Low-energy Neutrons Research Articles

The New Generation of Particle Therapy Focused on Boron Element (Boron Neutron Capture Therapy; BNCT) -The World's First Approved BNCT Drug

Boron neutron capture therapy (BNCT) is a type of radiation therapy and a new modality for cancer treatment. The radiation used in BNCT is a very low energy neutron called a "thermal neutron", and unlike other radiation, it has no effect on treating cancer on its own. However, when this neutron collides with boron-10 (10B), which is a stable isotope of boron, fission occurs into a high-energy helium nucleus (α-particle) and a lithium nucleus. Moreover, the effect of this fission reaction is limited to a range of about 10 μm, which corresponds to the approximate size of one cell. Therefore, the basic principle of BNCT is "cell-selective" radiation therapy that only damages cells that have taken up 10B present in the area irradiated with thermal neutrons. For the practical application of BNCT, it is indispensable to generate a boron drug capable of selectively accumulating 10B in cancer cells. We have successfully developed a boron drug for BNCT targeting amino acid transporters. We have obtained manufacturing and marketing approval for the world's first boron drug for BNCT, Steboronine® intravenous drip bag 9000 mg/300 mL (March 25, 2020), for indications of locally unresectable recurrent or advanced unresectable head and neck cancer. This uses Borofalan (10B), which is 10B introduced into l-phenylalanine, as a drug substance. This review describes the progress of drug development and future prospects of boron drugs for BNCT.

Quantifying spatial resolution in a fast neutron radiography system

Neutron imaging is a powerful nondestructive examination modality that has been employed in various applications. Fast neutrons provide advantages over lower energy neutrons, such as examining thicker samples and inducing negligible activation and transmutations. However, fast neutrons interact mostly via elastic scattering with both the neutron detector and the object, causing degradation in spatial resolution. This study explores the quantification of spatial resolution caused by the testing target itself and suggests proper candidate materials for characterizing spatial resolution in terms of modulation transfer function. Knife-edge radiographs of 3 mm, 6 mm, and 5 cm thick Tantalum (Ta) foils, and a 2.54 cm Tungsten (W) cube were acquired using a CCD-based imaging system and a Polyvinyl Toluene (PVT) scintillator at the Ohio State Research Reactor (OSURR)’s fast neutron beam facility. The spatial resolutions calculated were 195 ± 20μm, 224 ± 22μm, 248 ± 25μm, and 435 ± 44μm for 3 mm, 6 mm, and 5 cm Ta foils, and 2.54 cm W cube, respectively. The results showed a worsening spatial resolution with increasing target thickness. Simulations and calculations estimate that elastic scattering kinematics between neutrons and protons in the PVT medium also limits spatial resolution, and it sets a lower limit of ∼44μm on the spatial resolution for 2 MeV neutrons.

Assessment of secondary neutrons in particle therapy by Monte Carlo simulations

Objective. The purpose of this study is to estimate the energy and angular distribution of secondary neutrons inside a phantom in hadron therapy, which will support decisions on detector choice and experimental setup design for in-phantom secondary neutron measurements. Approach. Dedicated Monte Carlo simulations were implemented, considering clinically relevant energies of protons, helium and carbon ions. Since scored quantities can vary from different radiation transport models, the codes FLUKA, TOPAS and MCNP were used. The geometry of an active scanning beam delivery system for heavy ion treatment was implemented, and simulations of pristine and spread-out Bragg peaks were carried out. Previous studies, focused on specific ion types or single energies, are qualitatively in agreement with the obtained results. Main results. The secondary neutrons energy distributions present a continuous spectrum with two peaks, one centred on the thermal/epithermal region, and one on the high-energy region, with the most probable energy ranging from 19 up to 240 MeV, depending on the ion type and its initial energy. The simulations show that the secondary neutron energies may exceed 400 MeV and, therefore, suitable neutron detectors for this energy range shall be needed. Additionally, the angular distribution of the low energy neutrons is quite isotropic, whereas the fast/relativistic neutrons are mainly scattered in the down-stream direction. Significance. It would be possible to minimize the influence of the heavy ions when measuring the neutron-generated recoil protons by selecting appropriate measurement positions within the phantom. Although there are discrepancies among the three Monte Carlo codes, the results agree qualitatively and in order of magnitude, being sufficient to support further investigations with the ultimate goal of mapping the secondary neutron doses both in- and out-of-field in hadrontherapy. The obtained secondary neutron spectra are available as supplementary material.

