By combining geometric models of varying complexity on different length scales within a single simulation, the HetMS model can effectively account for both macroscopic and microscopic effects which must both be considered for accurate computation of energy deposition and DEFs for GNPT. Efficiency gains with the HetMS approach enable diverse calculations which would otherwise be prohibitively long. The HetMS model may be extended to diverse scenarios relevant for GNPT, providing further avenues for research and development.

To update the Carleton Laboratory for Radiotherapy Physics (CLRP) TG-43 dosimetry database for low-energy (≤50 keV) photon-emitting low-dose rate (LDR) brachytherapy sources utilizing the open-source EGSnrc application egs_brachy rather than the BrachyDose application used previously for 27 LDR sources in the 2008 CLRP version (CLRPv1). CLRPv2 covers 40 sources (103 Pd, 125 I, and 131 Cs). A comprehensive set of TG-43 parameters is calculated, including dose-rate constants, radial dose functions with functional fitting parameters, 1D and 2D anisotropy functions, along-away dose-rate tables, Primary-Scatter separation dose tables (for some sources), and mean photon energies at the surface of the sources. The database also documents the source models which will become part of the egs_brachy distribution. Acquisition and validation methods: Datasets are calculated after a systematic recoding of the source geometries using the egs++ geometry package and its egs_brachy extensions. Air-kerma strength per history is calculated for models of NIST's Wide-Angle Free-Air chamber (WAFAC) and for a point detector located at 10 cm on the source's transverse axis. Full scatter water phantoms with varying voxel resolutions in cylindrical coordinates are used for dose calculations. New statistical uncertainties of source volume corrections for phantom voxels which overlap with brachytherapy sources are implemented in egs_brachy, and all CLRPv2 data include these uncertainties. For validation, data are compared to CLRPv1 and other data in the literature. Data format and access: Data are available at https://physics.carleton.ca/clrp/egs_brachy/seed_da tabase_v2, http://doi.org/10.22215/clrp/tg43v2. As well as being presented graphically in comparisons to previous calculations, data are available in Excel (.xlsx) spreadsheets for each source. Potential applications: The database has applications in research, dosimetry, and brachytherapy treatment planning. This comprehensive update provides the medical physics community with more accurate TG-43 dose evaluation parameters, as well as fully benchmarked and described source models which are distributed with egs_brachy.

The combined effects of ocular and plaque media on dose are significant and vary with plaque model and radionuclide, suggesting the importance of model-based dose calculations employing accurate ocular and plaque media and geometries for eye plaque brachytherapy.

To update and extend version 2 of the Carleton Laboratory for Radiotherapy Physics (CLRP) TG-43 dosimetry database (CLRP_TG43v2) for high-energy (HE, ≥ 50 keV) brachytherapy sources (1 169 Yb, 23 192 Ir, 5 137 Cs, and 4 60 Co) using egs_brachy, an open-source EGSnrc application. A comprehensive dataset of TG-43 parameters is compiled, including detailed source descriptions, dose-rate constants, radial dose functions, 1D and 2D anisotropy functions, along-away dose-rate tables, Primary and Scatter Separated (PSS) dose tables, and mean photon energies escaping each source. The database also documents the source models which are freely distributed with egs_brachy. Acquisition and Validation Methods: Datasets are calculated after a recoding of the source geometries using the egs++ geometry package and its egs_brachy extensions. Air kerma per history is calculated in a 10 × 10 × 0.05 cm 3 voxel located 100 cm from the source along the transverse axis and then corrected for the lateral and thickness dimensions of the scoring voxel to give the air kerma on the central axis at a point 100 cm from the source's mid-point. Full-scatter water phantoms with varying voxel resolutions in cylindrical coordinates are used for dose calculations. Most data (except for 60 Co) are based on the assumption of charged particle equilibrium and ignore the potentially large effects of electron transport very close to the source and dose from initial beta particles. These effects are evaluated for four representative sources. For validation, data are compared to those from CLRP_TG43v1 and published data. Data Format and Access: Data are available at https://physics.carleton. ca/clrp/egs_brachy/seed_database_v2 or http://doi.org/10.22215/clrp/tg43v2 including in Excel (.xlsx) spreadsheets, and are presented graphically in comparisons to previously published data for each source. Potential Applications: The CLRP_TG43v2 database has applications in research, dosimetry, and brachytherapy planning. This comprehensive update provides the medical physics community with more precise and in some cases more accurate Monte Carlo (MC) TG-43 dose calculation parameters, as well as fully benchmarked and described source models which are distributed with egs_brachy.

