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Think before you ‘speak’: brain–computer interface restores speech in paralysed man

“Hello, World!” is a simple and commonly used code to introduce people to a programming language. Pronouncing “Hello, World!” out loud, however, while instinctive for most adults, involves a complex series of respiratory, phonetic and resonance tasks to produce sound and articulate the correct words.

Speech originates in the brain, with neural signals fired from the brain cortex effortlessly coordinating vocal tract muscles to communicate. However, for paralysed patients who have lost the ability to articulate speech (a condition called anarthria) due to a brain injury or neurological disorder, verbal communication is especially challenging. This can restrict their autonomy and impact quality-of-life, despite retaining intact cognitive function.

A team of neuroscientists and engineers at the University of California San Francisco (UCSF) used deep-learning and natural-language models to decode the brain waves of a clinical trial participant with severe paralysis and anarthria as he attempted to produce words and sentences. The study, published in the New England Journal of Medicine, showed a promising median decoding rate of 15.2 words per minute (with a median word error rate of 25.6%). This is approximately three times faster than the computer-based typing interface that the participant normally relies on for communication.

“We think that an ideal speech neuroprosthesis would allow a paralysed user to voluntarily and autonomously engage the system to communicate and interact with their personal devices,” explains David Moses, a postdoctoral fellow at UCSF and one of the lead authors in the study.

Recording the brain – restoring the speech link

To capture the cortical signals associated with speech in real time, the team used a high-density rectangular electrode array (67 × 35 × 0.51 mm) implanted on the surface of the brain to record electrical activity in multiple cortical brain regions involved in speech formulation.

Electrode placement — Illustration showing placement of the electrocorticography electrode on the participant’s speech motor cortex and the head stages used to connect the electrode to the computer. (Courtesy: Ken Probst, UCSF)

During speech tasks, a percutaneous connector secured to the participant’s cranium transmits the analogue brain signals – using a detachable link and cable – from the electrode array to a computer for signal processing and filtering.

Translating the speech-correlated filtered cortical brain signals into words restored the participant’s ability to communicate in real-time. Throughout the 81-week study period, the neural implant provided highly stable cortical signals without the need for frequent recalibration, which is desirable for long-term neuroprosthetic applications.

Decoding speech – words library

The researchers employed a set of 50 common English words as the baseline to form grammatically and semantically correct sentences. The participant attempted to produce individual words that appeared on a monitor and, on a subsequent task, create sequences to form sentences such as “hello how are you”, “I like my nurse” and “bring my glasses please”.

A variation of the speech tasks required the participant to formulate a unique response to prompts displayed in the monitor to actively engage him in a conversation.

The neural signals recorded throughout the isolated-word task were used to train word detection and classification models using deep learning. During sentence decoding, the word error rate using only the deep-learning models was 60.5%. When accounting for the next-word probabilities using a natural-language model, the word error rate dropped below 30%, making the neuroprosthetic suitable for real-time speech decoding.

The next step for this technology involves validation with other clinical trial participants. “We need to show that this method of decoding attempted speech from brain activity works with more than just one person and ideally with individuals who have other severe conditions, such as locked-in syndrome,” Moses tells Physics World.

Summer internships: Maria Violaris – ‘I developed general research skills, which are useful in both industry and academia’

For Maria Violaris, who graduated with a degree in physics from the University of Oxford in 2020, the main motivation to do a summer internship was to find out what it’s like to work in industry. She went to a careers fair hosted by her university, where she met employees of Innovia Technology – a Cambridge-based science innovation consultancy that helps its client companies improve products – and found out about its internship programme.

Although Violaris didn’t know before the event that science consultancies even existed, she thought that Innovia sounded like a fun place to work because of the variety of projects it does, which meant she could learn about lots of different areas of physics. She applied with a CV and cover letter, followed by a video call in which she was asked physics-related technical questions. Violaris was then invited to an in-person interview where she had to look at a case study and come up with ideas of how to approach it. While this may sound daunting, it is an excellent opportunity to practise for post-university job applications and interviews, many of which follow a similar process.