Using effective temperature as a measure of the thermal scattering law uncertainties to UOX fuel calculations from room temperature to 80°C

The effective temperature Teff is an important physical quantity in neutronic calculations. It can be introduced in a Free Gas Model to approximate crystal lattice effects in the Doppler broadening of the neutron cross sections. In the last decade, a few research works proposed analytical or Monte-Carlo perturbation schemes for estimating uncertainties in neutronic calculations due to thermal scattering laws. However, the relationship between the reported results with Teff was not discussed. The present work aims to show how the effective temperature can measure the impact of the thermal scattering law uncertainties on neutronic calculations. The discussions are illustrated with Monte-Carlo calculations performed with the TRIPOLI-4® code on the MISTRAL-1 benchmark carried out in the EOLE facility of CEA Cadarache (France) from room temperature to 354 K (80°C). The uncertainty analysis is focused on the impact of the thermal scattering laws of H2O and UO2 on the neutron multiplication factor keff for UOX fuel moderated by water. When using the H2O and UO2 candidate files for the JEFF-4 library, the variation range of Teff leads to a keff uncertainty of 2.3 pcm/K, on average. In the temperature range investigated in this work, Teff uncertainties of ±20 K for H2O and ±10 K for UO2 give uncertainties on the multiplication factor that remains close to ±50 pcm. Such a low uncertainty confirms the improved accuracy achieved on the modelisation of the latest thermal scattering laws of interest for light water reactors. In the future evaluated nuclear data libraries, uncertainty budget analysis associated with the low neutron energy scattering process will be a marginal contribution compared to the capture process.

High-sensitive colour indicator of absorbed dose of epithermal neutrons radiation

In our study, the high-sensitivity colour indicator of the absorbed dose of radiation of epithermal neutrons with energy 0 to 10 keV for dosimetry of low-energy neutrons was developed. We had been developed an indicator on the basis of the dye solution of arsenazo III and gadopentetic acid, allowing precisely define of absorbed dose in the range 2 to 103 Gy. The properties of arsenazo III as metallic indicator, which changes colour after binding of free ions of metals, were used. Colour of the indicator solution before irradiation and after it is stable enough in time at storage in the dark, at artificial illumination or at scattered sunlight. The developed indicator, consisting of a solution of arsenazo III and gadopentetic acid, allows estimating the absorbed dose of epithermal neutron irradiation with good accuracy and reduces the error of measurement related to changing colour of dye under the influence of other factors (light, temperature etc.) Dosimeter is tissue-equivalent and possesses a high-sensitivity neutron radiation due to the content of gadolinium in solution, which has great neutron capture cross-section. The developed dosimeter persists spectrophotometric characteristics after irradiaion within few weeks that allows to use it for measurement of the absorbed dose, both in real time mode and with the delayed measurement within few weeks.

Study of neutron capture reaction-induced displacement damage cross section and KERMA factor

Radiative neutron capture reaction is generally the main reaction inducing atomic displacements and nuclear heating for low incident neutron energy, even though its contribution to total displacement damage is quite limited in general. The multiple photon emission without identifying the correlations between photons leads the calculated recoil energy to be uncertain. The present work recommends a formula for computing the average recoil energy by assuming the isotropic photon emissions, while the upper limit has been implemented in some codes. The recommended method is identical to the one used in NJOY if the photon distributions are in MF12-MF15, whereas the photon yield is not included in NJOY when photon yields are included in MF6. The presently recommended method for KERMA factor calculation is numerically validated against Tripoli-4 neutron-photon coupling Monte Carlo simulations. Due to the negligible contribution of neutron kick, the correction of the kinematic KERMA factor is quasi-identical to that of photon kick by the yield Y (or Y2 for upper limit). This conclusion is however not applicable for displacement damage calculation if the maximum photon kick is close to the threshold displacement energy. In such a case, detailed consideration of photon emission cascades rather than approximate analytical formulae should be included for accurate calculation of neutron capture reaction-induced damage cross section.