Purpose: This work introduces a new lattice geometry library, egs_lattice, into the EGSnrc Monte Carlo code, which can be used for both modeling very large (previously unfeasible) quantities of geometries (e.g., cells or gold nanoparticles (GNPs)) and establishing recursive boundary conditions. The reliability of egs_lattice, as well as EGSnrc in general, is cross-validated and tested at short length scales and low energies. Methods: New Bravais, cubic, and hexagonal lattice geometries are defined in egs_lattice and their transport algorithms are described. Simulations of cells and GNP-containing cavities are implemented to compare to independent, published Geant4-DNA and PENELOPE results. Recursive boundary conditions, implemented through a cubic lattice, are used to perform electron Fano cavity tests. The Fano test is performed on three different-sized cells containing GNPs in the region around the nucleus for three source energies. Results: Lattices are successfully implemented in EGSnrc, and are used for validation. EGSnrc calculated the dose to cell cytoplasm and nucleus when irradiated by an internal electron source with a median difference of 0.6% compared to published Geant4-DNA results. EGSnrc calculated the ratio of dose to a microscopic cavity containing GNPs over dose to a cavity containing a homogeneous mixture of gold, and results generally agree (within 1%) with published PENELOPE results. The electron Fano cavity test is passed for all energies and cells considered, with sub-0.1% discrepancies between EGSnrc-calculated and expected values. Additionally, the recursive boundary conditions used for the Fano test provided a factor of over a million increase in efficiency in some cases. Conclusions: The egs_lattice geometry library, currently available as a pull request on the EGSnrc GitHub "develop" branch, is now freely accessible as open-source code. Lattice geometry implementations cross-validated with independent simulations in other MC codes and verified with the electron Fano cavity test demonstrate not only the reliability of egs_lattice, but also, by extension, EGSnrc's ability to simulate transport in nanometer geometries and score in microscopic cavities.

BackgroundGold NanoParticle (GNP) dose‐enhanced radiation therapy (GNPT) requires consideration of physics across macro‐ to microscopic length scales, however, this presents computational challenges that have limited previous investigations.PurposeTo develop and apply multiscale Monte Carlo (MC) simulations to assess variations in nucleus and cytoplasm dose enhancement factors (n,cDEFs) over tumor‐scale volumes.MethodsThe intrinsic variation of n,cDEFs (due to fluctuations in local gold concentration and cell/nucleus size variation) are estimated via MC modeling of varied cellular GNP uptake and cell/nucleus sizes. Then, the Heterogeneous MultiScale (HetMS) model is implemented in MC simulations by combining detailed models of populations of cells containing GNPs within simplified macroscopic tissue models to evaluate n,cDEFs. Simulations of tumors with spatially uniform gold concentrations (5, 10, or 20 mgAu/gtissue) and spatially varying gold concentrations eluted from a point are performed to determine n,cDEFs as a function of distance from the source for 10 to 370 keV photons. All simulations are performed for three different intracellular GNP configurations: GNPs distributed on the surface of the nucleus (perinuclear) and GNPs packed into one or four endosome(s).ResultsIntrinsic variations in n,cDEFs can be substantial, for example, if GNP uptake and cell/nucleus radii are varied by 20%, variations of up to 52% in nDEF and 25% in cDEF are observed compared to the nominal values for uniform cell/nucleus size and GNP concentration. In HetMS models of macroscopic tumors, subunity n,cDEFs (i.e., dose decreases) can occur for low energies and high gold concentrations due to attenuation of primary photons through the gold‐filled volumes, for example, n,cDEF<1 is observed 3 mm from a 20 keV source for the four endosome configuration. In HetMS simulations of tumors with spatially uniform gold concentrations, n,cDEFs decrease with depth into the tumor as photons are attenuated, with relative differences between GNP models remaining approximately constant with depth in the tumor. Similar initial n,cDEF decreases with radius are seen in the tumors with spatially varying gold concentrations, but the n,cDEFs for all of the GNP configurations converge to a single value for each energy as gold concentration reaches zero.ConclusionsThe HetMS framework has been implemented for multiscale MC simulations of GNPT to compute n,cDEFs over tumor‐scale volumes, with results demonstrating that cellular doses are highly sensitive to cell/nucleus size, GNP intracellular distribution, gold concentration, and cell position in tumor. This work demonstrates the importance of proper choice of computational model when simulating GNPT scenarios and the need to account for intrinsic variations in n,cDEFs due to variations in cell/nucleus size and gold concentration.

