Michael K. K. Leung

Irradiation of gold nanoparticles by x‐rays: Monte Carlo simulation of dose enhancements and the spatial properties of the secondary electrons production

PURPOSE The aim of this study is to understand the characteristics of secondary electrons generated from the interaction of gold nanoparticles (GNPs) with x-rays as a function of nanoparticle size and beam energy and thereby further the understanding of GNP-enhanced radiotherapy. METHODS The effective range, deflection angle, dose deposition, energy, and interaction processes of electrons produced from the interaction of x-rays with a GNP were calculated by Monte Carlo simulations. The GEANT4 code was used to simulate and track electrons generated from a 2, 50, and 100 nm diameter GNP when it is irradiated with a 50 kVp, 250 kVp, cobalt-60, and 6 MV photon beam in water. RESULTS When a GNP was present, depending on the beam energies used, secondary electron production was increased by 10- to 2000-fold compared to an absence of a GNP. Low-energy photon beams were much more efficient at interacting with the GNP by two to three orders of magnitude compared to MV energies and increased the deflection angle. GNPs with larger diameters also contributed more dose. The majority of the energy deposition was outside the GNP, rather than self-absorbed by the nanoparticle. The mean effective range of electron tracks for the beams tested ranged from approximately 3 microm to 1 mm. CONCLUSIONS These simulated results yield important insights concerning the spatial distributions and elevated dose in GNP-enhanced radiotherapy. The authors conclude that the irradiation of GNP at lower photon energies will be more efficient for cell killing. This conclusion is consistent with published studies.

Monte Carlo simulation on a gold nanoparticle irradiated by electron beams

This study investigated the secondary electron production from a gold nanoparticle (GNP) irradiated by monoenergetic electron beams using Monte Carlo (MC) simulation. Spherical GNPs with diameters of 2, 50 and 100 nm in water were irradiated by monoenergetic electron beams with energies equal to 50 keV, 250 keV, 1 MeV and 4 MeV. MC simulations were performed using the Geant4 toolkit to determine the energy of the secondary electrons emitted from the GNPs. The mean effective range and deflection angle of the secondary electrons were tracked. Energy depositions inside and outside the nanoparticles due to the secondary electrons were also calculated. For comparisons, simulations were repeated by replacing the GNPs with water. Our results show that the mean effective range of secondary electrons increased with an increase of the GNP size and electron beam energy. For the electron beam energy and GNP size used in this study, the mean effective range was 0.5-15 µm outside the nanoparticle, which is approximately within the dimension of a living cell. The mean deflection angles varied from 78 to 83 degrees as per our MC results. The proportion of energy deposition inside the GNP versus that outside increased with the GNP size. This is different from the results obtained from a previous study using photon beams. The secondary electron energy deposition ratio (energy deposition for GNP/energy deposition for water) was found to be highest for the smallest GNP of 2 nm diameter in this study. For the energy deposited by the secondary electron, we concluded that the addition of GNPs can increase the secondary electron energy deposition in water, though most of the energy was self-absorbed by the large nanoparticles (50 and 100 nm). In addition, an electron source in the presence of GNPs does not seem to be better than photons as the yield of secondary electrons per unit mass of gold is less than water.

Evaluation of the effect of patient dose from cone beam computed tomography on prostate IMRT using Monte Carlo simulation

The aim of this study is to evaluate the impact of the patient dose due to the kilovoltage cone beam computed tomography (kV-CBCT) in a prostate intensity-modulated radiation therapy (IMRT). The dose distributions for the five prostate IMRTs were calculated using the Pinnacle treatment planning system. To calculate the patient dose from CBCT, phase-space beams of a CBCT head based on the ELEKTA x-ray volume imaging system were generated using the Monte Carlo BEAMnr code for 100, 120, 130, and 140 kVp energies. An in-house graphical user interface called DOSCTP (DOSXYZnrc-based) developed using MATLAB was used to calculate the dose distributions due to a 360 degrees photon arc from the CBCT beam with the same patient CT image sets as used in Pinnacle. The two calculated dose distributions were added together by setting the CBCT doses equal to 1%, 1.5%, 2%, and 2.5% of the prescription dose of the prostate IMRT. The prostate plan and the summed dose distributions were then processed in the CERR platform to determine the dose-volume histograms (DVHs) of the regions of interest. Moreover, dose profiles along the x- and y-axes crossing the isocenter with and without addition of the CBCT dose were determined. It was found that the added doses due to CBCT are most significant at the femur heads. Higher doses were found at the bones for a relatively low energy CBCT beam such as 100 kVp. Apart from the bones, the CBCT dose was observed to be most concentrated on the anterior and posterior side of the patient anatomy. Analysis of the DVHs for the prostate and other critical tissues showed that they vary only slightly with the added CBCT dose at different beam energies. On the other hand, the changes of the DVHs for the femur heads due to the CBCT dose and beam energy were more significant than those of rectal and bladder wall. By analyzing the vertical and horizontal dose profiles crossing the femur heads and isocenter, with and without the CBCT dose equal to 2% of the prescribed dose, it was found that there is about a 5% increase of dose at the femur head. Still, such an increase in the femur head dose is well below the dose limit of the bone in our IMRT plans. Therefore, under these dose fractionation conditions, it is concluded that, though CBCT causes a higher dose deposited at the bones, there may be no significant effect in the DVHs of critical tissues in the prostate IMRT.

