Linear Energy Transfer Distributions Research Articles

Alanine dosimeters for LET measurement in proton radiotherapy

Proton radiotherapy enables highly conformal dose delivery to the tumor while minimizing exposure to healthy tissues surrounding the target. However, to achieve the most optimal treatment plan, it is necessary to consider various parameters, including variable relative biological effectiveness (RBE) and linear energy transfer (LET) within the target and in the normal tissues. The proton treatment planning systems (TPS) currently under development incorporate both of these parameters. However, before introducing biologically guided treatment planning into the clinic, commissioning and end-to-end tests must be conducted. These procedures require specific tools to verify the planned LET distribution. The same tools will also be necessary for subsequent patient-specific quality assurance (QA).The objective of this work was to evaluate the alanine/EPR dosimetry system developed at the Cyclotron Center Bronowice at the Institute of Nuclear Physics (CCB IFJ PAN) for verifying LET values in therapeutic proton fields. The change in the shape of the EPR spectra of alanine irradiated in proton fields of different LETs, described by the ratio of the intensities of the satellite and central lines (x/y ratio), was used to discriminate LET values. The method does not provide absolute LET values. However, as demonstrated, it can verify the LET values calculated in the TPS after calibration using Monte Carlo (MC) simulation.

The sensitivity of radiobiological models in carbon ion radiotherapy (CIRT) and its consequences on the clinical treatment plan: Differences between LEM and MKM models.

Carbon ion radiotherapy (CIRT) relies on relative biological effectiveness (RBE)-weighted dose calculations. Japanese clinics predominantly use the microdosimetric kinetic model (MKM), while European centers utilize the local effect model (LEM). Despite both models estimating RBE-distributions in tissue, their physical and mathematical assumptions differ, leading to significant disparities in RBE-weighted doses. Several European clinics adopted Japanese treatment schedules, necessitating adjustments in dose prescriptions and organ at risk (OAR) constraints. In the context of these two clinically used standards for RBE-weighted dose estimation, the objective of this study was to highlight specific scenarios for which the translations between models diverge, as shortcomings between them can influence clinical decisions. Our aim was to discuss planning strategies minimizing those discrepancies, ultimately striving for more accurate and robust treatments. Evaluations were conducted in a virtual water phantom and patient CT-geometry, optimizing LEM RBE-weighted dose first and recomputing MKM thereafter. Dose-averaged linear energy transfer (LETd) distributions were also assessed. Results demonstrate how various parameters influence LEM/MKM translation. Similar LEM-dose distributions lead to markedly different MKM-dose distributions and variations in LETd. Generally, a homogeneous LEM RBE-weighted dose aligns with lower MKM values in most of the target volume. Nevertheless, paradoxical MKM hotspots may emerge (at the end of the range), potentially influencing clinical outcomes. Therefore, translation between models requires great caution. Understanding the relationship between these two clinical standards enables combining European and Japanese based experiences. The implementation of optimal planning strategies ensures the safety and acceptability of the clinical plan for both models and therefore enhances plan robustness from the RBE-weighted dose and LETd distribution point of view. This study emphasizes the importance of optimal planning strategies and the need for comprehensive CIRT plan quality assessment tools. In situations where simultaneous LEM and MKM computation capabilities are lacking, it can provide guidance in plan design, ultimately contributing to enhanced CIRT outcomes.

Optimizing linear energy transfer distribution in intensity-modulated proton therapy using the alternating direction method of multipliers.

