Proton Beam Research Articles

FLIP: a novel method for patient-specific dose quantification in circulating blood in large vessels during proton or photon external beam radiotherapy treatments.

To provide a novel and personalized method (FLIP, FLowandIrradiation Personalized) using patient-specific circulating blood flows and individualized time-dependent irradiation distributions, to quantify the dose delivered to blood in large vessels during proton or photon external beam radiotherapy. Patient-specific data were obtained from ten cancer patients undergoing radiotherapy, including the blood velocity field in large vessels and the temporal irradiation scheme using photons or protons. The large vessels and the corresponding blood flow velocities are obtained from phase-contrast MRI sequences. The blood dose is obtained discretizing the fluid into individual blood particles (BPs). A Lagrangian approach was applied to simulate the BPs trajectories along the vascular velocity field flowlines. Beam delivery dynamics was obtained from beam delivery machine measurements. The whole irradiation sequence is split into a sequence of successive irradiation elements, each one with its constant dose rate, as well as its corresponding initial and final time. Calculating the dose rate and knowing the spatiotemporal distribution of BPs, the dose is computed by accumulating the energy received by each BP as the time-dependent irradiation beams take place during the treatment. Blood Dose Volume Histograms (DVHs) from proton therapy and photon radiotherapy (RT) patients were assessed. The irradiation times distribution is obtained for BPs in both modalities. Two dosimetric parameters are presented: (i) D3%, representing the minimum dose received by the 3% of BPs receiving the highest doses, and (ii) V0.5Gy, denoting the blood volume percentage that has received at least 0.5 Gy. A novel methodology is proposed for quantifying the circulating blood dose along large vessels. This methodology involves the use of patient-specific vasculature, blood flow velocity field, and dose delivery dynamics recovered from the irradiation machine. Relevant parameters that affect the dose received, as the distance between large vessels and CTV, are identified.

A Bayesian inverse approach to proton therapy dose delivery verification

This study presents a proof-of-concept for a novel Bayesian inverse method in a one-dimensional setting, aimed at proton beam therapy treatment verification. Our methodology is predicated on a hypothetical scenario wherein strategically positioned sensors detect prompt- γ s emitted from a proton beam when it interacts with defined layers of tissue. Using these data, we employ a Bayesian framework to estimate the proton beam’s energy deposition profile. We validate our Bayesian inverse estimations against a closed-form approximation of the Bragg Peak in a uniform medium and a layered lung tumour.

Multichannel Sensor Array Design for Minimizing Detector Complexity and Power Consumption in Ionoacoustic Proton Beam Tomography

Ionoacoustic tomography exploits the acoustic signal generated by the fast energy deposition along the path of pulsed particle beams to reconstruct with sub-mm precision the dose deposition, with promising envisioned applications in hadron therapy treatment monitoring. State-of-the-art ionoacoustic detectors mainly rely on single-channel sensors and time-of-flight measurements to provide 1D localization of the maximum dose deposition at the so-called Bragg peak. This work investigates the design challenges of multichannel sensors for ionoacoustic tomography in terms of their ability to accurately reconstruct the dose deposition of a 200 MeV clinical proton beam, highlighting the impact of the number of channels in the array and their directivity. A complete acoustic model of the sensors and environment has been developed and used to find an optimum tradeoff between accuracy, evaluated numerically through the gamma index, and hardware complexity due to higher channel numbers, thus minimizing the system-level power consumption of the detector.

Brainstem Toxicity Following Proton Beam Radiation Therapy in Pediatric Brain Tumors: A Systematic Review and Meta-Analysis

