scholarly journals Development of a Portable Hypoxia Chamber for Ultra-high Dose Rate Laser-Driven Proton Radiobiology Applications

Author(s):  
Pankaj Chaudhary ◽  
Deborah Caroline Gwynne ◽  
Boris Odlozilik ◽  
Aaron McMurray ◽  
Giuliana Milluzzo ◽  
...  

Abstract BackgroundThere is currently significant interest in assessing the role of oxygen in the radiobiological effects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing effect observed in FLASH radiotherapy, where particles are delivered at 40-1000 Gy/s. Furthermore, the development of laser-driven accelerators now enables radiobiology experiments in extreme regimes where dose rates can exceed 10^9 Gy/s, and predicted oxygen depletion effects on cellular response can be tested. Access to appropriate experimental enviroments, allowing measurements under controlled oxygenation conditions, is a key requirement for these studies. We report on the development and application of a bespoke portable hypoxia chamber specifically designed for experiments employing laser-driven sources, but also suitable for comparator studies under FLASH and conventional irradiation conditions.Materials and MethodsWe used oxygen concentration measurements to test the induction of hypoxia and the maintenance capacity of the chambers. Cellular hypoxia induction was verified using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic films and GEANT-4 simulations verified the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fibroblasts (AG01522B) and patient-derived glioblastoma (E2) cancer stem cells with laser-driven protons, conventional protons and reference 225 kVp X-rays to quantify DNA DSB damage and repair under hypoxia. We further measured the oxygen enhancement ratio for cell survival exposed to cyclotron-accelerated protons and X-rays in the normal fibroblast and radioresistant GBM stem cells. ResultsOxygen measurements showed that our chambers maintained a radiobiological hypoxic environment for at least 45 minutes and pathological hypoxia for up to 24 hrs after disconnecting the chambers from the gas supply. We observed a significant reduction in the 53BP1 foci induced by laser-driven protons, conventional protons and X-rays in the hypoxic cells compared to normoxic cells at 30 minutes post-irradiation. Under hypoxic irradiations, the Laser-driven protons induced significant residual DNA DSB damage in hypoxic AG01522 cells compared to the conventional dose rate protons suggesting an important impact of these extreme high dose-rate exposures. We obtained an oxygen enhancement ratio (OER) of 2.1 ± 0.108 and 2.501 ±0.125 respectively for the AG01522 and patient derived GBM stem cells for the X-rays using our hypoxia chambers for irradiation. ConclusionWe demonstrated the design and application of portable hypoxia chambers for studying cellular radiobiological endpoints after laser-driven protons at ultra-high dose, conventional protons and X-ray exposures. Good levels of reduced oxygen concentration could be maintained in the absence of external gassing to quantify hypoxic effects and the data obtained provided an indication of an enhanced residual DNA DSB damage under hypoxic conditions at ultra-high dose rate compared to the conventional protons or X-rays.

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3384-3389 ◽  
Author(s):  
R Storb ◽  
RF Raff ◽  
FR Appelbaum ◽  
HJ Deeg ◽  
TC Graham ◽  
...  

Abstract We explored in dogs the immunosuppressive properties of 450 cGy total body irradiation (TBI) delivered from two opposing 60Co sources, as assessed by the criterion of successful engraftment of allogeneic genotypically DLA-identical littermate marrow. Two questions were asked in this study. Firstly, does dose rate affect the immunosuppressive effect of TBI when administered in a single dose? Secondly, does fractionation alter the immunosuppression of TBI when delivered at a very fast dose rate? Dose rates studied included 7 and 70 cGy/min, and fractionation involved four fractions of 112.5 cGy each, with 6-hour minimum interfraction intervals. Six of 7 dogs receiving 450 cGy single- dose TBI at 70 cGy/min showed sustained engraftment of the allogeneic marrow, compared with 1 of 7 dogs receiving single-dose TBI at 7 cGy/min (P = .01). Fractionated TBI at 70 cGy/min resulted in sustained allogeneic engraftment in 3 of 10 dogs, a result that was statistically significantly worse than that with single-dose TBI at 70 cGy/min (P = .03) and not statistically different (P = .24) from that with fractionated TBI delivered at 7 cGy/min (0 of 5 dogs engrafted). A single dose of 450 cGy of TBI delivered at a rate of 70 cGy/min is significantly more immunosuppressive than the same total dose delivered at 7 cGy/min. Fractionated TBI at 70 cGy/min is significantly less immunosuppressive than single-dose TBI at 70 cGy/min and not significantly different from fractionated TBI administered at 7 cGy/min. Results are consistent with the notion that significant DNA repair in lymphoid cells is possible during interfraction intervals at the relatively high dose rate of 70 cGy/min.


