Sound Waves Shatter Cancer Cells: A New Era in Cancer Treatment

Connor Centner – connor.centner@louisville.edu
Twitter: @ConnorCentner

University of Louisville School of Medicine, University of Louisville Bioengeering, Louisville, KY, 40202, United States

Popular version of 1pBA14 – Miniature Histotripsy Device to Treat Human Pathologies
Presented at the 187th ASA Meeting
Read the abstract at https://eppro01.ativ.me//web/index.php?page=Session&project=ASAFALL24&id=3771191

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


Imagine a world where treating cancer doesn’t mean enduring invasive surgeries, long hospital stays, or intense side effects. Many researchers around the globe are working tirelessly to make that vision a reality. One approach could be ultrasound. Ultrasound has traditionally been associated with imaging, such as during pregnancy or heart examinations. Over the past few decades, however, scientists have reimagined its role in medicine, exploring ultrasound as a therapeutic tool to treat various diseases, including cancer. Histotripsy takes this idea to new heights. By directing focused ultrasound waves right into a tumor, we can quickly disrupt and break down cancer cells by forming tiny bubbles. When these bubbles collapse, they can collapse at speeds of several hundred meters per second, approaching speeds of a supersonic aircraft. Due to the focused nature of the device, it can protect nearby healthy cells. In fact, histotripsy is already FDA to treat certain cancers, such as liver cancer, and has shown tremendous success.

Yet, its application for colon cancer or lung cancer have yet to be fully explored. To target these cancers, a smaller device had to be developed. In fact, the device diameter is about half that of a penny (Figure 1). This would allow our device to be used with an endoscope, which means doctors can reach the tumor inside the body without needing to make big cuts.

This prototype device was recently studied in our lab. To explore the initial effectiveness of the device, lung and colon cancer cells were rapidly treated (2 minutes or less of treatment time). In fact, we were able to kill over 60% of the cells in sample (Figure 2). This highlights the versatility of the histotripsy device in treating various cancers and underscores its promising potential for a range of applications in cancer therapy. With continued research and development, this innovative technology may help improve cancer treatment and offer new hope to those affected by this disease.

Catch and Release Can Give Sea Turtles the Bends #ASA186

Catch and Release Can Give Sea Turtles the Bends #ASA186

Veterinarians team up with fishers to evaluate the health of accidentally caught sea turtles.

Media Contact:
AIP Media
301-209-3090
media@aip.org

OTTAWA, Ontario, May 13, 2024 – Six out of seven sea turtle species are endangered, and humans are primarily responsible. Commercial fishing activities are the largest human-caused disturbance to sea turtles due to accidental capture.

Fishers are typically unaware if a sea turtle is caught in their net until its completely pulled out of the water. However, releasing sea turtles without veterinary evaluations can be harmful. When accidentally caught, the turtles’ normal diving processes are interrupted, which can cause abnormal gas in their organs, gas emboli, to form. Veterinarians around the globe are working to understand the possible consequences of this pathology and determine the best treatment for turtles depending on when they surface. Here, they used ultrasound imaging to get a closer look at sea turtles’ bodies in realtime, focusing on the heart, liver, and kidney.

A sea turtle getting an ultrasound at Oceanogràfic as part of a veterinary procedure. (Photo taken by Katherine Eltz during her visit there to learn more about how this type of data is acquired for veterinary purposes)

Katherine Eltz, a first-year doctoral student at the University of North Carolina at Chapel Hill, determined that there are ways to differentiate gas levels over time in sea turtles. Eltz, whose home laboratory focuses on ultrasound imaging for decompression sickness mitigation in humans, collaborated with veterinarians who measured gas emboli in turtles in real time on fishing boats. She will present her work Monday, May 13, at 4:00 p.m. EDT as part of a joint meeting of the Acoustical Society of America and the Canadian Acoustical Association, running May 13-17 at the Shaw Centre located in downtown Ottawa, Ontario, Canada.

“Veterinarians can examine whole-body MRI or X-ray scans and find specific bubbles in a variety of different organs,” said Eltz. “The benefit of ultrasound is that we can see bubbles flowing through vessels or stationary in tissues. The portability of ultrasound means that it can be brought onto fishing boats, which we took advantage of to collect half of the data used in this project.”