Background: Proton beam radiation therapy (PBRT) is an advanced cancer treatment modality that utilizes the distinctive physical properties of protons to precisely deliver radiation to tumor targets while sparing healthy tissue. This cannot be obtained with photon radiation. In this systematic review and meta-analysis, we aimed to comprehensively assess the risk of brainstem toxicity in pediatric brain tumor patients undergoing PBRT. Methods: With adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a predetermined search strategy was used to identify eligible articles from PubMed, Web of Science, Scopus, and Cochrane Library through July 2024. Results: The current study included a total of 11 eligible articles. The pooled prevalence of patients who suffered from brainstem toxicity was 1.8% (95% CI: 1%, 2.6%). The pooled prevalences of patients with Grade 1 to Grade 5 brainstem toxicity were found to be 10.6% (95% CI: 8.8%, 30%), 1.5% (95% CI: 0.6%, 2.5%), 0.7% (95% CI: 0.3%, 1.1%), 0.4% (95% CI: 0.1%, 0.7%), and 0.4% (95% CI: 0.1%, 0.8%), respectively, with an overall pooled prevalence of 0.7% (95% CI: 0.4%, 1%). Conclusions: This study revealed a relatively low incidence of symptomatic brainstem toxicity and its related mortality in the pediatric population undergoing PBRT. However, further research is encouraged to study the broader effects of PBRT and to explore various factors that may influence the risk of brainstem toxicity in patients treated with PBRT.

SHIFT@LHC: Searches for new physics with shifted interaction on a fixed target at the Large Hadron Collider

New low-mass particles with very small couplings to standard model particles that travel significant distances before decaying are interesting candidates to address some of the most intriguing questions of modern physics. In this paper, I propose to extend the LHC’s research program by installing a gaseous fixed target referred to as SHIFT at around 160 meters from the CMS interaction point. When the LHC proton beam collides with this target, interactions at a center of mass energy of ≈113 GeV would occur. The particles produced in such collisions, or their decay products, would travel through the rock and other material on their path, potentially reaching the CMS detector where they can be registered and studied. Such an approach would allow us to access otherwise uncovered regions of parameters phase space at a relatively low cost since it does not require constructing a new detector. Various aspects such as angular and lifetime coverage or material survival probability have been studied. The results are interpreted within two new physics models, namely, the Dark Photons and the Hidden Valley scenarios, and compared with the standard proton-proton physics program of CMS. A comparison is also made with the fixed target program at LHCb, as well as parasitic detectors such as FASER or MATHUSLA. The obtained results indicate that, despite assuming just 1% of the nominal CMS luminosity to be available to SHIFT, the physics reach could be extended by a factor of up to 150 (1000) for Dark Photon (Hidden Valley) scenarios, depending on the signal model parameters.

Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum?

The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The primary advantage of using the “dose and LET” physical system is its relative simplicity, especially for presenting and recording results. Inclusion of additional information such as the energy spectrum of charged particles renders this approach adequate to describe the biological effects of large dose levels from homogeneous sources. The primary disadvantage of this system is that it does not provide a unique description of the stochastic nature of radiation interactions. We and others have used dose-averaged LET (LETd) as a correlative physical quantity to the relative biological effectiveness (RBE) of proton beams. This approach is based on established experimental findings that proton RBE increases with LETd. However, this approach might not be applicable to intensity-modulated proton therapy or other applications in which the proton energy spectrum is highly heterogeneous. In the current study, we irradiated cancer cells with scanning proton beams with identical LETd (3.4 keV/µm) but arising from two different proton energy/LET spectra (a narrow spectrum in group 1 and a widespread heterogeneous spectrum in group 2). Clonogenic survival after irradiation revealed significant differences in RBE at any cell surviving fraction: e.g., at a surviving fraction of 0.1, the RBE was 0.97 ± 0.03 in group 1 and 1.16 ± 0.04 in group 2 (p≤0.01), validating our hypothesis that LETd alone may not adequately indicate proton RBE. Further analysis showed that microdosimetric spectrum (the probability density function of the stochastic physical quantity lineal energy y) was helpful for interpreting observed differences in biological effects. However, more accurate use of microdosimetric spectrum to quantify RBE requires a cell line–specific mechanistic model.

