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Dose measurement system could improve phototherapy for jaundiced newborns

Neonatal jaundice is a common condition in newborn babies, caused by the build-up of bilirubin in the blood. While the majority of babies will recover naturally, if extremely high blood bilirubin levels are left untreated, there’s a small risk that the bilirubin could pass into the brain and cause brain damage. Such cases are usually treated using phototherapy, in which blue light shone onto the skin reduces the bilirubin values to safer levels.

Phototherapy is delivered using overhead lamps or blanket-style illumination devices. Previous studies, however, revealed that many such phototherapy devices fail to deliver the recommended irradiance levels. Now, researchers at University Hospital Coventry have developed the first system that can measure the integrated dose rate of light delivered to a neonate body shape. They describe their approach in Medical Engineering & Physics.

Detection array

Phototherapy devices are typically evaluated by measuring peak irradiance levels at various locations over a neonate’s body surface. But this approach cannot estimate the total rate of energy delivery within a specific spectral range over the entire exposed body surface.

“The integrated dose rate is the parameter that gives the best indication if phototherapy is likely to be appropriate,” explains first author Douglas Clarkson. “A single local intensity value can be misleading if the ‘light field’ size is small relative to the size of the neonate.”

To determine the integrated dose rate delivered by a phototherapy device within a selected wavelength interval, Clarkson and colleagues used an array of 192 blue-wavelength-enhanced silicon photodiodes to measure the dose contributions over the surface of a neonate body shape.

As the physical model for their experiments, the researchers used a body shape based on the  SimNewB simulator device, which has a shape that closely corresponds to a term neonate of average weight and height. They divided the surface into 12 anatomical regions and attached 16 calibrated photodiodes to each region. They then used this setup to estimate the dose contributions by anatomical region, in the spectral range 460–490 nm, for three neonatal phototherapy devices: Natus neoBlue; GE Medical BiliSoft blanket; and GE Medical Giraffe Spot.

As expected, the BiliSoft blanket delivered the majority of output to the rear torso, although the team noted a significant difference between dose to the right and left sides. The Giraffe Spot unit delivered light centred on the naval, with relatively little dose to the arms, legs and head. The Natus neoBlue delivered a more extensive light field, with the arms, legs and upper torso all receiving useful dose contributions.

The measurements revealed significant differences in delivered levels of phototherapy, which would likely also lead to differences in the relative clinical effectiveness of each phototherapy system.

Clinical impact

The reduction in serum bilirubin during treatment is a key parameter indicating the effectiveness of neonatal phototherapy. The test system’s ability to measure the dose rate within specific spectral bands enables the creation of a model relating the rate of energy delivery to the neonate to the rate of bilirubin decrease during treatment.

“Newborns get into a bilirubin imbalance due to breakdown of haemoglobin. It is important that the phototherapy dose rate is sufficiently high to counteract this factor and act to decrease it to safe levels,” says Clarkson, noting that the important clinical focus for this work was provided by consultant neonatologist Prakash Satodia at University Hospital Coventry.

The team also suggest that the technology could help develop a revised medical device equipment standard that allows determination of output power delivery within designated wavelength intervals for a specific neonate baby shape.

The researchers conclude that their system provides the “missing link” in determining the relative effectiveness of neonatal phototherapy lamps and optimizing clinical phototherapy. To provide a more practical measurement device, particularly for premature infant body shapes that would be challenging to cover in photodiodes, they are developing a modified design based on wrap-round thin-film photovoltaic technology.

Clarkson is also creating an interactive software tool to optimize phototherapy based on dose rates delivered within specific wavelength intervals. “It is hoped that this type of software, while having a research focus at this stage, will filter into clinical use as the best way to manage neonatal phototherapy,” he tells Physics World.

Ghost surface polaritons seen for the first time

Hyperbolic polariton illustration
Quasiparticles in motion: illustration of ghost polaritons in a calcite crystal being “launched” to record distances by a gold microdisk. (Courtesy: HUST)

The existence of ghost hyperbolic surface polaritons has been demonstrated by an international collaboration including researchers in China and the US. Based at Huazhong University of Science and Technology (HUST), National University of Singapore (NUS), National Center for Nanoscience and Technology (NCNST) and the City University of New York (CUNY), the team showed that the polariton – a hybrid light-matter quasiparticle – has a record-breaking propagation distance of three times its photon wavelength. This ghost polariton is an exciting discovery that has applications in sub-wavelength, low-loss imaging, sensing and information transfer. The full study is described in Nature.

