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Reimagining patient-specific QA in proton and ion therapy facilities

A ground-breaking R&D collaboration between clinical physicists at MedAustron and their industry partner IBA Dosimetry, a German supplier of independent QA solutions and services to radiation oncology clinics, is rewriting the rulebook on patient-specific QA for proton therapy. A case study in clinical translation, the partnership is focused on practical implementation of myQA iON, IBA Dosimetry’s patient QA dose-verification software, yielding operational insights and technical innovations that will enable proton therapy clinics to increase their workflow efficiency while simultaneously enhancing patient safety and treatment outcomes.

From a commercial perspective, IBA Dosimetry is positioning myQA iON as a “game-changer” in patient QA – a software-as-a-service solution that supports the planning, delivery and management of proton therapy while ensuring interoperability with the proton treatment systems of all leading radiotherapy equipment manufacturers. As such, myQA iON gives physicists and dosimetrists the flexibility to combine Monte Carlo dose recalculation, QA based on irradiation log files, plus real-world detector measurements within a unified, automated and web-based software verification system that enables users to access their QA on-campus or remotely from any device that connects to the hospital network.

A division of labour

Over the past 18 months, MedAustron, a cancer treatment centre specializing in proton and carbon-ion therapy and related research, has emerged as one of IBA Dosimetry’s flagship customer sites supporting the clinical roll-out of myQA iON. Joint activities have spanned beta testing, customer training as well as acceptance and commissioning, while subsequent physics and clinical validation by the MedAustron team enabled efficient implementation of myQA iON into the patient QA workflow. “Having the chance to collaborate with a company like IBA Dosimetry provides us with a long-term QA solution, including service and maintenance,” explains Loïc Grevillot, beam delivery and Monte Carlo simulation group leader at MedAustron.

That division of labour on QA is also driven by operational necessity, given that the MedAustron clinic is still work-in-progress. The facility currently has two clinical treatment rooms with fixed proton beam lines plus one treatment room set aside for clinical and preclinical research studies. A fourth treatment room with a proton gantry will come online next year, extending patient treatment hours across the site to full capacity. As such, measurement-based patient-specific QA (with set-up and beam time) is in direct competition for beam-time needed to support the commissioning effort at MedAustron. Beyond the commissioning phase, of course, patient-specific QA will need to be streamlined further in order to maximize the beam-time allocated for patient treatment. “That’s why MedAustron wanted to be a pioneer in Monte Carlo-based independent dose calculation,” Grevillot adds. “We’re now using myQA iON second-check calculations for a preselected subset of plans embedded in an extensive machine-based QA programme.”

So how did the MedAustron team set about integrating myQA iON into routine clinical practice? According to Grevillot’s colleague Ralf Dreindl, the first step is to identify the relevant commissioning tasks – covering beam-model aspects, CT calibration and clinical testing. “Our strategy involved moving from simple geometries in water and air phantoms to complex clinical cases in patient geometry in order to get the precise overall picture,” he explains. Other considerations include the clinical simulation settings – in terms of the trade-off between dosimetric accuracy and simulation times – as well as benchmarking the implemented gamma index for 3D dose verification. “Our clinical workflow foresees post-processing tasks that start immediately after the clinical approval of a treatment plan,” explains Dreindl. “One of these tasks is the independent dose calculation of the approved plan or beam set.”

Operationally, however, the rework of established clinical routines is always a delicate and nuanced undertaking. The MedAustron team therefore defined a two-month transition period for clinical implementation, with plan complexity being the main driver of dosimetric approval via myQA iON’s independent Monte Carlo dose calculations or the usual patient-specific QA measurements. “Since the transition period ended,” Dreindl adds, “we are now using myQA iON for all normofractionated proton treatments in the horizontal beam lines.”

Benefits realization

In-house analysis indicates significant – and immediate – efficiency gains since the MedAustron team implemented myQA iON clinically on the centre’s two horizontal proton beam lines. During the first two months of operation (starting in February 2021), Dreindl and colleagues noted an average 24% reduction in patient-specific QA measurements for single-field optimized proton beams (in which the spot positions and weights of each proton field are optimized individually, yielding uniform dose distribution over the tumour target). Multiple-field optimized beams (with highly conformal dose distributions to the target volume) are also now part of the mix for independent dose check, yielding up to a 50% reduction in patient-specific QA measurements since the beginning of April. For the near term, says Dreindl, hypofractionated treatment schedules will always be measured manually in addition to the independent dose check provided by myQA iON.

myQA iON
Game-changer: myQA iON combines Monte Carlo dose recalculation (shown here for a prostate case), QA based on irradiation log files, plus real-world detector measurements within a unified, automated and web-based software verification system. (Courtesy: MedAustron)

More broadly, the reduction in patient-specific QA measurements is strongly dependent on the “patient mix”. For the moment, MedAustron can only simulate horizontal proton beam lines, but there are plans to start with the vertical proton beam line in spring 2022 after commissioning is complete on the new treatment room with proton gantry. Other joint lines of enquiry with IBA Dosimetry include the implementation of irradiation log-based QA at MedAustron – to provide fraction-by-fraction monitoring and evaluation of treatment delivery accuracy – as well as the integration of the GATE-RTion/IDEAL Monte Carlo dose calculation engine (developed by MedAustron) into myQA iON to support the clinical implementation of independent dose check for carbon-ion therapy. “We cannot fully replace the patient-specific QA measurements with independent dose check,” notes Dreindl, “though the integration of log-file-based QA may be an interesting route to further reduce QA measurements beyond the current 50% threshold.”