A Boron Delivery Antibody (BDA) with Boronated Specific Residues: New Perspectives in Boron Neutron Capture Therapy from an In Silico Investigation.

Boron Neutron Capture Therapy (BNCT) is a tumor cell-selective radiotherapy based on a nuclear reaction that occurs when the isotope boron-10 (10B) is radiated by low-energy thermal neutrons or epithermal neutrons, triggering a nuclear fission response and enabling a selective administration of irradiation to cells. Hence, we need to create novel delivery agents containing 10B with high tumor selectivity, but also exhibiting low intrinsic toxicity, fast clearance from normal tissue and blood, and no pharmaceutical effects. In the past, boronated monoclonal antibodies have been proposed using large boron-containing molecules or dendrimers, but with no investigations in relation to maintaining antibody specificity and structural and functional features. This work aims at improving the potential of monoclonal antibodies applied to BNCT therapy, identifying in silico the best native residues suitable to be substituted with a boronated one, carefully evaluating the effect of boronation on the 3D structure of the monoclonal antibody and on its binding affinity. A boronated monoclonal antibody was thus generated for specific 10B delivery. In this context, we have developed a case study of Boron Delivery Antibody Identification Pipeline, which has been tested on cetuximab. Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor used in the treatment of metastatic colorectal cancer, metastatic non-small cell lung cancer, and head and neck cancer.

Formulation of Boron Encapsulated Smart Nanocapsules for Targeted Drug Delivery to the Brain

Drug delivery through the Blood–Brain Barrier (BBB) represents a significant challenge. Despite the current strategies to circumvent the BBB, nanotechnology offers unprecedented opportunities for combining selective delivery, improved bioavailability, drug protection, and enhanced pharmacokinetics profiles. Chitosan nanocarriers allow for a more efficacious strategy at the cellular and sub-cellular levels. Boron Neutron Capture Therapy (BNCT) is a targeted chemo-radiotherapeutic technique that allows the selective depletion of cancer cells by means of selective tagging of cancer cells with 10B, followed by irradiation with low-energy neutrons. Consequently, the combination of a polymer-based nanodelivery system enclosing an effective BNCT pharmacophore can potentially lead to the selective delivery of the load to cancer cells beyond the BBB. In this work, synthesized novel boronated agents based on carborane-functionalized Delocalized Lipophilic Cations (DLCs) are assessed for safety and selective targeting of tumour cells. The compounds are then encapsulated in nanocarriers constituted by chitosan to promote permeability through the BBB. Additionally, chitosan was used in combination with polypyrrole to form a smart composite nanocapsule, which is expected to release its drug load with variations in pH. Results indicate the achievement of more selective boron delivery to cells via carboranyl DLCs. Finally, preliminary cell studies indicate no toxicity was detected in chitosan nanocapsules, further enhancing its viability as a potential delivery vehicle in the BNCT of brain tumours.

Spectrometer design of low energy neutrons for boron neutron capture therapy

We designed a neutron spectrometer to measure low-energy neutron beam for boron neutron capture therapy (BNCT) without exchanging thicknesses of neutron moderator. The spectrometer consists of a boron carbide block as a neutron moderator and nine thin neutron silicon sensors with variable detection efficiency. Using the Monte Carlo technique, we simulated the spectrometer’s neutron energy response functions. It represented sharp rise in the response functions with various lower limits of neutron energies distributed over a wide range of neutron energy from a thermal energy to a few 100 keV. The lower limit of neutron energy was dependent on a depth in the boron carbide block. By applying thicker enriched 6LiF neutron converter and covering the deep positioned neutron sensors with polyethylene plates, neutron detection efficiencies were increased to be able to measure the BNCT neutron beam in a short time.

SIMULATION OF NEUTRON RESPONSE FUNCTIONS OF SILICON SENSOR APPLIED TO REAL-TIME PERSONAL ALBEDO NEUTRON DOSEMETER IN THE ENERGY RANGE BETWEEN 0.01EV AND 10KEV.

