High-resolution microvessel imaging using novel beamforming techniques and no microbubbles!

Michael Oelze – oelze@illinois.edu
X (Twitter): @Oelze_Url

University of Illinois at Urbana-Champaign
Urbana, IL 61801
United States

Zhengchang Kou
University of Illinois at Urbana-Champaign
Urbana, IL 61801
United States

Popular version of 1pBAb7 – Contrast-Free Microvessel Imaging Using Null Subtraction Imaging Combined with Harmonic Imaging
Presented at the 186th ASA Meeting
Read the abstract at https://eppro02.ativ.me/web/index.php?page=IntHtml&project=ASASPRING24&id=3675358

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

Bubbles? We don’t need no stinking bubbles!

In recent years, super resolution imaging techniques for imaging the microvasculature have been developed and demonstrated for applications such as functional ultrasound imaging in mice and assessing Alzheimer’s disease in pre-clinical models. While these novel super resolution techniques have produced images with incredible detail and vessel contrast, one drawback to the approach is the need to inject contrast agents, which consist of small gas-filled microbubbles. This reduces the clinical application and adoption of these techniques. Furthermore, the time required to construct these images can take hours because it involves localizing and tracking individual microbubbles as they progress through the vasculature.

FIGURE 1: Video of 3D rendering of rat brain using traditional approaches at a fundamental frequency (top left) and at twice the fundamental frequency (bottom left) compared to using our novel approach (NSI) at a fundamental frequency (top right) and at twice the fundamental frequency (bottom right) (please note this will be a playable video online)

In our novel approach to microvessel imaging, we don’t need no stinking microbubbles! Instead, we utilize a novel nonlinear beamforming approach that allows fast reconstructions with much better spatial resolution. This allows us to approach super resolution without the need to inject microbubbles into the body. Along with the beamforming approach we also use a pulse inversion scheme, where we transmit with one frequency and receive with twice the transmit frequency. This allows a doubling of the spatial resolution over receiving with the same transmit frequency. However, the use of pulse inversion scheme can introduce unwanted clutter into the image. With our novel beamforming approach, clutter is greatly reduced or eliminated from the images.

beamformingFIGURE 2 Single image frames comparing traditional power Doppler methods (left) with our novel approach (right).

We demonstrated our new technology in a rat brain (both 2D and a 3D rendering) and rabbit kidney and compared our images to traditional beamforming approaches without the use of contrast agents. The video shows a 3D rendering of the microvasculature of a rat brain and the corresponding figure shows a particular frame of the 3D rendering. We showed that our approach eliminates the clutter produced by the pulse inversion scheme, increases the contrast of microvessel images, results in more observable vessels, and produces a much finer spatial resolution better than one fourth of a wavelength. The time to reconstruct the images using our novel technique was a fraction of the time needed for current super resolution techniques that rely on localizing and tracking microbubbles in the vasculature. Therefore, our novel approach could provide microbubble-free technology to produce high-resolution power Doppler images of the microvasculature with the potential for clinical applications.

A general method to obtain clearer images at a higher resolution than theoretical limit

Jian-yu Lu – jian-yu.lu@ieee.org
X (Twitter): @Jianyu_lu
Instagram: @jianyu.lu01
Department of Bioengineering, College of Engineering, The University of Toledo, Toledo, Ohio, 43606, United States

Popular version of 1pBAb4 – Reconstruction methods for super-resolution imaging with PSF modulation
Presented at the 186 ASA Meeting
Read the abstract at https://eppro02.ativ.me/web/index.php?page=IntHtml&project=ASASPRING24&id=3675355

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

Imaging is an important fundamental tool to advance science, engineering, and medicine, and is indispensable in our daily life. Here we have a few examples: Acoustical and optical microscopes have helped to advance biology. Ultrasound imaging, X-ray radiography, X-ray computerized tomography (X-ray CT), magnetic resonance imaging (MRI), gamma camera, single-photon emission computerized tomography (SPECT), and positron emission tomography (PET) have been routinely used for medical diagnoses. Electron and scanning tunneling microscopes have revealed structures in nanometer or atomic scale, where one nanometer is one billionth of a meter. And photography, including the cameras in cell phones, is in our everyday life.

Despite the importance of imaging, it was first recognized by Ernest Abbe in 1873 that there is a fundamental limit known as the diffraction limit for resolution in wave-based imaging systems due to the diffraction of waves. This effects acoustical, optical, and electromagnetic waves, and so on.

