Maternal effects, reciprocal differences and combining ability study for yield and its component traits in maize (Zea mays L.) through modified diallel analysis.

Combining ability status of the inbred lines is crucial information for hybrid breeding program. Diallel or line × tester mating designs are frequently used to evaluate the combining ability. In the current study a modified diallel model was used, wherein the Griffing's combining ability effects were further partitioned to understand the effects due to maternal and reciprocal. To do this, eight parental lines of maize were crossed in full diallel method and the generated hybrids along with parents were phenotyped. The field data on the quantitative traits was analyzed using both Griffing's and the modified model to determine how well the parents' and the F1 hybrids combined. For each of the traits, a sizable reciprocal and maternal variance was observed. The number of kernel rows per cob variable had a ratio of additive variance to dominance variance greater than one. All other traits including grain yield had a ratio close to zero, suggesting that non-additive gene action was primarily responsible for the genetic control of most of the traits. The narrow sense heritability was low to moderate for majority of the variables, except for number of kernel rows per cob. With the help of the improved model, it was possible to choose superior parents and cross-parent pairings with accuracy. Based on the modified general combining ability effects and maternal effects, the parental line P5 was recognized as a potential female parent and P7 as a good male parent for grain yield and yield-attributing characteristics. The cross combination of P8×P1 had the highest specific combining ability effect on grain yield. P5×P6 cross had the highest reciprocal effect. The correlation analysis implies that the Griffing's general combining ability effects and specific combining ability effects were found to be less efficient in predicting F1 performance as compared to the modified model.

Robust optimization strategies for contour uncertainties in online adaptive radiation therapy.

OBJECTIVE: Online adaptive radiation therapy requires fast and automated contouring of daily scans for treatment plan re-optimization. However, automated contouring is imperfect and introduces contour uncertainties. This work aims at developing and comparing robust optimization strategies accounting for such uncertainties. Approach: A deep-learning method was used to predict the uncertainty of deformable image registration, and to generate a finite set of daily contour samples. Ten optimization strategies were compared: two baseline methods, five methods that convert contour samples into voxel-wise probabilities, and three methods accounting explicitly for contour samples as scenarios in robust optimization. Target coverage and organ-at-risk (OAR) sparing were evaluated robustly for simplified proton therapy plans for five head-and-neck cancer patients. Results: We found that explicitly including target contour uncertainty in robust optimization provides robust target coverage with better OAR sparing than the baseline methods, without increasing the optimization time. Although OAR doses first increased when increasing target robustness, this effect could be prevented by additionally including robustness to OAR contour uncertainty. Compared to the probability-based methods, the scenario-based methods spared the OARs more, but increased integral dose and required more computation time. Significance: This work proposed efficient and beneficial strategies to mitigate contour uncertainty in treatment plan optimization. This facilitates the adoption of automatic contouring in online adaptive radiation therapy and, more generally, enables mitigation also of other sources of contour uncertainty in treatment planning.

Multi-institutional experimental validation of online adaptive proton therapy workflows.

OBJECTIVE: To experimentally validate two online adaptive proton therapy (APT) workflows using Gafchromic EBT3 films and optically stimulated luminescent dosimeters (OSLDs) in an anthropomorphic head-and-neck phantom. Approach: A three-field proton plan was optimized on the planning CT of the head-and-neck phantom with 2.0 Gy(RBE) per fraction prescribed to the clinical target volume. Four fractions were simulated by varying the internal anatomy of the phantom. Three distinct methods were delivered: daily adaptive proton therapy researched by the Paul Scherrer Institute (DAPT_PSI), online adaptation researched by the Massachusetts General Hospital (OA_MGH), and a non-adaptive (NA) workflow. All methods were implemented and measured at PSI. DAPT_PSI performed full online replanning based on analytical dose calculation, optimizing to the same objectives as the initial treatment plan. OA_MGH performed Monte-Carlo-based online plan adaptation by only changing the fluences of a subset of proton beamlets, mimicking the planned dose distribution. NA delivered the initial plan with a couch-shift correction based on in-room-imaging. For all 12 deliveries, two films and two sets of OSLDs were placed at different locations in the phantom. Main results: Both adaptive methods showed improved dosimetric results compared to NA. For film measurements in the presence of anatomical variations, the [min-max] gamma pass rates (3%/3 mm) between measured and clinically approved doses were [91.5%-96.1%], [94.0%-95.8%], and [67.2%-93.1%] for DAPT_PSI, OA_MGH, and NA, respectively. The OSLDs confirmed the dose calculations in terms of absolute dosimetry. Between the two adaptive workflows, OA_MGH showed improved target coverage, while DAPT_PSI showed improved normal tissue sparing, particularly relevant for the brainstem. Significance: This is the first multi-institutional study to experimentally validate two different concepts with respect to online adaptive proton therapy workflows. It highlights their respective dosimetric advantages, particularly in managing interfractional variations in patient anatomy that cannot be addressed by non-adaptive methods, such as internal anatomy changes.