Neutron response functions of a silicon sensor, which is applied to a new real-time personal albedo neutron dosemeter, have been simulated for low energy neutrons from 0.01eV to 10keV using the Monte Carlo technique. The angular neutron response functions were obtained by multiplying simulated neutron energy spectra crossing the neutron sensor and the cross-section of the 6Li(n,t)4He reaction. The neutron response functions have been closed to the dose conversion coefficient of personal doses, Hp(10) recommended by the International Commission on Radiological Protection by selecting neutrons incident from angles of 105° to 180° with respect to an axis perpendicular to an acrylic phantom surface. From these simulation results, the neutron energy response function has been improved by shielding the sensor with cadmium box without a face toward the phantom. The neutron sensor provides a good conformance to the Hp(10) conversion coefficients within 15% for low energy neutrons.

On the eptihermal neutron energy limit for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT): Study and impact of new energy limits.

Accelerator-Based Boron Neutron Capture Therapy is a radiotherapy based on compact accelerator neutron sources requiring an epithermal neutron field for tumour irradiations. Neutrons of 10 keV are considered as the maximum optimised energy to treat deep-seated tumours. We investigated, by means of Monte Carlo simulations, the epithermal range from 10 eV to 10 keV in order to optimise the maximum epithermal neutron energy as a function of the tumour depth. A Snyder head phantom was simulated and mono-energetic neutrons with 4 different incident energies were used: 10 eV, 100 eV, 1 keV and 10 keV. 10B capture rates and absorbed dose composition on every tissue were calculated to describe and compare the effects of lowering the maximum epithermal energy. The Therapeutic Gain (TG) was estimated considering the whole brain volume. For tumours seated at 4 cm depth, 10 eV, 100 eV and 1 keV neutrons provided respectively 54%, 36% and 18% increase on the TG compared to 10 keV neutrons. Neutrons with energies between 10 eV and 1 keV provided higher TG than 10 keV neutrons for tumours seated up to 6.4 cm depth inside the head. The size of the tumour does not change these results. Using lower epithermal energy neutrons for AB-BNCT tumour irradiation could improve treatment efficacy, delivering more therapeutic dose while reducing the dose in healthy tissues. This could lead to new Beam Shape Assembly designs in order to optimise the BNCT irradiation.

Compact ultracold neutron source concept for low-energy accelerator-driven neutron sources

The concept of a small-scale, pulsed-proton accelerator-based compact ultracold neutron (UCN) source is presented. The essential idea of the compact UCN source is to enclose a volume of superfluid \(^{4}\hbox {He}\) converter with a supercold moderator in the vicinity of a low-radiation neutron production target from (p, n) reactions. The supercold moderator should possess an ability to produce cold neutron flux with a peak brightness near the single-phonon excitation band of the superfluid \(^{4}\hbox {He}\) converter, thereby augmenting the UCN production in the compact UCN source even with very low intensity of neutron brightness. The performance of the compact UCN source is studied in terms of the UCN production and thermal load in the UCN converter. With the proposed concept of the compact UCN source, a UCN production rate of \(P_\mathrm{{UCN}}=80\,\hbox {UCN/cm}^{3}/\hbox {s}\) in the UCN converter could be obtained while maintaining thermal load of the superfluid \(^{4}\hbox {He}\) and its container at a level of \(22~\hbox {mW}\). This study shows that the compact UCN source can produce a high enough density of UCNs at a small-scale, low-energy, pulsed-proton beam facility with reduced efforts on the cooling and radiation protection.

Boron rich nanotube drug carrier system is suited for boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a two-step therapeutic process that utilizes Boron-10 in combination with low energy neutrons to effectively eliminate targeted cells. This therapy is primarily used for difficult to treat head and neck carcinomas; recent advances have expanded this method to cover a broader range of carcinomas. However, it still remains an unconventional therapy where one of the barriers for widespread adoption is the adequate delivery of Boron-10 to target cells. In an effort to address this issue, we examined a unique nanoparticle drug delivery system based on a highly stable and modular proteinaceous nanotube. Initially, we confirmed and structurally analyzed ortho-carborane binding into the cavities of the nanotube. The high ratio of Boron to proteinaceous mass and excellent thermal stability suggest the nanotube system as a suitable candidate for drug delivery into cancer cells. The full physicochemical characterization of the nanotube then allowed for further mechanistic molecular dynamic studies of the ortho-carborane uptake and calculations of corresponding energy profiles. Visualization of the binding event highlighted the protein dynamics and the importance of the interhelical channel formation to allow movement of the boron cluster into the nanotube. Additionally, cell assays showed that the nanotube can penetrate outer membranes of cancer cells followed by localization around the cells’ nuclei. This work uses an integrative approach combining experimental data from structural, molecular dynamics simulations and biological experiments to thoroughly present an alternative drug delivery device for BNCT which offers additional benefits over current delivery methods.

