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Quality assurance of the Elekta Unity MR-Linac: a clinical experience

Want to learn more on this subject?

Join our webinar with Marcel Nachbar of the University Hospital of Tübingen, one of the first clinical sites to successfully implement the Elekta Unity high-field MR-Linac.

During the webinar, Marcel will talk about the technical and dosimetric challenges of the Elekta Unity system, provide an overview of dedicated PTW equipment and its effective use in clinical routine, and share his experience of establishing a comprehensive quality assurance programme.

Key topics covered in this webinar include:

Clinical applications and technical overview of the Elekta Unity high-field MR-Linac.
Clinical workflow and current limitations of the Elekta Unity system.
Quality assurance in MR-guided radiotherapy:
– Quality assurance of the MR imaging system for anatomical and functional imaging.
– Quality assurance of the medical linear accelerator using PTW equipment, including beam data collection; output check; profile check; isocenter check; and patient plan verification.
– Independent end-to-end testing.

Don’t miss this opportunity to learn more about safe and effective quality assurance in MR-guided radiotherapy.

Want to learn more on this subject?

Watch now

Marcel Nachbar, MSc, is a medical physics expert (MPE). He currently works at the Department of Radiation Oncology, University of Tübingen, Germany, and has QA responsibility for the Elekta Unity system. His professional focus is on MR-guided adaptive radiotherapy.

Gear-changing could allow colliders to smash particles with different velocities

Researchers in the US and Sweden have shown that it is possible to operate a particle collider like a set of gears, allowing particles to circulate at different velocities. This could be a boon for nuclear physicists, allowing them to smash together different types of ions at different energies without having to alter the size of their colliders.

A particle collider like the Large Hadron Collider (LHC) at CERN comprises two rings that circulate two beams of particles in opposite directions before colliding the particles in a detector (or detectors). Particles in the rings are circulated in bunches, so great care must be taken to ensure that the bunches collide at the interaction point within a detector.

Unlike the high-energy (and therefore highly relativistic) particles accelerated at the LHC, the lower-energy protons and ions used in nuclear physics experiments experience significant changes in velocity as a function of their kinetic energy. A particle dropping from 250 GeV to 25 GeV, for example, means a drop in velocity of about 0.07%.

This creates a problem when it comes to colliding particles moving at different velocities. Whether the collisions involve just protons and ions, or whether they also feature electrons (as will be the case with the Electron Ion Collider, to be built at the Brookhaven National Laboratory in the US), the two bunches must meet up at a detector’s interaction point.

Technically demanding and expensive

One way of achieving this is simply to change the circumference of the rings around which the two beams circulate continuously. This change needs to be in line with that of the velocity – so that a 0.07% change equates to an adjustment of about 2.1 m for a 3 km circumference ring. But mechanically moving an arc of that length would be technically demanding and expensive.

Hence the idea of “changing gears”, which would allow particles in the two rings to circulate at different speeds while still meeting up at the interaction point. This is achieved by having different numbers of bunches in each ring. In a very simple case, three bunches in one ring would each travel at 4/3 the velocity of four bunches in the other.

To show that such a scheme could in principle be made to work, Edith Nissen of the Thomas Jefferson National Accelerator Facility in Virginia, US, got together with Anders Källberg and Ansgar Simonsson at Stockholm University to work on a room-sized device in Stockholm known as the Double ElectroStatic Ion Ring ExpEriment (DESIREE). This consists of two miniature storage rings arranged so that one set of ions with an energy of no more than 25 keV can be merged with another at up to 100 keV while moving in the same direction.

Unequal numbers of bunches

Nissen and colleagues aimed to show that they could circulate unequal numbers of bunches in the two rings such that the ions from the different rings always merged in the same portion of the device. They did this using nitrogen ions with about twice the energy of carbon ions, measuring the very slight delay of the faster moving nitrogen at the start of the 1 m long merger region and a correspondingly slender lead at the end (which implies that the bunches in each case aligned exactly in the middle).

The researchers carried out their experiment in two configurations – four bunches versus three and five bunches versus four. By reducing the energy of the nitrogen ions to compensate for the smaller ratio in the second case, they showed that they could indeed mesh both sets of gears. They found that the timing differences at the two ends of the merger region corresponded with theoretical expectations given the velocity ratio in each case – showing that they could keep these timings constant over the course of thousands of cycles around the rings.

Nissen points out that the pattern of collisions in a gear-changing scheme is more complex than normal. Rather than each bunch in one beam interacting with just one specific bunch in the other – as would be the case if both beams had the same velocity – it interacts with many bunches, if not all.

Distorted bunches

That characteristic could be advantageous, argues Nissen, in that one poorly formed bunch would not significantly alter the quality of data in experiments where spin polarization, for example, is important. However, she says it could also create problems because colliding bunches will distort one another. If a bunch in one beam always meets the same bunch in the other, then those bunches will settle down to an equilibrium state. But if instead different bunches are colliding on each turn, then the beams could smear out, degrading the data.

Electron accelerator recycles energy

In fact, in 2013 Yue Hao and two other physicists at Brookhaven and Stony Brook University published a theoretical study showing how such distortions could seriously reduce the rate of collisions. Calculating the impact of several different effects – including instabilities in beam position and width – they concluded that gear-changing schemes “should be avoided”.

