Search Results (536)

This mini-review traces the evolution of axion searches at the CERN Super Proton Synchrotron (SPS), beginning with the early proposal by Guido Barbiellini in 1982 and culminating in the recent advances of the NA62 and NA64 experiments. We discuss the experimental strategies employed in early beam dump searches, the current status of axion and axion-like particle (ALP) searches at the CERN SPS and future directions. This review serves as a tribute to Guido Barbiellini’s scientific legacy and his visionary contributions to this field. Full article

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved. Full article

Cell migration assays provide valuable insights into pathological conditions, such as tumor metastasis and immune cell infiltration, and the regenerative capacity of tissues. In vitro tools commonly used for cell migration studies exploit commercial transwell systems, whose functionalities can be improved through engineering of the pore pattern. In this context, we propose the fabrication of a transwell-like device pursued by combining the proton beam writing (PBW) technique with wet etching onto thin layers of polydimethylsiloxane (PDMS). The resulting transwell-like device incorporates a PDMS membrane with finely controllable pore patterning that was used to study the arrangement and migration behavior of HCMEC/D3 cells, a well-established human brain microvascular endothelial cell model widely used to study vascular maturation in the brain. A comparison between commercial polycarbonate membranes and the PBW-holed membranes highlights the impact of the ordering of the pattern and porosity on cellular growth, self-organization, and transmigration by combining fluorescent microscopy and advanced digital processing. Endothelial cells were found to exhibit distinctive clustering, alignment, and migratory behavior close to the pores of the designed PBW-holed membrane. This is indicative of activation patterns associated with cytoskeletal remodeling, a critical element in the angiogenic process. This study stands up as a novel approach toward the development of more biomimetic barrier models (such as organ-on-chips). Full article

Background/Objectives: Within the range of spread-out Bragg peak (SOBP), LET (linear energy transfer) gradually increases from proton beam entrance point toward the beam exit direction. While it is expected that the change in LET would lead to correspondent change in RBE (relative biological effectiveness) on many human cell lines, the incomplete cell killing due to low LET can result in tumor recurrence. Hence, this study aimed to assess the RBE on different cancer cell lines along low-LET proton SOBP. Methods: The clonogenicity of A549 and Panc-1 cells after irradiation was evaluated for investigating cell radiosensitivity in response to different types of radiation. The isoeffect doses of 6-MV photon and low-LET proton beams that resulted in equivalent cell surviving fractions at proton dose of 2 or 4 Gy were compared. Results: Ratios of α/β of A549 and Panc-1 cells from photon irradiation are 51.69 and −0.7747, respectively; RBE (2 Gy proton SOBP) on A549 and Panc-1 cells are 0.7403 ± 0.3324 and 1.0986 ± 0.3984, respectively. In addition, the change in RBE with proton LET was in a cell-specific and dose-dependent manner (LET-RBE linear correlations: A549 cells [r = 0.4673, p = 0.2430] vs. Panc-1 cells at 4 Gy [r = 0.7085, p = 0.0492]; Panc-1 cells at 2 Gy [r = −0.4123, p = 0.3100] vs. 4 Gy [r = 0.7085, p = 0.0492]). Conclusions: Compared with A549 cells, Panc-1 cells present greater resistance to low-LET proton beams. In addition, currently employed generic RBE value at 1.1 for proton therapy neglected the variation in cell-/tumor-specific radiobiological responses toward different dose levels of proton beams. Full article

In this study, we describe the preparation of carbon dots (CDs) from natural charcoal by laser ablation in a liquid. A continuum wave (CW) laser diode operating at a wavelength of 450 nm, hitting a solid carbon target placed into a biocompatible liquid, constituted of a phosphate-buffered saline (PBS) solution and distilled water, was used for the generation of the CDs suspension. Exploring the practical applications of carbon dots, it was observed that the luminescence of the produced CDs can be used as bioimaging in living organisms, environmental monitoring, chemical analysis, targeted drug delivery, disease diagnosis, therapy, and others. The CDs’ luminescence can be induced by UV irradiation and, as demonstrated in this study, by energetic MeV proton beams. The fluorescence was revealed mainly at 480 nm when UV illuminated the CDs, and also in the region at 514–642 nm when the CDs were irradiated by energetic proton ions. Atomic force microscopy (AFM) of the CD films revealed their spherical shape with a size of about 10 nm. The significance of the manuscript lies in the use of CDs produced by laser ablation exhibiting luminescence under irradiation of an energetic proton beam. Full article