Comprehensive analysis of little leaf disease incidence and resistance in eggplant.

BACKGROUND: Little leaf disease caused by phytoplasma infection is a significant threat to eggplant (also known as brinjal) cultivation in India. This study focused on the molecular characterisation of the phytoplasma strains and insect vectors responsible for its transmission and screening of brinjal germplasm for resistance to little leaf disease. RESULTS: Surveys conducted across districts in the Tamil Nadu state of India during 2021-2022 showed a higher incidence of phytoplasma during the Zaid (March to June), followed by Kharif (June to November) and Rabi (November to March) seasons with mean incidence ranging from 22 to 27%. As the name indicates, phytoplasma infection results in little leaf (reduction in leaf size), excessive growth of axillary shoots, virescence, phyllody, stunted growth, leaf chlorosis and witches' broom symptoms. PCR amplification with phytoplasma-specific primers confirmed the presence of this pathogen in all symptomatic brinjal plants and in Hishimonus phycitis (leafhopper), providing valuable insights into the role of leafhoppers in disease transmission. BLAST search and phylogenetic analysis revealed the phytoplasma strain as "Candidatus Phytoplasma trifolii". Insect population and disease dynamics are highly influenced by environmental factors such as temperature, relative humidity and rainfall. Further, the evaluation of 22 eggplant accessions revealed immune to highly susceptible responses where over 50% of the entries were highly susceptible. Finally, additive main effect and multiplicative interaction (AMMI) and won-where biplot analyses identified G18 as a best-performing accession for little leaf resistance due to its consistent responses across multiple environments. CONCLUSIONS: This research contributes essential information on little leaf incidence, symptoms, transmission and resistance profiles of different brinjal genotypes, which together ensure effective and sustainable management of this important disease of eggplants.

Deformable vector fields warping for modelling of irregular breathing.

Purpose 4D computed tomography (4DCT) is the clinical standard to image organ motion in radiotherapy, although it is limited in imaging breathing variability. We propose a method to transfer breathing motion across longitudinal imaging datasets to include intra-patient variability and verify its performance in lung cancer patients. Methods Five repeated control 4DCTs for 6 non-small cell lung cancer patients were combined into multi-breath datasets (m4DCT) by merging stages of deformable image registration to isolate respiratory motion. The displacement of the centre of mass of the primary tumour and its volume changes were evaluated to quantify intra-patient differences. Internal target volumes defined on the m4DCT were compared with those conventionally drawn on the 4DCT. Results Motion analysis suggests no discontinuity at the junction between successive breaths, confirming the method's ability to merge repeated imaging into a continuum. Motion (variability) is primarily in superior-inferior direction and goes from 14.4 mm (8.7 mm) down to 0.1 mm (0.6 mm), respectively for tumours located in the lower lobes or most apical ones. On average, up to 65% and 74% of the tumour volume was subject to expansion or contraction in the inhalation and exhalation phases. These variations lead to an enlargement of the ITV up to 8% of its volume in our dataset. Conclusion 4DCT can be extended to model variable breathing motion by adding synthetic phases from multiple time-resolved images. The inclusion of this improved knowledge of patients' breathing allows better definition of treatment volumes and their margins for radiation therapy. .

Retrospective reconstruction of four-dimensional magnetic resonance from interleaved cine imaging - A comparative study with four-dimensional computed tomography in the lung.