Nissen acknowledges that DESIREE does not generate intense enough beams to study these distortions, but nevertheless reckons it could help counteract this problem in other machines by allowing scientists to refine the physics of gear changing. “This experiment was the first step in understanding gear changing in real-world colliders,” she says.

A preprint describing the latest research has been uploaded to arXiv.

Reflecting the community: Physics World’s new contributing columnists expand our team of opinion writers

Here at Physics World, we’re always striving to cover the full breadth of physics – from astrophysics and cosmology to particle physics and everything in-between. We also do our best to report on the subject wherever it’s going on in the world as you’ll have seen from our recent coverage of China, Japan and the US. But Physics World certainly needs to do more to ensure we’re showcasing everyone in physics – not just those who have followed conventional paths into the subject but also those who have faced barriers of gender, class or race.

To represent the full breadth and diversity of today’s physics community, Physics World is this month excited to introduce a pool of new contributing columnists. They are all active and thought-provoking physicists who will bring a new perspective to a range of professional matters such as education, careers, publishing, funding and diversity. They will join Robert P Crease (top, middle in the image above) and James McKenzie (middle, right) in our stable of regular opinion-writers for Physics World.

The first four columns by our contributing columists have appeared in the November issue of Physics World and will be published online on the Physics World website over the course of this week. These first articles focus on the challenges facing Black physicists, the importance of teachers, the need to support research in physics education and why it is important to seek out opportunities even during a pandemic.

For the record, here is the full list of the Physics World contributing columnists and make sure you keep an eye out for future columns in the magazine and online.

Yangyang Cheng (top, left) is a postdoctoral research associate at Cornell University, US, and a member of the CMS experiment at the CERN particle-physics lab. Cheng received her PhD in physics from the University of Chicago in 2015. Cheng writes the monthly Science and China column for SupChina, a New York-based digital publication covering contemporary China, and has written for the New York Times, the Guardian, Foreign Policy, MIT Technology Review, ChinaFile and Bulletin of the Atomic Scientists as well as appeared on the BBC, NPR and ABC Australia.

Caitlin Duffy (top, right) is a condensed-matter physics PhD student at the High Field Magnetic Laboratory in Nijmegen, Netherlands. When out of the lab, she happily spends her time weightlifting, running, practicing piano and chatting about all things whisky and wine.

Karel Green (middle, left) is an astrophysics PhD student at the University of Nottingham, UK. She founded and currently runs a social enterprise called POC², which works to remove the systematic biases that prevents people from marginalized backgrounds progressing in academia and also works to decolonize the current STEM curriculums.

Nicolas Labrosse (middle, middle) is a senior lecturer at the University of Glasgow, UK. He co-chairs the university’s Astronomy and Physics Education group and leads the Institute of Physics’ Higher Education Group committee.

Pruthvi Mehta (bottom, left) is a particle-physics PhD student at the University of Liverpool, UK. Her research is centred on the Tokai-to-Kamioka, Super-Kamiokande, and Hyper-Kamiokande neutrino experiments based in Japan. She is also a contributor for POC², a social enterprise which focuses on improving BAME diversity in STEM fields.

Chanda Prescod-Weinstein (bottom, middle) is an assistant professor of physics and astronomy, and core faculty in women’s and gender studies at the University of New Hampshire, US. A particle cosmologist by training, she is a dark-matter theorist and also conducts research in Black feminist science, technology and society studies. Prescod-Weinstein is one of under 100 Black American women to earn a PhD from a department of physics and is the recipient of the 2021 American Physical Society Edward A Bouchet Award. She is a monthly columnist for New Scientist and her forthcoming book The Disordered Cosmos: a Journey into Dark Matter, Spacetime, and Dreams Deferred will be released on 9 March 2021.

Jess Wade (bottom, right) is an Imperial College Research Fellow at Imperial College London, UK. She is the author of the Physics World Discovery ebook Printed Electronics. Wade is involved with several science communication and outreach initiatives and is committed to improving diversity in science, both online and offline. Since 2018 she has written hundreds of Wikipedia biographies of women and people of colour in science.

The importance of teachers to bridge the educational divide

As someone who works to improve the representation of women and people of colour in the community, I am often asked about the reasons for under-representation of certain groups in physics. This is a complex question that has been studied, discussed and written about a lot. The reasons are nuanced and various – gender discrimination is different to systemic racism, for example. But at a fundamental level, the answer is always the same: the quality of their physics teacher.

If you haven’t grown up in a family of physicists or engineers or haven’t got much “science capital”, the first time you will come across physics is via your secondary-school science teacher – an interaction that will likely dictate whether or not you continue with the subject. There is no shortage of anecdotes about the impact of an outstanding physics education. Julia Higgins, a former president of the Institute of Physics (IOP), once described her secondary-school physics teacher as “a revelation”, while astronomer and broadcaster Maggie Aderin-Pocock and Royal Society president Venki Ramakrishnan both credit their extraordinary careers to inspirational science and maths lessons.