Previously, hyperbolic polaritons, which arise from the strong coupling of electromagnetic radiation to lattice vibrations (phonons) in anisotropic crystals, had only been observed in two forms: bulk polaritons and surface polaritons. Bulk, volume-confined, hyperbolic polaritons (v-HPs) have a real out-of-plane wavevector and hence can propagate within the material supporting them. Surface-confined hyperbolic polaritons (s-HPs), however, have an entirely imaginary out-of-plane wavevector, and so decay exponentially away from the crystal surface, a property called evanescence. The hyperbolic dispersion of these polaritons is the result of the crystal’s dielectric anisotropy, which results in hyperbolic isofrequency contours in k-space (momentum space) and concave wavefronts in real space.

Most studies on v-HPs and s-HPs have been performed in thin layers of van der Waals crystals. These crystals comprise stacks of covalently bound 2D layers that are held together by weak van der Waals forces. However, in such crystal layers there is no control over the optical axis. This is the direction in which propagating light experiences no birefringence and it is typically aligned with the layers.

Friendly ghosts

Weiliang Ma and colleagues have exploited the fact that the optical axis in calcite (calcium carbonate), a bulk anisotropic crystal, can exist at an angle to the surface and can be selected at will by mechanical cutting. If the axis is indeed slanted, the optical properties of calcite in the mid-infrared region give rise to ghost hyperbolic phonon polaritons (g-HPs) that are highly anisotropic and highly collimated. These g-HPs propagate along the crystal surface and – similar to s-HPs – decay exponentially away from the surface. However, unlike conventional s-HPs, they are not purely evanescent inside the material and their wavefronts are oblique – which means they are not perpendicular to the direction of propagation.

The team was able to demonstrate the intriguing properties of g-HPs experimentally using nanoscale-resolution near-field imaging. They fabricated a gold microdisc on the surface of several calcite crystal samples and directed infrared light onto it. The disc acts as a nanoantenna, which collects the infrared illumination and “launches” two highly confined, diffraction-less polariton rays that travel up to 20 micron in different directions. In comparison, v-HP rays travel about 3 micron in van der Waals materials.

The experiment is depicted in the figure, where to the left of the infrared beam we can see the hyperbolic polariton wavefronts, and to the right we see the two highly-collimated polariton rays. The researchers showed that the angle between the two rays increases with increasing excitation frequency and increasing angle between the optical axis and the crystal surface. Additionally, the polariton confinement can be controlled by the disc diameter.

Polariton revolution

This is the first observation of ghost polaritons and the discovery offers offer multiple ways of controlling their behaviour. “Polaritonics […] has been truly revolutionizing optical sciences in the past few years. Our discovery is the latest example of the exciting science and surprising physics that can emerge from exploring polaritons in quite conventional materials like calcite, with exciting implications for nanophotonic technologies”, says Andrea Alù of the Photonics Initiative at the CUNY Advanced Science Research Center and a co-leader of the research.

Why open-source software is so powerful for physics: find out in the September 2021 issue of Physics World

Cover of Physics World September 2021 issue
Picture of success: The importance of open-source software to physics.

Twenty-three thousand. That’s roughly how many people helped create the first ever image of a black hole, taken by the Event Horizon Telescope (EHT) in 2019.

Not all are formal members of the EHT collaboration – the vast majority are those who write, maintain and support the free and open-source software tools that the researchers used in their work.

But without the imaging software all those people had written, it would never have been possible to extract the famous image from the EHT data.

It was perhaps the most high-profile example of how free and open-source software is becoming a powerful tool in academic research, helping scientists to collaborate better and work smarter.

In the September 2021 issue of Physics World, which is now out in print and digital formats, Achintya Rao investigates how such software is being used in physics research, and its role in the wider open-science movement.

If you’re a member of the Institute of Physics, you can read the whole of Physics World magazine every month via our digital apps for iOS, Android and Web browsers. Let us know what you think about the issue on Twitter, Facebook or by e-mailing us at pwld@ioppublishing.org.

For the record, here’s a run-down of what else is in the issue.

