This webinar will provide an overview of the High-Luminosity Large Hadron Collider (HL–LHC) upgrade project with highlights of the main challenges and technical innovations.
Presented by Oliver Brüning, the webinar will cover:
• An introduction to the HL–LHC project.
• An overview of the challenges of a high-energy, high-luminosity hadron collider.
• An outline of the performance reach in HE colliders over the next two decades.
Dr Oliver Brüning is the project leader for the HL–LHC project, an upgrade project to the LHC that is scheduled to finish its implementation by 2026. Oliver has a background in accelerator design, beam dynamics and machine operation. He started his career in accelerator physics at DESY where he worked on non-linear beam dynamics studies for HERA and was part of the initial commissioning team of the HERA accelerator. He joined CERN in 1995 and became part of the LHC design team just before the formal LHC approval by the CERN council. Up to 2012, he was working on the design and commissioning of the LHC and from 2005 until 2015 he served as head of the CERN accelerator theory group. Since 2008 he has been co-ordinating the LHeC accelerator system studies and was the deputy project leader for the HL–LHC project between 2010–2020.
Founded on 24 December 1970, the Institute for Nuclear Research of the Russian Academy of Sciences (INR RAS) is a large centre for particle physics in Moscow with wide participation in international projects. The INR RAS conducts work on cosmology, neutrino physics, astrophysics, high-energy physics, accelerator physics and technology, neutron research and nuclear medicine. It is most well-known for its unique research facilities that are spread all across Russia, and its large-scale collaborations in neutrino and high-energy physics. This includes experiments such as the Baksan Neutrino Observatory, and collaborations with a number of CERN experiments including CMS, ALICE, LHCb, NA61 and NA64.
The Institute was founded by the Decree of the Presidium of the USSR Academy of Sciences in accordance with the decision of the government. Theoretical physicist Moisey Markov had a crucial role in establishing the Institute and influenced the research that would later be undertaken. His ambition is seen in the decision to base INR RAS on three separate nuclear laboratories of the P.N. Lebedev Institute of Physics of the Academy of Sciences of the USSR. Each laboratory had a leading physicist in charge: the Atomic Nucleus Laboratory headed by Nobel laureate Ilya Frank; the Photonuclear Reactions Laboratory under the direction of Lyubov Lazareva; and a neutrino laboratory headed by Georgy Zatsepin and Alexander Chudakov. The man overseeing it all was the first director of INR RAS, Albert Tavkhelidze, a former researcher at the Joint Institute for Nuclear Research (JINR, Dubna). In 1987 he was replaced as director by Victor Matveev, then in 2014 by Leonid Kravchuk. Since 2020 the director of INR RAS is Maxim Libanov.
It (Troitsk) has the most powerful linear proton accelerator in the Euro-Asian region
From the very beginning, major efforts were focused on the construction and operation of large-scale research facilities. The hub of INR RAS was built 20 km outside of Moscow, in a town called Troitsk. In 1973 an accelerator division was created, with a long-term goal of creating a meson facility that would house a 600 MeV linear accelerator for protons and H- ions. The first beam was eventually accelerated to 20 MeV in 1988 and the facility was fully operational by 1993. Now known as the Moscow Meson Facility, it has the most powerful linear proton accelerator in the Euro-Asian region, providing fundamental and applied research in nuclear and neutron physics, condensed matter, development of technologies for the production of a wide range of radioisotopes, operation of a radiation therapy complex and many other applications.
A town called Neutrino
Over 1000 miles south from the Troitsk laboratory, an underground tunnel in the Caucasus mountains is the base of another INR RAS facility, the Baksan Neutrino Observatory (BNO). The facility was established in 1967 and the Baksan Underground Scintillation Telescope (BUST) started taking data in 1978. A town sensibly called “Neytrino” (Russian for neutrino) was constructed in parallel with the facility, and was where scientists and their families could live 1700 m above sea level next to the observatory. In 1987 BUST was one of the four neutrino detectors to first directly observe neutrinos from supernova SN1987A.
The observatory did not finish there, and the next step was the gallium-germanium neutrino telescope (GGNT), which was home to the Soviet–American Gallium Experiment (SAGE). The experiment contributed heavily towards solving the solar neutrino problem and simultaneously gave rise to a new problem known as the gallium anomaly, which is yet to be explained. SAGE is still well and truly alive, and with a recent upgrade of the GGNT completed in 2019, the team will now hunt for sterile neutrinos.
By 1990 another neutrino detector was under construction, following the original proposal of Markov and Chudakov. In collaboration with JINR, plans for an underwater neutrino telescope located at the world’s largest freshwater lake, Lake Baikal, took shape. Underwater telescopes use glass spheres that house photomultiplier tubes to detect Cherenkov light from the charged particles emerging from neutrino interactions in the lake water. The first detector developed for Lake Baikal was the NT200, which was constructed over five years from 1993–1998 and detected cosmic neutrinos for more than a decade. It has now been replaced with the Gigaton Volume Detector (Baikal-GVD), and plans were concluded in 2015 for the first phase of the telescope to be completed by 2021. Baikal-GVD has an effective volume of 1 km3 and is designed to register and study ultrahigh-energy neutrino fluxes from astrophysical sources.
Left a mark
There is no doubt that INR RAS has left its mark on high-energy physics. While the Institute’s most recognised work will be in neutrino physics, the Moscow Meson Facility has also contributed largely to other areas of the field. An experiment was created for direct measurement of the mass of the electron antineutrino via the beta decay of tritium. The “Troitsk nu-mass” experiment started in 1985 and its limit on the electron antineutrino mass was the world’s best for years. The improvement of this result became possible only in 2019 with the large-scale KATRIN experiment in Germany that was created in participation with INR RAS. In fact, the Troitsk nu-mass experiment was considered as a prototype for KATRIN.
Experimental data have been obtained on nuclear reactions with the participation of protons and neutrons of medium energies along with data on photonuclear reactions, including the study of the spin structure of a proton using an active polarised target. New effects in collisions of relativistic nuclei have been observed and a new scientific direction has been started, “nuclear photonics”. Two effects in astroparticle physics have been named after scientists from INR RAS: the “GZK cut-off”, which is high-energy cut-off in the spectrum of the ultrahigh-energy cosmic rays named after Kenneth Greisen (US), Georgy Zatsepin and Vadim Kuzmin (INR RAS); and the “Mikheyev–Smirnov–Wolfenstein effect” concerning neutrino oscillations in matter, named after Stanislav Mikheyev, Alexei Smirnov (INR RAS) and Lincoln Wolfenstein (US).