Better together

Just 18 months after they started working together, the collaboration between MedAustron and IBA Dosimetry is going from strength to strength. “As a clinical user, it’s essential for us to have a comprehensive tool like myQA iON which has undergone a certification process,” notes Markus Stock, head of the medical physics division at MedAustron. “Working as part of a collaboration, we always have a hot-line to the team at IBA Dosimetry for assistance on installation, commissioning and the testing of new functionality.”

One thing is certain: as cancer care providers seek continuous improvements in treatment efficacy, next-generation particle therapy systems will be pushed to the limits – of physics and engineering – when it comes to targeting accuracy, dose distribution accuracy and the sparing of healthy tissue. All of which translates into evolving and increasingly complex demands on patient, machine and workflow QA. “That’s why it’s essential for industry and clinical users to work hand-in-hand to deliver user-friendly, patient-centric QA technologies that support clinical decision-making and workflow efficiency,” concludes Stock.

First results from UK tokamak offers a STEP towards commercial fusion

The prospect of commercially viable, fusion-power plants based on the spherical tokamak has moved closer after a major experiment in the UK released its first results. Using a novel kind of exhaust, researchers at the Mega Amp Spherical Tokamak (MAST-U) at the Culham Centre for Fusion Energy in Oxfordshire were able to cut the waste heat load on the reactor walls ten-fold. If the results can be extrapolated to working fusion reactors, then exhaust material and other components would not need to be regularly changed – making such reactors more cost effective by allowing them to operational for longer.

Operated by the United Kingdom Atomic Energy Authority (UKAEA), the CCFE is already home to the Joint European Torus (JET) tokamak, which was built in 1983. MAST, however, is different to JET in that it features a spherical, cored-apple like plasma. JET, in contrast, has a doughnut-shaped device, as does the giant ITER experiment, which is currently being built in Cadarache, France.

This result shows so much promise for compact designs

Ian Chapman

Built in 1999, MAST has been used to confine highly pressurized plasmas with a lower magnetic field than those used in JET, which could help to build a more cost-effective fusion device. The plasma in MAST is created by letting in a small puff of deuterium gas, which is then heated by driving a current through it. This flow of charged particles around the tokamak’s wall starts off the plasma and gives it its initial heat. Magnetic fields then confine the hot plasma of deuterium and keep it away from the walls of the tokamak.

Following over a decade of research, in 2013 MAST underwent a major £55m overhaul – dubbed MAST-U – that involved the device being completely stripped and rebuilt.  The upgrade, funded by the Engineering and Physical Sciences Research Council, involved new power supplies, upgraded heating systems and diagnostic tools to help scientists not only study plasma conditions relevant to ITER, but also plan what kind of facility will be needed next to deliver the goal of providing fusion power to the grid.

Turning a corner

One of the biggest aspects of the upgrade involved installing a new kind of heat exhaust system known as a divertor.  The fact that spherical tokamaks are more efficient than their doughnut-shaped counterparts, with more power for a smaller volume, has its downsides. In particular, the waste heat from the plasma is more intense and it is through the divertor that this power must be funnelled.

In a spherical tokamak reactor, the exhaust carries a fifth of the energy of the fusion reaction. A standard divertor of the kind used at JET and ITER, which is like a bowl at the bottom of the reactor vessel, would not be good enough for a spherical tokamak scaled up to fusion-like conditions. Also, the heat load – running at tens of megawatts per square metre – would simply be too much to withstand and quickly degrade the material.

Researchers at Culham therefore built a new kind of divertor called “Super-X”. Tiled with graphite, Super-X is shaped like a funnel, with the idea being that the plasma load is spread over a larger area as it exits the tokamak. Simulations have shown that the Super-X divertor could decrease the heat flux and plasma temperature in the divertor  — taking a 50 MW/m2 heat load and reducing it to just 5 MW/m2.

MAST-U was completed in late 2019 and a year later achieved its first plasma of deuterium. Since then engineers and scientists have been conducting tests and have now confirmed what their simulations had shown – that the Super-X divertor can reduce the exhaust heat load ten-fold.