Background and purpose: Imaging of respiration-induced anatomical changes is essential to ensure high accuracy in radiotherapy of lung cancer. We expanded here on methods for retrospective reconstruction of time-resolved volumetric magnetic resonance (4DMR) of the thoracic region and benchmarked the results against 4D computed tomography (4DCT). Materials and method: MR data of six lung cancer patients were collected by interleaving cine-navigator images with 2D data frame images, acquired across the thorax. The data frame images have been stacked in volumes based on a similarity metric that considers the anatomical deformation of lungs, while addressing ambiguities in respiratory phase detection and interpolation of missing data. The resulting images were validated against cine-navigator images and compared to paired 4DCTs in terms of amplitude and period of motion, assessing differences in internal target volume (ITV) margin definition. Results: 4DMR-based motion amplitude was on average within 1.8 mm of that measured in the corresponding 2D cine-navigator images. In our dataset, the 4DCT motion and the 4DMR median amplitude were always within 3.8 mm. The median period was generally close to CT references, although deviations up to 24 % have been observed. These changes were reflected in the ITV, which was generally larger for MRI than for 4DCT (up to 39.7 %). Conclusions: The proposed algorithm for retrospective reconstruction of time-resolved volumetric MR provided quality anatomical images with high temporal resolution for motion modelling and treatment planning. The potential for imaging organ motion variability makes 4DMR a valuable complement to standard 4DCT imaging.

Exploring beamline momentum acceptance for tracking respiratory variability in lung cancer proton therapy: a simulation study.

Objective. Investigating the aspects of proton beam delivery to track organ motion with pencil beam scanning therapy. Considering current systems as a reference, specify requirements for next-generation units aiming at real-time image-guided treatments.Approach. Proton treatments for six non-small cell lung cancer (NSCLC) patients were simulated using repeated 4DCTs to model respiratory motion variability. Energy corrections required for this treatment site were evaluated for different approaches to tumour tracking, focusing on the potential for energy adjustment within beamline momentum acceptance (dp/p). A respiration-synchronised tracking, taking into account realistic machine delivery limits, was compared to ideal tracking scenarios, in which unconstrained energy corrections are possible. Rescanning and the use of multiple fields to mitigate residual interplay effects and dose degradation have also been investigated.Main results. Energy correction requirements increased with motion amplitudes, for all patients and tracking scenarios. Higher dose degradation was found for larger motion amplitudes, rescanning has beneficial effects and helped to improve dosimetry metrics for the investigated limited dp/pof 1.2% (realistic) and 2.4%. The median differences between ideal and respiratory-synchronised tracking show minimal discrepancies, 1% and 5% respectively for dose coverage (CTV V95) and homogeneity (D5-D95). Multiple-field planning improves D5-D95 up to 50% in the most extreme cases while it does not show a significant effect on V95.Significance. This work shows the potential of implementing tumour tracking in current proton therapy units and outlines design requirements for future developments. Energy regulation within momentum acceptance was investigated to tracking tumour motion with respiratory-synchronisation, achieving results in line with the performance of ideal tracking scenarios. ±5% Δp/p would allow to compensate for all range offsets in our NSCLC patient cohort, including breathing variability. However, the realistic momentum of 1.2% dp/prepresentative of existing medical units limitations, has been shown to preserve plan quality.

A bi-directional beam-line energy ramping for efficient patient treatment with scanned proton therapy.

Objective.The treatment of mobile tumours using Pencil Beam Scanning (PBS) has become more prevalent in the last decade. However, to achieve the same beam delivery quality as for static tumours, treatments have to be combined with motion mitigation techniques, not limited but including, breath hold, gating and re-scanning, which typically prolong treatment time. In this article we present a novel method of bi-directional energy modulation and demonstrate our initial experience in improvement of treatment efficiency. Approach.At Paul Scherrer Institute Gantry 2 mobile tumours are treated by combining PBS with gating and volumetric re-scanning (VR), where the target volume is irradiated multiple times. Initial implementation of VR used only descending beam energies, creating a substantial dead time due to the beam-line initialization (ramping) before each re-scan. In 2019 we commissioned an energy meandering strategy that allows us to avoid beam line ramping in-between energy series while maintaining beam delivery quality.Main results.The measured beam parameters difference for both energy sequence are in the order of the typical daily variations: 0.2 mm in beam position and 0.2 mm in range. Using machine log files, we performed point-to-point dose difference calculations between original and new applications where we observed dose differences of less than 2%. After three years of operation employing bi-directional energy modulation, we have analysed the individual beam delivery time for 181 patients and have compared this to simulations of the timing behaviour assuming uni-directional energy sequence application. Depending on treatment complexity, we obtained plan delivery time reductions of up to 55%, with a median time gain of 17% for all types of treatments.Significance. Bi-directional energy modulation can help improving patient treatment efficiency by reducing delivery times especially for complex and specialised irradiations. It could be implemented in many existing facilities without significant additional hardware upgrades.

