Principal component analysis modeling of Head-and-Neck anatomy using daily Cone Beam-CT images.

PURPOSE: To model Head-and-Neck anatomy from daily Cone Beam-CT (CBCT) images over the course of fractionated radiotherapy using principal component analysis (PCA). METHODS AND MATERIALS: Eighteen oropharyngeal Head-and-Neck cancer patients, treated with volumetric modulated arc therapy (VMAT), were included in this retrospective study. Normal organs, including the parotid and submandibular glands, mandible, pharyngeal constrictor muscles (PCMs), and spinal cord were contoured using daily CBCT image datasets. PCA models for each organ were developed for individual patients (IP) and the entire patient cohort/population (PP). The first 10 principal components (PCs) were extracted for all models. Analysis included cumulative and individual PCs for each organ and patient, as well as the aggregate organ/patient population; comparisons were made using the root-mean-square (RMS) of the percentage predicted spatial displacement for each PC. RESULTS: Overall, spatial displacement prediction was achieved at the 95% confidence level (CL) for the first three to four PCs for all organs, based on IP models. For PP models, the first four PCs predicted spatial displacement at the 80%-89% CL. Differences in percentage predicted spatial displacement between mean IP models for each organ ranged from 2.8% ± 1.8% (1st PC) to 0.6% ± 0.4% (4th PC). Differences in percentage predicted spatial displacement between IP models vs the mean IP model for each organ based on the 1st PC were <12.9% ± 6.9% for all organs. Differences in percentage predicted spatial displacement between IP and PP models based on all organs and patients for the 1st and 2nd PC were <11.7% ± 2.2%. CONCLUSION: Tissue changes during fractionated radiotherapy observed on daily CBCT in patients with Head-and-Neck cancers, were modeled using PCA. In general, spatial displacement for organs-at-risk was predicted for the first 4 principal components at the 95% confidence levels (CL), for individual patient (IP) models, and at the 80%-89% CL for population-based patient (PP) models. The IP and PP models were most predictive of changes in glandular organs and pharyngeal constrictor muscles, respectively.

Validation of GPU-accelerated superposition-convolution dose computations for the Small Animal Radiation Research Platform.

PURPOSE: The Small Animal Radiation Research Platform (SARRP) has been developed for conformal microirradiation with on-board cone beam CT (CBCT) guidance. The graphics processing unit (GPU)-accelerated Superposition-Convolution (SC) method for dose computation has been integrated into the treatment planning system (TPS) for SARRP. This paper describes the validation of the SC method for the kilovoltage energy by comparing with EBT2 film measurements and Monte Carlo (MC) simulations. METHODS: MC data were simulated by EGSnrc code with 3 × 108 -1.5 × 109 histories, while 21 photon energy bins were used to model the 220 kVp x-rays in the SC method. Various types of phantoms including plastic water, cork, graphite, and aluminum were used to encompass the range of densities of mouse organs. For the comparison, percentage depth dose (PDD) of SC, MC, and film measurements were analyzed. Cross beam (x,y) dosimetric profiles of SC and film measurements are also presented. Correction factors (CFz) to convert SC to MC dose-to-medium are derived from the SC and MC simulations in homogeneous phantoms of aluminum and graphite to improve the estimation. RESULTS: The SC method produces dose values that are within 5% of film measurements and MC simulations in the flat regions of the profile. The dose is less accurate at the edges, due to factors such as geometric uncertainties of film placement and difference in dose calculation grids. CONCLUSION: The GPU-accelerated Superposition-Convolution dose computation method was successfully validated with EBT2 film measurements and MC calculations. The SC method offers much faster computation speed than MC and provides calculations of both dose-to-water in medium and dose-to-medium in medium.

AGuIX nanoparticles as a promising platform for image-guided radiation therapy.

AGuIX are gadolinium-based nanoparticles developed mainly for imaging due to their MR contrast properties. They also have a potential role in radiation therapy as a radiosensitizer. We used MRI to quantify the uptake of AGuIX in pancreatic cancer cells, and TEM for intracellular localization. We measured the radiosensitization of a pancreatic cancer cell line in a low-energy (220 kVp) beam, a standard 6 MV beam (STD) and a flattening filter free 6 MV beam (FFF). We demonstrated that the presence of nanoparticles significantly decreases cell survival when combined with an X-ray beam with a large proportion of low-energy photons (close to the k-edge of the nanoparticles). The concentration of nanoparticles in the cell achieves its highest level after 15 min and then reaches a plateau. The accumulated nanoparticles are mainly localized in the cytoplasm, inside vesicles. We found that the 6 MV FFF beams offer the best trade-off between penetration depth and proportion of low-energy photons. At 10 cm depth, we measured a DEF20 % of 1.30 ± 0.47 for the 6 MV FFF beam, compared to 1.23 ± 0.26 for the 6 MV STD beam. Additional measurements with un-incubated nanoparticles provide evidence that chemical processes might also be contributing to the dose enhancement effect.

