Dose Point Kernels Research Articles

Quantitative CT imaging and radiation-absorbed dose estimations of 166Ho microspheres: paving the way for clinical application

BackgroundMicrobrachytherapy enables high local tumor doses sparing surrounding tissues by intratumoral injection of radioactive holmium-166 microspheres (166Ho-MS). Magnetic resonance imaging (MRI) cannot properly detect high local Ho-MS concentrations and single-photon emission computed tomography has insufficient resolution. Computed tomography (CT) is quicker and cheaper with high resolution and previously enabled Ho quantification. We aimed to optimize Ho quantification on CT and to implement corresponding dosimetry.MethodsTwo scanners were calibrated for Ho detection using phantoms and multiple settings. Quantification was evaluated in five phantoms and seven canine patients using subtraction and thresholding including influences of the target tissue, injected amounts, acquisition parameters, and quantification volumes. Radiation-absorbed dose estimation was implemented using a three-dimensional 166Ho specific dose point kernel generated with Monte Carlo simulations.ResultsCT calibration showed a near-perfect linear relation between radiodensity (HU) and Ho concentrations for all conditions, with differences between scanners. Ho detection during calibration was higher using lower tube voltages, soft-tissue kernels, and without a scanner detection limit. The most accurate Ho recovery in phantoms was 102 ± 11% using a threshold of mean tissue HU + (2 × standard deviation) and in patients 98 ± 31% using a 100 HU threshold. Thresholding allowed better recovery with less variation and dependency on the volume of interest compared to the subtraction of a single HU reference value. Corresponding doses and histograms were successfully generated.ConclusionCT quantification and dosimetry of 166Ho should be considered for further clinical application with on-site validation using radioactive measurements and intra-operative Ho-MS and dose visualizations.Relevance statementImage-guided holmium-166 microbrachytherapy currently lacks reliable quantification and dosimetry on CT to ensure treatment safety and efficacy, while it is the only imaging modality capable of quantifying high in vivo holmium concentrations.Key PointsLocal injection of 166Ho-MS enables high local tumor doses while sparing surrounding tissue.CT enables imaging-based quantification and radiation-absorbed dose estimation of concentrated Ho in vivo, essential for treatment safety and efficacy.Two different CT scanners and multiple acquisition and reconstruction parameters showed near-perfect linearity between radiodensity and Ho concentration.The most accurate Ho recoveries on CT were 102 ± 11% in five phantoms and 98 ± 31% in seven canine patients using thresholding methods.Dose estimations and volume histograms were successfully implemented for clinical application using a dose point kernel based on Monte Carlo simulations.Graphical

Nanoscale gold nanoparticle (GNP)-laden tumor cell model and its use for estimation of intracellular dose from GNP-induced secondary electrons.