Recently (see Lu, IEEE TUFFC, January 2024), the researcher developed a general method to overcome such a long-standing diffraction limit. This method is not only applicable to wave-based imaging systems such as ultrasound, optical, electromagnetic, radar, and sonar; it is in principle also applicable to other linear shift-invariant (LSI) imaging systems such as X-ray radiography, X-ray CT, MRI, gamma camera, SPECT, and PET since it increases image resolution by introducing high spatial frequencies through modulating the point-spread function (PSF) of an LSI imaging system. The modulation can be induced remotely from outside of an object to be imaged, or can be small particles introduced into or on the surface of the object and manipulated remotely. The LSI system can be understood with a geometric distortion corrected optical camera in the photography, where the photo of a person will be the same or invariant in terms of the size and shape if the person only shifts his/her position in the direction that is perpendicular to the camera optical axis within the camera field of view.

Figure 1 below demonstrates the efficacy of the method using an acoustical wave. The method was used to image a passive object (in the first row) through a pulse-echo imaging or to image wave source distributions (in the second row) with a receiver. The best images obtainable under the Abbe’s diffraction limit are in the second column, and the super-resolution (better than the diffraction limit) images obtained with the new method are in the last column. The super-resolution images had a resolution that was close to 1/3 of the wavelength used from a distance with an f-number (focal distance divided by the diameter of the transducer) close to 2.

Figure 1. This figure was modified in courtesy of IEEE (doi.org/10.1109/TUFFC.2023.3335883).

Because the method developed is based on the convolution theory of an LSI system and many practical imaging systems are LSI, the method opens an avenue for various new applications in science, engineering, and medicine. With a proper choice of a modulator and imaging system, nanoscale imaging with resolution similar to that of a scanning electron microscope (SEM) is possible even with visible or infrared light.

Wearable Ultrasound Monitor Can Aid Rehabilitation from Injury #Acoustics23

Wearable Ultrasound Monitor Can Aid Rehabilitation from Injury #Acoustics23

A new approach to ultrasound imaging can provide real-time insights into muscle dynamics.

SYDNEY, Dec. 5, 2023 – Millions suffer from musculoskeletal injuries every year, and the recovery process can often be long and difficult. Patients typically undergo rehabilitation, slowly rebuilding muscle strength as their injuries heal. Medical professionals routinely evaluate a patient’s progress via a series of tasks and exercises. However, because of the dynamic nature of these exercises, obtaining a clear picture of real-time muscle function is extremely challenging.

Parag Chitnis of George Mason University led a team that developed a wearable ultrasound system that can produce clinically relevant information about muscle function during dynamic physical activity. He will present his work Dec. 5 at 5:00 p.m. Australian Eastern Daylight Time, as part of Acoustics 2023 running Dec. 4-8 at the International Convention Centre Sydney

Wearable Ultrasound

A wearable ultrasound monitor can provide insight into dynamic muscle movement during activities like jumping. Credit: Parag Chitnis

Many medical technologies can give doctors a window into the inner workings of a patient’s body, but few can be used while that patient is moving. A wearable ultrasound monitor can move with the patient and provide an unprecedented level of insight into body dynamics.

“For instance, when an individual is performing a specific exercise for rehabilitation, our devices can be used to ensure that the target muscle is actually being activated and used correctly,” said Chitnis. “Other applications include providing athletes with insights into their physical fitness and performance, assessing and guiding recovery of motor function in stroke patients, and assessing balance and stability in elderly populations during routine everyday tasks.”

Designing a wearable ultrasound device took much more than simply strapping an existing ultrasound monitor to a patient. Chitnis and his team reinvented ultrasound technology nearly from scratch to produce the results they needed.

“We had to completely change the paradigm of ultrasound imaging,” said Chitnis. “Traditionally, ultrasound systems transmit short-duration pulses, and the echo signals are used to make clinically usefully images. Our systems use a patented approach that relies on transmission of long-duration chirps, which allows us to perform ultrasound sensing using the same components one might find in their car radio.”

This modified approach allowed the team to design a simpler, cheaper system that could be miniaturized and powered by batteries. This let them design an ultrasound monitor with a small, portable form factor that could be attached to a patient.

Soon, Chitnis hopes to further improve his device and develop software tools to more quickly interpret and analyze the ultrasound signals.

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

———————– MORE MEETING INFORMATION ———————–

The Acoustical Society of America is joining the Australian Acoustical Society to co-host Acoustics 2023 Sydney. This collaborative event will incorporate the Western Pacific Acoustics Conference and the Pacific Rim Underwater Acoustics Conference.