In vivo optical imaging of tumor and microvascular response to ionizing radiation.

Radiotherapy is a widely used cancer treatment. However, understanding how ionizing radiation affects tumor cells and their vasculature, particularly at cellular, subcellular, genetic, and protein levels, has been limited by an inability to visualize the response of these interdependent components within solid tumors over time and in vivo. Here we describe a new preclinical experimental platform combining intravital multimodal optical microscopy for cellular-level longitudinal imaging, a small animal x-ray microirradiator for reproducible spatially-localized millimeter-scale irradiations, and laser-capture microdissection of ex vivo tissues for transcriptomic profiling. Using this platform, we have developed new methods that exploit the power of optically-enabled microscopic imaging techniques to reveal the important role of the tumor microvasculature in radiation response of tumors. Furthermore, we demonstrate the potential of this preclinical platform to study quantitatively - with cellular and sub-cellular details - the spatio-temporal dynamics of the biological response of solid tumors to ionizing radiation in vivo.

Treatment planning for a small animal using Monte Carlo simulation

The development of a small animal model for radiotherapy research requires a complete setup of customized imaging equipment, irradiators, and planning software that matches the sizes of the subjects. The purpose of this study is to develop and demonstrate the use of a flexible in-house research environment for treatment planning on small animals. The software package, called DOSCTP, provides a user-friendly platform for DICOM computed tomography-based Monte Carlo dose calculation using the EGSnrcMP-based DOSXYZnrc code. Validation of the treatment planning was performed by comparing the dose distributions for simple photon beam geometries calculated through the Pinnacle3 treatment planning system and measurements. A treatment plan for a mouse based on a CT image set by a 360-deg photon arc is demonstrated. It is shown that it is possible to create 3D conformal treatment plans for small animals with consideration of inhomogeneities using small photon beam field sizes in the diameter range of 0.5-5 cm, with conformal dose covering the target volume while sparing the surrounding critical tissue. It is also found that Monte Carlo simulation is suitable to carry out treatment planning dose calculation for small animal anatomy with voxel size about one order of magnitude smaller than that of the human.

Dosimetric variation due to the photon beam energy in the small-animal irradiation: A Monte Carlo study

PURPOSE The impact of photon beam energy and tissue heterogeneities on dose distributions and dosimetric characteristics such as point dose, mean dose, and maximum dose was investigated in the context of small-animal irradiation using Monte Carlo simulations based on the EGSnrc code. METHODS Three Monte Carlo mouse phantoms, namely, heterogeneous, homogeneous, and bone homogeneous were generated based on the same mouse computed tomography image set. These phantoms were generated by overriding the tissue type of none of the voxels (heterogeneous), all voxels (homogeneous), and only the bone voxels (bone homogeneous) to that of soft tissue. Phase space files of the 100 and 225 kVp photon beams based on a small-animal irradiator (XRad225Cx, Precision X-Ray Inc., North Branford, CT) were generated using BEAMnrc. A 360° photon arc was simulated and three-dimensional (3D) dose calculations were carried out using the DOSXYZnrc code through DOSCTP in the above three phantoms. For comparison, the 3D dose distributions, dose profiles, mean, maximum, and point doses at different locations such as the isocenter, lung, rib, and spine were determined in the three phantoms. RESULTS The dose gradient resulting from the 225 kVp arc was found to be steeper than for the 100 kVp arc. The mean dose was found to be 1.29 and 1.14 times higher for the heterogeneous phantom when compared to the mean dose in the homogeneous phantom using the 100 and 225 kVp photon arcs, respectively. The bone doses (rib and spine) in the heterogeneous mouse phantom were about five (100 kVp) and three (225 kVp) times higher when compared to the homogeneous phantom. However, the lung dose did not vary significantly between the heterogeneous, homogeneous, and bone homogeneous phantom for the 225 kVp compared to the 100 kVp photon beams. CONCLUSIONS A significant bone dose enhancement was found when the 100 and 225 kVp photon beams were used in small-animal irradiation. This dosimetric effect, due to the presence of the bone heterogeneity, was more significant than that due to the lung heterogeneity. Hence, for kV photon energies of the range used in small-animal irradiation, the increase of the mean and bone dose due to the photoelectric effect could be a dosimetric concern.

