Characterisation and Quenching Correction for an Al2O3:C Optical Fibre Real Time System in Therapeutic Proton, Helium, and Carbon-Charged Beams.

Real time radioluminescence fibre-based detectors were investigated for application in proton, helium, and carbon therapy dosimetry. The Al2O3:C probes are made of one single crystal (1 mm) and two droplets of micro powder in two sizes (38 µm and 4 µm) mixed with a water-equivalent binder. The fibres were irradiated behind different thicknesses of solid slabs, and the Bragg curves presented a quenching effect attributed to the nonlinear response of the radioluminescence (RL) signal as a function of linear energy transfer (LET). Experimental data and Monte Carlo simulations were utilised to acquire a quenching correction method, adapted from Birks' formulation, to restore the linear dose-response for particle therapy beams. The method for quenching correction was applied and yielded the best results for the '4 µm' optical fibre probe, with an agreement at the Bragg peak of 1.4% (160 MeV), and 1.5% (230 MeV) for proton-charged particles; 2.4% (150 MeV/u) for helium-charged particles and of 4.8% (290 MeV/u) and 2.9% (400 MeV/u) for the carbon-charged particles. The most substantial deviations for the '4 µm' optical fibre probe were found at the falloff regions, with ~3% (protons), ~5% (helium) and 6% (carbon).

Visually guided inspiration breath-hold facilitated with nasal high flow therapy in locally advanced lung cancer.

BACKGROUND AND PURPOSE: Reducing breathing motion in radiotherapy (RT) is an attractive strategy to reduce margins and better spare normal tissues. The objective of this prospective study (NCT03729661) was to investigate the feasibility of irradiation of non-small cell lung cancer (NSCLC) with visually guided moderate deep inspiration breath-hold (IBH) using nasal high-flow therapy (NHFT). MATERIAL AND METHODS: Locally advanced NSCLC patients undergoing photon RT were given NHFT with heated humidified air (flow: 40 L/min with 80% oxygen) through a nasal cannula. IBH was monitored by optical surface tracking (OST) with visual feedback. At a training session, patients had to hold their breath as long as possible, without and with NHFT. For the daily cone beam CT (CBCT) and RT treatment in IBH, patients were instructed to keep their BH as long as it felt comfortable. OST was used to analyze stability and reproducibility of the BH, and CBCT to analyze daily tumor position. Subjective tolerance was measured with a questionnaire at 3 time points. RESULTS: Of 10 included patients, 9 were treated with RT. Seven (78%) completed the treatment with NHFT as planned. At the training session, the mean BH length without NHFT was 39 s (range 15-86 s), and with NHFT 78 s (range 29-223 s) (p = .005). NHFT prolonged the BH duration by a mean factor of 2.1 (range 1.1-3.9s). The mean overall stability and reproducibility were within 1 mm. Subjective tolerance was very good with the majority of patients having no or minor discomfort caused by the devices. The mean inter-fraction tumor position variability was 1.8 mm (-1.1-8.1 mm;SD 2.4 mm). CONCLUSION: NHFT for RT treatment of NSCLC in BH is feasible, well tolerated and significantly increases the breath-hold duration. Visually guided BH with OST is stable and reproducible. We therefore consider this an attractive patient-friendly approach to treat lung cancer patients with RT in BH.

Assessment of fluence- and dose-averaged linear energy transfer with passive luminescence detectors in clinical proton beams.

