Characterizing the voxel-based approaches in radioembolization dosimetry with reDoseMC.

BACKGROUND: Yttrium-90 ( 90 Y $^{90}{\rm {Y}}$ ) represents the primary radioisotope used in radioembolization procedures, while holmium-166 ( 166 Ho $^{166}{\rm {Ho}}$ ) is hypothesized to serve as a viable substitute for 90 Y $^{90}{\rm {Y}}$ due to its comparable therapeutic potential and improved quantitative imaging. Voxel-based dosimetry for these radioisotopes relies on activity images obtained through PET or SPECT and dosimetry methods, including the voxel S-value (VSV) and the local deposition method (LDM). However, the evaluation of the accuracy of absorbed dose calculations has been limited by the use of non-ideal reference standards and investigations restricted to the liver. The objective of this study was to expand upon these dosimetry characterizations by investigating the impact of image resolutions, voxel sizes, target volumes, and tissue materials on the accuracy of 90 Y $^{90}{\rm {Y}}$ and 166 Ho $^{166}{\rm {Ho}}$ dosimetry techniques. METHODS: A specialized radiopharmaceutical dosimetry software called reDoseMC was developed using the Geant4 Monte Carlo toolkit and validated by benchmarking the generated 90 Y $^{90}{\rm {Y}}$ kernels with published data. The decay spectra of both 90 Y $^{90}{\rm {Y}}$ and 166 Ho $^{166}{\rm {Ho}}$ were also compared. Multiple VSV kernels were generated for the liver, lungs, soft tissue, and bone for isotropic voxel sizes of 1 mm, 2 mm, and 4 mm. Three theoretical phantom setups were created with 20 or 40 mm activity and mass density inserts for the same three voxel sizes. To replicate the limited spatial resolutions present in PET and SPECT images, image resolutions were modeled using a 3D Gaussian kernel with a Full Width at Half Maximum (FWHM) ranging from 0 to 16 mm and with no added noise. The VSV and LDM dosimetry methods were evaluated by characterizing their respective kernels and analyzing their absorbed dose estimates calculated on theoretical phantoms. The ground truth for these estimations was calculated using reDoseMC. RESULTS: The decay spectra obtained through reDoseMC showed less than a 1% difference when compared to previously published experimental data for energies below 1.9 MeV in the case of 90 Y $^{90}{\rm {Y}}$ and less than 1% for energies below 1.5 MeV for 166 Ho $^{166}{\rm {Ho}}$ . Additionally, the validation kernels for 90 Y $^{90}{\rm {Y}}$ VSV exhibited results similar to those found in published Monte Carlo codes, with source dose depositions having less than a 3% error margin. Resolution thresholds ( FWHM thresh s ${\rm {FWHM}}_\mathrm{thresh}{\rm {s}}$ ), defined as resolutions that resulted in similar dose estimates between the LDM and VSV methods, were observed for 90 Y $^{90}{\rm {Y}}$ . They were 1.5 mm for bone, 2.5 mm for soft tissue and liver, and 8.5 mm for lungs. For 166 Ho $^{166}{\rm {Ho}}$ , the accuracy of absorbed dose deposition was found to be dependent on the contributions of absorbed dose from photons. Volume errors due to variations in voxel size impacted the final dose estimates. Larger target volumes yielded more accurate mean doses than smaller volumes. For both radioisotopes, the radial dose profiles for the VSV and LDM approximated but never matched the reference standard. CONCLUSIONS: reDoseMC was developed and validated for radiopharmaceutical dosimetry. The accuracy of voxel-based dosimetry was found to vary widely with changes in image resolutions, voxel sizes, chosen target volumes, and tissue material; hence, the standardization of dosimetry protocols was found to be of great importance for comparable dosimetry analysis.

Investigation of dosimetric characteristics of radiochromic film in response to alpha particles emitted from Americium-241.