Dosimetry of oblique tangential photon beams calculated by superposition/convolution algorithms: a Monte Carlo evaluation

Although there are many works on evaluating dose calculations of the anisotropic analytical algorithm (AAA) using various homogeneous and heterogeneous phantoms, related work concerning dosimetry due to tangential photon beam is lacking. In this study, dosimetry predicted by the AAA and collapsed cone convolution (CCC) algorithm was evaluated using the tangential photon beam and phantom geometry. The photon beams of 6 and 15 MV with field sizes of 4×4 (or 7×7), 10×10 and 20×20 cm2, produced by a Varian 21 EX linear accelerator, were used to test performances of the AAA and CCC using Monte Carlo (MC) simulation (EGSnrc‐based code) as a benchmark. Horizontal dose profiles at different depths, phantom skin profiles (i.e., vertical dose profiles at a distance of 2 mm from the phantom lateral surface), gamma dose distributions, and dose‐volume histograms (DVHs) of skin slab were determined. For dose profiles at different depths, the CCC agreed better with doses in the air‐phantom region, while both the AAA and CCC agreed well with doses in the penumbra region, when compared to the MC. Gamma evaluations between the AAA/CCC and MC showed that deviations of 2D dose distribution occurred in both beam edges in the phantom and air‐phantom interface. Moreover, the gamma dose deviation is less significant in the air‐phantom interface than the penumbra. DVHs of skin slab showed that both the AAA and CCC underestimated the width of the dose drop‐off region for both the 6 and 15MV photon beams. When the gantry angle was 0°, it was found that both the AAA and CCC overestimated doses in the phantom skin profiles compared to the MC, with various photon beam energies and field sizes. The mean dose differences with doses normalized to the prescription point for the AAA and CCC were respectively:7.6%±2.6% and 2.1%±1.3% for a 10×10 cm2 field, 6 MV; 16.3%±2.1% and 6.7%±2.1% for a 20×20 cm2 field, 6 MV; 5.5%±1.2% and 1.7%±1.4% for a 10×10 cm2, 15 MV; 18.0%±1.3% and 8.3%±1.8% for a 20×20 cm2, 15 MV. However, underestimations of doses in the phantom skin profile were found with small fields of 4×4 and 7×7 cm2 for the 6 and 15 MV photon beams, respectively, when the gantry was turned 5° anticlockwise. As surface dose with tangential photon beam geometry is important in some radiation treatment sites such as breast, chest wall and sarcoma, it is found that neither of the treatment planning system algorithms can predict the dose well at depths shallower than 2 mm. The dosimetry data and beam and phantom geometry in this study provide a better knowledge of a dose calculation algorithm in tangential‐like irradiation. PACS numbers: 87.55.‐x, 87.53.Bn, 87.55.K‐, 87.55.kh, 87.56.jf

Monte Carlo simulation on low-energy electrons from gold nanoparticle in radiotherapy

This study investigated the low-energy electrons (LEEs) produced when a gold nanoparticle (GNP) is irradiated by photon beams. The secondary electrons emitted from a GNP (diameter = 100 nm), interacting with photon beams with energies equal to 35, 73.3 and 600 keV, were simulated using the Geant4 Monte Carlo code. The phase spaces of the secondary electrons were then used to simulate the LEEs in water using the NOREC Monte Carlo code. All secondary electrons emitted by the GNP, and all LEEs produced by each secondary electron were tracked in Monte Carlo simulations. It is found that the energy distributions of the LEEs from the GNP do not vary significantly between different photon beam energies. Moreover, the 660 keV photon beam produced more LEEs travelling to a longer range than photon beams of lower energies (35 and 73.3 keV). This higher energy deposition and longer range LEEs produced by the 660 keV photon beam can enhance the cell kill. Based on our Monte Carlo results, it is concluded that the unexpected close of the radiosensitization enhancement factors of the 35 (1.66) and 660 keV (1.18) photon beams from our previous measurements is because of the cell kill enhancement with the increased LEE yield and range in the 660 keV photon beam.