Objective.This work investigates the use of passive luminescence detectors to determine different types of averaged linear energy transfer (LET-) for the energies relevant to proton therapy. The experimental results are compared to reference values obtained from Monte Carlo simulations.Approach.Optically stimulated luminescence detectors (OSLDs), fluorescent nuclear track detectors (FNTDs), and two different groups of thermoluminescence detectors (TLDs) were irradiated at four different radiation qualities. For each irradiation, the fluence- (LET-f) and dose-averaged LET (LET-d) were determined. For both quantities, two sub-types of averages were calculated, either considering the contributions from primary and secondary protons or from all protons and heavier, charged particles. Both simulated and experimental data were used in combination with a phenomenological model to estimate the relative biological effectiveness (RBE).Main results.All types ofLET-could be assessed with the luminescence detectors. The experimental determination ofLET-fis in agreement with reference data obtained from simulations across all measurement techniques and types of averaging. On the other hand,LET-dcan present challenges as a radiation quality metric to describe the detector response in mixed particle fields. However, excluding secondaries heavier than protons from theLET-dcalculation, as their contribution to the luminescence is suppressed by ionization quenching, leads to equal accuracy betweenLET-fandLET-d. Assessment of RBE through the experimentally determinedLET-dvalues agrees with independently acquired reference values, indicating that the investigated detectors can determineLET-with sufficient accuracy for proton therapy.Significance.OSLDs, TLDs, and FNTDs can be used to determineLET-and RBE in proton therapy. With the capability to determine dose through ionization quenching corrections derived fromLET-, OSLDs and TLDs can simultaneously ascertain dose,LET-, and RBE. This makes passive detectors appealing for measurements in phantoms to facilitate validation of clinical treatment plans or experiments related to proton therapy.

Towards a European prospective data registry for particle therapy.

The evidence for the value of particle therapy (PT) is still sparse. While randomized trials remain a cornerstone for robust comparisons with photon-based radiotherapy, data registries collecting real-world data can play a crucial role in building evidence for new developments. This Perspective describes how the European Particle Therapy Network (EPTN) is actively working on establishing a prospective data registry encompassing all patients undergoing PT in European centers. Several obstacles and hurdles are discussed, for instance harmonization of nomenclature and structure of technical and dosimetric data and data protection issues. A preferred approach is the adoption of a federated data registry model with transparent and agile governance to meet European requirements for data protection, transfer, and processing. Funding of the registry, especially for operation after the initial setup process, remains a major challenge.

Linear Energy Transfer and Relative Biological Effectiveness Investigation of Various Structures for a Cohort of Proton Patients With Brain Tumors.

Purpose: The current knowledge on biological effects associated with proton therapy is limited. Therefore, we investigated the distributions of dose, dose-averaged linear energy transfer (LETd), and the product between dose and LETd (DLETd) for a patient cohort treated with proton therapy. Different treatment planning system features and visualization tools were explored. Methods and Materials: For a cohort of 24 patients with brain tumors, the LETd, DLETd, and dose was calculated for a fixed relative biological effectiveness value and 2 variable models: plan-based and phenomenological. Dose threshold levels of 0, 5, and 20 Gy were imposed for LETd visualization. The relationship between physical dose and LETd and the frequency of LETd hotspots were investigated. Results: The phenomenological relative biological effectiveness model presented consistently higher dose values. For lower dose thresholds, the LETd distribution was steered toward higher values related to low treatment doses. Differences up to 26.0% were found according to the threshold. Maximum LETd values were identified in the brain, periventricular space, and ventricles. An inverse relationship between LETd and dose was observed. Frequency information to the domain of dose and LETd allowed for the identification of clusters, which steer the mean LETd values, and the identification of higher, but sparse, LETd values. Conclusions: Identifying, quantifying, and recording LET distributions in a standardized fashion is necessary, because concern exists over a link between toxicity and LET hotspots. Visualizing DLETd or dose × LETd during treatment planning could allow for clinicians to make informed decisions.

Automatic quality assurance of radiotherapy treatment plans using Bayesian networks: A multi-institutional study.

