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BackgroundIntensity-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). PurposeWe propose and evaluate a robust optimization approach to mitigate the effects of rotational uncertainty in the shields with respect to planning criteria. MethodsA previously suggested prototype for platinum-shielded prostate Yb-169-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 Ir-192 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 degrees and +/- 20 degrees, 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. ResultsWe compare dose plans obtained from standard models and their robust counterparts. With dwell times obtained from a linear penalty model (LPM), for 10 degrees errors, the dose to urethra (D0.1cc) and rectum (D0.1cc and D1cc) 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 degrees and while the deviations increased to a large extent with the standard models, the robust models were capable of handling even such large errors. ConclusionsWe conclude that robust optimization can be used to mitigate the effects from rotational uncertainty and to ensure the treatment plan quality of IMBT. Funding: Vetenskapsradet [VR-NT 2019-05416]; Cancerfonden [CAN 2017/1029]; Canada Research Chairs [252135]; Collaborative health research projects [523394-18]

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.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.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.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.

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 of G-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 1 µs. The temperatures varied from 25 °C to 150 °C. B) 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 simulate G-values for radiolytic species at different temperatures and pH values. Our temperature-dependent results agreed with experimental data within 0.64% to 9.79%, and with simulated data within 3.52% to 12.47%. The pH-dependent results agreed well with experimental data within 0.52% to 3.19% except at pH of 5 (15.99%) and with simulated data within 4.40% to 5.53%. The uncertainties were below ± 0.20%. Overall our results agreed better with experimental than simulation data. Significance: Modifications in GEANT4-DNA code enabled calculation of G-values for radiolytic species at different temperature and pH values.

Purpose Dynamic Positron Emission Tomography (dPET) requires 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 number of decay events are imported into the Geant4-based Monte Carlo software to run a simulation. In this study, 100 million decays of 18F and 68Ga 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% for 18F and by 51.7% for 68Ga 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.

PurposeTo provide the first clinical test case for commissioning of Ir-192 brachytherapy model-based dose calculation algorithms (MBDCAs) according to the AAPM TG-186 report workflow. Acquisition and Validation MethodsA computational patient phantom model was generated from a clinical multi-catheter Ir-192 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 Ir-192 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 NotesThe dataset is available online at ,. 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 ApplicationsThe 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.

BACKGROUND AND PURPOSE Despite the excellent clinical outcomes from brachytherapy treatments compared with other modalities and the low associated costs, there have been reports of a decline in utilization of brachytherapy. The aim of this study was to investigate in detail the trend in utilization of brachytherapy in the province of Quebec, Canada, from 2011 to 2019. MATERIALS AND METHODS All radiotherapy clinics in the province of Quebec, and among these the clinics that provide brachytherapy treatments, were identified. This observational retrospective cohort study involved analysis of data compiled by the Ministere de la Sante et des Services Sociaux du Quebec for the period of 2011 to end of 2019 on all brachytherapy procedures performed in the province of Quebec. Time series graphs were used to describe the number of high dose rate (HDR) and low dose rate (LDR) brachytherapy treatments during the studied time period. Statistical analysis was conducted using R statistical software. RESULTS Between 2011 and 2019, 12 hospitals in the province of Quebec provided radiotherapy treatments, and all of them offered brachytherapy services. The median annual number of brachytherapy sessions was 4413 (range 3930-4829). HDR brachytherapy represented over 90% of all brachytherapy treatments throughout the study period. Significant changes over time were observed in the number of treatments: at least 5% change was seen only for the two most common subtypes of brachytherapy, HDR interstitial and HDR intracavitary, with an increase of 9.6% and a decrease of 9.2%, respectively. The use of other subtypes of brachytherapy (HDR-plesiotherapy, LDR-interstitial, LDR-intracavitary, LDR-eye plaque) was stable between 2011 and 2019, with ≤ 2.5% variation. CONCLUSION This study demonstrates an overall steady use of brachytherapy between 2011 and 2019 in Quebec. Brachytherapy offers numerous advantages for the treatment of diverse cancer sites. Although more sophisticated external beam radiotherapy treatments have emerged in the last decades, the precision and cost-effectiveness of brachytherapy remain unbeaten. To ensure the continued use and availability of brachytherapy, governments must put in place policies and regulations to that effect. Training and exposure of future health care professionals to brachytherapy within Quebec and Canada is essential to provide all patients the same access to this life saving modality.

Background Multiple post-treatment dosimetry methods are currently under investigation for Yttrium-90 ($$^{90}\hbox {Y}$$ 90 Y ) radioembolization. Within each methodology, a variety of dosimetric inputs exists that affect the final dose estimates. Understanding their effects is essential to facilitating proper dose analysis and crucial in the eventual standardization of radioembolization dosimetry. The purpose of this study is to investigate the dose differences due to different self-calibrations and mass density assignments in the non-compartmental and local deposition methods. A practical mean correction method was introduced that permits dosimetry in images where the quality is compromised by patient motion and partial volume effects. Methods Twenty-one patients underwent $$^{90}\hbox {Y}$$ 90 Y radioembolization and were imaged with SPECT/CT. Five different self-calibrations (FOV, Body, OAR, Liverlung, and Liver) were implemented and dosimetrically compared. The non-compartmental and local deposition method were used to perform dosimetry based on either nominal- or CT calibration-based mass densities. A mean correction method was derived assuming homogeneous densities. Cumulative dose volume histograms, linear regressions, boxplots, and Bland Altman plots were utilized for analysis. Results Up to 270% weighted dose difference was found between self-calibrations with mean dose differences up to 50 Gy in the liver and 23 Gy in the lungs. Between the local deposition and non-compartmental methods, the liver and lung had dose differences within 0.71 Gy and 20 Gy, respectively. The local deposition method’s nominal and CT calibration-based mass density implementations dosimetric metrics were within 1.4% in the liver and 24% in the lungs. The mean lung doses calculated with the CT method were shown to be inflated. The mean correction method demonstrated that the corrected mean doses were greater by up to $$\sim 5$$ ∼ 5 Gy in the liver and lower by up to $$\sim 12$$ ∼ 12 Gy in the lungs. Conclusions The OAR calibration may be utilized as a potentially more accurate and precise self-calibration. The non-compartmental method was found more comparable to the local deposition method in organs that were more homogeneous in mass densities. Due to the potential for inflated lung mean doses, the non-compartmental and local deposition method implemented with nominal mass densities is recommended for more consistent dosimetric results. If patient motion and partial volume effects are present in the liver, our practical correction method will calculate more representative doses in images suboptimal for dosimetry.

