Proton Boron Research Articles

Evaluation of the effective dose during PBFT for brain cancer: A Monte Carlo Study

Introduction: Recently, an approach exploiting the proton therapy biological enhancement by using Boron atoms injected inside a tumor, has been proposed. Three alpha particles with an average energy around 4MeV are emitted from the point of reaction between a proton and boron. In addition, the 719 keV prompt gamma emitted by the proton Boron fusion reactions can be used for on-line proton beam imaging purposes. Materials and Methods: We simulated a proton beam passing through the Snyder head phantom with and without a boron uptake region (BUR) in the tumor to investigate the amplification of the proton’s maximum dose level using a Monte Carlo simulation. The proton’s maximum dose level obtained for different proton energies with considering distinction physical conditions (i.e. location and thickness of BUR, boron concentration). The percentage depth dose (PDD) of the proton in the Snyder phantom without the BUR obtained using the F6 tally. However, the counting of additional proton by alpha particle is based on the results by using F4 tally. The absorbed dose due to three alpha particle and proton components acquired for scalp, skull, tumor and brain. Results: The aim of this study is to compare the effectiveness between proton boron fusion therapy (PBFT) and proton therapy and to analyze dose escalation using a Monte Carlo simulation in the brain cancer. When the portion of the proton’s maximum dose (Bragg- peak) is included at tumor region, which is BUR, observed a dramatic therapy effect with less damage to normal tissue. The peak value of maximum dose level when the boron particle was accurately labeled at the region was 185% among the energies. Conclusion: The PDD of the proton beam from the Snyder phantom including the BURs shows more efficient than that of conventional proton therapy on tumor region. The utility of PBFT was verified using the simulation and it has a potential for application in radiotherapy. When the portion of the proton’s maximum dose (Bragg-peak) is included at tumor region, which is BUR, observed a dramatic therapy effect with less damage to normal tissue.

The Current Status and Perspectives of Delivery Strategy for Boronbased Drugs.

Boron-containing compounds are essential micronutrients for animals and plants despite their low-level natural occurrence. They can strengthen the cell walls of the plants and they play important role in supporting bone health. However, surprisingly, boron-containing compounds are seldom found in pharmaceutical drugs. In fact, there are no inherent disadvantages reported so far in terms of the incorporation of boron into medicines. Indeed, drugs based on boron-containing compounds, such as tavaborole (marked name Kerydin) and bortezomib (trade name Velcade) have been investigated and they are used in clinical treatment. In addition, following the advanced development of boron neutron capture therapy and a new emerging proton boron fusion therapy, more boron-containing medicinals are to be expected. This review discusses the current status and perspectives of delivery strategy for boron-containing drugs.

First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness

Protontherapy is hadrontherapy’s fastest-growing modality and a pillar in the battle against cancer. Hadrontherapy’s superiority lies in its inverted depth-dose profile, hence tumour-confined irradiation. Protons, however, lack distinct radiobiological advantages over photons or electrons. Higher LET (Linear Energy Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity increases with LET, resulting in efficient cell killing, i.e. higher Relative Biological Effectiveness (RBE). However, economic and radiobiological issues hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To this end, we exploited the p + 11B → 3α reaction to generate high-LET alpha particles with a clinical proton beam. To maximize the reaction rate, we used sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha particles. We recorded significantly increased cellular lethality and chromosome aberration complexity. A strategy combining protontherapy’s ballistic precision with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.

Quantitative analysis of prompt gamma ray imaging during proton boron fusion therapy according to boron concentration

The purpose of this study is to evaluate the prompt gamma ray imaging technique according to the clinical boron concentration range during proton boron fusion therapy (PBFT). To acquire a prompt gamma ray image from 32 projections, we simulated four head single photon emission computed tomography and a proton beam nozzle using a Monte Carlo simulation. We used modified ordered subset expectation maximization reconstruction algorithm with a graphic processing unit for fast image acquisition. Boron concentration was set as 20 to 100 μg at intervals of 20 μg. For quantitative analysis of the prompt gamma ray image, we acquired an image profile drawn through two boron uptake regions (BURs) and calculated the contrast value, signal-to-noise ratio (SNR), and difference between the physical target volume and volume of the prompt gamma ray image. The relative counts of prompt gamma rays were noticeably increased with increasing boron concentration. Although the intensities on the image profiles showed a similar tendency according to the boron concentration, the SNR and contrast value were improved with increasing boron concentration. This study suggests that a tumor monitoring technique using prompt gamma ray detection can be clinically applicable even if the boron concentration is relatively low.

