Ne Ion Beam Research Articles

Biological dose optimization incorporating intra-tumoural cellular radiosensitivity heterogeneity in ion-beam therapy treatment planning

Objective. Treatment plans of ion-beam therapy have been made under an assumption that all cancer cells within a tumour equally respond to a given radiation dose. However, an intra-tumoural cellular radiosensitivity heterogeneity clearly exists, and it may lead to an overestimation of therapeutic effects of the radiation. The purpose of this study is to develop a biological model that can incorporate the radiosensitivity heterogeneity into biological optimization for ion-beam therapy treatment planning. Approach. The radiosensitivity heterogeneity was modeled as the variability of a cell-line specific parameter in the microdosimetric kinetic model following the gamma distribution. To validate the developed intra-tumoural-radiosensitivity-heterogeneity-incorporated microdosimetric kinetic (HMK) model, a treatment plan with H-ion beams was made for a chordoma case, assuming a radiosensitivity heterogeneous region within the tumour. To investigate the effects of the radiosensitivity heterogeneity on the biological effectiveness of H-, He-, C-, O-, and Ne-ion beams, the relative biological effectiveness (RBE)-weighted dose distributions were planned for a cuboid target with the stated ion beams without considering the heterogeneity. The planned dose distributions were then recalculated by taking the heterogeneity into account. Main results. The cell survival fraction and corresponding RBE-weighted dose were formulated based on the HMK model. The first derivative of the RBE-weighted dose distribution was also derived, which is needed for fast biological optimization. For the patient plan, the biological optimization increased the dose to the radiosensitivity heterogeneous region to compensate for the heterogeneity-induced reduction in biological effectiveness of the H-ion beams. The reduction in biological effectiveness due to the heterogeneity was pronounced for low linear energy transfer (LET) beams but moderate for high-LET beams. The RBE-weighted dose in the cuboid target decreased by 7.6% for the H-ion beam, while it decreased by just 1.4% for the Ne-ion beam. Significance. Optimal treatment plans that consider intra-tumoural cellular radiosensitivity heterogeneity can be devised using the HMK model.

Nanostructuring, fractal characterization and wettability of ion irradiated Au thin films and their thickness effect

This study proposes a method for modifying the wettability of Au thin films of thicknesses 5 nm and 10 nm on Si substrates using 8 keV Ne ion beam irradiation at different fluences, thereby enabling surface wettability adjustment at the nano-scale and its thickness dependence. This advancement would be highly beneficial for applications such as high-resolution printing and nano-biotechnology. The contact angle of the irradiated region for the 5 nm thin film changed from hydrophobic to hydrophilic with increasing ion dosage, whereas for the 10 nm thin film, it changed from hydrophilic to hydrophobic under the same conditions. Fractal analysis was performed on pristine and ion beam modified surfaces to investigate the underlying nano-structuring process, with reported values for average roughness (Ra), Hurst exponent (H), fractal dimension (Df), contact angle (CA), and wettability at different ion dosages. Atomic Force Microscopy and Rutherford Backscattering Spectroscopy were used to examine surface roughness and depth profile. The process of sputtering becomes crucial when the ion range approaches the thickness of thin films, with the sputter yield showing dependence on the thickness of thin films at different ion fluence levels. Monte Carlo simulations SRIM/TRIM and TRIDYN were used for comparison with the experimental results, with TRIDYN taking into account dynamic changes in the target's morphology and composition.

Spot-scanning hadron arc (SHArc) therapy: A proof of concept using single- and multi-ion strategies with helium, carbon, oxygen, and neon ions.

