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Investigation of realistic PET simulations incorporating tumor patient's specificity using anthropomorphic models: Creation of an oncology database

Purpose: The GATE Monte Carlo simulation toolkit is used for the implementation of realistic PET simulations incorporating tumor heterogeneous activity distributions. The reconstructed patient images include noise from the acquisition process, imaging system's performance restrictions and have limited spatial resolution. For those reasons, the measured intensity cannot be simply introduced in GATE simulations, to reproduce clinical data. Investigation of the heterogeneity distribution within tumors applying partial volume correction (PVC) algorithms was assessed. The purpose of the present study was to create a simulated oncology database based on clinical data with realistic intratumor uptake heterogeneity properties.Methods: PET/CT data of seven oncology patients were used in order to create a realistic tumor database investigating the heterogeneity activity distribution of the simulated tumors. The anthropomorphic models (NURBS based cardiac torso and Zubal phantoms) were adapted to the CT data of each patient, and the activity distribution was extracted from the respective PET data. The patient-specific models were simulated with the Monte Carlo Geant4 application for tomography emission (GATE) in three different levels for each case: (a) using homogeneous activity within the tumor, (b) using heterogeneous activity distribution in every voxel within the tumor as it was extracted from the PET image, and (c) using heterogeneous activity distribution corresponding to the clinical image following PVC. The three different types of simulated data in each case were reconstructed with two iterations and filtered with a 3D Gaussian postfilter, in order to simulate the intratumor heterogeneous uptake. Heterogeneity in all generated images was quantified using textural feature derived parameters in 3D according to the ground truth of the simulation, and compared to clinical measurements. Finally, profiles were plotted in central slices of the tumors, across lines with heterogeneous activity distribution for visual assessment.Results: The accuracy of the simulated database was assessed against the original clinical images. The PVC simulated images matched the clinical ones best. Local, regional, and global features extracted from the PVC simulated images were closest to the clinical measurements, with the exception of the size zone variability and the mean intensity values, where heterogeneous tumors showed better reproducibility. The profiles on PVC simulated tumors after postfiltering seemed to represent the more realistic heterogeneous regions with respect to the clinical reference.Conclusions: In this study, the authors investigated the input activity map heterogeneity in the GATE simulations of tumors with heterogeneous activity distribution. The most realistic heterogeneous tumors were obtained by inserting PVC activity distributions from the clinical image into the activity map of the simulation. Partial volume effect (PVE) can play a crucial role in the quantification of heterogeneity within tumors and have an important impact on applications such as patient follow-up during treatment and assessment of tumor response to therapy. The development of such a database incorporating patient anatomical and functional variability can be used to evaluate new image processing or analysis algorithms, while providing control of the ground truth, which is not available when dealing with clinical datasets. The database includes all images used and generated in this study, as well as the sinograms and the attenuation phantoms for further investigation. It is freely available to the interested reader of the journal at http://www.med.upatras.gr/oncobase/.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Toward an organ based dose prescription method for the improved accuracy of murine dose in orthovoltage x-ray irradiators

Purpose: Accurate dosimetry is essential when irradiating mice to ensure that functional and molecular endpoints are well understood for the radiation dose delivered. Conventional methods of prescribing dose in mice involve the use of a single dose rate measurement and assume a uniform average dose throughout all organs of the entire mouse. Here, the authors report the individual average organ dose values for the irradiation of a 12, 23, and 33 g mouse on a 320 kVp x-ray irradiator and calculate the resulting error from using conventional dose prescription methods. Methods: Organ doses were simulated in the Geant4 application for tomographic emission toolkit using the MOBY mouse whole-body phantom. Dosimetry was performed for three beams utilizing filters A (1.65 mm Al), B (2.0 mm Al), and C (0.1 mm Cu + 2.5 mm Al), respectively. In addition, simulated x-ray spectra were validated with physical half-value layer measurements. Results: Average doses in soft-tissue organs were found to vary by as much as 23%–32% depending on the filter. Compared to filters A and B, filter C provided the hardest beam and had the lowest variation in soft-tissue average organ doses across all mouse sizes, with a difference of 23% for the median mouse size of 23 g. Conclusions: This work suggests a new dose prescription method in small animal dosimetry: it presents a departure from the conventional approach of assigninga single dose value for irradiation of mice to a more comprehensive approach of characterizing individual organ doses to minimize the error and uncertainty. In human radiation therapy, clinical treatment planning establishes the target dose as well as the dose distribution, however, this has generally not been done in small animal research. These results suggest that organ dose errors will be minimized by calibrating the dose rates for all filters, and using different dose rates for different organs.