Non-thermal laser driven plasma-blocks for proton boron avalanche fusion as direct drive option

Fusion energy from protons reacting with 11B, HB11, is extremely difficult or impossible when using thermal ignition by laser irradiation. This changes radically when using picosecond laser pulses with powers above petawatts dominated by nonlinear force driven ultrahigh acceleration of plasma blocks for a non-thermal initiation of igniting solid density HB11 fuel. For a cylindrical trapping of the reaction, laser produced ultrahigh magnetic fields above kiloTesla, have to be combined. The experimentally confirmed highly increased HB11 fusion gains due to avalanche reaction may lead to a scheme of an environmentally clean and economic power reactor.

Simulation of proton–boron nuclear burning in the potential well of virtual cathode at nanosecond vacuum discharge

The neutron-free reaction of proton-boron nuclear burning accompanied with the yield of three alpha particles (p + 11B → α + 8Be* → 3α) is of great fundamental and applied interest. However, the implementation of the synthesis of p +11B requires such extreme plasma parameters that are difficult to achieve at well-known schemes of controlled thermonuclear fusion. Earlier, the yield of DD neutrons in a compact nanosecond vacuum discharge (NVD) of low energy with deuterated Pd anode have been observed. Further detailed particle-in-cell simulation by the electrodynamic code have recognized that this experiment represents the realization of rather old scheme of inertial electrostatic confinement (IEC). This IEC scheme is one of the few where the energies of ions needed for p + 11B reaction are quite possible. The purpose of this work on simulation of proton–boron reaction is studying the features of possible p + 11B burning at the IEC scheme based on NVD, thus, to look forward and planning the real experiment.

The investigation of physical conditions of boron uptake region in proton boron fusion therapy (PBFT)

We conducted a quantitative study to identify the effectiveness of proton boron fusion therapy (PBFT). Four simulation scenarios were designed to investigate the escalation in total dose with the proton boron reaction using a Monte Carlo n-particle extended (MCNPX 2.6.0) simulation. The peak integrated dose was obtained for three different physical conditions (i.e., boron uptake region (BUR) thickness, BUR location, and boron concentration) with differing proton beam energy (60–90 MeV). We found that the peak integrated dose was increased by up to 96.62% compared to the pristine proton Bragg-peak. For the synergetic effect to take place with 60–70 MeV proton beam, the BUR had to be at least 0.3 cm thick while spanning the Bragg-peak. Similarly to the thickness, the BUR location needed to be within 0.3 cm from the Bragg-peak when the thickness was maintained at 0.9 cm. An effective proton boron reaction required the boron concentration to be equal to or greater than 14.4 mg/g. These results demonstrate the impact of various physical and beam conditions of the PBFT, which are critical environmental factors for the treatment planning. We envision that this study will advance our understanding of the PBFT, which can be an invaluable treatment method for maximizing the potential of proton therapy.

SU‐F‐T‐140: Assessment of the Proton Boron Fusion Reaction for Practical Radiation Therapy Applications Using MCNP6

Purpose:The proton boron fusion reaction is a reaction that describes the creation of three alpha particles as the result of the interaction of a proton incident upon a 11B target. Theoretically, the proton boron fusion reaction is a desirable reaction for radiation therapy applications in that, with the appropriate boron delivery agent, it could potentially combine the localized dose delivery protons exhibit (Bragg peak) and the local deposition of high LET alpha particles in cancerous sites. Previous efforts have shown significant dose enhancement using the proton boron fusion reaction; the overarching purpose of this work is an attempt to validate previous Monte Carlo results of the proton boron fusion reaction.Methods:The proton boron fusion reaction, 11B(p, 3α), is investigated using MCNP6 to assess the viability for potential use in radiation therapy. Simple simulations of a proton pencil beam incident upon both a water phantom and a water phantom with an axial region containing 100ppm boron were modeled using MCNP6 in order to determine the extent of the impact boron had upon the calculated energy deposition.Results:The maximum dose increase calculated was 0.026% for the incident 250 MeV proton beam scenario. The MCNP simulations performed demonstrated that the proton boron fusion reaction rate at clinically relevant boron concentrations was too small in order to have any measurable impact on the absorbed dose.Conclusion:For all MCNP6 simulations conducted, the increase of absorbed dose of a simple water phantom due to the 11B(p, 3α) reaction was found to be inconsequential. In addition, it was determined that there are no good evaluations of the 11B(p, 3α) reaction for use in MCNPX/6 and further work should be conducted in cross section evaluations in order to definitively evaluate the feasibility of the proton boron fusion reaction for use in radiation therapy applications.