After finding out she had been successful, Violaris moved to Cambridge for the summer of 2019, where she worked in multidisciplinary teams on several projects, including one looking at a cosmetic product made by one of Innovia’s clients. “We were trying to improve the texture of the product, so I was looking at the physics of how the fluid stretches, and the difference in how it behaves when tapped or rubbed onto skin. I worked with behavioural scientists who were investigating how people typically use the product, and with chemists who were looking at its chemical composition.” Over the course of the internship, Violaris also got involved in a project to improve surgical hammers to reduce their risk of being fractured, and a project to enhance the taste of a product for a food company.

Innovia encourages its interns to maintain a good work–life balance, which meant that Violaris had plenty of time for social activities, playing ultimate frisbee with her colleagues once a week and going to the pub together on Friday evenings. She even joined a yoga group at the company.

Having enjoyed her time at Innovia, Violaris sought out another internship for the summer of 2020. At this point she knew she was most excited by quantum physics. By searching online for quantum computing companies, she found the website of quantum software start-up Riverlane, also based in Cambridge, and discovered that it runs an internship programme, which she applied to successfully. “My project involved lots of coding. I put together some Raspberry Pis and circuit boards, and ran Riverlane’s quantum operating system on the circuit boards to create a model quantum computing lab,” says Violaris. “I used this model to create science-communication materials, including a video explaining how the system worked.”

At the time of Violaris’ internships, Riverlane was a start-up with around 30 employees, while Innovia was 20 years old and had 80 employees, so Violaris experienced working for both a new and a more established company. “The systems of work at Innovia were more established,” she says. “At Riverlane, there were more unknowns about how the company would develop, and there was more flexibility around how it collaborated with other companies.” However, both internships gave Violaris a positive experience of working in industry, and a useful insight for her future career. “I decided to do a PhD after graduating, because I really wanted to do research on quantum physics,” she says, “but I’m considering going into either research or industry afterwards. It was great to see a quantum computing company from inside, as that’s an area that I am keen to explore in the future.”

I developed general research skills and learnt how to find out about a topic quickly, which is useful in both industry and academia
Maria Violaris

Summer internships: Constantine Pelesis – ‘I built up my network and got an understanding of how a whole company works together’

Additionally, she gained some valuable skills that she has already been able to draw on during her PhD at Oxford, which she started in October 2020. “I developed general research skills and learnt how to find out about a topic quickly, which is useful in both industry and academia,” she says. “It was also interesting to see the companies’ productivity systems and how they manage teams of people.” In fact, during her final year as an undergraduate, Violaris started a quantum-information student society, where she used her experience to manage group projects.

As for making the most out of an internship, Violaris’ advice is “Ask a lot of questions, especially at the start, because this will help you get going quickly. And don’t be afraid to contribute your ideas. You may think you don’t have enough experience in the area to have useful ideas, but actually the opposite is true. You have a fresh perspective, and in my experience companies value that.”

New location technique shatters the diffraction limit

The diffraction limit has been beaten by a factor of 38 by a new technique that uses microwaves to locate objects. Developed by physicists in France and Germany, the technique is inspired by the coded aperture method and works by allowing light or sound waves to echo and randomly scatter within an enclosed space.

Developed by the trio of Michael del Hougne at the University of Würzburg, Sylvain Gigan of the Laboratoire Kastler Brossel and Philipp del Hougne at the University of Rennes, the technique has been used to determine position of a small cube to within 1/76th of the microwave wavelength used.

The diffraction limit places a stringent lower bound on the resolution of imaging and location techniques that use light, sound or other waves. The limit makes it impossible to use conventional methods to distinguish features that are slightly smaller than 1/2 the wavelength of the waves being used. This is a problem for some popular imaging and location techniques that use ultrasound, microwaves and radio waves – where wavelengths range from hundreds of microns to metres.

There are ways of overcoming the diffraction limit – such as placing a detector less than half a wavelength away from an object and detecting short-lived evanescent waves – but these techniques are often difficult or impractical to implement.

Irregularly shaped cavity

The trio took an alternative approach based on the coded aperture concept, which is used in specialized imaging applications. Here, a scattering structure such as an irregularly shaped cavity is placed between the illuminated object and a single-pixel detector. The scattering structure is altered using coded masks that block certain patterns of waves from reaching the detector. Multiple measurements are made, and the results are used to create a mathematical reconstruction of the object.