54 ENVIRONMENTAL SCIENCES↗

Improved proton computed tomography by dual modality image reconstruction

Purpose: Proton computed tomography (CT) is a promising image modality for improving the stopping power estimates and dose calculations for particle therapy. However, the finite range of about 33 cm of water of most commercial proton therapy systems limits the sites that can be scanned from a full 360° rotation. In this paper the authors propose a method to overcome the problem using a dual modality reconstruction (DMR) combining the proton data with a cone-beam x-ray prior. Methods: A Catphan 600 phantom was scanned using a cone beam x-ray CT scanner. A digital replica of the phantom was created in the Monte Carlo code Geant4 and a 360° proton CT scan was simulated, storing the entrance and exit position and momentum vector of every proton. Proton CT images were reconstructed using a varying number of angles from the scan. The proton CT images were reconstructed using a constrained nonlinear conjugate gradient algorithm, minimizing total variation and the x-ray CT prior while remaining consistent with the proton projection data. The proton histories were reconstructed along curved cubic-spline paths. Results: The spatial resolution of the cone beam CT prior was retained for the fully sampled case and the 90° interval case, with the MTF = 0.5 (modulation transfer function) ranging from 5.22 to 5.65 linepairs/cm. In the 45° interval case, the MTF = 0.5 dropped to 3.91 linepairs/cm For the fully sampled DMR, the maximal root mean square (RMS) error was 0.006 in units of relative stopping power. For the limited angle cases the maximal RMS error was 0.18, an almost five-fold improvement over the cone beam CT estimate. Conclusions: Dual modality reconstruction yields the high spatial resolution of cone beam x-ray CT while maintaining the improved stopping power estimation of proton CT. In the case of limited angles, the use of prior image proton CT greatly improves the resolution and stopping power estimate, but does not fully achieve the quality of a 360° proton CT scan.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Rapid Monte Carlo simulation of detector DQE(f)

Purpose: Performance optimization of indirect x-ray detectors requires proper characterization of both ionizing (gamma) and optical photon transport in a heterogeneous medium. As the tool of choice for modeling detector physics, Monte Carlo methods have failed to gain traction as a design utility, due mostly to excessive simulation times and a lack of convenient simulation packages. The most important figure-of-merit in assessing detector performance is the detective quantum efficiency (DQE), for which most of the computational burden has traditionally been associated with the determination of the noise power spectrum (NPS) from an ensemble of flood images, each conventionally having 10{sup 7} − 10{sup 9} detected gamma photons. In this work, the authors show that the idealized conditions inherent in a numerical simulation allow for a dramatic reduction in the number of gamma and optical photons required to accurately predict the NPS. Methods: The authors derived an expression for the mean squared error (MSE) of a simulated NPS when computed using the International Electrotechnical Commission-recommended technique based on taking the 2D Fourier transform of flood images. It is shown that the MSE is inversely proportional to the number of flood images, and is independent of the input fluence provided that the input fluence is above a minimal value that avoids biasing the estimate. The authors then propose to further lower the input fluence so that each event creates a point-spread function rather than a flood field. The authors use this finding as the foundation for a novel algorithm in which the characteristic MTF(f), NPS(f), and DQE(f) curves are simultaneously generated from the results of a single run. The authors also investigate lowering the number of optical photons used in a scintillator simulation to further increase efficiency. Simulation results are compared with measurements performed on a Varian AS1000 portal imager, and with a previously published simulation performed using clinical fluence levels. Results: On the order of only 10–100 gamma photons per flood image were required to be detected to avoid biasing the NPS estimate. This allowed for a factor of 10{sup 7} reduction in fluence compared to clinical levels with no loss of accuracy. An optimal signal-to-noise ratio (SNR) was achieved by increasing the number of flood images from a typical value of 100 up to 500, thereby illustrating the importance of flood image quantity over the number of gammas per flood. For the point-spread ensemble technique, an additional 2× reduction in the number of incident gammas was realized. As a result, when modeling gamma transport in a thick pixelated array, the simulation time was reduced from 2.5 × 10{sup 6} CPU min if using clinical fluence levels to 3.1 CPU min if using optimized fluence levels while also producing a higher SNR. The AS1000 DQE(f) simulation entailing both optical and radiative transport matched experimental results to within 11%, and required 14.5 min to complete on a single CPU. Conclusions: The authors demonstrate the feasibility of accurately modeling x-ray detector DQE(f) with completion times on the order of several minutes using a single CPU. Convenience of simulation can be achieved using GEANT4 which offers both gamma and optical photon transport capabilities.