Main meeting website: https://acoustics23sydney.org/
Technical program: https://eppro01.ativ.me/src/EventPilot/php/express/web/planner.php?id=ASAFALL23

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 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 (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/.

ABOUT THE AUSTRALIAN ACOUSTICAL SOCIETY
The Australian Acoustical Society (AAS) is the peak technical society for individuals working in acoustics in Australia. The AAS aims to promote and advance the science and practice of acoustics in all its branches to the wider community and provide support to acousticians. Its diverse membership is made up from academia, consultancies, industry, equipment manufacturers and retailers, and all levels of Government. The Society supports research and provides regular forums for those who practice or study acoustics across a wide range of fields The principal activities of the Society are technical meetings held by each State Division, annual conferences which are held by the State Divisions and the ASNZ in rotation, and publication of the journal Acoustics Australia. https://www.acoustics.org.au/

A Farsighted Approach to Tackle Nearsightedness #Acoustics23

A Farsighted Approach to Tackle Nearsightedness #Acoustics23

Acoustical imaging helps reveal causes and potential cures of myopia.

SYDNEY, Dec. 5, 2023 – Modern living may be contributing to an epidemic of nearsighted vision and related blindness. By 2050, it is estimated that half the world’s population will suffer from low vision due to myopia, a condition where the eye grows too large and can no longer focus on objects in the distance. Human eyes, honed by evolution to survive in the wild, are ill-adapted to city living, contributing to increased cases of myopia, among other factors.

For decades, researcher Sally McFadden from the University of Newcastle has investigated eyes and eyesight in humans and animals. She will present her work and the importance of acoustical imaging Dec. 5 at 10:40 a.m. Australian Eastern Daylight Time, as part of Acoustics 2023 Sydney, running Dec. 4-8 at the International Convention Centre Sydney.

Nearsightedness

Near-sightedness is on the rise, likely due to modern lifestyles that require seeing objects up close, rather than adjusting to vision in the distance. Credit: American Institute of Physics

As humans age, our eyes adjust based on how we use them, growing or shortening to focus where needed. We now know that blurred input to the eye while the eye is growing causes myopia. It is so specific that the eye grows exactly to compensate for the amount and the direction of blur. For example, if you put the focus behind the retina, the eye grows longer, while if you put the focus in front of the retina, the eye slows its growth and becomes shorter. If the eye grows too long, it becomes myopic or nearsighted. In extreme cases, high myopia is associated with glaucoma, and can increase the risk of retinal detachment and abnormal pathologies around the optic nerve which lead to profound blindness.

“Babies are generally born longsighted, and the changes in the optics of the eye have to coordinate with the eye growth to get to the perfect length for focused vision,” said McFadden. “The problem is that the human eye evolved to suit a hunter-gatherer lifestyle and is not adapted for modern living.”

McFadden and her team built a high-frequency ultrasonography system to measure eye size and how quickly eyes grow to better understand myopia and its contributing factors.

“Education level (amount of study) and the type of light stimulation to the eye all correlate with the amount of myopia you develop,” McFadden said. “Time spent outdoors is protective. Myopia is greater in cities than in rural populations, and even correlates with those that live in small homes.”

Currently, vision-correcting gear like glasses and contacts are the only solution for myopia. However, eyedrops for children with myopia are in development and could halt the vision from worsening. Teams from around the world are collaborating to develop treatments for high myopia to preserve our vision.

###

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

———————– MORE MEETING INFORMATION ———————–

The Acoustical Society of America is joining the Australian Acoustical Society to co-host Acoustics 2023 Sydney. This collaborative event will incorporate the Western Pacific Acoustics Conference and the Pacific Rim Underwater Acoustics Conference.

Main meeting website: https://acoustics23sydney.org/
Technical program: https://eppro01.ativ.me/src/EventPilot/php/express/web/planner.php?id=ASAFALL23

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 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 (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/.

ABOUT THE AUSTRALIAN ACOUSTICAL SOCIETY
The Australian Acoustical Society (AAS) is the peak technical society for individuals working in acoustics in Australia. The AAS aims to promote and advance the science and practice of acoustics in all its branches to the wider community and provide support to acousticians. Its diverse membership is made up from academia, consultancies, industry, equipment manufacturers and retailers, and all levels of Government. The Society supports research and provides regular forums for those who practice or study acoustics across a wide range of fields The principal activities of the Society are technical meetings held by each State Division, annual conferences which are held by the State Divisions and the ASNZ in rotation, and publication of the journal Acoustics Australia. https://www.acoustics.org.au/

Needle-Free Ultrasound Vaccine Delivery #Acoustics23

Needle-Free Ultrasound Vaccine Delivery #Acoustics23

Technique employs bubbles formed and popped in response to sound waves to deliver vaccines and achieve potentially improved immune response.