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.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.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: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 forThe 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.

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 (D M,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 which 125I 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 an r 2 kernel 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 CTV D 90 metric had an average difference of −0.1%. Average differences for OARs were −1.3%, 0.07%, and 4.9% for the rectum D 2cc, the bladder D 2cc, and the urethra D 0.1cc. The model took 1.8 ms to predict a complete 3D D M,M volume (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.

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.

The biological effects of ionizing radiation depend on the tissue, tumor type, radiation quality, and patient-specific factors. Inter-patient variation in cell/nucleus size may influence patient-specific dose response. However, this variability in dose response is not well investigated due to lack of available cell/nucleus size data. The aim of this study was to develop methods to derive cell/nucleus size distributions from digital images of 2D histopathological samples and use them to build digital 3D models for use in cellular dosimetry. Nineteen of sixty hematoxylin and eosin stained lung adenocarcinoma samples investigated passed exclusion criterion to be analyzed in the study. A difference of gaussians blob detection algorithm was used to identify nucleus centers and quantify cell spacing. Hematoxylin content was measured to determine nucleus radius. Pouring simulations were conducted to generate one-hundred 3D models containing volumes of equivalent cell spacing and nuclei radius to those in histopathological samples. The nuclei radius distributions of non-tumoral and cancerous regions appearing in the same slide were significantly different (p 0.01) in all samples analyzed. The median nuclear-cytoplasmic ratio was 0.36 for non-tumoral cells and 0.50 for cancerous cells. The average cellular and nucleus packing densities in the 3D models generated were 65.9% (SD: 1.5%) and 13.3% (SD: 0.3%) respectively. Software to determine cell spacing and nuclei radius from histopathological samples was developed. 3D digital tissue models containing volumes with equivalent cell spacing, nucleus radius, and packing density to cancerous tissues were generated.

PURPOSE A prototype 169 Yb source was developed in combination with a dynamic rotating platinum shield system (AIM-Brachy) to deliver intensity modulated brachytherapy (IMBT). The purpose of this study was to evaluate the dosimetric characteristics of the bare/shielded 169 Yb source using Monte Carlo (MC) simulations and perform an independent dose verification using a dosimetry platform based on a multipoint plastic scintillator detector (mPSD). METHODS The TG-43U1 dosimetric parameters were calculated for the source model using RapidBrachyMCTPS. Real-time dose rate measurements were performed in a water tank for both the bare/shielded source using a custom remote afterloader. For each dwell position, the dose rate was independently measured by the three scintillators (BCF-10, BCF-12, and BCF-60). For the bare source, dose rate was measured at distances up to 3 cm away from the source over a range of 7 cm along the catheter. For the shielded source, measurements were performed with the mPSD placed at 1 cm from the source at four different azimuthal angles ( 0∘ , 9 0∘ , 18 0∘ , and 27 0∘ ). RESULTS The dosimetric parameters were tabulated for the source model. For the bare source, differences between measured and calculated along-away dose rates were generally below 5-10%. Along the transverse axis, deviations were, on average (range), 3.3% (0.6-6.2%) for BCF-10, 1.7% (0.9-2.9%) for BCF-12, and 2.2% (0.3-4.4%) for BCF-60. The maximum dose rate reduction due to shielding at a radial distance of 1 cm was 88.8 ± 1.2%, compared to 83.5 ± 0.5% as calculated by MC. CONCLUSIONS The dose distribution for the bare/shielded 169 Yb source was independently verified using mPSD with good agreement in regions close to the source. The 169 Yb source coupled with the partial-shielding system is an effective technique to deliver IMBT.

The purpose of this study was to review the limitations of dose calculation formalisms for photon-emitting brachytherapy sources based on the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) report and to provide recommendations to transition to model-based dose calculation algorithms. Additionally, an overview of these algorithms and approaches is presented. The influence of tissue and seed/applicator heterogeneities on brachytherapy dose distributions for breast, gynecologic, head and neck, rectum, and prostate cancers as well as eye plaques and electronic brachytherapy treatments were investigated by comparing dose calculations based on the TG-43 formalism and model-based dose calculation algorithms.

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 − 10 cm − 1 / Hz from 30 kHz to 1 MHz, and a minimum value of 6.6 × 10 − 11 cm − 1 / Hz at 100 kHz, with 38 µW collected from the cavity’s circulating power.

