Riding sound waves in the brain

Brain tumours, brain haemorrhages and neurological and psychological conditions are often hard to treat with medication. And even when effective drugs are available, these tend to have severe side effects because they circulate throughout the brain and not just the area they are meant to treat. In light of this situation, researchers have high hopes of one day being able to provide a more targeted approach that would deliver medications to very specifically defined locations. To this end, they are in the process of developing mini-transporters that can be guided through the dense maze of blood vessels.

Researchers at ETH Zurich, the University of Zurich and the University Hospital Zurich have now managed for the first time to guide microvehicles through the blood vessels in the brain of an animal using ultrasound.

Ultrasound instead of magnetism

Compared to alternative navigation technologies such as those based on magnetic fields, ultrasound offers certain benefits.

Daniel Ahmed, Professor of Acoustic Robotics at ETH Zurich and supervisor of the study, explains: "In addition to being widely used in the medical field, ultrasound is safe and penetrates deep into the body."

For their microvehicle, Ahmed and his colleagues used gas-filled microbubbles coated in lipids -- the same substances that biological cell membranes are made of. The bubbles have a diameter of 1.5 micrometres and are currently used as contrast material in ultrasound imaging.

As the researchers have now shown, these microbubbles can be guided through blood vessels.

"Since these bubbles, or vesicles, are already approved for use in humans, it's likely that our technology will be approved and used in treatments for humans more quickly than other types of microvehicles currently in development," Ahmed says.

He was awarded a Starting Grant by the European Research Council ERC in 2019 for his project to research and develop this technology.

Another benefit of the ultrasound-guided microbubbles is that they dissolve in the body once they've done their job.

When using another approach, magnetic fields, the microvehicles have to be magnetic, and it's not easy to develop biodegradable microvehicles.

Moreover, the microbubbles developed by the ETH Zurich researchers are small and smooth.

"This makes it easy for us to guide them along narrow capillaries," says Alexia Del Campo Fonseca, a doctoral student in Ahmed's group and lead author of the study.

Going against the flow

Over the past few years, Ahmed and his group have been working in the lab to develop their method for guiding microbubbles through narrow vessels.

Now, in collaboration with researchers from the University of Zurich and University Hospital Zurich, they have tested this method on blood vessels in the brains of mice.

The researchers injected the bubbles into the rodents' circulatory system, where they are swept along in the bloodstream without any outside help.

However, the researchers managed to use ultrasound to hold the vesicles in place and guide them through the brain vessels against the direction of blood flow.

The researchers were even able to guide the bubbles through convoluted blood vessels or get them to change direction multiple times in order to steer them into the narrowest branches of the bloodstream.

To control the microvehicles' movements, the researchers also attached four small transducers to the outside of each mouse's skull.

These devices generate vibrations in the ultrasonic range, which spread through the brain as waves.

At certain points in the brain, the waves emitted by two or more transducers can either amplify each other or cancel each other out.

The researchers guide the bubbles using a sophisticated method of adjusting the output of each individual transducer.

Real-time imaging shows them what direction the bubbles are moving in.

To create the imaging for this study, the researchers used two-photon microscopy.

In the future, they also want to use ultrasound itself for imaging and plan to enhance ultrasound technology for this purpose.

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Physicists demonstrate how sound can be transmitted through vacuum

A classic movie was once promoted with the punchline: "In space, no one can hear you scream." Physicists Zhuoran Geng and Ilari Maasilta from the Nanoscience Center at the University of Jyväskylä, Finland, have demonstrated, on the contrary, that in certain situations sound can be transmitted strongly across a vacuum region!

In a recent publication they show that in some cases a sound wave can jump or "tunnel" fully across a vacuum gap between two solids if the materials in question are piezoelectric. In such materials, vibrations (sound waves) produce an electrical response, as well, and since an electric field can exist in vacuum, it can transmit the sound waves across. The requirement is that the size of the gap is smaller than the wavelength of the sound wave. This effect works not only in audio range of frequencies (Hz-kHz), but also in ultrasound (MHz) and hypersound (GHz) frequencies, as long as the vacuum gap is made smaller as the frequencies increase.

- In most cases the effect is small, but we also found situations, where the full energy of the wave jumps across the vacuum with 100 % efficiency, without any reflections. As such, the phenomenon could find applications in microelectromechanical components (MEMS, smartphone technology) and in the control of heat, says professor Ilari Maasilta from the Nanoscience Center at the University of Jyväskylä.

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Sonic advance: How sound waves could help regrow bones

Researchers have used sound waves to turn stem cells into bone cells, in a tissue engineering advance that could one day help patients regrow bone lost to cancer or degenerative disease.

The innovative stem cell treatment from researchers at RMIT University in Melbourne, Australia, offers a smart way forward for overcoming some of the field's biggest challenges, through the precision power of high-frequency sound waves.

Tissue engineering is an emerging field that aims to rebuild bone and muscle by harnessing the human body's natural ability to heal itself.