Theoretical studies at INR RAS are also widely known, including the development of perturbation theory methods, study of the ground state (vacuum) in gauge theories, methods for studying the dynamics of strong interactions of hadrons outside the framework of perturbation theory, the first ever brane-world models and the development of principles and the search for mechanisms for the formation of the baryon asymmetry of the universe.
There are plans to construct a large centre for nuclear medicine at the base of the linear accelerator centre
Scientists from INR RAS take an active part in the work of a number of large international experiments at CERN, JINR, Germany, Japan, Italy, USA, China, France, Spain and other countries. The Institute also conducts educational activities, having its own graduate school and teaching departments in nearby institutes such as the Moscow Institute for Physics and Technology.
The future of INR RAS is deeply rooted in its new large-scale infrastructures. Baikal-GVD will, along with the IceCube experiment at the South Pole, be able to register neutrinos of astrophysical origin in the hope of establishing their nature. A project has been prepared to modernise the linear proton accelerator in Troitsk using superconducting radio-frequency cavities, while there are also plans to construct a large centre for nuclear medicine at the base of the linear accelerator centre. There is a proposal to build the Baksan Large-Volume Scintillator Detector at BNO containing 10 ktons of ultra-pure liquid scintillator, which would be able to register neutrinos from the carbon–nitrogen–oxygen (CNO) fusion cycle in the Sun with a precision sufficient to discriminate between various solar models.
The past 50 years have seen consistent growth at INR RAS, and with world-leading future projects on the horizon, the Institute has no signs of slowing down.
The use of radioisotopes to treat cancer goes back to the late 19th century. Great strides have been made, and today radioisotopes are widely used by the medical community. Produced mostly in reactors and cyclotrons, radioisotopes are used both to diagnose cancers and other diseases, such as heart irregularities, as well as to deliver very small radiation doses exactly where they are needed to avoid destroying the surrounding healthy tissue.
However, many currently available isotopes do not combine the most appropriate physical and chemical properties and, in the case of certain tumours, a different type of radiation could be better suited. This is particularly true of the aggressive brain cancer glioblastoma multiforme and of pancreatic adenocarcinoma. Although external beam gamma radiation and chemotherapy can improve patient survival rates, there is a clear need for novel treatment modalities for these and other cancers.
On 12 December 2017, a new facility at CERN called MEDICIS produced its first radioisotopes for a batch of terbium (155Tb), which is part of a quadruplet of Tb isotopesconsidered promising for both diagnosis and treatment. MEDICIS is designed to produce unconventional radioisotopes with the right properties to enhance the precision of patient imaging and treatment, and already it has expanded the range of radioisotopes available for research projects.
Initiated in 2010, MEDICIS is driven by CERN’s Isotope Mass Separator Online (ISOLDE) facility. ISOLDE has been running for more than 50 years, producing 1300 different isotopes from 73 chemicals for research in many areas including fundamental nuclear research, astrophysics and life sciences. The year 2020 marks the 40th anniversary of the first biomedical imaging studies at ISOLDE with 167Tm, and a record operation performance for MEDICIS of 50% mass purification yield – a number which is very rarely met.
Although ISOLDE already produces isotopes for medical research, MEDICIS is now able to regularly produce isotopes with specific types of emission or new purity grades, such as the pure beta-emitter 169Er or 153Sm produced in nuclear reactors. These were restricted to niche treatments before MEDICIS could physically purify them during its 2019 and 2020 harvesting campaigns to grades that make them suitable for a new form of personalised medicine: targeted radioimmunotherapy.
ISOLDE directs a high-intensity proton beam from the Proton Synchrotron Booster onto specially developed thick targets, yielding a large variety of atomic fragments. During proton-beam operation, MEDICIS works by placing a second target behind ISOLDE’s: once the isotopes have been produced on the MEDICIS target, an automated conveyor belt carries them to a facility where the radioisotopes of interest are extracted via mass separation and implanted in a metallic foil. The final product is then delivered to local research facilities including the Paul Scherrer Institute, the University Hospital of Vaud, Geneva University Hospitals, or other laboratories such as the UK’s National Physical Laboratory.
Clinical setting
Once in a medical-research environment, researchers dissolve the isotope and attach it to a molecule, such as a protein or sugar, which is chosen to target the tumour precisely. This makes the isotope injectable, and the molecule can then adhere to the tumour or organ that needs imaging or treating. The first isotopes selected by the MEDICIS collaboration board were first tested in vitro, and in vivo by using mouse models of cancer, opening new territories for researchers in radiopharmaceuticals and molecular oncology.
MEDICIS is not just a world-class facility for novel radioisotopes. It also marks the entrance of CERN into the growing field of theranostics, whereby physicians verify and quantify the presence of cellular and molecular targets in a given patient with a diagnostic radioisotope, before treating the disease with the therapeutic radioisotope. Together with local leading institutes in life and medical sciences and a large network of laboratories, MEDICIS’s exciting scientific programme and technological breakthroughs have triggered a new project supported by the European Commission – PRISMAP, the European medical isotope programme – starting in 2021. Though still young, MEDICIS is a prime example of how accelerators are set to play an increasing role in the production of life-changing medical isotopes.
The second long shutdown of the LHC and its injector complex began two years ago, at the start of 2019. Since then, sweeping upgrades in the accelerator complex and key maintenance work have resulted in a rejuvenated accelerator complex with injectors fit for a decade or more of high-brightness beam production. With major detector upgrades proceeding in parallel, physicists are eyeing the final stretch of the road to Run 3 – which promises to deliver to the experiments an integrated luminosity twice that of Run 1 and Run 2 combined in less than three years of operations.
A large number of physicists, engineers and technicians have strived day-in day-out
Rende Steerenberg
The ceremonial key to the Super Proton Synchrotron (SPS) was handed over to SPS operations on 4 December, signalling the successful completion of the LHC Injectors Upgrade (LIU) programme. “The amazing accomplishment of delivering the machine keys with only a small delay is thanks to the hard work, dedication and flexibility of many,” says head of the operations group Rende Steerenberg, who emphasised the thoroughness with which special measures to ensure the safety of personnel during the COVID-19 pandemic were observed. “A large number of physicists, engineers and technicians strived day-in day-out to complete the upgrade and consolidation of the accelerator complex safely and efficiently following the spring lockdown.”