Purpose Intensity modulated brachytherapy (IMBT) is a novel high dose rate brachytherapy (HDR BT) technique which incorporates static or dynamic shielding to increase tumor coverage and/or spare healthy tissues. The purpose of this study is to present a novel delivery system (AIM-Brachy) design that can enable dynamic-shield IMBT for prostate cancer. Methods The AIM-Brachy system dynamically controls the rotation of platinum shields, placed within interstitial catheters, which partially collimate the radiation emitted from an 169 Yb source. Conventional HDR BT (10 Ci 192 Ir) and IMBT (18 Ci 169 Yb) plans were generated for 12 patients using an in-house column generation-based optimizer, coupled to a Geant4-based dose calculation engine, RapidBrachyMC. Treatment plans were normalized to match the same PTV D90 coverage as the clinical plan. Intershield attenuation effects were taken into account. A sensitivity analysis was performed to evaluate the dosimetric impact of systematic longitudinal source positioning errors ( ± 1 mm, ± 2 mm, and ± 3 mm) and rotational errors ( ± 5 ∘ , ± 10 ∘ , and ± 15 ∘ ) on clinically relevant parameters (PTV D90 and urethra D10 ). Results The platinum shield reduced the dose rate on the shielded side at 1 cm to 18.1% of the dose rate on the unshielded side. For equal PTV D90 coverage, the urethral D10 was reduced by 13.3% ± 4.7%, without change to other plan quality indices (PTV V100 , V150, V200 , bladder V75 , rectum V75 , HI, COIN). Delivery times for HDR BT and IMBT were 9.2 ± 1.6 min and 18.6 ± 4.0 min, respectively. In general, the PTV D90 was more sensitive to source positioning errors than rotational errors, while the urethral D10 was more sensitive to rotational errors than source positioning errors. For a typical range of positioning errors ( ± 1 mm, ± 5 ∘ ), the overall tolerance was Conclusions The AIM-Brachy system was proposed to deliver dynamic-shield IMBT for prostate cancer with the potential to create a low dose tunnel within the urethra. The urethra-sparing properties are desirable to minimize the occurrence and severity of urethral strictures or, alternatively, to provide a method for dose escalation.

Radioembolization gains continuous traction as a primarily palliative radiation treatment for hepatic tumours. A form of nuclear medicine therapy, Yttrium-90 containing microspheres are catheter guided and injected into the right, left, or a specifically selected hepatic artery. A multitude of comprehensive planning steps exist to ensure a thorough and successful treatment. Clear clinical and physiological guidelines have been established and nuclear imaging is used to plan and verify dose distributions. Radioembolization's treatment rationale is based on tumour and blood vessel dynamics that allow a targeted treatment approach. However, radioembolization's dosimetry is grossly oversimplified. In fact, the currently utilized clinical dosimetric standards (e.g. partition method) have persisted since the 1990s. Moreover, the multitude of radioembolization's intertwining components lies disjointed within the literature. Particularly relevant to new readers, this review provides a methodical guide that presents the treatment rationale behind every clinical step. The emerging dosimetry methods and its factors are further discussed to provide a comprehensive review on an essential research direction.

(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.

Purpose To investigate differences between prescribed and postimplant calculated dose in 192Ir high-dose-rate endorectal brachytherapy (HDR-EBT) by evaluating dose to clinical target volume (CTV) and organs at risk (OARs) calculated with a Monte Carlo–based dose calculation software, RapidBrachyMC. In addition, dose coverage, conformity, and homogeneity were compared among the radionuclides 192Ir, 75Se, and 169Yb for use in HDR-EBT. Methods and Materials Postimplant dosimetry was evaluated using 23 computed tomography (CT) images from patients treated with HDR-EBT using the 192Ir microSelectron v2 (Elekta AB, Stockholm, Sweden) source and the Intracavitary Mold Applicator Set (Elekta AB, Stockholm, Sweden), which is a flexible applicator capable of fitting a tungsten rod for OAR shielding. Four tissue segmentation schemes were evaluated: (1) TG-43 formalism, (2) materials and nominal densities assigned to contours of foreign objects, (3) materials and nominal densities assigned to contoured organs in addition to foreign objects, and (4) materials specified as in (3) but with voxel mass densities derived from CT Hounsfield units. Clinical plans optimized for 192Ir were used, with the results for 75Se and 169Yb normalized to the D90 of the 192Ir clinical plan. Results In comparison to segmentation scheme 4, TG-43–based dosimetry overestimates CTV D90 by 6% (P = .00003), rectum D50 by 24% (P = .00003), and pelvic bone D50 by 5% (P = .00003) for 192Ir. For 169Yb, CTV D90 is overestimated by 17% (P = .00003) and rectum D50 by 39% (P = .00003), and pelvic bone D50 is significantly underestimated by 27% (P = .007). Postimplant dosimetry calculations also showed that a 169Yb source would give 20% (P = .00003) lower rectum V60 and 17% (P = .00008) lower rectum D50. Conclusions Ignoring high-Z materials in dose calculation contributes to inaccuracies that may lead to suboptimal dose optimization and disagreement between prescribed and calculated dose. This is especially important for low-energy radionuclides. Our results also show that with future magnetic resonance imaging–based treatment planning, loss of CT density data will only affect calculated dose in nonbone OARs by 2% or less and bone OARs by 13% or less across all sources if material composition and nominal mass densities are correctly assigned.