This study develop a novel linear energy transfer (LET) optimization method for intensity-modulated proton therapy (IMPT) with minimum monitor unit (MMU) constraint using the alternating direction method of multipliers (ADMM). The novel LET optimization method (ADMM-LET) was proposed with (1) the dose objective and the LET objective as the optimization objective and (2) the non-convex MMU threshold as a constraint condition. ADMM was used to solve the optimization problem. In the ADMM-LET framework, the optimization process entails iteratively solving the dose sub-problem and the LET sub-problem, simultaneously ensuring compliance with the MMU constraint. Three representative cases, including brain, liver, and prostate cancer, were utilized to evaluate the performance of the proposed method. The dose and LET distributions from ADMM-LET were compared to those obtained using the published iterative convex relaxation (ICR-LET) method. The results demonstrate the superiority of ADMM-LET over ICR-LET in terms of LET distribution while achieving a comparable dose distribution. More specifically, for the brain case, the maximum LET (unit: keV/µm) at the optic nerve decreased from 5.45 (ICR-LET) to 1.97 (ADMM-LET). For the liver case, the mean LET (unit: keV/µm) at the clinical target volume increased from 4.98 (ICR-LET) to 5.50 (ADMM-LET). For the prostate case, the mean LET (unit: keV/µm) at the rectum decreased from 2.65 (ICR-LET) to 2.14 (ADMM-LET). This study establishes ADMM-LET as a new approach for LET optimization with the MMU constraint in IMPT, offering potential improvements in treatment outcomes and biological effects.

Effects of nuclear interaction corrections and trichrome fragment spectra modelling on dose and linear energy transfer distributions in carbon ion radiotherapy

Background and PurposeNuclear interaction correction (NIC) and trichrome fragment spectra modelling improve relative biological effectiveness-weighted dose (DRBE) and dose-averaged linear energy transfer (LETd) calculation for carbon ions. The effect of those novel approaches on the clinical dose and LET distributions was investigated. Materials and MethodsThe effect of the NIC and trichrome algorithm was assessed, creating single beam plans for a virtual water phantom with standard settings and NIC + trichrome corrections. Reference DRBE and LETd distributions were simulated using FLUKA version 2021.2.9. Thirty clinically applied scanned carbon ion treatment plans were recalculated applying NIC, trichrome and NIC + trichrome corrections, using the LEM low dose approximation and compared to clinical plans (base RS). Four treatment sites were analysed: six prostate adenocarcinoma, ten head and neck, nine locally advanced pancreatic adenocarcinoma and five sacral chordoma. The FLUKA and clinical plans were compared in terms of DRBE deviations for D98%, D50%, D2% for the clinical target volume (CTV) and D50% in ring-like dose regions retrieved from isodose curves in base RS plans. Additionally, region-based median LETd deviations and global gamma parameters were evaluated. ResultsDose deviations comparing baseRS and evaluation plans were within ± 1% supported by γ-pass rates over 97% for all cases. No significant LETd deviations were reported in the CTV, but significant median LETd deviations were up to 80% for very low dose regions. ConclusionOur results showed improved accuracy of the predicted DRBE and LETd. Considering clinically relevant constraints, no significant modifications of clinical protocols are expected with the introduction of NIC + trichrome.

Linear energy transfer (LET) distribution outside small radiotherapy field edges produced by 6 MV X-rays

In modern radiotherapy with photons, the absorbed dose outside the radiation field is generally investigated. But it is well known that the biological damage depends not only on the absorbed dose but also on LET. This work investigated the dose-average LET (LΔ,D) outside several small radiotherapy fields to provide information that can help for better evaluating the biological effect in organs at risk close to the tumour volume. The electron fluences produced in liquid water by a 6 MV X-rays Varian iX linac were calculated using the EGSnrc Monte Carlo code. With the electron spectra, LΔ,D calculations were made for eight open small square fields and the reference field at water depths of 0.15 cm, 1.35 cm, 9.85 cm and 19.85 cm and several off-axis distances. The variation of LΔ,D from the centre of the beam to 2 cm outside the field’s edge depends on the field size and water depth. Using radiobiological data reported in the literature for chromosomal aberrations as an endpoint for the induction of dicentrics determined in Human Lymphocytes, we estimated the maximum low-dose relative biological effectiveness, (RBEM) finding an increase of up to 100% from the centre of the beam to 2 cm from the field's edge.