In a year that has taught us – more than ever before – the importance of having a scientifically literate society, it is about time we started investing in and respecting our science teachers

Indeed, I have yet to meet a physics student or researcher who does not recognize the influence their teacher has had on them. I would even argue that physics teachers do more for physics – and society as a whole – than Nobel laureates. It is not easy to teach physics in an exciting and relevant way that communicates both the wonders and the technicalities of the subject. Good quality teachers are even more important if we are to entice students from under-represented backgrounds into physics.

After all, in 2008, when the IOP investigated the factors that influence Black and minority ethnic students’ likelihood to choose physics, it was found that the perceived difficulty of the subject or lack of role models were of little importance. What was significant was an enjoyment of physics, recognition of its relevance to everyday life and appreciation of career prospects. All of these “high-influence” factors come naturally from an inspiring and helpful teacher.

Addressing the shortage

Specialist teachers are therefore vital for the future of physics. Unfortunately, they are hard to come by. In 2017, for example, the Sutton Trust found that only half of those teaching physics in UK secondary schools have a relevant degree. With the demand for physics teachers far outweighing supply, their distribution across UK schools is unsurprisingly patchy. State schools and those with higher proportions of children on free school meals are the least likely to have teachers with a physics qualification. On the other hand, 91% of physics teachers in independent schools are specialists in their subject – with some 10% having PhDs.

Access to an education from a specialist science teacher is reflected in the demographics of young people who choose subjects like physics and further maths at A-level, and has been shown to be particularly important for students from groups that are historically underrepresented. In 2012 the IOP, which publishes Physics World, found that girls who attend single-sex, independent schools are considerably more likely to study physics at A-level than their counterparts at mixed state schools.

While this imbalance is partly due to reduced stereotyping in a single-sex environment, the fact is that girls at independent schools are simply more likely to be taught physics by someone who is passionately interested in the subject. Even as far back as the late-1800s, girls in independent schools were excelling in their scientific studies – they were being taught in well-equipped laboratories by overqualified teachers. Many of the teachers, however, were not permitted to formally graduate from university or become professional scientists because of society’s expectations of women.

If inequalities in physics teaching were exacerbated pre-pandemic, they are only going to accelerate following the impact of COVID-19. As independent schools spent the summer of 2020 investing in online platforms and keeping students engaged with virtual science clubs and guest speakers, 70% of children at state schools received either no lessons or only one online class per day (in any subject). As schools returned to face-to-face teaching this term, practical laboratory lessons have been adapted or cancelled altogether, which will leave a huge impact on students’ conceptual understanding and enjoyment of physics.

Science technicians, who are already overworked and underappreciated, are now being required to work around-the-clock to keep their classrooms COVID-safe. The increase in the number of teachers forced to self-isolate will be felt particularly acutely in physics classrooms, where it is likely that no-one in the school will be able to cover – placing an overwhelming demand on physics supply teachers. Science departments with big budgets, small class sizes and the flexibility to move online will weather this storm, further driving the physics education divide.

You might wonder why the UK has such a shortage of skills specialist physics teachers. Physicists are some of the most employable university graduates, and are highly sought after in areas such as research, finance, policy, engineering, medicine and gaming. Teacher salaries in the UK are well below the international average and, unlike most other countries, class sizes are increasing. In response, the UK’s Department for Education and the IOP offer physics graduates cash bonuses to train as teachers as well as juiced-up salaries. But of course, very few teachers would say they become teachers for the money. After all, in countries where teachers are respected – and where their insight and the importance of physics education are valued and where the economic impact of a science-minded population is recognized – such shortages do not exist.

In a year that has taught us – more than ever before – the importance of having a scientifically literate society, it is about time we started investing in and respecting our science teachers. It is only then that we will begin to close the divide.

Can low-dose radiotherapy treat COVID-19-related pneumonia?

In June of this year, results from the first trial in humans of low-dose radiation therapy (LD-RT) for COVID-19 pneumonia were made publicly available by researchers at Emory University. The study, now formally published in Cancer, was followed soon after by a paper in the Red Journal, which also reported on the use of LD-RT to treat patients with COVID-19 pneumonia. This study, from Iran, examined five COVID-19 patients who were hospitalized and receiving supplementary oxygen for pneumonia. All were treated with a single fraction of 0.5 Gy whole-lung irradiation. Both trials had encouraging results, with 80% response rates. Since then, other similar trials of low-dose radiotherapy have started in the USA and elsewhere.

“This research has sparked a lively debate in the field,” said ASTRO president Laura Dawson, a professor of radiation oncology at the University of Toronto. “Results from published trials show the potential of LD-RT, but not a definite benefit, as these small studies have not been randomized. Also the potential for adverse long-term effects of this approach cannot be forgotten.”

At the ASTRO 2020 Annual Meeting, Dawson introduced a panel discussion on “Low-dose radiation therapy and COVID-19-related pneumonia”. The first speaker, Mohammad Khan from Winship Cancer Institute of Emory University, shared the results of the RESCUE 1-19 trial.

“RESCUE 1-19 was based on the hypothesis that LD-RT may help eliminate storming cytokines and unchecked oedema in hospitalized COVID-19 patients,” Khan explained. “This was the first LD-RT trial in the world.”

