Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice.

The space radiation environment includes helium (4He) ions that may impact brain function. As little is known about the effects of exposures to 4He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation with 4He ions (250 MeV/n; linear energy transfer (LET) = 1.6 keV/μm; 0, 21, 42 or 168 cGy). Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. 4He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2) in the cortex. There was an effect of radiation on apolipoprotein E (apoE) levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued fear conditioning tests. Taken together, the results indicate that some aspects of cognitive performance are altered in male mice exposed to 4He ions, but that the response is task-dependent. Furthermore, the sensitive doses can vary within each task in a non-linear fashion. This highlights the importance of assessing the cognitive and behavioral effects of charged particle exposure with a variety of assays and at multiple doses, given the possibility that lower doses may be more damaging due to the absence of induced compensatory mechanisms at higher doses.

Helium Ion Microscope Fabrication Causing Changes in the Structure and Mechanical Behavior of Silicon Micropillars.

Silicon is used as a prominent case to demonstrate the dramatic effects of helium ion microscope nanofabrication. Structurally, a submicrometer Si pillar can turn completely amorphous at He+ doses typically used for micromachining, forming nanobubbles at higher doses. In terms of mechanical properties, the flow stress decreases markedly with increasing dosage, and the softened amorphous Si exhibits spread-out plastic flow.

Development and benchmarking of a dose rate engine for raster-scanned FLASH helium ions.

BACKGROUND: Radiotherapy with charged particles at high dose and ultra-high dose rate (uHDR) is a promising technique to further increase the therapeutic index of patient treatments. Dose rate is a key quantity to predict the so-called FLASH effect at uHDR settings. However, recent works introduced varying calculation models to report dose rate, which is susceptible to the delivery method, scanning path (in active beam delivery) and beam intensity. PURPOSE: This work introduces an analytical dose rate calculation engine for raster scanned charged particle beams that is able to predict dose rate from the irradiation plan and recorded beam intensity. The importance of standardized dose rate calculation methods is explored here. METHODS: Dose is obtained with an analytical pencil beam algorithm, using pre-calculated databases for integrated depth dose distributions and lateral penumbra. Dose rate is then calculated by combining dose information with the respective particle fluence (i.e., time information) using three dose-rate-calculation models (mean, instantaneous, and threshold-based). Dose rate predictions for all three models are compared to uHDR helium ion beam (145.7 MeV/u, range in water of approximatively 14.6 cm) measurements performed at the Heidelberg Ion Beam Therapy Center (HIT) with a diamond-detector prototype. Three scanning patterns (scanned or snake-like) and four field sizes are used to investigate the dose rate differences. RESULTS: Dose rate measurements were in good agreement with in-silico generated distributions using the here introduced engine. Relative differences in dose rate were below 10% for varying depths in water, from 2.3 to 14.8 cm, as well as laterally in a near Bragg peak area. In the entrance channel of the helium ion beam, dose rates were predicted within 7% on average for varying irradiated field sizes and scanning patterns. Large differences in absolute dose rate values were observed for varying calculation methods. For raster-scanned irradiations, the deviation between mean and threshold-based dose rate at the investigated point was found to increase with the field size up to 63% for a 10 mm × 10 mm field, while no significant differences were observed for snake-like scanning paths. CONCLUSIONS: This work introduces the first dose rate calculation engine benchmarked to instantaneous dose rate, enabling dose rate predictions for physical and biophysical experiments. Dose rate is greatly affected by varying particle fluence, scanning path, and calculation method, highlighting the need for a consensus among the FLASH community on how to calculate and report dose rate in the future. The here introduced engine could help provide the necessary details for the analysis of the sparing effect and uHDR conditions.

Radiation Effects in Tungsten and Tungsten-Copper Alloys Treated with Compression Plasma Flows and Irradiated with He Ions.

The paper presents the results of studying the structure and phase state of tungsten and tungsten-copper alloy after pulsed action of compression plasma flows and irradiation with helium ions. The compression plasma flows were used to modify the surface layer of tungsten, as well as to create an alloy based on tungsten and copper. Using scanning electron microscopy and X-ray structural analysis, the formation of radiation defects on the tungsten surface was detected in the form of local areas of exfoliation and destruction, which begin to form at helium ion irradiation doses of 2 × 1017 cm-2. It is shown that preliminary plasma treatment of the surface in the melting mode leads to the complete disappearance of surface radiation defects up to a dose of 2 × 1017 cm-2, which may be associated with the formation of a fine-crystalline grain structure, the intergranular boundaries of which serve as effective sinks for primary radiation defects.