A Novel Inverse Algorithm To Solve the Integrated Optimization of Dose, Dose Rate, and Linear Energy Transfer of Proton FLASH Therapy With Sparse Filters

Purpose:The recently proposed Integrated Physical Optimization Intensity Modulated Proton Therapy (IPO-IMPT) framework allows simultaneous optimization of dose, dose rate, and linear energy transfer (LET) for FLASH treatment planning. Finding solutions to IPO-IMPT is difficult due to computational intensiveness. Nevertheless, an inverse solution that simultaneously specifies the geometry of a sparse filter and weights of a proton intensity map is desirable for both clinical and preclinical applications. Such solutions can reduce effective biological dose to organs at risk in cancer patients as well as reduce the number of animal irradiations needed to derive extra biological dose models in preclinical studies. Methods:Unlike the initial forward heuristic, this inverse IPO-IMPT solution includes simultaneous optimization of sparse range compensation, sparse range modulation, and spot intensity. The daunting computational tasks vital to this endeavor were resolved iteratively with a distributed computing framework to enable Simultaneous Intensity and Energy Modulation and Compensation (SIEMAC). SIEMAC was demonstrated on a human central lung cancer patient and a minipig. Results:SIEMAC simultaneously improves maps of spot intensities and patient-field-specific sparse range compensators and range modulators. For the lung cancer patient, at our maximum nozzle current of 300 nA, dose rate coverage above 100 Gy/s increased from 57% to 96% in the lung and from 93% to 100% in the heart, and LET coverage above 4 keV/μm dropped from 68% to 9% in the lung and from 26% to <1% in the heart. For a simple minipig plan, the full-width-half-maximum of the dose, dose rate, and LET distributions decreased by 30%, 1.6%, and 57%, respectively, again with similar target dose coverage, thus reducing uncertainty in these quantities for preclinical studies. Conclusion:The inverse solution to IPO-IMPT demonstrated the capability to simultaneously modulate sub-spot proton energy and intensity distributions for clinical and preclinical studies.

A linear energy transfer distributions computation method for inhomogeneous medium by using the water equivalent ratio approximation.

Dose-averaged linear energy transfer (LET), LETd is widely used in proton therapy. Compared with analytical models, Monte Carlo (MC) simulations are more accurate in obtaining LETd distributions, but they are time-consuming. This study used the 3D LETd distributions of proton beam spots in water by MC simulations as a benchmark data set. Subsequently, by combining the water equivalent ratio of various human tissues, the 3D LETd distributions of clinical cases could be quickly obtained. Our method was applied to a single spot of 160MeV proton beam in a water-bone phantom and a pelvic case. We also computed the 3D LETd distributions for multiple proton beam spots in the pelvic case and a lung case. The results of our method were compared with the results of MC simulations, demonstrating that our method can rapidly provide 3D LETd distributions of clinical cases with acceptable differences from MC simulations.

A Novel Planning and Delivery Technology: Dose, Dose Rate and Linear Energy Transfer (LET) Optimization Based on Spot-Scanning Proton Arc Therapy FLASH (SPLASHLET)

To achieve a high conformal dose with Linear Energy Transfer (LET) optimized FLASH proton therapy, we introduced a new planning and delivery technique concept, the voxel-wised optimization of LET distribution and dose rate based on scanning arc therapy (SPLASHLET) MATERIALS/METHODS: The algorithm optimizes (1) the clinical dose-volume constraint based on dose distribution and (2) the clinical LET-volume constraint based on LET distribution using Alternating Direction Method of Multipliers (ADMM) with Limited-memory BFGS solver by minimizing the monitor unit (MU) constraint on spot weight and (3) the effective dose-average dose rate by minimizing the accelerator's beam current sequentially. Such optimization framework enables the high dose conformal dynamic arc therapy with the capability of LET painting with voxel-based FLASH dose rate in an open-source proton planning platform (MatRad, Department of Medical Physics in Radiation Oncology, German Cancer Research Center-DKFZ). It aiming to minimize the overall cost function value combined with plan quality and voxel-based LET and dose rate constraints. Three representative cases (brain, liver and prostate cancer) were used for testing purposes. Dose-volume histogram (DVH), LET volume histogram (LVH) dose rate volume histogram (DRVH) and dose rate map were assessed compared to the original SPArc plan (SPArcoriginal). SPLASHLET plan could offer comparable plan quality compared to SPArcoriginal plan. The DRVH results indicated that SPArcoriginal could not achieve FLASH using the clinic beam current configuration, while SPLASHLET could significantly not only improve V40Gy/s in target and region of interest (ROI) but also improve the mean LET in the target and reduce the high LET in organ at risk (OAR) in comparison with SPArcoriginal (Table 1). SPLASHLET offers the first LET painting with voxel-based ultra-dose-rate and high-dose conformity treatment using proton beam therapy. Such technique has the potential to take full vantage of LET painting, FLASH and SPArc.