Composition variations of major lunar elements: Possible impacts on lunar albedo spectra

Understanding the elemental composition of the lunar regolith is important for expanding our knowledge of the history and geology of the Moon. Several methods have already been used to achieve this purpose, including direct analysis of lunar samples and satellite spectroscopy. Since computer modeling is important for processing the collected data, and for the preparation of future missions, this work uses Monte Carlo simulations to study the radiation emitted by the lunar surface, via nuclear interactions between the incident radiation environment and lunar regolith, to characterize the elemental composition of the Moon. When high energy primary galactic cosmic rays and solar energetic particles strike the lunar surface, they either scatter to free space or produce secondaries through cascades of interactions, some of which escape the lunar surface. Both the scattered primaries and escaping secondaries constitute the lunar “albedo” particles studied in this paper. The purpose of this work is to determine whether enhancing the abundances of any of the major lunar elements (O, Na, Mg, Al, Si, Ca, Ti, Mn, and Fe) causes an observable difference in the spectra of albedo particles emitted by the regolith. The model-based results herein show that charged albedo particles do not display any significant differences for any element. They also confirm that low-energy neutrons and gamma rays produce observable variations with different lunar compositions. This provides evidence that albedo neutrons and/or gamma rays, and not protons, are the source of the variations observed in a recent map of the lunar albedo, generated by the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument.

Spin dynamics study and experimental realization of tunable single-ion anisotropy in multiferroic Ba2CoGe2O7 under external magnetic fields

We report a spin-wave study on multiferroic ${\mathrm{Ba}}_{2}{\mathrm{CoGe}}_{2}{\mathrm{O}}_{7}$ under magnetic fields up to 12 T using low-energy inelastic neutron scattering. In-plane transverse $({T}_{1})$ spin-wave modes are highly dispersive along $(h00)$ and rather flat but strong in intensity along $(30l)$. In addition, two dispersive electromagnon modes have been observed around 3.5 meV. Dispersion of the out-of-plane transverse modes $({T}_{2})$ under fields reveals that the single-ion anisotropy constant decreases with increasing magnetic field, which is consistent with the linear spin-wave theory. Our results imply that the field-dependent single-ion anisotropy plays a crucial role in determining the characteristics of ${T}_{2}$ and electromagnon modes in the three-dimensional anisotropic spin-wave spectrum.

Characterizing Energetic Dependence of Low-Energy Neutron-Induced SEU and MCU and Its Influence on Estimation of Terrestrial SER in 65-nm Bulk SRAM

Characterizing low-energy neutrons (<; 10 MeV)-induced single-event upsets (SEUs) and multiple cells upsets (MCUs) is essential to validate the current standard for terrestrial soft error rate (SER) and investigate its enhancement. Following our preliminary analysis on the contribution of the low-energy neutrons to the total terrestrial SER at the nominal operating voltage of 1.0 V by Liao et al. (2020), this article newly presents and analyzes the data measured at the low operating voltage of 0.4 V. The dependence of SEU cross section on the neutron energy is similar between the operating voltages of 0.4 and 1.0 V, including onset energy of around 6 MeV. The existence of MCUs at 4.1-MeV neutrons was also confirmed at both the operating voltages. Based on the measurement, we approximate the dependence of SEU and MCU cross sections as Weibull functions of the neutron energy. The terrestrial SER of SEUs and MCUs was calculated by folding the Weibull function and the flux spectrum. The calculated result indicates that the SER originating from the low-energy neutrons is less than 6% in the terrestrial environment at New York and Tokyo City. We confirm that disregarding the flux of neutrons below 10 MeV in the acceleration factor calculation at accelerated neutron tests, which follows the current standard defined in JESD89, could give a reasonable SER estimation accuracy for both SEUs and MCUs. On the other hand, for covering the beams having an extremely high proportion of low-energy neutrons, considering the flux of neutrons above 6 MeV would be an option for better SER estimation.

