Measuring the sounds of microbubbles for ultrasound therapy

T. Douglas mast – doug.mast@uc.edu

Instagram: @baglamist
University of Cincinnati, Cincinnati, OH, 45224, United States

Popular version of 2aBAa7 – Measure for measure: Diffraction correction for consistent quantification of bubble-related acoustic emissions
Presented at the 188th ASA Meeting
Read the abstract at https://eppro01.ativ.me/appinfo.php?page=Session&project=ASAICA25&id=3868554

–The research described in this Acoustics Lay Language Paper may not have yet been peer reviewed–

Microscopic bubbles, when caused to vibrate by ultrasound waves, can be powerful enough to break through the body’s natural barriers and even to destroy tissue. Growth, resonance, and violent collapse of these microbubbles, called acoustic cavitation, is enabling new medical therapies such as drug delivery through the skin, opening of the blood-brain barrier, and destruction of tumors. However, the biomedical effects of cavitation are still challenging to understand and control. A special session at the 188th meeting of the Acoustical Society of America, titled “Double, Double, Toil and Trouble – Towards a Cavitation Dose,” is bringing together researchers working on methods to consistently and accurately measure these bubble effects.

For more than 30 years, scientists have measured bubble activity by listening with electronic sensors, called passive cavitation detection. The detected sounds can resemble sustained musical tones, from continuously vibrating bubbles, or applause-like noise, from groups of collapsing bubbles. However, results are challenging to compare between different measurement configurations and therapeutic applications. Researchers at the University of Cincinnati are proposing a method for reliably characterizing the activity of cavitating bubbles by quantifying their radiated sound.

A passive cavitation detector (left) listens for sound waves radiated by a collection of cavitating bubbles (blue dots) within a region of interest (blue rectangle).

The Cincinnati researchers are trying to improve measurements of bubble activity by precisely accounting for the spatial sensitivity patterns of passive cavitation detectors. The result is a measure of cavitation dose, equal to the total sound power radiated from bubbles per unit area or volume of the treated tissue. The hope this approach will enable better prediction and monitoring of medical therapies based on acoustic cavitation.

Figure 1: In an experiment simulating drug delivery through the skin (left), a treatment source projects an ultrasound beam onto animal skin. A passive cavitation detector (PCD) listens for sound radiated by bubbles at the skin surface, while the skin’s permeability is measured from its electrical resistance. Measured bubble activity is quantified using the sensitivity pattern of the PCD within the treated region (highlighted blue circle).

The researchers reported results from two experiments testing their methods for characterizing cavitation. In experiments testing ultrasound methods for drug delivery through the skin (Figure 1), they found that total power of subharmonic acoustic emissions (like musical tones indicating sustained vibrations of resonating bubbles) per unit skin surface area consistently increased when the skin became more permeable, quantifying the role of bubble activity in drug delivery. In a second experiment (Figure 2), the researchers quantified bubble activity during heating of animal liver tissue by ultrasound, simulating cancer therapies called thermal ablation. They found that increased bubble activity could indicate both faster tissue heating near the treatment source and reduced heating further from the source.

Figure 2: An ultrasound (US) array sonicates animal liver tissue with a high-intensity ultrasound beam, causing tissue heating (thermal ablation) as used for liver tumor treatments. Increased bubble activity was found to reduce the depth of treatment, while sometimes also increasing the area of ablated tissue near the tissue surface.

This approach to measuring bubble activity could help to establish standard cavitation doses for many different ultrasound therapy methods. Quantitative measurements of bubble activity could help confirm treatment success, such as drug delivery through the skin, or to guide thermal treatments by optimizing bubble activity to heat tumors more efficiently. Standard measures of cavitation dose should also help scientists more rapidly develop new medical therapies based on ultrasound-activated microbubbles.

Tiny bubbles, big impact: Breaking up blood clots

Christy Holland – hollanck@ucmail.uc.edu

Internal Medicine, Division of Cardiovascular Health and Disease and Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio, 45267, United States

Kevin Haworth,
Internal Medicine, Division of Cardiovascular Health and Disease, Biomedical Engineering, and Pediatrics
University of Cincinnati
Cincinnati, OH 45267 USA

Popular version of 2aBAa5 – Bubble, bubble, sonic trouble: Cavitation dose and therapeutic close
Presented at the 188th ASA Meeting
Read the abstract at https://eppro01.ativ.me//web/index.php?page=Session&project=ASAICA25&id=3867184

–The research described in this Acoustics Lay Language Paper may not have yet been peer reviewed–

Imagine doctors activating tiny, drug-delivering bubbles in the body via a computer — almost like playing a video game — to treat life-threatening conditions. This futuristic approach is becoming a reality, thanks to advances in ultrasound technology and biomedical acoustics.