Purpose The purpose of this study was to evaluate the impact of dose reporting schemes and tissue/applicator heterogeneities for 192 Ir-, 75 Se-, and 169 Yb-based MRI-guided conventional and intensity-modulated brachytherapy. Methods and materials Treatment plans using a variety of dose reporting and tissue/applicator segmentation schemes were generated for a cohort (n = 10) of cervical cancer patients treated with 192 Ir-based Venezia brachytherapy. Dose calculations were performed using RapidBrachyMCTPS, a Geant4-based research Monte Carlo treatment planning system. Ultimately, five dose calculation scenarios were evaluated: (a) dose to water in water (Dw,w ); (b) Dw,w taking the applicator material into consideration (Dw,wApp ); (c) dose to water in medium (Dw,m ); (d and e) dose to medium in medium with mass densities assigned either nominally per structure (Dm,m (Nom) ) or voxel-by-voxel (Dm,m ). Results Ignoring the plastic Venezia applicator (Dw,wApp ) overestimates Dm,m by up to 1% (average) with high energy source (192 Ir and 75 Se) and up to 2% with 169 Yb. Scoring dose to water (Dw,wApp or Dw,m ) generally overestimates dose and this effect increases with decreasing photon energy. Reporting dose other than Dm,m (or Dm,m Nom ) for 169 Yb-based conventional and intensity-modulated brachytherapy leads to a simultaneous overestimation (up to 4%) of CTVHR D90 and underestimation (up to 2%) of bladder D2cc due to a significant dip in the mass-energy absorption ratios at the depths of nearby targets and OARs. Using a nominal mass-density assignment per structure, rather than a CT-derived voxel-by-voxel assignment for MRI-guided brachytherapy, amounts to a dose error up to 1% for all radionuclides considered. Conclusions The effects of the considered dose reporting schemes trend correspondingly between conventional and intensity-modulated brachytherapy. In the absence of CT-derived mass densities, MRI-only-based dosimetry can adequately approximate Dm,m by assigning nominal mass densities to structures. Tissue and applicator heterogeneities do not significantly impact dosimetry for 192 Ir and 75 Se, but do for 169 Yb; dose reporting must be explicitly defined since Dw,m and Dw,w may overstate the dosimetric benefits.

$\bf{Purpose:}$ The goal of this study was (i) to use artificial intelligence to automate the traditionally labor-intensive process of manual segmentation of tumor regions in pathology slides performed by a pathologist and (ii) to validate the use of a well-known and readily available deep learning architecture. Automation will reduce the human error involved in manual delineation, increase efficiency, and result in accurate and reproducible segmentation. This advancement will alleviate the bottleneck in the workflow in clinical and research applications due to a lack of pathologist time. Our application is patient-specific microdosimetry and radiobiological modeling, which builds on the contoured pathology slides. $\bf{Methods:}$ A U-Net architecture was used to segment tumor regions in pathology core biopsies of lung tissue with adenocarcinoma stained using hematoxylin and eosin. A pathologist manually contoured the tumor regions in 56 images with binary masks for training. Overlapping patch extraction with various patch sizes and image downsampling were investigated individually. Data augmentation and 8-fold cross-validation were used. $\bf{Results:}$ The U-Net achieved accuracy of 0.91$\pm$0.06, specificity of 0.90$\pm$0.08, sensitivity of 0.92$\pm$0.07, and precision of 0.8$\pm$0.1. The F1/DICE score was 0.85$\pm$0.07, with a segmentation time of 3.24$\pm$0.03 seconds per image, achieving a 370$\pm$3 times increased efficiency over manual segmentation. In some cases, the U-Net correctly delineated the tumor's stroma from its epithelial component in regions that were classified as tumor by the pathologist. $\bf{Conclusion:}$ The U-Net architecture can segment images with a level of efficiency and accuracy that makes it suitable for tumor segmentation of histopathological images in fields such as radiotherapy dosimetry, specifically in the subfields of microdosimetry., Comment: 17 pages, 5 figures, 2 tables

Kinetic modeling of positron emission tomography (PET) data can assess index rate of uptake, metabolism and predict disease progression more accurately than conventional static PET. However, it requires knowledge of the time-course of the arterial blood radioactivity concentration, called the arterial input function (AIF). The gold standard to acquire the AIF is by invasive means. The purpose of this study was to validate a previously developed dual readout scintillating fiber-based non-invasive positron detector, hereinafter called non-invasive detector (NID), developed to determine the AIF for dynamic PET measured from the human radial artery. The NID consisted of a 3 m long plastic scintillating fiber with each end coupled to a 5 m long transmission fiber followed by a silicon photomultiplier. The scintillating fiber was enclosed inside the grooves of a plastic cylindrical shell. Two sets of experiments were performed to test the NID against a previously validated microfluidic positron detector. A closed-loop microfluidic system combined with a wrist phantom was used. During the first experiment, the three PET radioisotopes 18F, 11C and 68Ga were tested. After optimizing the detector, a second series of tests were performed using only 18F and 11C. The maximum pulse amplitude to electronic noise ratio was 52 obtained with 11C. Linear regressions showed a linear relation between the two detectors. These preliminary results show that the NID can accurately detect positrons from a patient's wrist and has the potential to non-invasively measure the AIF during a dynamic PET scan. The accuracy of these measurements needs to be determined.