Author(s):  
Guoqing Zhang ◽  
Xuexin Wang ◽  
Jiangang Zhang ◽  
Dajie Zhuang ◽  
Chaoduan Li ◽  
...  

The isotopes of uranium and their daughter nuclides inside the UO2 pellet emit mono-energetic electrons and beta rays, which generate rather high dose rate near the UO2 pellet and could cause exposure to workers. In this work calculations of electron dose rates have been carried out with Monte Carlo codes, MCNPX and Geant4, for a UO2 pellet and a fuel rod. Comparisons between calculations and measurements have been carried out to verify the calculation results. The results could be used to estimate the dose produced by electrons and beta rays, which could be used to make optimization for radiation protection purpose.


1990 ◽  
Vol 201 ◽  
Author(s):  
E. Cortesi ◽  
F. Namavar ◽  
R. F. Pinizzotto ◽  
H. Yang

AbstractWe have studied Separation by IMplantation of OXygen (SIMOX) processes using very high dose rates (40–60 μA/cm2). For a dose of 4 × 1017 O+/cm2 at 160 keV, the structure formed by implantation at 50 μA/cm2 is very similar to that associated with lower dose rates. The same dose implanted at a dose rate of 60 μA/cm2, however, results in the formation of pits in the silicon surface as well as a somewhat different oxide structure. Implantation through a surface oxide layer appears to result in a structure similar to that associated with lower dose rate implantation. These and higher dose samples suggest that the threshold for pit formation is related to both dose rate and dose.


2007 ◽  
Vol 1056 ◽  
Author(s):  
Tina M. Nenoff ◽  
Jason C. Jones ◽  
Paula P. Provencio ◽  
Donald T. Berry

ABSTRACTWe report on a fundamental morphology growth of gold-based nanoparticles by solution radiolysis. Radiolysis of pure gold-polymer solutions of different dose rates and aging time is examined. A detailed description will be presented of the experimentation, testing and analysis. In particular, we will present data on the formation of gold nano-octahedra and -prism particles. The γ-irradiations were carried out with a 60Co source of 1.345 × 105 Ci (Sandia National Laboratories Gamma Irradiation Facility (GIF). Nanoparticle characterization techniques included are UV-vis and TEM. Similar to what has been seen in earlier silver nanoparticle studies, dose rate dictates the size of nanoparticles formed. At high dose rate, all reducing species are produced and scavenged within a short time, and then coalesce into separate nanoparticles. At low dose rate, the coalescence process is faster than the production rate of the reducing radicals. The reduction of radicals occurs mainly on clusters already formed. The differences in the morphologies result from a combination of dose rate, aging and lack of radical scavengers (e.g. isopropyl alcohol), resulting in either gold nano-spheres, octahedral or prism nanoparticles. The progressive evolution with dose rate of the UV-visible absorption spectra of radiation-induced metal clusters is discussed.


2021 ◽  
Vol 9 ◽  
Author(s):  
Pankaj Chaudhary ◽  
Giuliana Milluzzo ◽  
Hamad Ahmed ◽  
Boris Odlozilik ◽  
Aaron McMurray ◽  
...  