Purpose: Artificial intelligence applications in radiation oncology have been the focus of study in the last decade. The introduction of automated and intelligent solutions for routine clinical tasks, such as treatment planning and quality assurance, has the potential to increase safety and efficiency of radiotherapy. In this work, we present a multi-institutional study across three different institutions internationally on a Bayesian network (BN)-based initial plan review assistive tool that alerts radiotherapy professionals for potential erroneous or suboptimal treatment plans. Methods: Clinical data were collected from the oncology information systems in three institutes in Europe (Maastro clinic - 8753 patients treated between 2012 and 2020) and the United States of America (University of Vermont Medical Center [UVMMC] - 2733 patients, University of Washington [UW] - 6180 patients, treated between 2018 and 2021). We trained the BN model to detect potential errors in radiotherapy treatment plans using different combinations of institutional data and performed single-site and cross-site validation with simulated plans with embedded errors. The simulated errors consisted of three different categories: i) patient setup, ii) treatment planning and iii) prescription. We also compared the strategy of using only diagnostic parameters or all variables as evidence for the BN. We evaluated the model performance utilizing the area under the receiver-operating characteristic curve (AUC). Results: The best network performance was observed when the BN model is trained and validated using the dataset in the same center. In particular, the testing and validation using UVMMC data has achieved an AUC of 0.92 with all parameters used as evidence. In cross-validation studies, we observed that the BN model performed better when it was trained and validated in institutes with similar technology and treatment protocols (for instance, when testing on UVMMC data, the model trained on UW data achieved an AUC of 0.84, compared with an AUC of 0.64 for the model trained on Maastro data). Also, combining training data from larger clinics (UW and Maastro clinic) and using it on smaller clinics (UVMMC) leads to satisfactory performance with an AUC of 0.85. Lastly, we found that in general the BN model performed better when all variables are considered as evidence. Conclusion: We have developed and validated a Bayesian network model to assist initial treatment plan review using multi-institutional data with different technology and clinical practices. The model has shown good performance even when trained on data from clinics with divergent profiles, suggesting that the model is able to adapt to different data distributions.

Clinical implementation and validation of an automated adaptive workflow for proton therapy.

Background and purpose: Treatment quality of proton therapy can be monitored by repeat-computed tomography scans (reCTs). However, manual re-delineation of target contours can be time-consuming. To improve the workflow, we implemented an automated reCT evaluation, and assessed if automatic target contour propagation would lead to the same clinical decision for plan adaptation as the manual workflow. Materials and methods: This study included 79 consecutive patients with a total of 250 reCTs which had been manually evaluated. To assess the feasibility of automated reCT evaluation, we propagated the clinical target volumes (CTVs) deformably from the planning-CT to the reCTs in a commercial treatment planning system. The dose-volume-histogram parameters were extracted for manually re-delineated (CTVmanual) and deformably mapped target contours (CTVauto). It was compared if CTVmanual and CTVauto both satisfied/failed the clinical constraints. Duration of the reCT workflows was also recorded. Results: In 92% (N = 229) of the reCTs correct flagging was obtained. Only 4% (N = 9) of the reCTs presented with false negatives (i.e., at least one clinical constraint failed for CTVmanual, but all constraints were satisfied for CTVauto), while 5% (N = 12) of the reCTs led to a false positive. Only for one false negative reCT a plan adaption was made in clinical practice, i.e., only one adaptation would have been missed, suggesting that automated reCT evaluation was possible. Clinical introduction hereof led to a time reduction of 49 h (from 65 to 16 h). Conclusion: Deformable target contour propagation was clinically acceptable. A script-based automatic reCT evaluation workflow has been introduced in routine clinical practice.

Plan quality assessment in clinical practice: Results of the 2020 ESTRO survey on plan complexity and robustness.