The main objective of proton beam therapy is to precisely irradiate diseased tissue while minimizing damage to healthy cells. For effective treatment, the linear energy transfer (LET) is a key parameter in ensuring the destruction of diseased cells, and both the dose and LET are typically represented as functions of depth. The distribution of dose and LET in the target depends on the beam properties, including beam energy, energy spread, beam size, and beam emittance. The aim of this work is to present the method used to characterize the proton beam properties obtained from the machine employed in the simulation and to determine the dose and dose-averaged LET (LET_d) values, including their peak positions in depth. These results are used to predict the dose and LET_d at different depth positions under experimental conditions. We utilized GEANT4, a Monte Carlo (MC) simulation-based software, to examine the integral depth-dose position and the peak position of the LET_d. The proton source was obtained from a cyclotron accelerator, specifically the Varian ProBeam Compact spot scanning system at King Chulalongkorn Memorial Hospital in Bangkok, Thailand. The system provides proton energies ranging from 70 MeV to 220 MeV. In this study, four proton energies—70 MeV, 100 MeV, 150 MeV, and 220 MeV—were chosen to characterize the beam properties. The 80%–20% distal fall-off obtained from the simulation was used to determine the energy spread for each selected energy by matching the depth-dose peak with the measurement data. The optimal energy spreads were found to be 1.5%, 1.25%, 1%, and 0.5% for proton energies of 70 MeV, 100 MeV, 150 MeV, and 220 MeV, respectively. These energy spreads ensure that the difference in the depth-dose profile is below 1% when comparing the simulated and measured depth-dose profiles. Furthermore, the peak LET_d was found to be approximately 1 mm away from the R₈₀ position, a depth that corresponds to 80% of maximum dose, for each energy. This information can be used to guide the desired LET_d position by utilizing the R₈₀ depth position. Full article

This work presents the experimental results of a wavelet transform denoising algorithm (WTDA) that improves the ionoacoustic signal-to-noise ratio (SNR) and proton range measurement precision. Ionoacoustic detectors exploit the ultrasound signal generated by pulsed proton beams in energy absorbers (water or the human body) to localize the energy deposition with sub-millimeter precision, with interesting applications in beam monitoring during oncological hadron therapy treatments. By improving SNR and measurement precision, the WTDA allows significant reduction of the extra dose necessary for beam characterization. To validate the WTDA’s performance, two scenarios are presented. First, the WTDA was applied to the ionoacoustic signals from a 20 MeV proton beam, where it allowed for increasing the SNR by 17 dB and improving measurement precision by a factor of two. Then, the WTDA was applied to the simulated signals from a 200 MeV clinical beam where, compared to state-of-the-art algorithms, it achieved a −80% dose reduction when achieving the same 30 μm precision and a six-fold precision improvement for the same 17 Gy dose deposition. Full article

We developed a novel dosimetric method using DNA molecules as a radiation sensor. The amount of neutron or gamma rays irradiated DNA damage was determined by evaluating the amount of DNA serving as a template for qPCR. The absorbed doses in the samples were estimated using the tally of the “t-product” in the data from the PHITS Monte Carlo particle transport simulation code. The neutron fluence for each sample was measured using the niobium activation reaction ⁹³Nb (n, 2n) ^92mNb, and the absorbed dose per neutron fluence was estimated to be 7.1 × 10⁻¹¹ Gy/(n/cm²). Based on the PHITS modeling, the effects of neutron beams are attributed to the combination of proton and alpha particle beams. The results from qPCR showed that neutrons caused more DNA damage than gamma rays. The qPCR method demonstrated that neutron irradiation caused 1.13-fold more DNA damage compared to gamma ray irradiation; however, this result did not show a statistically significant difference. This method we developed, using DNA molecules as a radiation sensor, may be useful for biodosimetry. Full article

The experimental and computational characterization of a cold model prototype designed to test the electromagnetic properties of a new RFQ (Radio-Frequency Quadrupole) cavity is reported. This cavity is intended to be an essential part of a compact, high-gradient proton accelerator for medical purposes. The RFQ’s design employs a novel RF power-coupler injection solution. One common way to couple the RF power in proton RFQs has been the use of loop-couplers inserted into the mid-section of the RFQ’s lobe sections. This technique has been demonstrated to be reliable and effective but introduces a significant perturbation into the lobe that can be more noticeable when dealing with compact structures. We propose a RF injection scheme that uses direct transition from a coaxial cable to the RFQ by connecting the inner coaxial conductor to the RFQ vane body. As a consequence, the lobe geometry is not perturbed, and the transversal electrical fields are directly excited through the vanes. Moreover, by using a pair of such couplers connected to opposite vanes at a given transversal plane of the RFQ, it is also possible to excite the desired quadrupolar TE210 modes while avoiding the excitation of dipolar TE110 modes. The resonances corresponding to different RFQ modes have been characterized, and the dependence of the amplitude of the modes on the relative phase of the field injected through the RF power ports has been demonstrated both by measurements and simulations. Full article

