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O K Harling - One of the best experts on this subject based on the ideXlab platform.
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preliminary treatment planning and dosimetry for a clinical trial of Neutron capture therapy using a fission converter epithermal Neutron Beam
Applied Radiation and Isotopes, 2004Co-Authors: W S Kiger, Yasushi Shibata, O K Harling, Kent J Riley, Peter J Binns, Jody Kaplan, Hemant Patel, Robert G Zamenhof, Irving D Kaplan, Paul M BusseAbstract:Abstract A Phase I/II clinical trial of Neutron capture therapy (NCT) was conducted at Harvard–MIT using a fission converter epithermal Neutron Beam. This epithermal Neutron Beam has nearly ideal performance characteristics (high intensity and purity) and is well-suited for clinical use. Six glioblastoma multiforme (GBM) patients were treated with NCT by infusion of the tumor-selective amino acid boronophenylalanine-fructose (BPA-F) at a dose of 14.0 g/m 2 body surface area over 90 min followed by irradiation with epithermal Neutrons. Treatments were planned using NCTPlan and an accelerated version of the Monte Carlo radiation transport code MCNP 4B. Treatments were delivered in two fractions with two or three fields. Field order was reversed between fractions to equalize the average blood boron concentration between fields. The initial dose in the dose escalation study was 7.0 RBE Gy, prescribed as the mean dose to the whole brain volume. This prescription dose was increased by 10% to 7.7 RBE Gy in the second cohort of patients. A pharmacokinetic model was used to predict the blood boron concentration for determination of the required Beam monitor units with good accuracy; differences between prescribed and delivered doses were 1.5% or less. Estimates of average tumor doses ranged from 33.7 to 83.4 RBE Gy (median 57.8 RBE Gy), a substantial improvement over our previous trial where the median value of the average tumor dose was 25.8 RBE Gy.
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performance characteristics of the mit fission converter based epithermal Neutron Beam
Physics in Medicine and Biology, 2003Co-Authors: Kent J Riley, Peter J Binns, O K HarlingAbstract:A pre-clinical characterization of the first fission converter based epithermal Neutron Beam (FCB) designed for boron Neutron capture therapy (BNCT) has been performed. Calculated design parameters describing the physical performance of the aluminium and Teflon filtered Beam were confirmed from Neutron fluence and absorbed dose rate measurements performed with activation foils and paired ionization chambers. The facility currently provides an epithermal Neutron flux of 4.6 x 10(9) n cm(-2) s(-1) in-air at the patient position that makes it the most intense BNCT source in the world. This epithermal Neutron flux is accompanied by very low specific photon and fast Neutron absorbed doses of 3.5 +/- 0.5 and 1.4 +/- 0.2 x 10(-13) Gy cm2, respectively. A therapeutic dose rate of 1.7 RBE Gy min(-1) is achievable at the advantage depth of 97 mm when boronated phenylalanine (BPA) is used as the delivery agent, giving an average therapeutic ratio of 5.7. In clinical trials of normal tissue tolerance when using the FCB, the effective prescribed dose is due principally to Neutron interactions with the nonselectively absorbed BPA present in brain. If an advanced compound is considered, the dose to brain would instead be predominately from the photon kerma induced by thermal Neutron capture in hydrogen and advantage parameters of 0.88 Gy min(-1), 121 mm and 10.8 would be realized for the therapeutic dose rate, advantage depth and therapeutic ratio, respectively. This study confirms the success of a new approach to producing a high intensity, high purity epithermal Neutron source that attains near optimal physical performance and which is well suited to exploit the next generation of boron delivery agents.