In vitro validation of helium ion irradiations as a function of linear energy transfer in radioresistant human malignant cells.

PURPOSE: Based on considerable interest to enlarge the experimental database of radioresistant cells after their irradiation with helium ions, HTB140, MCF-7 and HTB177 human malignant cells are exposed to helium ion beams having different linear energy transfer (LET). MATERIALS AND METHODS: The cells are irradiated along the widened 62 MeV/u helium ion Bragg peak, providing LET of 4.9, 9.8, 23.4 and 36.8 keV/µm. Numerical simulations with the Geant4 toolkit are used for the experimental design. Cell survival is evaluated and compared with reference γ-rays. DNA double strand breaks are assessed via γ-H2AX foci. RESULTS: With the increase of LET, surviving fractions at 2 Gy decrease, while RBE (2 Gy, γ) gradually increase. For HTB140 cells, above the dose of 4 Gy, a slight saturation of survival is observed while the increase of RBE (2 Gy, γ) remains unaffected. With the increase of LET the increase of γ-H2AX foci is revealed at 0.5 h after irradiation. There is no significant difference in the number of foci between the cell lines for the same LET. From 0.5 to 24 h, the number of foci drops reaching its residual level. For each time point, there are small differences in DNA DSB among the three cell lines. CONCLUSION: Analyses of data acquired for the three cell lines irradiated by helium ions, having different LET, reveal high elimination capacity and creation of a large number of DNA DSB with respect to γ-rays, and are between those reported for protons and carbon ions.

Improving the Adhesion of Multi-Walled Carbon Nanotubes to Titanium by Irradiating the Interface with He+ Ions: Atomic Force Microscopy and X-ray Photoelectron Spectroscopy Study.

A complex study of the adhesion of multi-walled carbon nanotubes to a titanium surface, depending on the modes of irradiation with He+ ions of the "MWCNT/Ti" system, was conducted using atomic force microscopy and X-ray photoelectron spectroscopy. A quantitative assessment of the adhesion force at the interface, performed using atomic force microscopy, demonstrated its significant increase as a result of treatment of the "MWCNT/Ti" system with a beam of helium ions. The nature of the chemical bonding between multi-walled carbon nanotubes and the surface of the titanium substrate, which causes this increase in the adhesion of nanotubes to titanium as a result of ion irradiation, was investigated by X-ray photoelectron spectroscopy. It was established that this bonding is the result of the formation of chemical C-O-Ti bonds between titanium and carbon atoms with the participation of oxygen atoms of oxygen-containing functional groups, which are localized on defects in the nanotube walls formed during ion irradiation. It is significant that there are no signs of direct bonding between titanium and carbon atoms.

Development and benchmarking of the first fast Monte Carlo engine for helium ion beam dose calculation: MonteRay.