Building on this approach, the trio have found a way to make the technique more sensitive to sub-wavelength details. This involves placing both the object and the illumination source inside a cavity where waves can scatter off the walls (see figure). A key feature of the technique is that the waves encounter the object multiple times before arriving at the detector, which is inside the cavity. Also inside the cavity are programmable reflective metasurfaces, which alter the properties of the scattering structure.

Neural network

To test their technique, the trio placed a 4.5 cm metal cube within a metre-wide cavity. The cube was illuminated with 12 cm wavelength microwaves and the detector signals were processed using an artificial neural network.

When the cube was moved to different random locations within the box, the team was able to determine it position to within just 0.16 cm. At about 1/76 of the microwave wavelength, this is well below the diffraction limit. This spatial accuracy improved when the waves were left to echo for longer.

Although the concept is still some way from real-world application, the team believes it could be further developed to non-invasively locate small objects within large rooms, using the echoes of radio or acoustic waves.

The research is described in Physical Review Letters.

Introducing the non-radiating antenna

An international team of physicists has created what might seem like a contradiction in terms: a non-radiating source of electromagnetism. By placing antennas inside a hollow dielectric disc, the researchers exploited interference phenomena to create a non-radiative “meta-atom” that could have applications in several areas, including sensing and wireless power transfer.

Maxwell’s equations tell us that accelerating charges radiate energy in the form of electromagnetic waves. This idea has led to the development of much modern technology, most notably radio communications in all its various guises. But it also posed a challenge to early 20th century physicists seeking to explain the stability of atoms, given that electrons were thought to follow (curved) orbits around atomic nuclei and therefore continuously lose electromagnetic energy.

The response to that problem was Niels Bohr’s atom and the development of quantum mechanics – in particular, the idea that electrons can only occupy certain discrete energy levels. Beyond the quantum world, however, some physicists wondered whether it might be possible to create classical “meta-atoms”: macroscopic objects containing alternating currents that confine the electromagnetic energy they generate and so prevent emission to the far-field.

Electric moments without any poles

This idea received a boost in 1957 when the theoretical physicist Yakov Zel’dovich predicted that the effects of parity violation on electric charges would yield electric moments without any poles. These so-called anapole states were discovered in the late 1990s when researchers at the JILA centre in the US made measurements of parity non-conservation in caesium atoms. Since then, other physicists have suggested that these anapole states could help explain how dark matter remains hidden electromagnetically.

In practical electrodynamic terms, anapoles can be generated by precisely tailoring charge distributions in time and space. These distributions are represented as a series of point-like electric and magnetic multipoles, the emissions from which interfere destructively in the far-field, leaving electromagnetic energy confined within a small space around the sources.

The simplest way to generate anapoles is to superimpose the fields from an electric dipole and a toroidal dipole – the latter can be imagined as electric currents flowing around the cross section of a torus. This has been demonstrated experimentally several times over the last few years, with various research groups exploiting nanofabrication techniques and metamaterials to observe anapole states at different frequencies – from microwaves to the visible range.

Anapole observations

In the new work, Esmaeel Zanganeh and Polina Kapitanova at ITMO University in Saint Petersburg, together with colleagues in Russia, Germany, Australia and China, have put together a relatively simple system to observe both electrical and magnetic anapole states – something not achieved before. The set-up consists of a radiating antenna placed inside a thick, hollow disc shaped like a roll of sticky tape. The disc is made from a dielectric with extremely high permittivity, which allows the disc to be smaller than the wavelength of the radiation it emits. The idea is that the electromagnetic waves from the antenna interfere destructively with secondary waves produced by electric current induced in the dielectric – thereby yielding a non-radiating source.

Electric field of radiating and non-radiating states — **Close comparison** Measured and simulated vertical component of the near electric field distributions 1.5 cm above the non-radiating source prototype. The field amplitudes are normalized to their maximum. (Courtesy: Esmaeel Zanganeh *et al.*, “Anapole meta-atoms: Non-radiating electric and magnetic sources”, *Phys. Rev. Lett.* 2021)

The researchers first modelled their system numerically, assuming a 25 mm-long copper electric dipole antenna emitting radio waves and placed along the thickness of a 20 mm-diameter dielectric disc. Varying the frequency of the antenna, they compared the output of this source with that of the same antenna operating in free space. They found that at the disc’s resonant frequency (375 MHz), the system radiated slightly more power than the antenna alone, but that at a slightly higher frequency (411 MHz) the system’s radiated power dropped to seven orders of magnitude below that of the naked antenna.