Super synchrotrons
Major changes to the SPS include the dismantling and remounting of its radio-frequency cavities, the installation of new power amplifiers, and the installation of state-of-the-art beam-control and beam-dump systems. First beam from the new Linac 4 was injected into the upgraded Proton Synchrotron Booster (PSB) on 7 December. The PSB will undergo a commissioning period before injecting beam into the Proton Synchrotron (PS) on 1 March. It will then be the turn of the PS to be commissioned, before sending beam to the SPS on 12 April.
Among many changes to the LHC, all 1232 dipole-magnet interconnections were opened and their electrical insulation consolidated, removing the limitation that prevented the LHC from reaching 7 TeV per beam during Run 2. The cryogenics team cooled the first of the LHC’s eight sectors to its 1.9 K operational temperature on 15 November, with five other sectors being cooled in parallel and the full machine set to be cold by spring. After handing over to the electrical quality-assurance team for the final electrical tests, powering tests and a long campaign of quench training will take place to enable the LHC magnets to support fields in excess of those required during Run 2, when the beam energy was 6.5 TeV. Test beams are due to circulate at the end of September 2021, just four months later than planned before the COVID-19 pandemic.
All 1232 dipole-magnet interconnections were opened
Detector work
In parallel to work on CERN’s accelerator infrastructure, experimental physicists are working hard to complete major upgrades to the detectors which anticipate the stringent requirements of triggering and reconstructing events at the upgraded LHC. The refurbishment of trigger electronics for the ATLAS detector’s liquid-argon calorimeter is progressing quickly and the construction of the muon detector’s two new “small wheels” is set to be completed by October 2021. With a complex upgrade of the CMS detector’s muon system now complete, a newly built beam pipe will soon be fitted in the cavern, followed by the refurbished pixel detector with a new inner layer; magnet upgrades and shielding consolidation will then follow. With ALICE’s time-projection chamber now reinstalled, work is underway to install the detector’s new muon forward tracker, and a new 10 GPixel inner-tracking system will be installed in the first quarter of 2021. Meanwhile, the next steps for a significant revamp to the LHCb detector are the mounting of new vertex-locator modules and the first sensitive detector parts of the new ring-imaging Cherenkov detector during the first months of 2021. Following the completion of the upgrade programmes, Run 3 of the LHC will begin in March 2022.
Accelerator infrastructure relating to earlier stages in the lives of LHC protons is already beginning to be recommissioned. Hydrogen ions from a local source have been transferred to the ELENA ring to commission the newly installed transfer lines to CERN’s antimatter experiments. A newly developed source has fed lead ions into Linac 3, which provides ions to the LHC’s physics experiments, while pre-irradiated targets have provided stable isotopes to the ISOLDE nuclear-physics facility. Many experiments at ISOLDE and the PS-SPS complex will be able to start taking data in summer 2021.
No changes have been made to the LHC schedule beyond 2022. Following the completion of Run 3, the third long shutdown will begin at the start of 2025 for the LHC, and in early 2026 for the injector chain, and will end in mid-2027. During this time the installation of the High-Luminosity LHC (HL-LHC) will be completed, adding major high-technology upgrades to CERN’s flagship machine. In concert with the programme of injector upgrades completed in LS2, these will allow the HL-LHC to deliver an order-of-magnitude greater integrated luminosity to the experiments than its predecessor.
A quantum physicist has mysteriously disappeared, leaving behind two mirrors, a strange machine, hallucinogenic drugs and a diary filled with ramblings and Feynman diagrams. His last thoughts reveal his views on the many-worlds interpretation – the controversial idea that there are as many worlds as there are possible outcomes in quantum measurements.
The Mirror Trap is an online performance where the audience has the chance to experiment with the psychology of self-identity and explore the interpretations of quantum mechanics. The public is asked to draw Feynman diagrams on a mirror, plonk themselves down in front of it and listen to the play using headphones, thereby transforming a dimly lit room into a private theatrical space.
The experience is hypnotic, eerie and introspective. Ideas at the intersection between physics and psychology are described in a beautifully written monologue. The protagonist believes that he has devised a new way to access a parallel universe and replicate Schrödinger’s thought experiment; however, he must play the role of the cat, and be observed. Under severe emotional pressure, he begs the audience to witness his desperate attempt to reach a universe where he did not make the biggest mistake of his life.
Visual and auditory illusions play tricks with the participants’ brains
While the physicist is digging deep into his psyche and preparing for a leap into the unknown, visual and auditory illusions play tricks with the participants’ brains. From Snow White to Alice Through the Looking-Glass, mirrors have been linked to mysterious portals, superstition and fairy tales. In this play, they are portals to other worlds, and also tools to reflect about life, self and perception. Many people feel subjective sensations of otherness and report dissociative identity effects when looking at themselves in a mirror. This strange-face-in-the-mirror illusion is more pronounced in dim light and is associated with Troxler’s fading and neural adaptation: when we look at an unchanging image some features disappear temporarily from our perception and our brain fills this missing information with other elements. This effect is particularly spooky when applied to one’s own face.
The performance was written, created and played by biologist and science communicator Simon Watt, with assistance from playwright Alexandra Wood. The 20-minute piece was followed by a discussion and question-and-answer session with Watt, psychologist Julia Shaw, and physicist Harry Cliff of LHCb and the University of Cambridge, who was scientific consultant for this work and guest physicist at the Bloomsbury Festival, under the auspices of which the piece was performed. Watt is now looking for other researchers and festivals interested in collaborating.
As arts and science festivals have moved online because of Covid-19 restrictions, this show found a creative way to engage the public while sitting at home. A well-thought-out merging of drama and science engagement, The Mirror Trap is an intense and intriguing experience for physicists and non-physicists alike.