Salvage Reirradiation with Proton Beam Therapy for Locoregionally Recurrent Non-Small Cell Lung Cancer

Salvage Reirradiation with Proton Beam Therapy for Locoregionally Recurrent Non-Small Cell Lung Cancer

Fully Kinetic Simulations of Proton-beam-driven Instabilities from Parker Solar Probe Observations

The expanding solar wind plasma ubiquitously exhibits anisotropic nonthermal particle velocity distributions. Typically, proton velocity distribution functions (VDFs) show the presence of a core and a field-aligned beam. Novel observations made by the Parker Solar Probe (PSP) in the innermost heliosphere have revealed new complex features in the proton VDFs, namely anisotropic beams that sometimes experience perpendicular diffusion. In this study, we use a 2.5D fully kinetic simulation to investigate the stability of proton VDFs with anisotropic beams observed by PSP. Our setup consists of a core and an anisotropic beam population that drift with respect to each other. This configuration triggers a proton beam instability from which nearly parallel fast magnetosonic modes develop. Our results demonstrate that before this instability reaches saturation, the waves resonantly interact with the beam protons, causing perpendicular heating at the expense of the parallel temperature.

Development of an online neutron beam monitoring system for accelerator-based boron neutron capture therapy in a hospital.

Boron neutron capture therapy (BNCT) is a next-generation radiotherapy, utilizing both an external neutron beam and a -containing pharmaceutical. A compact accelerator for a high intensity neutron source was installed to conduct BNCT in a hospital. The dose administered to a patient was evaluated by measuring the proton beamcurrent. Neutron intensity should be monitored in real-time by measuring the neutrons emitted from the target during BNCT irradiation. This is crucial due to potential neutron target degradation. Online neutron beam monitoring systems are required for reliable measurements of the administered neutron dose. An online neutron beam monitoring system was developed to monitor neutron intensity irradiating on the patient at the National Cancer Center Hospital (NCCH). The neutron detector comprised a back-illuminated thin Si diode of 40- thickness and an ultrathin natural LiF neutron converter of 0.05- thickness. The neutron detector was installed on the neutron target unit, regardless of whether a patient was present, without any additional modifications to the setup. The response functions for high photon dose rates of upto 100 Gy/h were measured. The pulse heights were measured using the neutron beam monitor during BNCT neutron irradiation. Neutron temporal response measured using the online beam monitor was acquired and compared with the proton beam current and the measurements at a patient position. From this measurement at the patient position, the neutron fluence rate irradiating on a patient wasobtained. The neutron events were separated from the photon events. The neutron counting rates increased rapidly with the starting of proton beam irradiation and dropped to zero upon its termination. During intermittent drops and recoveries in the proton beam, the neutron beam monitor for counting rates responded quickly, synchronizing with the beam current. A scatter plot of the neutron counting rate and proton beam current indicated a good linear correlation. A direct relationship between the online neutron beam monitor's neutron counting rates and those of the patient neutron detector showed a good correlation coefficient of 0.84. A ratio of the both neutron counting rates showed a standard deviation of 6%. The correlation coefficient and standard deviation were improved to 0.94 and 1.5%, by re-binning the neutron temporal response with longer acquisition period than 1 s. Using the online neutron beam monitor, the neutron fluence rate was obtained from the direct relationship within 1.5%. Therefore, real-time monitoring of neutron intensity was achieved within the acceptable level as per the International Commission on Radiation Units and Measurementsreport. The online neutron beam monitoring system was developed to monitor the BNCT neutron beam intensity at NCCH. The temporal response of the neutron beam monitor was synchronized with the neutron counting rate at the patient position. Using the online neutron beam monitor, the neutron fluence rate irradiating on the patient can be monitored from the direct relationship. Fluctuation of the neutron beam intensity through BNCT irradiation and the degradation of the lithium target through the lifespan of the neutron target could be monitored using the neutron beammonitor.

Design of a compact beam transport system for laser-driven proton therapy

Abstract We put forward a new design of a compact beam transport system for intense laser-driven proton therapy, where instead of using conventional pulsed solenoids, our design relies on a helical coil irradiated by a nanosecond laser pulse to generate strong magnetic fields for focusing protons. A pair of dipole magnets and apertures are employed to further filter protons with large divergences and low energies. Our numerical studies combine particle-in-cell simulations for laser-plasma interaction to generate high-energy monoenergetic proton beams, finite element analysis for evaluating the magnetic field distribution inside the coil, and Monte-Carlo simulations for beam transport and energy deposition. Our results show that with this design, a spread-out Bragg peak in a range of several centimeters to a deep-seated tumor with a dose of approximately 16.5 cGy and fluctuation around 2% can be achieved. The instantaneous dose rate reaches up to 109 Gy/s, holding the potential for future FLASH radiotherapy research.