Background/Objectives: PBT enables precise targeting of tumors, which reduces side effects on surrounding organs, with particularly significant benefits for pediatric tumors. However, the efficacy of PBT compared to photon RT for pediatric medulloblastoma is unclear. A meta-analysis to assess the efficacy of PBT vs. photon RT for this disease was performed. Methods: Articles focusing on postoperative primary medulloblastoma from 1990 to 2022 were systematically reviewed and survival outcomes were extracted for medulloblastoma treated with PBT or photon RT. Meta-regression was used to identify predictive factors for treatment outcomes, including modality (PBT vs. photon RT), disease risk classification, gender, and age. Results: From 935 records, 18 articles were included (14 on photon RT, with 6 focusing on high-risk cases, and 4 on PBT). In standard-risk cases, the 1-, 3-, and 5-year overall survival (OS) rates were 95.5% (95% CI: 87.2–98.4%) vs. 96.7% (95% CI: 93.5–98.4%) (p = 0.1210); 89.8% (95% CI: 85.3–92.9%) vs. 88.0% (95% CI: 83.7–91.3%) (p = 0.5416); and 82.9% (95% CI: 76.6–87.6%) vs. 82.4% (95% CI: 77.2–86.5%) (p = 0.8313), respectively. For high-risk cases, the OS rates were 88.9% (95% CI: 85.5–91.6%); 73.6% (95% CI: 60.9–82.8%); and 68.6% (95% CI: 56.1–78.3%), respectively. The 1-, 3-, and 5-year progression-free survival (PFS) rates in standard-risk cases were 95.2% (95% CI: 91.8–97.2%) vs. 93.8% (95% CI: 89.4–96.5%) (p = 0.5275); 82.9% (95% CI: 77.3–87.2%) vs. 82.5% (95% CI: 80.1–84.7%) (p = 0.4294); and 79.6% (95% CI: 73.1–84.6%) vs. 77.0% (95% CI: 72.7–80.8%) (p = 0.3938), respectively. For high-risk cases, the PFS rates were 83.5% (95% CI: 77.0–88.3%); 64.8% (95% CI: 53.2–74.2%); and 60.4% (95% CI: 47.0–71.4%), respectively. Meta-regression analysis indicated no significant differences in 1- to 5-year OS and PFS between radiation modalities. Standard-risk cases were significantly associated with better OS and PFS. Younger age was significantly associated with 1- and 2-year OS and 1-year PFS, and male gender was significantly associated with 3-year OS and 3-year PFS. Conclusions: Postoperative irradiation for pediatric medulloblastoma using PBT has a therapeutic effect comparable to that of photon RT. This suggests that PBT is a useful option among RT modalities for medulloblastoma. Full article

Background: The use of nanoradiosensitizers is a promising strategy for the precision enhancement of tumor tissue damage during radiotherapy. Methods: Here, we propose a novel biocompatible theranostic agent based on gadolinium fluoride doped with cerium and terbium (Gd_0.7Ce_0.2Tb_0.1F₃ NPs), which showed pronounced radiocatalytic activity when exposed to photon or proton beam irradiation, as well as remarkable MRI contrast ability. A scheme for the production of biocompatible colloidally stable Gd_0.7Ce_0.2Tb_0.1F₃ NPs was developed. Comprehensive physicochemical characterization of these NPs was carried out, including TEM, SEM, XRD, DLS, and EDX analyses, as well as UV–vis spectroscopy and MRI relaxation assays. Results: Cytotoxicity analysis of Gd_0.7Ce_0.2Tb_0.1F₃ NPs in vitro and in vivo revealed a high level of biocompatibility. It was shown that Gd_0.7Ce_0.2Tb_0.1F₃ NPs effectively accumulate in MCF-7 tumor cells. A study of their radiosensitizing activity demonstrated that the combined effect of Gd_0.7Ce_0.2Tb_0.1F₃ NPs and X-ray irradiation leads to a dose-dependent decrease in mitochondrial membrane potential, a sharp increase in the level of intracellular ROS, and the subsequent development of radiation-induced apoptosis. Conclusions: This outstanding radiosensitizing effect is explained by the radiocatalytic generation of reactive oxygen species by the nanoparticles, which goes beyond direct physical dose enhancement. It emphasizes the importance of evaluating the molecular mechanisms underlying the sensitizing effectiveness of potential nanoradiosensitizers before choosing conditions for their testing in in vivo models. Full article