61 RADIATION PROTECTION AND DOSIMETRY↗

Influence of polarization and a source model for dose calculation in MRT

Purpose: Microbeam Radiation Therapy (MRT), an alternative preclinical treatment strategy using spatially modulated synchrotron radiation on a micrometer scale, has the great potential to cure malignant tumors (e.g., brain tumors) while having low side effects on normal tissue. Dose measurement and calculation in MRT is challenging because of the spatial accuracy required and the arising high dose differences. Dose calculation with Monte Carlo simulations is time consuming and their accuracy is still a matter of debate. In particular, the influence of photon polarization has been discussed in the literature. Moreover, it is controversial whether a complete knowledge of phase space trajectories, i.e., the simulation of the machine from the wiggler to the collimator, is necessary in order to accurately calculate the dose. Methods: With Monte Carlo simulations in the Geant4 toolkit, the authors investigate the influence of polarization on the dose distribution and the therapeutically important peak to valley dose ratios (PVDRs). Furthermore, the authors analyze in detail phase space information provided byMartínez-Rovira et al. [“Development and commissioning of a Monte Carlo photon model for the forthcoming clinical trials in microbeam radiation therapy,” Med. Phys. 39(1), 119–131 (2012)] and examine its influence on peak and valley doses. A simple source model is developed using parallel beams and its applicability is shown in a semiadjoint Monte Carlo simulation. Results are compared to measurements and previously published data. Results: Polarization has a significant influence on the scattered dose outside the microbeam field. In the radiation field, however, dose and PVDRs deduced from calculations without polarization and with polarization differ by less than 3%. The authors show that the key consequences from the phase space information for dose calculations are inhomogeneous primary photon flux, partial absorption due to inclined beam incidence outside the field center, increased beam width and center to center distance due to the beam propagation from the collimator to the phantom surface and imperfect absorption in the absorber material of the Multislit Collimator. These corrections have an effect of approximately 10% on the valley dose and suffice to describe doses in MRT within the measurement uncertainties of currently available dosimetry techniques. Conclusions: The source for the first clinical pet trials in MRT is characterized with respect to its phase space and the photon polarization. The results suggest the use of a presented simplified phase space model in dose calculations and hence pave the way for alternative and fast dose calculation algorithms. They also show that the polarization is of minor importance for the clinical important peak and valley doses inside the microbeam field.

61 RADIATION PROTECTION AND DOSIMETRY↗

Electron contamination modeling and reduction in a 1 T open bore inline MRI-linac system

Purpose: A potential side effect of inline MRI-linac systems is electron contamination focusing causing a high skin dose. In this work, the authors reexamine this prediction for an open bore 1 T MRI system being constructed for the Australian MRI-Linac Program. The efficiency of an electron contamination deflector (ECD) in purging electron contamination from the linac head is modeled, as well as the impact of a helium gas region between the deflector and phantom surface for lowering the amount of air-generated contamination. Methods: Magnetic modeling of the 1 T MRI was used to generate 3D magnetic field maps both with and without the presence of an ECD located immediately below the MLC’s. Forty-seven different ECD designs were modeled and for each the magnetic field map was imported into Geant4 Monte Carlo simulations including the linac head, ECD, and a 30 × 30 × 30 cm{sup 3} water phantom located at isocenter. For the first generation system, the x-ray source to isocenter distance (SID) will be 160 cm, resulting in an 81.2 cm long air gap from the base of the ECD to the phantom surface. The first 71.2 cm was modeled as air or helium gas, with the latter encased between two windows of 50 μm thick high density polyethlyene. 2D skin doses (at 70 μm depth) were calculated across the phantom surface at 1 × 1 mm{sup 2} resolution for 6 MV beams of field size of 5 × 5, 10 × 10, and 20 × 20 cm{sup 2}. Results: The skin dose was predicted to be of similar magnitude as the generic systems modeled in previous work, 230% to 1400% ofD {sub max} for 5 × 5 to 20 × 20 cm{sup 2}, respectively. Inclusion of the ECD introduced a nonuniformity to the MRI imaging field that ranged from ∼20 to ∼140 ppm while the net force acting on the ECD ranged from ∼151 N to ∼1773 N. Various ECD designs were 100% efficient at purging the electron contamination into the ECD magnet banks; however, a small percentage were scattered back into the beam and continued to the phantom surface. Replacing a large portion of the extended air-column between the ECD and phantom surface with helium gas is a key element as it significantly minimized the air-generated contamination. When using an optimal ECD and helium gas region, the 70 μm skin dose is predicted to increase moderately inside a small hot spot over that of the case with no magnetic field present for the jaw defined square beams examined here. These increases include from 12% to 40% of D {sub max} for 5 × 5 cm{sup 2}, 18% to 55% of D {sub max} for 10 × 10 cm{sup 2}, and from 23% to 65% of D {sub max} for 20 × 20 cm{sup 2}. Conclusions: Coupling an efficient ECD and helium gas region below the MLCs in the 160 cm isocenter MRI-linac system is predicted to ameliorate the impact electron contamination focusing has on skin dose increases. An ECD is practical as its impact on the MRI imaging distortion is correctable, and the mechanical forces acting on it manageable from an engineering point of view.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source