Prompt gamma ray imaging for verification of proton boron fusion therapy: A Monte Carlo study

PurposeThe purpose of this study was to verify acquisition feasibility of a single photon emission computed tomography image using prompt gamma rays for proton boron fusion therapy (PBFT) and to confirm an enhanced therapeutic effect of PBFT by comparison with conventional proton therapy without use of boron. MethodsMonte Carlo simulation was performed to acquire reconstructed image during PBFT. We acquired percentage depth dose (PDD) of the proton beams in a water phantom, energy spectrum of the prompt gamma rays, and tomographic images, including the boron uptake region (BUR; target). The prompt gamma ray image was reconstructed using maximum likelihood expectation maximisation (MLEM) with 64 projection raw data. To verify the reconstructed image, both an image profile and contrast analysis according to the iteration number were conducted. In addition, the physical distance between two BURs in the region of interest of each BUR was measured. ResultsThe PDD of the proton beam from the water phantom including the BURs shows more efficient than that of conventional proton therapy on tumour region. A 719keV prompt gamma ray peak was clearly observed in the prompt gamma ray energy spectrum. The prompt gamma ray image was reconstructed successfully using 64 projections. Different image profiles including two BURs were acquired from the reconstructed image according to the iteration number. ConclusionWe confirmed successful acquisition of a prompt gamma ray image during PBFT. In addition, the quantitative image analysis results showed relatively good performance for further study.

Avalanche boron fusion by laser picosecond block ignition with magnetic trapping for clean and economic reactor

Measured highly elevated gains of proton–boron (HB11) fusion (Picciotto et al., Phys. Rev. X 4, 031030 (2014)) confirmed the exceptional avalanche reaction process (Lalousis et al., Laser Part. Beams 32, 409 (2014); Hora et al., Laser Part. Beams 33, 607 (2015)) for the combination of the non-thermal block ignition using ultrahigh intensity laser pulses of picoseconds duration. The ultrahigh acceleration above $10^{20}~\text{cm}~\text{s}^{-2}$ for plasma blocks was theoretically and numerically predicted since 1978 (Hora, Physics of Laser Driven Plasmas (Wiley, 1981), pp. 178 and 179) and measured (Sauerbrey, Phys. Plasmas 3, 4712 (1996)) in exact agreement (Hora et al., Phys. Plasmas 14, 072701 (2007)) when the dominating force was overcoming thermal processes. This is based on Maxwell’s stress tensor by the dielectric properties of plasma leading to the nonlinear (ponderomotive) force $f_{\text{NL}}$ resulting in ultra-fast expanding plasma blocks by a dielectric explosion. Combining this with measured ultrahigh magnetic fields and the avalanche process opens an option for an environmentally absolute clean and economic boron fusion power reactor. This is supported also by other experiments with very high HB11 reactions under different conditions (Labaune et al., Nature Commun. 4, 2506 (2013)).

SU‐E‐T‐656: Quantitative Analysis of Proton Boron Fusion Therapy (PBFT) in Various Conditions

Purpose:Three alpha particles are concomitant of proton boron interaction, which can be used in radiotherapy applications. We performed simulation studies to determine the effectiveness of proton boron fusion therapy (PBFT) under various conditions.Methods:Boron uptake regions (BURs) of various widths and densities were implemented in Monte Carlo n‐particle extended (MCNPX) simulation code. The effect of proton beam energy was considered for different BURs. Four simulation scenarios were designed to verify the effectiveness of integrated boost that was observed in the proton boron reaction. In these simulations, the effect of proton beam energy was determined for different physical conditions, such as size, location, and boron concentration.Results:Proton dose amplification was confirmed for all proton beam energies considered (< 96.62%). Based on the simulation results for different physical conditions, the threshold for the range in which proton dose amplification occurred was estimated as 0.3 cm. Effective proton boron reaction requires the boron concentration to be equal to or greater than 14.4 mg/g.Conclusion:We established the effects of the PBFT with various conditions by using Monte Carlo simulation. The results of our research can be used for providing a PBFT dose database.