BACKGROUND: In radiotherapy, it is essential to deliver prescribed doses to tumors while minimizing damage to surrounding healthy tissue. Accurate measurements of absorbed dose are required for this purpose. Gafchromic® external beam therapy (EBT) radiochromic films have been widely used in radiotherapy. While the dosimetric characteristics of the EBT3 model film have been extensively studied for photon and charged particle beams (protons, electrons, and carbon ions), little research has been done on α $\alpha$ -particle dosimetry. α $\alpha$ -emitting radionuclides have gained popularity in cancer treatment due to their high linear energy transfer, short range in tissue, and ability to spare surrounding organs at risk, thereby delivering a more localized dose distribution to the tumor. Therefore, a dose-calibration film protocol for α $\alpha$ -particles is required. PURPOSE: This study aimed to develop a dose-calibration protocol for the α $\alpha$ -particle emitting radionuclide 241Am, using Monte Carlo (MC) simulations and measurements with unlaminated EBT3 films. METHODS: In this study, a MC-based user code was developed using the Geant4 simulation toolkit to model and simulate an 241Am source and an unlaminated EBT3 film. Two simulations were performed: one with voxelized geometries of the EBT3 active volume composition and the other using water. The dose rate was calculated within a region of interest in the voxelized geometries. Unlaminated EBT3 film pieces were irradiated with the 241Am source at various exposure times inside a black box. Film irradiations were compared to a 6-MV photon beam from a Varian TrueBeam machine. The simulated dose rate was used to convert the exposure times into absorbed doses to water, describing a radiochromic-film-based reference dosimetry protocol for α $\alpha$ -particles. The irradiated films were scanned and through an in-house Python script, the normalized pixel values from the green-color channel of scanned film images were analyzed. RESULTS: The 241Am energy spectra obtained from the simulations were in good agreement with IAEA and NIST databases, having differences < $<$ 0.516% for the emitted γ $\gamma$ -rays and produced characteristic x-rays and < $<$ 0.006% for the α $\alpha$ -particles. Due to the short range of α $\alpha$ -particles, there was no energy deposition in the voxels outside the active 241Am source region projected onto the film surface. Thus, the total dose rate within the voxels covering the source was 0.847 ± $\pm$ 0.003 Gy/min within the sensitive layer of the film (LiPCDA) and 0.847 ± $\pm$ 0.004 Gy/min in water, indicating that the active volume can be considered water equivalent for the 241Am beam quality. A novel approach was employed in α $\alpha$ -film dosimetry using an exponential fit for the green channel, which showed promising results by reducing the uncertainty in dose estimation within 5%. Although the statistical analysis did not reveal significant differences between the 6-MV photon beam and the α $\alpha$ calibration curves, the dose-response curves exhibited the expected behavior. CONCLUSIONS: The developed MC user code simulated the experimental setup for α $\alpha$ -dosimetry using radiochromic film with acceptable uncertainty. Unlaminated EBT3 film is suitable for the dosimetry of α $\alpha$ -radiation at low doses and can be used in conjunction with other unlaminated GafChromic® films for quality assurance and research purposes.

Penalty weight tuning in high dose rate brachytherapy using multi-objective Bayesian optimization.

Objective.Treatment plan optimization in high dose rate brachytherapy often requires manual fine-tuning of penalty weights for each objective, which can be time-consuming and dependent on the planner's experience. To automate this process, this study used a multi-criteria approach called multi-objective Bayesian optimization with q-noisy expected hypervolume improvement as its acquisition function (MOBO-qNEHVI).Approach.The treatment plans of 13 prostate cancer patients were retrospectively imported to a research treatment planning system, RapidBrachyMTPS, where fast mixed integer optimization (FMIO) performs dwell time optimization given a set of penalty weights to deliver 15 Gy to the target volume. MOBO-qNEHVI was used to find patient-specific Pareto optimal penalty weight vectors that yield clinically acceptable dose volume histogram metrics. The relationship between the number of MOBO-qNEHVI iterations and the number of clinically acceptable plans per patient (acceptance rate) was investigated. The performance time was obtained for various parameter configurations.Main results.MOBO-qNEHVI found clinically acceptable treatment plans for all patients. With increasing the number of MOBO-qNEHVI iterations, the acceptance rate grew logarithmically while the performance time grew exponentially. Fixing the penalty weight of the tumour volume to maximum value, adding the target dose as a parameter, initiating MOBO-qNEHVI with 25 parallel sampling of FMIO, and running 6 MOBO-qNEHVI iterations found solutions that delivered 15 Gy to the hottest 95% of the clinical target volume while respecting the dose constraints to the organs at risk. The average acceptance rate for each patient was 89.74% ± 8.11%, and performance time was 66.6 ± 12.6 s. The initiation took 22.47 ± 7.57 s, and each iteration took 7.35 ± 2.45 s to find one Pareto solution.Significance.MOBO-qNEHVI combined with FMIO can automatically explore the trade-offs between treatment plan objectives in a patient specific manner within a minute. This approach can reduce the dependency of plan quality on planner's experience and reduce dose to the organs at risk.

Deep learning for high-resolution dose prediction in high dose rate brachytherapy for breast cancer treatment.