Purpose: The recently updated guidelines for dosimetry in brachytherapy in TG-186 have recommended the use of model-based dosimetry calculations as a replacement for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43, particularly for low energy brachytherapy sources. The Xoft Axxent is a low energy (<50 kV) brachytherapy system used in accelerated partial breast irradiation (APBI). Breast tissue is a heterogeneous tissue in terms of density and composition. Dosimetric calculations of seven APBI patients treated with Axxent were made using a model-based Monte Carlo platform for a number of tissue models and dose reporting methods and compared to TG-43 based plans. Methods: A model of the Axxent source, the S700, was created and validated against experimental data. CT scans of the patients were used to create realistic multi-tissue/heterogeneous models with breast tissue segmented using a published technique. Alternative water models were used to isolate the influence of tissue heterogeneity and backscatter on the dose distribution. Dose calculations were performed using Geant4 according to the original treatment parameters. The effect of the Axxent balloon applicator used in APBI which could not be modeled in the CT-based model, was modeled using a novel technique that utilizes CAD-based geometries. These techniques were validated experimentally. Results were calculated using two dose reporting methods, dose to water (D{sub w,m}) and dose to medium (D{sub m,m}), for the heterogeneous simulations. All results were compared against TG-43-based dose distributions and evaluated using dose ratio maps and DVH metrics. Changes in skin and PTV dose were highlighted. Results: All simulated heterogeneous models showed a reduced dose to the DVH metrics that is dependent on the method of dose reporting and patient geometry. Based on a prescription dose of 34 Gy, the average D{sub 90} to PTV was reduced by between ∼4% and ∼40%, depending on the scoring method, compared to the TG-43 result. Peak skin dose is also reduced by 10%–15% due to the absence of backscatter not accounted for in TG-43. The balloon applicator also contributed to the reduced dose. Other ROIs showed a difference depending on the method of dose reporting. Conclusions: TG-186-based calculations produce results that are different from TG-43 for the Axxent source. The differences depend strongly on the method of dose reporting. This study highlights the importance of backscatter to peak skin dose. Tissue heterogeneities, applicator, and patient geometries demonstrate the need for a more robust dose calculation method for low energy brachytherapy sources.

61 RADIATION PROTECTION AND DOSIMETRY↗

Assessment of individual organ doses in a realistic human phantom from neutron and gamma stimulated spectroscopy of the breast and liver

Purpose: Understanding the radiation dose to a patient is essential when considering the use of an ionizing diagnostic imaging test for clinical diagnosis and screening. Using Monte Carlo simulations, the authors estimated the three-dimensional organ-dose distribution from neutron and gamma irradiation of the male liver, female liver, and female breasts for neutron- and gamma-stimulated spectroscopic imaging. Methods: Monte Carlo simulations were developed using the Geant4 GATE application and a voxelized XCAT human phantom. A male and a female whole body XCAT phantom was voxelized into 256 × 256 × 600 voxels (3.125 × 3.125 × 3.125 mm{sup 3}). A monoenergetic rectangular beam of 5.0 MeV neutrons or 7.0 MeV photons was made incident on a 2 cm thick slice of the phantom. The beam was rotated at eight different angles around the phantom ranging from 0° to 180°. Absorbed dose was calculated for each individual organ in the body and dose volume histograms were computed to analyze the absolute and relative doses in each organ. Results: The neutron irradiations of the liver showed the highest organ dose absorption in the liver, with appreciably lower doses in other proximal organs. The dose distribution within the irradiated slice exhibited substantial attenuation with increasing depth along the beam path, attenuating to ∼15% of the maximum value at the beam exit side. The gamma irradiation of the liver imparted the highest organ dose to the stomach wall. The dose distribution from the gammas showed a region of dose buildup at the beam entrance, followed by a relatively uniform dose distribution to all of the deep tissue structures, attenuating to ∼75% of the maximum value at the beam exit side. For the breast scans, both the neutron and gamma irradiation registered maximum organ doses in the breasts, with all other organs receiving less than 1% of the breast dose. Effective doses ranged from 0.22 to 0.37 mSv for the neutron scans and 41 to 66 mSv for the gamma scans. Conclusions: Neutron and gamma irradiation of a primary target organ was found to impart the majority of the total dose to the primary target organ (and other large organs) within the beam plane and considerably lower dose to proximal organs outside of the beam. These results also indicate that despite the use of a highly scattering particle such as a neutron, the dose from neutron stimulated emission computed tomography scans is on par with other clinical imaging techniques such as x-ray computed tomography (x-ray CT). Given the high nonuniformity in the dose across an organ during the neutron scan, care must be taken when computing average doses from neutron irradiations. The effective doses from neutron scanning were found to be comparable to x-ray CT. Further technique modifications are needed to reduce the effective dose levels from the gamma scans.