“This result shows so much promise for compact designs,” says Ian Chapman, UKAEA chief executive. “This means that materials in fusion plants will last a lot longer before needing to be replaced, which is crucial for a commercial reactor.” According to Andrew Kirk, MAST-U lead scientist, the result indicates that the divertor wall would only need to be replaced once during a power plant’s lifetime.

Research on MAST is informing the conceptual design of the UK’s prototype fusion power plant – Spherical Tokamak for Energy Production (STEP). Work on the £220m design is set to be complete by 2024 with the aim to build STEP by 2040. Chapman confirms that STEP will feature a Super-X divertor configuration and engineers will now spend the coming months on MAST-U studying how to minimize the heat around the divertor while trying to maximise the fusion performance of the plasma.

Infrared cloaking device could make objects invisible to thermal cameras

Cloaked Homer Simpson
D’oh: simulation of infrared radiation from a heat source being blocked by an object shaped like the head of Homer Simpson (left). The image on the right shows how the proposed cloaking device would make it appear as if the head were not there. (Courtesy: Fernando Guevara Vasquez)

A thermal cloaking technique that can hide warm objects from infrared cameras has been proposed by researchers in France, the US, and the UK. Fernando Guevara Vasquez at the University of Utah and colleagues have calculated that thermal cloaking can be achieved by surrounding objects with rings of tiny heat pumps that absorb and re-emit heat. Although further work is needed to demonstrate the technique in the lab, it could lead to better ways of protecting electrical circuits from heat damage.

Invisibility cloaking of objects has received much attention in recent years. It usually involves using advanced metamaterials to smoothly guide electromagnetic radiation around an opaque object so that the object does not appear to disturb the radiation – thereby rendering the object invisible to an observer.

Now, Guevara Vasquez and colleagues have considered an alternative approach for thermal cloaking that involves actively manipulating infrared radiation in the vicinity of the object to be cloaked. This involves absorbing infrared light using heat sinks and emitting it using thermal sources.

Tiny heat pumps

To do this, the researchers propose using tiny heat pumps based on the Peltier effect to create the sinks and sources. This effect involves passing electrical currents across metal-metal junctions, which can either emit or absorb heat depending on the configuration. In their simulations, they arranged cloaking elements in a ring surrounding the object to be cloaked, with heat sinks and sources paired together.

The sinks absorb the heat produced by an infrared source that illuminates the object from behind from an observer’s perspective. Using mathematical equations of heat flow, the team can calculate how this absorbed infrared radiation would appear on the opposite side of the ring, if the object was not in the way. This calculated radiation is re-emitted by the heat sources on the part of the ring facing the observer, which is a thermal camera.

In their simulations, this technique could make a uniform flow of heat to appear completely unaffected by objects with complex geometrical shapes – including a profile of the head of cartoon character Homer Simpson (see figure). The team also used the tuneability of Peltier elements to go beyond thermal cloaking. Using their mathematical model, they were able to make one object look like a completely different object to the thermal camera.

One drawback of the proposed cloaking system is that the temperature of the illuminating source must be known ahead of time, so further research is needed before a practical device can be built. Peltier elements are already widely available commercially, so the technology required is well within reach.

If thermal cloaking is realized, it could enable engineers to hide the heat-emitting parts of circuits such as power supplies, preventing them from interfering with heat-sensitive components such as thermal cameras. The technique could also be used in industrial processes to control the temperatures of materials.

The research is described in the Proceedings of the Royal Society A.

Combining physics and biology: lasers and machine learning for personalized medicine

Nabiha Saklayen is a physicist who has been fascinated with space and stars ever since childhood. “I was obsessed,” she says, adding that this feeling never went away as she got older. Saklayen would often immerse herself in astronomy books that her mum had bought her, dreaming of becoming an astronaut or an aerospace engineer. “They were my most prized possessions,” she recalls.

Growing up in various countries around the world, including Saudi Arabia, Germany and Sri Lanka, Saklayen excelled in science and in many other subjects, such as writing and music. However, she always felt drawn towards her quest to understand the universe, with her interest in physics being piqued while attending a science-focused international high school in Sri Lanka. It was simply the most challenging, appealing and rewarding subject for her. “It pushed me to think outside the box.”

Keen to continue with physics, Saklayen considered studying in the UK. However, she decided it was important to have a broader learning experience than was possible there. “I was committed to physics but I really wanted the option to explore other subjects,” she recalls. Saklayen decided to move to the US, attending Emory University in Atlanta, Georgia, where the interdisciplinary curriculum allowed her to take classes in linguistics, sociology and journalism, in addition to physics.

She graduated with highest distinction, in 2012, majoring in physics with a minor in mathematics. Saklayen points out that another advantage of Emory was the range of research opportunities for undergraduate students. “I started doing research on soft condensed matter, the summer of my freshman year of college in Eric Weeks’ lab, and later published my first paper. This helped me get into a top graduate school.”