Objective.Monte Carlo (MC) simulations are the benchmark for accurate radiotherapy dose calculations, notably in patient-specific high dose rate brachytherapy (HDR BT), in cases where considering tissue heterogeneities is critical. However, the lengthy computational time limits the practical application of MC simulations. Prior research used deep learning (DL) for dose prediction as an alternative to MC simulations. While accurate dose predictions akin to MC were attained, graphics processing unit limitations constrained these predictions to large voxels of 3 mm × 3 mm × 3 mm. This study aimed to enable dose predictions as accurate as MC simulations in 1 mm × 1 mm × 1 mm voxels within a clinically acceptable timeframe.Approach.Computed tomography scans of 98 breast cancer patients treated with Iridium-192-based HDR BT were used: 70 for training, 14 for validation, and 14 for testing. A new cropping strategy based on the distance to the seed was devised to reduce the volume size, enabling efficient training of 3D DL models using 1 mm × 1 mm × 1 mm dose grids. Additionally, novel DL architecture with layer-level fusion were proposed to predict MC simulated dose to medium-in-medium (Dm,m). These architectures fuse information from TG-43 dose to water-in-water (Dw,w) with patient tissue composition at the layer-level. Different inputs describing patient body composition were investigated.Main results.The proposed approach demonstrated state-of-the-art performance, on par with the MCDm,mmaps, but 300 times faster. The mean absolute percent error for dosimetric indices between the MC and DL-predicted complete treatment plans was 0.17% ± 0.15% for the planning target volumeV100, 0.30% ± 0.32% for the skinD2cc, 0.82% ± 0.79% for the lungD2cc, 0.34% ± 0.29% for the chest wallD2ccand 1.08% ± 0.98% for the heartD2cc.Significance.Unlike the time-consuming MC simulations, the proposed novel strategy efficiently converts TG-43Dw,wmaps into preciseDm,mmaps at high resolution, enabling clinical integration.

RapidBrachyTG43: A Geant4-based TG-43 parameter and dose calculation module for brachytherapy dosimetry.

BACKGROUND: The AAPM TG-43U1 formalism remains the clinical standard for dosimetry of low- and high-energy γ $\gamma$ -emitting brachytherapy sources. TG-43U1 and related reports provide consensus datasets of TG-43 parameters derived from various published measured data and Monte Carlo simulations. These data are used to perform standardized and fast dose calculations for brachytherapy treatment planning. PURPOSE: Monte Carlo TG-43 dosimetry parameters are commonly derived to characterize novel brachytherapy sources. RapidBrachyTG43 is a module of RapidBrachyMCTPS, a Monte Carlo-based treatment planning system, designed to automate this process, requiring minimal user input to prepare Geant4-based Monte Carlo simulations for a source. RapidBrachyTG43 may also perform a TG-43 dose to water-in-water calculation for a plan, substantially accelerating the same calculation performed using RapidBrachyMCTPS's Monte Carlo dose calculation engine. METHODS: TG-43 parameters S K / A $S_K/A$ , Λ $\Lambda$ , g L ( r ) $g_L(r)$ , and F ( r , θ ) $F(r,\theta)$ were calculated using three commercial source models, one each of 125 $^{125}$ I, 192 $^{192}$ Ir, and 60 $^{60}$ Co, and were benchmarked to published data. TG-43 dose to water was calculated for a clinical breast brachytherapy plan and was compared to a Monte Carlo dose calculation with all patient tissues, air, and catheters set to water. RESULTS: TG-43 parameters for the three simulated sources agreed with benchmark datasets within tolerances specified by the High Energy Brachytherapy Dosimetry working group. A gamma index comparison between the TG-43 and Monte Carlo dose-to-water calculations with a dose difference and difference to agreement criterion of 1%/1 mm yielded a 98.9% pass rate, with all relevant dose volume histogram metrics for the plan agreeing within 1%. Performing a TG-43-based dose calculation provided an acceleration of dose-to-water calculation by a factor of 165. CONCLUSIONS: Determination of TG-43 parameter data for novel brachytherapy sources may now be facilitated by RapidBrachyMCTPS. These parameter datasets and existing consensus or published datasets may also be used to determine the TG-43 dose for a plan in RapidBrachyMCTPS.

AAPM Medical Physics Practice Guideline 14.a: Yttrium-90 microsphere radioembolization.

Radioembolization using Yttrium-90 (90 Y) microspheres is widely used to treat primary and metastatic liver tumors. The present work provides minimum practice guidelines for establishing and supporting such a program. Medical physicists play a key role in patient and staff safety during these procedures. Products currently available are identified and their properties and suppliers summarized. Appropriateness for use is the domain of the treating physician. Patient work up starts with pre-treatment imaging. First, a mapping study using Technetium-99m (Tc-99m ) is carried out to quantify the lung shunt fraction (LSF) and to characterize the vascular supply of the liver. An MRI, CT, or a PET-CT scan is used to obtain information on the tumor burden. The tumor volume, LSF, tumor histology, and other pertinent patient characteristics are used to decide the type and quantity of 90 Y to be ordered. On the day of treatment, the appropriate dose is assayed using a dose calibrator with a calibration traceable to a national standard. In the treatment suite, the care team led by an interventional radiologist delivers the dose using real-time image guidance. The treatment suite is posted as a radioactive area during the procedure and staff wear radiation dosimeters. The treatment room, patient, and staff are surveyed post-procedure. The dose delivered to the patient is determined from the ratio of pre-treatment and residual waste exposure rate measurements. Establishing such a treatment modality is a major undertaking requiring an institutional radioactive materials license amendment complying with appropriate federal and state radiation regulations and appropriate staff training commensurate with their respective role and function in the planning and delivery of the procedure. Training, documentation, and areas for potential failure modes are identified and guidance is provided to ameliorate them.