61 RADIATION PROTECTION AND DOSIMETRY↗

Angular dependence of the response of the nanoDot OSLD system for measurements at depth in clinical megavoltage beams

Purpose: The purpose of this investigation was to assess the angular dependence of a commercial optically stimulated luminescence dosimeter (OSLD) dosimetry system in MV x-ray beams at depths beyondd{sub max} and to find ways to mitigate this dependence for measurements in phantoms. Methods: Two special holders were designed which allow a dosimeter to be rotated around the center of its sensitive volume. The dosimeter's sensitive volume is a disk, 5 mm in diameter and 0.2 mm thick. The first holder rotates the disk in the traditional way. It positions the disk perpendicular to the beam (gantry pointing to the floor) in the initial position (0°). When the holder is rotated the angle of the disk towards the beam increases until the disk is parallel with the beam (“edge on,” 90°). This is referred to as Setup 1. The second holder offers a new, alternative measurement position. It positions the disk parallel to the beam for all angles while rotating around its center (Setup 2). Measurements with five to ten dosimeters per point were carried out for 6 MV at 3 and 10 cm depth. Monte Carlo simulations using GEANT4 were performed to simulate the response of the active detector material for several angles. Detector and housing were simulated in detail based on microCT data and communications with the manufacturer. Various material compositions and an all-water geometry were considered. Results: For the traditional Setup 1 the response of the OSLD dropped on average by 1.4% ± 0.7% (measurement) and 2.1% ± 0.3% (Monte Carlo simulation) for the 90° orientation compared to 0°. Monte Carlo simulations also showed a strong dependence of the effect on the composition of the sensitive layer. Assuming the layer to completely consist of the active material (Al{sub 2}O{sub 3}) results in a 7% drop in response for 90° compared to 0°. Assuming the layer to be completely water, results in a flat response within the simulation uncertainty of about 1%. For the new Setup 2, measurements and Monte Carlo simulations found the angular dependence of the dosimeter to be below 1% and within the measurement uncertainty. Conclusions: The dosimeter system exhibits a small angular dependence of approximately 2% which needs to be considered for measurements involving other than normal incident beams angles. This applies in particular to clinicalin vivo measurements where the orientation of the dosimeter is dictated by clinical circumstances and cannot be optimized as otherwise suggested here. When measuring in a phantom, the proposed new setup should be considered. It changes the orientation of the dosimeter so that a coplanar beam arrangement always hits the disk shaped detector material from the thin side and thereby reduces the angular dependence of the response to within the measurement uncertainty of about 1%. This improvement makes the dosimeter more attractive for clinical measurements with multiple coplanar beams in phantoms, as the overall measurement uncertainty is reduced. Similarly, phantom based postal audits can transition from the traditional TLD to the more accurate and convenient OSLD.

61 RADIATION PROTECTION AND DOSIMETRY↗

On the dose calculation at the cellular level and its implications for the RBE of {sup 99m}Tc and {sup 123}I

Purpose: Based on the authors’ previous findings concerning the radiotoxicity of{sup 99m}Tc, the authors compared the cellular survival under the influence of this nuclide with that following exposure to the Auger electron emitter {sup 123}I. To evaluate the relative biological effectiveness (RBE) of both radionuclides, knowledge of the absorbed dose is essential. Thus, the authors present the dose calculations and discuss the results based on different models of the radionuclide distribution. Both different target volumes and the influence of the uptake kinetics were considered. Methods: Rat thyroid PC Cl3 cells in culture were incubated with either{sup 99m}Tc or {sup 123}I or were irradiated using 200 kV x-rays in the presence or absence of perchlorate. The clonogenic cell survival was measured via colony formation. In addition, the intracellular radionuclide uptake was quantified. Single-cell dose calculations were based on Monte Carlo simulations performed using Geant4. Results: Compared with external radiation using x-rays (D{sub 37} = 2.6 Gy), the radionuclides {sup 99m}Tc (D{sub 37} = 3.5 Gy), and {sup 123}I (D{sub 37} = 3.8 Gy) were less toxic in the presence of perchlorate. In the absence of perchlorate, the amount of activity a{sub 37} that was necessary to reduce the surviving fraction (SF) to 0.37 was 22.8 times lower for {sup 99m}Tc and 12.4 times lower for {sup 123}I because of the dose increase caused by intracellular radionuclide accumulation. When the cell nucleus was considered as the target for the dose calculation, the authors found a RBE of 2.18 for {sup 99m}Tc and RBE = 3.43 for {sup 123}I. Meanwhile, regarding the dose to the entire cell, RBE = 0.75 for {sup 99m}Tc and RBE = 1.87 for {sup 123}I. The dose to the entire cell was chosen as the dose criterion because of the intracellular radionuclide accumulation, which was found to occur solely in the cytoplasm. The calculated number of intracellular decays per cell was (975 ± 109) decays/MBq for {sup 99m}Tc and (221 ± 82) decays/MBq for {sup 123}I. Conclusions: The authors’ data indicate that extra-nuclear targets to Auger electrons exist, which is obvious from our dose calculations. When considering the dose to the cell nucleus, the authors found an enhanced RBE for{sup 99m}Tc and {sup 123}I relative to acute x-ray irradiation and pure extracellular irradiation with both radionuclides. Surprisingly, the authors did not find any radionuclide accumulation in the cell nucleus, indicating that there are additional radiosensitive targets besides the DNA. In addition, the authors demonstrated the necessity of cellular dose calculations in radiobiological experiments using unsealed radionuclides and identified the relevant parameters.

