Columbia University, 1210 Amsterdam Ave, New York, New York, 10027-7003, United States
Popular version of 2aBAa1 – Neuronavigated focused ultrasound for clinical bbb opening in alzheimer’s and brain cancer patients
Presented at the 184 ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0018295
Ultrasound is widely known as an imaging modality in obstetrics and cardiology as well as several other applications but less known regarding its therapeutic effects despite its recent approvals in the clinic for ablation of prostate cancer and essential tremors. In the studies presented, we demonstrate that focused ultrasound (FUS) can be used in conjunction with microbubbles to open the blood-brain barrier (BBB) through the intact scalp of Alzheimer’s and pediatric tumor patients. The BBB is the main defense of the brain against toxic molecules but also prevents drugs from treating brain disease. In the case of Alzheimer’s, we demonstrate for the first time that the BBB opening resulting from FUS in the prefrontal cortex acts as an antibody in the brain. BBB opening results into a beneficial immune response in the brain that significantly reduces the beta amyloid in the region where ultrasound opened the blood-brain barrier. This was shown in 5 patients with Alzheimer’s.
In the case of the pediatric tumor patients, we aimed into the stem, which is a critical region between the spinal cord and the brain. The tumors in the pediatric patients are gliomas that grow in the stem where critical nerve fibers run through and they are therefore inoperable. We showed for the first time that BBB opening can be repeatedly induced with FUS in conjunction with microbubbles safely and efficiently in patients with pediatric glioma tumors in the stem. In this case, we used FUS in conjunction with a drug that, when crossing the blood-brain barrier, increases its efficiency. The patients reported smoother limb movement after treatment with the drug potentially acting more potently on the tumor.
It was concluded that ultrasound can safely open the blood-brain barrier in both patients as young as 6 years old to as old as 83 years old completely noninvasively and more importantly reduce the disease pathology and/or symptoms. The system is thus versatile, does not require a dedicated MR system or to be performed in the MR scanner unlike other systems and the entire procedure can last less than 30 min from start to finish. Ultrasound can thus be used alone or in conjunction with a drug in order to change the current dire landscape of treatment of brain disease. Finally, we show how Alzheimer’s beta amyloid and tau are excreted from the brain and can be detected with a simple blood test.
University of Washington (UW), Department of Bioengineering, 616 NE Northlake Pl, Benjamin Hall bld, room 363, SEATTLE, WA, 98105, United States
Mitchell A. Kirby, Peijun Tang, Gabriel Regnault, Maju Kuriakose, Matthew O’Donnell, Ruikang K. Wang
University of Washington, Department of Bioengineering
Russell Ettinger
University of Washington, Burn and Plastic Surgery Clinics at Harborview
Tam Pham
University of Washington, Regional Burn Center at Harborview
Popular version of 4aBAa2 – Quantification of Elastic Anisotropy of Human Skin in vivo with Dynamic Optical Coherence Elastography and Polarization-sensitive OCT
Presented at the 184 ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0018793
We believe that mapping skin elasticity with sub-mm resolution may have tremendous impact in dermatology, transplantology and plastic surgery, dramatically improving current monitoring of wound healing and tissue recovery, reducing surgical failure rates, providing immediate quantitative feedback on all procedures, and opening many new opportunities for reconstructive medicine.
Skin grafting is one of the oldest and most widely used reconstructive techniques, finding clinical applications across many surgical and cosmetic areas. Factors related to skin’s elastic properties (such as contractions and shearing forces) are among the most common complications of full thickness skin grafts (FTSGs). Recent studies show that the recipient site work best when its elastic properties are matched by transplanted donor tissue. With tens of millions of aesthetic procedures performed every year in the USA, surgical cosmetology is clearly critical, especially when procedures are performed on the face, neck or breast. Currently there are no tools that can quantitatively map skin’s elasticity in living people.