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sensitivity studies of Beam directionality Beam size and Neutron spectrum for a fission converter based epithermal Neutron Beam for boron Neutron capture therapy
Medical Physics, 1999Co-Authors: S Sakamoto, W S Kiger, O K HarlingAbstract:Sensitivity studies of epithermal Neutron Beam performance in boronNeutron capture therapy are presented for realistic Neutron Beams with varying filter/moderator and collimator/delimiter designs to examine the relative importance of Neutron Beam spectrum, directionality, and size. Figures of merit for in-air and in-phantom Beam performance are calculated via the Monte Carlo technique for different well-optimized designs of a fission converter-based epithermal Neutron Beam with head phantoms as the irradiation target. It is shown that increasing J/φ, a measure of Beam directionality, does not always lead to corresponding monotonic improvements in Beam performance. Due to the relatively low significance, for most configurations, of its effect on in-phantom performance and the large intensity losses required to produce Beams with very high J/φ, Beam directionality should not be considered an important figure of merit in epithermal Neutron Beam design except in terms of its consequences on patient positioning and collateral dose. Hardening the epithermal Beam spectrum, while maintaining the specific fast Neutron dose well below the inherent hydrogen capture dose, improves Beam penetration and advantage depth and, as a desirable by-product, significantly increases Beam intensity. Beam figures of merit are shown to be strongly dependent on Beam size relative to target size. Beam designs with J/φ≈0.65–0.7, specific fast Neutron doses of 2–2.6×10 −13 Gy cm 2 /n and Beam sizes equal to or larger than the size of the head target produced the deepest useful penetration, highest therapeutic ratios, and highest intensities.
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Neutronic design of a fission converter based epithermal Neutron Beam for Neutron capture therapy
Nuclear Science and Engineering, 1999Co-Authors: W S Kiger, S Sakamoto, O K HarlingAbstract:To meet the needs for Neutron capture theory (NCT) irradiations, a high-intensity, high-quality fusion converter-based epithermal Neutron Beam has been designed for the MITR-II research reactor. This epithermal Neutron Beam, capable of delivering treatments in a few minutes with negligible background contamination from fast Neutrons and photons, will be installed in the present thermal column and hohlraum of the 5-MW MITR-II research reactor. Spent or fresh MITR-II fuel elements will be used to fuel the converter. With a fission converter power of {approximately}80 kW using spent fuel, epithermal fluxes (1 eV < E < 10 keV) in excess of 10{sup 10} n/cm{sup 2} {center_dot} s are achievable at the target position with negligible photon and fast Neutron contamination, i.e., <2 {times} 10{sup {minus}11}cGy-cm{sup 2}/n. With the currently available {sup 10}B delivery compound boronophenylalanine-fructose, average therapeutic ratios of {approximately}5 can be achieved using this Beam for brain irradiations with deep effective penetration ({approximately}9.5 cm) and high dose rates of up to 400 to 600 RBE cGy/min. If NCT becomes an accepted therapy, fission converter-based Beams constructed at existing reactors could meet a large fraction of the projected requirements for intense, low-background epithermal Neutron Beams at a relatively low cost. The resultsmore » of an extensive set of Neutronic design studies investigating all components of the Beam are presented. These detailed studies can be useful as guidance for others who may wish to use the fission converter approach to develop epithermal Beams for NCT.« less
R Hallwilton - One of the best experts on this subject based on the ideXlab platform.
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parasitic Neutron Beam monitoring proof of concept on gamma monitoring of Neutron chopper phases
EPL, 2020Co-Authors: F Issa, R Hallwilton, A Quintanilla, M Olsson, D Zielinski, K Kanaki, Nikolaos TsapatsarisAbstract:Neutron Beam monitors are an essential diagnostic component of Neutron scattering facilities. They are used to measure Neutron flux, calibrating experiments performed on the instruments, allowing measurement of facility performance, understanding of the effect on the Neutrons of Beam-line components (such as choppers), calibration of detectors and tracking of Beam stability. Ideally Beam monitors should not perturb the Beam. Previous work shows commercial Beam monitors attenuate the Beam by a few percent in the worst case due to the 1–2 mm thick aluminium entrance and exit windows and the material inside. Parasitic methods of Neutron Beam diagnostics, where there is no Beam monitor directly in the Beam, would be preferable. This paper presents the concept of a parasitic method of monitoring the Beam which can be used for Neutron chopper phasing. This is achieved by placing a gamma detector close to a rotating chopper and measuring a signal proportional to the flux absorbed by the chopper. Neutrons interact with the boron absorber on the chopper disc leading to gamma emission at 480 keV. Detection of these gamma rays is used to determine the chopper phasing and timing. Potentially information on the flux of the Beamline can be extracted. Results from a proof of concept implementation show that diagnosis of Neutron chopper phases is feasible.