PURPOSE: Plan complexity and robustness are two essential aspects of treatment plan quality but there is a great variability in their management in clinical practice. This study reports the results of the 2020 ESTRO survey on plan complexity and robustness to identify needs and guide future discussions and consensus. METHODS: A survey was distributed online to ESTRO members. Plan complexity was defined as the modulation of machine parameters and increased uncertainty in dose calculation and delivery. Robustness was defined as a dose distribution's sensitivity towards errors stemming from treatment uncertainties, patient setup, or anatomical changes. RESULTS: A total of 126 radiotherapy centres from 33 countries participated, 95 of them (75%) from Europe and Central Asia. The majority controlled and evaluated plan complexity using monitor units (56 centres) and aperture shapes (38 centres). To control robustness, 98 (97% of question responses) photon and 5 (50%) proton centres used PTV margins for plan optimization while 75 (94%) and 5 (50%), respectively, used margins for plan evaluation. Seventeen (21%) photon and 8 (80%) proton centres used robust optimisation, while 10 (13%) and 8 (80%), respectively, used robust evaluation. Primary uncertainties considered were patient setup (photons and protons) and range calculation uncertainties (protons). Participants expressed the need for improved commercial tools to control and evaluate plan complexity and robustness. CONCLUSION: Clinical implementation of methods to control and evaluate plan complexity and robustness is very heterogeneous. Better tools are needed to manage complexity and robustness in treatment planning systems. International guidelines may promote harmonization.

Evaluation of measures for assessing time-saving of automatic organ-at-risk segmentation in radiotherapy.

BACKGROUND AND PURPOSE: In radiotherapy, automatic organ-at-risk segmentation algorithms allow faster delineation times, but clinically relevant contour evaluation remains challenging. Commonly used measures to assess automatic contours, such as volumetric Dice Similarity Coefficient (DSC) or Hausdorff distance, have shown to be good measures for geometric similarity, but do not always correlate with clinical applicability of the contours, or time needed to adjust them. This study aimed to evaluate the correlation of new and commonly used evaluation measures with time-saving during contouring. MATERIALS AND METHODS: Twenty lung cancer patients were used to compare user-adjustments after atlas-based and deep-learning contouring with manual contouring. The absolute time needed (s) of adjusting the auto-contour compared to manual contouring was recorded, from this relative time-saving (%) was calculated. New evaluation measures (surface DSC and added path length, APL) and conventional evaluation measures (volumetric DSC and Hausdorff distance) were correlated with time-recordings and time-savings, quantified with the Pearson correlation coefficient, R. RESULTS: The highest correlation (R = 0.87) was found between APL and absolute adaption time. Lower correlations were found for APL with relative time-saving (R = -0.38), for surface DSC with absolute adaption time (R = -0.69) and relative time-saving (R = 0.57). Volumetric DSC and Hausdorff distance also showed lower correlation coefficients for absolute adaptation time (R = -0.32 and 0.64, respectively) and relative time-saving (R = 0.44 and -0.64, respectively). CONCLUSION: Surface DSC and APL are better indicators for contour adaptation time and time-saving when using auto-segmentation and provide more clinically relevant and better quantitative measures for automatically-generated contour quality, compared to commonly-used geometry-based measures.

Treatment plan quality assessment for radiotherapy of rectal cancer patients using prediction of organ-at-risk dose metrics.

BACKGROUND AND PURPOSE: Radiotherapy centers frequently lack simple tools for periodic treatment plan verification and feedback on current plan quality. It is difficult to measure treatment quality over different years or during the planning process. Here, we implemented plan quality assurance (QA) by developing a database of dose-volume histogram (DVH) metrics and a prediction model. These tools were used to assess automatically optimized treatment plans for rectal cancer patients, based on cohort analysis. MATERIAL AND METHODS: A treatment plan QA framework was established and an overlap volume histogram based model was used to predict DVH parameters for cohorts of patients treated in 2018 and 2019 and grouped according to planning technique. A training cohort of 22 re-optimized treatment plans was used to make the prediction model. The prediction model was validated on 95 automatically generated treatment plans (automatically optimized cohort) and 93 manually optimized plans (manually optimized cohort). RESULTS: For the manually optimized cohort, on average the prediction deviated less than 0.3 ± 1.4 Gy and -4.3 ± 5.5 Gy, for the mean doses to the bowel bag and bladder, respectively; for the automatically optimized cohort a smaller deviation was observed: -0.1 ± 1.1 Gy and -0.2 ± 2.5 Gy, respectively. The interquartile range of DVH parameters was on average smaller for the automatically optimized cohort, indicating less variation within each parameter compared to manual planning. CONCLUSION: An automated framework to monitor treatment quality with a DVH prediction model was successfully implemented clinically and revealed less variation in DVH parameters for automated in comparison to manually optimized plans. The framework also allowed for individual feedback and DVH estimation.