60 APPLIED LIFE SCIENCES↗

Concept and simulation study of a novel localization method for robotic endoscopic capsules using multiple positron emission markers

Purpose: Over the last decade, wireless capsule endoscope has been the tool of choice for noninvasive inspection of the gastrointestinal tract, especially in the small intestine. However, the latest clinical products have not been equipped with a sufficiently accurate localization system which makes it difficult to determine the location of intestinal abnormalities, and to apply follow-up interventions such as biopsy or drug delivery. In this paper, the authors present a novel localization method based on tracking three positron emission markers embedded inside an endoscopic capsule. Methods: Three spherical {sup 22}Na markers with diameters of less than 1 mm are embedded in the cover of the capsule. Gamma ray detectors are arranged around a patient body to detect coincidence gamma rays emitted from the three markers. The position of each marker can then be estimated using the collected data by the authors’ tracking algorithm which consists of four consecutive steps: a method to remove corrupted data, an initialization method, a clustering method based on the Fuzzy C-means clustering algorithm, and a failure prediction method. Results: The tracking algorithm has been implemented inMATLAB utilizing simulation data generated from the Geant4 Application for Emission Tomography toolkit. The results show that this localization method can achieve real-time tracking with an average position error of less than 0.4 mm and an average orientation error of less than 2°. Conclusions: The authors conclude that this study has proven the feasibility and potential of the proposed technique in effectively determining the position and orientation of a robotic endoscopic capsule.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

SU-E-I-11: Cascaded Linear System Model for Columnar CsI Flat Panel Imagers with Depth Dependent Gain and Blur

Purpose: To implement a depth dependent gain and blur cascaded linear system model (CLSM) for optimizing columnar structured CsI indirect conversion flat panel imager (FPI) for advanced imaging applications. Methods: For experimental validation, depth dependent escape efficiency, e(z), was extracted from PHS measurement of different CsI scintillators (thickness, substrate and light output). The inherent MTF and DQE of CsI was measured using high resolution CMOS sensor. For CLSM, e(z) and the depth dependent MTF(f,z), were estimated using Monte Carlo simulation (Geant4) of optical photon transport through columnar CsI. Previous work showed that Monte Carlo simulation for CsI was hindered by the non-ideality of its columnar structure. In the present work we allowed variation in columnar width with depth, and assumed diffusive reflective backing and columns. Monte Carlo simulation was performed using an optical point source placed at different depth of the CsI layer, from which MTF(z,f) and e(z) were computed. The resulting e(z) with excellent matching with experimental measurements were then applied to the CLSM, Monte Carlo simulation was repeated until the modeled MTF, DQE(f) also match experimental measurement. Results: For a 150 micron FOS HL type CsI, e(z) varies between 0.56 to 0.45, and the MTF at 14 cycles/mm varies between 62.1% to 3.9%, from the front to the back of the scintillator. The overall MTF and DQE(f) at all frequencies are in excellent agreement with experimental measurements at all frequencies. Conclusion: We have developed a CLSM for columnar CsI scintillators with depth dependent gain and MTF, which were estimated from Monte Carlo simulation with novel optical simulation settings. Preliminary results showed excellent agreement between simulation results and experimental measurements. Future work is aimed at extending this approach to optimize CsI screen optic design and sensor structure for achieving higher DQE(f) in cone-beam CT, which uses high kVp.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

SU-E-I-67: X-Ray Fluorescence for Energy Response Calibration of a Photon Counting Detector: A Simulation Study

