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Displaying One Session

Thu, 01.01.1970

Session Type
FLASH Modalities Track (Oral Presentations)
Date
Thu, 02.12.2021
Session Time
15:10 - 16:10
Room
Room 2.31

CALORIMETRY TECHNIQUES FOR ABSOLUTE DOSIMETRY OF LASER-DRIVEN IONS BEAMS

Session Type
FLASH Modalities Track (Oral Presentations)
Date
Thu, 02.12.2021
Session Time
15:10 - 16:10
Room
Room 2.31
Lecture Time
15:10 - 15:20

Abstract

Background and Aims

Advancement in accelerator technology has led to the development of systems capable of generating particle beams with ultra-high dose rates per pulse, facilitating investigations of radiation therapy modalities characterized by dose deliveries exceeding several hundred Gy/s. The FLASH effect is induced at rates greater than 40 Gy/s, subsequently reducing undesired healthy tissue damage, whilst maintaining comparable tumour control to conventional techniques. Further, laser-driven acceleration of charged particle beams produced with compact “plasma accelerators” are characterized by even higher dose rates per pulse (up to 109 Gy/s) at quasi-instantaneous irradiations.

Methods

Despite this, dosimetry of these beams has proven to be technically challenging, requiring the development of novel strategies to replace already established methods for conventional radiotherapy. As such, a small portable graphite calorimeter has been developed and modified at National Physical Laboratory (NPL) to conduct absolute dose measurements of high dose rate per pulse proton beams.

Results

Proof of principle measurement of the absorbed dose of laser-driven proton beams have been carried out with this device, representing the first ever based on calorimetry techniques. Energetic proton beams of up to 40 MeV were produced using the VULCAN petawatt laser system of the Central Laser Facility of the Rutherford Appleton Laboratory. Doses per pulse of up to 3 Gy were measured, with negligible electromagnetic pulse (EMP) contribution to the signal.

Conclusions

This project 18HLT04 UHDpulse has received funding from the EMPIR programme co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme.

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LASER-DRIVEN PROTON ACCELERATION AT DRACO PW: A NOVEL PLATFORM FOR ULTRA-HIGH DOSE RATE RADIOBIOLOGY.

Session Type
FLASH Modalities Track (Oral Presentations)
Date
Thu, 02.12.2021
Session Time
15:10 - 16:10
Room
Room 2.31
Lecture Time
15:20 - 15:30

Abstract

Background and Aims

After the rediscovery of the normal tissue sparing FLASH effect of high dose rate radiation, research activities on this topic have been revived. But especially for protons, the portfolio of accelerators capable of performing studies at ultra-high dose rates is limited. Laser-plasma accelerators (LPA) can generate extremely intense proton bunches of many 10 MeV kinetic energy. In combination with dedicated dose delivery systems, LPA proton sources facilitate peak dose rates well above 108 Gy/s in a pulse structure regime complementary to conventional accelerators.

Methods

The reliable generation of proton spectra beyond 60 MeV at DRACO-PW [Ziegler et al, SciRep2021], combined with a dedicated energy selective pulsed magnet beam transport system [Brack et al, SciRep2020], allows tailored sample-specific dose distributions. Adapted on-shot dosimetry enables the required spectral monitoring of every proton bunch. Two irradiation series on volumetric biological samples were performed at DRACO-PW, accompanied by reference irradiations at the University Proton Therapy Dresden.

Results

The first small animal pilot study at a laser-driven proton source was conducted successfully. The mouse-ear tumor model’s requirements [Beyreuther et al, PLoS One2018] were fulfilled and verified at high precision (+/- 5%) concerning predefined dose value and conformity. Complementary, a study investigating dose-rate effects such as FLASH was performed irradiating zebrafish embryos with above 109 Gy/s.

Conclusions

We present a laser-based irradiation platform at the DRACO-PW facility that enables systematic radiobiological studies, laying the foundations for further studies at LPA sources exploring ultra-high dose-rate effects, such as FLASH, over previously unreachable parameter space.

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DOSIMETRY AND BEAM DELIVERY ARRANGEMENTS FOR SINGLE-SHOT, ULTRA-HIGH DOSE-RATE RADIOBIOLOGY EXPERIMENTS EMPLOYING LASER-ACCELERATED IONS

Session Type
FLASH Modalities Track (Oral Presentations)
Date
Thu, 02.12.2021
Session Time
15:10 - 16:10
Room
Room 2.31
Lecture Time
15:30 - 15:40

Abstract

Background and Aims

Laser-driven ion acceleration is attracting significant interest in the radiobiological community, as it allows to deliver dose in ultrashort bursts with high dose rates (109-1010 Gy/s), opening up for investigation novel regimes of radiobiology. These studies require the implementation of bespoke and innovative arrangements for beam delivery and dosimetry.