Backing their modelling up with analytical calculations, the researchers showed that the sharp drop in power resulted from the antenna and disc generating equal and opposite radiation fields at 411 MHz, leaving just the confined electromagnetic field inside the source. They also did similar calculations involving a magnetic loop antenna – one that intercepts the magnetic field of electromagnetic waves – in place of the electric dipole device. Here, too, they found that by tuning the antenna away from its resonant frequency they could reduce the radiated (magnetic) power to near zero, and about three orders of magnitude lower than that of the antenna alone.

Finally, Zanganeh and colleagues tested their system experimentally, albeit at microwave rather than radio frequencies due to difficulties with materials and testing facilities. By placing a 6.4 mm-diameter disc containing an 18 mm long antenna in an anechoic chamber and using a horn antenna to pick up its far-field emissions, they measured a radiation pattern that closely matched their simulations.

The researchers believe that their new “meta-atoms” could have several practical applications. In particular, the very small radiative output of such devices, coupled with a larger concentration of electromagnetic energy in their immediate vicinity, could see them used for sensing, radiofrequency identification or near-field wireless power transfer, they say.

The research is published in Physical Review Letters.

Protons combine with photons to optimize cancer treatments

Proton-photon combination — Combining proton and photon beams provides the optimal dose distribution for a head-and-neck cancer treatment. (Courtesy: Jan Unkelbach)

Proton therapy offers precision tumour targeting with low integral dose to normal tissue. But for certain situations, photon-based radiotherapy may hold the advantage. In some cases, the penumbra of a photon beam may be sharper, for example, while proton treatments of lung or breast cancer can suffer from robustness problems.

Proton therapy is also a limited resource, with roughly 100 proton therapy centres worldwide compared with more than 10,000 conventional linear accelerators (linacs). In addition, some facilities only have a fixed proton beamline with limited beam angles, making proton treatments suboptimal. The answer to all of these problems, according to Jan Unkelbach from the University of Zurich, may lie in combined proton–photon radiotherapy. Speaking at the recent AAPM Annual Meeting, he explained the rationale.

The size and expense of proton gantries have hindered the widespread implantation of proton therapy systems. But with the introduction of compact accelerators that can fit into a bunker designed for a standard linac, it becomes possible to install fixed proton beamlines into existing radiotherapy departments more easily and at much lower costs.

“The idea is that we have a treatment room with a robotic couch and a standard linac, and we now add a fixed proton beamline equipped with pencil-beam scanning to that treatment room,” Unkelbach explained. This set-up could deliver both proton and photon beams in the same room, during the same treatment fraction and using the same patient immobilization devices.

Unkelbach described an example of a head-and-neck cancer treatment. With a fixed horizonal proton beamline and the treated patient lying on a couch, the proton beams can only be delivered in the coronal plane, which is not ideal for head-and-neck cancer. “If you can only irradiate from left and right, you have to irradiate through the parotid gland to treat the target volume,” he explained.

Using volumetric modulated arc therapy (VMAT) to deliver photons will better spare the parotid, but delivers a dose bath to surrounding normal tissue. “So we would like to combine protons and photons in an optimal way, and we can do this by simultaneously optimizing intensity-modulated photon and proton plans,” Unkelbach explained. “Indeed, both modalities combined gave the desired dose distribution in the target.”

Coronal dose — In the coronal plane, most dose is delivered with protons; the use of photons is restricted to areas where they are needed to improve conformity or spare organs-at-risk. (Courtesy: Jan Unkelbach)

He presented a similar example for a breast cancer case. Here, the optimal treatment combined tangential photon beams to treat the majority of the target with proton beams to deliver dose to lymph nodes and the target periphery. The team is also evaluating the potential of this approach for many other treatment sites.

Optimizing resources

Photons could also play an important role within existing proton therapy facilities, via combined treatments in which some fractions are delivered using protons and the rest using photons. As well as potentially improving treatment plans (for some patients), the approach could help address limited resources. Ultimately, by distributing proton resources over a larger number of cancer patients it may be possible to increase the benefit of proton therapy for the entire patient population.