Saklayen continued her studies at Harvard University in Cambridge, Massachusetts, and earned her PhD in physics, focusing on biophotonics, in 2017. “I merged physics and biology together. My specific training was in laser physics and I worked with mammalian cells, such as stem cells and blood cells,” she says, adding that she specifically chose biophysics because “it was the closest to real-world applications”.

During her PhD, Saklayen invented new and cheaper laser-based nanopatterned surfaces to engineer cells with precision. “These laser-based methods allow you to create transient pores in cells and deliver cargoes or genetic materials into cells while keeping them healthy and alive,” she explains. Saklayen’s research was carried out in collaboration with many eminent scientists at Harvard Medical School, including the stem cell biologist Derrick Rossi who founded Moderna, haematologist-oncologist David Scadden, and geneticist George Church. “They all were very excited about this laser-based technology and encouraged me to pursue entrepreneurship – and that’s what happened,” she explains. “It was not something I considered for myself.”

Building a multidisciplinary team

After her PhD, in 2017, Saklayen launched a start-up company with physicists Marinna Madrid and Matthias Wagner, initially setting out to treat blood diseases with the technology. She had met Madrid previously when working in the same research group. “We had a fantastic working relationship for many years, so it made sense,” says Saklayen, adding “if she wasn’t my teammate, I don’t know if I would have come this far or if I would have even started the company.”

Later the same year, they met their third co-founder and chief technology officer, Wagner, a serial entrepreneur in the optics field who had previously built and run three start-up companies. Wagner developed the platform technology for commercialization. “Actually, our first version of the platform was built in what I like to call Matthias’ garage,” says Saklayen.

Over the next year, Saklayen narrowed down the potential applications for their platform by researching what the life sciences industry needed. To the team’s surprise, it was more important to be able to remove low-quality cells in a cell culture with the laser than to deliver cargoes into the cell. So this is what they did. “I had not expected this because it’s much easier to remove unwanted cells,” says Saklayen. “That was a pivotal moment.”

For Saklayen, the key thing is that business decisions evolve over time and cannot be based simply on the interests or intellectual curiosity you might have had as a research scientist or a PhD student. “It’s about what is useful for the industry and what customers are willing to pay for,” she says. Soon after, the team met its first seed investors in the form of The Engine, a venture firm spun out of MIT that operates as an accelerator and provides co-working space to its companies. This led them to start working full time on Cellino Biotech in 2018.

We became a unified team across physics and biology, which was very special – not many companies have this type of team that is very balanced across disciplines

Nabiha Saklayen

With the business premises sorted, in Cambridge, Massachusetts, the team immediately hired biologists. “When we first brought our biologists onto the team, we became a unified team across physics and biology, which was very special – there’s not that many companies that have this type of team that is very balanced across different disciplines,” says Saklayen. Cellino Biotech grew again in 2019, when Wagner came up with the idea to form a machine learning team and automate some of the complex processes that are normally done manually by scientists.

“We now use machine learning to train image-based algorithms to decipher which cells are high versus low quality and then we use a laser system to remove any unwanted cells with precision based on those algorithmic decisions,” Saklayen explains. “There are no humans involved in any part of this process.”

The 14 team members working at Cellino Biotech now include four physicists, two biologists and two machine-learning engineers, and the start-up has 12 patents pending. Despite “speaking different scientific languages”, Saklayen stresses how important it has been to work with her multidisciplinary team at Cellino Biotech and make sure everyone communicates well. “It is one of our biggest strengths,” she says. Although she no longer does the science herself, she enjoys being around scientists, advising them and seeing their ideas materialized. “I feel plenty of ownership of our collective efforts,” says Saklayen.

Working hard

As Cellino Biotech’s chief executive, Saklayen’s job is varied and fast-paced: she leads the company’s vision; hires and trains employees; manages her team; organizes logistics and budgets; and fundraises. “Everything moves 100 times faster than anything we ever did in academia,” she says. “I love that energy because you can see that we’re taking massive jumps forward every year.”

However, being an entrepreneur is not easy. “I thought I worked hard on my PhD, but the start-up is even harder,” Saklayen says, noting that she has to constantly think in multiple dimensions. But she finds that being a physicist has really paid off. “It has given me a unique set of tools where I’m able to look at problems from a universal lens and come up with solutions,” she says.

During her PhD, Saklayen ran the biophotonics sub-group at Harvard with five or six undergraduate, graduate and postdoctoral students – just like a start-up. “It was unusual but my PhD adviser was completely hands-off,” she says. Saklayen also recalls her previous experience running Model United Nations as an undergraduate student and managing about 100 people. “Both of these experiences built a very strong leadership foundation for me to start from, so I came into this as an experienced leader,” she says. “My mom says I was preparing for this CEO role my whole life without knowing it and there’s some truth in that.”