Her collaborators from the Oceanogràfic Foundation were the first to report decompression sickness in turtles. Eltz examined ultrasound data collected from sea turtles found off the coast of Brazil, Italy, and Spain, though this issue is found in sea turtles worldwide. The data collection from Eltz’s collaborators at Oceanogràfic comes from veterinarians who joined fishers off the coasts of these countries and imaged the turtles immediately to monitor their bubbles after surfacing.

Eltz’s results come from two experimental groups with different circumstances regarding time and gas severity. The brightness from the ultrasounds taken from the groups is a valuable quantitative metric to separate each ultrasound by grade. These findings can help veterinarians better treat sea turtles presenting with gas embolism. Ultrasound brightness could become a quantitative metric for veterinarians to determine which turtles need hyperbaric oxygen treatment and which can be released.

“The largest task still at hand is to work towards standardizing the acquisition of the ultrasound data collected for this project,” said Eltz. “Now, I can work with veterinarians to help adjust their methods, including improved image processing to standardize the data in post-processing.”

With a rich dataset from Oceanogràfic at her disposal, Eltz hopes to examine other possible factors that may be related to gas severity. These insights all help lead to better prediction of the outcomes for bycaught sea turtles.

———————– MORE MEETING INFORMATION ———————–
​Main Meeting Website: https://acousticalsociety.org/ottawa/    
Technical Program: https://eppro02.ativ.me/src/EventPilot/php/express/web/planner.php?id=ASASPRING24

ASA PRESS ROOM
In the coming weeks, ASA’s Press Room will be updated with newsworthy stories and the press conference schedule at https://acoustics.org/asa-press-room/.

LAY LANGUAGE PAPERS
ASA will also share dozens of lay language papers about topics covered at the conference. Lay language papers are summaries (300-500 words) of presentations written by scientists for a general audience. They will be accompanied by photos, audio, and video. Learn more at https://acoustics.org/lay-language-papers/.

PRESS REGISTRATION
ASA will grant free registration to credentialed and professional freelance journalists. If you are a reporter and would like to attend the in-person meeting or virtual press conferences, contact AIP Media Services at media@aip.org. For urgent requests, AIP staff can also help with setting up interviews and obtaining images, sound clips, or background information.

ABOUT THE ACOUSTICAL SOCIETY OF AMERICA
The Acoustical Society of America is the premier international scientific society in acoustics devoted to the science and technology of sound. Its 7,000 members worldwide represent a broad spectrum of the study of acoustics. ASA publications include The Journal of the Acoustical Society of America (the world’s leading journal on acoustics), JASA Express Letters, Proceedings of Meetings on Acoustics, Acoustics Today magazine, books, and standards on acoustics. The society also holds two major scientific meetings each year. See https://acousticalsociety.org/.

ABOUT THE CANADIAN ACOUSTICAL ASSOCIATION/ASSOCIATION CANADIENNE D’ACOUSTIQUE

  • fosters communication among people working in all areas of acoustics in Canada
  • promotes the growth and practical application of knowledge in acoustics
  • encourages education, research, protection of the environment, and employment in acoustics
  • is an umbrella organization through which general issues in education, employment and research can be addressed at a national and multidisciplinary level

The CAA is a member society of the International Institute of Noise Control Engineering (I-INCE) and the International Commission for Acoustics (ICA), and is an affiliate society of the International Institute of Acoustics and Vibration (IIAV). Visit https://caa-aca.ca/.

Intense Ultrasound Extracts Genetic Info for Less Invasive Cancer Biopsies #ASA186

Intense Ultrasound Extracts Genetic Info for Less Invasive Cancer Biopsies #ASA186

Upcoming technology can extract cancer biomarkers from cells to enable affordable, noninvasive, and regular cancer screening.

Media Contact:
AIP Media
301-209-3090
media@aip.org

OTTAWA, Ontario, May 13, 2024 – Ultrasound imaging offers a valuable and noninvasive way to find and monitor cancerous tumors. However, much of the most crucial information about a cancer, such as specific cell types and mutations, cannot be learned from imaging and requires invasive and damaging biopsies. One research group developed a way to employ ultrasound to extract this genetic information in a gentler way.