Improved Algorithm for Estimation of Linear Energy Transfer in Carbon Ion Radiotherapy Plans.

This study aimed to develop an improved algorithm for linear energy transfer (LET) estimation in carbon ion radiotherapy (CIRT) using relative biological effectiveness (RBE) and to establish a clinical pipeline for LET assessment. New approximation functions for LET versus RBE were developed for the overkill region. LET estimation performance was examined at two facilities (A and B) using archival- and Monte Carlo simulation-derived LET data, respectively, as a reference. A clinical pipeline for LET assessment was developed using Python and treatment planning systems (TPS). In dataset A, LET estimation accuracy in the overkill region was improved by 80.0%. In dataset B, estimation accuracy was 2.3%±0.67% across 5 data points examined. LET distribution and LET-volume histograms were visualized for multiple CIRT plans. The new algorithm showed a greater LET estimation performance at multiple facilities using the same TPS. A clinical pipeline for LET assessment was established.

Investigating Slit-Collimator-Produced Carbon Ion Minibeams with High-Resolution CMOS Sensors

Particle minibeam therapy has demonstrated the potential for better healthy tissue sparing due to spatial fractionation of the delivered dose. Especially for heavy ions, the spatial fractionation could enhance the already favorable differential biological effectiveness at the target and the entrance region. Moreover, spatial fractionation could even be a viable option for bringing ions heavier than carbon back into patient application. To understand the effect of minibeam therapy, however, requires careful conduction of pre-clinical experiments, for which precise knowledge of the minibeam characteristics is crucial. This work introduces the use of high-spatial-resolution CMOS sensors to characterize collimator-produced carbon ion minibeams in terms of lateral fluence distribution, secondary fragments, track-averaged linear energy transfer distribution, and collimator alignment. Additional simulations were performed to further analyze the parameter space of the carbon ion minibeams in terms of beam characteristics, collimator positioning, and collimator manufacturing accuracy. Finally, a new concept for reducing the neutron dose to the patient by means of an additional neutron shield added to the collimator setup is proposed and validated in simulation. The carbon ion minibeam collimator characterized in this work is used in ongoing pre-clinical experiments on heavy ion minibeam therapy at the GSI.

PO-1961 Linear Energy Transfer Distributions for Pencil Beam Scanning of Pediatric Brain Tumors

PO-1961 Linear Energy Transfer Distributions for Pencil Beam Scanning of Pediatric Brain Tumors

Spot scanning proton arc therapy reduces toxicity in oropharyngeal cancer patients.