Gold nanoparticles (GNPs) accumulated within tumor cells have been shown to sensitize tumors to radiotherapy. From a physics point of view, the observed GNP-mediated radiosensitization is due to various downstream effects of the secondary electron (SE) production from internalized GNPs such as GNP-mediated dose enhancement. Over the years, numerous computational investigations on GNP-mediated dose enhancement/radiosensitization have been conducted. However, such investigations have relied mostly on simple cellular geometry models and/or artificial GNP distributions. Thus, it is at least desirable, if not necessary, to conduct further investigations using cellular geometry models that properly reflect realistic cell morphology as well as internalized GNP distributions at the nanoscale. The primary aim of this study was to develop a nanometer-resolution geometry model of a GNP-laden tumor cell for computational investigations of GNP-mediated dose enhancement/radiosensitization. The secondary aim was to demonstrate the utility of this model by quantifying GNP-induced SE tracks/dose distribution at sub-cellular levels for further validation of a nanoscopic dose point kernel (nDPK) method against full-fledged Geant4 Monte Carlo (MC) simulation. A transmission electron microscopy (TEM) image of a single cell showing cytoplasm, cellular nucleus, and internalized GNPs in the cellular endosome was segmented into sub-cellular levels based on pixel value thresholding. A corresponding material density was allocated to each pixel, and, by adding a thickness, each pixel was transformed to a geometric voxel and imported as a Geant4-acceptable input geometry file. In Geant4-Penelope MC simulation, a clinical 6MV photon beam was applied, vertically or horizontally to the cell surface, and energy deposition to the cellular nucleus and cytoplasm, due to SEs emitted by internalized GNPs, was scored. Next, nDPK calculations were performed by generating virtual electron tracks from each GNP voxel to all nucleus and cytoplasm voxels. Subsequently, another set of Geant4 simulation was performed with both Penelope and DNA physics models under the geometry closely mimicking in vitro cell irradiation with a clinical 6MV photon beam, allowing for derivation of nDPK specific to this geometry and further comparison between Gean4 simulation and nDPK method. The Geant4-calculated SE tracks and associated energy depositions showed significant dependence on photon incidence angle. For perpendicular incidence, nDPK results showed good agreement (average percentage pixel-to-pixel difference of 0.4% for cytoplasm and 0.5% for nucleus) with Geant4 results, while, for parallel incidence, the agreement became worse (-1.7%-0.7% for cytoplasm and -5.5%-0.8% for nucleus). Under the 6MV cell irradiation geometry, nDPK results showed reasonable agreement (pixel-to-pixel Pearson's product moment correlation coefficient of 0.91 for cytoplasm and 0.98 for nucleus) with Geant4 results. The currently developed TEM-based model of a GNP-laden cell offers unprecedented details of realistic intracellular GNP distributions for nanoscopic computational investigations of GNP-mediated dose enhancement/radiosensitization. A benchmarking study performed with this model showed reasonable agreement between Geant4- and nDPK-calculated intracellular dose deposition by SEs emitted from internalized GNPs, especially under perpendicular incidence - a popular cell irradiation geometry and when the Geant4-Penelope physics model was used.

A Gaussian-plume based Monte Carlo method for calculating radiation dose in the near field of buildings

A Monte Carlo (MC) programme was written using the dose point kernel method to calculate doses in the roof zone of a building from nearby releases of radioactive gases. A Gaussian Plume Model (GPM) was parameterised to account for near-field building effects on plume spread and reflection from the roof. Rooftop recirculation zones and building-generated plume spread effects were accounted in a novel Dual Gaussian Plume (DGP) formulation used with the MC model, which allowed for the selection of angle of approach flow, plume release height in relation to the building and position of the release point in relation to the leading edge of the building. Three-dimensional wind tunnel concentration field data were used for the parameterisation. The MC code used the parameterised concentration field to calculate the contributions to effective dose from inhalation, cloud immersion from positron/beta particles, and gamma-ray dose for a wide range of receptor dose positions in the roof zone, including receptor positions at different heights above the roof. Broad trends in predicted radiation dose with angle of approach flow, release position in relation to the building and release height are shown. Alternative approaches for the derivation of the concentration field are discussed.

A diffusion-leakage model coupled with dose point kernels (DPK) for dosimetry of diffusing alpha-emitters radiation therapy (DaRT).

Diffusing alpha-emitters radiation therapy (DaRT) is a novel brachytherapy technique that leverages the diffusive flow of 224Ra progeny within the tumor volume over the course of the treatment. Cell killing is achieved by the emitted alpha particles that have a short range in tissue and high linear energy transfer. The current proposed absorbed dose calculation method for DaRT is based on a diffusion-leakage (DL) model that neglects absorbed dose from beta particles. This work aimed to couple the DL model with dose point kernels (DPKs) to account for dose from beta particles as well as to consider the non-local deposition of energy. The DaRT seed was modeled using COMSOL multiphysics and the DL model was implemented to extract the spatial information of the diffusing daughters. Using Monte-Carlo (MC) methods, DPKs were generated for 212Pb, 212Bi, and their progenies since they were considered to be the dominant beta emitters in the 224Ra radioactive decay chain. A convolution operation was performed between the integrated number densities of the diffusing daughters and DPKs to calculate the total absorbed dose over a 30-day treatment period. Both high-diffusion and low-diffusion cases were considered. The calculated DPKs showed non-negligible energy deposition over several millimeters from the source location. An absorbed dose>10Gy was deposited within a 1.8mm radial distance for the low diffusion case and a 2.2mm radial distance for the high diffusion case. When the DPK method was compared with the local energy deposition method that solely considered dose from alpha particles, differences above 1Gy were found within 1.3 and 1.8mm radial distances from the surface of the source for the low diffusion and high diffusion cases, respectively. The proposed method enhances the accuracy of the dose calculation method used for the DaRT technique.