The trial, which examined COVID-19 patients who were hospitalized and required supplemental oxygen, comprised two phases. In phase one, the team treated five patients with 1.5 Gy whole-lung LD-RT, with a pre-planned day-seven interim safety analysis. By day seven, four of these patients exhibited significant clinical improvements and overall survival was 100%. The time to clinical recovery (no longer needing oxygen or being discharged from hospital) was 1.5 days, suggesting a possible benefit of LD-RT, without significant toxicity.

Following this finding, the team obtained approval to treat five more patients, as part of a phase two trial to assess the efficacy of LD-RT. These 10 patients’ outcomes were compared against 10 other patients that were age and comorbidity matched.

At day 28, the median time to clinical recovery was three days in the LD-RT group versus 12 days in the control group. Patients treated with LD-RT also left hospital earlier (median of 12 versus 20 days) and had lower intubation rates (10% versus 40%) compared with the controls. “LD-RT seems to suggest a statistically significant improvement in time to clinical recovery, at least in this cohort,” noted Khan.

The full study, reported in medRxiv and currently under peer review, also revealed differences in several inflammatory, cardiac and hepatic biomarkers between the two patient groups. The team also observed an improvement in serial X-rays in the LD-RT group within a few days.

“LD-RT for COVID-19 appears to be safe; there may be improvements in oxygen status, delirium, radiographic and other biomarkers when compared against matched cohorts treated with best COVID-directed therapies,” Khan concluded. “However this was only a small trial, confirmatory larger trials are needed.”

Randomized study

The next speaker, Arnab Chakravarti of The Ohio State University Comprehensive Cancer Center, is leading two ongoing trials examining ultralow-dose thoracic radiation for COVID-19 patients.

The first, VENTED, is a phase II study of ultralow-dose whole-lung radiotherapy in critically ill patients with COVID-19 pneumonia. All patients in the study had been mechanically ventilated, and were treated with at least one dose of 80 cGy to whole thorax bilaterally, with the option for a second dose.

“Our hypothesis here is that low-dose thoracic radiation will decrease inflammation and improve outcomes for these intubated COVID-19 patients,” said Chakravarti. The trial’s primary objective is to evaluate the 30-day mortality rate after whole-lung LD-RT. The secondary objectives are primarily to assess the feasibility, safety and tolerability of this approach.

The second study is a multisite trial called PREVENT, which includes hospitalized COVID-19 patients who have severe respiratory compromise but are not yet intubated. The trial is currently running at several US institutions, with more sites scheduled to join shortly, including sites in other countries.

Step one of this trial compares patients randomized to receive either 35 cGy LD-RT, 100 cGy LD-RT or standard-of-care treatment. After interim dose selection, step two will compare patients treated with the preferred dose against the control group. The primary objectives are to determine which dose level is most efficacious and whether LD-RT at this dose is of clinical benefit. Secondary objectives include assessing the cost of care and patients’ quality-of-life.

“The ultimate question, to which we remain agnostic as a study team, is whether the potential benefits of LD-RT outweigh the risks,” emphasized Chakravarti. He noted that prior to launching these trials, the team had heard of institutions globally who were looking to treat patients using this LD-RT regimen off-protocol. “That drew a lot of concern from our study community and that was the rationale behind launching these two studies,” he explained.

Pros and cons

Also speaking in the panel session, Ramesh Rengan from University of Washington School of Medicine and Deborah Citrin of the National Cancer Institute examined the potential benefits and concerns of using LD-RT for COVID-19 patients.

“The question that we are wrestling with, with these studies, is whether or not LD-RT may have some value in short-term clinical management of the severe pulmonary inflammation rendered in patients due to COVID-19,” said Rengan.

This is a reasonable question to ask, he explained. In COVID-19, the viral infection triggers an inflammatory cascade – the cytokine storm – that overwhelms the lungs and can lead to respiratory failure. Currently, the only way to stop this is via corticosteroids, a systemic immunosuppressant. But as inflammatory cells are highly sensitive to radiation, and LD-RT has historically been used to effectively treat inflammatory diseases, could LD-RT could be used instead to suppress inflammation specifically within the lung?

Citrin explained how cells of different types have varying radiosensitivity, with most lung cells relatively resistant compared with immune cells. “Low-dose radiation can have not just killing effects on these immune cells but also change the way that some of the cells function,” she explained. For example, LD-RT can reduce the oxidative burst produced by macrophages that can damage lung tissue, and it can stop the growth of fibrocytes, the cells that make scar tissue and leads to lung fibrosis.

There are, however, important caveats to consider when irradiating the lungs. For starters, while LD-RT may confer an immediate benefit in terms of sterilizing inflammatory cells, if the radiation injures normal lung tissue, will this lead to inflammation weeks or months later?

“One of biggest concerns is the risk of long-term toxicity,” said Citrin. “In patients who are extremely ill, we have to balance the risk of injury or death from the virus, but we also need to consider the risk of long-term damage to heart or lung. We know that even at 1 Gy, there is a risk of cancer or cardiac damage.”

Such risks could be mitigated by treating patients at lower risk of second cancers or cardiac damage (those with shorter overall life expectancy), Citrin says. Long-term toxicity could also be reduced by finding the lowest dose that achieves a successful outcome, and determining whether to give the radiation in one low single dose or several even smaller doses.