In the Netherlands, Unkelbach explained, the decision whether to treat with proton or photon therapy is based on the calculated difference in normal tissue complication probability (NTCP) between a proton plan and a photon plan. “But rather than asking who should receive protons and who should not, could we ask how many proton fractions should each patient receive?” he suggested.

He noted that proton fractions have a diminishing return on the NTCP, with the first proton fraction giving a relatively large benefit, and the last few proton fractions having a smaller impact. There’s also a trade-off between making sure all proton therapy slots are used, while not blocking slots with patients who would only gain a mediocre benefit.

Unkelbach presented the example of a clinic with a single proton therapy system that has capacity for three head-and-neck treatments each day. The clinic treats around 100 head-and-neck cancer patients per year with 30 fractions each, giving an average of 12 patient treatments each day. But with only three proton slots available per day, the goal is to use these proton fractions optimally to minimize the total number of complications seen across all of the patients.

To achieve this, the clinic can perform daily proton slot re-assignment, in which the incremental NTCP reduction is calculated for each patient requiring treatment that day, and proton therapy is delivered to those who would benefit the most from an additional proton fraction. To test this scheme, Unkelbach and colleagues simulated the mean doses to relevant organs-at-risk from intensity-modulated radiotherapy and proton therapy, calculating the NTCP for each.

A simulation of 100 cases resulted in some patients receiving only photons, a few receiving protons only and many receiving combined treatments. Switching all patients from photons to protons reduced the average NTCP by about 15%. But even with only three proton slots available, combined treatments with daily slot re-assignment realised about 5% NTCP reduction – roughly 1% more than the existing patient-based selection scheme.

“Combined proton–photon radiotherapy may enable the development of cost-effective forms of proton therapy , which may allow for more widespread implementation of protons,” Unkelbach concluded. “Secondly, combined treatments with some fractions delivered with protons and others with photons may play a role in optimally using proton resources for the entire population of cancer patients.”

Spending your summer wisely: internships special

When you’re a student, the summer holiday is a chance to recharge and recover from all your hard work during term time, but it is also an opportunity to gain some valuable experience for your post-university career. Through doing a summer internship, you can develop skills to boost your employability, while earning money and getting an insight into the type of work you enjoy. On top of that, internships can be a lot of fun too.

Below you will find three short case studies of former interns and their experiences, as well as a box of links to four longer case studies that we’re publishing throughout August.

As the varied experiences of these former interns show, placements come in all shapes and sizes, and there are plenty of them out there if you know where to look. Go to your university’s next careers fair, ask a careers adviser, or simply search online. Don’t be afraid to apply for things and try them out, even if you’re not sure they’re right for you in the long run. An internship is only three months, but you never know what you might learn or where it might lead you.

Jacob Austin Marks

Internship at: CERN

Found it through: Yale University programme

The project: fine-tuning neural network algorithms to distinguish between bottom and charm quarks more reliably

Outside work: explored Switzerland and France with other CERN interns

Top tip: “Go in with an open mind and try to have as many different experiences as possible. That will help to shape your perspective on physics, research and life in general, and will help you to find out what you’re most interested in.”

Lisa Tse

Internship at: Imperial College London

Found it through: Imperial website

The project: coding to try and degrade the performance of algorithms, to understand their weaknesses

Outside work: still based in London, where she studied, so she could meet up with friends

Top tip: “Try to find out beforehand who you’ll be working with and what their expertise is. No-one I was working with was familiar with the specific Python package I was using during my internship, so I couldn’t ask others for help if I had difficulties with the package. That wasn’t a problem for me, but it’s useful to know these things in advance, so you know what you’re getting yourself into.”

Jack Foster

Internship at: Crossfield Fusion, Harwell, Oxfordshire, UK

Found it through: SEPnet

The project: using two different types of software to model fusion reactions in different reactor designs

Outside work: internship was during 2020, so activities were restricted by COVID

Top tip: “Make sure that you read up on the company and any information that they provide you with, because it will really help you to hit the ground running.”

Summer internship case studies

For the lowdown on summer internships and more advice from people who took part in them, check out these longer case studies from the August 2021 issue of Physics World that we’re publishing throughout this month.