• Steven Weinberg: a legend is lost – By unifying the electromagnetic and weak forces, Steven Weinberg was vital to the formation of the Standard Model of particle physics. Michael Banks looks back at a giant of theoretical physics

• John Enderby: a passion for physics and publishing – Michael Banks joins the tributes to Sir John Enderby, the physicist and former chief scientific adviser to IOP Publishing, who died last month aged 90

• Exploring other worlds – Ling Xin talks to Su Yan from the National Astronomical  Observatories of China, Chinese Academy of Sciences, about China’s rise in lunar science

• The wonder of Weinberg – Matin Durrani recalls his brushes with Steven Weinberg,  was probably the greatest theorist of his age

• Where did all the calculus go? – Niki Bell argues that mathematics A-level could be reformed so that it does more to support physics students

• Competitive instincts – Physicists are competitive, but that doesn’t make them cutthroat, argues Robert P Crease

• Crossing the valley – In his third article on funding hi-tech firms, James McKenzie looks at recent initiatives to help them jump over the “valley of death”

• Standing on the shoulders of programmers – Free and open-source software is growing to be a powerful tool in academic research, helping scientists to collaborate better and work smarter. Achintya Rao investigates how such software is being used in physics research, and its role in the wider open-science movement

• Imaging metabolism in action – From improving the sensitivity of ion sources to boosting image resolution, Felicia Green and Anna Simmonds unveil the ambitious biological mass spectrometry programme at the Rosalind Franklin Institute to image molecular interactions in tissues

• The enduring mystery of the solar corona – Physicists have long known that the Sun’s magnetic fields make its corona much hotter than the surface of the star itself. But how – and why – those fields transport and deposit their energy is still a mystery, as Philip G Judge explains

• Keeping nuclear secrets – Margaret Harris reviews Restricted Data: the History of  Nuclear Secrecy in the United States by Alex Wellerstein

• Flights of fancy, feet on the ground – Philip Moriarty reviews Fear of a Black Universe: an Outsider’s Guide to the Future of Physics by Stephon Alexander

• Physics for biological breakthroughs – The European Molecular Biology Laboratory is a highly multidisciplinary place, employing people from across all scientific fields. Laura Hiscott speaks to Wolfgang Huber, a physicist at the lab who uses his mathematical skills to contribute to the life sciences

• Ask me Anything – Careers advice from Joanne O’Meara, professor of physics at the University of Guelph, Ontario, Canada

•A demon of a puzzle – In 1871 James Clerk Maxwell proposed a puzzle now known as “Maxwell’s Demon” in his book Theory of Heat. We celebrate its 150th anniversary in this thermodynamics-themed cryptic crossword compiled by Ian Randall

Wave–particle duality quantified for the first time

One of the most counterintuitive concepts in physics – the idea that quantum objects are complementary, behaving like waves in some situations and like particles in others – just got a new and more quantitative foundation. In a twist on the classic double-slit experiment, scientists at Korea’s Institute for Basic Sciences (IBS) used precisely controlled photon sources to measure a photon’s degree of wave-ness and particle-ness. Their results, published in Science Advances, show that the properties of the photon’s source influence its wave and particle character – a discovery that complicates and challenges the common understanding of complementarity.

The double-slit experiment is the archetypal example of complementarity at work. When a single photon encounters a barrier with two thin openings, it produces an interference pattern on a screen placed behind the openings – but only if the photon’s path is not observed. This interference pattern identifies the photon as a wave since a particle would create only one point of light on the screen. However, if detectors are placed at the openings to determine which slit the photon went through, the interference pattern disappears, and the photon behaves like a particle. The principle of complementarity states that both experimental outcomes are needed to fully understand the photon’s quantum nature.

Signal and idler

The new study adds to this principle by showing that the properties of the slits also matter. In their experiment, the IBS researchers shone so-called “seed beams” of laser light onto two crystals of lithium niobate. Each crystal produces two photons when illuminated: a “signal” photon and an “idler” photon. The researchers sent the signal photon into an interferometer to create interference patterns and quantify the photon’s wave nature, while observing the path of the idler photon to pinpoint its particle character. Because the signal and idler photons are produced together, they form a single quantum state described by both the wave and the particle property measurements.

Diagram of the optical system used in experiments that quantified wave-particle duality
Waves and particles The experimental set-up. (Courtesy: Institute for Basic Science)

By changing the intensity of the seed beams in each crystal, the researchers independently altered the crystals’ chances of emitting photons – a process akin to controlling a photon’s “attraction” to each slit in the classic experiment. When one of the crystals was very likely to emit photons, the pattern the interferometer produced was barely visible, implying that the photon was mostly particle-like. When the crystals’ emission probabilities were equal, the interference pattern was sharp, highlighting the photon’s wave character. “The wave nature of the photon could be extracted as a visibility of the interference pattern,” explains Tai Hyun Yoon, a physicist at IBS and a co-author of the study.