There are also practical concerns when actively bringing COVID-19 patients into radiotherapy clinics: would this put particularly vulnerable cancer patients at increased infection risk? While early data are promising, there’s now a need for randomized trials, larger patient numbers and longer follow-up times to determine whether the immediate benefit is maintained.

“There are 15 ongoing multi-institutional prospective trials of LD-RT, some of which are randomized,” said Rengan. “These trials are important not only for providing information on the therapeutic benefit of LD-RT, but also to inform radiotherapy clinics about risk mitigation in terms of infection transmission and to help us understand how radiotherapy can best play a role as an immunosuppressive agent.”

Planets and stars could form as ‘siblings’ at the same time

**Sibling rings** ALMA image of the young planet-forming dust rings surrounding the IRS 63 protostar. (Courtesy: MPE/D Segura-Cox)

Detailed ring structures have been spotted for the first time in a young star-forming disc. This suggests that planets may form at the same time as their host stars – rather than towards the end of the star formation process. The observation was made by Dominique Segura-Cox at the Max Planck Institute for Extraterrestrial Physics and colleagues and it could offer new clues about how the solar system formed.

Concentric bright rings in the discs surrounding newly forming stars (called protostars) are widely believed to be clear evidence for ongoing planet formation. As nascent planets accrete gas and dust, many theories suggest that they carve out gaps in the disc, creating distinctive radial patterns. So far, these structures have been discovered in abundance around class II protostars, which are about one million years old. These protostars are close to becoming main sequence stars, and often feature discs that have separated into clearly defined rings.

The high contrast between the light and dark regions of these discs suggests that planet formation is already well underway in class II protostar systems. This means that planet formation probably starts earlier on when protostars are still in their class I phase. At this stage, protostars are 100,000s of years old and embedded within thick envelopes of gas and dust.

Using the Atacama Large Millimetre Array (ALMA) radio telescope in Chile, Segura-Cox’s team has found clear evidence for star formation in a disc surrounding the class I protostar IRS 63. This system is in the L1709 interstellar cloud about 470 light-years away.

Two concentric rings

Less than 500,000 years old, IRS 63 is one of the brightest known class I protostars at millimetre wavelengths. Within its disc, the researchers found two distinct concentric rings, together containing dust with a total mass of about half that of Jupiter. The radii of the rings are greater than 20 times the distance between the Earth and Sun. With such large amounts of material, these rings could coalesce into the solid cores of gas-giant planets. As a result, the planets and their star could be forming as “siblings” at the same time.

In addition, Segura-Cox and colleagues showed that the existence of these rings could solve the “radial-drift” problem. As dust particles become bigger, they experience more aerodynamic drag from the gas in the disc. As a result, dust particles are expected to lose angular momentum and fall into the protostar before they can join together to form a planet.

In contrast, the team’s observations suggest that rings with higher dust densities than the rest of the disc could create a series of maxima in gas pressure; efficiently trapping solid material to prevent inspiralling. If planets can form far out around a protostar as young as IRS 63, the team say that that radial drift is not a problem.

Since IRS 63 has a similar size and mass to the solar system, it may also offer astronomers a rare glimpse into how our own planetary neighbours first formed. For example, Jupiter’s core could have formed at about six times its current distance from the Sun, before migrating inwards.

The research is described in Nature.

Nader Engheta wins Isaac Newton medal and Prize

The optical physicist Nader Engheta has won the 2020 Isaac Newton Medal and Prize for “groundbreaking innovation and transformative contributions to electromagnetic complex materials and nanoscale optics, and for pioneering development of the fields of near-zero-index metamaterials, and material-inspired analogue computation and optical nanocircuitry”. Presented by the Institute of Physics (IOP), which publishes Physics World, the international award is given annually for “world-leading contributions to physics”.

The Isaac Newton Medal and Prize attracts an award of £1000 and is the only one of the IOP’s prizes that is open to physicists worldwide. Previous winners include Thomas Kibble, Deborah Jin and Ed Witten.

Engheta is an Iranian-American scientist based at the University of Pennsylvania. He did a BSc in electrical engineering at the University of Tehran graduating in 1978 before heading to the US and studying a MS and then PhD in electrical engineering at the California Institute of Technology. From 1983 to 1987 he remained at Caltech before moving to the University of Pennsylvania.

He has been awarded the Newton medal and prize thanks to his work on nanoscale optics and metamaterials. Engheta has pioneered several fields in optics including unifying electronic and optics with nanocircuit elements for photons and electrons and he has led the development of phenomena such as metamaterial cloaking.

Rewarding excellence

The IOP has also announced the winners of its other awards. Among them are Myriam P Sarachik who receives the President’s Medal “for her fundamental contributions to condensed-matter physics, lifetime service to the physics community and efforts to defend the human rights of scientists and the principles of diversity and inclusion in physics”. The President’s Medal is awarded to both physicists and non-physicists who have contributed to physics in general and the IOP in particular.

“Congratulations to all the winners of this year’s IOP awards, which recognize and reward excellence in individuals and teams and their contribution to physics,” says IOP president Jonathan Flint. “We’re delighted to celebrate the winners’ extraordinary achievements.”