Detection of range shifts in proton beam therapy using the J-PET scanner: a patient simulation study.

OBJECTIVE: The Jagiellonian PET (J-PET) technology, based on plastic scintillators, has been proposed as a cost effective tool for detecting range deviations during proton therapy. This study investigates the feasibility of using J-PET for range monitoring by means of a detailed Monte Carlo simulation study of 95 patients who underwent proton therapy at the Cyclotron Centre Bronowice (CCB) in Krakow, Poland. Approach: Discrepancies between prescribed and delivered treatments were artificially introduced in the simulations by means of shifts in patient positioning and in the Hounsfield unit to the relative proton stopping power calibration curve. A dual-layer, cylindrical J-PET geometry was simulated in an in-room monitoring scenario and a triple-layer, dual-head geometry in an in-beam protocol. The distribution of range shifts in reconstructed PET activity was visualised in the beam's eye view. Linear prediction models were constructed from all patients in the cohort, using the mean shift in reconstructed PET activity as a predictor of the mean proton range deviation. Main results: Maps of deviations in the range of reconstructed PET distributions showed agreement with those of deviations in dose range in most patients. The linear prediction model showed a good fit, with coefficient of determination r^2 = 0.84 (in-room) and 0.75 (in-beam). Residual standard error was below 1 mm: 0.33 mm (in-room) and 0.23 mm (in-beam). Significance: The precision of the proposed prediction models shows the sensitivity of the proposed J-PET scanners to shifts in proton range for a wide range of clinical treatment plans. Furthermore, it motivates the use of such models as a tool for predicting proton range deviations and opens up new prospects for investigations into the use of intra-treatment PET images for predicting clinical metrics that aid in the assessment of the quality of delivered treatment. .

Detailed Monte-Carlo characterization of a Faraday cup for proton therapy.

BACKGROUND: Experiments with ultra-high dose rates in proton therapy are of increasing interest for potential treatment benefits. The Faraday Cup (FC) is an important detector for the dosimetry of such ultra-high dose rate beams. So far, there is no consensus on the optimal design of a FC, or on the influence of beam properties and magnetic fields on shielding of the FC from secondary charged particles. PURPOSE: To perform detailed Monte Carlo simulations of a Faraday cup to identify and quantify all the charge contributions from primary protons and secondary particles that modify the efficiency of the FC response as a function of a magnetic field employed to improve the detector's reading. METHODS: In this paper, a Monte Carlo (MC) approach was used to investigate the Paul Scherrer Institute (PSI) FC and quantify contributions of charged particles to its signal for beam energies of 70, 150, and 228 MeV and magnetic fields between 0 and 25 mT. Finally, we compared our MC simulations to measurements of the response of the PSI FC. RESULTS: For maximum magnetic fields, the efficiency (signal of the FC normalized to charged delivered by protons) of the PSI FC varied between 99.97% and 100.22% for the lowest and highest beam energy. We have shown that this beam energy-dependence is mainly caused by contributions of secondary charged particles, which cannot be fully suppressed by the magnetic field. Additionally, it has been demonstrated that these contributions persist, making the FC efficiency beam energy dependent for fields up to 250 mT, posing inevitable limits on the accuracy of FC measurements if not corrected. In particular, we have identified a so far unreported loss of electrons via the outer surfaces of the absorber block and show the energy distributions of secondary electrons ejected from the vacuum window (VW) (up to several hundred keV), together with electrons ejected from the absorber block (up to several MeV). Even though, in general, simulations and measurements were well in agreement, the limitation of the current MC calculations to produce secondary electrons below 990 eV posed a limit in the efficiency simulations in the absence of a magnetic field as compared to the experimental data. CONCLUSION: TOPAS-based MC simulations allowed to identify various and previously unreported contributions to the FC signal, which are likely to be present in other FC designs. Estimating the beam energy dependence of the PSI FC for additional beam energies could allow for the implementation of an energy-dependent correction factor to the signal. Dose estimates, based on accurate measurements of the number of delivered protons, provided a valid instrument to challenge the dose determined by reference ionization chambers, not only at ultra-high dose rates but also at conventional dose rates.

