Ultrasound-Assisted Laser Technique Vaporizes Artery Plaque

Ultrasound-Assisted Laser Technique Vaporizes Artery Plaque

Method avoids complications from using high-power lasers, extends to other medical applications

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

DENVER, May 24, 2022 – Atherosclerosis, a buildup of plaque, can lead to heart disease, artery disease, and chronic kidney disease and is traditionally treated by inserting and inflating a balloon to expand the artery. Other treatments based on lasers can remove blockages rather than simply compressing them but are used infrequently, because they have a high risk of complication and low efficacy.

Rohit Singh, of the University of Kansas, and other researchers developed a method that combines a low-power laser with ultrasound to remove arterial plaque safely and efficiently. Singh will describe preliminary results in his presentation, “A novel ultrasound-assisted laser technique to remove atherosclerotic plaques,” at the 182nd Meeting of the Acoustical Society of America. The session will take place May 24 at 5:05 p.m. Eastern U.S. at the Sheraton Denver Downtown Hotel.

High-power laser treatments direct thermal energy to vaporize water in the artery and create a vapor bubble, which expands and collapses to break the plaque. Similarly, the technology, pioneered by Xinmai Yang, doctoral advisor for the team, uses a low-power nanosecond pulsed laser to produce microbubbles. The addition of irradiation from ultrasound causes the microbubbles to expand, collapse, and disrupt the plaque.

“In conventional laser angioplasty, a high laser power is required for the entire cavitation process, whereas in our technology, a lower laser power is only required for initiating the cavitation process,” said Singh. “Overall, the combination of ultrasound and laser reduces the need for laser power and improves the efficiency of atherosclerotic plaque removal.”

Because it destroys rather than compresses the plaque, the combination technique will have a lower restenosis rate, or re-narrowing of the artery, compared to balloon angioplasty or stenting. The control provided by the ultrasound and the low-power laser will lower the risk of dissection and perforation in arteries.

The team performed ex vivo experiments on carotid artery plaque samples and pork belly samples, and they are currently planning to perform in vivo experiments. Both the laser and ultrasound techniques are commonly used by clinicians and should be easy to teach and implement following the in vivo studies.

Combining low-power lasers and ultrasound techniques is not limited to atherosclerosis treatments. Singh and collaborators are also using the methodology for photo-mediated ultrasound therapy and ultrasound-assisted endovascular laser thrombolysis. The former can be used to remove abnormal microvessels in the eye to prevent blindness, while the latter can dissolve blood clots in veins.

Singh will expand upon these additional applications in poster sessions at the ASA meeting, with “Analysis of cavitation induced stresses on blood vessel wall during photo-mediated ultrasound therapy using finite-element based numerical models” and “Combining ultrasound and endovascular laser for thrombolysis,” on May 25, 5-7 p.m. Eastern U.S.

———————– MORE MEETING INFORMATION ———————–
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In the coming weeks, ASA’s Worldwide Press Room will be updated with additional tips on dozens of newsworthy stories and with lay language papers, which are 300 to 500 word summaries of presentations written by scientists for a general audience and accompanied by photos, audio and video. You can visit the site during the meeting at https://acoustics.org/world-wide-press-room/.

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We will grant free registration to credentialed journalists and professional freelance journalists. If you are a reporter and would like to attend, contact AIP Media Services at media@aip.org. For urgent requests, staff at media@aip.org 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 (ASA) 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/.

Sidekick Microbubbles Carry Anti-Cancer Drugs, Damage Tumor Vessels

Sidekick Microbubbles Carry Anti-Cancer Drugs, Damage Tumor Vessels

Ultrasound-stimulated, drug-loaded bubbles for cancer therapy

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

DENVER, May 24, 2022 – Microbubbles can assist with localized drug delivery in a patient’s body by popping at a target site to create enhanced permeability of tumor blood vessels. By temporarily increasing the porosity of the blood vessels, the microbubbles can create a means for coinjected anti-cancer drugs to preferentially leak into the tumor for treatment.

Naomi Matsuura, of the University of Toronto, and her team are adapting microbubbles to become more potent tools for cancer therapy. By shrinking the bubbles and directly loading them with anti-cancer drugs, the bubbles can lower the dose of free drug that is injected and diffuses into nontumor tissue in the body. This results in more targeted treatment and fewer side effects for the patient.

Matsuura will discuss her team’s results in her presentation, “Ultrasound-stimulated, drug-loaded bubbles for cancer therapy,” as part of the 182nd Meeting of the Acoustical Society of America at the Sheraton Denver Downtown Hotel. The session will take place May 24 at 11:30 a.m. Eastern U.S.