Proton arc technology has recently shown dosimetric gains for various treatment indications. The increased number of beams and energy layers (ELs) in proton arc plans, increases the degrees of freedom in plan optimization and thereby flexibility to spare dose in organs at risk (OARs). A relationship exists between dosimetric plan quality, delivery efficiency, the number of ELs -and beams in a proton arcplan. This work aims to investigate the effect of the number of beams and ELs in a proton arc plan, on toxicity and delivery time for oropharyngeal cancer patients (OPC) selected for intensity modulated proton therapy (IMPT) based on the Dutch model-basedapproach. The EL reduction algorithm iteratively selects ELs from beams equidistantly spaced over a 360° arc. The beams in the final plan may contain multiple ELs, making them suited for static delivery on the studied treatment machine. The produced plans can therefore be called "step and shoot" proton arc plans. The number of beams and ELs were varied to determine the relationship with the planning cost function value, normal tissue complication probability (NTCP) and delivery time. Proton arc plans with robust target coverage and optimal energy layer reduction (ELR) settings to reduce NTCP, were generated for 10 OPC patients. Proton arc plans were compared to clinical volumetric modulated arc therapy (VMAT) and IMPT plans in terms of integral dose, OAR dose, NTCP for xerostomia and dysphagia and delivery time. Furthermore, dose-weighted average linear energy transfer (LETd ) distributions were compared between the IMPT and proton arc plans. A dry run delivery of a plan containing 20 beams and 360 ELs was performed to evaluate delivery time andaccuracy. We found 360 ELs distributed over 30 beams generated proton arc plans with near minimal expected plan toxicity. Relative to corresponding IMPT and VMAT plans, an average reduction of 21 ± 3% and 58 ± 10% in integral dose was observed. D was reduced most in the pharyngeal constrictor muscle (PCM) medius structure, with on average 9.0 ± 4.2 Gy(RBE) (p = 0.0002) compared to the clinical IMPT plans. The average NTCP for grade≥2 and grade≥3 xerostomia at 6 months after treatment significantly decreased with 4.7 ± 1.8% (p = 0.002) and 1.7 ± 0.8% (p = 0.002), respectively, while the average NTCP for grade≥2 and grade≥3 dysphagia decreased with 4.4 ± 2.9% (p = 0.002) and 0.9 ± 0.4% (p = 0.002), respectively, increasing the benefit of protons relative to VMAT. For a "step and shoot" proton arc delivery with auto beam sequencing the estimated delivery time is 11 min, similar to the delivery time of a 6-field IMPT treatment. Gamma analysis between the planned and delivered dose distribution resulted in a 99.99% pass rate using 1mm/1% dose difference/distance to agreement criteria. "Step and shoot" proton arc demonstrates potential to further reduce toxicity compared to IMPT and VMAT in OPC treatment. By employing 360 ELs and 30 beams in the proposed ELR method, delivery time can reach clinically acceptable levels without compromising plan toxicity when automatic beam sequencing isavailable.

Proposing a Clinical Model for RBE Based on Proton Track-End Counts

In proton therapy, the clinical application of linear energy transfer (LET) optimization remains contentious, in part because of challenges associated with the definition and calculation of LET and its exact relationship with relative biological effectiveness (RBE) because of large variation in experimental in vitro data. This has raised interest in other metrics with favorable properties for biological optimization, such as the number of proton track ends in a voxel. In this work, we propose a novel model for clinical calculations of RBE, based on proton track end counts. We developed an effective dose concept to translate between the total proton track-end count per unit mass in a voxel and a proton RBE value. Dose, track end, and dose-averaged LET (LETd) distributions were simulated using Monte Carlo models for a series of water phantoms, in vitro radiobiological studies, and patient treatment plans. We evaluated the correlation between track ends and regions of elevated biological effectiveness in comparison to LETd-based models of RBE. Track ends were found to correlate with biological effects in in vitro experiments with an accuracy comparable to LETd. In patient simulations, our track end model identified the same biological hotspots as predicted by LETd-based radiobiological models of proton RBE. These results suggest that, for clinical optimization and evaluation, an RBE model based on proton track end counts may match LETd-based models in terms of information provided while also offering superior statistical properties.

Radio-fluorogenic nanoclay gel dosimeters with reduced linear energy transfer dependence for carbon-ion beam radiotherapy.

The precise assessment of the dose distribution of high linear energy transfer (LET) radiation remains a challenge, because the signal of most dosimeters will be saturated due to the high ionization density. Such measurements are particularly important for heavy-ion beam cancer therapy. On this basis, the present work examined the high LET effect associated with three-dimensional gel dosimetry based on radiation-induced chemical reactions. The purpose of this study was to create an ion beam radio-fluorogenic gel dosimeter with a reduced effect of LET. Nanoclay radio-fluorogenic gel (NC-RFG) dosimeters were prepared, typically containing 100μM dihydrorhodamine 123 (DHR123) and 2.0wt% nanoclay together with catalytic additives promoting Fenton or Fenton-like reactions. The radiological properties of NC-RFG dosimeters having different compositions in response to a carbon-ion beam were investigated using a fluorescence gel scanner. An NC-RFG dosimeter capable of generating a fluorescence intensity distribution reflecting the carbon-ion beam dose profile was obtained. It was clarified that the reduction of the unfavorable LET dependence results from an acceleration of the reactions between DHR123 and H2 O2 , which is a molecular radiolysis product. The effects of varying the preparation conditions on the radiological properties of these gels were also examined. The optimum H2 O2 catalyst was determined to include 1mM Fe3+ ions, and the addition of 100mM pyridine was also found to increase the sensitivity. This technique allows the first-ever evaluation of the depth-dose profile of a carbon-ion beam at typical therapeutic levels of several Gy without LET effect.