PURPOSE To present a novel, MRI-compatible dynamicshield intensity modulated brachytherapy (IMBT) applicator and delivery system using 192 Ir, 75 Se, and 169 Yb radioisotopes for the treatment of locally advanced cervical cancer. Needle-free IMBT is a promising technique for improving target coverage and organs at risk (OAR) sparing. METHODS AND MATERIALS The IMBT delivery system dynamically controls the rotation of a novel tungsten shield placed inside an MRI-compatible, 6-mm wide intrauterine tandem. Using 36 cervical cancer cases, conventional intracavitary brachytherapy (IC-BT) and intracavitary/interstitial brachytherapy (IC/IS-BT) (10Ci 192 Ir) plans were compared to IMBT (10Ci 192 Ir; 11.5Ci 75 Se; 44Ci 169 Yb). All plans were generated using the Geant4-based Monte Carlo dose calculation engine, RapidBrachyMC. Treatment plans were optimized then normalized to the same high-risk clinical target volume (HR-CTV) D90 and the D2cc for bladder, rectum, and sigmoid in the research brachytherapy planning system, RapidBrachyMCTPS. Plans were renormalized until either of the three OAR reached dose limits to calculate the maximum achievable HR-CTV D90 and D98 . RESULTS Compared to IC-BT, IMBT with either of the three radionuclides significantly improves the HR-CTV D90 and D98 by up to 5.2% ± 0.3% (P

A prototypeThe TG-43U1 dosimetric parameters were calculated for the source model using RapidBrachyMCTPS. Real-time dose rate measurements were performed in a water tank for both the bare/shielded source using a custom remote afterloader. For each dwell position, the dose rate was independently measured by the three scintillators (BCF-10, BCF-12, and BCF-60). For the bare source, dose rate was measured at distances up to 3 cm away from the source over a range of 7 cm along the catheter. For the shielded source, measurements were performed with the mPSD placed at 1 cm from the source at four different azimuthal angles (The dosimetric parameters were tabulated for the source model. For the bare source, differences between measured and calculated along-away dose rates were generally below 5-10%. Along the transverse axis, deviations were, on average (range), 3.3% (0.6-6.2%) for BCF-10, 1.7% (0.9-2.9%) for BCF-12, and 2.2% (0.3-4.4%) for BCF-60. The maximum dose rate reduction due to shielding at a radial distance of 1 cm was 88.8 ± 1.2%, compared to 83.5 ± 0.5% as calculated by MC.The dose distribution for the bare/shielded

Purpose Detailed and accurate absorbed dose calculations from radiation interactions with the human body can be obtained with the Monte Carlo (MC) method. However, the MC method can be slow for use in the time-sensitive clinical workflow. The aim of this study was to provide a solution to the accuracy-time trade-off for 192Ir-based high-dose-rate brachytherapy by using deep learning. Methods and Materials RapidBrachyDL, a 3-dimensional deep convolutional neural network (CNN) model, is proposed to predict dose distributions calculated with the MC method given a patient’s computed tomography images, contours of clinical target volume (CTV) and organs at risk, and treatment plan. Sixty-one patients with prostate cancer and 10 patients with cervical cancer were included in this study, with data from 47 patients with prostate cancer being used to train the model. Results Compared with ground truth MC simulations, the predicted dose distributions by RapidBrachyDL showed a consistent shape in the dose-volume histograms (DVHs); comparable DVH dosimetric indices including 0.73% difference for prostate CTV D90, 1.1% for rectum D2cc, 1.45% for urethra D0.1cc, and 1.05% for bladder D2cc; and substantially smaller prediction time, acceleration by a factor of 300. RapidBrachyDL also demonstrated good generalization to cervical data with 1.73%, 2.46%, 1.68%, and 1.74% difference for CTV D90, rectum D2cc, sigmoid D2cc, and bladder D2cc, respectively, which was unseen during the training. Conclusion Deep CNN-based dose estimation is a promising method for patient-specific brachytherapy dosimetry. Desired radiation quantities can be obtained with accuracies arbitrarily close to those of the source MC algorithm, but with much faster computation times. The idea behind deep CNN-based dose estimation can be safely extended to other radiation sources and tumor sites by following a similar training process.

This work presents Monte Carlo (MC) study of a novel non-invasive positron detector, hereinafter called NID, designed to measure the arterial input function (AIF) through the wrist of a patient for use with dynamic positron emission tomography (PET). The goal of the study was to optimize a previously developed NID prototype, to determine its efficiency and ability to distinguish between the arterial and venous portions of the signal escaping a wrist phantom. A user code based on the Geant4 MC toolkit was developed to model the NID and a wrist phantom. The scintillator based detectors were modelled as 64 polystyrene cylinders, 0.97 mm in diameter, 10 cm long and capped with cylindrical photomultiplier tubes. The scintillator fibers were arranged in a single band around a 64.13 mm polyethylene cylinder representing a model of the wrist. Two cylinders, 2.30 mm in diameter were placed 6 mm apart, 2 mm below the surface of the wrist phantom representing the radial artery and vein. Two simulations were performed by placing 100 million decay events of oxygen-15 (15O) or fluorine-18 (18F), randomly distributed between the artery and vein. Visible wavelength photon tracking was enabled, and Photomultiplier tubes were simulated to collect the visible photons. Deposited energy per event and location of energy deposition were calculated. A python algorithm was used to analyse the results. The arterial signal produced a 5.28 mm and 10.32 mm FWHM for 15O and 18F respectively. The algorithm could determine the correct location of interaction 98% of the time. The NID can resolve the arterial and venous signal and is thus suitable for determining the AIF for dynamic PET.