The team loaded taxanes, a commonly used anti-cancer drug, onto the bubbles. Because the drug is hydrophobic, it avoids water and sticks to the bubble easily, avoiding any leakage into the bloodstream or surrounding tissue until the bubble is stimulated by ultrasound.

They plan to extend the bubbles to carry other types of drugs as well, but the drug loading tends to be lower and less stable for hydrophilic materials.

“We are also modifying the pattern of the sound waves in a way that makes the anti-cancer drug more potent in comparison to a regular intravenous drug injection,” said Matsuura.

“If we can combine lower side effects from direct drug loading with a more potent effect of the drug by modifying systems that are already in place for patients, we have a chance to make an impact on the outcomes of cancer patients in a relatively short period of time.”

———————– MORE MEETING INFORMATION ———————–
USEFUL LINKS
Main meeting website: https://acousticalsociety.org/asa-meetings/
Technical program: https://eventpilotadmin.com/web/planner.php?id=ASASPRING22
Press Room: https://acoustics.org/world-wide-press-room/

WORLDWIDE PRESS ROOM
In the coming weeks, ASA’s Worldwide Press Room will be updated with additional tips on dozens of newsworthy stories and with lay language papers, which are 300 to 500 word summaries of presentations written by scientists for a general audience and accompanied by photos, audio and video. You can visit the site during the meeting at https://acoustics.org/world-wide-press-room/.

PRESS REGISTRATION
We will grant free registration to credentialed journalists and professional freelance journalists. If you are a reporter and would like to attend, contact AIP Media Services at media@aip.org. For urgent requests, staff at media@aip.org 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 (ASA) 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/.

4pBA8 – Charging devices inside the body or outside: Ultrasound Wireless Powering offers several possibilities

Inder Makin, inder.makin@gmail.com
Piezo Energy Technologies, LLC
Mesa, AZ

Popular version of 4pBA8 – Charging of devices for healthcare applications, using ultrasound wireless power
Presented Thursday afternoon, May 26, 2022
182nd ASA Meeting
Click here to read the abstract

The current technology in our daily lives including medical devices, requires electrical power. Preferably, these devices use batteries, making the systems portable and easy to use. Alas we all have experienced a power-deprived cell phone or tablet, which we wished would be easily chargeable without a cable. Similarly, devices such as pacemakers and neurostimulators, implanted inside the patient’s body need charging. Each of these scenarios – from real-world power needs to powering implants, would best require a wireless solution to keep the batteries charged, and devices functioning.

The “high-school taught” piezo-electric effect, is practically leveraged by Arizona scientists, Drs. Inder Makin and Leon Radziemski, to provide wireless ultrasound powering (UWP) for several applications. A mm-thin (1/32”), ultrasound disk vibrates at a fixed pitch (frequency), when a voltage is applied across its face. The vibrations propagate through material, such as body tissue (not very efficient in air!). Conversely, a similar disk placed in a material medium where a vibrational beam is present, will generate a voltage at the frequency of the vibration, converting ultrasound to electrical power. The use of an ultrasound transmitter and receiver approach has enabled wireless ultrasound powering (UWP), from sophisticated body-implant powering to charging batteries for digital devices, like smartphones and tablets used primarily in healthcare settings – clinics, emergency rooms, procedure suites.

The video below demonstrates the charging of an implant battery – UltraSound electrical Recharging (USer), using a simple, light device the size of a hockey puck that is attached to the skin. The transmitter senses the need for power in the implant, charges the battery, and communicates to the end user, that it is done.

 

This concept was tested in live animal studies, in order to prove feasibility and safety of the procedure. When a miniaturized implant prototype with a piezo-receiver, was placed inside a pig’s body. The ultrasound transmitter safely charged the implant battery in less than 30 minutes.

Since ultrasound energy can be steered electronically, while the device is compact, the USer concept can be made fully hands free as shown in the figure below. Sensors on the Transmitter and Receiver sense the misalignment and the beam corrects itself to efficiently charge the battery.

Broadening its applications, Piezo Energy Technologies, has demonstrated the charging of smart phones and other digital devices, without wires, using their patented technology. The picture below shows prototypes which are used for efficient charging of a smartphone.

Multiple devices can be charged simultaneously, such as on top of a Ultrasound-PowerTM Pod. In these days of infection control requirements, using a wireless charging system is highly desired, anyway.

Why ultrasound? Compared to existing electromagnetic wireless devices, ultrasound can propagate efficiently through several solid and liquid materials, including metals. The transmitted ultrasound beam is like a flashlight, causing no stray energy, especially due to very inefficient ultrasound propagation through air.

