–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.
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
–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.
Popular version of 1aMU8 – Effect of years of voice training on chest and head register tongue shape variability
Presented at the 187th ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0034945
–The research described in this Acoustics Lay Language Paper may not have yet been peer reviewed–
Imagine being in a voice lesson, and as you try to hit a high note, your voice coach says, “suppress your tongue” or “pretend your tongue doesn’t exist!” What does this mean, and why do singers do this?
One vocal technique used by professional singers is to sing in different vocal registers. Generally, a man’s natural speaking voice and the voice people use to sing lower notes is called the chest voice—you can feel a vibration in your chest if you place your hand over it as you vocalize. When moving to higher notes, singers shift to their head voice, where vibrations feel stronger in the head. However, what role does the tongue play in this transition? Do all singers, including amateurs, naturally adjust their tongue when switching registers, or is this adjustment a learned skill?
Figure 1: Approximate location of feeling/sensation for chest and head voice.
We are interested in vowels and the pitch range during the passaggio, which is the shift or transition point between different vocal registers. The voice is very unstable and prone to audible cracking during the passaggio, and singers are trained to navigate it smoothly. We also know that different vowels are produced in different locations in the mouth and possess different qualities. One way that singers successfully navigate the passaggio is by altering the vowel through slight adjustments to tongue shape. To study this, we utilized ultrasound imaging to monitor the position and shape of the tongue while participants with varying levels of vocal training sang vowels across their pitch range, similar to a vocal warm-up.
Video 1: Example of ultrasound recording
The results indicated that, in head voice, the tongue is generally positioned higher in the mouth than in chest voice. Unsurprisingly, this difference is more pronounced for certain vowels than for others.
Figure 2: Tongue position in chest and head voice for front and back vowel groups. Overlapping shades indicate that there is virtually no difference.
Singers’ tongues are also shaped by training. Recall the voice coach’s advice to lower your jaw and tongue while singing—this technique is employed to create more space in the mouth to enhance resonance and vocal projection. Indeed, trained singers generally have a lower overall tongue position.
As professional singers’ transitions between registers sound more seamless, we speculated that trained singers would exhibit smaller differences in tongue position between registers than untrained singers, who have less developed tongue control. In fact, it turns out that the opposite is true: the tongue behaves differently in chest voice and head voice, but only for individuals with vocal training.
Figure 3: Tongue position in chest and head voice for singers with different levels of training.
In summary, our research suggests that tongue adjustments for register shifts may be a learned technique. The manner in which singers adjust their tongues for different vowels and vocal registers could be an essential component in achieving a seamless transition between registers, as well as in the effective use of various vocal qualities. Understanding the interactions among vowels, registers, and the tongue provides insight into the mechanisms of human vocal production and voice pedagogy.
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.
Figure 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.
Chemical Engineering Department, Indian Institute of Technology Gandhinagar, Gandhinagar, Gujarat, 382355, India
Sameer V. Dalvi – sameervd@iitgn.ac.in
Chemical Engineering Department,
Indian Institute of Technology Gandhinagar
Gandhinagar, Gujarat 382355
India
Popular version of 4pBAa3 – Ultrasound Responsive Multi-Layered Emulsions for Drug Delivery
Presented at the 186th ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0027523
–The research described in this Acoustics Lay Language Paper may not have yet been peer reviewed–
What are popping droplets? Imagine you are making popcorn in a pot. Each little popcorn seed consists of a tiny bit of water. When you heat the seeds, the water inside them gets hot and turns into steam. This makes the seed pop and turn into a popcorn. Similarly, think of each popcorn seed as a droplet. The special liquid used to create popping droplets is called perfluoropentane (PFP), which is similar to the water inside the corn seed. PFP can boil at low temperatures and turn into a bubble, which makes it perfect for crafting these special droplets.
Vaporizable/Popping droplets hold great promise in the fields of both diagnosis and therapy. By using sound waves to vaporize PFP present in the droplets, medicine (drugs) can be delivered efficiently to specific areas in the body, such as tumors, while minimizing impacts on healthy tissues. This targeted approach has the potential to improve the safety and effectiveness of therapy, ultimately benefiting patients.
Figure 1. Vaporizable/popping droplets with perfluoropentane (PFP) in the core with successive layers of water and oil
What do we propose? Researchers have been exploring complex structures like double emulsions to load drugs onto droplets (just like filling a backpack with books), especially those that are water-soluble. Building on this, our study introduces multi-layered droplets featuring a vaporizable core (Fig.1). This design enables the incorporation of both water-soluble and insoluble drugs into separate layers within the same droplet. To better visualize this, imagine a club sandwich with layers of bread stacked on top of each other, each layer containing a different filling. Alternatively, picture an onion with multiple stacked layers that can be peeled off one by one. Similarly, multi-layered droplets comprise stacked layers, each capable of holding various substances, such as drugs or therapeutic agents.
To explore the features of the multi-layered droplets further, we carried out two separate studies. First, we estimated the peak negative pressure of the sound wave at which the PFP in the droplets vaporize. This is similar to how water boils at 100°C (212°F) under standard atmospheric pressure, but at low/negative pressure (like under a vacuum), water can boil at low temperatures. Sound waves are known to induce both positive and negative pressure changes. During instances of negative pressure, the pressure drops below the atmospheric pressure, creating a vacuum-like effect. This decrease in pressure can trigger the vaporization of the perfluoropentane (PFP) in the droplets at room temperatures.
Secondly, we loaded a water-insoluble drug, curcumin, which is an anti-inflammatory drug, in the oil layer and estimated the amount of drug loading (just like counting number of books in the backpack).
Figure 2. Relationship between Mean Grayscale (mean brightness) and soundwave pressure for droplet vaporization
Figure 2 depicts the relationship between the increase in mean grayscale (just like the increase in bright areas or brightness of a black-and-white picture) and the peak negative pressure of the sound wave. Based on our study, the peak negative pressure at which the PFP in the droplets was found to vaporize was 6.7 MPa. Furthermore, the loading for curcumin was estimated to be 0.87 ± 0.1 milligrams (mg), which indicates a higher drug loading capacity in multi-layered droplets.
These studies are essential because they help us determine two critical things. The first one allows us to figure out the exact sound wave pressure needed to make the droplets pop. This is useful for the controlled release of drugs in targeted areas. The second study tells us how much drug these droplets can hold, which is helpful in designing drug delivery systems.
Together, these studies enhance our understanding of multi-layered droplets and pave the way for a new targeted therapy, where popping droplets serve as vehicles for delivering drugs or therapeutic agents to specific locations upon activation by sound waves.
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).
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).
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).
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).
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.
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.
Figure 1: Approximate location of feeling/sensation for chest and head voice.
Figure 2: Tongue position in chest and head voice for front and back vowel groups. Overlapping shades indicate that there is virtually no difference.
Figure 3: Tongue position in chest and head voice for singers with different levels of training.
Figure 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.
Figure 1. Vaporizable/popping droplets with perfluoropentane (PFP) in the core with successive layers of water and oil
Figure 2. Relationship between Mean Grayscale (mean brightness) and soundwave pressure for droplet vaporization