Risk factors for distal construct failure in posterior spinal instrumented fusion for adolescent idiopathic scoliosis: a retrospective cohort study.

PURPOSE: To evaluate risk factors for distal construct failure (DCF) in posterior spinal instrumented fusion (PSIF) in adolescent idiopathic scoliosis (AIS). We hypothesise increased inferior angulation of the pedicle screw in the lowest instrumented vertebra (LIV) predisposes to failure and aim to find the critical angle that predisposes to failure. METHODS: A retrospective cohort study was performed on all patients who underwent PSIF for AIS at our institution from 2010 to 2020. On lateral radiographs, the angle between the superior endplate of the LIV was measured against its pedicle screw trajectory. Data on demographics, Cobb angle, Lenke classification, instrumentation density, rod protrusion from the most inferior screw, implants and reasons for revision were collected. RESULTS: Of 256 patients, 9 patients had DCF with 3 further failures post-revision, giving 12 cases to analyse. The DCF rate was 4.6%. The mean trajectory angle of DCF patients compared to non-DCF was 13.3° (95% CI 9.2° to 17.4°) vs. 7.6° (7.0° to 8.2°), p = 0.0002. The critical angle is less than 11° (p = 0.0076), OR 5.15. Lenke 5 and C curves, lower preoperative Cobb angle, titanium only rod constructs and one surgeon had higher failure rates. 9.6% of rods protruding less than 3 mm from its distal screw disengaged. CONCLUSION: Increased inferior trajectory of the LIV screw increases the rate of DCF; inferior trajectory greater than 11° predisposes to failure. Rod protrusion less than 3 mm from the distal screw increases rate of disengagement. LEVEL OF EVIDENCE: III.

Clinical outcome after pencil beam scanning proton therapy and dysphagia/xerostomia NTCP calculations of proton and photon radiotherapy delivered to patients with cancer of the major salivary glands.

OBJECTIVES: The purpose of this study is to report the oncological outcome, observed toxicities and normal tissue complication probability (NTCP) calculation for pencil beam scanning (PBS) PT delivered to salivary gland tumour (SGT) patients. METHODS: We retrospectively reviewed 26 SGT patients treated with PBSPT (median dose, 67.5 Gy(RBE)) between 2005 and 2020 at our institute. Toxicities were recorded according to CTCAEv.4.1. Overall survival (OS), local control (LC), locoregional control (LRC) and distant control (DC) were estimated. For all patients, a photon plan was re-calculated in order to assess the photon/proton NTCP. RESULTS: With a median follow-up time of 46 months (range, 3-118), 5 (19%), 2 (8%), 3 (12%) and 2 (8%) patients presented after PT with distant, local, locoregional failures and death, respectively. The estimated 4 year OS, LC, LCR and DC were 90%, 90%, 87 and 77%, respectively. Grade 3 late toxicity was observed in 2 (8%) patients. The estimated 4 year late high-grade (≥3) toxicity-free survival was 78.4%. The calculated mean difference of NTCP-values after PBSPT and VMAT plans for developing Grade 2 or 3 xerostomia were 3.8 and 2.9%, respectively. For Grade 2-3 dysphagia, the grade corresponding percentages were 8.6 and 1.9%. Not using an up-front model-based approach to select patients for PT, only 40% of our patients met the Dutch eligibility criteria. CONCLUSION: Our data suggest excellent oncological outcome and low late toxicity rates for patients with SGT treated with PBSPT. NTCP calculation showed a substantial risk reduction for Grade 2 or 3 xerostomia and dysphagia in some SGT patients, while for others, no clear benefit was seen with protons, suggesting that comparative planning should be performed routinely for these patients. ADVANCES IN KNOWLEDGE: We have reported that the clinical outcome of SGT patients treated with PT and compared IMPT to VMAT for the treatment of salivary gland tumour and have observed that protons delivered significantly less dose to organs at risks and were associated with less NTCP for xerostomia and dysphagia. Noteworthy, not using an up-front model-based approach, only 40% of our patients met the Dutch eligibility criteria.