Electron Absorbed Fractions and S Factors for Intermediate Size Target Volumes: Comparison of Analytic Calculations and Monte Carlo Simulations

The absorbed fraction and the S factor represent fundamental quantities in MIRD-based dosimetry of radiopharmaceutical therapy (RPT). Although Monte Carlo (MC) simulations represent the gold standard in RPT dosimetry, dose point kernels (DPK) obtained from analytic range–energy relations offer a more practical alternative for charged-particle dosimetry (β- or α-emitters). In this work, we perform DPK- and MC-based calculations of the self-absorbed fractions and S factors for monoenergetic electrons uniformly distributed in intermediate-size target volumes (~mm to cm) relevant to micrometastasis and disseminated disease. Specifically, the aim of the present work is as follows: (i) the development of an analytic range–energy relation, effective over a broad energy range (100 keV–20 MeV) covering most applications of radiotherapeutic interest; (ii) the application of the new formula to DPK-based calculations of the absorbed fraction and S factor and comparison against MC simulations (both published and present work data) as well as the MIRDcell V2.0.16 software, which uses a similar analytic methodology; and (iii) the study of the influence of simulation parameters (step-size, tracking/production cut-off energies, and ionization model) in Geant4-based calculations of S factors. It is shown that the present DPK-based calculations are in excellent agreement (within 1.5%) with the MIRDcell software, while also being in fair agreement with published MC data as well as with the new Geant4 simulations, with average differences of ~20% for the (sub) mm-sized volumes and ~10% for the cm-sized volumes. The effect of the choice of Geant4 simulation parameters was found to be negligible for the examined target volumes (~mm), except for the use of the Penelope ionization model, which may exhibit noticeable discrepancies (up to ~20%) against the Standard and Livermore models. The present work provides quantitative information that may be useful to both the MC- and DPK-based beta dosimetry of micrometastasis and disseminated disease, which represents an important field of application of RPT.

A machine learning-based model for a dose point kernel calculation

PurposeAbsorbed dose calculation by kernel convolution requires the prior determination of dose point kernels (DPK). This study reports on the design, implementation, and test of a multi-target regressor approach to generate the DPKs for monoenergetic sources and a model to obtain DPKs for beta emitters.MethodsDPK for monoenergetic electron sources were calculated using the FLUKA Monte Carlo (MC) code for many materials of clinical interest and initial energies ranging from 10 to 3000 keV. Regressor Chains (RC) with three different coefficients regularization/shrinkage models were used as base regressors. Electron monoenergetic scaled DPKs (sDPKs) were used to assess the corresponding sDPKs for beta emitters typically used in nuclear medicine, which were compared against reference published data. Finally, the beta emitters sDPK were applied to a patient-specific case calculating the Voxel Dose Kernel (VDK) for a hepatic radioembolization treatment with ^{90}Y.ResultsThe three trained machine learning models demonstrated a promising capacity to predict the sDPK for both monoenergetic emissions and beta emitters of clinical interest attaining differences lower than 10% in the mean average percentage error (MAPE) as compared with previous studies. Furthermore, differences lower than 7 % were obtained for the absorbed dose in patient-specific dosimetry comparing against full stochastic MC calculations.ConclusionAn ML model was developed to assess dosimetry calculations in nuclear medicine. The implemented approach has shown the capacity to accurately predict the sDPK for monoenergetic beta sources in a wide range of energy in different materials. The ML model to calculate the sDPK for beta-emitting radionuclides allowed to obtain VDK useful to achieve reliable patient-specific absorbed dose distributions required short computation times.