Having ended up in a career that she hadn’t planned for, Saklayen believes today’s physics graduates have to keep an open mind and talk to scientists in other disciplines to widen their opportunities. “As physicists we’re often very elitist in how we view other disciplines, but don’t fall into that,” she says. As a woman of colour in physics, she also has a message for minority groups in the field. “Don’t let the world get to you; you’re smart, you’re brilliant and you have to keep going,” she says. “It’s an opportunity to educate the world that physicists can look different.”

A comprehensive compendium of bioimaging and microscopy technologies

bio ebook covers
Imaging Modalities for Biological and Preclinical Research provides the first all-inclusive collection of imaging techniques used in biological and preclinical research. (Courtesy: IOP Publishing)

Imaging technologies play a vital role in the advancement of life sciences. In recent years, novel imaging techniques and tools have emerged that allow characterization of molecular mechanisms and biophysical properties of tissue with unprecedented resolution. Alongside, we’ve seen a shift towards exploiting the correlation and combination of complementary imaging modalities. Until now, however, no single publication has provided information on all of the imaging modalities available for biological and preclinical research.

A new book aims to address this shortfall, by compiling a comprehensive collection of bioimaging modalities and microscopy techniques, and explaining how to fully exploit their potential. The book – Imaging Modalities for Biological and Preclinical Research: A Compendium – brings together a series of articles covering a vast range of imaging modalities. The book is divided into two volumes: volume 1 focuses on ex vivo biological imaging and microscopy, while volume 2 examines in vivo imaging, multimodality techniques and emerging technologies.

Andreas Walter is director of Austrian BioImaging/CMI.

“Imaging is becoming an indispensable toolset for biomedical research, as it can illustrate all relevant processes of life and disease,” explains editor Andreas Walter. “An overview of available solutions to tackle research questions is essential. It is specifically important for us to bring together the fields of biological microscopy and in vivo preclinical imaging to create synergies and learn from established standards in the different communities. So far, each imaging community has worked in isolation on their advancements, but joint efforts would be beneficial to biomedical sciences.”

The idea for the book arose during a conference run by COMULIS (Correlated Multimodal Imaging in Life Sciences), a network of some 500 imaging scientists working in diverse fields. Walter, who is chair of COMULIS, worked with co-editors Julia Mannheim and Carmel Caruana to create a publication that encompasses all currently available imaging modalities. “It was really a joint effort between medical physicists, biologists and imaging scientists across various fields,” he notes, adding that most of the book’s authors were recruited from the COMULIS network.

Designed to act as a valuable reference work, the book provides overviews of each imaging modality – from fluorescence microscopy to electron microscopy, ultrasound to MRI, and many more. Every chapter guides the reader through the physical principles and biomedical applications of each modality, and includes a discussion on the technique’s strengths and limitations, as well as future developments. To highlight the importance and benefits of multimodality approaches, the editors included a dedicated section on correlative multimodality imaging and image data fusion.

The book is targeted at researchers, physicians, physicists and life scientists working in universities, industry and research labs who wish to deepen their knowledge of bioimaging and the wide range of associated applications. It is also suitable reading for students looking for insight into the complex topics of microscopy and bioimaging.

While most areas of biomedical research can now be addressed with bioimaging, many biomedical scientists are still unaware of the multitude of imaging techniques and their potential. Walter hopes that by introducing the capabilities and limits of bioimaging methods, and providing a basic understanding of contrast mechanisms and biomedical applicability, the book will help such biomedical scientists select the right imaging technique. “The knowledge about and inclusion of bioimaging might even allow them to tackle previously inaccessible research questions,” he says.

  • Individual copies of Imaging Modalities for Biological and Preclinical Research can be purchased at the IOP Publishing Bookstore.

Subradiance stores light in dense atomic clouds

Subradiance, whereby excited atoms decay more slowly than usual, has been spotted in a dense atomic cloud for the first time. Giovanni Ferioli and colleagues at the University of Paris-Saclay prepared longer-lived “subradiant” atomic states using optical tweezers and laser pulses. With further improvements their technique could have applications in optics and quantum computing.

An atom in an excited state will decay back into its ground state by spontaneously emitting a photon. In 1954, the American physicist Robert Dicke showed that this decay process can be enhanced within dense ensembles of atoms where the average atomic separation is smaller than the wavelength of the emitted photon. Through this effect of superradiance, photons emitted by the atoms constructively interfere with each other resulting in a burst of light that is shorter and more intense than would occur if the decays occurred independently,

More recently, physicists have discovered that the opposite effect called subradiance can also occur.  Here, emitted photons destructively interfere with each other, inhibiting the decay of excited states. While subradiance has been seen in dilute atomic ensembles and ordered atomic arrays, it had not been observed before in dense clouds of atoms.

In a pinch

Now, the Paris team has seen subradiance within dense, disordered clouds of cold rubidium atoms, which were confined within an optical-tweezer trap. After being excited by a laser pulse, the rubidium atoms decay rapidly at first because the laser mostly couples to superradiant states. Over time, however, subradiance emerges through a combination of two mechanisms. First, the weakly-excited subradiant states of the atoms far outlive their superradiant states, and eventually came to dominate the cloud’s overall emission. Second, a certain fraction of the superradiant states will leak into subradiant states.