This year’s gala dinner to honour the awardees, which usually happens this month, has been cancelled due to the COVID-19 pandemic.

The full list of 2020 award winners is available here.

Dynamic PET edges closer to clinical prime time

© AuntMinnieEurope.com — (Courtesy: AuntMinnieEurope.com)

Dynamic whole-body PET is evolving fast and showing considerable clinical promise, a leading French molecular imaging expert told the opening plenary session at the annual congress of the European Association of Nuclear Medicine (EANM 2020). The technique is benefiting from artificial intelligence (AI)-based assistance to simplify the challenging and time-consuming tasks associated with the acquisition and analysis of data.

The advent of total-body PET prompts discussion as to whether the time to perform dynamic PET in routine has come, noted Irène Buvat, a physicist at the Curie Institute and France’s national institute of health and medical research (Institut national de la santé et de la recherche médicale, INSERM). Speaking on 22 October, she explained that performing dynamic PET enables the investigation of tracer pharmacokinetics through the acquisition of dynamic images and modelling.

Also, published evidence strongly suggests that parametric images from dynamic PET facilitate image interpretation or carry significant prognostic value (for example, using Patlak analysis, the tumour contrast can be clearly much higher on the Ki image compared with the standardized uptake values [SUV] image). Dynamic PET protocols are now available on some vendors’ PET scanners, she added.

Dynamic whole-body PET involves dynamic data acquisition over an extended axial range, capturing tracer kinetic information not available with conventional static acquisition protocols. It can be performed within reasonable clinical imaging times, and enables the generation of multiple types of PET images with complementary information in a single imaging session. It can be used to produce multiparametric images of Patlak slope (influx rate) and intercept (or “distribution volume”), while also providing a conventional SUV-equivalent image for certain protocols.

Buvat said that in any discussion of the technology, two important questions must be addressed: Why is dynamic PET scanning not used much? Can total-body PET and long-axial field-of-view (FOV) PET be game changers?

Complicated protocols

The first hurdle is the complicated acquisition protocol of dynamic PET. However, using a total-body PET scanner, the protocol is highly simplified because everything can be captured in one acquisition, she commented. With rapid-time sampling at the beginning of the acquisition, doctors can obtain the data needed to estimate an image-derived input function, followed by any time sampling for a dynamic series of whole-body images without any bed motion.

Dynamic PET hurdles — The hurdles facing dynamic PET and the role of total-body (TB) or long-axial field-of-view (LAF) PET. (Courtesy: Irène Buvat, Curie Institute, INSERM)

This said, another reason dynamic imaging isn’t used is that to explore dynamic scans, and to perform subsequent kinetic analysis, arterial input function measurement is needed, Buvat continued. The gold standard approach to obtain arterial input function is to perform arterial blood sampling, but this is too invasive for routine use, and an alternative approach is to derive the arterial input function from the image by drawing a small region-of-interest in a large arterial vessel such as the descending aorta.

“Using current PET/CT or PET/MR scanners this works only if the large vessel is within the field-of-view. However, with total-body PET an image-derived input function can always be measured as large vessels are always included in the field-of-view,” she said.

Image-derived input function is still not completely satisfactory, she noted, because it cannot be easily corrected for the fraction of radioactive metabolites. However, the availability of total-body PET makes it possible to precisely investigate the impact of the volume-of-interest (VOI) used for deriving the input function. By using a fine time sampling, it even enables the definition of a dual input function to distinguish between the left ventricle and right ventricle blood supply, she added.

Complicated protocols made easy — Total-body PET will allow simplification of complicated dynamic PET protocols. (Courtesy: Irène Buvat, Curie Institute, INSERM)

Denoising data

Another limitation encountered in dynamic PET is that it generates many relatively short time frames that have to be reconstructed. In current PET/CT, a short time frame is associated with noisy sinograms, hence noisy reconstructed images and as a result, parametric images calculated from dynamic PET such as a Ki image from a Patlak analysis, are often noisier than usual SUV images.

However there are at least three approaches to avoid this high noise in parametric imaging, EANM delegates heard. The first is to reconstruct directly the kinetic parameters, instead of first reconstructing the images and then performing a voxel-wise fit to the parametric model.

A second approach is using deep learning methods for so-called denoising. Third, the use of total-body PET hugely increases sensitivity resulting in Ki images that are of excellent quality compared with SUV images. So again, total-body PET or large actual field-of-view PET can help to solve the problem of noise in dynamic PET scans.

Clinical application

Another constraint is that dynamic PET scans have to last long enough to capture the tracer kinetics. Typically the acquisitions are between 30 and 60 minutes, considerably reducing patient throughput.

One solution, however, involves developing simplified protocols. Ki images can be obtained using a simplified protocol involving only two scans of five minutes each and the use of a population-based input function.

Irène Buvat. (Courtesy: Irène Buvat, Curie Institute, INSERM)

“The availability of total-body PET could actually help us design and validate simplified protocols that could be more compatible with daily routine,” Buvat continued.

Although there is evidence that dynamic PET has added value in certain applications, more data were needed to clarify the difference it makes to patient management, she continued, pointing to how in one recent study involving over 100 patients with over 300 lesions, the authors revealed that four false positives seen on SUV images were avoided using the parametric images.