BACKGROUND: Monte Carlo (MC) simulations are considered the gold-standard for accuracy in radiotherapy dose calculation; however, general purpose MC engines are computationally demanding and require long runtimes. For this reason, several groups have recently developed fast MC systems dedicated mainly to photon and proton external beam therapy, affording both speed and accuracy. PURPOSE: To support research and clinical activities at the Heidelberg Ion-beam Therapy Center (HIT) with actively scanned helium ion beams, this work presents MonteRay, the first fast MC dose calculation engine for helium ion therapy. METHODS: MonteRay is a CPU MC dose calculation engine written in C++, capable of simulating therapeutic proton and helium ion beams. In this work, development steps taken to include helium ion beams in MonteRay are presented. A detailed description of the newly implemented physics models for helium ions, for example, for multiple coulomb scattering and inelastic nuclear interactions, is provided. MonteRay dose computations of helium ion beams are evaluated using a comprehensive validation dataset, including measurements of spread-out Bragg peaks (SOBPs) with varying penetration depths/field sizes, measurements with an anthropomorphic phantom and FLUKA simulations of a patient plan. Improvement in computational speed is demonstrated in comparison against reference FLUKA simulations. RESULTS: Dosimetric comparisons between MonteRay and measurements demonstrated good agreement. Comparing SOBPs at 5, 12.5, and 20 cm depth, mean absolute percent dose differences were 0.7%, 0.7%, and 1.4%, respectively. Comparison against measurements behind an anthropomorphic head phantom revealed mean absolute dose differences of about 1.2% (FLUKA: 1.5%) with per voxel errors ranging from -4.5% to 4.1% (FLUKA: -6% to 3%). Computed global 3%/3 mm 3D-gamma passing rates of ∼99% were achieved, exceeding those previously reported for an analytical dose engine. Comparisons against FLUKA simulations for a patient plan revealed local 2%/2 mm 3D-gamma passing rates of 98%. Compared to FLUKA in voxelized geometries, MonteRay saw run-time reductions ranging from 20× to 60×, depending on the beam's energy. CONCLUSIONS: MonteRay, the first fast MC engine dedicated to helium ion therapy, has been successfully developed with a focus on both speed and accuracy. Validations against dosimetric measurements in homogeneous and heterogeneous scenarios and FLUKA MC calculations have proven the validity of the physical models implemented. Timing comparisons have shown significant speedups between 20 and 60 when compared to FLUKA, making MonteRay viable for clinical routine. MonteRay will support research and clinical practice at HIT, for example, TPS development, validation and treatment design for upcoming clinical trials for raster-scanned helium ion therapy.

Radiotherapy with Helium Ions Has the Potential to Improve Both Endocrine and Neurocognitive Outcome in Pediatric Patients with Ependymoma.

Ependymomas are the third most-frequent pediatric brain tumors. To prevent local recurrence, the resection site should be irradiated. Compared to photon radiation treatment, proton therapy often achieves even better results regarding target coverage and organ-sparing. Due to their physical properties, helium ions could further reduce side effects, providing better protection of healthy tissue despite similar target coverage. In our in silico study, 15 pediatric ependymoma patients were considered. All patients underwent adjuvant radiotherapeutic treatment with active-scanned protons at Heidelberg Ion Beam Therapy Center (HIT). Both helium ion and highly conformal IMRT plans were calculated to evaluate the potential dosimetric advantage of ion beam therapy compared to the current state-of-the-art photon-based treatments. To estimate the potential clinical benefit of helium ions, normal tissue complication probabilities (NTCP) were calculated. Target coverage was comparable in all three modalities. As expected, the integral dose absorbed by healthy brain tissue could be significantly reduced with protons by up to -48% vs. IMRT. Even compared to actively scanned protons, relative dose reductions for critical neuronal structures of up to another -39% were achieved when using helium ions. The dose distribution of helium ions is significantly superior when compared to proton therapy and IMRT due to the improved sparing of OAR. In fact, previous studies could clearly demonstrate that the dosimetric advantage of protons translates into a measurable clinical benefit for pediatric patients with brain tumors. Given the dose-response relationship of critical organs at risk combined with NTCP calculation, the results of our study provide a strong rationale that the use of helium ions has the potential to even further reduce the risk for treatment related sequelae.

Human mesenchymal stromal cells maintain their stem cell traits after high-LET particle irradiation - Potential implications for particle radiotherapy and manned space missions.

The influence of high-linear energy transfer (LET) particle radiation on the functionalities of mesenchymal stromal cells (MSCs) is largely unknown. Here, we analyzed the effects of proton (1H), helium (4He), carbon (12C) and oxygen (16O) ions on human bone marrow-MSCs. Cell cycle distribution and apoptosis induction were examined by flow cytometry, and DNA damage was quantified using γH2AX immunofluorescence and Western blots. Relative biological effectiveness values of MSCs amounted to 1.0-1.1 for 1H, 1.7-2.3 for 4He, 2.9-3.4 for 12C and 2.6-3.3 for 16O. Particle radiation did not alter the MSCs' characteristic surface marker pattern, and MSCs maintained their multi-lineage differentiation capabilities. Apoptosis rates ranged low for all radiation modalities. At 24 h after irradiation, particle radiation-induced ATM and CHK2 phosphorylation as well as γH2AX foci numbers returned to baseline levels. The resistance of human MSCs to high-LET irradiation suggests that MSCs remain functional after exposure to moderate doses of particle radiation as seen in normal tissues after particle radiotherapy or during manned space flights. In the future, in vivo models focusing on long-term consequences of particle irradiation on the bone marrow niche and MSCs are needed.