The use of new approach methodologies for the environmental risk assessment of food and feed chemicals.

New Approach Methodologies (NAMs) provide tools for supporting both human and environmental risk assessment (HRA and ERA). This short review provides recent insights regarding the use of NAMs in ERA of food and feed chemicals. We highlight the usefulness of tiered methods supporting weight-of-evidence approaches in relation to problem formulation (i.e., data availability, time, and resource availability). In silico models, including quantitative structure activity relationship models, support filling data gaps when no chemical property or ecotoxicological data are available, and biologically-based models (e.g., toxicokinetic-toxicodynamic models, dynamic energy models, physiologically-based models and species sensitivity distributions) are applicable in more data rich situations, including landscape-based modelling approaches. Particular attention is given to provide practical examples to apply the approaches described in real-world settings. We conclude with future perspectives, with regards to the need for addressing complex challenges such as chemical mixtures and multiple stressors in a wide range of organisms and ecosystems.

Fatigue Analysis of a 40 ft LNG ISO Tank Container.

The demand for Liquefied natural gas (LNG) has rapidly increased over the past few years. This is because of increasingly stringent environmental regulations to curb harmful emissions from fossil fuels. LNG is one of the clean energy sources that has attracted a great deal of research. In the Republic of Korea, the use of LNG has been implemented in various sectors, including public transport buses, domestic applications, power generation, and in huge marine engines. Therefore, a proper, flexible, and safe transport system should be put in place to meet the high demand. In this work, finite element analysis (FEA) was performed on a domestically developed 40 ft ISO LNG tank using Ansys Mechanical software under low- and high-cycle conditions. The results showed that the fatigue damage factor for all the test cases was much lower than 1. The maximum principal stress generated in the 40 ft LNG ISO tank container did not exceed the yield strength of the calculated material (carbon steel). Maximum principal stress of 123.2 MPa and 107.61 MPa was obtained with low-cycle and high-cycle analysis, respectively, which is 50.28% less than the yield strength of carbon steel. The total number of cycles was greater than the total number of design cycles, and the 40 ft LNG ISO tank container was satisfied with a fatigue life of 20 years.

The impact of organ motion and the appliance of mitigation strategies on the effectiveness of hypoxia-guided proton therapy for non-small cell lung cancer.

BACKGROUND AND PURPOSE: To investigate the impact of organ motion on hypoxia-guided proton therapy treatments for non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Hypoxia PET and 4D imaging data of six NSCLC patients were used to simulate hypoxia-guided proton therapy with different motion mitigation strategies including rescanning, breath-hold, respiratory gating and tumour tracking. Motion-induced dose degradation was estimated for treatment plans with dose painting of hypoxic tumour sub-volumes at escalated dose levels. Tumour control probability (TCP) and dosimetry indices were assessed to weigh the clinical benefit of dose escalation and motion mitigation. In addition, the difference in normal tissue complication probability (NTCP) between escalated proton and photon VMAT treatments has been assessed. RESULTS: Motion-induced dose degradation was found for target coverage (CTV V95% up to -4%) and quality of the dose-escalation-by-contour (QRMS up to 6%) as a function of motion amplitude and amount of dose escalation. The TCP benefit coming from dose escalation (+4-13%) outweighs the motion-induced losses (<2%). Significant average NTCP reductions of dose-escalated proton plans were found for lungs (-14%), oesophagus (-10%) and heart (-16%) compared to conventional VMAT plans. The best plan dosimetry was obtained with breath hold and respiratory gating with rescanning. CONCLUSION: NSCLC affected by hypoxia appears to be a prime target for proton therapy which, by dose-escalation, allows to mitigate hypoxia-induced radio-resistance despite the sensitivity to organ motion. Furthermore, substantial reduction in normal tissue toxicity can be expected compared to conventional VMAT. Accessibility and standardization of hypoxia imaging and clinical trials are necessary to confirm these findings in a clinical setting.

Universal and dynamic ridge filter for pencil beam scanning particle therapy: a novel concept for ultra-fast treatment delivery.