At the University of Alberta, a team led by Roger Zemp explored how intense ultrasound can release biological indicators of disease, or biomarkers, from cells. These biomarkers, like miRNA, mRNA, DNA, or other genetic mutations, can help identify different types of cancer and inform the subsequent therapy. Zemp will present this work Monday, May 13, at 8:30 a.m. EDT as part of a joint meeting of the Acoustical Society of America and the Canadian Acoustical Association, running May 13-17 at the Shaw Centre located in downtown Ottawa, Ontario, Canada.

ultrasound

Ultrasound image of micro-histotripsy liberation of biomarkers in a tumor. Image Credit: Joy Wang and Pradyumna Kedarisetti.

“Ultrasound, at exposure levels higher than is used for imaging, can create tiny pores in cell membranes, which safely reseal,” Zemp said. “This process is known as sonoporation. The pores formed due to sonoporation were previously used to get drugs into cells and tissues. In our case, we care about releasing the contents of cells for diagnostics.”

The ultrasound releases biomarkers from the cells into the bloodstream, increasing their concentration to a level high enough for detection. Using this method, oncologists can detect cancer and monitor its progression or treatment without the need for painful biopsies. Instead, they can use blood samples, which are easier to procure and less expensive.

“Ultrasound can enhance the levels of these genetic and vesicle biomarkers in blood samples by over 100 times,” said Zemp. “We were able to detect panels of tumor-specific mutations, and now epigenetic mutations that were not otherwise detectable in blood samples.”

Not only was this approach successful at detecting biomarkers, but it also boasts a lower price compared to conventional testing. 

“We’ve also found that we can conduct ultrasound-aided blood testing to look for circulating tumor cells in blood samples with single-cell sensitivity for the price of a COVID test,” said Zemp. “This is significantly cheaper than the current methods, which cost about $10,000 per test.”

The team also demonstrated the potential for applying intense ultrasound to liquefy small volumes of tissue for biomarker detection. The liquified tissue can be retrieved from blood samples or through fine-needle syringes, a much more comfortable option compared to the damaging core-needle alternative.

More accessible techniques to identify cancer will not only allow for earlier detection and treatment but will also allow medical practitioners to be nimble in their approach. They can establish if certain therapies are working without the risks and expenses often associated with repeated biopsies.

“We hope that our ultrasound technologies will benefit patients by providing clinicians a new kind of molecular readout of cells and tissues with minimal discomfort,” said Zemp.

———————– MORE MEETING INFORMATION ———————–
​Main Meeting Website: https://acousticalsociety.org/ottawa/    
Technical Program: https://eppro02.ativ.me/src/EventPilot/php/express/web/planner.php?id=ASASPRING24

ASA PRESS ROOM
In the coming weeks, ASA’s Press Room will be updated with newsworthy stories and the press conference schedule at https://acoustics.org/asa-press-room/.

LAY LANGUAGE PAPERS
ASA will also share dozens of lay language papers about topics covered at the conference. Lay language papers are summaries (300-500 words) of presentations written by scientists for a general audience. They will be accompanied by photos, audio, and video. Learn more at https://acoustics.org/lay-language-papers/.

PRESS REGISTRATION
ASA will grant free registration to credentialed and professional freelance journalists. If you are a reporter and would like to attend the in-person meeting or virtual press conferences, contact AIP Media Services at media@aip.org. For urgent requests, AIP staff can also help with setting up interviews and obtaining images, sound clips, or background information.

ABOUT THE ACOUSTICAL SOCIETY OF AMERICA
The Acoustical Society of America is the premier international scientific society in acoustics devoted to the science and technology of sound. Its 7,000 members worldwide represent a broad spectrum of the study of acoustics. ASA publications include The Journal of the Acoustical Society of America (the world’s leading journal on acoustics), JASA Express Letters, Proceedings of Meetings on Acoustics, Acoustics Today magazine, books, and standards on acoustics. The society also holds two major scientific meetings each year. See https://acousticalsociety.org/.