Modelling of the focal spot intensity distribution and the off-focal spot radiation in kilovoltage x-ray tubes for imaging.

X-ray tubes for medical applications typically generate x-rays by accelerating electrons, emitted from a cathode, with an interelectrode electric field, towards an anode target. X-rays are not emitted from one point, but from an irregularly shaped area on the anode, the focal spot. Focal spot intensity distributions and off-focal radiation negatively affect the imaging spatial resolution and broadens the beam penumbra. In this study, a Monte Carlo simulation model of an x-ray tube was developed to evaluate the spectral and spatial characteristics of off-focal radiation for multiple photon energies. Slit camera measurements were used to determine the horizontal and vertical intensity profiles of the small and the large focal spot of a diagnostic x-ray tube. First, electron beamlet weighting factors were obtained via an iterative optimization method to represent both focal spot sizes. These weighting factors were then used to extract off-focal spot radiation characteristics for the small and large focal spot sizes at 80, 100, and 120 kV. Finally, 120 kV simulations of a steel sphere (d = 4 mm) were performed to investigate image blurring with a point source, the small focal spot, and the large focal spot. The magnitude of off-focal radiation strongly depends on the anode size and the electric field coverage, and only minimally on the tube potential and the primary focal spot size. In conclusion, an x-ray tube Monte Carlo simulation model was developed to simulate focal spot intensity distributions and to evaluate off-focal radiation characteristics at several energies. This model can be further employed to investigate focal spot correction methods and to improve cone-beam CT image quality.

What is plan quality in radiotherapy? The importance of evaluating dose metrics, complexity, and robustness of treatment plans.

Plan evaluation is a key step in the radiotherapy treatment workflow. Central to this step is the assessment of treatment plan quality. Hence, it is important to agree on what we mean by plan quality and to be fully aware of which parameters it depends on. We understand plan quality in radiotherapy as the clinical suitability of the delivered dose distribution that can be realistically expected from a treatment plan. Plan quality is commonly assessed by evaluating the dose distribution calculated by the treatment planning system (TPS). Evaluating the 3D dose distribution is not easy, however; it is hard to fully evaluate its spatial characteristics and we still lack the knowledge for personalising the prediction of the clinical outcome based on individual patient characteristics. This advocates for standardisation and systematic collection of clinical data and outcomes after radiotherapy. Additionally, the calculated dose distribution is not exactly the dose delivered to the patient due to uncertainties in the dose calculation and the treatment delivery, including variations in the patient set-up and anatomy. Consequently, plan quality also depends on the robustness and complexity of the treatment plan. We believe that future work and consensus on the best metrics for quality indices are required. Better tools are needed in TPSs for the evaluation of dose distributions, for the robust evaluation and optimisation of treatment plans, and for controlling and reporting plan complexity. Implementation of such tools and a better understanding of these concepts will facilitate the handling of these characteristics in clinical practice and be helpful to increase the overall quality of treatment plans in radiotherapy.

Dose to water versus dose to medium from cavity theory applied to small animal irradiation with kilovolt x-rays.