Cavitation is the formation and movement of tiny gas bubbles when ultrasound waves pass through the body. While cavitation might sound like a side effect from ultrasound, scientists have found a way to harness effervescence to improve medication delivery.

Doctors can use cavitation to help medications reach their targets faster and more effectively. One example is tissue plasminogen activator (tPA), a drug used to dissolve blood clots. When paired with cavitation, tPA can penetrate more deeply into clots. That makes it particularly useful in treating serious conditions, including blood clots in the leg known as deep vein thrombosis and pulmonary embolism, a potentially life-threatening blockage in the lungs.

The challenge lies in finding the right amount of cavitation. Too little bubble activity may have little effect, while too much could damage the surrounding blood vessel. So, medical researchers are working to define a safe and effective “cavitation dose” — the ideal amount of bubble activity to enhance treatment, much like a doctor prescribes a certain dose of medicine for a patient to take.

To help strike this balance, scientists are using a new imaging tool to visualize cavitation as it happens. First, a catheter with tiny built-in ultrasound sources is inserted into a blood vessel to generate cavitation. Then, an ultrasound transducer — similar to one used in fetal imaging — is specially programmed to capture images of cavitation around the treatment area. This view helps doctors understand where bubbles are and how they’re vibrating, so they can adjust the treatment in real time.

The bubbles themselves are made of octafluoropropane (OFP)  — a safe, colorless gas often used in diagnostic ultrasound imaging of the heart and liver. Thanks to a technique called passive cavitation imaging (PCI), researchers can now track cavitation without interfering with the treatment itself.

Leading this innovative work are Kevin Haworth, PhD, and Christy Holland, PhD, both from the University of Cincinnati College of Medicine. Haworth is principal investigator of the Biomedical Ultrasonics and Cavitation Laboratory, while Holland directs the Image-Guided Ultrasound Therapeutic Laboratories, as well as the Center for Cardiovascular Research. By visualizing and guiding these tiny bubbles, doctors may soon be able to deliver treatments with greater precision — helping patients recover faster and more safely than ever before.

Listening for bubbles to make scuba diving safer

Joshua Currens – jcurrens@unc.edu

Department of Radiology; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, United States

Popular version of 5aBAb8 – Towards real-time decompression sickness mitigation using wearable capacitive micromachined ultrasonic transducer arrays
Presented at the 186th ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0027683

–The research described in this Acoustics Lay Language Paper may not have yet been peer reviewed–

Scuba diving is a fun recreational activity but carries the risk of decompression sickness (DCS), commonly known as ‘the bends’. This condition occurs when divers ascend too quickly, causing gas that has accumulated in their bodies to expand rapidly into larger bubbles—similar to the fizz when a soda can is opened.

To prevent this, divers will follow specific safety protocols that limit how fast they rise to the surface and stop at predetermined depths to allow bubbles in their body to dissipate. However, these are general guidelines that do not account for every person in every situation. This limitation can make it harder to prevent DCS effectively in all individuals without unnecessarily lengthening the time to ascend for a large portion of divers. Traditionally, these bubbles have only been detected with ultrasound technology after the diver has surfaced, so it is a challenge to predict DCS before it occurs (Figure 1b&c). Early identification of these bubbles could allow for the development of personalized underwater instructions to bring divers back to the surface and minimize the risk of DCS.

To address this challenge, our team is creating a wearable ultrasound device that divers can use underwater.

Ultrasound works by sending sound waves into the body and then receiving the echoes that bounce back. Bubbles reflect these sound waves strongly, making them visible in ultrasound images (Figure 1d). Unlike traditional ultrasound systems that are too large and not suited for underwater use, our innovative device will be compact and efficient, designed specifically for real-time bubble monitoring while diving.