Corroborating theoretical results

In their experiments, Yoon and co-author Minhaeng Cho focused on regimes where the photon was acting partly as a wave and partly as a particle. Previous theoretical studies indicated that the amount of wave-ness and particle-ness in such a system should satisfy a simple equation involving source purity – that is, the likelihood that a particular crystal source will be the one that emits light. The new study is the first complementarity experiment to account for and precisely control this source purity, and it corroborates a prediction made by Xiaofeng Qian and colleagues that source purity µs, interference pattern visibility V and path distinguishability P are related through the expression P2 + V2 = μs2.

“Having this experimental capability makes it possible to confirm the theoretical structures that we were discussing, to test how the source is controlling a single quantum particle’s wave–particle duality,” says Qian, a physicist at Stevens Institute of Technology in New Jersey, US who was not involved in the present study. “This was a great achievement, that they could produce a single photon state where all the parameters were at their control,” agrees Girish Agrawal, a physicist at Texas A&M University, US and Qian’s collaborator on this earlier theoretical work.

The new study also showed that controlling and quantitatively measuring the photon’s wave and particle character can be recast as measuring the entanglement between idler photons and the detectors that identified their path. In this way, researchers connected complementarity to a property of photons that is commonly exploited in practical quantum devices. “This extra controllability [in our set-up] could be an interesting and useful way to quantum engineer states that might be of interest in quantum information,” says Cho.

Besides its possible applied value, the researchers say that their study challenges physicists’ traditional thinking about complementarity. “In the context of pure theory and fundamental experiments, this experiment does add something new,” agrees Peter Milonni, a physicist at the University of Rochester, US who was not an author of the present paper. Qian adds that the experiment quantitatively proves that instead of a photon behaving as a particle or a wave only, the characteristics of the source that produces it – like the slits in the classic experiment – influence how much of each character it has. “This experimental test and the theoretical quantitative analysis really deliver the message that a quantum particle can behave simultaneously, but partially, as both,” he concludes.

Tracking China’s rapid rise in lunar exploration

As chief designer of the data acquisition systems for China’s lunar and Mars missions, what are you currently working on?

I oversee developing and running ground-based antennas and receivers for China’s lunar and Mars missions. We have built three 40–50 m-level steerable radio tele­scopes in Beijing and Kunming to obtain data from the lunar missions and last year we completed a 70 m telescope in Tianjin for the Mars mission. I am also overseeing data processing related to various ­microwave-band scientific payloads. This includes the lunar penetrating radar on the Chang’e-3 mission and the low-frequency radio spectrometer on Chang’e-4. That will also apply for the upcoming lunar regolith penetrating radar on Chang’e-5. In addition, I oversee radar data from the orbiter and rover of the current Mars mission Tianwen-1.

Planetary science is thriving in China and the number of planetary scientists has increased exponentially over the past decade

Su Yan

How does that work differ for the lunar and Mars missions?

Mars is much more distant than the Moon so the technologies involved are quite different. For instance, we can use a 50 m telescope to receive data from the Moon, but it won’t work for Mars since the signals are extremely weak. That is why we built the new telescope in Tianjin and integrated the four telescopes so they now function as a 103 m-aperture telescope. This way, we can meet the massive data needs from a total of 13 scientific instruments onboard the orbiter and rover of Tianwen-1.

How did you get involved in lunar exploration?

I was very lucky. My background is in electrical engineering and as a graduate student I joined the pre-research team of the Five-hundred-meter Aperture Spherical radio Telescope (FAST) under the supervision of Nan Rendong. I spent a lot of time at the Miyun ground station in suburban Beijing developing receivers for pulsar signals. I also had the opportunity to spend a year at the Jodrell Bank Observatory in the UK, where I developed feeds and the “orthomode” transducer for a radio telescope array called MERLIN.

How important were those early days on FAST?

FAST was then in the design phase and the budget to construct it seemed astronomical. However, Nan never stopped advocating for the project even when he was diagnosed with cancer. I admire his devotion to FAST. He used to say “No matter what we accomplish, it’s going to be trivial compared to the vast universe out there. What’s important is to enjoy the process of life.” I will always remember that.

Speaking of enjoyment, you must have had some unforgettable moments in the lunar control room

I still remember how nervous we were when the Chang’e-1 orbiter was supposed to start transferring data and there was no signal on the screen. I was nervous, but a few minutes later the data came pouring in. Another intense moment was when we learned that the Chang’e-3 lander had just touched down safely on the Moon’s surface. We were thrilled! Our team was the first to confirm the success and the landing images we received were so much better than what we had expected.

Which findings from the Chang’e missions excite you the most?