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parasitic Neutron Beam monitoring proof of concept on gamma monitoring of Neutron chopper phases
arXiv: Instrumentation and Detectors, 2020Co-Authors: F Issa, R Hallwilton, A Quintanilla, M Olsson, D Zielinski, K Kanaki, Nikolaos TsapatsarisAbstract:Neutron Beam monitors are an essential diagnostic component of Neutron scattering facilities. They are used to measure Neutron flux, calibrating experiments performed on the instruments, allowing measurement of facility performance, understanding of the effect on the Neutrons of Beam-line components (such as choppers), calibration of detectors and tracking of Beam stability. Ideally Beam monitors {should} not perturb the Beam. Previous work shows commercial Beam monitors attenuate the Beam by a few percent in the worst case due to the 1-2 mm thick Aluminium entrance and exit windows and the material inside. Parasitic methods of Neutron Beam diagnostics, where there is no Beam monitor directly in the Beam, would be preferable. This paper presents the concept of a parasitic method of monitoring the Beam which can be used for Neutron chopper phasing. This is achieved by placing a gamma detector close to a rotating chopper and measures a signal proportional to the flux absorbed by the chopper. Neutrons interact with the Boron absorber on the chopper disc lead to gamma emission at 480 keV. Detection of these gamma rays is used to determine the chopper phasing and timing. Potentially information on the flux of the Beamline can be extracted. Results from a proof of concept implementation show that diagnosis of Neutron chopper phases is feasible.
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boron 10 lined rpcs for sub millimeter resolution thermal Neutron detectors feasibility study in a thermal Neutron Beam
arXiv: Instrumentation and Detectors, 2018Co-Authors: L M S Margato, R Hallwilton, A Morozov, A Blanco, P Fonte, F A F Fraga, Bruno Guerard, Carina HoglundAbstract:The results of an experimental feasibility study of a position sensitive thermal Neutron detector based on a resistive plate chamber (RPC) are presented. The detector prototype features a thin-gap (0.35 mm) hybrid RPC with an aluminium cathode lined with a 2 ${\mu}$m thick $^{10}B{_4}C$ Neutron converter layer enriched in $^{10}B$ and a float glass anode. A detection efficiency of ${\approx}$ 6.2 ${\%}$ was measured for the Neutron Beam (${\lambda}$ =2.5 $A$) at normal incidence. A spatial resolution better than 0.5 mm FWHM was demonstrated.
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characterization of thermal Neutron Beam monitors
arXiv: Instrumentation and Detectors, 2017Co-Authors: F Issa, A Khaplanov, R Hallwilton, I Llamas, Dalseth M Riktor, S R Brattheim, H PerreyAbstract:Neutron Beam monitors with high efficiency, low gamma sensitivity, high time and space resolution are required in Neutron Beam experiments to continuously diagnose the delivered Beam. In this work, commercially available Neutron Beam monitors have been characterized using the R2D2 Beamline at IFE (Norway) and using a Be-based Neutron source. For the gamma sensitivity measurements different gamma sources have been used. The evaluation of the monitors includes, the study of their efficiency, attenuation, scattering and sensitivity to gamma. In this work we report the results of this characterization.
F Issa - One of the best experts on this subject based on the ideXlab platform.
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parasitic Neutron Beam monitoring proof of concept on gamma monitoring of Neutron chopper phases
EPL, 2020Co-Authors: F Issa, R Hallwilton, A Quintanilla, M Olsson, D Zielinski, K Kanaki, Nikolaos TsapatsarisAbstract:Neutron Beam monitors are an essential diagnostic component of Neutron scattering facilities. They are used to measure Neutron flux, calibrating experiments performed on the instruments, allowing measurement of facility performance, understanding of the effect on the Neutrons of Beam-line components (such as choppers), calibration of detectors and tracking of Beam stability. Ideally Beam monitors should not perturb the Beam. Previous work shows commercial Beam monitors attenuate the Beam by a few percent in the worst case due to the 1–2 mm thick aluminium entrance and exit windows and the material inside. Parasitic methods of Neutron Beam diagnostics, where there is no Beam monitor directly in the Beam, would be preferable. This paper presents the concept of a parasitic method of monitoring the Beam which can be used for Neutron chopper phasing. This is achieved by placing a gamma detector close to a rotating chopper and measuring a signal proportional to the flux absorbed by the chopper. Neutrons interact with the boron absorber on the chopper disc leading to gamma emission at 480 keV. Detection of these gamma rays is used to determine the chopper phasing and timing. Potentially information on the flux of the Beamline can be extracted. Results from a proof of concept implementation show that diagnosis of Neutron chopper phases is feasible.