To present particle arc therapy treatments using single and multi-ion therapy optimization strategies with helium (4 He), carbon (12 C), oxygen (16 O), and neon (20 Ne) ion beams. An optimization procedure and workflow were devised for spot-scanning hadron arc therapy (SHArc) treatment planning in the PRECISE (PaRticle thErapy using single and Combined Ion optimization StratEgies) treatment planning system (TPS). Physical and biological beam models were developed for helium, carbon, oxygen, and neon ions via FLUKA MC simulation. SHArc treatments were optimized using both single-ion (12 C, 16 O, or 20 Ne) and multi-ion therapy (16 O+4 He or 20 Ne+4 He) applying variable relative biological effectiveness (RBE) modeling using a modified microdosimetric kinetic model (mMKM) with (α/β)x values of 2, 5, and 3.1Gy, respectively, for glioblastoma, pancreatic adenocarcinoma, and prostate adenocarcinoma patient cases. Dose, effective dose, linear energy transfer (LET), and RBE were computed with the GPU-accelerated dose engine FRoG and dosimetric/biophysical attributes were evaluated in the context of conventional particle and photon-based therapies (e.g., volumetric modulated arc therapy [VMAT]). All SHArc plans met the target optimization goals (3GyRBE) and demonstrated increased target conformity and substantially lower low-dose bath to surrounding normal tissues than VMAT. SHArc plans using a singleion species (12 C, 16 O, or 20 Ne) exhibited favorable LET distributions with the highest-LET components centralized in the target volume, with values ranging from ∼80-170keV/μm, ∼130-220keV/μm, and ∼180-350keV/μm for 12 C, 16 O, or 20 Ne, respectively, exceeding mean target LET of conventional particle therapy (12 C:∼55, 16 O:∼75 20 Ne:∼95keV/μm). Multi-ion therapy with SHArc delivery (SHArcMIT ) provided a similar level of target LET enhancement as SHArc compared to conventional planning, however, with additional benefits of homogenous physical dose and RBE distributions. Here, we demonstrate that arc delivery of light and heavy ion beams, using either a single-ion species (12 C, 16 O, or 20 Ne) or combining two ions in a single fraction (16 O+4 He or 20 Ne+4 He) affords enhanced physical and biological distributions (e.g., LET) compared with conventional delivery with photons or particle beams. SHArc marks the first single- and multi-ion arc therapy treatment optimization approach using light and heavy ions.

Identification and characterization of inheritable structural variations induced by ion beam radiations in rice.

High energy ion beams are effective physical mutagens for mutation induction in plants. Due to their high linear energy transfer (LET) property, they are known to generate single nucleotide variations (SNVs) and insertion/deletions (InDels, <50 bp) as well as structural variations (SVs). However, due to the technical difficulties to identify SVs, studies on ion beam induced SVs by genome sequencing have so far been limited in numbers and inadequate in nature, and knowledge of SVs is scarce with regards to their characteristics. In the present study, we identified and validated SVs in six M4 plants (designated as Ar_50, Ar_100, C_150, C_200, Ne_50 and Ne_100 according to ion beam types and irradiation doses), two each induced by argon (40Ar18+), carbon (12C6+) and neon (20Ne10+) ion beams and performed in depth analyses of their characteristics. In total, 22 SVs were identified and validated, consisting of 11 deletions, 1 duplication, and 4 intra-chromosomal and 6 inter-chromosomal translocations. There were several SVs larger than 1 kbp. The SVs were distributed across the whole genome with an aggregation with SNVs and InDels only in the Ne_50 mutants. An enrichment of a 11-bp wide G-rich DNA motif 'GAAGGWGGRGG' was identified around the SV breakpoints. Three mechanisms might be involved in the SV formation, i.e., the expansion of tandem repeats, transposable element insertion, and non-allelic homologous recombination. Put together, the present study provides a preliminary view of SVs induced by Ar, C and Ne ion beam radiations, and as a pilot study, it contributes to our understanding of how SVs might form after ion beam irradiation in rice.

EVALUATION OF NEUTRON AMBIENT DOSE EQUIVALENT IN INTENSITY-MODULATED COMPOSITE PARTICLE THERAPY.