M-TAG: A modular teaching-aid for Geant4.

Geant4 is a versatile Monte Carlo radiation transport simulation toolkit with a steep learning curve. This work introduces a user-code called M-TAG (Modular Radiation Teaching-Aid for Geant4), built on top of Geant4. M-TAG is designed to help gradually introduce the Geant4 toolkit to new users. The goal of Geant4 is to record quantities from the simulated radiation as it is transported through geometries. M-TAG simplifies the inclusion of new geometric elements and detector components in the simulation by including new classes. M-TAG also provides basic validated examples for some common detector development tasks. Geant4 intercom modules, called messenger classes, manage these classes. To validate M-TAG, simulations were performed to calculate the range of positrons in water. One hundred million decays at the center of a water-filled sphere with a radius of 1 m were allowed for fluorine-18, carbon-11, oxygen-15 and gallium-68. These results were compared to literature values. An inexperienced Geant4 user was tasked with creating a simulation model for a plastic scintillator-based detector and conducting basic tests to assess the effectiveness of M-TAG as a teaching tool. The simulation involved calculating the dose to the detector's sensitive volume using a 2x2 cm planar monoenergetic photon source spanning energies from 20 to 100 keV. One billion particles were simulated twice: once with the actual detector geometry and once with the sensitive volume replaced by water. The validity of M-TAG was also verified by computing dose ratios and comparing them with mass-attenuation ratios obtained from NIST XCOM data sets. The mean positron travel distances were within the distribution of literature values. Simulated positron energy spectra means were within 1.8% of literature means. Simulated dose ratios agreed with literature values within uncertainties. We have developed and verified a modular Geant4 teaching aid called M-TAG. It was used to introduce a new user to Geant4, who used it to perform further validation simulations.

Dosimetry of [18F]TRACK, the first PET tracer for imaging of TrkB/C receptors in humans.

BACKGROUND: Reduced expression or impaired signalling of tropomyosin receptor kinases (Trk receptors) are found in a vast spectrum of CNS disorders. [18F]TRACK is the first PET radioligand for TrkB/C with proven in vivo brain penetration and on-target specific signal. Here we report dosimetry data for [18F]TRACK in healthy humans. 6 healthy participants (age 22-61 y, 3 female) were scanned on a General Electric Discovery PET/CT 690 scanner. [18F]TRACK was synthesized with high molar activities (Am = 250 ± 75 GBq/µmol), and a dynamic series of 12 whole-body scans were acquired after injection of 129 to 147 MBq of the tracer. Images were reconstructed with standard corrections using the manufacturer's OSEM algorithm. Tracer concentration time-activity curves (TACs) were obtained using CT-derived volumes-of-interest. Organ-specific doses and the total effective dose were estimated using the Committee on Medical Internal Radiation Dose equation for adults and tabulated Source tissue values (S values). RESULTS: Average organ absorbed dose was highest for liver and gall bladder with 6.1E-2 (± 1.06E-2) mGy/MBq and 4.6 (± 1.18E-2) mGy/MBq, respectively. Total detriment weighted effective dose EDW was 1.63E-2 ± 1.68E-3 mSv/MBq. Organ-specific TACs indicated predominantly hepatic tracer elimination. CONCLUSION: Total and organ-specific effective doses for [18F]TRACK are low and the dosimetry profile is similar to other 18F-labelled radio tracers currently used in clinical settings.

Development of a hydrated electron dosimeter for radiotherapy applications: A proof of concept.

BACKGROUND: Hydrated electrons, which are short-lived products of radiolysis in water, increase the optical absorption of water, providing a pathway toward near-tissue-equivalent clinical radiation dosimeters. This has been demonstrated in high-dose-per-pulse radiochemistry research, but, owing to the weak absorption signal, its application in existing low-dose-per-pulse radiotherapy provided by clinical linear accelerators (linacs) has yet to be investigated. PURPOSE: The aims of this study were to measure the optical absorption associated with hydrated electrons produced by clinical linacs and to assess the suitability of the technique for radiotherapy (⩽ 1 cGy per pulse) applications. METHODS: 40 mW of 660-nm laser light was sent five passes through deionized water contained in a 10 × 4 × $\times 4\times$ 2 cm3 glass-walled cavity by using four broadband dielectric mirrors, two on each side of the cavity. The light was collected with a biased silicon photodetector. The water cavity was then irradiated by a Varian TrueBeam linac with both photon (10 MV FFF, 6 MV FFF, 6 MV) and electron beams (6 MeV) while monitoring the transmitted laser power for absorption transients. Radiochromic EBT3 film measurements were also performed for comparison. RESULTS: Examination of the absorbance profiles showed clear absorption changes in the water when radiation pulses were delivered. Both the amplitude and the decay time of the signal appeared consistent with the absorbed dose and the characteristics of the hydrated electrons. By using literature value for the hydrated electron radiation chemical yield (3.0±0.3), we inferred doses of 2.1±0.2 mGy (10 MV FFF), 1.3±0.1 mGy (6 MV FFF), 0.45±0.06 mGy (6 MV) for photons, and 0.47±0.05 mGy (6 MeV) for electrons, which differed from EBT3 film measurements by 0.6%, 0.8%, 10%, and 15.7%, respectively. The half-life of the hydrated electrons in the solution was ∼ 24 µ $\umu$ s. CONCLUSIONS: By measuring 660-nm laser light transmitted through a cm-scale, multi-pass water cavity, we observed absorption transients consistent with hydrated electrons generated by clinical linac radiation. The agreement between our inferred dose and EBT3 film measurements suggests this proof-of-concept system represents a viable pathway toward tissue-equivalent dosimeters for clinical radiotherapy applications.

