Radiobiology Experiments With Ultra-high Dose Rate Laser-Driven Protons: Methodology and State-of-the-Art

Chaudhary, Pankaj; Milluzzo, G.; Ahmed, H.; Odlozilik, Boris; McMurray, Aaron; Prise, Kevin M.; Borghesi, M.

doi:10.3389/fphy.2021.624963

Cited by 45 publications

(28 citation statements)

References 134 publications

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“…Independent of the development of FLASH, several groups of researchers studied the biological effects of UHDR in the context of the development of laser-driven radiotherapy 102 .…”

Section: -Laser-driven Beamsmentioning

confidence: 99%

“…Independent of the development of FLASH, several groups of researchers studied the biological effects of UHDR in the context of the development of laser-driven RT. 125 Laser-driven electrons, photons, protons, or heavy ion beams originally were proposed as a less expensive alternative to conventional accelerators in producing high energy beams for tumor therapy. 126,127 Recently, the potential benefits arising from their special beam characteristics were advocated.…”

Section: Laser-driven Beamsmentioning

confidence: 99%

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Radiobiology of the FLASH effect

et al. 2021

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Radiation exposures at ultra-high dose rates (UHDR) at several orders of magnitude greater than in current clinical radiotherapy have been shown to manifest differential radiobiological responses compared to conventional dose rates (CONV). This has led to studies investigating the application of UHDR for therapeutic advantage (FLASH-RT) which have gained significant interest since the initial discovery in 2014 that demonstrated reduced lung toxicity with equivalent levels of tumour control compared with conventional dose-rate radiotherapy. Many subsequent studies have demonstrated the potential protective role of FLASH-RT in normal tissues, yet the underlying molecular and cellular mechanisms of the FLASH effect remain to be fully elucidated. Here, we summarise the current evidence of the FLASH effect and review FLASH-RT studies performed in preclinical models of normal tissue response. To critically examine the underlying biological mechanisms of responses to UHDR radiation exposures, we evaluate in vitro studies performed with normal and tumour cells. Differential responses to UHDR vs CONV irradiation recurrently involve reduced inflammatory processes and differential expression of pro-and anti-inflammatory genes. In addition, frequently reduced levels of DNA damage or misrepair products are seen after UHDR irradiation. So far, it is not clear what signal elicits these differential responses, but there are indications for involvement of reactive species. Different susceptibility to FLASH effects observed between normal and tumour cells may result from altered metabolic and detoxification pathways and/or repair pathways used by tumour cells. We summarize the current theories that may explain the FLASH effect and highlight This article is protected by copyright. All rights reserved.3 important research questions which are key to a better mechanistic understanding and, thus, the future implementation of FLASH-RT in the clinic. -INTRODUCTIONRadiation therapy (RT) remains a critical part of clinical cancer care prescribed to > 50% of patients in high-income countries and contributes to more than 30% of all long-term cancer survivors 1,2 . Technological advances in imaging and RT delivery techniques have resulted in major improvements in patient survival through improved precision and ability to conform dose to the tumour targets whilst minimising dose to surrounding organs at risk (OARs). In addition to improvements in technical radiotherapy, major research efforts have been made to exploit the unique radiobiological responses that occur at ultra-high dose rates (UHDR). In comparison to conventional clinical dose rates (CONV) in the region of 0.01-0.40 Gy/s, UHDR radiotherapy was originally established using microsecond pulses of 5 MeV electrons with intra-pulse dose rate in the range 10 6 -10 7 Gy/s, time-averaged dose rate > 40 Gy/s and

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“…Independent of the development of FLASH, several groups of researchers studied the biological effects of UHDR in the context of the development of laser-driven radiotherapy 102 .…”

Section: -Laser-driven Beamsmentioning

confidence: 99%

Section: Laser-driven Beamsmentioning

confidence: 99%

Radiobiology of the FLASH effect

et al. 2021

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“…Full control of high-intensity laser-matter interaction is key to enable applications like fast ignition for inertial confinement fusion 1 , 2 or laser-plasma driven particle sources 3 for warm dense matter research 4 , time-resolved studies of transient fields 5 and translational research for radiation oncology 6 . It requires predictive power of simulation tools in quantitative agreement with experimental results and it is still challenging to achieve for laser-solid interactions 3 .…”