Maria Violaris “I developed general research skills, which are useful in both industry and academia”

Constantine Pelesis “I built up my network and got an understanding of how a whole company works together”

Marion Cromb “I learnt good coding practice, and the code was actually sold to customers at the end”

Claire Houghton “I got to see real scientific experiments, where no-one knows exactly what’s going to happen”

‘Bogolons’ make graphene superconducting

Graphene can be made to superconduct by placing it next to a Bose–Einstein condensate – a form of matter in which all the atoms are in the same quantum state. According to the theorists who discovered it, this new type of superconductivity stems from interactions between the electrons in graphene and quasiparticles called “bogolons” in the condensate. If demonstrated experimentally, the work could make it possible to develop new types of hybrid superconducting devices for applications in quantum sensing and quantum computing.

Conventional superconductivity occurs when phonons – quasiparticles that arise from vibrations in a material’s crystal lattice – cause electrons in the material to pair up despite their mutual electromagnetic repulsion. If the material is cooled to sufficiently low temperatures, these paired electrons (known as Cooper pairs) can travel through it without any resistance.

Bose–Einstein condensates (BECs) form when bosons, or particles with integer quantum spin, are cooled until they are all in the same quantum state. Within this special “fifth state of matter”, quasiparticles called Bogoliubov excitations can develop. Named after the Russian physicist Nikolaï Bogoliubov, who was the first to provide a theoretical description of them, these quasiparticles are usually known as bogolons. Ivan Savenko, who led the research at the Institute for Basic Science (IBS) in Korea, explains that bogolons are similar to phonons in the sense that they also serve as mediators for electron-electron attractions.

Good conductor, bad superconductor

Graphene – a honeycomb-like lattice of carbon just one atom thick – has several unique electronic properties. Many of them stem from the fact that it is a semimetal with no energy gap between its valence and conduction bands. In the region where these two bands meet (known as the Dirac point), the relationship between the energy and momentum of charge carriers (electrons and holes) in graphene is described by the Dirac equation, rather than the standard Schrödinger equation as is the case for most crystalline materials. The presence of these unusual band structures (known as Dirac cones) enables the charge carriers in graphene to behave like massless particles.

This effective masslessness makes the electrons in graphene highly mobile, meaning that the material is a very good conductor. However, it is only weakly superconducting because the density of electronic states near its Dirac point is small. This means that graphene must be cooled to extremely low temperatures before it becomes a superconductor – in line with a rule that “good” conductors (including metals like gold and copper as well as graphene) make “bad” superconductors.

Bogolon pairs

Savenko and his colleagues have now found a way to make graphene break this rule. In their calculations, they showed that if graphene is placed in the vicinity of a BEC, the interactions between single bogolons and electrons (which have half-integer quantum spin and are therefore fermions rather than bosons) are quite weak. However, the situation changes once pairs of bogolons are involved. “In this case, we can achieve robust, relatively high-temperature superconductivity,” Savenko tells Physics World, adding that the team calculated a superconducting transition temperature of 70 K.

The researchers, who report their work in 2D Materials, are now exploring whether other boson systems could also make graphene superconduct. These other systems may include polaritons and magnons, Savenko says.

Novel PET tracer sheds light on plaque formation in Alzheimer’s disease

A new PET tracer proved for the first time that it can be used to identify brain activity involved in the formation of plaque in people with cognitive impairment and Alzheimer’s disease, according to a study published in Molecular Psychiatry.

The researchers studied the uptake of carbon-11 (¹¹C)-BU99008 in diseased brain regions of patients with late-life cognitive impairment compared with healthy patients. They found direct evidence that the tracer can identify activity involved in the development of amyloid plaque, a hallmark biomarker of neurodegeneration.

The study advances efforts to understand the pathology involved in the formation of amyloid plaque in Alzheimer’s disease and other neurodegenerative conditions and could lead to earlier treatments.

“We believe that ¹¹C-BU99008 is a potential new tracer for assessment of the trajectory of in vivo astrocyte reactivity with Alzheimer’s and other late-life neurodegenerative diseases,” wrote Paul Edison of Imperial College London and colleagues.