Several studies have reported benefits derived from cancer treatment using various heavy-ion beams. Based on these reports, the National Institutes for Quantum and Radiological Science and Technology started developing intensity-modulated composite particle therapy (IMPACT) using He-, C-, O-, and Ne-ions. In ion beam therapy, nuclear interactions in the beamline devices or patient produce secondary neutrons. This study evaluated the characteristics of secondary neutrons in IMPACT. Neutron ambient dose equivalents were measured using WENDI-II. Measurements were performed under realistic case scenarios using He-, C-, O- and Ne-ion beams. Moreover, neutron ambient dose equivalents generated by He-, C-, O- and Ne-ion beams were compared with neutron ambient dose equivalents in proton therapy. No differences exist in the distance-dependence even when the primary ions are different. Neutrons generated by primary ion beams of high atomic numbers tend to emit forward. Moreover, in contrast with proton therapy, IMPACT can reduce neutron doses.

Investigation of NanoSQUIDs Fabricated with a Range of Focused Ion Beam Sources

SQUIDs (Superconducting Quantum Interference Devices) are macroscopic quantum devices capable of detecting and measuring a wide variety of physical parameters with unprecedented sensitivity. SQUIDs based on nanobridge weak links have shown increasing promise for quantum information and quantum sensing applications such as single spin detection. Focussed ion beam etched nanobridges have properties which can enhance nanoSQUID device performance but are often limited in terms of their non-hysteretic operating temperature range. Here we describe measurements of FIB-milled nanobridges, as single weak links or in nanoSQUIDs, made using either Ga, Xe or Ne ion beam sources. Their properties as a function of temperature, bias current, magnetic field and microwave power are measured and modelled according to a range of superconductivity models, as a means for improved understanding of the associated nanobridge parameters. We further propose techniques to extend the non-hysteretic operating temperature range of the devices.

Mutagenic Effect of Three Ion Beams on Rice and Identification of Heritable Mutations by Whole Genome Sequencing.

High-energy ion beams are known to be an effective and unique type of physical mutagen in plants. However, no study on the mutagenic effect of argon (Ar) ion beam radiation on rice has been reported. Genome-wide studies on induced mutations are important to comprehend their characteristics for establishing knowledge-based protocols for mutation induction and breeding, which are still very limited in rice. The present study aimed to investigate the mutagenic effect of three ion beams, i.e., Ar, carbon (C) and neon (Ne) on rice and identify and characterize heritable induced mutations by the whole genome sequencing of six M4 plants. Dose-dependent damage effects were observed on M1 plants, which were developed from ion beam irradiated dry seeds of two indica (LH15, T23) and two japonica (DS551, DS48) rice lines. High frequencies of chlorophyll-deficient seedlings and male-sterile plants were observed in all M2 populations (up to ~30% on M1 plant basis); plants from the seeds of different panicles of a common M1 plant appeared to have different mutations; the whole genome-sequencing demonstrated that there were 236–453 mutations in each of the six M4 plants, including single base substitutions (SBSs) and small insertion/deletions (InDels), with the number of SBSs ~ 4–8 times greater than that of InDels; SBS and InDel mutations were distributed across different genomic regions of all 12 chromosomes, however, only a small number of mutations (0–6) were present in exonic regions that might have an impact on gene function. In summary, the present study demonstrates that Ar, C and Ne ion beam radiation are all effective for mutation induction in rice and has revealed at the genome level the characteristics of the mutations induced by the three ion beams. The findings are of importance to the efficient use of ion beam radiation for the generation and utilization of mutants in rice.