The electronically steerable energy travels to the receiver where it is needed, and reduces one less source of wireless electromagnetic radiation in our daily environment!

4aBA13 – In-vivo assessment of lymph nodes using quantitative ultrasound on a clinical scanner: a preliminary study

Cameron Hoerig, Ph.D., cah4016@med.cornell.edu

Weill Cornell Medicine
Department of Radiology
416 E 55th St., MR-007
New York, NY 10022

Popular version of 4aBA13 – In vivo assessment of lymph nodes using quantitative ultrasound on a clinical scanner: A preliminary study
Presented Thursday morning, May 26, 2022
182nd ASA Meeting, Denver
Click here to read the abstract

Cancer can spread through the body via the lymphatic system. When a primary tumor is found in a patient, biopsies may be performed on one or more nearby lymph nodes (LNs) to look for evidence of cancerous cells and aid in disease staging and treatment planning. LN biopsies typically involve first removing the node, slicing it into very thin sections (thinner than a human hair), and staining the sections. Next, a pathologist views these sections under a microscope to look for abnormal cells. Because the tissue sections are so thin and the node is comparatively large, it is infeasible for a pathologist to look at every slide for each LN. Consequently, small clumps of cancerous cells may be missed. Similarly, biopsies performed via fine needle aspiration (FNA) – wherein a very thin needle is used to extract very small tissue samples throughout a LN while it is still in the body – also comes with the risk of missing cancerous cells. As an example, the false-negative rate for biopsies on axillary lymph nodes is as high as 10%!

In this work, we are using an ultrasonography technique called quantitative ultrasound (QUS) to assess LNs in vivo and determine if metastatic cells are present without the need for biopsy. Different tissue types scatter the ultrasound wave in different ways. However, the processing that typically occurs in clinical scanners strips this information away before displaying conventional B-mode images. Examples of B-mode images from benign and metastatic lymph nodes are displayed in Fig. 1 along with optical microscopy pictures of corresponding FNA results. The microscopy images show a clear contrast in the microstructure between normal and cancerous cells that is not invisible in the ultrasound B-mode images.

“(Left column) B-mode images of metastatic and benign lymph nodes. (Right column) The corresponding optical microscopy images of stained tissue samples from FNA biopsy show the difference in tissue microstructure between benign and metastatic lymph nodes.”

QUS methods extract information from the ultrasonic signal before the typical image processing steps to make inferences about tissue microstructure. Theoretically, these methods are independent of the scanner and operator, meaning the same information can be obtained by any sonographer using any scanner and the information obtained depends only on the underlying tissue microstructure. QUS methods used in this study glean information about the scatterer diameter, effective acoustic concentration, and scatterer organization (randomly positioned vs organized).

“Left and middle columns are representative color overlays of scatterer diameter and acoustic concentration from QUS processing. The right column is the resulting classification from the trained LDA.”

We have thus far collected data on 16 LNs from 15 cancer patients with a known primary tumor. The same clinical GE Logiq E9 scanner was used to collect ultrasound echo data for QUS processing and for ultrasound-guided FNA. Metastatic status of the LNs was determined from the FNA results. QUS methods were applied to the US images to obtain a total of 9 parameters. From these, we determined scatterer diameter and effective acoustic concentration were most effective at differentiating benign and metastatic nodes. Using these two parameters as input to a linear discriminant analysis (LDA) – a type of machine learning algorithm – we correctly classified 95% of US images as containing a benign or metastatic LN. Examples of QUS parameter maps overlayed on B-mode images, and the resulting classification by LDA, are provided in Fig. 2. The associated ROC plot had an area under the ROC curve of 0.90, showing excellent ability of LDA to identify metastatic nodes from only two QUS parameters. These preliminary results demonstrate the feasibility of characterizing LNs in vivo at conventional frequencies using a clinical scanner, potentially offering a means to complement US-FNA practice and reduce unnecessary LN biopsies.