Internal Bremsstrahlung, the missing process in beta decay Monte Carlo simulation: The relevance in 32P Dose-Point-Kernel estimation

PurposeIn nuclear medicine, Dose Point Kernels (DPKs), representing the energy deposited all around a point isotropic source, are extensively used for dosimetry and are usually obtained by Monte Carlo (MC) simulations. For beta-decaying nuclides, DPK is usually estimated neglecting Internal Bremsstrahlung (IB) emission, a process always accompanying the beta decay and consisting in the emission of photons having a continuous spectral distribution. This work aims to study the significance of IB emission for DPK estimation in the case of 32P and provide DPK values corrected for the IB photon contribution. MethodsDPK, in terms of the scaled absorbed dose fraction, F(R/X90), was first estimated by GAMOS MC simulation using the standard beta decay spectrum of 32P, Fβ(R/X90). Subsequently, an additional source term accounting for IB photons and their spectral distribution was defined and used for a further MC simulation, thus evaluating the contribution of IB emission to DPK values, Fβ+IB(R/X90). The relative percent difference, δ, between the DPKs obtained by the two approaches, Fβ+IB vs. Fβ, was studied as a function of the radial distance, R. ResultsAs far as the energy deposition is mainly due to the beta particles, IB photons does not significantly contribute to DPK; conversely, for larger R, Fβ+IB values are higher by 30–40% than Fβ. ConclusionsThe inclusion of IB emission in the MC simulations for DPK estimations is recommended, as well as the use of the DPK values corrected for IB photons, here provided.

Technical note: The contribution of internal bremsstrahlung to the 90 Y dose point kernel.

Internal dosimetry has an increasing role in the planning and verification of nuclear medicine therapies with radiopharmaceuticals. Dose Point Kernels (DPKs), quantifying the energy deposition all around a point source, in a homogenous medium, are extensively used for 3D dosimetry and nowadays are mostly evaluated by Monte Carlo (MC) simulation. To our knowledge, DPK for beta emitters is estimated neglecting the continuous photon emission due to the Internal Bremsstrahlung (IB), whose contribution to the absorbed dose can be relevant beyond the maximum range of betas, as evidenced in recent works. Aim of this study was to investigate and quantify, by means of MC simulations, the contribution of IB photons to DPK calculated for 90 Y and provide the updated 90 Y DPK. The overall radiation due to the decay of a 90 Y point source, placed at the centre of concentric water shells of increasing radii from 0.02 cm to 20 cm, was simulated with GAMOS, including the IB source term whose spectral distribution was described by an analytical model. Energy deposition was scored in the shells as a function of the distance from the source, R, and DPK was estimated in terms of the scaled absorbed dose fraction, F(R/X90 ), where X90 is the range within which the beta particles deposit 90% of their energy. A comparison between the two simulated absorbed dose distributions, calculated with or without IB, clearly shows that the latter (incomplete) choice is consistent with the findings of other Authors and systematically underestimates the absorbed dose imparted to the tissue. 90 Y DPK values currently used are underestimated by 20%-34% for R>2X90 . The revised values provided in this work suggest that the inclusion of IB emission in DPK evaluations is advisable for pure beta emitters.

Specific Absorbed Fractions for Spontaneous Fission Neutron Emitters in the ICRP Reference Pediatric Voxel Phantom Series.

Specific absorbed fractions (SAFs) are key components in the workflow of internal exposure assessment following the intake of a radionuclide, allowing quick conversion of particle energy released in a source region to the expected absorbed dose in target regions throughout the body. For data completeness, SAFs for spontaneous fission neutron emitters are currently needed for the recently adopted ICRP reference pediatric voxel phantom series. With 77 source regions within each reference individual and 28 radionuclides decaying via spontaneous fission, full Monte Carlo simulation requires significant computation time. In order to reduce this burden, a novel method for neutron SAF estimation was undertaken. The Monte Carlo N-Particle version 6.1 (MCNP6) simulation package was chosen to simulate the 252 Cf Watt fission neutron spectrum originating from 15 source regions in each phantom; dose estimation within 41 target tissues allowed for assessment of the SAF value for each source-target pair. For the remaining source regions, chord length distributions were computed using MATLAB code to determine the separation between the source-target pairs within the pediatric phantom series. These distance distributions were used in conjunction with a 252 Cf neutron dose point kernel calculated in soft tissue, which was modified to account for the source region's depth from the surface of the body. Lastly, the 252 Cf SAF dataset was extended to the other 27 spontaneous fission neutron emitters based on differences in the Watt fission spectrum parameters of each radionuclide. This methodology has been shown to accurately estimate spontaneous fission neutron SAFs to within 20% of the Monte Carlo estimated value for most source-target pairs in the ICRP reference pediatric series.