“Why do you give all those secrets to the Russians?” So teases an inebriated Mary Bunemann, confidante to the leading nuclear physicists at the UK’s Atomic Energy Research Establishment, at the emotional climax of Frank Close’s new book Trinity: The Treachery and Pursuit of the Most Dangerous Spy in History. The scene is a party on New Year’s Eve in 1949, in the cloistered laboratory at Harwell, in the Berkshire countryside. With her voice audible across a room populated by his close colleagues and friends, Bunemann unwittingly confronted theoretical physicist Klaus Fuchs with the truth of his double life. As Close’s text suspensefully unfolds, the biggest brain working on Britain’s effort to build a nuclear arsenal had been faced with the very same allegation by an MI5 interrogator just 10 days earlier.
Close’s story expands dramatically in scope when Peierls and Fuchs are recruited to the Manhattan Project
Klaus Fuchs began working on nuclear weapons in 1941, when he was recruited by Rudolf Peierls – the “midwife to the atomic age”, in Close’s estimation. Both men were refugees from Nazi Germany. A few years older, and better established in Britain, Peierls would become a friend and mentor to Fuchs. A quarter of a century later, Peierls would also establish a relationship with a young Frank Close, when he arrived at Oxford’s theoretical physics department. Close has now been able to make a poignant contribution to the literature of the bomb by sharing the witness of his connection to the Peierls family, who felt Fuchs’ betrayal bitterly, and were personally affected by the suspicion engendered by his espionage.
Close’s story expands dramatically in scope when Peierls and Fuchs are recruited to the Manhattan Project. Though Peierls was among the first to glimpse the power of atomic weapons, Fuchs began to exceed him in significance to the project during this period. In one of the strongest portions of the book, Close balances physics, politics and the intrigue of shady meetings with Fuchs’ handlers at a time when he passed to the Soviet Union a complete set of instructions for building the first stage of a uranium bomb, a full description of the plutonium bomb used in the Trinity test in the New Mexico desert, and detailed notes on Enrico Fermi’s lectures on the hydrogen bomb.
Intensely claustrophobic
The story becomes intensely claustrophobic when Fuchs returns to England to head the theoretical physics department at Harwell. Here, Close evokes the contradictions in Fuchs’ character: his conviction that nuclear knowledge should be shared between great powers to avert war; his principled but tested faith in communism, awakened while protesting the rise of Nazism; his devoted pastoral care for members of his inner circle at Harwell, even as the net closed around him; and his willingness to share not only nuclear secrets but also the bed of his colleague’s wife. Close has a particular obsession with the question of whether Fuchs’ eventual confession was induced by unrealistic suggestions that he could be forgiven and continue his work. But inducement did not jeopardise Fuchs’ ultimate conviction and imprisonment, despite MI5’s fears, and Close judges his 14-year sentence, later reduced, to be just. Even here, however, the Soviets had the last laugh, with Fuchs’ apprehension not only depriving the British nuclear programme of its greatest intellectual asset, but also precipitating the defection of Bruno Pontecorvo.
Close chose an ideal moment to research his history, writing with the benefit of newly released MI5 records, and before several others were withdrawn without notice. He applies forensic attention to the agency’s pursuit of the nuclear spy. Occasionally, however, this is to the detriment of the reader, with events seemingly diffracted onto the pages – both prefigured and returned to as the story progresses and new evidence comes to light. We step through time in Fuchs’ shoes, for example only learning at the end of the book that two other spies at the Manhattan Project were also passing information to the Russians. While Close’s inclination to let the evidence speak for itself is surely the mark of a good physicist, readers in search of a more analytical history may wish to also consult Mike Rossiter’s 2014 biography The Spy Who Changed the World: Klaus Fuchs and the secrets of the nuclear bomb, which offers a more rounded presentation of the Russian and American perspectives.
By bringing physics expertise, personal connections and impressive attention to detail to bear, Frank Close’s latest book has much to offer readers seeking insights into a formative time for the field, when the most talented minds in nuclear physics also bore the weight of world politics on their shoulders. He eloquently tells the tragedy of “the most dangerous spy in history”, as it played out between the trinity of Fuchs, his mentor Peierls and a shadowy network of spooks. Above all, the text is an intimate portrait of the inner struggles of a principled man who betrayed his adopted homeland, even as he grew to love it, and by doing so helped to shape the latter half of the 20th century.
Radiotherapy (RT) is a fundamental component of effective cancer treatment and control. More than 10,000 electron linear accelerators are currently used worldwide to treat patients with RT, most operating in the low beam-energy range of 5–15 MeV. Usually the electrons are directed at high-density targets to generate bremsstrahlung, and it is the resulting photon beams that are used for therapy. While low-energy electrons have been used to treat cancer for more than five decades, their very low penetration depth tends to limit their application to superficial tumours. The use of high-energy electrons (up to 50 MeV) was studied in the 1980s, but not clinically implemented.
More recently, the idea of using very high-energy (50–250 MeV) electron beams for RT has gained interest. For higher energy electrons, the penetration becomes deeper and the transverse penumbra sharper, potentially enabling the treatment of deep-seated tumours. While the longitudinal dose deposition is also distributed over a larger area, this can be controlled by focusing the electron beam.
The production of very high-energy electrons (VHEE) for RT was the subject of the VHEE 2020 International Workshop, organised by CERN and held remotely from 5–7 October. More than 400 scientists, ranging from clinicians to biologists, and from accelerator physicists to dosimetry experts, gathered virtually to evaluate the perspectives of this novel technique.
FLASH effect
VHEE beams offer several benefits. First, small-diameter high-energy beams can be scanned and focused easily, enabling finer resolution for intensity-modulated treatments than is possible for photon beams. Second, electron accelerators are more compact and significantly cheaper than current installations required for proton therapy. Third, VHEE beams can operate at very high dose rates, possibly compatible with the generation of the “FLASH effect”.
FLASH-RT is a paradigm-shifting method for delivering ultra-high doses within an extremely short irradiation time (tenths of a second). The technique has recently been shown to preserve normal tissue in various species and organs while still maintaining anti-tumour efficacy equivalent to conventional RT at the same dose level, in part due to decreased production of toxic reactive oxygen species. The FLASH effect has been shown to take place with electron, photon and more recently proton beams. However, electron beams promise to deliver an intrinsically higher dose compared to protons and photons, especially over large areas as would be needed for large tumours. Most of the preclinical data demonstrating the increased therapeutic index of FLASH are based ona single fraction and hypo-fractionated regimen of RT and 4–6 MeV beams, which do not allow treatments of deep-seated tumours and trigger large lateral penumbra. This problem can be solved by increasing the electron energy to values higher than 50 MeV, where the penetration depth is larger.