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Vanadium-based Neutron Beam monitor
Physical Review Accelerators and Beams, 2020Co-Authors: V. Maulerova, F Issa, Kalliopi Kanaki, P. M. Kadletz, Robin Woracek, T. Wilpert, Kevin Fissum, A. Laloni, N. Mauritzson, Richard Hall-wiltonAbstract:A prototype invasive (quasi-parasitic) thermal-Neutron Beam monitor based on isotropic Neutron scattering from a thin natural Vanadium foil and standard $^3$He proportional counters has been conceptualized, designed, simulated, calibrated, and commissioned. As the Beam monitor is invasive, very low Neutron-Beam attenuation is a necessary characteristic. Further, response linearity over as wide a range of rates as possible is highly desirable. The prototype was first calibrated using radioactive Neutron sources at the Source-Testing Facility at the Division of Nuclear Physics in Lund, Sweden. Subsequently, the prototype was commissioned with Beams of Neutrons at the V17 and V20 Beamlines of the Helmholtz Zentrum in Berlin, Germany. Both low attenuation and response linearity have been successfully demonstrated, indicating the concept is viable and worth continued development efforts. In this thesis, a monographic overview of the development of the prototype is presented. (Less)
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parasitic Neutron Beam monitoring proof of concept on gamma monitoring of Neutron chopper phases
arXiv: Instrumentation and Detectors, 2020Co-Authors: F Issa, R Hallwilton, A Quintanilla, M Olsson, D Zielinski, K Kanaki, Nikolaos TsapatsarisAbstract:Neutron Beam monitors are an essential diagnostic component of Neutron scattering facilities. They are used to measure Neutron flux, calibrating experiments performed on the instruments, allowing measurement of facility performance, understanding of the effect on the Neutrons of Beam-line components (such as choppers), calibration of detectors and tracking of Beam stability. Ideally Beam monitors {should} not perturb the Beam. Previous work shows commercial Beam monitors attenuate the Beam by a few percent in the worst case due to the 1-2 mm thick Aluminium entrance and exit windows and the material inside. Parasitic methods of Neutron Beam diagnostics, where there is no Beam monitor directly in the Beam, would be preferable. This paper presents the concept of a parasitic method of monitoring the Beam which can be used for Neutron chopper phasing. This is achieved by placing a gamma detector close to a rotating chopper and measures a signal proportional to the flux absorbed by the chopper. Neutrons interact with the Boron absorber on the chopper disc lead to gamma emission at 480 keV. Detection of these gamma rays is used to determine the chopper phasing and timing. Potentially information on the flux of the Beamline can be extracted. Results from a proof of concept implementation show that diagnosis of Neutron chopper phases is feasible.
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Characterization of Thermal Neutron Beam Monitors
Physical Review Accelerators and Beams, 2017Co-Authors: F Issa, A Khaplanov, I Llamas, S R Brattheim, Richard Hall-wilton, M. Dalseth Riktor, H PerreyAbstract:Neutron Beam monitors with a wide range of efficiencies, low $\ensuremath{\gamma}$ sensitivity, and high time and space resolution are required in Neutron Beam experiments to continuously diagnose the delivered Beam. In this work, commercially available Neutron Beam monitors have been characterized using the R2D2 Beamline at IFE (Norway) and using a Be-based Neutron source. For the $\ensuremath{\gamma}$ sensitivity measurements different $\ensuremath{\gamma}$ sources have been used. The evaluation of the monitors includes, the study of their efficiency, attenuation, scattering, and sensitivity to $\ensuremath{\gamma}$. In this work we report the results of this characterization.