Simulation of [formula omitted]I Auger emission spectrum with new atomic parameters from MCDHF calculations

New 125I atomic decay emission data of medical interest are presented. The calculations are based on two atomic structure codes that implement the multi-configuration Dirac-Hartree-Fock method. Radiative and non-radiative ransition rates are calculated in this method and then used to generate the atomic deexcitation cascade. Subshell transition rates, level widths and fluorescence yields are compared to the Evaluated Atomic Data Library. Coster-Kronig and Auger electron emission yields are also compared with results from other authors. The comparison with the experimental electron emission spectrum shows that the new calculations can reproduce very well the structure of the K-LL Auger electron peaks and improve the description of the M Auger peaks below 300 eV. The 125I dose-point kernel is also simulated using the new data, resulting in higher values below 10 nm when compared those obtained with the Evaluated Atomic Data Library.

Microdosimetry modeling with Auger emitters in generalized cell geometry

A microdosimetry model was developed for the prediction of cell viability for irregular non-spherical cells that were irradiated by low energy, short range Auger electrons. Measured cell survival rates for LNCaP prostate cancer were compared to the computational results for the radioisotopes 177Lu and 161Tb (conjugated to PSMA). The cell geometries used for the computations were derived directly from the cell culture images. A general computational approach was developed to handle arbitrary cell geometries, based on distance probability distribution functions (PDFs) derived from basic image processing. The radiation calculations were done per coarse grained PDF bin to reduce computation time, rather than on a pixel/voxel basis. The radiation dose point kernels over the full electron spectrum were derived using Monte Carlo simulations for energies below 50 eV to account for the propagation of Auger electrons over length scales at and below a cellular radius. The relative importance of short range Auger electrons were evaluated between the two nuclide types. The microdosimetry results were consistent with the cell viability measurements, and it was found that 161Tb was more efficient than 177Lu primarily due to the short range Auger electrons. We foresee that imaging based microdosimetry can be used to evaluate the relative therapeutic effect between various nuclide candidates.

Implementation of dose point kernel (DPK) for dose optimization of 177Lu/90Y cocktail radionuclides in internal dosimetry

BackgroundDue to the importance of choosing the applicable dosimetry method in radionuclide therapy, the present study was conducted to investigate the efficiency of the implementation of Dose Point Kernel (DPK) for dose optimization of 177Lu/90Y Cocktail Radionuclides in internal Dosimetry. MethodsIn this study, simulations and calculations of DPK were performed using the GATE/GEANT4 Monte Carlo code. For specific liver dosimetry, the NCAT phantom and convolution algorithm-based Fast Fourier Transform method was used by MATLAB software. ResultsThe self-dose of 177Lu and 90Y radionuclides in the liver of NCAT phantom were 1.1708E-13, and 4.8420E-11 (Gy/Bq), respectively, and the cross-dose of 177Lu and 90Y radionuclides out of the liver of NCAT phantom were 2.03615E-16, and 0.8422E-13 (Gy/Bq) respectively. Overall results showed that with an increase the value of 90Y with quarter steps in a cocktail, the amount of the self-dose increase 1.5, 6, and 29 times respectively, and with an increase the value of 177Lu in quarter step in a cocktail, the amount of the cross dose decrease 3, 15 and 68 percent respectively. ConclusionGenerally, the present results indicate that the calculated DPK functions of 177Lu and 90Y cocktails can play an important role in choosing the best combination of radionuclide to optimize treatment planning in cocktail radionuclide therapy.