A graphical user interface for calculating the arterial input function during dynamic positron emission tomography.

Purpose.Dynamic positron emission tomography (dPET) requires the acquisition of the arterial input function (AIF), conventionally obtained via invasive arterial blood sampling. To obtain the AIF non-invasively, our group developed and combined two novel solutions consisting of (1) a detector, placed on a patient's wrist during the PET scans to measure the radiation leaving the wrist and (2) a Geant4-based Monte Carlo simulation software. The simulations require patient-specific wrist geometry. The aim of this study was to develop a graphical user interface (GUI) allowing the user to import 2D ultrasound scans of a patient's wrist, and measure the wrist features needed to calculate the AIF.Methods.The GUI elements were implemented using Qt5 and VTK-8.2.0. The user imports a patient's wrist ultrasound scans, measures the radial artery and veins' surface and depth to model a wrist phantom, then specifies the radioactive source used during the dPET scan. The phantom, the source, and the number of decay events are imported into the Geant4-based Monte Carlo software to run a simulation. In this study, 100 million decays of18F and68Ga were simulated in a wrist phantom designed based on an ultrasound scan. The detector's efficiency was calculated and the results were analyzed using a clinical data processing algorithm developed in a previous study.Results.The detector's total efficiency decreased by 3.5% for18F and by 51.7% for68Ga when using a phantom based on ultrasound scans compared to a generic wrist phantom. Similarly, the data processing algorithm's accuracy decreased when using the patient-specific phantom, giving errors greater than 1.0% for both radioisotopes.Conclusions.This toolkit enables the user to run Geant4-based Monte Carlo simulations for dPET detector development applications using a patient-specific wrist phantom. Leading to a more precise simulation of the developed detector during dPET and the calculation of a personalized AIF.

A MC-based anthropomorphic test case for commissioning model-based dose calculation in interstitial breast 192-Ir HDR brachytherapy.

PURPOSE: To provide the first clinical test case for commissioning of 192 Ir brachytherapy model-based dose calculation algorithms (MBDCAs) according to the AAPM TG-186 report workflow. ACQUISITION AND VALIDATION METHODS: A computational patient phantom model was generated from a clinical multi-catheter 192 Ir HDR breast brachytherapy case. Regions of interest (ROIs) were contoured and digitized on the patient CT images and the model was written to a series of DICOM CT images using MATLAB. The model was imported into two commercial treatment planning systems (TPSs) currently incorporating an MBDCA. Identical treatment plans were prepared using a generic 192 Ir HDR source and the TG-43-based algorithm of each TPS. This was followed by dose to medium in medium calculations using the MBDCA option of each TPS. Monte Carlo (MC) simulation was performed in the model using three different codes and information parsed from the treatment plan exported in DICOM radiation therapy (RT) format. Results were found to agree within statistical uncertainty and the dataset with the lowest uncertainty was assigned as the reference MC dose distribution. DATA FORMAT AND USAGE NOTES: The dataset is available online at http://irochouston.mdanderson.org/rpc/BrachySeeds/BrachySeeds/index.html,https://doi.org/10.52519/00005. Files include the treatment plan for each TPS in DICOM RT format, reference MC dose data in RT Dose format, as well as a guide for database users and all files necessary to repeat the MC simulations. POTENTIAL APPLICATIONS: The dataset facilitates the commissioning of brachytherapy MBDCAs using TPS embedded tools and establishes a methodology for the development of future clinical test cases. It is also useful to non-MBDCA adopters for intercomparing MBDCAs and exploring their benefits and limitations, as well as to brachytherapy researchers in need of a dosimetric and/or a DICOM RT information parsing benchmark. Limitations include specificity in terms of radionuclide, source model, clinical scenario, and MBDCA version used for its preparation.

GEANT4-DNA simulation of temperature-dependent and pH-dependent yields of chemical radiolytic species.