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characterization of thermal Neutron Beam monitors
arXiv: Instrumentation and Detectors, 2017Co-Authors: F Issa, A Khaplanov, R Hallwilton, I Llamas, Dalseth M Riktor, S R Brattheim, H PerreyAbstract:Neutron Beam monitors with high efficiency, low gamma sensitivity, high time and space resolution are required in Neutron Beam experiments to continuously diagnose the delivered Beam. In this work, commercially available Neutron Beam monitors have been characterized using the R2D2 Beamline at IFE (Norway) and using a Be-based Neutron source. For the gamma sensitivity measurements different gamma sources have been used. The evaluation of the monitors includes, the study of their efficiency, attenuation, scattering and sensitivity to gamma. In this work we report the results of this characterization.
Nikolaos Tsapatsaris - One of the best experts on this subject based on the ideXlab platform.
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parasitic Neutron Beam monitoring proof of concept on gamma monitoring of Neutron chopper phases
EPL, 2020Co-Authors: F Issa, R Hallwilton, A Quintanilla, M Olsson, D Zielinski, K Kanaki, Nikolaos TsapatsarisAbstract:Neutron Beam monitors are an essential diagnostic component of Neutron scattering facilities. They are used to measure Neutron flux, calibrating experiments performed on the instruments, allowing measurement of facility performance, understanding of the effect on the Neutrons of Beam-line components (such as choppers), calibration of detectors and tracking of Beam stability. Ideally Beam monitors should not perturb the Beam. Previous work shows commercial Beam monitors attenuate the Beam by a few percent in the worst case due to the 1–2 mm thick aluminium entrance and exit windows and the material inside. Parasitic methods of Neutron Beam diagnostics, where there is no Beam monitor directly in the Beam, would be preferable. This paper presents the concept of a parasitic method of monitoring the Beam which can be used for Neutron chopper phasing. This is achieved by placing a gamma detector close to a rotating chopper and measuring a signal proportional to the flux absorbed by the chopper. Neutrons interact with the boron absorber on the chopper disc leading to gamma emission at 480 keV. Detection of these gamma rays is used to determine the chopper phasing and timing. Potentially information on the flux of the Beamline can be extracted. Results from a proof of concept implementation show that diagnosis of Neutron chopper phases is feasible.
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parasitic Neutron Beam monitoring proof of concept on gamma monitoring of Neutron chopper phases
arXiv: Instrumentation and Detectors, 2020Co-Authors: F Issa, R Hallwilton, A Quintanilla, M Olsson, D Zielinski, K Kanaki, Nikolaos TsapatsarisAbstract:Neutron Beam monitors are an essential diagnostic component of Neutron scattering facilities. They are used to measure Neutron flux, calibrating experiments performed on the instruments, allowing measurement of facility performance, understanding of the effect on the Neutrons of Beam-line components (such as choppers), calibration of detectors and tracking of Beam stability. Ideally Beam monitors {should} not perturb the Beam. Previous work shows commercial Beam monitors attenuate the Beam by a few percent in the worst case due to the 1-2 mm thick Aluminium entrance and exit windows and the material inside. Parasitic methods of Neutron Beam diagnostics, where there is no Beam monitor directly in the Beam, would be preferable. This paper presents the concept of a parasitic method of monitoring the Beam which can be used for Neutron chopper phasing. This is achieved by placing a gamma detector close to a rotating chopper and measures a signal proportional to the flux absorbed by the chopper. Neutrons interact with the Boron absorber on the chopper disc lead to gamma emission at 480 keV. Detection of these gamma rays is used to determine the chopper phasing and timing. Potentially information on the flux of the Beamline can be extracted. Results from a proof of concept implementation show that diagnosis of Neutron chopper phases is feasible.
Kent J Riley - One of the best experts on this subject based on the ideXlab platform.