Prediction of tumor response and patient outcome after radioembolization of hepatocellular carcinoma using 90Y-PET-computed tomography dosimetry.

90Y-radioembolization using glass or resin microspheres is increasingly used for the treatment of hepatocellular carcinoma (HCC). The aim of this retrospective study is to determine the prognostic relevance of dosimetric parameters defined with 90Y-PET-CT obtained immediately after radioembolization. Forty-five HCC patients, mostly with multiple lesions, were treated by radioembolization between 2011 and 2017. After treatment, all underwent a 90Y PET-CT with time of flight reconstruction (90Y-TOF-PET-CT). Tumor absorbed dose and cumulative tumor dose-volume histogram were calculated using a dose point Kernel convolution algorithm. The radiological tumor response was assessed using modified (m)-RECIST criteria. Progression-free-survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression analysis. Twenty-six patients were treated with glass microspheres (73 lesions) and nineteen with resin microspheres (60 lesions). Thresholds of 118 and 61 Gy for glass and resin microspheres respectively correlate well with radiological response with a positive predictive value (PPV) of 98 and 80% and discriminate patient outcome with regard to PFS (P = 0.03 and 0.005) and OS (P = 0.003 and 0.007). Using dose volume histogram, a minimal absorbed dose of 40 Gy in 66% of the tumor volume (defined as D66) was highly predictive of radiological response (PPV = 94%), PFS (P < 0.001) and OS (P = 0. 008), for either device. Dosimetric parameters obtained using 90Y-PET-CT are predictive of tumor response, PFS and OS. In clinical practice, a systematic dosimetric evaluation using 90Y PET should be implemented to help predicting patient outcomes.

Calculation of dose point kernel values for monoenergetic electrons and beta emitting radionuclides: Intercomparison of Monte Carlo codes

Targeted radionuclide therapy (TRT) and beta-emitting seeds brachytherapy (BSBT) exploit the characteristics of energy deposited by beta-emitting radionuclides. Monte Carlo (MC) modelling of electron transport is crucial for calculations of absorbed dose for TRT and BSBT. However, computer codes capable of providing consistent results are still limited. Since experimental validations show several difficulties, the estimation of electron dose point kernel (DPK) is often used to verify the accuracy of different MC codes. In this work, we compared DPK calculations for various point, isotropic and monoenergetic electron sources and several beta-emitting radioisotopes using the codes MCNP, EGSnrc, PENELOPE and TOPAS with different simulation options. The simulations were performed using latest versions of EGSnrc and Penelope, TOPAS version 3.3.1 and MCNP version 6.1 Monte Carlo codes. In our simulations, the geometrical model consists of a point electron source placed at the center of a water sphere emitting isotropically. The water sphere was divided into 28 shells and the energy deposition was scored within these shells. The radius of the outermost shell was 1.2R0, where R0 is the continuous slowing down approximation (CSDA) range. Five monoenergetic beta sources with energies of 0.05, 0.1, 0.5, 1 and 3 MeV were studied. Six beta-emitting radionuclides were also simulated: Lu-177, Sm-153, Ho-166, Sr-89, I-131 and Y-90. Monoenergetic electron simulations showed large deviations among the codes, larger than 13% depending on the electron energy and the distance from the source. In the cases where beta spectra of radionuclides were simulated, all MC codes showed differences from EGSnrc (used as reference value - RV) less than 3% within rE90 range (radius of the sphere in which 90% of the energy of the spectrum electrons would be deposited). TOPAS showed results comparable to EGSnrc and PENELOPE. DPK values for 0.1 MeV monoenergetic electrons, calculated using MCNP6, led to differences higher than ±5% from RV despite our attempts to tune electron transport algorithms and physics parameters.

A Monte Carlo Investigation of Dose Point Kernel Scaling for α-Emitting Radionuclides.