The goal of this study was to investigate the production, purification and immobilization techniques for a 153Gd brachytherapy source. We have investigated the maximum attainable specific activity of 153Gd through the irradiation of Gd2O3 enriched to 30.6% 152Gd at McMaster Nuclear Reactor. The advantage of producing 153Gd through this production pathway is the possibility to irradiate pre-sealed pellets of 152Gd enriched Gd2O3, thereby removing the need to perform chemical separation with large quantities of radio-impurities. However, small amounts of long-lived impurities are produced from the irradiation of enriched 152Gd targets due to traces of Eu in the sample. If the amount of impurities produced is deemed unacceptable, 153Gd can be isolated as an aqueous solution, chemically separated from impurities and loaded onto a sorbent with a high affinity for Gd before encapsulation.

Microscopic energy deposition distributions from ionizing radiation are used to predict the biological effects of an irradiation and vary depending on biological target size. Ionizing radiation is thought to kill cells or inhibit cell cycling mainly by damaging DNA in the cell nucleus. The size of cells and nuclei depends on tissue type, cell cycle, and malignancy, all of which vary between patients. The aim of this study was to develop methods to perform patient-specific microdosimetry, that being, determining microdosimetric quantities in volumes that correspond to the sizes of cells and nuclei observed in a patient's tissue. A histopathological sample extracted from a stage I lung adenocarcinoma patient was analyzed. A pouring simulation was used to generate a three-dimensional tissue model from cell and nucleus size information determined from the histopathological sample. Microdosimetric distributions including f(y) and d(y) were determined for Co-60,Ir-192,Yb-169 and I-125 in a patient-specific model containing a distribution of cell and nucleus sizes. Fixed radius models and a summation method (where f(y) from many fixed radii models are summed) were compared to the full patient-specific model to evaluate their suitability for fast determination of patient-specific microdosimetric parameters. Fixed radius models do not provide a close approximation of the full patient-specific model y _f or y _d for the lower energy sources investigated, Yb-169 and I-125. The higher energy sources investigated, Co-60 and Ir-192 are less sensitive to target size variation than Yb-169 and I-125. A summation method yields the most accurate approximation of the full model d(y) for all radioisotopes investigated. A summation method allows for the computation of patient-specific microdosimetric distributions with the computing power of a personal computer. With appropriate biological inputs the microdosimetric distributions computed using these methods can yield a patient-specific relative biological effectiveness as part of a multiscale treatment planning approach.

The aim of this study was to calculate microdosimetric distributions for low energy electrons simulated using the Monte Carlo track structure code Geant4-DNA. Tracks for monoenergetic electrons with kinetic energies ranging from 100 eV to 1 MeV were simulated in an infinite spherical water phantom using the Geant4-DNA extension included in Geant4 toolkit version 10.2 (patch 02). The microdosimetric distributions were obtained through random sampling of transfer points and overlaying scoring volumes within the associated volume of the tracks. Relative frequency distributions of energy deposition f(>E)/f(>0) and dose mean lineal energy ([Formula: see text]) values were calculated in nanometer-sized spherical and cylindrical targets. The effects of scoring volume and scoring techniques were examined. The results were compared with published data generated using MOCA8B and KURBUC. Geant4-DNA produces a lower frequency of higher energy deposits than MOCA8B. The [Formula: see text] values calculated with Geant4-DNA are smaller than those calculated using MOCA8B and KURBUC. The differences are mainly due to the lower ionization and excitation cross sections of Geant4-DNA for low energy electrons. To a lesser extent, discrepancies can also be attributed to the implementation in this study of a new and fast scoring technique that differs from that used in previous studies. For the same mean chord length ([Formula: see text]), the [Formula: see text] calculated in cylindrical volumes are larger than those calculated in spherical volumes. The discrepancies due to cross sections and scoring geometries increase with decreasing scoring site dimensions. A new set of [Formula: see text] values has been presented for monoenergetic electrons using a fast track sampling algorithm and the most recent physics models implemented in Geant4-DNA. This dataset can be combined with primary electron spectra to predict the radiation quality of photon and electron beams.

Purpose Coronary artery disease involves the deposition of plaque along the walls of a coronary artery leading to narrowed or blocked vessels (stenosis) and is one of the main causes of death in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is used to reverse stenosis. Restenosis (renarrowing) of the treated vessel is a major complication of PTCA. A metal mesh tube (stent) can be placed inside the vessel to prevent restenosis. Tissue stress incurred during PTCA and stenting can provoke neointimal cell proliferation leading to in-stent restenosis (ISR). Intravascular brachytherapy (IVBT), a form of internal radiotherapy, is used to treat ISR. Renewed interest in IVBT is being expressed as a treatment for patients with ISR in drug-eluting stents. Current treatment planning (TP) of IVBT is extremely limited and assumes human tissue can be approximated by water. The interactions of arterial plaque, guidewires, and the stent have been shown to attenuate radiation significantly but are ignored in TP. Other models have determined the degree of attenuation by each factor in isolation. For the first time, we create a model with several inhomogenities present to determine whether attenuation by multiple inhomogenities combines linearly or if a larger dose reduction than anticipated is realized. We are also able to evaluate a spatial distribution of dose around the source and in arterial walls. Methods and Materials A dosimetric analysis of two commercially available IVBT systems was performed in a Monte Carlo–based particle simulation (Geant4). Absorbed dose was calculated using a model of a human coronary artery with a calcified plaque and stent. Dose delivered in water was also calculated to evaluate the accuracy of a water approximation. Results Dose as a function of θ shows significant variation around IVBT sources. For the Guidant Galileo, dose is reduced by 20% behind stent struts and as much as 66% in a region occluded by the guidewire, plaque, and stent. For the Novoste Beta Cath device, delivered dose is reduced by 19% and 58%, respectively, in the same regions. Conclusions Our findings show that the water approximation used in clinical practice to calculate dose is inaccurate when inhomogeneities are present. Methods proposed for calculating dose perturbations in IVBT may underestimate the magnitude of dose reduction. Increasing source dwell time seems unlikely to resolve dosimetric issues in IVBT. The effectiveness of currently existing β-emitting devices may be reduced in patients with complex lesions at the treatment site. Investigation of new radioisotopes and off-centering devices should be considered to improve dose outcomes.