Effect of plasma and beam parameters on focal dimensions in micrometer charged particle optics: Enhanced nonlinear demagnification below the Debye length

Detailed experiments and computer simulations employing two beam computational tools commonly used for benchmarking ion beam optics, AXCEL-INP and SIMION, are carried out to investigate the dependence of focal dimensions FD (length and image size) of ion beams extracted from a compact electromagnetic wave driven plasma source. The effect of plasma parameters, such as space potential VP, Bohm velocity vB, and the associated initial kinetic energy Ei, electron Te and ion temperatures Ti, ion mass M, ion current density Ji, and beam related parameters such as beam energy EB, plasma and beam limiter (BL) electrode aperture sizes, and potential applied to lenses (EL1 and EL2), on the FD are investigated. Variation of the focal length fl with vB, VP, and Ei indicates that fl increases with the increase in these parameters; however, it decreases with EB. fl is found to decrease with M and is independent of the BL aperture size; however, it is found to increase with extraction voltage V1 (EL1). Two different theoretical models to estimate the focal length of the combined lens system are developed, and the estimated values of fl are found to agree reasonably well with the experimental and simulation results. The sharpness of focus characterized by the beam angle at the focal point is determined for Ar, Kr, and Ne ion beams. A remarkable feature of nonlinear demagnification in plasma based beams is observed with significant enhancement when the plasma electrode aperture size is reduced to below the Debye length.

Biological effects of ion beam irradiation on perennial gentian and apple.

The development of new varieties of perennial plants generally requires lengthy and laborious procedures. In this study, we used ion beam irradiation mutagenesis in an attempt to accelerate the breeding process for perennial plants. We evaluated the biological effects of five ion beam sources (carbon, neon, argon, silicon, and iron) and neutron irradiation on Japanese gentian and apple. These treatments were applied at the National Institute of Radiological Sciences (NIRS) using the Heavy Ion Medical Accelerator in Chiba (HIMAC) and the Neutron-exposure Accelerator System for Biological Effect Experiments (NASBEE). Biological effects were observed in in vitro gentian plants after irradiation with ion beams at <10 Gy, whereas apple trees were less sensitive to ion beam irradiation. The growth of gentians in vitro was repressed by 3 Gy neutron irradiation, while that of grafted apple trees was not affected by 4 Gy neutron irradiation. During in vitro proliferation, seven pink-flowered lines were obtained from originally blue-flowered gentian after C and Ne ion beam irradiation treatments. Genomic and reverse transcription-PCR analyses of these lines suggested that the mutations occurred in the genomic region containing F3'5'H (encoding flavonoid 3',5'-hydroxylase). These results provide useful information for the mutagenesis and breeding of gentian, apple, and other perennial plants.

The effect of bombardment with neutralized neon ions on the roughness of a fused silica and beryllium surface

The effect of Ne ion beam etching on the roughness of materials for optical substrates—fused silica and beryllium—is studied. It is shown that the treatment of a fused silica surface by neutralized Ne ions with an energy of 400–800 eV makes it possible to smooth roughnessed in the range of higher spatial frequencies of 3–63 μm–1 at an incidence angle of 0°–30°. For beryllium, the possibility of smoothing the surface roughness at an ion energy of 400 eV is found.

Deuterium retention in recrystallized tungsten irradiated with simultaneous deuterium–neon ion beams

Although neon has been considered for impurity seeding in the ITER tungsten divertor, there have been few studies on its effects on deuterium retention in tungsten. We investigate the effects of simultaneous (SIM) D-2.5% Ne ion beam irradiation on D retention in recrystallized W at 300–700K, with 500eV/D+ and 1keV/Ne+ ion energies, and compare to the effects of SIM D-3% He irradiation with 500eV/He+. Thermal desorption spectroscopy (TDS) up to 1473K, nuclear reaction analysis (NRA), and elastic recoil detection analysis (ERDA) are used to measure D, He, and Ne in the specimens. Ne is more effective than He at reducing D retention for higher exposure temperatures, even though less Ne is retained than He. He appears to modify the D TDS spectra peak shapes more than Ne, while He addition leads to increased D trapping within a few µm depth according to NRA. D retention may be reduced due to Ne sputtering, as well as a near surface interaction with Ne which blocks D diffusion past the implantation range and leads to higher surface re-emission.