Effect of Hydrogen on Albedo Neutrons in the Lunar Surface

The remote sensing observations of the lunar soil by using neutron spectroscopy as well as infrared spectroscopy in various studies suggest the presence of hydrogen in the lunar surface, particularly around the lunar polar regions. Additionally, the cosmic ray protons incident on the lunar surface induce the generation of secondary neutrons depending on the composition of the surface soil and the associated density, a certain number of which, called albedo neutrons, leak from the lunar regolith. Motivated by the interaction of the cosmic ray protons with the lunar surface in the absence and presence of hydrogen, a series of GEANT4 simulations are employed in the current study to unveil the influence of hydrogen on the energy spectrum of the albedo neutrons that escape from the lunar surface. Initially, a discrete 69-bin proton energy spectrum between 0.4 and 115 GeV based on the PAMELA spectrometer is implemented into GEANT4. Subsequently, a single-volume lunar surface of 2-m thickness is constructed where it is assumed that a single layer of either 1.6 or 1.93 g/cm^3 constitutes the lunar regolith. The material composition in the present study includes 43.7 wt.% oxygen, 0.3 wt.% sodium, 5.6 wt.% magnesium, 9 wt.% aluminium, 21.1 wt.% silicon, 8.5 wt.% calcium, 1.5 wt.% titanium, 0.1 wt.% manganese, and 10.2 wt.% iron in accordance with another study. Then, 0.1 wt.% hydrogen is introduced by replacing oxygen in order to assess the impact of hydrogen on the secondary neutrons. In the wake of irradiating a lunar surface of 3*2*3 m^3 with a planar vertical PAMELA proton beam of 20*20 cm^2, the depth profile of the generated neutrons as well as the corresponding initial energy spectrum is primarily obtained in the absence and presence of 0.1 wt.% hydrogen by voxelizing the entire geometry with 100 cells of 2-cm thickness. Next, a surface detector is placed at the top of the lunar surface in order to collect the albedo neutrons in both cases, and the energy spectra of the albedo neutrons are acquired in terms of thermal, epithermal, and fast neutrons. From the GEANT4 simulations in this study, it is shown that the presence of 0.1 wt.% hydrogen is observable in each energy regime of the albedo neutrons at the lunar surface, thereby providing an indication about the elemental variation of the lunar soil.

Searching for long-lived light neutralinos and axionlike particles at the SHiNESS experiment

Recently, Soleti [] proposed a new experiment called SHiNESS at the upcoming European Spallation Source (ESS) facility, making use of the 2-GeV proton beam there impinging on a fixed target, in order to search for hidden sterile neutrinos that could lie in different mass ranges and arise with distinct signatures. Such signatures include excesses in electron-positron pairs that may originate from displaced decays of long-lived particles (LLPs). At the ESS, the dominant sources of such LLPs are decays at rest of π+ mesons and μ+ leptons. We choose to investigate theoretical scenarios of long-lived light neutralinos in the R-parity-violating supersymmetry and long-lived weak-violating electrophilic axionlike particles, as these LLPs can be produced from decays of π+ and μ+. Since the π+’s and μ+’s decay at rest at the ESS, we compute the spectra of the therefrom produced LLPs and thus estimate the expected sensitivity reach of SHiNESS to the LLPs in these two scenarios. Our calculation shows that in multiple relevant benchmark scenarios, SHiNESS can probe large parameter regions of these models beyond the existing bounds, in just a couple of years of data-collection time. Published by the American Physical Society 2024

Variable-RBE-induced NTCP predictions for various side-effects following proton therapy for brain tumors – Identification of high-risk patients and risk mitigation