The accuracy of helium ion CT based particle therapy range prediction: an experimental study comparing different particle and x-ray CT modalities.

This work provides a quantitative assessment of helium ion CT (HeCT) for particle therapy treatment planning. For the first time, HeCT based range prediction accuracy in a heterogeneous tissue phantom is presented and compared to single-energy x-ray CT (SECT), dual-energy x-ray CT (DECT) and proton CT (pCT). HeCT and pCT scans were acquired using the US pCT collaboration prototype particle CT scanner at the Heidelberg Ion-Beam Therapy Center. SECT and DECT scans were done with a Siemens Somatom Definition Flash and converted to RSP. A Catphan CTP404 module was used to study the RSP accuracy of HeCT. A custom phantom of 20 cm diameter containing several tissue equivalent plastic cubes was used to assess the spatial resolution of HeCT and compare it to DECT. A clinically realistic heterogeneous tissue phantom was constructed using cranial slices from a pig head placed inside a cylindrical phantom (ø150 mm). A proton beam (84.67 mm range) depth-dose measurement was acquired using a stack of GafchromicTM EBT-XD films in a central dosimetry insert in the phantom. CT scans of the phantom were acquired with each modality, and proton depth-dose estimates were simulated based on the reconstructions. The RSP accuracy of HeCT for the plastic phantom was found to be 0.3 ± 0.1%. The spatial resolution for HeCT of the cube phantom was 5.9 ± 0.4 lp cm-1for central, and 7.6 ± 0.8 lp cm-1for peripheral cubes, comparable to DECT spatial resolution (7.7 ± 0.3 lp cm-1and 7.4 ± 0.2 lp cm-1, respectively). For the pig head, HeCT, SECT, DECT and pCT predicted range accuracy was 0.25%, -1.40%, -0.45% and 0.39%, respectively. In this study, HeCT acquired with a prototype system showed potential for particle therapy treatment planning, offering RSP accuracy, spatial resolution, and range prediction accuracy comparable to that achieved with a commercial DECT scanner. Still, technical improvements of HeCT are needed to enable clinical implementation.

DOSE COEFFICIENTS OF MESH-TYPE ICRP REFERENCE COMPUTATIONAL PHANTOMS FOR EXTERNAL EXPOSURES OF NEUTRONS, PROTONS, AND HELIUM IONS.

To overcome inherent limitations of the Voxel-type Reference Computational Phantoms (VRCPs) due to the limited voxel resolutions and the nature of voxel geometry, the International Commission on Radiological Protection (ICRP) has developed the adult male and female Mesh-type Reference Computational Phantoms (MRCPs). We previously used the MRCPs to calculate a complete set of dose coefficients (DCs) for idealized external exposures of photons and electrons (Yeom et al. NET in press). In the present study, we extended the previous study to include additional radiation particles (neutrons, protons, and helium ions) into the DC library by conducing Monte Carlo radiation transport simulations with the Geant4 code. The MRPC-based DCs were compared with the existing reference DCs of ICRP Publication 116 which are based on the ICRP VRCPs to investigate impact of the new mesh-type reference phantoms on the DC values. We found that the MRCPs generally provide DCs of organ/tissue doses and effective doses similar to those from the VRCPs for penetrating radiations (uncharged particles), whereas significant DC differences were observed for weakly penetrating radiations (charged particles) mainly due to the improved representation of the detailed anatomical structures in the MRCPs over the VRCPs.

Effects of Six Sequential Charged Particle Beams on Behavioral and Cognitive Performance in B6D2F1 Female and Male Mice.