Today, after three decades of research into linear colliders, it is possible to build compact high-gradient (~100 MV/m) linacs, making a compact and cost effective VHEE RT accelerator a reality. Furthermore, the use of novel accelerator techniques such as laser-plasma acceleration is also starting to be applied in the VHEE field. These are currently the subject of a wide international study, as was presented at the VHEE workshop.
At the same time pioneering preliminary work on FLASH was being carried out by researchers at Lausanne University Hospital (CHUV) in Switzerland and the Curie Institute in France, high-gradient linac technology advances for VHEE were being made at CERN for the proposed Compact Linear Collider (CLIC). An extensive R&D program on normal-conducting radio-frequency accelerating structures has been carried out to obtain the demanding performances of the CLIC linac: an accelerating gradient of 100 MV/m, low breakdown rate, micron-tolerance alignment and a high RF-to-beam efficiency (around 30%). All this is now being applied in the conceptual designs of new RT facilities, such as one jointly being developed by CHUV and CERN.
Many challenges, both technological and biological, have to be addressed and overcome for the ultimate goal of using VHEE and VHEE-FLASH as an innovative modality for effective cancer treatment with minimal damage to healthy tissues. All of these were extensively covered and discussed in the different sessions of VHEE 2020.
From the accelerator-technology point of view an important point is to assess the possibility of focusing and transversely scanning the beam, thereby overcoming the disadvantages associated in the past with low-energy-electron- and photon-beam irradiation. In particular, in the case of VHEE–FLASH it has to be ensured that the biological effect is maintained. Stability, reliability and repeatability are other mandatory ingredients for accelerators to be operated in a medical environment.
The major challenge for VHEE–FLASH is the delivery of a very high dose-rate, possibly over a large area, providing a uniform dose distribution throughout the target. Also the parameter window in which the FLASH effect takes place has still to be thoroughly defined, as does its effectiveness as a function of the physical parameters of the electron beam. This, together with a clear understanding of the underlying biological processes, will likely prove essential in order to fully optimise the FLASH RT technique. Of particular importance, as was repeatedly pointed out during the workshop, is the development of reliable online dosimetry for very high dose rates, a regime not adapted to the current standard dosimetry techniques for RT. Ionisation chambers, routinely used in medical linacs, suffer from nonlinear effects at very high dose rates. To obtain reliable measurements, R&D is needed to develop novel ion chambers or explore alternative possibilities such as solid-state detectors or the use of calibrated beam diagnostics.
All this demands a large test activity across different laboratories to experimentally characterise VHEE beams and their ability to produce the FLASH effect, and to provide a testbed for the associated technologies. It is also important to compare the properties of the electron beams depending on the way they are produced (radio-frequency or laser-plasma accelerator technologies).
A number of experimental test facilities are already available to perform these ambitious objectives: the CERN Linear Electron Accelerator for Research (CLEAR), so far rather unique in being able to provide both high-energy (50–250 MeV) and high-charge beams; VELA–CLARA at Daresbury Laboratory; PITZ at DESY and finally ELBE–HZDR using the superconducting radio-frequency technology at Dresden. Further radiobiology studies with laser-plasma accelerated electron beams are currently being performed at the DRACO PetaWatt laser facility at the ELBE Center at HZDR-Dresden and at the Laboratoire d’Optique Appliqué in the Institute Polytechnique de Paris. Future facilities, as exemplified by the previously mentioned CERN–CHUV facility or the PHASER proposal at SLAC, are also on the horizon.
Establishing innovative treatment modalities for cancer is a major 21st century health challenge. By 2040, cancer is predicted to be the leading cause of death, with approximatively 27.5 million newly diagnosed patients and 16.3 million related deaths per year. The October VHEE workshop demonstrated the continuing potential of accelerator physics to drive new RT treatments, and also included a lively session dedicated to industrial partners. The large increase in attendance since the first workshop in 2017 in Daresbury, UK, shows the vitality and increasing interest in this field.
Twenty years ago, pioneering work at CERN helped propel Europe to the forefront of cancer treatment with hadron beams. The Proton Ion Medical Machine Study (PIMMS), founded in 1996 by a CERN–TERA Foundation-MedAustron–Oncology2000 collaboration, paved the way to the construction of two hadron-therapy centres: CNAO in Pavia (Italy) and MedAustron in Wiener Neustadt (Austria). A parallel pioneering development at GSI produced two similar centres in Germany (HIT in Heidelberg and MIT in Marburg). Since the commissioning of the first facility in 2009, the four European hadron-therapy centres have treated more than 10,000 patients with protons or carbon ions. The improved health and life expectancy of these individuals is the best reward to the vision of all those at CERN and GSI who laid the foundations for this new type of cancer treatment.
Almost four million new cancer cases are diagnosed per year in Europe, around half of which can be effectively treated with X-rays at relatively low cost. Where hadrons are advantageous is in the treatment of deep tumours close to critical organs or of paediatric tumours. For these cancers, the “Bragg peak” energy-deposition characteristic of charged particles reduces the radiation dose to organs surrounding the tumour, increasing survival rates and reducing negative side effects and the risk of recurrency. With respect to protons, carbon ions have the additional advantages of hitting the target more precisely with higher biological effect, and of being effective against radioresistant hypoxic tumours, which constitute between 1 and 3% of all radiation-therapy cases. Present facilities treat only a small fraction of all patients who could take advantage of hadron therapy, however. The diffusion of this relatively novel cancer treatment is primarily limited by its cost, and by the need for more pre-clinical and clinical research to fully exploit its potential.
Given these limitations, how can the scientific community contribute to extending the benefits of hadron therapy to a larger number of cancer patients? To review this and similar questions, CERN has recently given a new boost to its medical accelerator activities, after a long interruption corresponding to the time when CERN resources where directed mainly towards LHC construction. The framework for this renewed effort was provided by the CERN Council in 2017 when it approved a strategy concerning knowledge-transfer for the benefit of medical applications. This strategy specifically encouraged new initiatives to leverage existing and upcoming CERN technologies and expertise in accelerator technologies towards the design of a new generation of light-ion accelerators for medicine.