Monte Carlo simulation of a prototypical patient dosimetry system for fluoroscopic procedures.

The purpose of this study is to investigate feasibility of a novel real-time dosimetry method for fluoroscopically guided interventions utilizing thin-film detector arrays in several potential locations with respect to the patient and x-ray equipment. We employed Monte Carlo (MC) simulation to establish the fluoroscopic beam model to determine dosimetric quantities directly from measured doses in thin-film detector arrays at three positions: A-attached to the x-ray source, B-on the couch under the patient and C-attached to the fluoroscopic imager. Next, we developed a calibration method to determine skin dose at the entry of the beam ([Formula: see text]) as well as the dose distribution along each ray of the beam in a water-equivalent patient model. We utilized the concept of water-equivalent thickness to determine the dose inside the patient based on doses measured outside of the patient by the thin-film detector array layers: (a) A, (b) B, or (c) B and C. In the process of calibration we determined a correction factor that characterizes the material-specific response of the detector, backscatter factor and attenuation factor for slab water phantoms of various thicknesses. Application of this method to an anthropomorphic phantom showed accuracy of about 1% for [Formula: see text] and up to about 10% for integral dose along the beam path when compared to a direct simulation of dose by MC.

New potential for enhancing concomitant chemoradiotherapy with FDA approved concentrations of cisplatin via the photoelectric effect.

We predict, for the first time, that by using United States Food and Drug Administration approved concentrations of cisplatin, major radiosensitization may be achieved via photoelectric mechanism during concomitant chemoradiotherapy (CCRT). Our analytical calculations estimate that radiotherapy (RT) dose to cancer cells may be enhanced via this mechanism by over 100% during CCRT. The results proffer new potential for significantly enhancing CCRT via an emerging clinical scenario, where the cisplatin is released in-situ from RT biomaterials loaded with cisplatin nanoparticles.

Dependence of Monte Carlo microdosimetric computations on the simulation geometry of gold nanoparticles.

Recently, interactions of x-rays with gold nanoparticles (GNPs) and the resulting dose enhancement have been studied using several Monte Carlo (MC) codes (Jones et al 2010 Med. Phys. 37 3809-16, Lechtman et al 2011 Phys. Med. Biol. 56 4631-47, McMahon et al 2011 Sci. Rep. 1 1-9, Leung et al 2011 Med. Phys. 38 624-31). These MC simulations were carried out in simplified geometries and provided encouraging preliminary data in support of GNP radiotherapy. As these studies showed, radiation transport computations of clinical beams to obtain dose enhancement from nanoparticles has several challenges, mostly arising from the requirement of high spatial resolution and from the approximations used at the interface between the macroscopic clinical beam transport and the nanoscopic electron transport originating in the nanoparticle or its vicinity. We investigate the impact of MC simulation geometry on the energy deposition due to the presence of GNPs, including the effects of particle clustering and morphology. Dose enhancement due to a single and multiple GNPs using various simulation geometries is computed using GEANT4 MC radiation transport code. Various approximations in the geometry and in the phase space transition from macro- to micro-beams incident on GNPs are analyzed. Simulations using GEANT4 are compared to a deterministic code CEPXS/ONEDANT for microscopic (nm-µm) geometry. Dependence on the following microscopic (µ) geometry parameters is investigated: µ-source-to-GNP distance (µSAD), µ-beam size (µS), and GNP size (µC). Because a micro-beam represents clinical beam properties at the microscopic scale, the effect of using different types of micro-beams is also investigated. In particular, a micro-beam with the phase space of a clinical beam versus a plane-parallel beam with an equivalent photon spectrum is characterized. Furthermore, the spatial anisotropy of energy deposition around a nanoparticle is analyzed. Finally, dependence of dose enhancement on the number of GNPs in a finite cluster of nanoparticles is determined. Simulations were performed for 100 nm GNPs irradiated in water phantom by various monoenergetic (11 keV-1 MeV) and spectral (50 kVp) sources. The dose enhancement ratio (DER) is very sensitive to the specific simulation geometry (µSAD, µS, µC parameters) and µ-source type. For a single GNP the spatial distribution of DER is found to be nearly isotropic with limited magnitude and relatively short range (∼100-200 nm for DER significantly greater than 1). For a cluster of GNPs both the magnitude and range are found much greater (∼1-2 µm). The relation between DER for a cluster of GNPs and a single GNP is strongly nonlinear. Relatively strong dependence of DER on the simulation micro-geometry cautions future studies and the interpretation of existing MC results obtained in different simulations geometries. The nonlinear relation between DER for a single and multiple GNPs suggests that parameters such as the number of adjacent nanoparticles per cell and the distances between the GNPs and the cellular target may be important in assessing the biological effectiveness associated with GNP.

The effect of flattening filter free delivery on endothelial dose enhancement with gold nanoparticles.