A key challenge in regrowing bone is the need for large amounts of bone cells that will thrive and flourish once implanted in the target area.

To date, experimental processes to change adult stem cells into bone cells have used complicated and expensive equipment and have struggled with mass production, making widespread clinical application unrealistic.

Additionally, the few clinical trials attempting to regrow bone have largely used stem cells extracted from a patient's bone marrow -- a highly painful procedure.

In a new study published in the journal Small, the RMIT research team showed stem cells treated with high-frequency sound waves turned into bone cells quickly and efficiently.

Importantly, the treatment was effective on multiple types of cells including fat-derived stem cells, which are far less painful to extract from a patient.

Fast and simple

Co-lead researcher Dr Amy Gelmi said the new approach was faster and simpler than other methods.

"The sound waves cut the treatment time usually required to get stem cells to begin to turn into bone cells by several days," said Gelmi, a Vice-Chancellor's Research Fellow at RMIT.

"This method also doesn't require any special 'bone-inducing' drugs and it's very easy to apply to the stem cells.

"Our study found this new approach has strong potential to be used for treating the stem cells, before we either coat them onto an implant or inject them directly into the body for tissue engineering."

The high-frequency sound waves used in the stem cell treatment were generated on a low-cost microchip device developed by RMIT.

Co-lead researcher Distinguished Professor Leslie Yeo and his team have spent over a decade researching the interaction of sound waves at frequencies above 10 MHz with different materials.

The sound wave-generating device they developed can be used to precisely manipulate cells, fluids or materials.

"We can use the sound waves to apply just the right amount of pressure in the right places to the stem cells, to trigger the change process," Yeo said.

"Our device is cheap and simple to use, so could easily be upscaled for treating large numbers of cells simultaneously -- vital for effective tissue engineering."

The next stage in the research is investigating methods to upscale the platform, working towards the development of practical bioreactors to drive efficient stem cell differentiation.

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Acoustic illusions

When listening to music, we don't just hear the notes produced by the instruments, we are also immersed in its echoes from our surroundings. Sound waves bounce back off the walls and objects around us, forming a characteristic sound effect -- a specific acoustic field. This explains why the same piece of music sounds very different when played in an old church or a modern concrete building.

Architects have long been capitalising on this fact when building, say, concert halls. However, the principle can also be transferred to other applications: objects hidden underground can be visualised by measuring how sound waves from a known source are reflected.

Active and passive manipulation

Some scientists want to go one step further and systematically manipulate the acoustic field to achieve an effect that shouldn't exist per se, given the real-life situation. For instance, they are attempting to create an illusory audio experience that tricks the listener into believing they are in a concrete building or an old church. Alternatively, objects can be made invisible by manipulating the acoustic field in such a way that the listener no longer perceives them.

Usually, the desired illusion relies on using passive methods that involve structuring the surfaces with the help of what are known as metamaterials. One way of hiding an object acoustically is to coat its surface and stop it from reflecting any sound waves. However, this approach is inflexible and usually works only within a limited frequency range, making it unsuitable for many applications.

Active methods seek to achieve the illusion by superimposing another layer of sound waves. In other words, by adding a second signal to the initial acoustic field. However, until now the scope for using this approach has also been limited, as it works only if the initial field can be predicted with some certainty.

Real-time illusion

Now the group headed by Johan Robertsson, Professor of Applied Geophysics at ETH Zurich, has worked with scientists from the University of Edinburgh to develop a new concept that significantly improves the active illusion. Led by Theodor Becker, a postdoc in Robertsson's group, and Dirk-Jan van Manen, the senior scientist who was instrumental in designing the experiments, the researchers have managed to augment the initial field in real time, as they report in the latest issue of the journal Science Advances. As a result, they can make objects disappear and they can mimic non-existent ones.

To achieve the special acoustic effects, the researchers installed a large test facility for the project in the Centre for Immersive Wave Experimentation at the Switzerland Innovation Park Zurich in Dübendorf. Specifically, this facility allows them to mask the existence of an object measuring roughly 12 centimetres or simulate an imaginary object of equal size.

The target object is enclosed in an outer ring of microphones as control sensors and an inner ring of loudspeakers as control sources. The control sensors register which external acoustic signals reach the object from the initial field. Based on these measurements, a computer then calculates which secondary sounds the control sources must produce to achieve the desired augmentation of the initial field.

Sophisticated technology

To mask the object, the control sources emit a signal that completely obliterates the sound waves reflected off the object. By contrast, to simulate an object (also known as holography), the control sources augment the initial acoustic field as if sound waves were bouncing off an object at the centre of the two rings.

For this augmentation to work, the data measured by the control sensors must be transformed instantaneously into instructions for the control sources. To control the system, the researchers therefore use field-programmable gate arrays (FPGAs) with an extremely short response time.