2aPAb – Ultrasound technology to remove kidney stones

Mohamed A. Ghanem – mghanem@uw.edu
Adam D.  Maxwell – amax38@uw.edu
Oleg A. Sapozhnikov – olegs@uw.edu
Michael R. Bailey – mbailey@uw.edu

University of Washington
1013 NE 40th St.
Seattle WA 98105

Popular version of 2aPAb – Designing an array for acoustic manipulation of kidney stones
Presented Tuesday morning, May 24, 2022
182nd ASA Meeting
Click here to read the abstract

Ultrasound technology is becoming an important treatment tool. For instance, sound waves can apply a radiation pressure that can displace an object. Multi-element arrays are complex ultrasound sources that consist of several small transducers that can be driven in sync or a specific order to output pressure waves with different shapes. Pressure wave shapes that have a doughnut shape or a long tube are useful as they can trap an object in the center and as we control the location of the doughnut the object follows. This technology can be used to trap small kidney stones or stone fragments and move them from the kidney collection areas toward the kidney exit without surgery. We have demonstrated the ability to move kidney stone models in the bladders transcutaneously in live pigs under anesthesia. We are currently designing a new multi-element array that will enable us to adapt this technology to move stones in the complex structure of the kidney over larger distances. This technology will reduce the surgery associated with kidney stone treatments by removing small stones or fragments before they become larger, which will lead to surgery, and eliminating emergency room visits by relieving blockages from these stones or fragments.

Controlled steering of kidney stones toward  the kidney exit with an ultrasound array.

2aBAb1 – Using ultrasound imaging to predict type1 diabetes development

Richard KP Benninger – richard.benninger@cuanschutz.edu
University of Colorado Anschutz medical campus
1775 Aurora Ct
Aurora, CO. 80045

Popular version of 2aBAb1 – Applying ultrasound phase-change contrast agents to guide therapeutic intervention in type 1 diabetes
Presented Tuesday morning, May 24th, 2022
182nd ASA Meeting
Click here to read the abstract

Type1 diabetes is an autoimmune disease in which the insulin-producing cells in the pancreas are destroyed. As a result people with type1 diabetes have to take insulin for the rest of their life. This is not a cure, and as well as the significant patient burden there are still risks for complications of diabetes that include eye, kidney and heart damage, as well as potentially falling into a coma from insulin overdose and low blood sugar. Strategies have been developed to prevent type1 diabetes through immune therapies that stop the destruction of insulin producing cells. Treatment early in the disease process, before significant destruction of insulin producing cells will be needed. However it is challenging to predict if an individual will get type1 diabetes and when, limiting the ability to intervene early.

Imaging approaches have been explored to detect the presence of autoimmune disease and concurrent inflammation in the pancreas, and loss of the insulin-producing cells. However there have been limited successes. A potential approach is based on the blood vessels become leaky during the autoimmune disease and inflammation in the pancreas. Thus small particles below 1um diameter can leak and accumulate in the diseased tissue. We have proposed to leverage the inherent advantages of ultrasound imaging that include deployability, cost-effectiveness and safety profile. Ultrasound contrast agents consist of gas filled bubbles (microbubbles). However the size of thee microbubbles means that they cannot access diseased tissue and are restricted to blood vessels. We have utilized a novel phase-change ultrasound contrast agent that consists of a condensed liquid droplet that is stable at body temperature and in circulation. However the acoustic beam from an ultrasound transducer can vaporize these droplets into microbubbles that provide ultrasound contrast. Thus these phase-change agents serve as circulating microbubble precursors that can access diseased tissue.

We tested whether these ultrasound phase change agents can access the injured tissue in the pancreas resulting from autoimmune disease, and whether accumulation of the contrast agents could be detected in ultrasound imaging. We found in pre-clinical models of type1 diabetes that significant accumulation of ultrasound phase change agents were observed in the pancreas, which was measurable by ultrasound (Figure 1). This accumulation correlated with the presence of autoimmune disease and decline in insulin-producing cells. Importantly the accumulation and ultrasound contrast was only present in the pancreas in models of diabetes: no accumulation was observed in non-diseased tissues. Further the accumulation of ultrasound phase change agents and ultrasound contrast correlated with the development of diabetes: models that developed diabetes rapidly or lacked therapeutic prevention showed a much higher contrast than those models that  developed diabetes slowly or showed therapeutic prevention of diabetes. Most importantly elevated contrast was measured very early in the disease process, earlier than the current gold standard measurement of circulating insulin autoantibodies.

As such the use of phase-change ultrasound contrast agents shows significant promise for detecting and tracking the presence of autoimmune disease and inflammation in the pancreas that heralds the development of type1 diabetes (Figure 2). Such a measurement would guide therapeutic intervention to prevent type1 diabetes, as well as assess the efficacy of such a treatment. Successful disease prevention will avoid the need for lifelong insulin therapy and complications of diabetes.

INSERT Figure 1: Conventional B-mode and contrast mode images before and after infusion and activation of phase-change ultrasound contrast agent. P=Pancreas, K=Kidney, S=Spleen.

INSERT Figure 2: Schematic illustrating use of phase-change ultrasound contrast agents to detect autoimmune disease in the pancreas.