Together, these factors lead to a long tail of emission that persists after the excitation has occurred. The team also observed that the lifetime of the subradiance increases as more atoms are added to the cloud.

By increasing the intensity of their laser pulse, Ferioli’s team could put the atoms into a quantum superposition of excited states. While initially decaying via superradiance, these multiple states can eventually become trapped in a “dark” state; with destructive interference preventing further decays. The researchers showed that firing a subsequent laser pulse at the atoms can cause the cloud to emerge from its dark state and release a sudden burst of light.

In the future, Ferioli and colleagues hope to gain more control over the lifetimes of their excited atoms. If achieved, this could enable researchers to prepare long-lived and highly reliable networks of entangled atoms. This could lead to applications in areas including optics, metrology and quantum computing.

The research is described in Physical Review X.

MRI reveals deterioration of brain’s reward circuitry in younger-onset dementia

MR brain images
MR images show that anhedonia, a distinct clinical feature of frontotemporal dementia, is correlated with decreased grey matter intensity in different brain regions (the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), insula and striatum) to those seen in apathy or depression. (Courtesy: S R Shaw et al Brain 10.1093/brain/awab032)

Frontotemporal dementia (FTD) is a brain disorder that most commonly affects those under the age of 60. Due to an overlap of clinical symptoms (for example, loss of enthusiasm, empathy or motivation) with other neurological disorders, as well as the gradual nature of its onset, it is not uncommon for patients with FTD to be misdiagnosed with late-life depression. Therefore, it is critical to find a distinct symptom that can be used to diagnose FTD.

Muireann Irish and her team at The University of Sydney are the first to differentiate a distinct symptom in patients with FTD: anhedonia, the inability to enjoy pleasant experiences. Their research, published in Brain, also gives insight into the neurobiological workings of anhedonia, distinguishing it from other neuropsychiatric conditions such as apathy and depression.

“We are very excited by these findings as they reveal a symptom that has not previously been documented in frontotemporal dementia, as well as the neural bases of this symptom, opening the door to potential treatments,” explains Irish.

A unique symptom of frontotemporal dementia

In a study of FTD patients, patients with Alzheimer’s disease and healthy controls, the researchers strove to characterize this multi-faceted condition through two diagnostic approaches: cognitive and neuroimaging assessments. Behavioural tests revealed a high prevalence of anhedonia in FTD syndromes as opposed to other forms of dementia. Specifically, FTD patients with anhedonia would experience a lack of interest in rewarding experiences and enjoyable hobbies, such as eating a favourite meal or spending time with friends.

Grey matter degeneration
Patterns of grey matter degeneration seen within two variants of FTD (A, B) differ from the pattern seen in Alzheimer’s disease (C). (Courtesy: S R Shaw et al Brain 10.1093/brain/awab032)

The researchers then performed voxel-based morphometry analysis of participants’ whole-brain MR images to examine voxel-by-voxel changes in grey matter signal intensities. They discovered that that the neural circuitry of anhedonia differs from that of apathy and depression. Specifically, FTD patients diagnosed with anhedonia show deterioration mostly within a frontostriatal grey matter network responsible for experiencing pleasure.

The researchers note that participants with Alzheimer’s disease, who did not show clinically significant anhedonia, exhibited different patterns of grey matter atrophy to the FTD patients.

Shedding light on anhedonia

While this work provides insight on potential treatment areas that could improve the quality of life for these patients, more research is needed to gain a comprehensive understanding of anhedonia in FTD. Future investigations would focus on the relationship between the deterioration of the brain’s reward circuit and the manifestation of anhedonia in the patient’s everyday life.

“Our findings are also important for understanding the subjective experience of the person living with dementia, for the delivery of personalized care, as well as revealing broader insights into a fundamental aspect of the human condition,” says Irish. “If we pause to consider what it might be like to lose our capacity to experience pleasure, we can appreciate the immense need for future work in this field to restore some of the simple pleasures in life to those affected by these cruel disorders.”

Superfluidity seen in a 2D Fermi gas

Physicists in Germany say they have found definitive evidence for the existence of superfluidity in an extremely cold 2D gas of fermions. Their experiment involved confining a few thousand lithium atoms inside a specially designed trap, and they say that the finding could help shed light on the role of reduced dimensionality in high-temperature superconductors.

Understanding the mechanisms that allow electrical current to flow without resistance inside cuprate materials at ambient pressure and at temperatures of up to 133 K is one of the biggest outstanding challenges in condensed-matter physics. Although scientists can explain the process behind more conventional, lower-temperature superconductivity, they are still trying to work out how the phenomenon can take place at high temperatures in what are essentially 2D materials (cuprates being made up of layers of copper oxide). Such low-dimensional materials are prone to fluctuations that prevent the long-range coherence thought to be essential for superconductivity.