Background: Density-based dose point kernel (DPK) scaling accuracy was investigated in various homogeneous tissue media. Methods: Using GEometry ANd Tracking 4 Monte Carlo code, DPKs were generated for 5, 8 MeV monoenergetic α particles and 223Ra, 225Ac, and 227Th. Dose was scored in 1 μm thick concentric shells and DPKs were scaled based on the tissue's mass density and compared with the water DPK. Results: Scaled kernels agreed within ±5% except near the Bragg peaks, where they differed up to 25%. Conclusions: The authors conclude that kernel scaling based on mass density of the transport medium can be utilized accurately up to 5%, excluding Bragg peak regions.

Monte Carlo assessment of low energy electron range in liquid water and dosimetry effects

The effects of low energy electrons in biological tissues have proved to lead to severe damages at the cellular and sub-cellular level. It is due to an increase in the relative biological effectiveness (RBE) of these electrons with a decrease in their penetration range. That is, lower the range higher will be its RBE.Therefore, accurate determination of low energy electron range becomes a key issue for radiation dosimetry. This work reports on in-water electron tracks evaluated at low kinetic energy (1–50 keV) using isotropic mono-energetic point source approach suitably implemented by different general-purpose Monte Carlo codes. For this aim, simulations were performed using PENELOPE, EGSnrc, MCNP6, FLUKA and Geant4-DNA Monte Carlo codes to obtain the particle range, R,R90,R50. Finally, evaluation of dose point kernel (DPK), as used for internal dosimetry, was carried out as an application example. Scaled dose point kernels (sDPK) were estimated for a range of mono-energetic low energy electron sources. The non-negligible differences among the calculated sDPK using different codes were obtained for energy electrons up to 5 keV. It was also observed that differences of in-water range for low-energy electrons, due to the different general-purpose Monte Carlo codes, affected the DPKs used for dosimetry by convolution approach. Finally, the 3D dosimetry was found to be almost not affected at macroscopic clinical scale, whereas non-negligible differences appeared at the microscopic level. Hence, a thorough validation of the used sDPKs have to be performed before they could be used in applications to derive any conclusions.

Impact of the dosimetry approach on the resulting 90Y radioembolization planned absorbed doses based on 99mTc-MAA SPECT-CT: is there agreement between dosimetry methods?

BackgroundPrior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues.Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images.MethodsAbsorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new “Multi-tumor Partition Model” (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest.ResultsDifferences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches.DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed.ConclusionsSignificant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver.An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used.

Monte Carlo simulations of energy deposition and DNA damage using TOPAS-nBio

Purpose. Monte Carlo (MC) track structure codes are commonly used for predicting energy deposition and radiation-induced DNA damage at the nanometer scale. Various simulation parameters such as physics model, DNA model, and direct damage threshold have been developed. The differences in adopted parameters lead to disparity in calculation results, which requires quantitative evaluation. Methods. Three simulation configurations were implemented in TOPAS-nBio MC toolkit to investigate the impact of physics models, DNA model, and direct damage threshold on the prediction of energy deposition and DNA damage. Dose point kernels (DPKs) of electrons and nanometer-sized volumes irradiated with electrons, protons, and alpha particles were utilized to evaluate the impact of physics models on energy deposition. Proton irradiation of plasmid DNA was used to investigate the disparity in single-strand break and double-strand break (DSB) yields caused by differences in physics models, DNA models, and direct damage thresholds. Results. Electron DPKs obtained with different physics models show similar trends but different diffusiveness and maximums. Energy deposition distributions in nanometer-sized volumes irradiated with electrons, protons, and alpha particles calculated using different physics models have the same trend although discrepancies can be observed at the lowest and highest energy deposits. Strand breaks from incident protons in DNA plasmids vary with adopted parameters. For the configurations in this study, changing physics model, DNA model, and direct damage threshold can cause differences of up to 57%, 69%, and 15% in DSB yields, respectively. All these simulation results are essentially in agreement with previously published simulation or experimental studies. Conclusion. All the physics models, DNA models, and direct damage thresholds investigated in this study are applicable to predict energy deposition and DNA damage. Although the choice of parameters can lead to disparity in simulation results, which serves as a reference for future studies.