There now remains the need for more studies to determine how dynamic PET fits in the future of both clinical PET and PET-based research for lesion detection and characterisation, patient monitoring, prognostication, characterization of heterogeneity of tumours within a single patient, and for pharmaco-imaging.

The availability of total-body PET will facilitate these studies and will contribute to overcoming the hurdles of dynamic PET and to its development, she told delegates.

“This should help us determine the role dynamic PET should play in the future both for the clinics and in research. Importantly, the availability of dynamic PET might help us discover new applications that are currently not possible with conventional PET/CT and PET/MR scanners,” Buvat concluded.

This article was originally published on AuntMinnieEurope.com ©2020 by AuntMinnieEurope.com. Any copying, republication or redistribution of AuntMinnieEurope.com content is expressly prohibited without the prior written consent of AuntMinnieEurope.com.

Physicists measure energy of lowest nuclear excited state

Nuclear clocks are a tick closer to reality thanks to experiments that measured the energy of the lowest excited state of a thorium-229 nucleus to the highest precision ever. A clock based on transitions between such nuclear states would be much more accurate than existing atomic clocks and would therefore place tighter constraints on the Standard Model of particle physics.

Atomic clocks “tick” at frequencies set by the regular transitions of electrons within atoms or ions, as measured by a laser kept in resonance with these transitions. Today’s best atomic clocks are accurate to within one part in 10¹⁸, which means they would slow down by less than one second if left running for 13 billion years (the age of the universe). However, a clock that relied on nuclear transitions would be more accurate still, because the small size of an atomic nucleus relative to an atom’s electron shell means that the behaviour of the former is less affected by external electromagnetic fields.

Too low to be detected?

One promising candidate for a nuclear “clock” transition is the one between the ground state of the thorium-229 nucleus and its lowest nuclear excited state, thorium-229m. This state is sometimes called the isomer state due to its long lifetime, and it was discovered by the physicists L A Kroger and C W Reich in 1976 during an analysis of thorium’s nuclear level structure.

The energy difference between ground-state thorium-229 and excited thorium-229m is so small that Kroger and Reich were unable to observe separate spectral lines for the transition using the technology available to them at the time. Instead, they inferred the existence of thorium-229m from an anomaly in their measurements: one of the gamma-ray energies predicted by theory was missing in the measured signals.

Since then, physicists have learned that the excitation energy of thorium-229m (and thus the energy of the radiation given off when the thorium nucleus returns to its ground state) is the lowest out of all nuclear excited states, corresponding to a frequency in the upper UV rather than the gamma-ray region of the electromagnetic spectrum. According to Thorsten Schumm of Austria’s Vienna University of Technology, who initiated the new research effort, it is therefore possible to “promote” a thorium nucleus into its lowest excited state simply by shining UV light onto it with a table-top laser. Once this feat is achieved in a controlled way, a nuclear clock could then be realized by measuring the oscillation frequency of the thorium nucleus as it transitions between thorium-229 and thorium-229m.

Detecting low-energy “UV gamma rays”

The catch is that the energy of the excited state is not yet known with high enough precision to determine the exact wavelength of UV light needed to drive such a transition. Christian Enss and Andreas Fleischmann of the Kirchhoff Institute for Physics at the University of Heidelberg, Germany, have now taken an important step towards overcoming this problem. They did so by repeating Kroger and Reich’s gamma spectroscopy measurement with a new, specially-designed state-of-the-art gamma spectrometer: a magnetic micro-calorimeter cooled to a fraction of a degree above absolute zero (-273 °C).

This micro-calorimeter, known as maXs30, detects the low-energy “UV gamma rays” emitted during the transition from thorium-229m to thorium-229 by monitoring the tiny temperature increase that occurs whenever a gamma ray is absorbed in the device. The heat increase changes the magnetization of the detector and this change is then converted into an electric signal using SQUID magnetometers similar to those routinely employed in magnetic resonance tomography.

Challenging measurement

While the technique is similar to that used in some previous studies, the new measurements, reported in Physical Review Letters, have produced much more accurate values for the thorium-229m energy thanks to the resolution of the calorimeter. The researchers also went to great lengths to “clean up” their thorium-229 samples. They obtained their samples via an established technique based on the alpha decay of radioactive uranium-233. This decay process generates thorium-229 nuclei in various states, including thorium-229m, and it is accompanied by the emission of multiple gamma rays, each of which corresponds to a transition between specific nuclear levels of thorium-229. The energy of thorium-229m can then be calculated by subtracting the measured energies of appropriate gamma-ray lines.

To make such measurements possible, though, the uranium-233 sample produced by Christoph Düllmann’s team at Johannes Gutenberg University Mainz first had to be chemically treated to remove all “daughter” decay products that had built up over time. The researchers also removed unwanted radioisotopes, the decay of which can produce an unwanted background in the signal they wished to measure. They then designed a source and sample container in a special geometry that minimized any interference to the weak signals as they travelled from the sample to the calorimeter. All these precautions are necessary, the researchers explain, because only one in 10,000 decay processes produces a useful signal for determining the thorium-229m energy.