"Our facility allows us to manipulate the acoustic field over a frequency range of more than three and a half octaves," Robertsson says. The maximum frequency for cloaking is 8,700 Hz and 5,900 Hz for simulating. To date, the researchers have been able to manipulate the acoustic field on a surface in two dimensions. As a next step, they want to increase the process to three dimensions and extend its functional range. The system currently augments airborne sound waves. However, Robertsson explains, the new process could also produce acoustic illusions under water. He envisages a vast array of potential uses in different fields, such as sensor technology, architecture and communications, as well as in the education sector.

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NASA's TESS tunes into an all-sky 'symphony' of red giant stars

Using observations from NASA's Transiting Exoplanet Survey Satellite (TESS), astronomers have identified an unprecedented collection of pulsating red giant stars all across the sky. These stars, whose rhythms arise from internal sound waves, provide the opening chords of a symphonic exploration of our galactic neighborhood.

TESS primarily hunts for worlds beyond our solar system, also known as exoplanets. But its sensitive measurements of stellar brightness make TESS ideal for studying stellar oscillations, an area of research called asteroseismology.

Hon presented the research during the second TESS Science Conference, an event supported by the Massachusetts Institute of Technology in Cambridge -- held virtually from Aug. 2 to 6 -- where scientists discuss all aspects of the mission. The Astrophysical Journal has accepted a paper describing the findings, led by Hon.

Sound waves traveling through any object -- a guitar string, an organ pipe, or the interiors of Earth and the Sun -- can reflect and interact, reinforcing some waves and canceling out others. This can result in orderly motion called standing waves, which create the tones in musical instruments.

Just below the surfaces of stars like the Sun, hot gas rises, cools, and then sinks, where it heats up again, much like a pan of boiling water on a hot stove. This motion produces waves of changing pressure -- sound waves -- that interact, ultimately driving stable oscillations with periods of a few minutes that produce subtle brightness changes. For the Sun, these variations amount to a few parts per million. Giant stars with masses similar to the Sun's pulsate much more slowly, and the corresponding brightness changes can be hundreds of times greater.

Oscillations in the Sun were first observed in the 1960s. Solar-like oscillations were detected in thousands of stars by the French-led Convection, Rotation and planetary Transits (CoRoT) space telescope, which operated from 2006 to 2013. NASA's Kepler and K2 missions, which surveyed the sky from 2009 to 2018, found tens of thousands of oscillating giants. Now TESS extends this number by another 10 times.

"With a sample this large, giants that might occur only 1% of the time become pretty common," said co-author Jamie Tayar, a Hubble Fellow at the University of Hawaii. "Now we can start thinking about finding even rarer examples."

The physical differences between a cello and a violin produce their distinctive voices. Similarly, the stellar oscillations astronomers observe depend on each star's interior structure, mass, and size. This means asteroseismology can help determine fundamental properties for large numbers of stars with accuracies not achievable in any other way.

"Our initial result, using stellar measurements across TESS's first two years, shows that we can determine the masses and sizes of these oscillating giants with precision that will only improve as TESS goes on," said Marc Hon, a NASA Hubble Fellow at the University of Hawaii in Honolulu. "What's really unparalleled here is that TESS's broad coverage allows us to make these measurements uniformly across almost the entire sky."

When stars similar in mass to the Sun evolve into red giants, the penultimate phase of their stellar lives, their outer layers expand by 10 or more times. These vast gaseous envelopes pulsate with longer periods and larger amplitudes, which means their oscillations can be observed in fainter and more numerous stars.

TESS monitors large swaths of the sky for about a month at a time using its four cameras. During its two-year primary mission, TESS covered about 75% of the sky, each camera capturing a full image measuring 24-by-24 degrees every 30 minutes. In mid-2020, the cameras began collecting these images at an even faster pace, every 10 minutes.

The images were used to develop light curves -- graphs of changing brightness -- for nearly 24 million stars over 27 days, the length of time TESS stares at each swath of the sky. To sift through this immense accumulation of measurements, Hon and his colleagues taught a computer to recognize pulsating giants. The team used machine learning, a form of artificial intelligence that trains computers to make decisions based on general patterns without explicitly programming them.

To train the system, the team used Kepler light curves for more than 150,000 stars, of which some 20,000 were oscillating red giants. When the neural network finished processing all of the TESS data, it had identified a chorus of 158,505 pulsating giants.

Next, the team found distances for each giant using data from ESA's (the European Space Agency's) Gaia mission, and plotted the masses of these stars across the sky. Stars more massive than the Sun evolve faster, becoming giants at younger ages. A fundamental prediction in galactic astronomy is that younger, higher-mass stars should lie closer to the plane of the galaxy, which is marked by the high density of stars that create the glowing band of the Milky Way in the night sky.

"Our map demonstrates for the first time empirically that this is indeed the case across nearly the whole sky," said co-author Daniel Huber, an assistant professor for astronomy at the University of Hawaii. "With the help of Gaia, TESS has now given us tickets to a red giant concert in the sky."

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