Absorbed dose distributions from beta-decaying radionuclides: Experimental validation of Monte Carlo tools for radiopharmaceutical dosimetry.

This study aims to experimentally validate the Monte Carlo generated absorbed doses from the beta particles emitted by 90 Y and 177 Lu using radiochromic EBT3 film-based dosimetry. Line sources of 90 Y and 177 Lu were inserted longitudinally through blocks of low-density polyethylene and tissue-equivalent slabs of cortical bone and lung equivalent plastics. Radiochromic film (Gafchromic EBT3) was laser cut to accommodate orthogonal line sources of radioactivity, and the film was sandwiched intimately between the rectangular blocks to achieve charged particle equilibrium. Line sources consisted of plastic capillary tube of length (13±0.1)cm, with 0.42-mm inner diameter and a wall thickness of 0.21mm. 90 Y line sources were prepared from a solution of dissolved 90 Y resin microspheres. 177 Lu line sources were prepared from an aliquot of 177 Lu-DOTATATE. Film exposures were conducted for durations ranging from 10min to 38h. Radiochromic film calibration was performed by irradiation with 6-MV-bremsstrahlung x rays from a calibrated linear accelerator, in accordance with literature recommendations. Experimental geometries were precisely simulated within the GATE Monte Carlo toolkit, which has previously been used for the generation of dose point kernels. The mean percentage difference between measured and simulated absorbed doses were 5.04% and 7.21% for 90 Y and 177 Lu beta absorbed dose in the range of (0.1-10)Gy. Additionally, 1D gamma analysis using a local 10%/1mm gamma criterion was performed to compare the absorbed dose distributions. The percentage of measurement points passing the gamma criterion, averaged over all tests, was 93.5%. We report the experimental validation of Monte Carlo derived beta absorbed dose distributions for 90 Y and 177 Lu, solidifying the validity of using Monte Carlo-based methods for estimating absorbed dose from beta emitters. Overall, excellent agreement was observed between the experimental beta absorbed doses in the linear region of the radiochromic film and the GATE Monte Carlo simulations demonstrating that radiochromic film dosimetry has sufficient sensitivity and spatial resolution to be used as a tool for measuring beta decay absorbed dose distributions.

Comparison of posttherapy 90Y positron emission tomography/computed tomography dosimetry methods in liver therapy with 90Y microspheres.

The aim of our study was to compare dosimetry methods for yttrium-90 (90Y) positron emission tomography/computed tomography (PET/CT). Twenty-five patients were taken to a PET/CT suite following therapy with 90Y microspheres. The low mA, nondiagnostic CT images were used for attenuation correction and localization of the 90Y microspheres. The acquisition time was 15 min, the reconstruction matrix size was 200 mm × 200 mm × 75 mm, and voxel size was 4.07 mm × 4.07 mm × 3.00 mm. Two software packages, MIM 6.8 and Planet Dose, were utilized to calculate 90Y dosimetry. Three methods were used for voxel-based dosimetry calculations: the local deposition method (LDM), LDM with scaling (LDMwS) for known injected activity, and a dose point kernel (DPK) method using the MIRD kernel. Only the DPK approach was applied to the Planet Dose software. LDM and LDMwS were only applied to the MIM software. The average total liver dosimetry values (mean ± standard deviation) were 60.93 ± 28.62 Gy, 53.59 ± 23.47 Gy, 55.33 ± 24.80 Gy, and 54.25 ± 23.70 Gy for LDMwS, LDM, DPK with MIM, and DPK with Planet Dose (DOSI), respectively. In most cases, the LDMwS method produced slightly higher dosimetry values than the other methods. The MIM and Planet Dose DPK dosimetry values (i.e., DPK vs. DOSI) were highly comparable. Bland–Altman analysis calculated a mean difference of 1.1 ± 2.2 Gy. The repeatability coefficient was 4.4 (7.9% of the mean). The MIM and Planet Dose DPK dosimetry values were practically interchangeable. 90Y dosimetry values obtained by all methods were similar, but LDMwS tended to produce slightly higher values.