Background and purposeDisregarding the increase of relative biological effectiveness (RBE) may raise the risk of acute and late adverse events after proton beam therapy (PBT). This study aims to explore the relationship between variable RBE (above 1.1)-induced normal tissue complication probabilities (NTCP) and patient-specific factors, identify patients at high risk of RBE-induced NTCP increase, and assess risk mitigation by incorporating RBE variability into treatment planning. Materials and methodsWe retrospectively analyzed 105 primary brain tumor patients treated with PBT (RBE = 1.1). We calculated differences in estimated NTCP (ΔNTCP) using a variable RBE-weighted dose (DRBE, Wedenberg model) and a constant RBE-weighted dose (DRBE=1.1), across 16 NTCP models. These differences were correlated with patient-specific characteristics. Based on ΔNTCP, patients were classified as high risk (32 %) or low risk (68 %) for adverse events due to RBE-induced NTCP. This classification was compared with alternative classifications based on (a) relevant patient-specific characteristics, (b) DRBE=1.1, and (c) the difference between DRBE and DRBE=1.1 (ΔD), assessing the balanced accuracy. The potential to reduce RBE-induced NTCP through track-end and linear energy transfer (LET) optimization was evaluated in six example patients. ResultsUsing a variable RBE instead of a constant one resulted in NTCP increases (up to 32 percentage points). Variable-RBE-induced NTCP increases were strongly negatively correlated with the distance between the clinical target volume (CTV) and the organ at risk (OAR) for most side-effects, and positively correlated with CTV volume for certain side-effects. High increases were associated with (a) specific patient factors, particularly the proximity of the CTV to OARs, (b) DRBE=1.1, and (c) ΔD, with a balanced accuracy of 0.88, 0.94, and 0.86, respectively. Optimization of track-ends and LET considerably reduced NTCP values, achieving a mean reduction of 31 % for optimized OARs. ConclusionThe risk of variable-RBE-induced NTCP strongly depends on patient-specific factors and the considered side-effect. A small distance between the tumor and OARs notably increases the risk. Integrating biologically-guided objectives into treatment planning can effectively mitigate the risk.

Proton Therapy in Uveal Melanoma

Background/Objectives: Uveal melanoma is the most common primary intraocular malignancy in adults. Treatment options for localized, early-stage disease include enucleation, brachytherapy, and proton beam therapy. This review aims to evaluate the role of proton therapy in the definitive management of uveal melanoma, focusing on its physics, radiobiology, treatment techniques, and associated outcomes. Methods: This narrative review synthesizes current literature on proton therapy for uveal melanoma, emphasizing case selection, treatment efficacy, and side effects. Results: Proton therapy offers significant advantages for thicker uveal melanomas (over 8 mm) due to its unique physical properties, including a rapid dose fall-off that protects critical structures like the retina and optic nerve. Proton therapy may have benefits in tumor control for ocular melanomas given its increased relative biological effectiveness relative to photon therapy for these typically more radioresistant melanomas. Proton therapy may also hold special value for uveal melanomas in close proximity to the optic nerve, as patients are at high risk of visual toxicities with brachytherapy. The review discusses the efficacy of proton therapy across small, medium, and large tumors, along with strategies for improving patient survival through combined systemic therapy. Additionally, the potential of ocular reirradiation with proton therapy is addressed. Conclusions: Proton therapy is an effective treatment for uveal melanoma. It offers advantages over brachytherapy for large tumors, tumors that are close to the optic nerve or insertion of extra-ocular muscles.

Dosimetry in MRgPT: Impact of magnetic fields on TLD dose response during proton irradiation.