Most precise value

Ultimately, this hard work paid off: the team’s result represents the most precise value of the isomer state’s energy ever measured, at 8.10(17) eV (the numbers in brackets denote the uncertainty of the last digits). This result compares well to the best previously-measured value of 8.28(0.17) eV, and corresponds to light with a wavelength of 153.1(32) nm.

Since there are at present no continuous-wave lasers operating at such wavelengths, the researchers are instead using frequency combs – laser sources with spectra containing equidistant lines that allow for incredibly precise spectroscopic measurements – to promote thorium-229 into its excited state.

“The more precise energy value is of great importance for obtaining a direct laser excitation of the nuclear transition, which will open a new field of research and bring us closer to a nuclear clock”, says Ekkehard Peik from PTB, Germany’s National Metrology Institute, who was not involved in the work. Such a clock, first proposed in 2003, would be extremely sensitive to the value of the fine structure constant 𝛼, which measures the strength of the electromagnetic interaction – one of the four physical forces in nature. This extra sensitivity could make it possible for physicists to determine whether this constant is indeed always constant, or whether it varies under certain conditions. Variations, if discovered, might imply physics beyond the Standard Model of particle physics.

The challenges facing Black physicists

In 1987 the US Public Broadcasting Service began airing a 14-part documentary about the civil rights movement called Eyes on the Prize. I was five at the time and my mother, who is not at all tech savvy, figured out how to record the series using our VCR. In subsequent years I saw every episode and it was my earliest education in Black American history. My parents are both grassroots activists, so I didn’t walk away from Eyes thinking that all problems were solved or that racism was over. I watched daily as my parents organized to support primarily low-income people of colour, especially mothers. I got a sense of the moral arc of the universe – not one that bends because some physical law mandates it, but rather one where people put their bodies on the line, leading to change. For better or for worse, I think this is one reason I was attracted to physics as a line of thought and way of life. It is not that I didn’t want to help, but physics seemed like exactly the escape humanity needed from its own mess.

More than 30 years later, I sometimes think that one of my tasks as an adult is to soothe the inner child who is constantly mourning how naïve and wrong she was. As a university student, I learned how entangled physics classrooms were with social traditions of racism and sexism. As a postdoctoral fellow, I had to grapple with how physics and astronomy supported, and were in turn shaped by, colonialism. And there is still the larger world to contend with.

As a young adult, I never expected to live through and try to do physics during a year like 2020, which has been profoundly shaped by structural racism. I thought that police would no longer be shooting Black and Brown folks in the streets as they had done in the 1980s Los Angeles where I grew up. It never occurred to me that the shootings might get worse. That in the aftermath of 9/11 police forces would militarize and all that weaponry would be used on the civil rights protestors – Black Lives Matter protestors – on a scale that Americans had not witnessed since the late 1960s. I also did not imagine living under a president whose choices would lead to the deaths of 200,000 US residents in just a few months. I know my Black peers in the UK are experiencing a similar social and political environment, albeit with its own distinct unique contours.

When I look back, the challenges are still there for the people coming after me

At a point in my career when I need to “shut up and calculate”, my heart is being pulled in several directions all at once. I am filled with grief and terror at the thought of losing a beloved family member if the cops pull them over, perhaps with a child in the car. I also fear that my family will be mistreated in hospital during a pandemic that has disproportionately killed Black, Brown and Indigenous people. I am expected to keep calculating through these fears. I am expected, as a junior faculty member, to keep saying yes to prestigious speaking opportunities that are globally broadcast, even as I need time to rest my weary heart.

Keep your head up

When I was a 17-year-old first-year university student, I thought that being one of the first Black Americans to earn a PhD in particle theory would, of course, be hard work punctuated by a series of moments of triumph. It is instead hard work persistently disrupted by the need to fight – for the lives of my community members, myself and other Black physicists – to have access to resources. Indeed, by many metrics I have been incredibly successful: I am one of fewer than 100 Black American women to earn a PhD from a physics department and I am the first Black woman to hold a faculty position in both theoretical cosmology and particle theory.

One might think I saw barriers and rammed through them. But in reality, while I have sometimes clambered over these barriers, it took something from me physically to do so. When I look back, the challenges are still there for the people coming after me. Occasionally people interpret this to mean that I didn’t do enough, but the reality is that the system is setup to make it hard to eliminate roadblocks on the path to success. To start, even if racism in hiring goes away, we still worry about safely getting to our office without being harassed by vigilantes and racists on the street. When I look ahead, I see all the barriers I have yet to get through.

I better understand now the sacrifices that the people featured in Eyes on the Prize were making. They accepted that they might not live to see tomorrow, but they fought because they wanted to live in a better tomorrow. And they accepted that even if they did not make it to the promised land, their children might have a chance to glory in it. Part of what has sustained me on what has been a difficult journey, especially in this tragic year, is my belief that knowing the marvellous mathematics that underpins particle physics is part of the glory that awaits us in that promised land. It is my task to shape the arc of the moral universe so that it bends toward a delicious justice filled with the right to food, housing, clean water, and the right to know and love the night sky. While I struggle to focus amid global calamity, I keep my eyes on that prize.

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