Tests of fundamental quantum mechanics and dark interactions with low-energy neutrons

Among the known particles, the neutron takes a special position, as it provides experimental access to all four fundamental forces and a wide range of hypothetical interactions. Despite being unstable, free neutrons live long enough to be used as test particles in interferometric, spectroscopic, and scattering experiments probing low-energy scales. As was already recognized in the 1970s, fundamental concepts of quantum mechanics can be tested in neutron interferometry using silicon perfect-single-crystals. Besides allowing for tests of uncertainty relations, Bell inequalities and alike, neutrons offer the opportunity to observe the effects of gravity and hypothetical dark forces acting on extended matter wave functions. Such tests gain importance in the light of recent discoveries of inconsistencies in our understanding of cosmology as well as the incompatibility between quantum mechanics and general relativity. Experiments with low-energy neutrons are thus indispensable tools for probing fundamental physics and represent a complementary approach to colliders. In this review we discuss the history and experimental methods used at this low-energy frontier of physics and collect bounds and limits on quantum mechanical relations and dark energy interactions.

SINQ—Performance of the New Neutron Delivery System

The Swiss spallation neutron source SINQ at Paul Scherrer Institute (PSI) has been in operation since 1996 using an optical guide system to transport low-energy neutrons from the source to the neutron beam lines. Clear signs of degradation in the guide system motivated us to redesign all neutron guides, which were then replaced in 2019–2020. All instruments received new tailored guides and SINQ operation was resumed in July 2020. Neutron flux measurements before and after the upgrade show that the expected instrument-dependent flux gain of a factor 2–10 was achieved. Furthermore, the fast-neutron background in the guide hall could be suppressed with an improved shielding in the guide bunker. The upgrade was completed with a slight delay due to the corona pandemic and in full compliance with the financial budget.

Real-time nuclear activation detectors for measuring neutron angular distributions at the National Ignition Facility (invited).

The Real Time Nuclear Activation Detector (RTNAD) array at NIF measures the distribution of 14MeV neutrons emitted by deuterium-tritium (DT) fueled inertial confinement fusion implosions. The uniformity of the neutron distribution is an important indication of implosion symmetry and DT shell integrity. The array consists of 48 LaBr3(Ce) crystal gamma-ray spectrometers mounted outside the NIF target chamber, which continuously monitor the slow decay of the 909 keV gamma-ray line from activated 89Zr located in Zr cups surrounding each crystal. The measured decay rate dramatically increases during a DT implosion in proportion to the number of 14MeV neutrons striking each Zr cup. The neutrons produce activated 89Zr through an (n, 2n) reaction on 90Zr, which is insensitive to low energy neutrons. The neutron flux along the detector line-of-sight at shot time is determined by extrapolating the fitted 909 keV decay curve back to shot time. Automatic analysis algorithms were developed to handle the non-stop data stream. The large number of detectors and the high statistical accuracy of the array enable the spherical harmonic modes of the neutron angular distribution to be measured up to L ≤ 4 to provide a better understanding of implosion dynamics. In addition, these data combined with measurements of the down-scattered neutrons can be used to derive fuel areal density distributions. This paper will describe the RTNAD hardware and analysis procedures.

Detection of Kardar–Parisi–Zhang hydrodynamics in a quantum Heisenberg spin-1/2 chain

Classical hydrodynamics is a remarkably versatile description of the coarse-grained behavior of many-particle systems once local equilibrium has been established. The form of the hydrodynamical equations is determined primarily by the conserved quantities present in a system. Some quantum spin chains are known to possess, even in the simplest cases, a greatly expanded set of conservation laws, and recent work suggests that these laws strongly modify collective spin dynamics even at high temperature. Here, by probing the dynamical exponent of the one-dimensional Heisenberg antiferromagnet KCuF$_3$ with neutron scattering, we find evidence that the spin dynamics are well described by the dynamical exponent $z=3/2$, which is consistent with the recent theoretical conjecture that the dynamics of this quantum system are described by the Kardar-Parisi-Zhang universality class. This observation shows that low-energy inelastic neutron scattering at moderate temperatures can reveal the details of emergent quantum fluid properties like those arising in non-Fermi liquids in higher dimensions.