A graphical user interface for calculation of 3D dose distribution using Monte Carlo simulations

A software graphical user interface (GUI) for calculation of 3D dose distribution using Monte Carlo (MC) simulation is developed using MATLAB. This GUI (DOSCTP) provides a user-friendly platform for DICOM CT-based dose calculation using EGSnrcMP-based DOSXYZnrc code. It offers numerous features not found in DOSXYZnrc, such as the ability to use multiple beams from different phase-space files, and has built-in dose analysis and visualization tools. DOSCTP is written completely in MATLAB, with integrated access to DOSXYZnrc and CTCREATE. The program function may be divided into four subgroups, namely, beam placement, MC simulation with DOSXYZnrc, dose visualization, and export. Each is controlled by separate routines. The verification of DOSCTP was carried out by comparing plans with different beam arrangements (multi-beam/photon arc) on an inhomogeneous phantom as well as patient CT between the GUI and Pinnacle3. DOSCTP was developed and verified with the following features: (1) a built-in voxel editor to modify CT-based DOSXYZnrc phantoms for research purposes; (2) multi-beam placement is possible, which cannot be achieved using the current DOSXYZnrc code; (3) the treatment plan, including the dose distributions, contours and image set can be exported to a commercial treatment planning system such as Pinnacle3 or to CERR using RTOG format for plan evaluation and comparison; (4) a built-in RTOG-compatible dose reviewer for dose visualization and analysis such as finding the volume of hot/cold spots in the 3D dose distributions based on a user threshold. DOSCTP greatly simplifies the use of DOSXYZnrc and CTCREATE, and offers numerous features that not found in the original user-code. Moreover, since phase-space beams can be defined and generated by the user, it is a particularly useful tool to carry out plans using specifically designed irradiators/accelerators that cannot be found in the Linac library of commercial treatment planning systems.

Monte Carlo simulation of MOSFET dosimeter for electron backscatter using the GEANT4 code

The aim of this study is to investigate the influence of the body of the metal-oxide-semiconductor field effect transistor (MOSFET) dosimeter in measuring the electron backscatter from lead. The electron backscatter factor (EBF), which is defined as the ratio of dose at the tissue-lead interface to the dose at the same point without the presence of backscatter, was calculated by the Monte Carlo simulation using the GEANT4 code. Electron beams with energies of 4, 6, 9, and 12 MeV were used in the simulation. It was found that in the presence of the MOSFET body, the EBFs were underestimated by about 2%-0.9% for electron beam energies of 4-12 MeV, respectively. The trend of the decrease of EBF with an increase of electron energy can be explained by the small MOSFET dosimeter, mainly made of epoxy and silicon, not only attenuated the electron fluence of the electron beam from upstream, but also the electron backscatter generated by the lead underneath the dosimeter. However, this variation of the EBF underestimation is within the same order of the statistical uncertainties as the Monte Carlo simulations, which ranged from 1.3% to 0.8% for the electron energies of 4-12 MeV, due to the small dosimetric volume. Such small EBF deviation is therefore insignificant when the uncertainty of the Monte Carlo simulation is taken into account. Corresponding measurements were carried out and uncertainties compared to Monte Carlo results were within +/- 2%. Spectra of energy deposited by the backscattered electrons in dosimetric volumes with and without the lead and MOSFET were determined by Monte Carlo simulations. It was found that in both cases, when the MOSFET body is either present or absent in the simulation, deviations of electron energy spectra with and without the lead decrease with an increase of the electron beam energy. Moreover, the softer spectrum of the backscattered electron when lead is present can result in a reduction of the MOSFET response due to stronger recombination in the SiO2 gate. It is concluded that the MOSFET dosimeter performed well for measuring the electron backscatter from lead using electron beams. The uncertainty of EBF determined by comparing the results of Monte Carlo simulations and measurements is well within the accuracy of the MOSFET dosimeter (< +/- 4.2%) provided by the manufacturer.