Proton beam therapy, when integrated with MRI guidance, presents complex dosimetric challenges due to interactions with magnetic fields. Prior research has emphasized the nuanced impact of magnetic fields on dosimetry. For thermoluminescent dosimeters (TLDs) the electron-return effect, alongside small air cavities surrounding the pellets, can lead to nonuniform dose distributions. Future MR-guided proton therapy will require reliable methods for end-to-end tests and dosimetric audits, which so far are often performed using TLDs equipped with phantoms. This implicates the necessity of accounting for theseinteractions. This study investigates the influence of magnetic fields on TLDs at two proton energies, using magnetic field strengths of 0, 0.25, and , aiming to clarify their impact on dose measurementaccuracy. The study was conducted at a synchrotron-based ion beam therapy beam line, enhanced by a resistive dipole magnet for creating magnetic fields up to to simulate MR-guided proton therapy. Individual correction factors were applied for TLD measurements. The impact of air gaps on the TLD signal was evaluated using three dedicated TLD holders with air gaps of 0.1, 0.25, and 0.5 mm surrounding the TLD pellets using the highest available proton energy of . Additionally, the influence of the magnetic field strength on the TLD response was evaluated for two proton energies of and . The study found no statistically significant variation in TLD dose response attributable to changes in the air gap or the presence of magnetic fields. A power analysis indicated an upper limit on a potential change in dose-response as small as 1.5%. The findings suggested that the impact of air gap variations and magnetic field strengths on the TLD response was below the detection threshold of TLD sensitivity. This emphasizes the suitability of TLDs for dose measurement in MR-guided proton therapy, indicating that additional correction factors may not be necessary despite the influence of magneticfields.

Direct and Indirect Effects for Radiosensitization of Gold Nanoparticles in Proton Therapy.

The radiosensitization characteristics of gold nanoparticles (GNPs) have been investigated in a single cell irradiated with monoenergetic beams of protons of various energies using TOPAS-nBio, an advanced toolkit of TOPAS. Both direct and indirect effects against single-strand breaks (SSBs) are investigated and their double-strand breaks (DSBs) have been calculated. A single spherical cell interaction with a detailed DNA structure has been modeled and simulated under different conditions such as particle sizes and concentrations of GNPs, their biodistributions and associated proton energies. The physical interaction among protons, suspension water and GNPs has been simulated using a dual physics approach, while the interaction between water radiolysis and OH radicals was considered in the chemical process to save computational time. The present simulations involve irradiating the cell geometry with a dose of 1 Gy. The range of DSBs (Gy-1 Gbp-1) obtained was 2.1 ± 0.09 to 21.74 ± 0.4 for all GNPs of sizes 6-50 nm the proton energies in the range of 5-50 MeV. Regardless of proton energy and GNP size, the calculations showed that the contribution of indirect and hybrid DSBs remains higher in all simulation types than that of direct DSBs. New simulation outcomes of the indirect DSBs illustrate a percentage increase, while we cannot get an increase in the direct and hybrid DSBs in most cases when compared with no GNPs cases. The indirect DSBs provide the highest enhancement factor of 1.89 at 30 nm GNPs in size for 30 MeV protons energy, and the direct and hybrid DSBs indicate a slight increase in enhancement. The work indicates that the use of GNPs increased indirect DNA DSBs, while hybrid DSBs show only a slight increase in enhancement, and no enhancement is shown in direct DNA DSBs. It is significant to consider other mechanisms such as DNA damage repair when investigating DNA damage.

Experimental Study and Quantitative Analysis of the Physical Parameters of the Proton Therapy Scanning Beam Delivery System

The development of proton therapy techniques imposes strict requirements for the accuracy of proton beam delivery. Existing methods for determining the planning target volume allow one to take into account only the influence of patient positioning errors before the start of irradiation. In this paper, the results of work on taking into account proton therapy system beam delivery errors for determining the planning target volume are presented. The technique for measuring the proton beam parameters and analyzing the measurement results is described. The calculation of the minimum required margin from the clinical target volume is carried out to guarantee its irradiation, taking into account the errors in beam delivery by the proton therapy system.

The Histopathology of Chronic "Radiation Conjunctivitis" Shows Diagnostic Features Similar to Those Seen in Radiation Dermatitis, Including Radiation Fibroblasts.