Three-dimensional dose and LETD prediction in proton therapy using artificial neural networks.

Challenges in proton therapy include identifying patients most likely to benefit; ensuring consistent, high-quality plans as its adoption becomes more widespread; and recognizing biological uncertainties that may be related to increased relative biologic effectiveness driven by linear energy transfer (LET). Knowledge-based planning (KBP) is a domain that may help to address all three. Artificial neural networks were trained using 117 unique treatment plans and associated dose and dose-weighted LET (LETD ) distributions. The data set was split into training (n=82), validation (n=17), and test (n=18) sets. Model performance was evaluated on the test set using dose- and LETD -volume metrics in the clinical target volume (CTV) and nearby organs at risk and Dice similarity coefficients (DSC) comparing predicted and planned isodose lines at 50%, 75%, and 95% of the prescription dose. Dose-volume metrics significantly differed (α=0.05) between predicted and planned dose distributions in only one dose-volume metric, D2% to the CTV. The maximum observed root mean square (RMS) difference between corresponding metrics was 4.3 GyRBE (8% of prescription) for D1cc to optic chiasm. DSC were 0.90, 0.93, and 0.88 for the 50%, 75%, and 95% isodose lines, respectively. LETD -volume metrics significantly differed in all but one metric, L0.1cc of the brainstem. The maximum observed difference in RMS differences for LETD metrics was 1.0keV/μm for L0.1cc to brainstem. We have devised the first three-dimensional dose and LETD -prediction model for cranial proton radiation therapy has been developed. Dose accuracy compared favorably with that of previously published models in other treatment sites. The agreement in LETD supports future investigations with biological doses in mind to enable the full potential of KBP in proton therapy.

Characterization of Stray Radiation Produced by a Proton Beam in an Anthropomorphic Phantom with Dental Implants Using a Pixel Detector

<h3>Purpose/Objective(s)</h3> We investigated the scattered radiation produced by a collimated proton beam in the case of head and neck cancer using an anthropomorphic head phantom with human-like anatomy, with two dental implants inserted. Using high-resolution semiconductor pixel detectors, we measured and analyzed the backscatter radiation with particle identification resolving power. This research is focused on giving quantitative information about the radiation field components. <h3>Materials/Methods</h3> A treatment plan was designed on a standard X-ray CT which contained the implants at the center of the tumor. Two irradiations of an anthropomorphic head phantom were performed with clinical proton beams: one without metallic implants (plastic inserts) and one with dental implants. Two titanium cylindrical inserts of 1 cm length and 0.33 cm diameter were placed in the phantom's upper jaw like the molar's replacements. The planning target volume (PTV) is shaped so that the dental inserts are centered in the target volume. A scattered fixed proton beam with a nominal energy of 170 MeV was delivered to the phantom using collimators and boluses designed to shape and stop the beam according to the treatment plan. Scattered primary and secondary radiation was detected with hybrid semiconductor pixel detectors, placed at 4 cm behind the PTV. Detailed description of the mixed-radiation field was performed with spectral (energy loss) and tracking (direction) sensitivity. <h3>Results</h3> Measurements included a low intensity proton beam to assess the particle tracking response and identification resolving power in both situations (with and without implants). In this manner, the components of the radiation field were observed and analyzed. Based on their characteristic directional-sensitive spectral-track signal in the detector, both primary and secondary protons can be distinguished from light charged particles. This was done by analyzing single particle pixelated clusters morphology, spectral and directional sensitive parameters. Directional fluxes and linear energy transfer (LET) spectra of charged particle groups provide information about the scattered radiation field. <h3>Conclusion</h3> We present novel information about dental metallic implants' influences in a proton-based treatment. Preliminary results show differences in the LET distributions of the scattered radiation when the implants are in place, respectively, when they are missing. Further analyses will be done to provide a detailed dissemination of contribution for every type of particle.