Objective.In pencil beam scanning particle therapy, a short treatment delivery time is paramount for the efficient treatment of moving targets with motion mitigation techniques (such as breath-hold, rescanning, and gating). Energy and spot position change time are limiting factors in reducing treatment time. In this study, we designed a universal and dynamic energy modulator (ridge filter, RF) to broaden the Bragg peak, to reduce the number of energies and spots required to cover the target volume, thus lowering the treatment time.Approach. Our RF unit comprises two identical RFs placed just before the isocenter. Both RFs move relative to each other, changing the Bragg peak's characteristics dynamically. We simulated different Bragg peak shapes with the RF in Monte Carlo simulation code (TOPAS) and validated them experimentally. We then delivered single-field plans with 1 Gy/fraction to different geometrical targets in water, to measure the dose delivery time using the RF and compare it with the clinical settings.Main results.Aligning the RFs in different positions produces different broadening in the Bragg peak; we achieved a maximum broadening of 2.5 cm. With RF we reduced the number of energies in a field by more than 60%, and the dose delivery time by 50%, for all geometrical targets investigated, without compromising the dose distribution transverse and distal fall-off.Significance. Our novel universal and dynamic RF allows for the adaptation of the Bragg peak broadening for a spot and/or energy layer based on the requirement of dose shaping in the target volume. It significantly reduces the number of energy layers and spots to cover the target volume, and thus the treatment time. This RF design is ideal for ultra-fast treatment delivery within a single breath-hold (5-10 s), efficient delivery of motion mitigation techniques, and small animal irradiation with ultra-high dose rates (FLASH).

ProTheRaMon - a GATE simulation framework for proton therapy range monitoring using PET imaging.

OBJECTIVE: This paper reports on the implementation and shows examples of the use of the ProTheRaMon framework for simulating the delivery of proton therapy treatment plans and range monitoring using positron emission tomography (PET). ProTheRaMon offers complete processing of proton therapy treatment plans, patient CT geometries, and intra-treatment PET imaging, taking into account therapy and imaging coordinate systems and activity decay during the PET imaging protocol specific to a given proton therapy facility. We present the ProTheRaMon framework and illustrate its potential use case and data processing steps for a patient treated at the Cyclotron Centre Bronowice (CCB) proton therapy center in Krakow, Poland. APPROACH: The ProTheRaMon framework is based on GATE Monte Carlo software, the CASToR reconstruction package and in-house developed Python and bash scripts. The framework consists of five separated simulation and data processing steps, that can be further optimized according to the user's needs and specific settings of a given proton therapy facility and PET scanner design. MAIN RESULTS: ProTheRaMon is presented using example data from a patient treated at CCB and the J-PET scanner to demonstrate the application of the framework for proton therapy range monitoring. The output of each simulation and data processing stage is described and visualized. SIGNIFICANCE: We demonstrate that the ProTheRaMon simulation platform is a high-performance tool, capable of running on a computational cluster and suitable for multi-parameter studies, with databases consisting of large number of patients, as well as different PET scanner geometries and settings for range monitoring in a clinical environment. Due to its modular structure, the ProTheRaMon framework can be adjusted for different proton therapy centers and/or different PET detector geometries. It is available to the community via github.

Combined proton-photon therapy for non-small cell lung cancer.

PURPOSE: Advanced non-small cell lung cancer (NSCLC) is still a challenging indication for conventional photon radiotherapy. Proton therapy has the potential to improve outcomes, but proton treatment slots remain a limited resource despite an increasing number of proton therapy facilities. This work investigates the potential benefits of optimally combined proton-photon therapy delivered using a fixed horizontal proton beam line in combination with a photon Linac, which could increase accessibility to proton therapy for such a patient cohort. MATERIALS AND METHODS: A treatment planning study has been conducted on a patient cohort of seven advanced NSCLC patients. Each patient had a planning computed tomography scan (CT) and multiple repeated CTs from three different days and for different breath-holds on each day. Treatment plans for combined proton-photon therapy (CPPT) were calculated for individual patients by optimizing the combined cumulative dose on the initial planning CT only (non-adapted) as well as on each daily CT respectively (adapted). The impact of inter-fractional changes and/or breath-hold variability was then assessed on the repeat breath-hold CTs. Results were compared to plans for IMRT or IMPT alone, as well as against combined treatments assuming a proton gantry. Plan quality was assessed in terms of dosimetric, robustness and NTCP metrics. RESULTS: Combined treatment plans improved plan quality compared to IMRT treatments, especially in regard to reductions of low and medium doses to organs at risk (OARs), which translated into lower NTCP estimates for three side effects. For most patients, combined treatments achieved results close to IMPT-only plans. Inter-fractional changes impact mainly the target coverage of combined and IMPT treatments, while OARs doses were less affected by these changes. With plan adaptation however, target coverage of combined treatments remained high even when taking variability between breath-holds into account. CONCLUSIONS: Optimally combined proton-photon plans improve treatment plan quality compared to IMRT only, potentially reducing the risk of toxicity while also allowing to potentially increase accessibility to proton therapy for NSCLC patients.