ABOUT THE CANADIAN ACOUSTICAL ASSOCIATION/ASSOCIATION CANADIENNE D’ACOUSTIQUE

  • fosters communication among people working in all areas of acoustics in Canada
  • promotes the growth and practical application of knowledge in acoustics
  • encourages education, research, protection of the environment, and employment in acoustics
  • is an umbrella organization through which general issues in education, employment and research can be addressed at a national and multidisciplinary level

The CAA is a member society of the International Institute of Noise Control Engineering (I-INCE) and the International Commission for Acoustics (ICA), and is an affiliate society of the International Institute of Acoustics and Vibration (IIAV). Visit https://caa-aca.ca/.

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.

Popping Droplets for Drug Delivery

Aaqib Khan – aaqib.khan@iitgn.ac.in

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.

Using rays to describe spinning sound

Chirag Gokani – chiragokani@gmail.com

University of Texas at Austin, Applied Research Laboratories and Walker Department of Mechanical Engineering, Austin, Texas, 78766-9767, United States

Michael R. Haberman; Mark F. Hamilton (both at Applied Research Laboratories and Walker Department of Mechanical Engineering)

Popular version of 5pPA13 – Effects of increasing orbital number on the field transformation in focused vortex beams
Presented at the 186th ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0027778

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

When a chef tosses pizza dough, the spinning motion stretches the dough into a circular disk. The more rapidly the dough is spun, the wider the disk becomes.

Fig 1. Pizza dough gets stretched out into a circular disk when it is spun. Source

 

A similar phenomenon occurs when sound waves are subjected to spinning motion: the beam spreads out more rapidly with increased spinning. One can use the theory of diffraction—the study of how waves constructively and destructively interfere to form a field pattern that evolves with distance—to explain this unique sound field, known as a vortex beam.

Fig 2. The wavefronts of vortex beams are helical in shape, like the threads on a screw. Adapted from Jiang et al., Phys. Rev. Lett. 117, 034301 (2016).

 

In addition to exhibiting a helical field structure, vortex beams can be focused, the same way sunlight passing through a magnifying glass can be focused to a bright spot. When sound is simultaneously spun and focused, something unexpected happens. Rather than converging to a point, the combination of spinning and focusing can cause the sound field to create a region of zero acoustic pressure, analogous to a shadow in optics, between the source and focal point, the shape of which resembles a rugby ball.

While the theory of diffraction predicts this effect, it does not provide insight into what creates the shadow region when the acoustic field is simultaneously spun and focused. To understand why this happens, one can resort to a simpler concept that approximates sound as a collection of rays. This simpler description, known as ray theory, is based on the assumption that waves do not interfere with one another, and that the sound field can be described by straight arrows emerging from a source, just like sun rays emerging from behind a cloud. According to this description, the pressure is proportional to the number of rays present in a given region in space.

Fig 3. Rays in a vortex beam. Adapted from Richard et al., New J. Phys. 22, 063021 (2020).

 

Analysis of the paths of individual sound rays permits one to unravel how the overall shape and intensity of the beam are affected by spinning and focusing. One key finding is the formation of an annular channel, resembling a tunnel, within the beam’s structure. This channel is created by a multitude of individual sound rays that are converging due to focusing but are skewed away from the beam axis due to spinning.

By studying this channel, one can calculate the amplitude of the sound field according to ray theory, offering perspectives that the theory of diffraction does not readily reveal. Specifically, the annular channels reveal that the sound field is greatest on the surface of a spheroid, coinciding with the feature shaped like a rugby ball predicted by the theory of diffraction.

In the figure below from the work of Gokani et al., the annular channels and spheroidal shadow zone predicted by ray theory are overlaid as white lines on the upper half of the field predicted by the theory of diffraction, represented by colors corresponding to intensity increasing from blue to red. The amount by which the sound is spun is characterized by ℓ, the orbital number, which increases from left to right in the figure.

Fig 4. Annular channels (thin white lines) and spheroidal shadow zones (thick white lines) overlaid on the diffraction pattern (colors). From Gokani et al., J. Acoust. Soc. Am. 155, 2707-2723 (2024).

 

As can be seen from Fig. 4, ray theory distills the intricate dynamics of sound that is spun and focused to a tractable geometry problem. Insights gained from this theory not only expand one’s fundamental knowledge of sound and waves but also have practical applications related to particle manipulation, biomedical ultrasonics, and acoustic communications.