Section: Introductionmentioning

confidence: 99%

Off-harmonic optical probing of high intensity laser plasma expansion dynamics in solid density hydrogen jets

Bernert

Assenbaum

Brack

et al. 2022

Sci Rep

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Due to the non-linear nature of relativistic laser induced plasma processes, the development of laser-plasma accelerators requires precise numerical modeling. Especially high intensity laser-solid interactions are sensitive to the temporal laser rising edge and the predictive capability of simulations suffers from incomplete information on the plasma state at the onset of the relativistic interaction. Experimental diagnostics utilizing ultra-fast optical backlighters can help to ease this challenge by providing temporally resolved inside into the plasma density evolution. We present the successful implementation of an off-harmonic optical probe laser setup to investigate the interaction of a high-intensity laser at $$5.4\times 10^{21}\,\hbox {W/cm}^{2}$$ 5.4 × 10 21 W/cm 2 peak intensity with a solid-density cylindrical cryogenic hydrogen jet target of $${5}\,{\upmu }\mathrm{m}$$ 5 μ m diameter as a target test bed. The temporal synchronization of pump and probe laser, spectral filtering and spectrally resolved data of the parasitic plasma self-emission are discussed. The probing technique mitigates detector saturation by self-emission and allowed to record a temporal scan of shadowgraphy data revealing details of the target ionization and expansion dynamics that were so far not accessible for the given laser intensity. Plasma expansion speeds of up to $$(2.3 \pm 0.4)\times 10^{7}\,\hbox {m/s}$$ ( 2.3 ± 0.4 ) × 10 7 m/s followed by full target transparency at $${1.4}\,{\mathrm{ps}}$$ 1.4 ps after the high intensity laser peak are observed. A three dimensional particle-in-cell simulation initiated with the diagnosed target pre-expansion at $${-0.2}\,{\mathrm{ps}}$$ - 0.2 ps and post processed by ray tracing simulations supports the experimental observations and demonstrates the capability of time resolved optical diagnostics to provide quantitative input and feedback to the numerical treatment within the time frame of the relativistic laser-plasma interaction.

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“…Practical solutions are small dosimeters, such as alanin pellets, and radiochromic films that can be cut into user-defined shapes and sizes [51][52][53]. Experiments with new radiation qualities, such as FLASH radiotherapy, laser-driven sources or proton mini-beams, demand for adapted solutions with respect to sample positioning and dosimetry [54][55][56][57]. Moreover, point-like measurements with small dosimeters can be supported by simulations [58] to resolve proton dose distributions [59,60].…”

Section: The Physicist's Point Of Viewmentioning

confidence: 99%

Models for Translational Proton Radiobiology—From Bench to Bedside and Back

Suckert

Nexhipi

Dietrich

et al. 2021

Cancers

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The number of proton therapy centers worldwide are increasing steadily, with more than two million cancer patients treated so far. Despite this development, pending questions on proton radiobiology still call for basic and translational preclinical research. Open issues are the on-going discussion on an energy-dependent varying proton RBE (relative biological effectiveness), a better characterization of normal tissue side effects and combination treatments with drugs originally developed for photon therapy. At the same time, novel possibilities arise, such as radioimmunotherapy, and new proton therapy schemata, such as FLASH irradiation and proton mini-beams. The study of those aspects demands for radiobiological models at different stages along the translational chain, allowing the investigation of mechanisms from the molecular level to whole organisms. Focusing on the challenges and specifics of proton research, this review summarizes the different available models, ranging from in vitro systems to animal studies of increasing complexity as well as complementing in silico approaches.

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Radiobiology Experiments With Ultra-high Dose Rate Laser-Driven Protons: Methodology and State-of-the-Art

Cited by 45 publications

References 134 publications

Radiobiology of the FLASH effect

Radiobiology of the FLASH effect

Off-harmonic optical probing of high intensity laser plasma expansion dynamics in solid density hydrogen jets

Models for Translational Proton Radiobiology—From Bench to Bedside and Back

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