2D Fermi gases can serve as model systems to try and help clear up this mystery, having strong and tuneable correlations between their constituent fermions that can mimic interactions in superconductors.  Macroscopic quantum phenomena such as Bose–Einstein condensation involve large numbers of bosons – particles with integer spin – co-existing in a single quantum state. Fermions, in contrast, have half-integer spin and are subject to the Pauli exclusion principle – which precludes multiple particles sharing quantum states. But fermions can get around this restriction by pairing up and combining their spins.

Superfluidity too relies on a macroscopic quantum state of bosons, occurring at very low temperatures and causing the fluid in question to flow without viscosity. While 3D Fermi gases have previously been shown to exhibit superfluidity, only indirect evidence had been gleaned for the phenomenon in such gases restricted to 2D. But Lennart Sobirey and colleagues at the University of Hamburg have now observed superfluidity in a 2D Fermi gas thanks in part to a special kind of trap they initially demonstrated in 2017.

Box potential

The researchers carried out their experiment using a Fermi gas of about 6000 lithium-6 atoms. As is the case with 3D demonstrations, they first used a series of optical and magnetic techniques to cool the atoms down to a fraction of a degree above absolute zero and hold them in place. The difference this time was that they created what is known as a box potential, by loading the gas into an optical lattice created by two blue lasers. This tightly confined the gas to a very thin layer, with the energy needed to move atoms in the vertical direction exceeding the thermal energy and chemical potential of the gas.

To establish whether their gas was a superfluid, the team turned to the Landau criterion. This stipulates that excitations can only occur within a superfluid when there is movement above a certain minimum velocity. In other words, there will be no friction between the superfluid and any impurity that moves through it more slowly than this.

The impurity created by the researchers came in the form of a moving lattice of light. They directed two red laser beams at the centre of their trap, so creating an interference pattern with a sinusoidal potential. By offsetting the frequency of the two beams very slightly, they were able to move the lattice through the gas with a certain speed.

Temperature changes

They did this for a range of different velocities and in each case measured the system’s change in temperature – a measure of how many excitations were created. They found that as they increased the velocity the movement remained frictionless, until they reached a certain critical value. At this point the movement started to generate heat.

The researchers carried out this procedure both when the fermions interacted strongly to create a Bose–Einstein condensate and when they formed more weakly bound Cooper pairs. Although the precise response in the two states was different, in both cases they observed a critical velocity below which movement was frictionless. This, they say, “constitutes conclusive evidence of superfluidity”.

What’s more, the researchers found that this superfluidity was temperature dependent. By preparing the gas at different temperatures and in each case moving the lattice through the gas at a variety of speeds, they observed the critical velocity came into play at low temperatures but not at higher ones. In other words, the gas went through a phase transition from a superfluid to a normal fluid at a certain critical temperature. They determined that temperature to be 35 nK, which, they say, agrees very well with theoretical predictions.

John Thomas of North Carolina State University in the US, who was not involved with the research, points out that the experiments show a clear peak in the critical speed at the crossover from a Bose–Einstein condensate to a Fermi gas – where the gas is most strongly correlated. This, he says, “already provides new insights into the nature of superfluidity in 2D systems”. He adds that the work paves the way for studying the effects of dimensionality, which, he points out, can be smoothly tuned from 2D to 3D by reducing the strength of the confining potential.

The research is described in Science.

The story of science fiction and society

Rachel Carson’s Silent Spring – the famous 1962 book on the devastating impact of pesticides like DDT – is credited with revitalizing the environmental movement. It also helped to accelerate the transition of science journalism from its former stance as largely uncritical cheerleader to something more like a “watchdog” of the fourth estate, as well as paving the way for the founding of the US Environmental Protection Agency. Interestingly, Carson’s book did not begin with history or scientific fact, but instead with a form of science fiction, in which ecosystem disruption caused by unregulated pesticide use has killed off all life in Anytown, USA.

With its use of fiction next to fact and its demonstrable impact on society, Silent Spring was an excellent case study and just one of the examples analysed in Science Fiction, an elegantly written new book by media and cultural studies researcher Sherryl Vint. At the heart of this captivating book is the long and complicated relationship between science and sci-fi, in which fiction serves to reflect and reflect upon science, the production of which has in turn been influenced by science fiction. The work is the latest in the MIT Press “Essential Knowledge” series, which, as the publisher puts it, offers “accessible, concise, beautifully produced pocket-size books” delivering “expert overviews” on topics ranging from neuroplasticity and quantum entanglement to fMRI and nihilism.