I was thrilled about the world’s first high-resolution radar image of the Moon’s far side, taken by the ground penetrating radar on the Chang’e-4 rover. For the first time, the image showed three distinct ­geological ­layers less than 40 m below the lunar surface (Science Advances 6 eaay6898). The rover has travelled nearly 700 m so far on the far side and we hope that it will continue to head west to “see” a different geo­logical landscape that is mainly made up of basalts.

What is the most challenging part of your job?

I always enjoy field work, but sometimes it is difficult. For example, to test the ground-penetrating radar on the Mars rover, we went to the Laohugou glaciers in western China because the dielectric constant of the glaciers is like the Martian regolith. The site was more than 4400 m above sea level and I suffered from severe altitude sickness. I felt weak, but we had to get the work done. During one outing, the snow was so heavy that we had to carry all the instruments up the glaciers ourselves. It was very challenging physically and mentally for the whole team.

I sincerely hope more young people who are passionate about space exploration will join us

Su Yan

What are you working on next?

We need to complete the data processing for the Chang’e-4 radar and the instruments on Tianwen-1 to see if there are interesting findings. I am also involved in the development of radar devices on future missions such as China’s asteroid probe.

Planetary science is thriving in China and the number of planetary scientists has increased exponentially over the past decade. I sincerely hope more young people who are passionate about space exploration will join us.

Smart inflatable hand offers lighter, more affordable prosthetic

So many of the actions that we perform every day rely on the precise movements of our hands. For people who have had an upper-limb amputation, prosthetics could give back some amount of this function that most take for granted. However, these prosthetics are often heavy, rigid and expensive. Researchers from Massachusetts Institute of Technology (MIT) and Shanghai Jiao Tong University aim to restore function with their high-tech, inflatable neuroprosthetic hand, which they describe in Nature Biomedical Engineering.

More than a feeling

Neuroprosthetics are smart bionic limbs that not only look like the missing body part, but also use the person’s own remaining nerve signals to control movement in the prosthetic. This gives the user back some of the functional movements of their hand. But we don’t only use our hands as grabbing devices – hands also provide tactile feedback on whatever we are touching. To best replicate the human hand, an ideal neuroprosthetic would combine both of these features in a light and flexible package.

The research team explored a new direction when designing their prosthetic. They replaced rigid metal elements with soft and stretchy elastomer controlled by precise inflation of the balloon-like fingers, using a simple pneumatic system instead of electrical motors. Using computer modelling of the required pressures, the pneumatic pumps can achieve five different common grips. Sensors detecting electrical signals from the user’s limb control these pumps to deliver whichever movement the user wishes to perform.

And the user can do more than just control the position of the prosthetic fingers. Thanks to pressure sensors in the fingertips, an electrical signal sent back up the limb provides feedback about what each finger is touching. These electrical impulses enable the user to “feel” the pressure on the artificial fingers and to know, for instance, which finger on the hand is being touched.

Getting hands-on

When the researchers tested this new smart prosthetic hand with volunteers, it worked at least as well as traditional neuroprosthetics in typical tests of hand function. The users were able to handle food, objects and tools, and use them naturally, whilst also being able to interact with people, animals and their environment. Even delicate tasks, such as precisely inserting complex shapes into corresponding slots, were possible.

Going further than typical neuroprosthetics, the researchers also demonstrated that the tactile feedback worked in a blindfolded test, where the user could feel whether an object was in their grasp and lift it if they felt they were holding onto it. This step-change in prosthetic capabilities is made possible by the addition of the pressure sensors.

Importantly, the lightweight design doesn’t sacrifice durability. Despite weighing less than one third of a kilogram and being made of an elastomer, the prosthetic resisted being hit with a hammer or run over with a car,  recovering to remain functional.

Whilst further work is needed to make this new prosthetic a viable option for patients who have undergone amputation, the researchers are optimistic about its potential. “This is not a product yet, but the performance is already similar or superior to existing neuroprosthetics, which we’re excited about,” says co-senior author Xuanhe Zhao. “There’s huge potential to make this soft prosthetic very low cost, for low-income families who have suffered from amputation.”

Were high-energy neutrinos from a supernova detected 34 years ago?

Data collected more than thirty years ago contain what could be evidence of high-energy neutrinos generated by a supernova. That is the claim of Yuichi Oyama, a physicist at the KEK research institute in Japan, who worked on one of two experiments that he says appear to have intercepted such particles from the SN1987A event but which did not release the relevant data at the time. The find could help explain the origin of the most energetic cosmic rays, but other experts reckon the evidence does not stack up.

