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.

How loud is traffic near you?

Mylan Cook – mylan.cook@gmail.com

Brigham Young University, Provo, Utah, 84602, United States

Kent. L. Gee, Mark K. Transtrum, Shane V. Lympany

Popular version of 4aCA5 – Big data to streamlined app: Nationwide traffic noise prediction
Presented at the 184 ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0018816

VROOM! Vehicles are loud, and we hear them all the time. But how loud is it near your home, or at the park across town? The National Transportation Noise Map can’t give you more than an average daily sound level, even though it’s probably a lot quieter at night and louder during rush hour. So, we created an app that can predict the noise where, when, and how you want. How loud is it by that interstate at 3 AM, or at 5 PM? Using physics-based modeling, we can predict that for you. Why does the noise sound lower in pitch near the freeway than near other roads? Probably because of all the large trucks. How does the noise on your street during the winter compare to that across town, or on the other side of the country? Our app can predict that for you in a snap.

This (aptly named) app is called VROOM, for the Vehicular Reduced-Order Observation-based Model. It was made by using observed hourly traffic counts at stations across the country. It also uses information such as the average percentage of heavy trucks on freeways at night and the average number of delivery trucks on smaller roads on weekdays to predict sound characteristics across the nation. The app includes a user-friendly interface, and with only 700 MB of stored data can predict traffic noise for roads throughout the country, including near where you live. You don’t need a supercomputer to get a good estimate. The app will show you the sound levels by creating an interactive map  so you can zoom in to see what the noise looks like downtown or near your home.

So how loud is traffic near you?

Improving pitch sensitivity by cochlear-implant users

John Middlebrooks – middlebj@hs.uci.edu

University of California, Irvine, Irvine, CA, 92697-5310, United States

Matthew Richardson and Harrison Lin
University of California, Irvine

Robert Carlyon
University of Cambridge

Popular version of 2aPP6 – Temporal pitch processing in an animal model of normal and electrical hearing
Presented at the 184 ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0018352

A cochlear implant can restore reasonable speech perception to a deaf individual. Sensitivity to the pitches of sounds, however, typically is negligible. Lack of pitch sensitivity deprives implant users of appreciation of musical melodies, disrupts pitch cues that are important for picking out a voice amid competing sounds, and impairs understanding of lexical tones in tonal languages (like Mandarin or Vietnamese, for example). Efforts to improve pitch perception by cochlear-implant users could benefit from studies in experimental animals, in which the investigator can control the history of deafness and electrical stimulation and can evaluate novel implanted devices. We are evaluating cats for studies of pitch perception in normal and electrical hearing.

We train normal-hearing cats to detect changes in the pitches of trains of sound pulses – this is “temporal pitch” sensitivity. The cat presses a pedal to start a pulse train at a particular base rate. After a random delay, the pulse rate is changed and the cat can release the pedal to receive a food reward. The range of temporal pitch sensitivity by cats corresponds well to that of humans, although the pitch range of cats is shifted somewhat higher in frequency in keeping with the cat’s higher frequency range of hearing.

We record small voltages from the scalps of sedated cats. The frequency-following response (FFR) consists of voltages originating in the brainstem that synchronize to the stimulus pulses. We can detect FFR signals across the range of pulse rates that is relevant for temporal pitch sensitivity. The acoustic change complex (ACC) is a voltage that arises from the auditory cortex in response to a change in an ongoing stimulus. We can record ACC signals in response to pitch changes across ranges similar to the sensitive ranges seen in the behavioral trials in normal-hearing cats.

We have implanted cats with devices like cochlear implants used by humans. Both FFR and ACC could be recorded in response to electrical stimulation of the implants.

The ACC could serve as a surrogate for behavioral training for conditions in which a cat’s learning might not keep up with changes in stimulation strategies, like when a cochlear implant is newly implanted or a novel stimulating pattern is tested.

We have found previously in short-term experiments in anesthetized cats that an electrode inserted into the auditory (hearing) nerve can selectively stimulate pathways that are specialized for transmission of timing information, e.g., for pitch sensation. In ongoing experiments, we plan to place long-term indwelling electrodes in the auditory nerve. Pitch sensitivity with those electrodes will be evaluated with FFR and ACC recording. If performance of the auditory nerve electrodes in the animal model turns out as anticipated, such electrode could offer improved pitch sensitivity to human cochlear implant users.

Here we are…Hear our story! Brothertown Indian Heritage, through acoustic research and technology

seth wenger – seth.wenger@nyu.edu

Settler Scholar and Public Historian with Brothertown Indian Nation, Ridgewood, NY, 11385, United States

Jessica Ryan – Vice Chair of the Brothertown Tribal Council

Popular version of 3pAA6 – Case study of a Brothertown Indian Nation cultural heritage site–toward a framework for acoustics heritage research in simulation, analysis, and auralization
Presented at the 184 ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0018718

The Brothertown Indian Nation has a centuries old heritage of group singing. Although this singing is an intangible heritage, these aural practices have left a tangible record through published music, as well as extensive personal correspondence and journal entries about the importance of singing in the political formation of the Tribe. One specific tangible artifact of Brothertown ancestral aural heritage–and focus of the acoustic research in this case study–is a house built in the 18th century by Andrew Curricomp, a Tunxis Indian.