Methods

The PW VULCAN and GEMINI laser systems at the Rutherford Appleton laboratory were used to generate, respectively, proton and carbon ion bunches. 35 MeV protons and 10 MeV/u carbon ions were magnetically selected and used to irradiate 2D and 3D biological samples, in single exposures. The 2D-samples were plated on a dish and placed inside a vertical holder while 3D models (Glioblastoma neurospheres) were immersed in cell culture medium and placed at the bottom of a thin-walled 3 mm diameter polypropylene tube. Dosimetry was performed on every shot by employing previously calibrated, unlaminated EBT3-Radio-Chromic Film (RCF) for carbon ion dosimetry, while standard EBT3-RCF was used for the proton measurements.

Results

Doses in the 1-5 Gy range with 10% dose variation over 3x3 mm2 surface, were delivered to the cells and measured. The proton depth-dose profile along the 3 mm thick tube was evaluated with an EBT3-RCF stack phantom, showing a 5% dose uniformity along the whole tube thickness.

Conclusions

The irradiation and dosimetry approach enabled controlled irradiation of 2D and 3D samples, with a shot-to-shot precise dose determination.

Acknowledgements

This project 18HLT04 UHDpulse has received funding from the EMPIR programme co-financed by the Participating States and from the European Union’s Horizon 2020 programme.

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LASER-DRIVEN PROTON SOURCE FOR IN-VITRO AND IN-VIVO HIGH DOSE, ULTRA-HIGH DOSE-RATE EXPERIMENTS

Session Type
FLASH Modalities Track (Oral Presentations)
Date
Thu, 02.12.2021
Session Time
15:10 - 16:10
Room
Room 2.31
Lecture Time
15:40 - 15:50

Abstract

Background and Aims

Laser-driven proton acceleration produces short radiation bunches with a continuous energy spectrum up to a sharp cutoff; in previous experiments our group proved the biological effect of a “laser-driven fast-fractionation” modality, where the target dose is deposited by a number of ultra-short radiation pulses at ultra-high instantaneous dose-rate. In a new experiment we aim at reaching the relevant target dose in a single laser pulse (which would be a million times shorter that the accepted limit for FLASH effect) and using multiple spectral components to produce an SOBP for thicker biological samples.

Methods

We used the pico2000/LULI laser facility for proton acceleration, using 12.5um gold targets. The particle transport was ensured by a remotely-controlled beam-line composed by two permanent-magnet quadrupoles (LMU) and a scattering system. Dosimetry measurements were performed with radiochromic films, previously calibrated on the CPO/Institut Curie medical accelerator.

Results

A total charge exceeding 150nC/shot was measured, in a continuous spectrum up to 16MeV. At the biological sample plane a maximum deposited dose of 20Gy/shot could be obtained on a surface of 1cm2 and within an estimated deposition time of 10ns. Dose escalation at the irradiation plane, ensured by variable quadrupole configurations, was applied on monolayer cell cultures and on zebrafish embryos. A precise modelling of the dosimetric data is currently being realised.

Conclusions

A high-energy-laser-driven proton irradiation line capable of producing FLASH-like conditions on a mm thick sample in a sub-us time was demonstrated. Fixed, post-development embryos and cell survival assays are currently under analysis.

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FIRST RADIOBIOLOGICAL EVIDENCE OF LASER-DRIVEN CARBON ION EFFECTIVENESS AT ULTRA-HIGH DOSE RATE

Session Type
FLASH Modalities Track (Oral Presentations)
Date
Thu, 02.12.2021
Session Time
15:10 - 16:10
Room
Room 2.31
Lecture Time
15:50 - 16:00

Abstract

Background and Aims

The normal tissue sparing effects of FLASH radiotherapy have revived interest in ultra-short pulse, ultra-high dose rate (UHDR) radiobiology, with several recent FLASH and UHDR pre-clinical studies using low-LET radiation. High power lasers enable the delivery of Gy level carbon dose at dose rates > 109 Gy/sec, opening up to investigation the still unknown radiobiology of UHDR, high-LET radiation

Methods

At the Gemini Laser of the Central Laser Facility, Rutherford Appleton Laboratory, Glioblastoma stem like cells (GSCs) were exposed to 1 Gy of 10 MeV/n carbon ions in single pulses of ~ 400-picosecond duration, at a dose rate of 2.5 x109 Gy/sec. Carbon ions were accelerated by focussing 45 fs, 6 J laser pulses onto 10-25 nm thick carbon foils at intensity ~ 6 1020 W/cm2. We used the 53BP1 foci assay to study carbon ions induced DNA damage and compared the results with 225kVp X-rays induced DSB damage in the GSCs.

Results

Laser-driven carbon ions induced complex DNA DSB damage, as seen through persistent 53BP1 foci (11.3 ± 0.5 foci per cell) at 24 hrs, compared to X-rays where the foci levels reduced to near the background levels. The relative foci induction values of laser-driven carbon ions normalized to X-rays was found to be 5.75 ± 0.51

Conclusions

Overall, this is the first study to report the radiobiological effectiveness of laser-accelerated carbon ions, demonstrating a method to accelerate and deliver high LET carbon ions in radioresistant GBM stem cell models in single ultrashort single sub-nanosecond pulses.

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