PURPOSE: The aim of this study is to quantify and to compare the dose enhancement factor from gold nanoparticles (AuNP) to tumor endothelial cells for different concentrations of AuNP, and clinical MV beam configurations. METHODS: Tumor endothelial cells are modeled as slabs measuring 10 × 10 × 2 µm. A spherical AuNP is simulated on the surface of the endothelial cell, within the blood vessel. 6 MV photon beams with and without the flattening filter are investigated for different field sizes, depths in material and beam modulation. The incident photon energy spectra for each configuration is generated using EGSnrc. The dose enhancement in the tumor endothelial cell is found using an analytical calculation. The endothelial dose enhancement factor is defined to be the ratio of the dose deposited with and without AuNPs. RESULTS: It is found that clinical beam parameters may be chosen to maximize the effect of gold nanoparticles during radiotherapy. This effect is further amplified ~20% by the removal of the flattening filter. Modulation of the clinical beam with the multileaf collimator tends to decrease the proportion of low energy photons, therefore providing less enhancement than the corresponding open field. CONCLUSIONS: The results of this work predict a dose enhancement to tumor blood vessel endothelial cells using conventional therapeutic (MV) x-rays and quantify the relative change in enhancement with treatment depth and field size.

A stochastic model of cell survival for high-Z nanoparticle radiotherapy.

PURPOSE: The authors present a stochastic framework for the assessment of cell survival in gold nanoparticle radiotherapy. METHODS: The authors derive the equations for the effective macroscopic dose enhancement for a population of cells with nonideal distribution of gold nanoparticles (GNP), allowing different number of GNP per cell and different distances with respect to the cellular target. They use the mixed Poisson distribution formalism to model the impact of the aforementioned physical factors on the effective dose enhancement. RESULTS: The authors show relatively large differences in the estimation of cell survival arising from using approximated formulae. They predict degeneration of the cell killing capacity due to different number of GNP per cell and different distances with respect to the cellular target. CONCLUSIONS: The presented stochastic framework can be used in interpretation of experimental cell survival or tumor control probability studies.

Impact of beam quality on megavoltage radiotherapy treatment techniques utilizing gold nanoparticles for dose enhancement.

This study determines the optimal clinical scenarios for gold nanoparticle dose enhancement as a function of irradiation conditions and potential biological targets using megavoltage x-ray beams. Four hundred and eighty clinical beams were studied for different potential cellular or sub-cellular targets. Beam quality was determined based on a 6 MV linac with and without a flattening filter for various delivery conditions. Dose enhancement ratios DER = D(GNP)/D(water) were calculated for all cases using the GEANT4 Monte Carlo code and the CEPXS/ONEDANT radiation transport deterministic code. Dose enhancement using GEANT4 agreed with CEPXS/ONEDANT. DER for unflattened beams is ∼2 times larger than for flattened beams. The maximum DER values were calculated for split-IMRT fields (∼6) and for out-of-field areas of an unflattened linac (∼17). In-field DER values, at the surface of gold nanoparticles, ranged from 2.2 to 4.2 (flattened beam) and from 3 to 4.7 (unflattened beams). For a GNP cluster with thicknesses of 10 and 100 nm, the DER ranges from 14% to 287%. DER is the greatest for split-IMRT, larger depths, out-of-field areas and/or unflattened linac. Mapping of a GNP location in tumor and normal tissue is essential for efficient and safe delivery of nanoparticle-enhanced radiotherapy.

A multipurpose quality assurance phantom for the small animal radiation research platform (SARRP).

In this work, the suitability and performance of a mouse-size MOSFET (Mousefet) phantom is investigated for routine quality assurance (QA) of the small animal radiation research platform (SARRP). This Mousefet phantom is a simple construction consisting of five micro-MOSFETS custom integrated in a quincunx pattern within a tissue-equivalent phantom, allowing repeat/multiple QA tasks to be quickly performed in one experimental set-up. The Mousefet phantom is particularly evaluated for facilitating SARRP QA tasks which may warrant daily evaluation, including output constancy, isocenter congruency test and cone beam computed tomography (CBCT) image geometric accuracy. Results for the output constancy measurements showed a maximum daily variation of less than 2.6% for all MOSFETS, in consonance with observations from concurrent ion chamber measurements. It is also shown that the design of the Mousefet phantom allows the output check data to be used for prompt verification of beam energy and cone profile constancy. For the isocenter congruency test, it is demonstrated that the Mousefet phantom can detect 0.3 mm deviations of the CBCT isocenter from the radiation isocenter. Meanwhile, results for CBCT image geometric accuracy were consistently found to be within 2% of the expected value. Other CBCT image quality parameters could also be assessed in terms of image intensity constancy, noise and image uniformity. Overall, the results establish the Mousefet phantom as a simple and time-efficient multipurpose tool that could be employed effectively for routine QA of the SARRP.