Objective.GEANT4-DNA can simulate radiation chemical yield (G-value) for radiolytic species such as the hydrated electron (eaq-) with the independent reaction times (IRT) method, however, only at room temperature and neutral pH. This work aims to modify the GEANT4-DNA source code to enable the calculation ofG-values for radiolytic species at different temperatures and pH values.Approach.In the GEANT4-DNA source code, values of chemical parameters such as reaction rate constant, diffusion coefficient, Onsager radius, and water density were replaced by corresponding temperature-dependent polynomials. The initial concentration of hydrogen ion (H+)/hydronium ion (H3O+) was scaled for a desired pH using the relationship pH = -log10[H+]. To validate our modifications, two sets of simulations were performed. (A) A water cube with 1.0 km sides and a pH of 7 was irradiated with an isotropic electron source of 1 MeV. The end time was 1µs. The temperatures varied from 25 °C to 150 °C. (B) The same setup as (A) was used, however, the temperature was set to 25 °C while the pH varied from 5 to 9. The results were compared with published experimental and simulated work.Main results.The IRT method in GEANT4-DNA was successfully modified to simulateG-values for radiolytic species at different temperatures and pH values. Our temperature-dependent results agreed with experimental data within 0.64%-9.79%, and with simulated data within 3.52%-12.47%. The pH-dependent results agreed well with experimental data within 0.52% to 3.19% except at a pH of 5 (15.99%) and with simulated data within 4.40%-5.53%. The uncertainties were below ±0.20%. Overall our results agreed better with experimental than simulation data.Significance.Modifications in the GEANT4-DNA code enabled the calculation ofG-values for radiolytic species at different temperatures and pH values.

FastDM,Mcalculation in LDR brachytherapy using deep learning methods.

Objective.The Monte Carlo (MC) method provides a complete solution to the tissue heterogeneity effects in low-energy low-dose rate (LDR) brachytherapy. However, long computation times limit the clinical implementation of MC-based treatment planning solutions. This work aims to apply deep learning (DL) methods, specifically a model trained with MC simulations, to predict accurate dose to medium in medium (DM,M) distributions in LDR prostate brachytherapy.Approach.To train the DL model, 2369 single-seed configurations, corresponding to 44 prostate patient plans, were used. These patients underwent LDR brachytherapy treatments in which125I SelectSeed sources were implanted. For each seed configuration, the patient geometry, the MC dose volume and the single-seed plan volume were used to train a 3D Unet convolutional neural network. Previous knowledge was included in the network as anr2kernel related to the first-order dose dependency in brachytherapy. MC and DL dose distributions were compared through the dose maps, isodose lines, and dose-volume histograms. Features enclosed in the model were visualized.Main results.Model features started from the symmetrical kernel and finalized with an anisotropic representation that considered the patient organs and their interfaces, the source position, and the low- and high-dose regions. For a full prostate patient, small differences were seen below the 20% isodose line. When comparing DL-based and MC-based calculations, the predicted CTVD90metric had an average difference of -0.1%. Average differences for OARs were -1.3%, 0.07%, and 4.9% for the rectumD2cc, the bladderD2cc, and the urethraD0.1cc. The model took 1.8 ms to predict a complete 3DDM,Mvolume (1.18 M voxels).Significance.The proposed DL model stands for a simple and fast engine which includes prior physics knowledge of the problem. Such an engine considers the anisotropy of a brachytherapy source and the patient tissue composition.

Applying the column generation method to the intensity modulated high dose rate brachytherapy inverse planning problem.

Objective.Intensity modulated high dose rate brachytherapy (IMBT) is a rapidly developing application of brachytherapy where anisotropic dose distributions can be produced at each source dwell position. This technique is made possible by placing rotating metallic shields inside brachytherapy needles or catheters. By dynamically directing the radiation towards the tumours and away from the healthy tissues, a more conformal dose distribution can be obtained. The resulting treatment planning involves optimizing dwell position and shield angle (DPSA). The aim of this study was to investigate the column generation method for IMBT treatment plan optimization.Approach.A column generation optimization algorithm was developed to optimize the dwell times and shield angles. A retrospective study was performed on 10 prostate cases using RapidBrachyMCTPS. At every iteration, the plan was optimized with the chosen DPSA which would best improve the cost function that was added to the plan. The optimization process was stopped when the remaining DPSAs would not add value to the plan to limit the plan complexity.Main results.The average number of DPSAs and voxels were 2270 and 7997, respectively. The column generation approach yielded near-optimal treatment plans by using only 11% of available DPSAs on average in ten prostate cases. The coverage and organs at risk constraints passed in all ten cases.Significance.The column generation method produced high-quality deliverable prostate IMBT plans. The treatment plan quality reached a plateau, where adding more DPSAs had a minimal effect on dose volume histogram parameters. The iterative nature of the column generation method allows early termination of the treatment plan creation process as soon as the dosimetric indices from dose volume histogram satisfy the clinical requirements or if their values stabilize.