Influence of Radiation Dose, Photon Energy, and Reconstruction Kernel on rho/z Analysis in Spectral Computer Tomography: A Phantom Study.

BACKGROUND/AIM: The effective atomic number (Zeff) and electron density relative to water (ρe or Rho) of elements can be derived in dual-energy computed tomography (DECT). The aim of this phantom study was to investigate the effect of different photon energies, radiation doses, and reconstruction kernels on Zeff and Rho measured in DECT. MATERIALS AND METHODS: An anthropomorphic head phantom including five probes of known composition was scanned under three tube-voltage combinations in DECT: Sn140/100 kV, 140/80 kV and Sn140/80 kV with incremented radiation doses. Raw data were reconstructed with four reconstruction kernels (I30, I40, I50, and I70). Rho and Zeff were measured for each probe for all possible combinations of scan and reconstruction parameters. RESULTS: DECT-based Rho and Zeff closely approached the reference values with a mean and maximum error of 1.7% and 6.8%, respectively. Rho was lower for 140/80 kV compared with Sn140/100 kV and Sn140/80 kV with differences being 0.009. Zeff differed among all tube voltages with the most prominent difference being 0.28 between 140/80 kV and Sn140/100 kV. Zeff was lower in I70 compared with those of I30 and I40 with a difference of 0.07. Varying radiation dose yielded a variation of 0.0002 in Rho and 0.03 in Z, both considered negligible in practice. CONCLUSION: DECT comprises a feasible method for the extraction of material-specific information. Slight variations should be taken into account when different radiation doses, photon energies, and kernels are applied; however, they are considered small and in practice not crucial for an effective tissue differentiation.

Increase of the transmission and emittance acceptance through a cyclotron-based proton therapy gantry.

PURPOSE: In proton therapy, the gantry, as the final part of the beamline, has a major effect on beam intensity and beam size at the isocenter. Most of the conventional beam optics of cyclotron-based proton gantries have been designed with an imaging factor between 1 and 2 from the coupling point (CP) at the gantry entrance to the isocenter (patient location) meaning that to achieve a clinically desirable (small) beam size at isocenter, a small beam size is also required at the CP. Here we will show that such imaging factors are limiting the emittance which can be transported through the gantry. We, therefore, propose the use of large beam size and low divergence beam at the CP along with an imaging factor of 0.5 (2:1) in a new design of gantry beam optics to achieve substantial improvements in transmission and thus increase beam intensity at the isocenter. METHODS: The beam optics of our gantry have been re-designed to transport higher emittance without the need of any mechanical modifications to the gantry beamline. The beam optics has been designed using TRANSPORT, with the resulting transmissions being calculated using Monte Carlo simulations (BDSIM code). Finally, the new beam optics have been tested with measurements performed on our Gantry 2 at PSI. RESULTS: With the new beam optics, we could maximize transmission through the gantry for a fixed emittance value. Additionally, we could transport almost four times higher emittance through the gantry compared to conventional optics, whilst achieving good transmissions through the gantry (>50%) with no increased losses in the gantry. As such, the overall transmission (cyclotron to isocenter) can be increased by almost a factor of 6 for low energies. Additionally, the point-to-point imaging inherent to the optics allows adjustment of the beam size at the isocenter by simply changing the beam size at the CP. CONCLUSION: We have developed a new gantry beam optics which, by selecting a large beam size and low divergence at the gantry entrance and using an imaging factor of 0.5 (2:1), increases the emittance acceptance of the gantry, leading to a substantial increase in beam intensity at low energies. We expect that this approach could easily be adapted for most types of existing gantries.