Low energy Ne ion beam induced-modifications of magnetic properties in MnAs thin films

Investigations of the complex behavior of the magnetization of manganese arsenide thin films due to defects induced by irradiation of slow heavy ions are presented. In addition to the thermal hysteresis suppression already highlighted in Trassinelli et al (2014 Appl. Phys. Lett. 104 081906), we report here on new local magnetic features recorded by a magnetic force microscope at different temperatures close to the characteristic sample phase transition. Complementary measurements of the global magnetization in different conditions (applied magnetic field and temperatures) enable the film characterization to be completed. The obtained results suggest that the ion bombardment produces regions where the local mechanical constraints are significantly different from the average, promoting the local presence of magneto-structural phases far from the equilibrium. These regions could be responsible for the thermal hysteresis suppression previously reported, irradiation-induced defects acting as seeds in the phase transition.

Evaluation of Neon Focused Ion Beam Milling for TEM Sample Preparation

Gallium-based focused ion beams generated from liquid-metal sources are widely used in micromachining and sample preparation for transmission electron microscopy, with well-known drawbacks such as sample damage and contamination. In this work, an alternative (neon) focused ion beam generated by a gas field-ionization source is evaluated for the preparation of electron-transparent specimens. To do so, electron-transparent sections of Si and an Al alloy are prepared with both Ga and Ne ion beams for direct comparison. Diffraction-contrast imaging and energy dispersive x-ray spectroscopy are used to evaluate the relative damage induced by the two beams, and cross-sections of milled trenches are examined to compare the implantation depth with theoretical predictions from Monte Carlo simulations. Our results show that for the beam voltages and materials systems investigated, Ne ion beam milling does not significantly reduce the focused ion beam induced artefacts. However, the Ne ion beam does enable more precise milling and may be of interest in cases where Ga contamination cannot be tolerated.

The Physics of Spin-Transfer Torque Switching in Magnetic Tunneling Junctions in Sub-10 nm Size Range

The spin-transfer torque magnetic tunneling junction (MTJ) technology may pave a way to a universal memory paradigm. MTJ devices with perpendicular magnetic anisotropy have the potential to have high thermal stability, high tunneling magnetoresistance, and low critical current for energy-efficient current-induced magnetization switching. Using devices fabricated through focused ion beam etching with Ga- and Ne-ion beams, this paper aimed to understand the size dependence of the current/voltage characteristics in the sub-10 nm range. The switching current density drastically dropped around 1 MA/cm $^{\mathrm { {2}}}$ as the device size was reduced below 10 nm. A stability of over 22 kT measured for a 5 nm device indicated a significantly reduced spin relaxation time.

Evaluation of neon focused ion beam milling for TEM sample preparation.

Gallium-based focused ion beams generated from liquid-metal sources are widely used in micromachining and sample preparation for transmission electron microscopy, with well-known drawbacks such as sample damage and contamination. In this work, an alternative (neon) focused ion beam generated by a gas field-ionization source is evaluated for the preparation of electron-transparent specimens. To do so, electron-transparent sections of Si and an Al alloy are prepared with both Ga and Ne ion beams for direct comparison. Diffraction-contrast imaging and energy dispersive x-ray spectroscopy are used to evaluate the relative damage induced by the two beams, and cross-sections of milled trenches are examined to compare the implantation depth with theoretical predictions from Monte Carlo simulations. Our results show that for the beam voltages and materials systems investigated, Ne ion beam milling does not significantly reduce the focused ion beam induced artefacts. However, the Ne ion beam does enable more precise milling and may be of interest in cases where Ga contamination cannot be tolerated.