SU-D-304-07: Application of Proton Boron Fusion Reaction to Radiation Therapy

Purpose: we present the introduction of a therapy method using the proton boron fusion reaction. The purpose of this study is to verify the theoretical validity of proton boron fusion therapy using Monte Carlo simulations. Methods: After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton’s maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here we show that the effectiveness of the proton boron fusion therapy (PBFT) was verified using Monte Carlo simulations. Results: We found that a dramatic increase by more than half of the proton’s maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton’s maximum dose point was located within the boron uptake region (BUR). In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. Conclusion: This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improvedmore » therapy effects, and the monitoring of the therapy region during treatment.« less

MO‐F‐CAMPUS‐J‐05: Verification for Prompt Gamma Ray Imaging During Proton Boron Fusion Therapy

Purpose:The purpose of this study is to verify the acquisition of the three dimensional single photon emission computed tomography (SPECT) image using prompt gamma ray originated from proton boron fusion therapy (PBFT).Methods:The real‐time imaging system during the PBFT was simulated to acquire the tomographic image of the prompt gamma ray from treated tumor by the proton boron reaction, using Monte Carlo simulation (MCNPX). We acquired percentage depth dose (PDD) of the proton beam in the water phantom including the boron uptake region (BUR), the energy spectra of the prompt gamma ray and tomographic image which can show treated tumor regions. The prompt gamma ray image was reconstructed using maximum likelihood estimation maximization (MLEM) reconstruction algorithm with 64 projections. In addition, in order to evaluate the reconstructed image, the image profiles between BURs were extracted from the image.Results:In the PDD results, the Bragg‐peak was amplified definitely when the proton's maximum dose level was located at the BUR. This amplification is based on the generation of alpha particles. In addition, the prompt gamma ray peak of 719 keV was observed from the energy spectrum. Through the previous process, the tomographic image of prompt gamma ray from the BUR was reconstructed. The line profile was extracted from image including BURs, and it shows high signal‐to‐noise ratio.Conclusion:We confirmed that the real‐time prompt gamma ray image during the PBFT was successfully deducted, and results of quantitative image analysis show good agreement with the original pattern of the BUR. This study first verified the imaging capability of the PBFT‐SPECT system. In conclusion, the PBFT‐SPECT system can realize the treated tumor monitoring during the PBFT.

Application of proton boron fusion reaction to radiation therapy: A Monte Carlo simulation study

Three alpha particles are emitted from the point of reaction between a proton and boron. The alpha particles are effective in inducing the death of a tumor cell. After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton's maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here, we show that the effectiveness of the proton boron fusion therapy was verified using Monte Carlo simulations. We found that a dramatic increase by more than half of the proton's maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton's maximum dose point was located within the boron uptake region. In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.

Advanced scheme for high-yield laser driven nuclear reactions

The use of a low contrast nanosecond laser pulse with a relatively low intensity (3 × 1016 W cm−2) allowed the enhancing of the yield of induced nuclear reactions in advanced solid targets. In particular the ‘ultraclean’ proton–boron fusion reaction, producing energetic alpha particles without neutron generation, was chosen. A spatially well-defined layer of boron dopants in a hydrogen-enriched silicon substrate was used as a target. A combination of the specific target composition and the laser pulse temporal shape allowed the enhancing of the yield of alpha particles up to 109 per steradian. This result can be ascribed to the interaction of the long-laser pre-pulse with the target and to the optimal target geometry and composition.

Etch pit investigation of free electron concentration controlled 4H-SiC

Etch pits were investigated using the molten KOH selective etching method to examine dependence of etch pit shape and size on free electron concentration. The free electron concentrations of highly doped 4H-silicon carbide (SiC) were controlled by proton irradiation and thermal annealing, which was confirmed by a frequency shift in the LO-phonon–plasmon-coupled (LOPC) mode on micro-Raman spectroscopy. The proton irradiated sample with 5×1015cm−2 fluence and an intrinsic semi-insulating sample showed clearly classified etch pits but different ratios of threading screw dislocation (TSD) and threading edge dislocation (TED) sizes. Easily classified TEDs and TSDs on proton irradiated 4H-SiC were restored as highly doped 4H-SiC after thermal annealing due to the recovered carrier concentrations. The etched surface of proton irradiated 4H-SiC and boron implanted SiC showed different surface conditions after activation.