Purpose: To investigate the feasibility of energy calibration and energy response characterization of a photon counting detector using x-ray fluorescence. Methods: A comprehensive Monte Carlo simulation study was done to investigate the influence of various geometric components on the x-ray fluorescence measurement. Different materials, sizes, and detection angles were simulated using Geant4 Application for Tomographic Emission (GATE) Monte Carlo package. Simulations were conducted using 100 kVp tungsten-anode spectra with 2 mm Al filter for a single pixel cadmium telluride (CdTe) detector with 3 × 3 mm2 in detection area. The fluorescence material was placed 300 mm away from both the x-ray source and the detector. For angular dependence measurement, the distance was decreased to 30 mm to reduce the simulation time. Compound materials, containing silver, barium, gadolinium, hafnium, and gold in cylindrical shape, were simulated. The object size varied from 5 to 100 mm in diameter. The angular dependence of fluorescence and scatter were simulated from 20° to 170° with an incremental step of 10° to optimize the fluorescence to scatter ratio. Furthermore, the angular dependence was also experimentally measured using a spectrometer (X-123CdTe, Amptek Inc., MA) to validate the simulation results. Results: The detection angle between 120° to 160° resulted in more optimal x-ray fluorescence to scatter ratio. At a detection angle of 120°, the object size did not have a significant effect on the fluorescence to scatter ratio. The experimental results of fluorescence angular dependence are in good agreement with the simulation results. The Kα and Kβ peaks of five materials could be identified. Conclusion: The simulation results show that the x-ray fluorescence procedure has the potential to be used for detector energy calibration and detector response characteristics by using the optimal system geometry.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

SU-E-J-03: A Comprehensive Comparison Between Alpha and Beta Emitters for Cancer Radioimmunotherapy

Purpose: The purpose of this study is to perform a comprehensive comparison of the therapeutic efficacy and cytotoxicity of alpha and beta emitters for Radioimmunotherapy (RIT). For each stage of cancer development, specific models were built for the separate objectives of RIT to be addressed:a) kill isolated cancer cells in transit in the lymphatic and vascular circulation,b) regress avascular cell clusters,c) regress tumor vasculature and tumors. Methods: Because of the nature of short range, high LET alpha and long energy beta radiation and heterogeneous antigen expression among cancer cells, the microdosimetric approach is essential for the RIT assessment. Geant4 based microdosimetric models are developed for the three different stages of cancer progression: cancer cells, cell clusters and tumors. The energy deposition, specific energy resulted from different source distribution in the three models was calculated separately for 4 alpha emitting radioisotopes ({sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac) and 6 beta emitters ({sup 32}P, {sup 33}P, {sup 67}Cu, {sup 90}Y, {sup 131}I and {sup 177}Lu). The cell survival, therapeutic efficacy and cytotoxicity are determined and compared between alpha and beta emitters. Results: We show that internal targeted alpha radiation has advantages over beta radiation for killing isolated cancer cells, regressing small cell clusters and also solid tumors. Alpha particles have much higher dose specificity and potency than beta particles. They can deposit 3 logs more dose than beta emitters to single cells and solid tumor. Tumor control probability relies on deep penetration of radioisotopes to cancer cell clusters and solid tumors. Conclusion: The results of this study provide a quantitative understanding of the efficacy and cytotoxicity of RIT for each stage of cancer development.

60 APPLIED LIFE SCIENCES↗

SU-E-J-09: A Monte Carlo Analysis of the Relationship Between Cherenkov Light Emission and Dose for Electrons, Protons, and X-Ray Photons

Purpose: A number of recent studies have proposed that light emitted by the Cherenkov effect may be used for a number of radiation therapy dosimetry applications. Here we investigate the fundamental nature and accuracy of the technique for the first time by using a theoretical and Monte Carlo based analysis. Methods: Using the GEANT4 architecture for medically-oriented simulations (GAMOS) and BEAMnrc for phase space file generation, the light yield, material variability, field size and energy dependence, and overall agreement between the Cherenkov light emission and dose deposition for electron, proton, and flattened, unflattened, and parallel opposed x-ray photon beams was explored. Results: Due to the exponential attenuation of x-ray photons, Cherenkov light emission and dose deposition were identical for monoenergetic pencil beams. However, polyenergetic beams exhibited errors with depth due to beam hardening, with the error being inversely related to beam energy. For finite field sizes, the error with depth was inversely proportional to field size, and lateral errors in the umbra were greater for larger field sizes. For opposed beams, the technique was most accurate due to an averaging out of beam hardening in a single beam. The technique was found to be not suitable for measuring electron beams, except for relative dosimetry of a plane at a single depth. Due to a lack of light emission, the technique was found to be unsuitable for proton beams. Conclusions: The results from this exploratory study suggest that optical dosimetry by the Cherenkov effect may be most applicable to near monoenergetic x-ray photon beams (e.g. Co-60), dynamic IMRT and VMAT plans, as well as narrow beams used for SRT and SRS. For electron beams, the technique would be best suited for superficial dosimetry, and for protons the technique is not applicable due to a lack of light emission. NIH R01CA109558 and R21EB017559.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

SU-E-J-215: Onboard Split PET Including the Effects of Attenuation, Scatter, and Random Events