The radiation environment astronauts are exposed to in deep space includes galactic cosmic radiation (GCR) with different proportions of all naturally occurring ions. To assist NASA with assessment of risk to the brain following exposure to a mixture of ions broadly representative of the GCR, we assessed the behavioral and cognitive performance of female and male C57BL/6J × DBA2/J F1 (B6D2F1) mice two months following rapidly delivered, sequential 6 beam irradiation with protons (1 GeV, LET = 0.24 keV, 50%), 4He ions (250 MeV/n, LET = 1.6 keV/µm, 20%), 16O ions (250 MeV/n, LET = 25 keV/µm 7.5%), 28Si ions (263 MeV/n, LET = 78 keV/µm, 7.5%), 48Ti ions (1 GeV/n, LET = 107 keV/µm, 7.5%), and 56Fe ions (1 GeV/n, LET = 151 keV/µm, 7.5%) at 0, 25, 50, or 200 cGy) at 4-6 months of age. When the activity over 3 days of open field habituation was analyzed in female mice, those irradiated with 50 cGy moved less and spent less time in the center than sham-irradiated mice. Sham-irradiated female mice and those irradiated with 25 cGy showed object recognition. However, female mice exposed to 50 or 200 cGy did not show object recognition. When fear memory was assessed in passive avoidance tests, sham-irradiated mice and mice irradiated with 25 cGy showed memory retention while mice exposed to 50 or 200 cGy did not. The effects of radiation passive avoidance memory retention were not sex-dependent. There was no effect of radiation on depressive-like behavior in the forced swim test. There was a trend toward an effect of radiation on BDNF levels in the cortex of males, but not for females, with higher levels in male mice irradiated with 50 cGy than sham-irradiated. Finally, sequential 6-ion irradiation impacted the composition of the gut microbiome in a sex-dependent fashion. Taxa were uncovered whose relative abundance in the gut was associated with the radiation dose received. Thus, exposure to sequential six-beam irradiation significantly affects behavioral and cognitive performance and the gut microbiome.

Biophysical modeling and experimental validation of relative biological effectiveness (RBE) for 4He ion beam therapy.

BACKGROUND: Helium (4He) ion beam therapy provides favorable biophysical characteristics compared to currently administered particle therapies, i.e., reduced lateral scattering and enhanced biological damage to deep-seated tumors like heavier ions, while simultaneously lessened particle fragmentation in distal healthy tissues as observed with lighter protons. Despite these biophysical advantages, raster-scanning 4He ion therapy remains poorly explored e.g., clinical translational is hampered by the lack of reliable and robust estimation of physical and radiobiological uncertainties. Therefore, prior to the upcoming 4He ion therapy program at the Heidelberg Ion-beam Therapy Center (HIT), we aimed to characterize the biophysical phenomena of 4He ion beams and various aspects of the associated models for clinical integration. METHODS: Characterization of biological effect for 4He ion beams was performed in both homogenous and patient-like treatment scenarios using innovative models for estimation of relative biological effectiveness (RBE) in silico and their experimental validation using clonogenic cell survival as the gold-standard surrogate. Towards translation of RBE models in patients, the first GPU-based treatment planning system (non-commercial) for raster-scanning 4He ion beams was devised in-house (FRoG). RESULTS: Our data indicate clinically relevant uncertainty of ±5-10% across different model simulations, highlighting their distinct biological and computational methodologies. The in vitro surrogate for highly radio-resistant tissues presented large RBE variability and uncertainty within the clinical dose range. CONCLUSIONS: Existing phenomenological and mechanistic/biophysical models were successfully integrated and validated in both Monte Carlo and GPU-accelerated analytical platforms against in vitro experiments, and tested using pristine peaks and clinical fields in highly radio-resistant tissues where models exhibit the greatest RBE uncertainty. Together, these efforts mark an important step towards clinical translation of raster-scanning 4He ion beam therapy to the clinic.

Improving the dose distributions in minibeam radiation therapy: Helium ions vs protons.