Effects of incoming particle energy and cluster size on the G-value of hydrated electrons.

In hydrated electron (e-aq) dosimetry, absorbed radiation dose to water is measured by monitoring the concentration of radiation-induced e-aq. However, to obtain accurate dose, the radiation chemical yield of e-aq, G(e-aq), is needed for the radiation quality/setup under investigation. The aim of this study was to investigate the time-evolution of the G-values for the main generated reactive species during water radiolysis using GEANT4-DNA. The effects of cluster size and linear energy transfer (LET) on G(e-aq) were examined. Validity of GEANT4-DNA for calculation of G(e-aq) for clinically relevant energies was studied. Three scenarios were investigated with different phantom sizes and incoming electron energies (1 keV to 1 MeV). The time evolution of G(e-aq) was in good agreement with published data and did not change with decreasing phantom size. The time-evolution of the G-values increases with increasing LET for all radiolytic species. The particle tracks formed with high-energy electrons are separated and the resulting reactive species develop independently in time. With decreasing energy, the mean separation distance between reactive species decreases. The particle tracks might not initially overlap but will overlap shortly thereafter due to diffusion of reactive species, increasing the probability of e-aq recombination with other species. This also explains the decrease of G(e-aq) with cluster size and LET. Finally, if all factors are kept constant, as the incoming electron energy increases to clinically relevant energies, G(e-aq) remains similar to its value at 1 MeV, hence GEANT4-DNA can be used for clinically relevant energies.

Simulation of a novel, non-invasive radiation detector to measure the arterial input function for dynamic positron emission tomography.

BACKGROUND: Dynamic positron emission tomography (dPET) is a nuclear medicine imaging technique providing functional images for organs of interest with applications in oncology, cardiology, and drug discovery. This technique requires the acquisition of the time-course arterial plasma activity concentration, called the arterial input function (AIF), which is conventionally acquired via arterial blood sampling. PURPOSE: The aim of this study was to (A) optimize the geometry for a novel and cost efficient non-invasive detector called NID designed to measure the AIF for dPET scans through Monte Carlo simulations and (B) develop a clinical data analysis chain to successfully separate the arterial component of a simulated AIF signal from the venous component. METHODS: The NID was optimized by using an in-house Geant4-based software package. The sensitive volume of the NID consists of a band of 10 cm long and 1 mm in diameter scintillating fibers placed over a wrist phantom. The phantom was simulated as a cylinder, 10 cm long and 6.413 cm in diameter comprised of polyethylene with two holes placed through it to simulate the patient's radial artery and vein. This phantom design was chosen to match the wrist phantom used in our previous proof of concept work. Two geometries were simulated with different arrangements of scintillating fibers. The first design used a single layer of 64 fibers. The second used two layers, an inner layer with 29 fibers and an outer layer with 30 fibers. Four positron emitting radioisotopes were simulated: 18 F, 11 C, 15 O, and 68 Ga with 100 million simulated decay events per run. The total and intrinsic efficiencies of both designs were calculated as well as the full width half maximum (FWHM) of the signal. In addition, contribution by the annihilation photons versus positrons to the signal was investigated. The results obtained from the two simulated detector models were compared. A clinical data analysis chain using an expectation maximization maximum likelihood algorithm was tested. This analysis chain will be used to separate arterial counts from the total signal. RESULTS: The second NID design with two layers of scintillating fibers had a higher efficiency for all simulations with a maximum increase of 17% total efficiency for 11 C simulation. All simulations had a significant annihilation photon contribution. The signal for 18 F and 11 C was almost entirely due to photons. The clinical data analysis chain was within 1% of the true value for 434 out of 440 trials. Further experimental studies to validate these simulations will be required. CONCLUSIONS: The design of the NID was optimized and its efficiency increased through Monte Carlo simulations. A clinical data analysis chain was successfully developed to separate the arterial component of an AIF signal from the venous component. The simulations show that the NID can be used to accurately measure the AIF non-invasively for dPET scans.

Dosimetric impact of a robust optimization approach to mitigate effects from rotational uncertainty in prostate intensity-modulated brachytherapy.