Currently, our research involves testing this technology and optimizing imaging parameters in controlled environments like hyperbaric chambers. These are specialized rooms where underwater conditions can be replicated by increasing the inside pressure. We recently collected the first ultrasound scans of human divers during a hyperbaric chamber dive with a research ultrasound system, and next we plan to use it with our first prototype. With this data, we hope to find changes in the images that indicate where bubbles are forming. In the future, we plan to start testing our custom ultrasound tool on divers, which will be a big step towards continuously monitoring divers underwater, and eventually personalized DCS prevention.

divingFigure 1. (a) Scuba diver underwater. (b) Post-dive monitoring for bubbles using ultrasound. (c) Typical ultrasound system (developed using Biorender). (d) Bubbles detected in ultrasound images as bright spots in heart. Images courtesy of JC, unless otherwise noted.

2pAOb – Methane in the ocean: observing gas bubbles from afar

Tom Weber – tom.weber@unh.edu
University of New Hampshire
24 Colovos Road
Durham, NH 03824

Popular version of paper 2pAOb
Presented Tuesday Afternoon, November 29, 2016
172nd ASA Meeting, Honolulu

The more we look, the more we find bubbles of methane, a greenhouse gas, leaking from the ocean floor (e.g., [1]). Some of the methane in these gas bubbles may travel to the ocean surface where it enters the atmosphere, and some is consumed by microbes, generating biomass and the greenhouse gas carbon dioxide in the process [2]. Given the vast quantities of methane thought to be contained beneath the ocean seabed [3], understanding how much methane goes where is an important component of understanding climate change and the global carbon cycle.

Fortunately, gas bubbles are really easy to observe acoustically. The gas inside the bubble acts like a very soft-spring compared to the nearly incompressible ocean water surrounding it. If we compress this spring with an acoustic wave, the water surrounding the bubble moves with it as an entrained mass. This simple mass-spring system isn’t conceptually different than the suspension system (the spring) on your car (the mass): driving over a wash-board dirt road at the wrong speed (using the right acoustic frequency) can elicit a very uncomfortable (or loud) response. We try to avoid these conditions in our vehicles, but exploiting the acoustic resonance of a gas bubble helps us detect centimeter-sized (or smaller) bubbles when they are kilometers away (Fig. 1).

weber_figure1 - methane gas bubbles

Figure 1. Top row: observations of methane gas bubbles exiting the ocean floor (picture credit: NOAA OER). The red circle shows methane hydrate (methane ice). Bottom row: acoustic observations of methane gas bubbles rising through the water column.

Methane bubbles rising from the ocean floor undergo a complicated evolution as they rise through the water column: gas is transferred both into and out of the surrounding bubble causing the gas composition of a bubble near the sea surface to look very different than at its ocean floor origin, and coatings on the bubble wall can change both the speed at which the bubble rises as well as the rate at which gas enters or exits the bubble. Understanding the various ways in which methane bubbles contribute to the global carbon cycle requires understanding these complicated details of a methane bubble’s lifetime in the ocean. We can use acoustic remote sensing techniques, combined with our understanding of the acoustic response of resonant bubbles, to help answer the question of where the methane gas goes. In doing so we map the locations of methane gas bubble sources on the seafloor (Fig. 2), measure how high up into the water column we observe gas bubbles rising, and use calibrated acoustic measurements to help constrain models of how bubbles change during their ascent through the water column.

weber_figure2 - methane gas bubbles

Figure 2. A map of acoustically detected methane gas bubble seeps (blue dots) in the northern Gulf of Mexico in water depths of approximately 1000-2000 m. Oil pipelines on the seabed are shown as yellow lines.

Not surprisingly, working on answering these questions generates new questions to answer, including how the acoustic response of large, wobbly bubbles (Fig. 3) differs from small, spherical ones and what the impact of methane hydrate (methane-ice) coatings are on both the fate of the bubbles and the acoustic response. Given how much of the ocean remains unexplored, we expect to be learning about methane gas seeps and their role in our climate for a long time to come.

weber_figure3

Figure 3. Images of large, wobbly bubbles that are approximately 1 cm in size. These type of bubbles are being investigated to help understand how their acoustic response differs from an ideal, spherical bubble. Picture credit: Alex Padilla.

[1] Skarke, A., Ruppel, C., Kodis, M., Brothers, D., & Lobecker, E. (2014). Widespread methane leakage from the sea floor on the northern US Atlantic margin. Nature Geoscience, 7(9), 657-661.

[2] Kessler, J. (2014). Seafloor methane: Atlantic bubble bath. Nature Geoscience, 7(9), 625-626.

[3] Ruppel, C. D. “Methane hydrates and contemporary climate change.” Nature Education Knowledge 3, no. 10 (2011): 29.