The hadron-therapy landscape in 2020 is very different from what it was 20 years ago. The principal reason is that industry has entered the field and developed a new generation of compact cyclotrons for proton therapy. Beyond the four hadron (proton and ion) centres there are now 23 industry-built facilities in Europe providing only proton therapy to about 4000 patients per year. Thanks to this new set of facilities, proton therapy is now highly developed and is progressively extending its reach in competition with more conventional X-ray radiation therapy.
Despite its many advantages over X-rays and protons, therapy with ions (mainly carbon, but other ions like helium or oxygen are under study) is still administered in Europe only by the four large hadron-therapy facilities. In comparison, eight ion-therapy accelerators are in operation in Asia, most of them in Japan, and four others are under construction. The development of new specific instruments for cancer therapy with ions is an ideal application for CERN technologies, in line with CERN’s role of promoting the adoption of cutting-edge technologies that might result in innovative products and open new markets.
Next-generation accelerators
To propel the use of cancer therapy with ions we need a next-generation accelerator, capable of bringing beams of carbon ions to the 430 MeV/u energy required to cover the full body, with smaller dimensions and cost compared to the PIMMS-type machines. A new accelerator design with improved intensity and operational flexibility would also enable a wide research programme to optimise ion species and treatment modalities, in line with what was foreseen by the cancelled BioLEIR programme at CERN. This would allow the exploration of innovative paths to the treatment of cancer such as ultra-short FLASH therapy or the promising combination of ion therapy with immunotherapy, which is expected to trigger an immune response against diffused cancers and metastasis. Moreover, a more compact accelerator could be installed in, or very close to, existing hospitals to fully integrate ion therapy in cancer-treatment protocols while minimising the need to transport patients over long distances.
The development of new specific instruments for cancer therapy with ions is an ideal application for CERN technologies
These considerations are the foundation for the Next Ion Medical Machine Study (NIMMS), a new CERN initiative that aims to develop specific accelerator technologies for the next generation of ion-therapy facilities and help catalyse a new European collective action for therapy with ion beams. The NIMMS activities were launched in 2019, following a workshop at ESI Archamps in 2018 where the medical and accelerator communities agreed on basic specifications for a new-generation machine. In addition to smaller dimensions and cost, these include a higher beam current for faster treatment, operation with multiple ions, and irradiation from different angles using a gantry system.
In addressing the challenges of new designs with reduced dimensions, CERN is building on the development work promoted in the last decade by the TERA Foundation. Reducing the accelerator dimensions from the conventional synchrotrons used so far can take different directions, out of which two are particularly promising. The first is the classic approach of using superconductivity to increase the magnetic field and decrease the radius of the synchrotron, and the second consists of replacing the synchrotron with a high-gradient linear accelerator with a new design – in line with the proton therapy linac being developed by ADAM, a spin-off company of CERN and TERA now part of the AVO group. The goal in both designs is to reduce the surface occupied by the accelerator by more than a factor of two, from about 1200 to 500 m2. With these considerations in mind, the NIMMS study has been structured in four work packages.
The main avenue to reduced dimensions is superconductivity, and the goal of the first work package is to develop new superconducting magnet designs for pulsed operation, with large apertures and curvatures – suitable for an ideal “square” synchrotron layout with only four 90 degree magnets. Different concepts are being explored, with some attention to the so-called canted cosine-theta design (see “Combined windings”) used for example in orbit correctors for the high-luminosity LHC, of which a team at Lawrence Berkeley National Laboratory has recently developed a curved prototype for medical applications. Other options under study are based on more traditional cosine-theta designs (see “Split yoke”), and on exploiting the potential of modern high-temperature superconductors.
The second work package covers the design of a compact linear accelerator optimised for installation in hospitals. Operating at 3 GHz with high field gradients, this linac design profits from the expertise gained with accelerating structures developed for the proposed Compact Linear Collider (CLIC), and uses as an injector a novel source for fully-stripped carbon based on the REX-ISOLDE design. The source is followed by a 750 MHz radio-frequency quadrupole using the design recently developed at CERN for medical and industrial applications.
The third NIMMS work package focuses on compact superconducting designs for the gantry, the large element required to precisely deliver ion beams to the patient that is critical for the cost and performance of an ion-therapy facility. The problem of integrating a large-acceptance beam optics with a compact superconducting magnetic system within a robust mechanical structure is an ideal challenge for the expertise of the CERN accelerator groups. Two designs are being considered: a lightweight rotational gantry covering only 180 degrees originally proposed by TERA, and the GaToroid toroidal gantry being developed at CERN.
NIMMS will consider new designs for the injector linac, with reduced cost and dimensions
The fourth work package is dedicated to the development of new high-current synchrotron designs, and to their integration in future cancer research and therapy facilities. To reduce treatment time, the goal is to accelerate more than an order of magnitude higher current than in the present European facilities. This requires careful multi-turn injection into the ring and strict control of beam optics, which add to other specific features of the new design, including a fast extraction that will make tests with the new ultra-fast FLASH treatment modality possible. Two synchrotron layouts are being considered, a more conventional one with room-temperature magnets (see “Ions for therapy”), and a very compact superconducting one of only 27 m circumference. The latter, equipped with a gantry of new design, would allow a single-room carbon-therapy facility to be realised in an area of about 1000 m2. Additionally, NIMMS will consider new designs for the injector linac, with reduced cost and dimensions and including the option of being used for production of medical radioisotopes – for imaging and therapy – during the otherwise idle time between two synchrotron injections.
Ambitious work plan
This ambitious work plan exceeds the resources that CERN can allocate to this study, and its development requires collaborations at different levels. The first enthusiastic partner is the new SEEIIST (South East European International Institute for Sustainable Technologies) organisation, which aims at building a pan-European facility for cancer research and therapy with ions (see “Ions for therapy”). SEEIIST is already joining forces with NIMMS by supporting staff working at CERN on synchrotron and gantry design. The second partnership is with the ion therapy centres CNAO and MedAustron, which are evaluating the proposed superconducting gantry design in view of extending the treatment capabilities of their facilities. A third critical partner is CIEMAT, which will build the high-frequency linac pre-injector and validate it with beam. Other partners participating in the study at different levels are GSI, PSI, HIT, INFN, Melbourne University, Imperial College, and of course TERA which remains one of the driving forces behind medical-accelerator developments. This wide collaboration has been successful in attracting additional support from the European Commission via two recently approved projects beginning in 2021. The multidisciplinary HITRIplus project on ion therapy includes work packages dedicated to accelerator, gantry and superconducting magnet design, while the IFAST project for cutting-edge accelerator R&D contains an ambitious programme focusing on the optimisation and prototyping of superconducting magnets for ion therapy with industry.