Figure 1: Images courtesy of authors

In step with the construction of the house at Tunxis Sepus, Brothertown political formation also solidified in the 18th century between members of seven parent Tribes: various Native communities of Southern New England including Mohegan, Montauk, Narragansett, Niantic, Stonington (Pequot), Groton/Mashantucket (Pequot) and Farmington (Tunxis). Settler colonial pressure along the Northern Atlantic coast forced Brothertown Indian ancestors to leave various Indigenous towns and settlements to form into a body politic named Brotherton (Eeyamquittoowauconnuck). Nearly a century later, after multiple forced relocations, the Tribe–including many of Andrew Curricomp’s grand, and great grandchildren–were displaced again to the Midwest. Today, after nearly two more centuries, the Brothertown Indian Nation Community Center and museum are located in Fond du Lac, WI, just south of their original Midwestern settlement.

During contemporary trips back to visit parent tribes, members of the Brothertown Indian Nation have visited the Curricomp House at Tunxis Sepus.

Figure 2: Image courtesy of authors

However, by then it was known as the William Day Museum of Indian Artifacts. After the many relocations of Brothertown and their parent Tribes, the Curricomp house was purchased by a local landowner of European descent. The man’s groundskeeper, Bill Day, had a hobby of collecting stone lithic artifacts he would find during his gardening around the property. The land owner decided that having the Curricomp house would be a perfect home for his groundskeeper’s musings, as it was locally told that the house belonged to the last living Indian in the town. He had the Curricomp House moved to his property and named it for his gardener, the William Day Museum of Indian Artifacts.

The myth of the vanishing Indian is a commonly held trope in popular Western Culture. This colonial, or “last living Indian” history that dominates the archive, includes no real information about what Native communities actually used the space for, or where the descendants of Tunxis are now living. This acoustics case study intends for the living descendants of Tunxis Sepus to have sovereignty over the digital content created, as the house serves as a tangible cultural signifier of their intangible aural heritage.

Architectural acoustic heritage throughout Brothertown’s history of displacement is of value to their vibrant contemporary culture. Many of these tangible heritage sites have been made intangible to the Brothertown Community, as they are settler owned, demolished, or geographically inaccessible to the Brothertown diaspora–requiring creative solutions to make this heritage available. Both in-situ and web-based immersive interfaces are being designed to interact with the acoustic properties of the Curricomp house.

Figure 3: Image courtesy of authors

These interfaces use various music and speech source media that feature Brothertown aural Heritage. The acoustic simulations and auralizations created during this case study of the Curricomp House are tools: a means by which living descendants might hear one another in the difficult to access acoustic environments of their ancestors.

Mapping the directional elasticity in living human skin with air-coupled ultrasound and light

Ivan (Vanya) Pelivanov – ivanp3@uw.edu

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]

Acoustics should be a bigger piece in the building decarbonization puzzle

Jonathan Broyles – j.broyles@psu.edu

The Pennsylvania State University, University Park, PA, 16801, United States

Popular version of 5aAA6 – Acoustic design trade-offs when reducing the carbon footprint of buildings
Presented at the 184 ASA Meeting
Read the abstract at https://doi.org/10.1121/10.0019111

The built environment is responsible for upwards of 40% of global carbon emissions and has sparked a change in how buildings are designed in an effort to mitigate the global climate crisis. Design goals to reduce the carbon footprint of a building directly affects acoustics, potentially causing unintended acoustical consequences. Yet building acoustics is often considered much later in the design of a building, if at all, resulting in missed opportunities to harmonize sustainable and acoustical design goals. Significant research is needed to further understand acoustic-decarbonization trade-offs, as preliminary results found that research at the intersection of building decarbonization and acoustic design lacks well behind other building disciplines (see Figure 1). Despite the lack of published work, several studies suggest that holistic building design solutions are possible, including the balancing the mass distribution of structures to achieve high sound insulation with less material, designing with natural materials that can reduce echoes, and selecting efficient mechanical systems that prevent unwanted noise.

Figure 1: Publication trends for five building disciplines and building decarbonization.

Building carbon emissions can be reduced by designing sustainable structural elements (including green roofs and mass timber structures) and reducing the material consumption of structures with high carbon emissions (such as concrete floors, as shown in Figure 2). Innovations in building and construction materials can further improve carbon emission savings, from reducing carbon emissions during material manufacturing and during building operation. Such strategies include the use of natural materials (including straw bales and compressed earth blocks), concrete mixes with lower cement proportions, and material optimization. Carbon emissions during the service life of a building can be reduced by selecting more efficient systems (such as multi-pane windows) and smart mechanical systems. These solutions also highlight the interdisciplinary nature of building design, as decisions in one discipline can directly influence acoustic performance.

Figure 2: Example of synergizing sustainable, acoustical, and structural design goals. Image courtesy of Broyles et al., 2023.

Many of the strategies to reduce carbon emissions while balancing acoustic design goals have important trade-offs that should be further studied. Many sustainable structures can have unfavorable sound insulation due to a lack of mass. Many natural materials deteriorate at a faster rate than conventional materials. Lastly, the upfront cost and maintenance of efficient systems can make these solutions unattractive to building owners. This emphasizes the importance for further research at the intersection of building decarbonization and acoustics to better understand how to provide sustainable solutions that benefit the planet, building occupants, and building owners. Future decarbonization technologies will need to consider the acoustic implications to prevent post-construction retrofits and other design modifications. As the building industry continues to pursue aggressive sustainable targets, a holistic approach to building design is needed to truly provide a sustainable building.