Simulations of effective heating in heavy-ion beam-fusion: High density plasmas in plasma focus devices

In order to understand the heating process during proton–boron 11 ( P – B 11 ) fusion in a high density pinched plasma, we investigate the coalescence of two current loops, consisting of two ion species (protons, boron), using an electromagnetic relativistic particle-in-cell code. We found that the boron and protons can be heated up to energies of respectively MeV and 400 keV, in the direction perpendicular to the current. The electron temperature in the x- and y-direction is approximately 100 keV. The heating mechanism is due to the generation of transverse electric fields by the spacial charge separation of the two ion species. The plasma is confined near to the core of pinched filament by a 180 million gauss magnetic field. We found that the ratio between the output fusion power density and the initial input energy density is approximately 330 without considering the energy losses. The real gain can be calculated from the ratio between the fusion power density and the Bremsstrahlung power density, which is about 1.6. We conclude that P – B 11 fusion using a high density plasma in a plasma focus device is achievable.

Current practices and future directions of therapeutic strategy in glioblastoma: Survival benefit and indication of BNCT

Since 1998, we are performing clinical studies on treatment of GBM using conventional fractionated photon radiation therapy (CRT), proton beam therapy (PBT) or boron neutron capture therapy (BNCT). We investigated whether these radiation modalities improves the survival of patients with GBM. Sixty-eight cases of newly diagnosed GBM have been treated in our institution. After surgery, radiation therapy was performed using CRT with a dose of 60.0–61.2 Gy ( n=36), hyperfractionated PBT concomitant with fractionated photon irradiation with a total dose of 96.6 Gy ( n=17), or a single fraction of BNCT ( n=15). In PBT, the surrounding volume of 2 cm from main tumor mass and the volume of perifocal edema were irradiated at dose of 75.6 and 60 Gy, respectively. The median OS time of the case series of BNCT for GBM has been reported as 13–20.7 M. In this study, the median OS and median time to MR change (TTM) for all patients were 25.7 and 11.9 M, respectively. The 1- and 2-year survival rates were 85.7% and 45.5%, respectively. On the other hand, in the patients who underwent CRT and ACNU-based chemotherapy, OS and 2-year survival rate were 14.2 M and 17.9%, respectively. In the patients who underwent high-dose PBT, OS and 2-year survival rate were 21.3 M and 38.5%, respectively. The present small case series of selected patients showed survival benefit after BNCT. The comparison using previously reported prognostic factor-based classifications suggest that outcome of BNCT in terms of survival appeared to have non-inferiority compared to the standard therapy. With respect to the case series as a high-dose radiation trial, the outcome (OS: 9.5–25 M) of previously reported may still be comparable to that of BNCT. Randomized trials of comparably selected patients are required to demonstrate conclusively that prolonged survival is a result of this tumor-selective radiotherapy.

Fusion energy in degenerate plasmas

In inertial confinement fusion (ICF), a high density, low temperature plasma can be obtained during the compression phase, so minimizing the energy needed for compression. If the final temperature reached is low enough, the electrons of the plasma can be degenerate. In this case, bremsstrahlung emission is strongly suppressed and ignition temperature becomes lower than in classical plasmas, which offers a new design window for ICF. Fusion ignition can then be triggered by an additional energy beam. The main difficulties to produce degenerate plasmas are the compression energy and the compression performance needed for it. Besides that, the low specific heat of degenerate electrons (as compared to classical values) is also a problem because of the rapid heating of the plasma. The main contribution of the Letter is to show that the plasma degeneracy lowers the ignition temperature for DT plasmas, but it does not increase the target energy gain. Some numerical results are given on that. In the case of proton–boron 11 plasmas, the densities have to be extremely high in order to reduce the ignition temperature, but even so the energy gains remain rather low.

Material activation observation on the Tore Supra Tokamak

Radioactive isotopes are produced in Tokamaks that use deuterium plasmas. Although only produced in small quantities, their study is of major interest, first for the safe operation of these devices, and second to forecast what can be expected in larger future machines. Analysis performed on the Tore Supra Tokamak has shown that three main processes are involved in the production of these radioactive elements: the capture of the neutrons produced by the plasma, photo-nuclear reactions caused by runaway electrons and proton–boron fusion reaction, which produces the radio-nuclide Be 7. On intermediate size machines, such as Tore Supra, the observed activities and dose rates are too low to justify any remote handling operation. A threshold can be defined in the neutron production for the limit between hands-on and remote maintenance, which is found around 10 20 neutrons per year, or 100 MJ of D–D fusion energy.