SYDNEY, Dec. 4, 2023 – An estimated quarter of adults and two-thirds of children have strong fears around needles, according to the U.S. Centers for Disease Control and Prevention. Yet, public health depends on people being willing to receive vaccines, which are often administered by a jab.

Darcy Dunn-Lawless, a doctoral student at the University of Oxford’s Institute of Biomedical Engineering, is investigating the potential of a painless, needle-free vaccine delivery by ultrasound. He will share the recent advancements in this promising technique as part of Acoustics 2023 Sydney, running Dec. 4-8 at the International Convention Centre Sydney. His presentation will take place Dec. 4 at 11:00 a.m. Australian Eastern Daylight Time.

“Our method relies on an acoustic effect called ‘cavitation,’ which is the formation and popping of bubbles in response to a sound wave,” said Dunn-Lawless. “We aim to harness the concentrated bursts of mechanical energy produced by these bubble collapses in three main ways. First, to clear passages through the outer layer of dead skin cells and allow vaccine molecules to pass through. Second, to act as a pump that drives the drug molecules into these passages. Lastly, to open up the membranes surrounding the cells themselves, since some types of vaccine must get inside a cell to function.”

Though initial in vivo tests reported 700 times fewer vaccine molecules were delivered by the cavitation approach compared to conventional injection, the cavitation approach produced a higher immune response. The researchers theorize this could be due to the immune-rich skin the ultrasonic delivery targets in contrast to the muscles that receive the jab. The result is a more efficient vaccine that could help reduce costs and increase efficacy with little risk of side effects.

“In my opinion, the main potential side effect is universal to all physical techniques in medicine: If you apply too much energy to the body, you can damage tissue,” Dunn-Lawless said. “Exposure to excessive cavitation can cause mechanical damage to cells and structures. However, there is good evidence that such damage can be avoided by limiting exposure, so a key part of my research is to try and fully identify where this safety threshold lies for vaccine delivery.”

Vaccine

Ultrasound pulses deliver vaccines through the skin without needles. This technique, which employs sound waves to create bubbles that forge a path for the vaccine, may be especially helpful for DNA vaccines. Credit: Darcy Dunn-Lawless

Dunn-Lawless works as part of a larger team under the supervision of Dr. Mike Gray, Professor Bob Carlisle, and Professor Constantin Coussios within Oxford’s Biomedical Ultrasonics, Biotherapy and Biopharmaceuticals Laboratory (BUBBL). Their cavitation approach may be particularly conducing to DNA vaccines that are currently difficult to deliver. With cavitation able to help crack open the membranes blocking therapeutic access to the cell nucleus, the other advantages of DNA vaccines, like a focused immune response, low infection risk, and shelf stability, can be better utilized.

###

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

———————– MORE MEETING INFORMATION ———————–

The Acoustical Society of America is joining the Australian Acoustical Society to co-host Acoustics 2023 Sydney. This collaborative event will incorporate the Western Pacific Acoustics Conference and the Pacific Rim Underwater Acoustics Conference.

Main meeting website: https://acoustics23sydney.org/
Technical program: https://eppro01.ativ.me/src/EventPilot/php/express/web/planner.php?id=ASAFALL23

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 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 (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/.

ABOUT THE AUSTRALIAN ACOUSTICAL SOCIETY
The Australian Acoustical Society (AAS) is the peak technical society for individuals working in acoustics in Australia. The AAS aims to promote and advance the science and practice of acoustics in all its branches to the wider community and provide support to acousticians. Its diverse membership is made up from academia, consultancies, industry, equipment manufacturers and retailers, and all levels of Government. The Society supports research and provides regular forums for those who practice or study acoustics across a wide range of fields The principal activities of the Society are technical meetings held by each State Division, annual conferences which are held by the State Divisions and the ASNZ in rotation, and publication of the journal Acoustics Australia. https://www.acoustics.org.au/

Using ultrasound as an antibody in Alzheimer’s and as a drug dose enhancer in cancer patients

Elisa Konofagou – ek2191@columbia.edu

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.