Largely eschewing a potentially lengthy discourse on both the origins and history of science fiction, as well as the fool’s game of trying to define its boundaries, Vint instead concentrates on the core of the so-called genre: “a vision of the world made otherwise and what possibilities might flow from such otherness”. Science Fiction begins by briefly exploring sci-fi’s early grounding in utopian writings – and its more recent shift towards the dystopian tradition. The first half of the book also covers sci-fi’s popular associations with futurology and speculative design, as well as a relationship to colonialism that has long been baked into the texture of the genre.

The second half of the work, meanwhile, focuses on science fiction as a medium through which the reader can contemplate our relationship with both existing and potential scientific and technological advances in robotics and genomics, as well as with forces that are shaping our society, like climate change and the increasing dominance of finance in the economy.

Throughout, Vint is engaging and critical, and demonstrates a formidable command of the science fiction canon, from which she draws examples to show the breadth of topics onto which the genre can provide a lens. My primary regret, however, is that the book is not longer – and does not embrace wider themes. At the outset (and even on the back cover blurb), Vint makes it quite clear that her goal is to explore the engagement between science fiction and current research in science and technology, a place where visions of future technological changes might be imagined and interrogated. Such a frame likely aligns well with the interests of the Physics World readership.

Nevertheless, as Vint does note, “social as well as technological change is at stake in SF”. As a reader who has some background in the liberal arts and also in science, I feel that Science Fiction lacks important chapters for what is supposed to be an introductory text. I was anticipating, for example, some discussion of science fiction’s intersection with gender, race, sexuality and class. This is not to say that these topics are not touched upon – Afrofuturism, for example, gets a few mentions, with reference to the iconic works of individuals like Octavia Butler, Sun Ra and Janelle Monáe. However, these examinations are fleeting for a cultural-studies text that acknowledges that, as well as exploring plausible scientific extrapolation, science fiction equally serves “as a literature of social change, often using futuristic technologies to establish that its stories take place in different worlds, but remaining more interested in social than scientific change”.

I’m not against pull quotes in principle, but the value they add should exceed their capacity to disrupt the flow of one’s reading

My other criticism concerns a peculiar design choice that I suspect might be endemic to the “Essential Knowledge” series: the off-putting decision to punctuate every 10-or-so pages with full-page, inverted-colour pull quotes. I’m not against pull quotes in principle, but the value they add should exceed their capacity to disrupt the flow of one’s reading (which their scale does here in a way that, say, a picture would not have). I can’t help but feel their utility lies in attracting the interest of prospective buyers leafing through the work in a bookstore – but to the detriment of the ultimate readership.

These issues aside, Science Fiction nevertheless left me very open to more – both of Vint’s insights into science-fiction studies and also to some of the other, less familiar, offerings in the “Essential Knowledge” series. Overall, this is well worth a read.

  • 2021 MIT Press $15.95pb 224pp

3D printing technique keeps brittle tungsten crack-free

Tungsten has many excellent properties. It resists corrosion, and its melting point of 3422 °C is the highest of all metals, making it an ideal material for components that operate at extreme temperatures. There is a problem, though: it is highly brittle at room temperature, which means it is hard to process using conventional techniques.

Researchers at the Karlsruhe Institute of Technology (KIT) in Germany have now addressed this problem by adapting an additive manufacturing technique called electron beam melting (EBM) for use in tungsten processing. The resulting crack-free metal could be used in high-temperature components such as rocket nozzles, heating elements for furnaces, or parts for fusion reactors and medical imaging systems.

Additive manufacture

The KIT researchers, led by Steffen Antusch from the Institute for Applied Materials – Materials Science and Engineering (IAM-WK), have studied several ways of using additive manufacturing (also known as 3D printing) to make tungsten components that require little to no post-production processing. In their latest work, they used EBM to reduce strain in tungsten during processing and thus produce a soft material with no cracks that is easier to handle.

The EBM technique uses electrons accelerated in a vacuum to melt metal powder. By moving the electron beam, it is possible to produce a 3D component from the metal in an additive way – that is, layer-by-layer. The technique was originally developed for titanium alloys and materials requiring high processing temperatures.

Pre-heating reduces deformation and inherent stress

To create 3D-printed parts from tungsten instead, Antusch and colleagues used the electron beam in the EBM machine to pre-heat the tungsten metal powder before melting it. The researchers explain that this pre-heating procedure reduces deformation and inherent stress in the metal, making it possible to process materials that break easily at room temperature but can be deformed when hot.

Compared to other techniques, such as laser printing, the new approach is much better at producing crack-free tungsten, Antusch tells Physics World. And unlike powder injection moulding — another widely-employed advanced manufacturing technology for fabricating complex, high volume net-shape components – Antusch notes that with the new method “you don’t need expensive tools and are free to design the printed parts”.

The IAM-WK researchers are involved in work for the Helmholtz Association and the European Fusion Programme (EUROfusion), with the long-term goal of developing materials and processes for high-temperature applications in fusion energy and medical engineering (such as making parts for CT scanners). They now plan to characterize and test the mechanical properties of their printed tungsten materials for use in such applications.

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