Dose reporting is a matter of concern in the preclinical field as the different dose descriptors dose-to-water-in-medium [Formula: see text] and dose-to-medium-in-medium [Formula: see text] coexist. For kV photons differences between both quantities are expected to be amplified due to photon energy absorption coefficients differences for different media, and could represent a limiting factor for accurate translation of pre-clinical research into clinical trials. The main goal of this study was to analyse the relationship between [Formula: see text] and [Formula: see text] for kV irradiation of small animals, using different flavours of the intermediate cavity theory (ICT). Irradiations of mathematical phantoms and a mouse CT scan, both with different voxel sizes and materials, were investigated. A modified version of the Monte Carlo code DOSXYZnrc was used to derive [Formula: see text] and convert to [Formula: see text] using ICT. Local photon spectra were generated in different regions of the mouse. Depending on energy and cavity size, which we equate to the voxel size, [Formula: see text] ranged from 0.68 to 4.37 times [Formula: see text]. Higher kV energy combined with very small cavity sizes yielded decreased [Formula: see text] in comparison to [Formula: see text]; this behaviour was reversed for larger cavities combined with lower kV energies. Hence, the impact of the cavity dimensions on estimated [Formula: see text] is significant on pre-clinical kV beams. [Formula: see text] and [Formula: see text] in the ex vivo male mouse were found to differ by -29% to 286%. Caution is advised when using the ICT due to a lack of consensus on weighting factor (d-parameter) deriving methods; for the same irradiation conditions, different d-values affected [Formula: see text] up to 20%. Pre-clinically, such divergence between dose descriptors could enable biological damage. The abiding debate over which quantity to favour is foreseen to linger while it is unclear which quantity correlates better with the biological effects of ionizing irradiation: preclinical radiotherapy might represent an ideal platform for measurement-based studies to settle this fundamental question. Finally, dose distribution comparisons require caution and should use the same reporting quantity.

On the determination of planning target margins due to motion for mice lung tumours using a four-dimensional MOBY phantom.

OBJECTIVE:: This work aims to analyse the effect of respiratory motion on optimal irradiation margins for murine lung tumour models. METHODS:: Four-dimensional mathematical phantoms with different lung tumour locations affected by respiratory motion were created. Two extreme breathing curves were adopted and divided into time-points. Each time-point was loaded in a treatment planning system and Monte Carlo (MC) dose calculations were performed for a 360° arc plan. A time-resolved dose was derived, considering the gantry rotation and the breathing motion. Radiotherapy metrics were derived to assess the final treatment plans. An interpolation function was investigated to reduce calculation cost. RESULTS:: The effect of respiratory motion on the treatment plan quality is strongly dependent on the breathing pattern and the tumour position. Tumours located closer to the diaphragm required a compromise between tumour conformity and healthy tissue damage. A recipe, which considers collimator size, was proposed to derive tumour margins and spare the organs at risk (OARs) by respecting constraints on user-defined metrics. CONCLUSION:: It is recommended to add a target margin, especially on sites where movement is substantial. A simple recipe to derive tumour margins was developed. ADVANCES IN KNOWLEDGE:: This work is a first step towards a standard planning target volume concept in pre-clinical radiotherapy.

Murine vs human tissue compositions: implications of using human tissue compositions for photon energy absorption in mice.

METHODS:: Dual energy CT (DECT) images of 9 female mice were used to extract the effective atomic number Zeff and the relative electron density ρe for each voxel in the images. To investigate the influence of the tissue compositions on the absorbed radiation dose for a typical kilovoltage photon beam, mass energy-absorption coefficients µen/ρ were calculated for 10 different tissues in each mouse. RESULTS: Differences between human and murine tissue compositions can lead to errors around 7.5 % for soft tissues and 20.1 % for bone tissues in µen/ρ values for kilovoltage photon beams. When considering the spread within tissues, these errors can increase up to 17.5 % for soft tissues and 53.9 % for bone tissues within only a single standard deviation away from the mean tissue value. CONCLUSION:: This study illustrates the need for murine reference tissue data. However, assigning only a single mean reference value to an entire tissue can still lead to large errors in dose calculations given the large spread within tissues of µen/ρ values found in this study. Therefore, new methods such as DECT and spectral CT imaging need to be explored, which can be important next steps in improving tissue assignment for dose calculations in small animal radiotherapy. ADVANCES IN KNOWLEDGE:: This is the first study that investigates the implications of using human tissue compositions for dose calculations in mice for kilovoltage photon beams.