Astrocyte reactivity is the overproliferation of glial cells called astrocytes, due to damage of nearby neurons from trauma, infection or neurodegeneration, for instance. Studies suggest reactive astrogliosis may precede early pathological signs of Alzheimer’s disease, including the formation of amyloid plaque and tau tangles.

By identifying astrocytes with PET tracers, the researchers hope to visualize their involvement in the development of the neurodegenerative disease.

Edison and colleagues have been studying ¹¹C-BU99008 since it was synthesized in 2012. In April, a separate group of Swiss researchers published the first results showing the tracer was effective in human Alzheimer’s disease tissue samples.

In this study, the group from Imperial College London tested for the first time whether the uptake of ¹¹C-BU99008 is increased in older cognitively impaired patients compared with healthy people of the same age.

Brain imaging — Statistical parametric mapping analysis of significantly increased ¹¹C-BU99008 uptake as a group for (a) all cognitively impaired (CI) subjects and (b) beta amyloid-positive CI subjects compared with healthy controls. (Courtesy: CC BY 4.0/*Mol. Psychiatry* 10.1038/s41380-021-01193-z)

Eleven patients clinically diagnosed with probable dementia or mild cognitive impairment due to Alzheimer’s disease were recruited and matched against nine healthy patients. Beta-amyloid plaque was identified in patients on PET imaging with ¹⁸F-florbetaben (Neuraceq), a tracer approved for that purpose in the US in 2014. ¹¹C-BU99008 was synthesized onsite and imaging was performed using a PET/CT scanner (Biograph TruePoint, Siemens Healthineers).

The researchers found that ¹¹C-BU99008 uptake was higher in eight beta amyloid-positive patients with cognitive impairment across the whole brain, but particularly in frontal, temporal, medial temporal and occipital lobes, compared with the control group. Global tracer uptake was 82.7 for cognitively impaired subjects and 77.7 in healthy patients.

“This proof-of-concept study provides direct evidence that ¹¹C-BU99008 can measure in vivo astrocyte reactivity in people with late-life cognitive impairment and Alzheimer’s disease. Our results confirm that increased astrocyte reactivity is found particularly in cortical regions with high beta-amyloid load,” the researchers wrote.

While this was only a pilot study, it suggests the potential for using ¹¹C-BU99008 for longitudinal studies of relationships between astrocyte reactivity and other neuropathological and clinical features in vivo and for exploring the impact of therapeutic approaches targeting astrocyte reactivity, the researchers wrote.

“Future studies now can explore how clinical expression of disease varies with astrocyte reactivity,” the team concluded.

This article was originally published on AuntMinnieEurope.com ©2021 by AuntMinnieEurope.com. Any copying, republication or redistribution of AuntMinnieEurope.com content is expressly prohibited without the prior written consent of AuntMinnieEurope.com.

Metamaterial sculpts heart-shaped darkness from light

Heart-shaped singularity — Heart of the matter: cross-section of the designed heart-shaped phase singularity sheet (left). The extended dark region in the centre image is a cross-section of the singularity sheet. The phase (right) is undefined on the singularity sheet. (Courtesy: Daniel Lim/Harvard SEAS)

Researchers in the US have shown for the first time how regions of complete darkness within a beam of light can be shaped precisely. Using specially engineered metasurfaces, Federico Capasso and colleagues at Harvard University generated curved 2D sheets where the light intensities are zero. Remarkably, the sheets resemble heart-shaped cookie cutters (see figure). Their technique has a wide array of potential applications including trapping particles and the optical imaging of structures on sub-wavelength scales.

Optical phase singularities describe regions within a beam of light with exactly zero intensity and are ubiquitous within systems of complex waves. So far, the most widely studied examples of these features are found in optical vortices with helical wavefronts, which contain stable, one-dimensional singularities along their axes of propagation. Recently, physicists have begun to envisage a more diverse family of singularities beyond simple lines – including zero-dimensional points and curved 2D sheets.

Titanium dioxide nanopillars

Owing to their stringent requirements in wave phase alignment, these more complex singularities usually occur in extremely rare scenarios. Through the use of advanced new materials, however, techniques are emerging that could artificially produce the required interference patterns. In their study, Capasso’s team generated these features by designing a metasurface comprising cylindrical titanium dioxide nanopillars on a glass substrate.

