadband transcranial focused ultrasound in a site-specific, patient-specific manner. The group introduced a dual mode ultrasound array and used it to determine the acoustic properties of the skull, provide better penetration, and reduce beam aberrations. Their methodology also allowed them to identify the optimal frequency for providing low reflection and high transmission in different parts of the skull. Abstract #4pBAa1.
- A collaborative group based at INSERM LabTAU in Lyon, France, presented two different platforms with integrated low-energy focused ultrasound stimulation systems and electrophysiological tools commonly used in neurosciences for the in vitro study of biological mechanisms involved in ultrasound neuromodulation or neurostimulation. Applying low-energy ultrasound modulated the inherent neural function of individual excitable neurons by changing the action potential threshold and stimulating inhibitory and excitatory potentials in a studying using hippocampal brain slices from mice. Abstract #4pBAa2 and Abstract #4pBAa3.
Drug Delivery
- To improve the delivery of therapeutic agents across the blood-brain barrier, Costas Arvanitis’ group at the Georgia Institute of Technology tested various parameters for the use of focused ultrasound plus microbubbles and then focused ultrasound plus temperature-sensitive liposomes loaded with doxorubicin in mice. Their strategies improved the delivery of loaded nanoparticles in the setting of the brain tumor microenvironment. Abstract #1aBAB6.
This work was featured in Science Daily. - Tatiana Khokhlova presented an invited paper from multidisciplinary teams at the University of Washington and Lomonosov Moscow State University describing the use of pulsed focused ultrasound for tissue permeabilization without contrast agents. The group applied ultrasound bursts of shock waves to create sparse cavitation clouds and showed that such efforts can be controlled by varying the F-number of the transducer. This “fan out proliferation” of bubble clouds is a milder version of histotripsy (slower process at lower pressures) that could be used in drug delivery applications. Invited paper #4aBAa6.
- Researchers at the University of Colorado developed a model for lipid-encapsulated microbubbles using a transient theory that incorporates the microscale physics of lipid-lipid interactions. Their model could provide valuable insight into the microbubble dynamics used for both imaging and therapeutic applications. Abstract #4pBAa8.
Bone/Musculoskeletal
- The Modélisation et Simulation Multi Echelle (MSME) laboratory group in Paris estimated the influence of compressive stresses on the ultrasonic response of bone implant interfaces. They used quantitative ultrasound to determine the heterogeneity and distribution of such stresses for assessing the stability of bone implants for osseointegration. The same group presented work on characterization of wave propagation in dental implants for further assessment of their stability. Abstract #4aBAb1.
- Researchers at Pennsylvania State University tested various histotripsy parameters to compare mechanical fractionation versus thermal denaturation changes in collagenous tendons. Abstract #4aBAa11.
Kidney
- The University of Washington group used acoustic radiation force and vortex beams to trap and control the 3D motion of milimeter-sized dense objects in a fluid. The proof-of-concept study included beads with different diameters and materials, thus providing future therapeutic perspectives for the guiding and eventual removal of small kidney stones or stone fragments after lithotripsy through the urinary tract. Abstract #4aBAb3.
- The Mayo Clinic studied the use of optical coherence elastography (OCE) for the evaluation of Rayleigh propagation in soft matter micellar fluids. The technique uses ultrasound excitation to produce Rayleigh waves and could potentially be used to measure the viscosity and other mechanical properties of micellar fluids (such as mucus) for evaluation of infections. The same group presented work showing that OCE could also be used to probe and assess the mechanical properties of bulk materials (such as renal tissue) for the evaluation of chronic kidney disease or renal transplant rejection. Abstract #4pBAa9.
Cardiovascular
- Elisa Konofagou’s group at Columbia University used low-intensity, continuous wave focused ultrasound to reversibly depress heart rate in anesthetized mice. They aimed to measure changes in autonomic nervous system regulation caused by focused ultrasound—based neuromodulation. Abstract #3pBA15.
- Researchers in Montreal studied the dynamics of ultrasound localization microscopy (ULM), which localizes and tracks microbubbles at very high image acquisition speeds, to achieve subwavelength spatial resolution of blood vessels. The group developed an anatomically realistic simulation tool, based on two-photon microscopy, as a validation framework for ULM image formation algorithms. Their study also investigated the impact of microbubble concentration on the accuracy of the localization. Abstract #4pBAa5.
- Paul Dayton’s group at the University of North Carolina presented collaborative work developing a dual frequency (4/22 MHz) transducer for contrast agent—enhanced intravascular acoustic angiography. The device transmits low frequency waves to excite the contrast agents while simultaneously receiving high frequency signals emitted by the microbubble oscillations for high resolution vessel imaging. Abstract #4pBAa7.
Miscellaneous
- Subha Maruvada from the US Food and Drug Administration presented an overview of how biomedical acoustics is breaking barriers in science and medicine. Focused ultrasound as a therapeutic modality and a tool for opening the blood-brain barrier were included topics. Abstract #2pIDb4.
- Alex Peek presented a paper from the University of Washington/Lomonosov Moscow State University group on their development of a novel bilayer aberration-inducing gel phantom for focused ultrasound applications. Invited Paper #5aBA13.
- The University of Washington/Lomonosov Moscow State University group pursued aberration correction using nonlinear backscattered signals from the focus of an ultrasound beam. A multi-element high-intensity focused ultrasound array was used for both emitting and receiving backscattered ultrasound waves. Abstract #5aBA6.
- Yak-Nam Wang from the University of Washington group presented the study on testing the use of histotripsy to treat abscesses in a novel porcine model. The team was able to liquefy the viscous pus contents and produce a 5-fold reduction in bacterial viability. Abstract #4aBAa12.
- Researchers at Nanyang Technological University in Singapore sought to characterize the antibacterial effects of ultrasound on biofilms. Ultrasound exposure increased c-di-GMP expression in bacterial colonies to strengthen (rather than the expected debilitation) the bacterial colonies. Abstract #4pBAa4.
- The Nanyang group also used focused ultrasound to evaluate remote hydrogelation by metal-ligand coordination (Abstract #3pBA11) and studied the cavitation response from multi-cavity and porous PLGA microparticles (Abstract #1aBAb5).
All abstracts can be found in the online meeting program. The Foundation thanks Ivan Suarez, PhD, a postdoctoral researcher at INSERM LabTAU in Lyon, France, and Vera Khokhlova, PhD, Senior Principal Engineer in the Center for Industrial and Medical Ultrasound at the University of Washington, for writing this meeting report. LabTAU is a focused ultrasound Center of Excellence.
The next meeting is scheduled for May 11-15, 2020, in Chicago.