Every technology starts from a dream, and particle accelerators are there to fulfil one of the oldest: looking inside the human body and curing it without bloodshed. It is up to us to further develop the tools to realise this dream.
About 30–40% of people will develop cancer during their lifetimes. Surgery, chemotherapy, immunotherapy and radiotherapy (RT) are used to cure or manage the disease. But around a third of cancers are multi-resistant to all forms of therapies, defining a need for more efficient and better tolerated treatments. Technological advances in the past decade or so have transformed RT into a precise and powerful treatment for cancer patients. Nevertheless, the treatment of radiation-resistant tumours is complicated by the need to limit doses to surrounding normal tissue.
A paradigm-shifting technique called FLASH therapy, which is able to deliver doses of radiation in milliseconds instead of minutes as for conventional RT, is opening new avenues for more effective and less toxic RT. Pre-clinical studies have shown that the extremely short exposure time of FLASH therapy spares healthy tissue from the hazardous effect of radiation without reducing its efficacy on tumours.
First studied in the 1970s, it is only during the past few years that FLASH therapy has caught the attention of oncologists. The catalyst was a 2014 study carried out by researchers from Lausanne University Hospital (CHUV), Switzerland, and from the Institute Curie in Paris, which showed an outstanding differential FLASH effect between tumours and normal tissues in mice. The results were later confirmed by several other leading institutes. Then, in 2019, CHUV used FLASH to treat a multi-resistant skin cancer in a human patient, causing the tumour to completely disappear with nearly no side effects.
The consistency of pre-clinical data showing a striking protection of normal tissues with FLASH compared to conventional RT offers a new opportunity to improve cancer treatment, especially for multi-resistant tumours. The very short “radiation beam-on-time” of FLASH therapy could also eliminate the need for motion management, which is currently necessary when irradiating tumours that move with respiration. Furthermore, since FLASH therapy operates best with high single doses, it requires only one or two RT sessions as opposed to multiple sessions over a period of several weeks in the case of conventional RT. This promises to reduce oncology workloads and patient waiting lists, while improving treatment access in low-population density environments. Altogether, these advantages could turn FLASH therapy into a powerful new tool for cancer treatment, providing a better quality of life for patients.
The key requirements for CLIC correspond astonishingly well with the requirements for a FLASH facility
CERN and CHUV join forces
CHUV is undertaking a comprehensive research program to translate FLASH therapy to a clinical environment. No clinical prototype is currently available for treating patients with FLASH therapy, especially for deep-seated tumours. Such treatments require very high-energy beams (see p12) and face technological challenges that can currently be solved only by a very limited number of institutions worldwide. As the world’s largest particle-physics laboratory, CERN is one of them. In 2019, CHUV and CERN joined forces with the aim of building a high-energy, clinical FLASH facility.
The need to deliver a full treatment dose over a large area in a short period of time demands an accelerator that can produce a high-intensity beam. Amongst the current radiation tools available for RT – X-rays, electrons, protons and ions – electrons stand out for their unique combination of attributes. Electrons with an energy of around 100 MeV penetrate many tens of centimetres in tissue so have the potential to reach tumours deep inside the body. This is also true for the other radiation modalities but it is technically simpler to produce intense beams of electrons. For example, electron beams are routinely used to produce X-rays in imaging systems such as CT scanners and in industrial applications such as electron beam-welding machines. In addition, it is comparatively simple to accelerate electrons in linear accelerators and guide them using modest magnets. A FLASH-therapy facility based on 100 MeV-range electrons is therefore a highly compelling option.
Demonstrating the unexpected practical benefits of fundamental research, the emergence of FLASH therapy as a potentially major clinical advance coincides with the maturing of accelerator technology developed for the CLIC electron–positron collider. In a further coincidence, the focus of FLASH development has been at CHUV, in Lausanne, and CLIC development at CERN, in Geneva, just 60 km away. CLIC is one of the potential options for a post-LHC collider and the design of the facility, as well as the development of key technologies, has been underway for more than 20 years. A recent update of the design, now optimized for a 380 GeV initial-energy stage, and updated prototype testing were completed in 2018.
Despite the differences in scale and application, the key requirements for CLIC correspond astonishingly well with the requirements for a FLASH facility. First, CLIC requires high-luminosity collisions, for example to allow the study of rare interaction processes. This is achieved by colliding very high-intensity and precisely controlled beams: the average current during a pulse of CLIC is 1 A and the linac hardware is designed to allow two beams less than 1 nm in diameter to collide at the interaction point. High levels of current that are superbly controlled are also needed for FLASH to cover large tumours in short times. Second, CLIC requires a high accelerating gradient (72 MV/m in the initial stage) to achieve its required collision energy in a reasonably sized facility (11 km for a 380 GeV first stage). A FLASH facility using 100 MeV electrons based on an optimised implementation of the same technology requires an accelerator of just a couple of metres long. Other system elements such as diagnostics, beam shaping and delivery as well as radiation shielding make the footprint of the full facility somewhat larger. Overall, however, the compact accelerator technology developed for CLIC gives the possibility of clinical facilities built within the confines of typical hospital campus and integrated with existing oncology departments.
Over the decades, CLIC has invested significant resources into developing its high-current and high-gradient technology. Numerous high-power radio-frequency test stands have been built and operated, serving as prototypes for the radio-frequency system units that make up a linear accelerator. The high-current-beam test accelerator “CTF3” enabled beam dynamic simulation codes to be benchmarked and the formation, manipulation and control of very intense electron beams to be demonstrated. Further beam-dynamics validations and relevant experiments have been carried out at different laboratories including ATF2 at KEK, FACET at SLAC and ATF at Argonne. CERN also operates the Linear Electron Accelerator for Research (CLEAR) facility, where it can accelerate electrons up to 250 MeV, thus matching the energy requirements of FLASH radiotherapy. For the past several years, and beyond the collaboration between CERN and CHUV, the CLEAR facility has been involved in dosimetry studies for FLASH radiotherapy.