Supernovae are enormous explosions occurring when heavy stars run out of nuclear fuel and implode, in the process creating shock waves that eject the star’s exterior. SN1987A was the closest supernova to be seen for well over 300 years, taking place about 170,000 light–years from Earth in the Large Magellanic Cloud. Its light arrived on 23 February 1987 and reached peak brightness three months later. It was also the first supernova from which physicists detected neutrinos, with 25 of the elusive subatomic particles being registered by two underground experiments – Kamiokande-II in Japan and IMB in the US.

Those neutrinos were all detected within the space of just 13 s, confirming existing models of supernovae and earning the then Kamiokande-II spokesperson, Masatoshi Koshiba, a share of the 2002 physics Nobel prize. However, the neutrinos all had relatively low energies – a few tens of millions of electronvolts. Theory predicts that such supernovae should also give off neutrinos with billions of electronvolts within about a year of the explosion. This is the result of the decay of pions produced when protons accelerated by the remnant star collide with the ejected material.

Formidable task

Observation of these high-energy neutrinos would confirm that at least some of the extremely energetic cosmic-ray protons reaching Earth are accelerated within supernovae. But identifying such particles is a formidable task. To detect neutrinos, scientists fill huge tanks with water or other liquids and measure the Cherenkov light given off when muons created by the interaction of neutrinos with nuclei in surrounding rock pass through the liquid. But to do so researchers must screen-out detections of muons produced by cosmic ray protons in the atmosphere (the cosmic rays themselves being susceptible to magnetic deflection on their journey to Earth and therefore unable to reveal their own points of origin).

The trick in the case of high-energy neutrinos from supernovae is to look only for those neutrinos reaching detectors from below, having passed through the Earth to get there. Any muon generated by cosmic ray protons in the atmosphere on the far side of the planet will penetrate a few kilometres at most into the Earth’s crust, and therefore cannot be confused with the muons of interest.

In a preprint he recently uploaded to the arXiv server, Oyama analyses the “upward-going muons” recorded by Kamiokande-II and IMB. To work out how many of these events can be tied to high-energy neutrinos from SN1987A, he whittles them down using two criteria. One, that they occurred between 11 August and 20 October 1987. And two, that they were no more than 10° away from the direction of SN1987A. Doing so, he finds four such events that fit the bill – two in each of the experiments.

As Oyama points out, these events might still be noise – specifically, neutrinos generated by cosmic rays on the far side of the Earth. But such background neutrinos are themselves rare. Indeed, he says the Kamiokande-II and IMB data show that not even one such neutrino would be expected in the spatial and temporal window he selected. Combining the individual probabilities that each of the four events is background, he calculates that the odds of their not having originated in SN1987A to be 0.27%.

“First evidence”

As such, he concludes, these events “might be the first evidence of high energy neutrinos from a supernova explosion”.

As to why he is only now publishing the analysis, Oyama says that neither the Kamiokande-II or IMB collaborations considered their respective detections to constitute statistically-significant evidence, and that they only learned of their counterparts’ data when some of the IMB members went to work in Japan in 2004. But even at that point no announcement was forthcoming, and he says he then waited until the death of Koshiba – in November last year – to make the results public.

In doing so, Oyama is sticking his neck out. He released his paper only after having tried, and failed, to persuade the remaining members of the two collaborations to issue a joint publication. Indeed, one former colleague from Kamiokande-II does not agree with how the analysis was done, arguing that it relies on an a-posteriori statistical calculation.

Blind analysis

These doubts are shared by Francis Halzen of the University of Wisconsin-Madison in the US, principal investigator of the IceCube neutrino detector in the South Pole. He points out that Oyama has not employed a “blind analysis”, in which the time period and angular window would be chosen before the data are known.

Indeed, Halzen contrasts the latest research unfavourably with work from his own collaboration, which in 2018 reported that it had identified a specific giant elliptical galaxy as being the source of one high-energy neutrino detected by IceCube. That study, he says, involved a blind analysis, yielded much higher-probability evidence and was corroborated by observations at various electromagnetic wavelengths.

Oyama acknowledges that he did not carry out a blind analysis but points out it was impossible to do so on data more than 30 years old. He says that in any case he tried to guard against making the choice of spatial and temporal windows “too intentional”, adding that very slightly smaller windows would have boosted the statistical significance considerably. The important thing, he maintains, is to release the data and let others decide for themselves on their significance.