Purpose: To investigate dose enhancement to cellular compartments following gold nanoparticle (GNP) uptake in tissue, varying cell and tissue morphology, intra and extracellular GNP distribution, and source energy using Monte Carlo (MC) simulations. Methods: Models of single and multiple cells are developed for normal and cancerous tissues; cells (outer radii 5–10 µm) are modeled as concentric spheres comprising the nucleus (radii 2.5–7.5 µm) and cytoplasm. GNP distributions modeled include homogeneous distributions throughout the cytoplasm, variable numbers of GNP‐containing endosomes within the cytoplasm, or distributed in a spherical shell about the nucleus. Gold concentrations range from 1 to 30 mg/g. Dose to nucleus and to cytoplasm for simulations including GNPs are compared to simulations without GNPs to compute Nuclear and Cytoplasm Dose Enhancement Factors (NDEF, CDEF). Photon source energies are between 20 keV and 1.25 MeV. Results: DEFs are highly sensitive to GNP intracellular distribution; for a 2.5 µm radius nucleus irradiated by a 30 keV source, NDEF varies from 1.2 for a single endosome containing all GNPs to 8.2 for GNPs distributed about the nucleus (7 mg/g). DEFs vary with cell dimensions and source energy: NDEFs vary from 2.5 (90 keV) to 8.2 (30 keV) for a 2.5 µm radius nucleus and from 1.1 (90 keV) to 1.3 (30 keV) for a 7.5 µm radius nucleus, both with GNPs in a spherical shell about the nucleus (7 mg/g). NDEF and CDEF are generally different within a single cell. For multicell models, the presence of gold within intervening tissues between source and target perturbs the fluence reaching cellular targets, resulting in DEF inhomogeneities within a population of irradiated cells. Conclusion: DEFs vary by an order of magnitude for different cell models, GNP distributions, and source energies, demonstrating the importance of detailed modelling for advancing GNP development for radiotherapy. Funding provided by the Natural Sciences and Engineering Council of Canada (NSERC), and the Canada Research Chairs Program (CRC)

Background: The introduction of Gold NanoParticles (GNPs) in radiotherapy treatments necessitates considerations such as GNP size, location, and quantity, as well as patient geometry and beam quality. Physics considerations span length scales across many orders of magnitude (nanometer-to-centimeter), presenting challenges that often limit the scope of dosimetric studies to either micro-or macroscopic scales. Purpose: To investigate GNP dose-enhanced radiation Therapy (GNPT) through Monte Carlo (MC) simulations that bridge micro-to-macroscopic scales. The work is presented in two parts, with Part I (this work) investigating accurate and efficient MC modeling at the single cell level to calculate nucleus and cytoplasm Dose Enhancement Factors (n,cDEFs), considering a broad parameter space including GNP concentration, GNP intracellular distribution, cell size, and incident photon energy. Part II then evaluates cell dose enhancement factors across macroscopic (tumor) length scales. Methods: Different methods of modeling gold within cells are compared, from a contiguous volume of either pure gold or gold-tissue mixture to discrete GNPs in a hexagonal close-packed lattice. MC simulations with EGSnrc are performed to calculate n,cDEF for a cell with radius r cell = 7.35 µm and nucleus r nuc = 5 µm considering 10 to 370 keV incident photons, gold concentrations from 4 to 24 mg Au /g tissue , and three different GNP configurations within the cell: GNPs distributed around the surface of the nucleus (perinuclear) or GNPs packed into one (or four) endosome(s). Select simulations are extended to cells with different cell (and nucleus) sizes: 5 µm (2, 3, and 4 µm), 7.35 µm (4 and 6 µm), and 10 µm (7, 8, and 9 µm). Results: n,cDEFs are sensitive to the method of modeling gold in the cell, with differences of up to 17% observed; the hexagonal lattice of GNPs is chosen (as the most realistic model) for all subsequent simulations. Across cell/nucleus radii, source energies, and gold concentrations, both nDEF and cDEF are highest for GNPs in the perinuclear configuration, compared with GNPs in one (or four) endosome(s). Across all simulations of the (r cell , r nuc ) = (7.35, 5) µm cell, nDEFs and cDEFs range from unity to 6.83 and 3.87, respectively. Including different cell sizes, nDEFs and cDEFs as