Purpose: Positron emission tomography (PET) using split PET geometry was investigated as an on-board system for functional imaging and PET marker tracking, specifically with tomotherapy. The open dual ring PET would allow measurement of both inter and intra-fractional variation, improving the delineation of tumor volume at any stage in the radiation treatment delivery process. We present results from data obtained using Monte Carlo simulations including the effects of attenuation, random events, and scatter. Methods: PET design was accomplished via Monte Carlo simulations with GATE, the Geant4 Application for Emission Tomography. Images were reconstructed using Software for Image Reconstruction (STIR) with a fully 3D ordered subset expectation maximization (OSEM) image reconstruction technique. Results: Monte Carlo simulations of the split PET geometry indicate that including physical factors that degrade image quality such as attenuation, random events, and scatter still prove the feasibility of near real-time PET for both inter and intra-fractional radiation delivery. The image quality of scan times under 1 minute reveals that it is possible to utilize PET scanning and reconstruction during the treatment session intrafractionally. GATE also simulates the depth information but does not correct obliqueness of the path of line of response so the data is much more realistic than the data obtained with ray tracing. Conclusion: Onboard split PET with TomoTherapy can generate quality images under 1 minute scan times without the need to correct for attenuation, scatter, random events, or depth information of the interaction.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

SU-E-J-247: A Simulation of X-Ray Emission with Gold Nanoparticle Irradiated by Energetic Proton Beam

Purpose: To investigate the proton induced X-ray emissions in gold-water mixture materials. Methods: In this study a Monte Carlo simulation was created using the GEANT4 toolkit (version 4.9.6). The geometry in this setup includes a 2 cm × 2 cm × 2 cm target, a scoring sphere (radius = 10 cm) and a 65 MeV planar proton source (2 cm × 2 cm). Four concentrations of a gold-water solution were irradiated with 5×10{sup 5} incident protons at a distance of 0.5 cm perpendicular to the surface of the target. The solutions of gold-water mixture had 10%, 5%, 1% and 0.5% of gold by mass, respectively. The number of photon emitting for the target was counted in the scoring sphere for the energy range of 0-86.0 keV in 0.1 keV bins. For this study the reference physics list PhysListEmStandard was used together with the x-ray fluorescence, Auger electron and PIXE (particle induced xray emission) options enabled. The range cuts for photons and electrons were set at 0.5 mm and 1.0 mm, respectively. Results: In the energy spectra of emitting X-ray fluorescence, peaks from gold K shell characteristic x-rays (68.8 and 66.9 keV) were observed. The number of counts under the peaks of Ka1 and Ka2 was found to increase with the increasing of the gold concentrations in the mixture materials. The X-ray yields (for both Ka1 and Ka2) when fitted with least-square method as a function of gold concentration demonstrate a linear dependency with R{sup 2} > 0.96. The Ka1yield per incident proton was found to be 0.0016 for 10% gold-water mixture solutions. Conclusion: This preliminary study with PIXE technique with gold nanoparticle has demonstrated potentials for its utilization in the development of range and dose verification methodology that is currently of great interest in the field of proton radiation therapy.

07 ISOTOPE AND RADIATION SOURCES↗

SU-E-T-26: A Study On the Influence of Photonuclear Reactions On the Biological Effectiveness of Therapeutic High Energy X-Ray Beam

Purpose: Photons from a modern high-energy therapeutic linear accelerator used in X-ray radiotherapy causes photonuclear reactions in an accelerator or patient's body. The aim of this study is to evaluate the biological effectiveness including these particles by Microdosimetric Kinetic Model (MKM) based on microdosimetry. Methods: A linear accelerator operating at 15 MV was used. CR-39 was used to obtain LET spectra of secondary ions selectively, as CR-39 is regarded insensitive to photons. CR-39 was put on the central axis of the X-ray beam at depths of 0, 5 and 10 cm in plastic phantom at a source to detector distance of 100 cm. Pits formed by the traversal of ions were etched then analyzed to obtain restricted LET distribution. Frequency-mean and dose-mean lineal energy was evaluated from the relationship between the restricted LET and the lineal energy required to evaluate the biological effectiveness by MKM. The relationship was calculated by Monte Carlo simulations with GEANT4. Results: Restricted LET distributions of secondary particles showed broad distributions that decreases exponentially with increasing LET. Frequency-mean and dose-mean lineal energy were determined uniquely within the scope of the energies of secondary particles generated from photons of 15 MeV. The frequency-mean lineal energies at the depth of 0, 5 and 10 cm were 15.1, 16.0 and 19.7 keV/μm respectively, and the dose-mean lineal energies were 18.6, 20.5 and 19.6 keV/μm, respectively. RBE of secondary particles for HSG cell evaluated by MKM was about 2.0 at all depths, and RBE of all particles including photons was evaluated 1.0. Conclusion: We investigated the biological effectiveness of secondary particles by photonuclear reactions. The method to evaluate RBE by MKM was established with measurements and simulations. However, the influence of these secondary ions on RBE was found negligible in the entire biological effectiveness of the high-energy X-ray. This study has been supported by JSPS KAKENHI Grant Number 25861144.

60 APPLIED LIFE SCIENCES↗