Within this structure, complex patterns of “superpixels” were made up of uniform nanopillar arrays, separated by carefully chosen sub-wavelength distances. As the metasurface interacted with a uniform incoming wavefront of light, the resulting interference patterns in the transmitted light featured singularities with highly specific shapes.

Sculpting darkness

As a proof-of-concept, Capasso and colleagues designed a metasurface to generate both optical phase and polarization singularity sheets, each curved in such a way to produce a heart-shaped cross-section. The researchers now hope that their demonstration will pave the way for advanced new techniques for sculpting optical patterns out of darkness, just as existing optical materials can sculpt patterns out of light.

Applications of the technique could include new ways to trap particles between regions of high intensity light. The same principles apply to sound waves, and the research could also lead to new acoustic metasurfaces that create silent zones within loud, complex soundscapes.

Perhaps the most important potential use of the technology lies in high-resolution imaging: while the resolution of conventional optical imaging is limited to half the wavelength of the light being used, darkness has no such diffraction limit.

As a result, as darkness interacts with structures over length scales far smaller than the wavelengths of optical light, resulting in characteristic phase or polarization singularities. For the first time, this technique could enable researchers to determine the shapes, sizes, and orientations of nanoparticles from optical images alone.

The research is described in Nature Communications.

Luminescent nanoparticles identify defects in electrical appliances

A new technique that identifies defective components in electrical appliances by determining whether they have overheated could help extend the useful life of electronic devices. The technique, developed by researchers at the Friedrich-Alexander-University (FAU) in Erlangen-Nürnberg, Germany, works by monitoring the intensity of light emitted by micron-sized “supraparticles” that are embedded in the appliances and contain heat-sensitive luminescent nanoparticles.

Electronic (or e-) waste is the world’s fastest growing domestic waste stream, notes Jakob Reichstein, a PhD student at FAU and lead author of a new paper on the technique. Repairing complex electrical devices is time consuming and can be expensive. Many devices cannot easily be recycled either, which means that valuable resources end up in landfills.

Red, green and blue-light-emitting particles

Reichstein and colleagues chose to address this problem via so-called “smart” additives. Unlike classical additives, smart additives are not designed to improve the physical properties of a material or product. Instead, Reichstein explains that they add information to it. “The microparticles we have developed allow defective components in electrical appliances to be identified more quickly and easily using light signals,” he says. By making repairs easier, Reichstein adds, the technique “could lead to a paradigm change in how we deal with e-waste”.

The team made its microparticles from three different types of nanoparticle: one that emits blue light, another green and the third red. They produced these nanoparticles separately using two different wet-chemistry processes, then combined the red and green building blocks using a droplet-evaporation technique similar to the spray-drying process used to produce milk powder. This process forces the nanoparticles together into a raspberry-like structure, and the resulting red-green light-emitting particles make up the core, or signal element, of the finished supraparticles. In the final step, the FAU team encapsulates this signal element with blue-light-emitting organic nanoparticles to create a core-satellite structure.

The three nanoparticles play different roles within the finished supraparticles. While the ratio of the light intensities of the red and green signal elements indicates the particle’s identity, the blue nanoparticles act as thermal history recorders. “If the particle has been exposed to temperature higher than a specific temperature, the blue signal decreases in intensity,” Reichstein explains. “An overheated, and therefore usually damaged, micro-component in a device can therefore be detected by the weaker blue light signals it emits.”

Simple optical readout

Because the identity and temperature sensitivity signals are determined by the structure and quantity ratio of the nanoparticles, it is possible to tailor them to specific electronic devices simply by changing the composition of the supraparticles, Reichstein says. Another advantage of the FAU team’s technique is that the information provided by the smart supraparticle can be read out using a simple optical method.

Looking forward, the researchers hope to combine different luminescent indicators into a single supraparticle to record other potentially damaging triggers, such as moisture and temperature, as well as heat. “In the longer term, we plan to fabricate customized smart additives that record all such triggers in a product and therefore allow us to monitor the functional status of an object at any time,” says team leader Karl Mandel. “The mission of our group is to turn materials into intelligent objects and bridge the analogue and digital world via communicating particles.”

The research is detailed in Advanced Materials.

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