Background: Pediatric high-grade glioma (pHGG) is a highly aggressive cancer with unique biology distinct from adult high-grade glioma, limiting the effectiveness of standard treatment protocols derived from adult research. Objective: The purpose of this report is to present preliminary results from an ongoing pilot study integrating spectroscopic magnetic resonance imaging (sMRI) to guide proton beam therapy and longitudinal imaging analysis in pediatric patients with high-grade glioma (pHGG). Methods: Thirteen pediatric patients under 21 years old with supratentorial WHO grade III-IV glioma underwent baseline and serial whole-brain spectroscopic MRI alongside standard structural MRIs. Radiation targets were defined using T1-weighted contrast enhanced, T2-FLAIR, and Cho/NAA ≥ 2X maps. Longitudinal analyses included voxel-level metabolic change maps and spatial overlap metrics comparing pre-proton therapy and post-. Results: Six patients had sufficient longitudinal data; five received sMRI-guided PBT. Significant positive correlation (R² = 0.89, p < 0.0001) was observed between T2-FLAIR and Cho/NAA ≥ 2X volumes. Voxel-level difference maps of Cho/NAA and Choline revealed dynamic metabolic changes across follow-up scans. Analyzing Cho/NAA and Cho changes over time allowed differentiation between true progression and pseudoprogression, which conventional MRI alone struggles to achieve. Conclusions: Longitudinal sMRI enhanced metabolic tracking in pHGG, detects early tumor changes, and refines RT targeting beyond structural imaging. This first in-kind study highlights the potential of sMRI biomarkers in tracking treatment effects and emphasizes the complementary roles of metabolic and radiographic metrics in evaluating therapy response in pHGG. Full article

Recently, studies on accelerator-based boron neutron capture therapy (AB-BNCT) systems for cancer treatment have attracted the attention of researchers around the world. A neutron source can be obtained through the impingement of high-intensity proton beams emitted from the accelerator onto the target. This process would deposit a large amount of heat within this target. A thermal management system design is needed for AB-BNCT systems to prevent the degradation of the target due to thermal/mechanical loading. However, there are few studies that investigate this topic. In this paper, a cooling channel with a boiling heat transfer mechanism is numerically designed for thermal management in order to remove heat deposited in the Be target of the AB-BNCT system of Heron Neutron Medical Corp. A three-dimensional (3D) CFD methodology with a two-fluid model and an RPI wall boiling model is developed to investigate its availability. Two subcooled boiling experiments from previous works are adopted to validate the present CFD boiling model. This validated model can be confidently applied to assist in thermal management design for the AB-BNCT system. Based on the simulation results under the typical operating conditions of the AB-BNCT system set by Heron Neutron Medical Corp., the present coolant channel employing the boiling heat transfer mechanism can efficiently remove the heat deposited in the Be target, as well as maintain its integrity during long-term operation. In addition, compared with the channel with the single-phase convection traditionally designed for an AB-BNCT system, the boiling heat transfer mechanism can result in a lower peak temperature in the Be target and its corresponding deformation. Full article

This study aimed to investigate the distribution of thermal neutron fluence generated during proton-beam therapy (PBT) scanning, focusing on neutrons produced within the body using Monte Carlo simulations (MCSs). MCSs used the Particle and Heavy Ion Treatment Code System to define a 35 × 35 × 35 cm³ water phantom, and proton-beam energies ranging from 70.2 to 228.7 MeV were investigated. The MCS results were compared with neutron fluence measurements obtained from gold activation analysis, showing good agreement with a difference of 3.54%. The internal thermal neutron distribution generated by PBT was isotropic around the proton-beam axis, with the Bragg peak depth varying between 3.45 and 31.9 cm, while the thermal neutron peak depth ranged from 5.41 to 15.9 cm. Thermal neutron generation depended on proton-beam energy, irradiated particle count, and depth. Particularly, the peak of the thermal neutron fluence did not occur within the treatment target volume but in a location outside the target, closer to the source. This discrepancy between the Bragg peak and the thermal neutron fluence peak is a key finding of this study. These data are crucial for optimizing beam angles to maximize dose enhancement within the target during clinical applications of neutron capture-enhanced particle therapy. Full article