I spy: a virtual reality system in the MRI

Virtual reality in an MRI scanner
Virtual reality timeline: As patients are introduced to the MRI scanner, the environment synchronizes with their movements. Following an initial calibration, patients can select the content they’d like to experience during virtual reality immersion. (Courtesy: CC BY 4.0/Sci. Rep. 10.1038/s41598-021-95634-y)

The bore of a magnetic resonance imaging (MRI) machine can be intimidating. The claustrophobic atmosphere, paired with knocking sounds that are sometimes louder than an aircraft flyover, can frighten even those comfortable with medical procedures. Children are especially susceptible to these fears, and as a result, MR scanning failure rates can be as high as 50% in young children.

MR technicians employ many simple methods to distract patients during imaging, including audiovisual systems, which they can also use to stimulate brain activity for functional MRI scanning. However, these techniques fail to remove the sensation of entering the MRI bore or assuage the jarring sensations that arise during its function. A research team centred at King’s College London envisioned a technology that would immerse patients in a game environment, distracting them and even replacing the sensations of being inside an MRI machine. The team, led by MRI specialists Kun Qian, Tomoki Arichi and Jo Hajnal, published the study findings in Scientific Reports.

The group investigated a virtual reality (VR) system that replaces the visual scene seen by a patient with immersive and tailored content, in an attempt to alleviate claustrophobia and allow more effective scanning of vulnerable groups like children. The system consists of a 3D-printed headset, a projector and multiple MRI-compatible cameras used to record the patient’s eye movements. The cameras allow the subject to control a VR environment using gaze tracking.

VR system utilizing gaze tracking
Follow the eyes: By identifying the patient’s eye corners, the VR system can utilize gaze tracking information to trigger interactions in the virtual world. (Courtesy: CC BY 4.0/Sci. Rep. 10.1038/s41598-021-95634-y)

The gaze tracking system acts as the crux of the VR system, as it allows immersive control of the environment without bodily movement. First, the cameras obtain images of the patient’s eyes and surrounding areas. A computer then identifies the coordinates of the eye corners and pupils on these images and feeds this information into a progressive interaction interface. The patient then calibrates the system by gazing at dots on the screen. Their gaze coordinates at these times are fed into a regression model, which is constantly updated, improving robustness as they interact with the scene.

Participants reported more attention diversion when playing the video game than they did while watching a film, and no subjects required selection support from carers while exploring the system.

The researchers note that maintaining congruence with external physical stimuli was especially important to the subject’s immersion experience. Therefore, in addition to standard audio-visual stimuli from the VR system, the system integrated external stimuli into its storyline and function. For example, the system integrates the loud knocking and vibration of the MRI scanner by introducing construction characters into the scene, whose tools would be likely to cause said disturbances. If the subject gazes at these characters, they apologize for causing the disruption.

Further, to fully immerse the user in the virtual environment from the start, the system synchronizes the environment with the movement of the patient table sliding into the bore. In this way, subjects of the study noted that they were left without the impression of even having entered the scanner bore.

This technology demonstrates the potential to act as an immersive, engaging escape for patients requiring MRI scans. The researchers call for more in-depth testing of the VR system, especially for integration of full MRI exams and systematic studies with children.

Blood test detects brain tumours at an early stage

Detecting a brain tumour at the earliest possible stage enables faster treatment and safer surgery, which are essential to improve the patient’s chance of a good clinical outcome. But brain tumour diagnosis is a difficult task, as common symptoms such as headaches or memory change are not specific to cancer. As such, many tumours remain undetected until they are larger or of a higher grade. A research team in the UK has now demonstrated that spectroscopic liquid biopsy can detect both small and low-grade gliomas – and could increase the likelihood of early diagnosis.

Liquid biopsies are a minimally invasive diagnostic tool in which small samples of blood are analysed. For cancer diagnostics, most liquid biopsies detect genetic material such as circulating DNA. But early-stage tumours can have extremely low levels of cancerous genetic material in the blood, and for brain tumours, the blood–brain barrier creates further limitations.

The researchers are developing an alternative approach. Instead of detecting specific genetic material, they analyse the molecular composition of a blood sample using attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy combined with machine learning algorithms.

“The spectroscopy is used as a broad assessment of the entire composition of the blood sample, which contains over 20,000 molecules,” explains first author Ashton Theakstone from the University of Strathclyde.

Serum sample studies

In their latest study, described in Cancers, Theakstone and colleagues examined 177 blood serum samples from patients with varying sizes of brain tumours, including 90 patients with high- and low-grade gliomas, as well as 87 asymptomatic controls. They measured the tumour volumes using MR imaging and divided the patients were into two groups depending on their MRI parameters (T1-weighted with contrast enhancement, or T2-weighted/FLAIR).