All of this accumulated experience and expertise is now being used to design and construct a FLASH facility. The collaboration between CERN and CHUV is a shining example of knowledge transfer, where technology developed for fundamental research is used to develop a therapeutic facility. While the technical aspects of the project have been defined via exchanges between medical researchers and accelerator experts, the CERN knowledge-transfer group and CHUV’s management have addressed contractual aspects and identified a strategy for intellectual property ownership. This global approach provides a clear roadmap for transforming the conceptual facility into a clinical reality. From the perspective of high-energy physics, the adoption of CLIC technology in commercially supplied medical facilities would significantly reduce technological risk and increase the industrial supplier base.
An interdisciplinary team comprising medical doctors, medical physicists, radiation biologists and accelerator physicists and engineers was formed
The collaboration between CHUV and CERN was catalysed by a workshop on FLASH therapy hosted by CHUV in September 2018, when it was realised that an electron-beam facility based on CLIC technology offers the possibility for a high-performance clinical FLASH facility. An interdisciplinary team comprising medical doctors, medical physicists, radiation biologists and accelerator physicists and engineers was formed to study the possibilities in greater depth. In an intense exchange during the months following the workshop, where requirements and capabilities were brought together and balanced, a clear picture of the parameters of a clinical FLASH facility emerged. Subsequently, the team studied critical issues in detail, validating that such a facility is in fact feasible. It is now working towards the details of a baseline design, with parameters specified at the system level, and the implementation of entirely new perspectives that were triggered by the study. A conceptual design report for the facility will be finished by the end of 2020. CHUV is actively seeking funding for the facility, which would require approximately three years for construction through beam commissioning.
The basic accelerator elements of the 100 MeV-range FLASH facility that emerged from this design process consist of: a photo-injector electron source; a linac optimised for high-current transport and maximum radio-frequency-power to beam-energy-transfer efficiency; and a beam-delivery system which forms the beam shape for individual treatment and directs it towards the patient. In addition, accelerator and clinical instrumentation are being designed which must work together to provide the necessary level of precision and repeatability required for patient treatment. This latter issue is of particular criticality in FLASH treatment, which must be administered with all feedback and correction of delivered dose to clinical levels completed in substantially less than a second. The radiation field is one area where the requirements of CLIC and FLASH are quite different. In CLIC the beam is focused to a very small spot (roughly 150 nm wide and 3 nm high) for maximum luminosity, whereas in FLASH the beam must be expanded to cover a large area (up to 10 cm) of irregular cross section and with high levels of dose uniformity. Although this requires a very different implementation of the beam-delivery systems, both CLIC and FLASH are designed using the same beam-dynamics tools and design methodologies.
Many challenges will have to be overcome, not least obtaining regulatory approval for such a novel system, but we are convinced that the fundamental ideas are sound and that the goal is within reach. A clinical FLASH facility based on CLIC technology is set to be an excellent example of the impact of developments made in the pursuit of fundamental science can have in society.
The Cabibbo–Kobayashi–Maskawa (CKM) matrix element Vub describes the coupling between u and b quarks in the weak interaction, and is one of the fundamental parameters of the Standard Model (SM). Though it was first observed to be non-zero 30 years ago, its value is still debated. |Vub| determines the length of the least well-known side of the corresponding unitarity triangle, and is therefore a key ingredient for testing the consistency of the SM in the flavour sector. LHCb has recently published a new result on |Vub| using the first ever measurement of the Bs0 → K–μ+νμ decay.
|Vub| and |Vcb| are the focus of a longstanding puzzle. When comparing the world-average values derived from inclusive and exclusive B-meson decays, respectively, the inclusive and exclusive measurements disagree by more than three standard deviations, for measurements of both |Vub| and |Vcb|. Traditionally, the exclusive |Vub| determination requires the reconstruction of the semileptonic b → u decay B0 → π–μ+νμ. LHCb also has access to Bs0 meson and b-baryon decays, but the missing neutrino makes it difficult to isolate the signal from the copious background. Defying expectations, however, in 2015 LHCb managed to observe the Λb0 → pμ–νμ decay, and used the normalisation channel Λb0 → Λ+cμ–νμ to determine |Vub|/ |Vcb|. The main difficulty in this type of analysis resides in the fact that only two charged particles are reconstructed in decays such as Bs0 → K–μ+νμ and Λb0 → pμ–νμ. A huge background arising from other sources dominates the selected data sample. Machine-learning algorithms are therefore used to isolate the signal from the various background categories consisting of decays with additional charged and/or neutral particles in the final state. The remaining irreducible background is modelled by using both simulation and control samples extracted from data.
This is the first experimental test of the form-factor calculations
First observation
In a recent paper, the LHCb collaboration presented the first observation of the decay Bs0 → K–μ+νμ. The decay Bs0 → Ds– μ+νμ is used as a normalisation channel to minimise experimental systematic uncertainties. The study was performed in two regions of the squared invariant mass (or momentum transfer) q2 of the muon and the neutrino below and above 7 GeV2. The observed total yield was about 13,000 events, corresponding to a branching fraction of (1.06 ± 0.10) × 10–4, of which about one third stemmed from the low q2 range (figure 1).
The extraction of the ratio |Vub|/|Vcb| requires external knowledge of the form factors describing the strong Bs0 → K– and Bs0 → Ds– transitions, to account for the interactions of the quarks bound in mesons. These vary with the momentum transfer and are calculated using non-perturbative techniques, such as lattice QCD (LQCD) and light-cone sum rules (LCSR). As LQCD and LCSR calculations are more accurate at high and low q2, respectively, they are used in the corresponding q2 regions. The obtained value of |Vub|/|Vcb| = 0.095 ± 0.008 in the high q2 interval shows agreement with the world average of exclusive measurements, and with the LHCb result using Λb0 → pμ–νμ decays, while in the low q2 region, |Vub|/|Vcb| = 0.061 ± 0.004 is significantly lower (figure 2). This is the first experimental test of the form-factor calculations, and new results are expected in the near future. These will help settle the exclusive versus inclusive debate surrounding the values of |Vub| and |Vcb|, and provide further constraints on the unitarity triangle.
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