BACKGROUND: Intensity-modulated brachytherapy (IMBT) is an emerging technology for cancer treatment, in which radiation sources are shielded to shape the dose distribution. The rotatable shields provide an additional degree of freedom, but also introduce an additional, directional, type of uncertainty, compared to conventional high-dose-rate brachytherapy (HDR BT). PURPOSE: We propose and evaluate a robust optimization approach to mitigate the effects of rotational uncertainty in the shields with respect to planning criteria. METHODS: A previously suggested prototype for platinum-shielded prostate 169 Yb-based dynamic IMBT is considered. We study a retrospective patient data set (anatomical contours and catheter placement) from two clinics, consisting of six patients that had previously undergone conventional 192 Ir HDR BT treatment. The Monte Carlo-based treatment planning software RapidBrachyMCTPS is used for dose calculations. In our computational experiments, we investigate systematic rotational shield errors of ±10° and ±20°, and the same systematic error is applied to all dwell positions in each scenario. This gives us three scenarios, one nominal and two with errors. The robust optimization approach finds a compromise between the average and worst-case scenario outcomes. RESULTS: We compare dose plans obtained from standard models and their robust counterparts. With dwell times obtained from a linear penalty model (LPM), for 10° errors, the dose to urethra ( D 0.1 c c $D_{0.1cc}$ ) and rectum ( D 0.1 c c $D_{0.1cc}$ and D 1 c c $D_{1cc}$ ) increase with up to 5% and 7%, respectively, in the worst-case scenario, while with the robust counterpart, the corresponding increases were 3% and 3%. For all patients and all evaluated criteria, the worst-case scenario outcome with the robust approach had lower deviation compared to the standard model, without compromising target coverage. We also evaluated shield errors up to 20° and while the deviations increased to a large extent with the standard models, the robust models were capable of handling even such large errors. CONCLUSIONS: We conclude that robust optimization can be used to mitigate the effects from rotational uncertainty and to ensure the treatment plan quality of IMBT.

Image-Guided Brachytherapy for Rectal Cancer: Reviewing the Past Two Decades of Clinical Investigation.

(1) Background: The introduction of total mesorectal excision (TME) for rectal cancer has led to improvement in local recurrence (LR) outcomes. Furthermore, the addition of preoperative external beam radiotherapy to TME reduces LR to less than 6%. As a trade-off to these gradual improvements in local therapies, the oncology community's work is now focusing on mitigating treatment-related toxicities. In other words, if a small proportion of 4-6% of rectal cancer patients benefit from additional local therapy beyond TME, the burden of acute and long-term side effects must be considered with care. (2) Methods: With the introduction of better-quality imaging for tumor visualization and treatment planning, a new conformed radiation treatment was introduced with high-dose-rate endorectal brachytherapy. The treatment concept was tested in phase I and II studies: first in the pre-operative setting, and then as a boost after external beam radiation therapy, as a dose-escalation study, to achieve higher local tumor control. (3) Results: HDREBT is safe and effective in achieving a high tumor regression rate and was well tolerated in a phase II multicenter and two matched-pair studies. (4) Conclusions: HDREBT is a conformed radiation therapy that is safe and effective, and is presently explored in a phase III dose-escalation study in the NOM of patients with operable rectal cancer.

Approaching automated applicator digitization from a new angle: Using sagittal images to improve deep learning accuracy and robustness in high-dose-rate prostate brachytherapy.

PURPOSE: To automate the segmentation of treatment applicators on computed tomography (CT) images for high-dose-rate (HDR) brachytherapy prostate patients implanted with titanium needles with the goals of improving plan quality and reducing the patient's time under anesthesia. METHODS: The investigation was performed using 57 retrospective, interstitial prostate treatments randomly assigned to training (n = 27), validation (n = 10), and testing (n = 20). Unique to this work, the CT image set was reformatted into 2D sagittal slices instead of the default axial orientation. A deep learning-based segmentation was performed using a 2D U-Net architecture followed by a density-based linkage clustering algorithm to classify individual catheters in 3D. Potential confounders, such as gold seeds and conjoined applicators with intersecting needle geometries, were corrected using a customized polynomial fitting algorithm. The geometric agreement of the automated digitization was evaluated against the clinically treated manual digitization to measure tip and shaft errors in the reconstruction. RESULTS: The proposed algorithm achieved tip and shaft agreements of -0.1 ± 0.6 mm (range -1.8 mm to 1.4 mm) and 0.13 ± 0.09 mm (maximum 0.96 mm), respectively on a data set with 20 patients and 353 total needles. Our method was able to separate all intersecting applicators reliably. The time to generate the automated applicator digitization averaged approximately 1 min. CONCLUSIONS: Using sagittal instead of axial images for 2D segmentation of interstitial brachytherapy applicators produced submillimeter agreement with manual segmentation. The automated digitization of interstitial applicators in prostate brachytherapy has the potential to improve quality and consistency while reducing the patient's time under anesthesia.

Sideband cavity absorption readout (SideCAR) with a robust frequency lock.

We present a simple, continuous, cavity-enhanced optical absorption measurement technique based on high-bandwidth Pound-Drever-Hall (PDH) sideband locking. The technique provides a resonant amplitude quadrature readout that can be mapped onto the cavity's internal loss rate and is naturally compatible with weak probe beams. With a proof-of-concept 5-cm-long Fabry-Perot cavity, we measure an absorption sensitivity ∼10-10cm-1/Hz from 30 kHz to 1 MHz, and a minimum value of 6.6×10-11cm-1/Hz at 100 kHz, with 38 µW collected from the cavity's circulating power.