–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.
–The research described in this Acoustics Lay Language Paper may not have yet been peer reviewed–
Almost everyone experiences back pain at some point in their lives. For many, this pain becomes long-lasting and difficult to manage. One possible cause of chronic back pain is myofascial trigger points. These are small, sensitive knots or tight spots in muscles that not only hurt when pressed but can also spread pain to other areas. Although physicians know these trigger points exist, they are very difficult to detect with current available medical imaging tools. This makes diagnosis and treatment more challenging.
In this research, we are developing a new ultrasound-based method to find these hidden painful spots more accurately. We tested this method on 32 volunteers,16 who had chronic low back pain and known trigger points, and 16 healthy individuals without pain. Our approach uses a small vibrating device placed on the lower back skin. This device produces vibration inside the lower back tissue so that the vibration wave propagates through the skin and muscles of the subject. The propagation speed of this wave called shear wave speed is directly related to stiffness of the tissues. We used an advanced type of three-dimensional ultrasound probe to capture how these waves traveled inside the muscles in three different directions.
Figure 1: experiment setup
By measuring the speed of the waves moving through the muscles, we could assess their stiffness knowing high speed indicates stiffer tissue. Our early results showed that muscles with trigger points had higher wave speeds, meaning they were stiffer compared to muscles without pain points. This finding is important because increased muscle stiffness could be a sign of the presence of painful trigger points.
Video 1: Black and white image showing different layers of lower back tissue using 3D ultrasound. Colorful waves indicating corresponding shear wave propagation through the lower back tissue.
If future studies confirm these findings, this technique could provide physicians with a valuable new tool for diagnosing chronic back pain related to myofascial trigger points. Unlike current methods that mostly rely on physical examination and patient reports, this method could offer objective and visual evidence of muscle problems. This might help guide treatment decisions and track patient progress more accurately.
By improving the way we see and measure muscle stiffness, this research could lead to better care for the many people experiencing chronic low back pain.
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.
–The research described in this Acoustics Lay Language Paper may not have yet been peer reviewed–
Super-resolution ultrasound is a technique for assessing the microvasculature of tissues. It achieves higher resolution than ultrasound detectors by using advanced methods to locate and track ultrasound contrast agents (microbubbles). The latter are known from GPS or RADAR. This allows comprehensive characterisation of anatomical and functional features at the level of a single microvessel. Multiple features can then be obtained and used to identify vascular patterns. We can show that super-resolution ultrasound can predict which breast cancer patients will respond to standard neoadjuvant chemotherapy and which will require a modified treatment plan, which is critical to their overall prognosis. In addition, in the kidney, we can visualise glomeruli (important functional units), the number of which indicates chronic kidney disease long before functional deficits occur. This would allow early treatment and could help to minimise the need for biopsies, which is currently the only method that can provide this information. In addition, we show that super-resolution ultrasound also provides valuable physiological information about kidney function. As breast cancer and chronic kidney disease are very common, a large population could benefit from the clinical implementation of super-resolution ultrasound imaging. In addition, many other conditions, such as inflammatory bowel disease, diabetic microvascular disease and cerebral ischaemia, are being investigated and may expand the application of this technology.
–The research described in this Acoustics Lay Language Paper may not have yet been peer reviewed–
Preeclampsia is a life-threatening pregnancy disorder that currently has no cure and is a significant cause of death for expecting mothers and their babies worldwide. A recent study by researchers at Tulane University and Weill Cornell Medicine has shown that quantitative ultrasound imaging of the placenta may help doctors detect preeclampsia earlier. Through this collaboration, the researchers discovered a connection between quantitative ultrasound images and the size of biological structures in the placenta. This preliminary study in rats also saw a significant difference between normal and preeclamptic placentas using quantitative ultrasound (Figure 1, bottom row), opening the door for potential applications in human medicine.
During normal pregnancies, the placenta delivers nutrients from the mother to the fetus and undergoes microscopic changes in its structure that allow it to deliver more nutrients as the fetus grows larger. For women with preeclampsia, the placenta fails to develop correctly, resulting in significant microstructural changes that cause high blood pressure, birth defects, and organ failure. The only way that doctors can alleviate the mother’s symptoms from preeclampsia is by delivering the baby and placenta early, which puts the baby at risk for developing complications associated with premature birth.
Ultrasound imaging is the most common method that doctors use to monitor pregnancies, but the ultrasound imaging methods currently used in clinics cannot detect the microstructural changes in the placenta that occur during preeclampsia (Figure 1, top row). Instead, preeclampsia is often detected when the mother has already developed high blood pressure and kidney failure, which can lead to further heart and kidney disease complications in the mother, even after the baby and placenta are delivered. Doctors need a better way to monitor the placenta for preeclampsia so that they can better understand how the disease develops and diagnose at risk women earlier.
Quantitative ultrasound imaging methods apply mathematical models of sound interactions and statistics to quantify the microscopic structural elements’ size, structure, and organization in human organs. With quantitative ultrasound, doctors will be able to diagnose diseases that would be impossible to detect using current ultrasound imaging methods. So, researchers studying the placenta in the Department of Biomedical Engineering at Tulane University decided to team up with researchers developing quantitative ultrasound algorithms in the Department of Radiology at Weill Cornell Medicine to investigate how quantitative ultrasound could help to diagnose preeclampsia. The research team is currently conducting a pilot study with human placentas after birth to determine how quantitative ultrasound images can help doctors diagnose preeclampsia in the clinic. Earlier diagnosis of preeclampsia could have a major impact on the way that doctors study and treat the disease, potentially saving the lives of thousands of women and children all around the world.
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://doi.org/10.1121/10.0035013
–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.
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.