The researchers performed the liquid biopsies by depositing 3 µl of each patient’s serum onto an optical sample slide and collecting nine spectra per patient, which typically took 15 minutes. They collected spectra in the wavenumber range 4000–450 cm-1, with spectral analysis focused on the fingerprint region (1800–1000 cm−1).

The team first used principal component analysis (PCA) to examine spectra from the T1 group, all of whom had grade IV glioblastoma tumours, and from control patients. PCA provides clear visualization of any variation between these datasets and identifies important wavenumber regions within the spectral data. The analysis revealed a distinction between tumours and controls, which the researchers used to determine the wavenumber bands responsible for this separation.

“Any variances within particular wavenumber regions correspond to certain functional groups that are known within the literature,” Theakstone explains. “For example, the region between roughly 1700 to 1500 cm-1 corresponds to the amide I and amide II of proteins, therefore variances within this region relate to fluctuations in protein content within the blood.”

Cancer classification

Next, the team examined the ability of three classification models (random forest, partial least squares-discriminant analysis (PLS-DA) and support vector machine) to differentiate these high-grade tumours from controls. For each model, the data were split into a training set, used to identify biosignatures, and a test set.

The PLS-DA model had the greatest predictive ability, with a sensitivity of 98.5%, specificity of 95.1% and balanced accuracy of 96.8%. The team repeated this process with the T2/FLAIR group, which included mostly low-grade (grade II) tumours and some grade III tumours. Again, PLS-DA performed the best in differentiating tumours from controls, with a sensitivity of 88.7%, specificity of 94.7% and balanced accuracy of 91.7%.

To minimize sensitivity and specificity errors whilst also minimizing analysis time, the researchers repeated each classification 51 times. They note that the first iteration for each classification model gave correct predictions for all patients within the T1 cohort and the majority of the T2/FLAIR group.

Significantly, the model correctly identified a patient with a tumour size of just 0.2 cm3 as a cancer patient for each iteration and for all nine of their recorded spectra. “Therefore, we can confidently state that this model will identify tumours as small as 0.2 cm3 with 100% success rate in this particular example,” says Theakstone.

The researchers conclude that their spectroscopic liquid biopsy shows great promise as a potential diagnostic tool for early diagnosis of brain tumours. Importantly, and unlike other liquid biopsies, this approach appears insensitive to tumour volume. They note that the test could be used to fast track patients who need medical imaging, and are continuing this research to deliver an early-stage triage tool for brain cancer detection.

Furthermore, Glasgow-based Dxcover, a spin-out from the University of Strathclyde, is commercializing an early detection platform based on the spectroscopic liquid biopsy technique.

“This breakthrough is a watershed moment in the development of early cancer detection,” says Matthew Baker, Dxcover’s chief technical officer and co-founder, in a press statement. “The study demonstrates the effectiveness of our Dxcover Brain Cancer Liquid Biopsy at detecting even the smallest brain tumours, which is great news for the care of future brain cancer patients, increasing treatment options and potentially extending life expectancy.”

An inventory of cosmological mysteries

The Eridanus supervoid
(Courtesy: NASA/JPL-Caltech and Planck US Data Center at IPAC/ESO/Piquito veloz)

Over thousands of years, humans have never tired of pondering the universe and our place in it. But as our knowledge has advanced, the specific questions we ask have changed. What’s Eating the Universe and Other Cosmic Questions by physicist and writer Paul Davies is a whistle-stop tour of the biggest mysteries that cosmologists are investigating today.

Each of the 30 chapters is devoted to a different question. The chapters are only about two to five pages long each, but they are not there to provide answers, nor even to deeply explore any theories. The author briefly explains where each question arose from, and some of the suggested solutions, occasionally opining on whether he thinks any are convincing.

This structure makes for a nice overview of the state of cosmology. After all, science is driven by questions, so summarising the questions that scientists are currently asking is a good way of describing the state of the field. Some chapters look at problems I had already heard of, such as the mysterious fine-tuning of fundamental constants that allows life to exist. Others were new to me – the eponymous chapter details an unexpected void-like cold spot that astronomers have found in the constellation of Eridanus. Speculations follow that our universe might be spontaneously engulfed by a collision with another, or by the quantum vacuum decaying to a lower energy level. If you can bear to contemplate such scary prospects, this book is a fun way of making sure you’re all caught up on where cosmology is at today.

  • 2021 Allen Lane £16.99hb 192pp
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