What does elasticity mean for soft tissue? In general, tissue elasticity defines how it changes shape due to an applied external force. It can be complicated depending on tissue structural organization. For many tissue types like kidney, liver, or breast), however, elastic properties are isotropic (that is, independent of the direction of applied force) and can be described by a single parameter called the shear modulus. This parameter has very important diagnostic power because it correlates well with what a physician feels when compressing also known as palpating, tissue. Hematoma, different lesions and nodules, cysts, or scar feel very different compared to normal tissue due to shear modulus changes.
What do we propose? Skin is a complex organ with directional dependence of mechanical properties mainly governed by the local orientation of collagen fibers in the dermis. This means that skin deforms differently when it is stretched in different directions, for instance, either along or across fibers. To characterize skin’s arbitrary deformation, a single shear modulus (as for isotropic organs) is not enough; instead, 3 independent elastic moduli are required. We propose to map these moduli in skin using a noncontact, fully non-invasive method, with sub-mm spatial resolution and nearly in real time. We hypothesize that quantifying skin elasticity in living patients will enable significant innovation within all areas of dermatology and plastic, burn, or oncologic surgery, that will modify a patient’s tissue quality and reduce unintended outcomes from medical, radiologic, or surgical intervention.
How do we measure elastic properties in skin? Over the last twenty-five years, elastography using magnetic resonance imaging (MRI) and ultrasound systems has evolved from an interesting concept into an important clinical tool. In skin, however, MRE resolution is insufficient, and no contact as in ultrasound, can be applied to tissue for many important medical conditions. Our method is based on noncontact dynamic Optical Coherence Elastography (OCE) where mechanical waves in skin are launched with an air-coupled acoustic transducer, meaning, through air, and recorded in space and time with Optical Coherence Tomography (OCT, Fig. 1a). Video snapshots clearly show high variation in the surface wave speed (Fig. 1c) for different, even close body sites (Fig. 1b). In addition, different OCT modalities can measure skin’s structure (Fig. 2e), local fiber orientation (Figs. 2c, g) and its vascularization (Fig. 2f), providing very rich information on its structural and functional properties.
Figure 1. (a) – Diagram of Optical Coherence Elastography (OCE) measurements in human skin. (b) – Example imaging sites in palm and wrist. (c) – Snapshots of propagating mechanical waves over skin surface in two imaging locations and corresponding wave speed maps at these locations. Click here to see the full video. Image courtesy of [SOURCE]
Our findings: We studied skin elasticity in healthy volunteers in vivo. By measuring the speed of mechanical waves propagating in different directions (Fig. 2a) along the skin surface in the forearm (Fig. 2b), we determined all three elastic moduli in skin and identified local collagen fiber orientation (blue dashed line in Fig. 2b). Polarization-sensitive Optical Coherence Tomography produced the same fiber orientation (red dashed line in Fig. 2b) from pure optical measurements (Fig. 2c). We also showed that all parameters differ markedly in scar (Fig. 2d) compared to surrounding normal skin (Figs. 2e-h).
Figure 2. (a) – Diagram of Optical Coherence Elastography (OCE) scanning orientation in the forearm in vivo. (b) – mechanical wave anisotropy in human skin with reconstructed collagen fiber orientation and elastic indexes. (c) – imaging fiber orientation with polarization-sensitive Optical Coherence Tomography (PS-OCT). Dashed blue and red lines in (b) correspond to the local fiber orientation reconstructed with OCE and PS-OCT respectively. (d) – imaging of human scar with structural OCT (e), OCT angiography (f), PS-OCT (g) and OCE (h). Images were adapted from https://www.nature.com/articles/s41598-022-07775-3. Image courtesy of [SOURCE]
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.
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/.
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.”
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/.
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!
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.
We believe that mapping skin elasticity with sub-mm resolution may have tremendous impact in dermatology, transplantology and plastic surgery, dramatically improving current monitoring of wound healing and tissue recovery, reducing surgical failure rates, providing immediate quantitative feedback on all procedures, and opening many new opportunities for reconstructive medicine.
Figure 1. (a) – Diagram of Optical Coherence Elastography (OCE) measurements in human skin. (b) – Example imaging sites in palm and wrist. (c) – Snapshots of propagating mechanical waves over skin surface in two imaging locations and corresponding wave speed maps at these locations. 