PURPOSE: Charged particle minibeam radiation therapy is a novel therapeutic strategy aiming at reducing the normal tissue complication probability by combining the normal tissue sparing of submillimetric, spatially fractionated beams with the improved dose deposition of ions. This may allow a safe dose escalation in the tumor and other targets. In particular, proton minibeam radiation therapy has already proven a remarkable increase of the therapeutic index for high-grade gliomas in animal experiments. The reduced multiple Coulomb scattering and nuclear fragmentation of helium ions compared to protons and heavier ions, respectively, make them a good candidate for minibeam radiation therapy (MBRT). The purpose of the present work was to perform a comprehensive dosimetric comparison between proton and helium MBRT (pMBRT and HeMBRT). METHODS: Proton and helium minibeams of the same range (7.7 cm) have been simulated in a water phantom and in CT images of an anonymized human head. The Monte Carlo simulation toolkit GATE v8.0 was used. Different beam sizes (1 and 3 mm) and multiple beam spacings were evaluated. Depth dose curves, lateral profiles, peak-to-valley dose ratios (PVDR), and dose-averaged linear energy transfer (LET) were assessed. Furthermore, evaluations of the secondary products in the valley regions were carried out and a basic example of a treatment plan in pMBRT and HeMBRT was considered. RESULTS: Compared to protons, helium ions yield a significantly improved Bragg-peak-to-entrance dose ratio (BEDR) and higher PVDR at equal minibeam spacing. At the same time, due to the lower lateral scattering, dose homogenization in the target becomes more difficult for helium ions than for protons. To achieve a homogeneous target dose in HeMBRT, the minibeam spacing has to be reduced which in turn decreases the PVDR in normal tissues to values lower than those observed for protons. LET maps show up to 20%-30% higher values in the valley regions than in the peak regions for all evaluated cases. Helium ions lead to higher LET than protons at all depths, including the entrance region. However, this is compensated by a lower dose at shallow depths thanks to the improved BEDR of HeMBRT. CONCLUSIONS: Helium ions might offer a good choice for minibeam radiation therapy. They provide a more pronounced spatial fractionation than protons without the possible drawbacks linked to nuclear fragmentation of heavier ions. However, biological experiments are needed to evaluate whether the higher dose heterogeneity in the target volume in HeMBRT would still lead to an efficient tumor control, as in the case of pMBRT.

Proton and helium ion radiotherapy for meningioma tumors: a Monte Carlo-based treatment planning comparison.

BACKGROUND: Due to their favorable physical and biological properties, helium ion beams are increasingly considered a promising alternative to proton beams for radiation therapy. Hence, this work aims at comparing in-silico the treatment of brain and ocular meningiomas with protons and helium ions, using for the first time a dedicated Monte Carlo (MC) based treatment planning engine (MCTP) thoroughly validated both in terms of physical and biological models. METHODS: Starting from clinical treatment plans of four patients undergoing proton therapy with a fixed relative biological effectiveness (RBE) of 1.1 and a fraction dose of 1.8 Gy(RBE), new treatment plans were optimized with MCTP for both protons (with variable and fixed RBE) and helium ions (with variable RBE) under the same constraints derived from the initial clinical plans. The resulting dose distributions were dosimetrically compared in terms of dose volume histograms (DVH) parameters for the planning target volume (PTV) and the organs at risk (OARs), as well as dose difference maps. RESULTS: In most of the cases helium ion plans provided a similar PTV coverage as protons with a consistent trend of superior OAR sparing. The latter finding was attributed to the ability of helium ions to offer sharper distal and lateral dose fall-offs, as well as a more favorable differential RBE variation in target and normal tissue. CONCLUSIONS: Although more studies are needed to investigate the clinical potential of helium ions for different tumour entities, the results of this work based on an experimentally validated MC engine support the promise of this modality with state-of-the-art pencil beam scanning delivery, especially in case of tumours growing in close proximity of multiple OARs such as meningiomas.

Morphological and Functional Modifications of Optical Thin Films for Space Applications Irradiated with Low-Energy Helium Ions.

Future space missions will operate in increasingly hostile environments, such as those in low-perihelion solar orbits and Jovian magnetosphere. This exploration involves the selection of optical materials and components resistant to the environmental agents. The conditions in space are reproduced on ground through the use of ion accelerators. The effects of He particles coming from the solar wind impinging on a gold thin film have been systematically investigated, considering absorbed doses compatible with the duration of the European Space Agency Solar Orbiter mission. Structural and morphological changes have been proved to be dependent not only on the dose but also on the irradiation flux. A predictive model of the variation of thin film reflectance has been developed for the case of lower flux irradiation. The results are discussed regarding reliability and limitations of laboratory testing. The outcomes are important to address the procedures for the space qualification tests of optical coatings.