Purpose Intensity modulated brachytherapy (IMBT) with rotating metal shields enables dose modulation that can better conform to the tumor while reducing OAR doses. In this work, we investigate novel rotating shields, compatible with MRI-compatible tandems used for cervix brachytherapy. Three unique shields were evaluated using the traditional 192Ir source. Additionally, 75Se and 169Yb isotopes were investigated as alternative sources. Methods Three different IMBT shields were modeled and simulated in RapidBrachyMCTPS. Each tungsten shield was designed to fit inside a 6 mm-wide MRI-compatible tandem. The active core of the source was replaced with 192Ir, 75Se and 169Yb. Transmission factors (TFs) were calculated and defined as the dose ratio at 1 cm on opposite sides of the shielded tandem on the transverse plane. Polar and azimuthal anisotropy plots were extracted from simulations. Dose homogeneities V 200 % V 100 % were calculated for all radionuclide-shield combinations. Results TFs are favorable for IMBT and ranged between 12.9% and 32.2% for 192Ir, 4.0%-16.1% for 75Se and 1.2–6.4% for 169Yb for all shield designs. Average beam-widths in the polar and azimuthal directions were reduced to the range of 42°–112° and 27°–107°, respectively, for all shield-radionuclide combinations. Dose homogeneities for all the radionuclide-shield combinations were within 12% of the non-IMBT tandem. Conclusions This study has quantitatively assessed the influence of various rotating cervical cancer-specific IMBT tandem shields on dosimetry. The dynamic single-channel shields and narrow beam-widths in the polar and azimuthal direction give rise to highly anisotropic distributions. Intermediate-to-high energy radionuclides, 75Se and 169Yb substantially improve the modulation capacity of IMBT and pave the way for treating large and complex cervical cancer without interstitial needle implantation.

Purpose Several radionuclides with high (60Co, 75Se) and intermediate (169Yb, 153Gd) energies have been investigated as alternatives to 192Ir for high-dose-rate brachytherapy. The purpose of this study was to evaluate the impact of tissue heterogeneities for these five high- to intermediate-energy sources in prostate and head & neck brachytherapy. Methods and Materials Treatment plans were generated for a cohort of prostate (n = 10) and oral tongue (n = 10) patients. Dose calculations were performed using RapidBrachyMCTPS, an in-house Geant4-based Monte Carlo treatment planning system. Treatment plans were simulated using 60Co, 192Ir, 75Se, 169Yb, and 153Gd as the active core of the microSelectron v2 source. Two dose calculation scenarios were presented: (1) dose to water in water (Dw,w), and (2) dose to medium in medium (Dm,m). Results Dw,w overestimates planning target volume coverage compared with Dm,m, regardless of photon energy. The average planning target volume D90 reduction was ∼1% for high-energy sources, whereas larger differences were observed for intermediate-energy sources (1%–2% for prostate and 4%–7% for oral tongue). Dose differences were not clinically relevant ( Conclusions Dw,w underestimates the dose to bones and, to a lesser extent, overestimates the dose to soft tissues for radionuclides with average energies lower than 192Ir. Further studies regarding bone toxicities are needed before intermediate-energy sources can be adopted in cases where bones are in close vicinity to the tumor.

Purpose: Manual and automatic blood sampling at different time intervals is considered the gold standard to determine the arterial input function (AIF) in dynamic positron emission tomography (PET). However, blood sampling is characterized by poor time resolution and is an invasive procedure. The aim of this study was to characterize the scintillating fibers used to develop a non-invasive positron detector. Methods: The detector consists of a scintillating fiber coupled at each end to transmission fiber-optic cables that are connected to photo multiplier tubes in a dual readout setup. The detector is designed to be wrapped around the wrist of the patient undergoing dynamic PET. The attenuation length and bending losses were measured with excitation from gamma radiation (137Cs) and ultraviolet (UV) light. The response to positron-emitting radio-tracers was evaluated with 18F and 11C. Results: The attenuation length for a 3.0 m and 1.5 m long scintillating fiber both coincides with the attenuation length given by the manufacturer when excited with the 137Cs source, but not with the UV source due to the differences in scintillation mechanisms. The bending losses are smaller than the measurement uncertainty for the 137Cs source irradiation, and increase when the bending radius decrease for the UV source irradiation. The signal-to-noise ratio for 18F and 11C solutions are 1.98 and 22.54 respectively. The measured decay constant of 11C agrees with its characteristic value. Conclusion: The performed measurements in the dual readout configuration suggest that scintillating fibers may be suitable to determine the AIF non-invasively.

Intensity modulated brachytherapy (IMBT) is a novel high dose rate brachytherapy (HDR BT) technique which incorporates static or dynamic shielding to increase tumor coverage and/or spare healthy tissues. The purpose of this study is to present a novel delivery system (AIM-Brachy) design that can enable dynamic-shield IMBT for prostate cancer.The AIM-Brachy system dynamically controls the rotation of platinum shields, placed within interstitial catheters, which partially collimate the radiation emitted from anThe platinum shield reduced the dose rate on the shielded side at 1 cm to 18.1% of the dose rate on the unshielded side. For equal PTV DThe AIM-Brachy system was proposed to deliver dynamic-shield IMBT for prostate cancer with the potential to create a low dose tunnel within the urethra. The urethra-sparing properties are desirable to minimize the occurrence and severity of urethral strictures or, alternatively, to provide a method for dose escalation.