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selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells
Proceedings of the National Academy of Sciences of the United States of America, 2006Co-Authors: Bradley W Schuller, Kent J Riley, Peter J Binns, Frederick M Hawthorne, Jeffrey A CoderreAbstract:The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received whole-body epithermal Neutron irradiation at a dose rate of 0.57 ± 0.04 Gy·min−1. An additional dose was selectively targeted to endothelial cells from the short-ranged (5–9 μm) particles released from Neutron capture reactions in 10B confined to the blood by incorporation into liposomes 70–90 nm in diameter. Different liposome formulations produced 45 ± 7 or 118 ± 12 μg/g 10B in the blood at the time of Neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 ± 0.09 or 1.90 ± 0.16 Gy·min−1, respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2- to 3-fold increased doses to the microvasculature, relative to the nonspecific whole-body Neutron Beam doses, caused no additional crypt stem cell loss beyond that produced by the Neutron Beam alone. The threshold dose for death from the GI syndrome after Neutron-Beam-only irradiation was 9.0 ± 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received Neutron Beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome.
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preliminary treatment planning and dosimetry for a clinical trial of Neutron capture therapy using a fission converter epithermal Neutron Beam
Applied Radiation and Isotopes, 2004Co-Authors: W S Kiger, Yasushi Shibata, O K Harling, Kent J Riley, Peter J Binns, Jody Kaplan, Hemant Patel, Robert G Zamenhof, Irving D Kaplan, Paul M BusseAbstract:Abstract A Phase I/II clinical trial of Neutron capture therapy (NCT) was conducted at Harvard–MIT using a fission converter epithermal Neutron Beam. This epithermal Neutron Beam has nearly ideal performance characteristics (high intensity and purity) and is well-suited for clinical use. Six glioblastoma multiforme (GBM) patients were treated with NCT by infusion of the tumor-selective amino acid boronophenylalanine-fructose (BPA-F) at a dose of 14.0 g/m 2 body surface area over 90 min followed by irradiation with epithermal Neutrons. Treatments were planned using NCTPlan and an accelerated version of the Monte Carlo radiation transport code MCNP 4B. Treatments were delivered in two fractions with two or three fields. Field order was reversed between fractions to equalize the average blood boron concentration between fields. The initial dose in the dose escalation study was 7.0 RBE Gy, prescribed as the mean dose to the whole brain volume. This prescription dose was increased by 10% to 7.7 RBE Gy in the second cohort of patients. A pharmacokinetic model was used to predict the blood boron concentration for determination of the required Beam monitor units with good accuracy; differences between prescribed and delivered doses were 1.5% or less. Estimates of average tumor doses ranged from 33.7 to 83.4 RBE Gy (median 57.8 RBE Gy), a substantial improvement over our previous trial where the median value of the average tumor dose was 25.8 RBE Gy.
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performance characteristics of the mit fission converter based epithermal Neutron Beam
Physics in Medicine and Biology, 2003Co-Authors: Kent J Riley, Peter J Binns, O K HarlingAbstract:A pre-clinical characterization of the first fission converter based epithermal Neutron Beam (FCB) designed for boron Neutron capture therapy (BNCT) has been performed. Calculated design parameters describing the physical performance of the aluminium and Teflon filtered Beam were confirmed from Neutron fluence and absorbed dose rate measurements performed with activation foils and paired ionization chambers. The facility currently provides an epithermal Neutron flux of 4.6 x 10(9) n cm(-2) s(-1) in-air at the patient position that makes it the most intense BNCT source in the world. This epithermal Neutron flux is accompanied by very low specific photon and fast Neutron absorbed doses of 3.5 +/- 0.5 and 1.4 +/- 0.2 x 10(-13) Gy cm2, respectively. A therapeutic dose rate of 1.7 RBE Gy min(-1) is achievable at the advantage depth of 97 mm when boronated phenylalanine (BPA) is used as the delivery agent, giving an average therapeutic ratio of 5.7. In clinical trials of normal tissue tolerance when using the FCB, the effective prescribed dose is due principally to Neutron interactions with the nonselectively absorbed BPA present in brain. If an advanced compound is considered, the dose to brain would instead be predominately from the photon kerma induced by thermal Neutron capture in hydrogen and advantage parameters of 0.88 Gy min(-1), 121 mm and 10.8 would be realized for the therapeutic dose rate, advantage depth and therapeutic ratio, respectively. This study confirms the success of a new approach to producing a high intensity, high purity epithermal Neutron source that attains near optimal physical performance and which is well suited to exploit the next generation of boron delivery agents.