In situ TEM investigation of amorphization and recrystallization of Zr(Fe,Cr,Nb)2 precipitates under Ne ion irradiation

The behavior of the Zr(Fe,Cr,Nb)2 precipitate in a China-brand Zr–Sn–Nb–Fe–Cr alloy under a 500 keV Ne ion beam irradiation and post heating were studied by in-situ transmission electron microscopy (TEM). It is found that the Zr(Fe,Cr,Nb)2 precipitate with the hexagonal close packed (hcp) structure is the major secondary phase particle (SPP) in this zirconium alloy. At the temperature of 310 °C, the precipitate starts to be amorphized after having been irradiated to 0.5 displacement per atom (dpa). The critical irradiation dose for the precipitate to be completely amorphized is 1.0 dpa. The amorphized Zr(Fe,Cr,Nb)2 precipitate starts to be recrystallized when it was heated up to 600 °C. The temperature for the recrystallization of the amorphized Zr(Fe,Cr,Nb)2 precipitate is determined to be between 450 °C and 600 °C. Instead of forming large single grain crystals, some nanocrystals that have the same crystal structure to that of the precipitate before being amorphized were formed during the recrystallization.

Corrections: in the article “Inactivation of Aerobic and Hypoxic Cells from Three Different Cell Lines by Accelerated3He-,12C- and20Ne-Ion Beams” by Furusawaet al.

Corrections: in the article “Inactivation of Aerobic and Hypoxic Cells from Three Different Cell Lines by Accelerated³He-,¹²C- and²⁰Ne-Ion Beams” by Furusawa<i>et al</i>.

Effect of Ion-Beam Gas Species on Magnetic Softness in Fe-Co Thin-Film Etching

The effect of ion-beam (IB) gas species on magnetic softness in etching of Fe-Co thin films was evaluated by means of in situ magnetoresistance (MR) measurements. A 25-nm Fe70Co30 film was etched by Ar, Ne, or Kr IB, and successive MR measurements were performed in the same IB etching chamber. The IB etching and MR measurements were performed alternately in vacuum; therefore, it was possible to evaluate the etching gas effect on magnetic softness of the single sample in nanometer scale without the need to deposit a capping layer. Higher energy IB of 600 V showed larger gas species dependence of the deterioration than lower energy of 250 V. In the case of 600-V etching, Kr IB showed better softness compared with those of Ar and Ne IBs, whose etching surface was the smoothest among the etching conditions. Structural analysis revealed that surface roughness has an important role for magnetic softness and MR ratio in the thinner region of less than about 5 nm.

Experimental evaluation of CaO, SrO and BaO sputtering yields by Ne+ or Xe+ ions

Barrier coating materials used in plasma display panel (PDP) cells strongly affect the discharge voltages. Although magnesium oxide (MgO) is widely used for barrier coating in the current generation of commercial PDP cells, other alkaline earth oxides have been studied as alternatives and indeed some of them are now known to have lower discharge breakdown voltages for PDP cells, which would increase the energy efficiency of the cells. On the other hand, the resistance against physical sputtering is another critical parameter for barrier coating. In this work, sputtering yields of CaO, SrO and BaO by monochromatic Ne or Xe ion beams are obtained experimentally as functions of beam energy in the range 100–300 eV. Despite the large differences in mass among the targets and incident ions, sputtering yields are found to be similar in magnitude among them for a given incident energy.

Effects of heavy-ion beams on chromosomes of common wheat, Triticum aestivum

To investigate the nature of plant chromosomes irradiated by heavy-ion beams, the effects of nitrogen (N) and neon (Ne) ion beams on hexaploid wheat chromosomes were compared with those of X-ray. Chromosome aberrations, such as short, ring and dicentric chromosomes appeared in high frequency. The average numbers of chromosome breaks at LD-50 by irradiation with X-ray, N and Ne ion beams were 32, 20 and 20, respectively. These values may be underestimated because chromosome rearrangement without change in chromosome morphology was not counted. Thus, we subsequently used a wheat line with a pair of extra chromosomes from an alien species ( Leymus racemosus) and observed the fate of the irradiated marker chromosomes by genomic in situ hybridization. This analysis revealed that 50 Gy of neon beam induced about eight times more breaks than those induced by X-ray. This result suggests that heavy-ion beams induce chromosome rearrangement in high frequency rather than loss of gene function. This suggests further that most of the novel mutations produced by ion beam irradiation, which have been used in plant breeding, may not be caused by ordinary gene disruption but by chromosome rearrangements.