Radiation therapy is a treatment modality for various ocular and ocular adnexal tumors. The histopathology of chronic radiation dermatitis has been well-described. The authors present two cases demonstrating and characterizing "chronic radiation conjunctivitis" which has not been histopathologically illustrated in detail. Retrospective case review of two patients who received proton beam irradiation for an anterior uveal melanoma and external beam radiation for conjunctival lymphoma, and developed leukoplakia and/or thickening of the eyelid margin and symblepharon. Hematoxylin and eosin-stained sections of eyelid margin and conjunctival biopsies as well as clinical histories were reviewed. Conjunctival biopsies in both cases revealed squamous epithelial metaplasia, chronic inflammation and bizarre-appearing stromal cells with hyperchromatic nuclei in a fibrotic/sclerotic stroma, consistent with chronic radiation conjunctivitis. These stromal cells are believed to be the same "radiation fibroblasts" described in chronic radiation dermatitis. The radiation fibroblast is characteristic for the diagnosis of chronic radiation conjunctivitis, as it is in radiation dermatitis. Features of squamous metaplasia of conjunctival epithelium, keratinization, subepithelial fibrosis/sclerosis and chronic inflammation are frequently found but not specific. A detailed history and other ancillary tests help differentiate cicatrizing conjunctival conditions, and biopsy should be performed in the setting of suspicion for a secondary malignancy.

Phase-change ultrasound contrast agents for proton range verification: towards an in vivo application

Objective.In proton therapy, range uncertainties prevent optimal benefit from the superior depth-dose characteristics of proton beams over conventional photon-based radiotherapy. To reduce these uncertainties we recently proposed the use of phase-change ultrasound contrast agents as an affordable and effective range verification tool. In particular, superheated nanodroplets can convert into echogenic microbubbles upon proton irradiation, whereby the resulting ultrasound contrast relates to the proton range with high reproducibility. Here, we provide a firstin vivoproof-of-concept of this technology.Approach.First, thein vitrobiocompatibility of radiation-sensitive poly(vinyl alcohol) perfluorobutane nanodroplets was investigated using several colorimetric assays. Then,in vivoultrasound contrast was characterized using acoustic droplet vaporization (ADV) and later using proton beam irradiations at varying energies (49.7 MeV and 62 MeV) in healthy Sprague Dawley rats. A preliminary evaluation of thein vivobiocompatibility was performed using ADV and a combination of physiology monitoring and histology.Main results.Nanodroplets were non-toxic over a wide concentration range (<1 mM). In healthy rats, intravenously injected nanodroplets primarily accumulated in the organs of the reticuloendothelial system, where the lifetime of the generated ultrasound contrast (<30 min) was compatible with a typical radiotherapy fraction (<5 min). Spontaneous droplet vaporization did not result in significant background signals. Online ultrasound imaging of the liver of droplet-injected rats demonstrated an energy-dependent proton response, which can be tuned by varying the nanodroplet concentration. However, caution is warranted when deciding on the exact nanodroplet dose regimen as a mild physiological response (drop in cardiac rate, granuloma formation) was observed after ADV.Significance.These findings underline the potential of phase-change ultrasound contrast agents forin vivoproton range verification and provide the next step towards eventual clinical applications.

Measurement of cross section of proton-induced reactions on oxygen with silicon dioxide target

Oxygen is one of the most common elements in the human body. Proton beams used in therapy induce nuclear reactions that cause a loss of fluence along the beam path. These reactions often lead to production of β+\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta ^+$$\\end{document} emitters with relatively short half-lives (less than 20 min). Cross sections for reactions on oxygen are not sufficiently known, particularly at proton energies above few tens of MeV. This contribution presents the results of an experiment, where silicon dioxide targets were used to study nuclear reactions induced by protons with energy below 60 MeV on oxygen. The proton beam was delivered by the AIC-144 cyclotron of the Institute of Nuclear Physics in Kraków. Cross sections of reactions leading to production of 11\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ ^{11}$$\\end{document}C, 13\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ ^{13}$$\\end{document}N and 15\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ ^{15}$$\\end{document}O were obtained. They agree well with the measurements using Cherenkov radiation in bulk SiO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_2$$\\end{document}. The recent measurements performed with a PET scanner provided similar results, except in the case of 16\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ ^{16}$$\\end{document}O(p,x)11\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ ^{11}$$\\end{document}C reaction studied in the energy of up to 200 MeV, where our results are 30% lower.