Compact portable sources of high-LET radiation: Validation and potential application for galactic cosmic radiation countermeasure discovery

Implementation of a systematic program for galactic cosmic radiation (GCR) countermeasure discovery will require convenient access to ground-based space radiation analogs. The current gold standard approach for GCR simulation is to use a particle accelerator for sequential irradiation with ion beams representing different GCR components. This has limitations, particularly for studies of non-acute responses, strategies that require robotic instrumentation, or implementation of complex in vitro models that are emerging as alternatives to animal experimentation. Here we explore theoretical and practical issues relating to a different approach to provide a high-LET radiation field for space radiation countermeasure discovery, based on use of compact portable sources to generate neutron-induced charged particles. We present modeling studies showing that DD and DT neutron generators, as well as an AmBe radionuclide-based source, generate charged particles with a linear energy transfer (LET) distribution that, within a range of biological interest extending from about 10 to 200 keV/μm, resembles the LET distribution of reference GCR radiation fields experienced in a spacecraft or on the lunar surface. We also demonstrate the feasibility of using DD neutrons to induce 53BP1 DNA double-strand break repair foci in the HBEC3-KT line of human bronchial epithelial cells, which are widely used for studies of lung carcinogenesis. The neutron-induced foci are larger and more persistent than X ray-induced foci, consistent with the induction of complex, difficult-to-repair DNA damage characteristic of exposure to high-LET (>10 keV/μm) radiation. We discuss limitations of the neutron approach, including low fluence in the low LET range (<10 keV/μm) and the absence of certain long-range features of high charge and energy particle tracks. We present a concept for integration of a compact portable source with a multiplex microfluidic in vitro culture system, and we discuss a pathway for further validation of the use of compact portable sources for countermeasure discovery.

Linear energy transfer (LET) spectroscopy and relative biological effect estimation by SiC-based dosimeter at clinical carbon-beam cancer therapy field

A radiation-tolerant silicon carbide (SiC) based dosimeter was developed for the measurement of linear energy transfer (LET) distributions along the Bragg curve for pristine and spread-out Bragg peak (SOBP) clinical carbon beam. Since the conventional ionized chamber is not suitable and effective for LET measurement, several energy-dispersive dosimeters are being developed and tested in the clinical field. While most of the detector lacks radiation hardness against carbon beam, we have utilized wide-bandgap semiconductors of SiC with different epitaxial layers from 25, 69, and 170 μm as a dosimeter for the clinical carbon field at Gunma University Heavy Ion Medical Center (GHMC). LET spectra were obtained not only for pristine carbon beams with an energy of 290 MeV/n but also SOBP conditions. It was confirmed through the changes in LET distribution, primally carbons and fragments are identified, and those energy depositions are successfully obtained by the fabricated SiC dosimeter. The distribution of relative biological effectiveness (RBE) was estimated from LET through biological estimation models. Results suggested that SiC-based dosimeter is successful in being utilized in the detailed characterization of the clinical carbon therapy field.

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.

Transient Current Analysis of Silicon Carbide Neutron Detector Using SRIM and TCAD

Since neutrons are electrically neutral, the methods used to detect neutrons generally rely on secondary charged particles, which are produced by the interaction of neutrons and neutron conversion materials (such as <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> LiF, <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">10</sup> B). In this report, the SRIM code has been used to analyze the ionization properties of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\alpha $ </tex-math></inline-formula> particles and <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> H particles traveling through the Silicon Carbide (SiC) diode, and subsequently, the final Bragg ionization distribution has been obtained. Next, according to the obtained ionization distribution of secondary particles, the linear energy transfer (LET) distribution of the secondary particles is extraced accurately. Finally, based on the distribution of LET, Technology Computer Aided Design (TCAD) simulations are utilized to analyze the transient current pulses of thin-film-coated and trench-type SiC diodes. In addition, the effects of particle energy and applied reverse bias on the output pulse characteristics of SiC diodes are also explored. Essentially, this paper augments the understanding of output response from SiC neutron detectors, and for trench-type detectors, the order of output current pulse amplitude decreases significantly and has a long-tail. Therefore, the trench-type detectors not only need a more advanced fabrication process but also require the design of dedicated readout electronics.