The use of particle accelerators in radiotherapy has significantly changed the therapeutic outcomes for many types of solid tumours. In particular, protons are well known for sparing normal tissues and increasing the overall therapeutic index. Recent studies show that normal tissue sparing can be further enhanced through proton delivery at 100 Gy/s and above, in the so-called FLASH regime. This has generated very significant interest in assessing the biological effects of proton pulses delivered at very high dose rates. Laser-accelerated proton beams have unique temporal emission properties, which can be exploited to deliver Gy level doses in single or multiple pulses at dose rates exceeding by many orders of magnitude those currently used in FLASH approaches. An extensive investigation of the radiobiology of laser-driven protons is therefore not only necessary for future clinical application, but also offers the opportunity of accessing yet untested regimes of radiobiology. This paper provides an updated review of the recent progress achieved in ultra-high dose rate radiobiology experiments employing laser-driven protons, including a brief discussion of the relevant methodology and dosimetry approaches.


2021 ◽  
Author(s):  
Martin Precek ◽  
Petr Kubelik ◽  
Ludek Vysin ◽  
Uli Schmidhammer ◽  
Jean-Philippe Larbre ◽  
...  

The development of ultra-intense electron pulse for applications needs to be accompanied by the implementation of a practical dosimetry system. In this study four different systems were investigated as dosimeters for low doses with a very high-dose-rate source. First, the effects of ultra-short pulses were investigated for the yields of the Fricke dosimeter based on acidic solutions of ferrous sulfate; it was established that the yields were not significantly affected by the high dose rates, so the Fricke dosimeter system was used as a reference. Then, aqueous solutions of three compounds as fluorescence chemical dosimeters were utilized, each operated at a different solution pH: terephthalic acid - basic, trimesic acid - acidic, and coumarin-3- carboxylic acid (C3CA) - neutral. Fluorescence chemical dosimeters offer an attractive alternative to chemical dosimeters based on optical absorption for measuring biologically relevant low doses because of their higher sensitivity. The effects of very intense dose rate (TGy/s) from pulses of fast electrons generated by a picosecond linear accelerator on the chemical yields of fluorescence chemical dosimeters were investigated at low peak doses (<20 Gy) and compared with yields determined under low-dose-rate irradiation from a 60 Co gamma-ray source (mGy/s). For the terephthalate and the trimesic acid dosimeters changes in the yields were not detected within the estimated (∼10%) precision of the experiments, but, due to the complexity of the mechanism of the hydroxyl radical initiated reactions in solutions of the relevant aromatic compounds, significant reductions of the chemical yield (–60%) were observed when the C3CA dosimeter was irradiated with the ultra-short pulses.


2012 ◽  
Vol 1 (1) ◽  
pp. 27-34
Author(s):  
C. Jewett ◽  
J. Chow ◽  
D. Comeau ◽  
G. Jonkmans ◽  
B. Smith ◽  
...  

The positions of the components of a reactor can change over time, due to radiation damage, sagging, etc. Thus, it is important to determine their positions. To satisfy this requirement of the staff at the Point Lepreau Generating Station, a method to determine the positions of reactor components has been developed and demonstrated. This method combines the use of dose rate measurements and Monte Carlo simulations. It first involves measuring the high γ-ray dose rates as a function of position within a reactor. Then it entails comparing these measurements with Monte Carlo simulations. In order to perform such measurements, a silicon diode detector and a scan drive system have been developed. In 2009, measurements of the γ-ray dose rate profile of the shut down Point Lepreau Generating Station reactor were conducted. By comparing the locations of the local peaks in the dose rate data, it was possible to determine the distances between the steel reactor components. The measured data were then compared with Monte Carlo simulations to determine how precisely one could locate the positions of the adjuster rods. Using this technique, it was found that the retracted adjuster rods were 440 ± 60 mm below their designed positions.


Sign in / Sign up

Export Citation Format

Share Document