The effect of different image reconstruction techniques on pre-clinical quantitative imaging and dual-energy CT.

OBJECTIVE:: To analyse the effect of different image reconstruction techniques on image quality and dual energy CT (DECT) imaging metrics. METHODS:: A software platform for pre-clinical cone beam CT X-ray image reconstruction was built using the open-source reconstruction toolkit. Pre-processed projections were reconstructed with filtered back-projection and iterative algorithms, namely Feldkamp, Davis, and Kress (FDK), Iterative FDK, simultaneous algebraic reconstruction technique (SART), simultaneous iterative reconstruction technique and conjugate gradient. Imaging metrics were quantitatively assessed, using a quality assurance phantom, and DECT analysis was performed to determine the influence of each reconstruction technique on the relative electron density (ρe) and effective atomic number (Zeff) values. RESULTS:: Iterative reconstruction had favourable results for the DECT analysis: a significantly smaller spread for each material in the ρe-Zeff space and lower Zeff and ρe residuals (on average 24 and 25% lower, respectively). In terms of image quality assurance, the techniques FDK, Iterative FDK and SART provided acceptable results. The three reconstruction methods showed similar geometric accuracy, uniformity and CT number results. The technique SART had a contrast-to-noise ratio up to 76% higher for solid water and twice as high for Teflon, but resolution was up to 28% lower when compared to the other two techniques. CONCLUSIONS:: Advanced image reconstruction can be beneficial, but the benefit is small, and calculation times may be unacceptable with current technology. The use of targeted and downscaled reconstruction grids, larger, yet practicable, pixel sizes and GPU are recommended. ADVANCES IN KNOWLEDGE:: An iterative CBCT reconstruction platform was build using RTK.

Exploring the feasibility of a clinical proton beam with an adaptive aperture for pre-clinical research.

OBJECTIVE:: To investigate whether the Mevion S250i with HYPERSCAN clinical proton system could be used for pre-clinical research with millimetric beams. METHODS:: The nozzle of the proton beam line, consisting of an energy modulation system (EMS) and an adaptive aperture (AA), was modelled with the TOPAS Monte Carlo Simulation Toolkit. With the EMS, the 230 MeV beam nominal range can be decreased in multiples of 2.1 mm. Monte Carlo dose calculations were performed in a mouse lung tumour CT image. The AA allows fields as small as 5 × 1 mm2 to be used for irradiation. The best plans to give 2 Gy to the tumour were derived from a set of discrete energies allowed by the EMS, different field sizes and beam directions. The final proton plans were compared to a precision photon irradiation plan. Treatment times were also assessed. RESULTS:: Seven different proton beam plans were investigated, with a good coverage to the tumour (D95 > 1.95 Gy, D5 < 2.3 Gy) and with potentially less damage to the organs at risk than the photon plan. For very small fields and low energies, the number of protons arriving to the target drops to 1-3%, nevertheless the treatment times would be below 5 s. CONCLUSION:: The proton plans made in this study, collimated by an AA, could be used for animal irradiation. ADVANCES IN KNOWLEDGE:: This is one of the first study to demonstrate the feasibility of pre-clinical research with a clinical proton beam with an adaptive aperture used to create small fields.

An orthotopic non-small cell lung cancer model for image-guided small animal radiotherapy platforms.