Radioembolization gains continuous traction as a primarily palliative radiation treatment for hepatic tumours. A form of nuclear medicine therapy, Yttrium-90 containing microspheres are catheter guided and injected into the right, left, or a specifically selected hepatic artery. A multitude of comprehensive planning steps exist to ensure a thorough and successful treatment. Clear clinical and physiological guidelines have been established and nuclear imaging is used to plan and verify dose distributions. Radioembolization's treatment rationale is based on tumour and blood vessel dynamics that allow a targeted treatment approach. However, radioembolization's dosimetry is grossly oversimplified. In fact, the currently utilized clinical dosimetric standards (e.g. partition method) have persisted since the 1990s. Moreover, the multitude of radioembolization's intertwining components lies disjointed within the literature. Particularly relevant to new readers, this review provides a methodical guide that presents the treatment rationale behind every clinical step. The emerging dosimetry methods and its factors are further discussed to provide a comprehensive review on an essential research direction.

Introduction In photon brachytherapy (BT), experimental dosimetry is needed to verify treatment plans if planning algorithms neglect varying attenuation, absorption or scattering conditions. The detector’s response is energy dependent, including the detector material to water dose ratio and the intrinsic mechanisms. The local mean photon energy E ¯ ( r ) must be known or another equivalent energy quality parameter used. We propose the brachytherapy photon radiation quality index Q BT ( E ¯ ) , to characterize the photon radiation quality in view of measurements of distributions of the absorbed dose to water, D w , around BT sources. Materials and methods While the external photon beam radiotherapy (EBRT) radiation quality index Q EBRT ( E ¯ ) = TPR 10 20 ( E ¯ ) is not applicable to BT, the authors have applied a novel energy dependent parameter, called brachytherapy photon radiation quality index, defined as Q BT ( E ¯ ) = D prim ( r = 2 cm, θ 0 = 90 ° ) / D prim ( r 0 = 1 cm, θ 0 = 90 ° ) , utilizing precise primary absorbed dose data, Dprim, from source reference databases, without additional MC-calculations. Results and discussion For BT photon sources used clinically, Q BT ( E ¯ ) enables to determine the effective mean linear attenuation coefficient μ ¯ ( E ) and thus the effective energy of the primary photons E prim eff ( r 0 , θ 0 ) at the TG-43 reference position P ref ( r 0 = 1 cm, θ 0 = 90 ° ) , being close to the mean total photon energy E ¯ tot ( r 0 , θ 0 ) . If one has calibrated detectors, published E ¯ tot ( r ) and the BT radiation quality correction factor k Q , Q 0 BT ( E ¯ , r , θ ) for different BT radiation qualities Q and Q 0 , the detector’s response can be determined and D w ( r , θ ) measured in the vicinity of BT photon sources. Conclusions This novel brachytherapy photon radiation quality index Q BT characterizes sufficiently accurate and precise the primary photon‘s penetration probability and scattering potential.

Purpose: To present and characterize a Monte Carlo(MC) tool for the simulation of the relative biological effectiveness for the induction of direct DNA double strand breaks ( RBE DSB direct ) for protons and light ions. Methods: The MC tool uses a pregenerated event-by-event tracks library of protons and light ions that are overlaid on a cell nucleus model. The cell nucleus model is a cylindrical arrangement of nucleosome structures consisting of 198 DNA base pairs. An algorithm relying on k-dimensional trees and cylindrical symmetries is used to search coincidences of energy deposition sites with volumes corresponding to the sugar–phosphate backbone of the DNA molecule. Strand breaks (SBs) are scored when energy higher than a threshold is reached in these volumes. Based on the number of affected strands, they are categorized into either single strand break (SSB) or double strand break (DSB) lesions. The number of SBs composing each lesion (i.e., its size) is also recorded. RBE DSB direct is obtained by taking the ratio of DSB yields of a given radiation field to a 60Co field. The MC tool was used to obtain SSB yields, DSB yields, and RBE DSB direct as a function of linear energy transfer (LET) for protons (1H+), 4He2+, 7Li3+, and 12C6+ ions. Results: For protons, the SSB yields decreased and the DSB yields increased with LET. At ≈24.5 keV μm−1, protons generated 15% more DSBs than 12C6+ ions. The RBE DSB direct varied between 1.24 and 1.77 for proton fields between 8.5 and 30.2 keV μm−1, and it was higher for iso-LET ions with lowest atomic number. The SSB and DSB lesion sizes showed significant differences for all radiation fields. Generally, the yields of SSB lesions of sizes ≥2 and the yields of DSB lesions of sizes ≥3 increased with LET and increased for iso-LET ions of lower atomic number. On the other hand, the ratios of SSB to DSB lesions of sizes 2–4 did not show variability with LET nor projectile atomic number, suggesting that these metrics are independent of the radiation quality. Finally, a variance of up to 8% in the DSB yields was observed as a function of the particle incidence angle on the cell nucleus. This simulation effect is due to the preferential alignment of ion tracks with the DNA nucleosomes at specific angles. Conclusions: The MC tool can predict SSB and DSB yields for light ions of various LET and estimate RBE DSB direct . In addition, it can calculate the frequencies of different DNA lesion sizes, which is of interest in the context of biologically relevant absolute dosimetry of particle beams.