METHODS:: An orthotopic non-small cell lung cancer model in NMRI-nude mice was established to investigate the complementary information acquired from 80 kVp microcone-beam CT (micro-CBCT) and bioluminescence imaging (BLI) using different angles and filter settings. Different micro-CBCT-based radiation-delivery plans were evaluated based on their dose-volume histogram metrics of tumor and organs at risk to select the optimal treatment plan. RESULTS:: H1299 cell suspensions injected directly into the lung render exponentially growing single tumor nodules whose CBCT-based volume quantification strongly correlated with BLI-integrated intensity. Parallel-opposed single angle beam plans through a single lung are preferred for smaller tumors, whereas for larger tumors, plans that spread the radiation dose across healthy tissues are favored. CONCLUSIONS:: Closely mimicking a clinical setting for lung cancer with highly advanced preclinical radiation treatment planning is possible in mice developing orthotopic lung tumors. ADVANCES IN KNOWLEDGE:: BLI and CBCT imaging of orthotopic lung tumors provide complementary information in a temporal manner. The optimal radiotherapy plan is tumor volume-dependent.

Automatic multiatlas based organ at risk segmentation in mice.

OBJECTIVE:: During the treatment planning of a preclinical small animal irradiation, which has time limitations for reasons of animal wellbeing and workflow efficiency, the time consuming organ at risk (OAR) delineation is performed manually. This work aimed to develop, demonstrate, and quantitatively evaluate an automated contouring method for six OARs in a preclinical irritation treatment workflow. METHODS:: Microcone beam CT images of nine healthy mice were contoured with an in-house developed multiatlas-based image segmentation (MABIS) algorithm for six OARs: kidneys, eyes, heart, and brain. The automatic contouring was compared with the manual delineation using three quantitative metrics: the Dice Similarity Coefficient (DSC), 95th percentile Hausdorff Distance, and the centre of mass displacement. RESULTS:: A good agreement between manual and automatic contouring was found for OARs with sharp organ boundaries. For the brain and the heart, the median DSC was larger than 0.94, the median 95th Hausdorff Distance smaller than 0.44 mm, and the median centre of mass displacement smaller than 0.20 mm. Lower DSC values were obtained for the other OARs, but the median DSC was still larger than 0.74 for the left eye, 0.69 for the right eye, 0.89 for the left kidney and 0.80 for the right kidney. CONCLUSION:: The MABIS algorithm was able to delineate six OARs with a relatively high accuracy. Segmenting OARs with sharp organ boundaries performed better than low contrast OARs. ADVANCES IN KNOWLEDGE:: A MABIS algorithm is developed, evaluated, and demonstrated in a preclinical small animal irradiation research workflow.

VOXSI: A voxelized single- and dual-energy CT scenario generator for quantitative imaging.

BACKGROUND AND PURPOSE: Dedicated CT simulation models have the potential to investigate several acquisition, reconstruction, or post-processing parameters without giving any radiation dose to patients. A software program was developed for the simulation and the analysis of single-energy and dual-energy CT images. Simulation and analysis functionalities of the software are described. MATERIALS AND METHODS: In the software, named VOXSI (VOXelized CT SImulator), the X-ray source, user specified simulation geometry, CT setup and the detector energy response can be varied. CT image reconstructions can be performed with an implementation of the ASTRA toolbox. In the DECT post processing toolkit, GUI tools are provided to calculate effective atomic number, relative electron density, pseudo-monoenergetic images, and material map images. Quantitative CT number validation, based on a RMI 467 tissue characterization phantom model, was performed between experimental and simulated CT scans at three different X-ray tube potentials (80, 120, and 140 kVp) with a third generation CT scanner. RESULTS: Overall, a good agreement was found for the mean CT numbers of the RMI 467 inserts. For all energies, the maximum difference in CT numbers between experimental and simulated data was below 17 HU for the soft tissues and below 48 HU for the osseous tissues. CONCLUSION: The software's simulation algorithm showed a good agreement between the CT measurements and CT simulations of the RMI 467 phantom at different energies. The capabilities of the software are demonstrated by an elaborated dual-energy CT research example.