Effect of Statistical Fluctuation in Monte Carlo Based Photon Beam Dose Calculation on Gamma Index Evaluation

The gamma-index test has been commonly adopted to quantify the degree of agreement between a reference dose distribution and an evaluation dose distribution. Monte Carlo (MC) simulation has been widely used for the radiotherapy dose calculation for both clinical and research purposes. The goal of this work is to investigate both theoretically and experimentally the impact of the MC statistical fluctuation on the gamma-index test when the fluctuation exists in the reference, the evaluation, or both dose distributions. To the first order approximation, we theoretically demonstrated in a simplified model that the statistical fluctuation tends to overestimate gamma-index values when existing in the reference dose distribution and underestimate gamma-index values when existing in the evaluation dose distribution given the original gamma-index is relatively large for the statistical fluctuation. Our numerical experiments using clinical photon radiation therapy cases have shown that 1) when performing a gamma-index test between an MC reference dose and a non-MC evaluation dose, the average gamma-index is overestimated and the passing rate decreases with the increase of the noise level in the reference dose; 2) when performing a gamma-index test between a non-MC reference dose and an MC evaluation dose, the average gamma-index is underestimated when they are within the clinically relevant range and the passing rate increases with the increase of the noise level in the evaluation dose; 3) when performing a gamma-index test between an MC reference dose and an MC evaluation dose, the passing rate is overestimated due to the noise in the evaluation dose and underestimated due to the noise in the reference dose. We conclude that the gamma-index test should be used with caution when comparing dose distributions computed with Monte Carlo simulation

The residual STL volume as a metric to evaluate accuracy and reproducibility of anatomic models for 3D printing: application in the validation of 3D-printable models of maxillofacial bone from reduced radiation dose CT images.

BackgroundThe effects of reduced radiation dose CT for the generation of maxillofacial bone STL models for 3D printing is currently unknown. Images of two full-face transplantation patients scanned with non-contrast 320-detector row CT were reconstructed at fractions of the acquisition radiation dose using noise simulation software and both filtered back-projection (FBP) and Adaptive Iterative Dose Reduction 3D (AIDR3D). The maxillofacial bone STL model segmented with thresholding from AIDR3D images at 100 % dose was considered the reference. For all other dose/reconstruction method combinations, a "residual STL volume" was calculated as the topologic subtraction of the STL model derived from that dataset from the reference and correlated to radiation dose.ResultsThe residual volume decreased with increasing radiation dose and was lower for AIDR3D compared to FBP reconstructions at all doses. As a fraction of the reference STL volume, the residual volume decreased from 2.9 % (20 % dose) to 1.4 % (50 % dose) in patient 1, and from 4.1 % to 1.9 %, respectively in patient 2 for AIDR3D reconstructions. For FBP reconstructions it decreased from 3.3 % (20 % dose) to 1.0 % (100 % dose) in patient 1, and from 5.5 % to 1.6 %, respectively in patient 2. Its morphology resembled a thin shell on the osseous surface with average thickness <0.1 mm.ConclusionThe residual volume, a topological difference metric of STL models of tissue depicted in DICOM images supports that reduction of CT dose by up to 80 % of the clinical acquisition in conjunction with iterative reconstruction yields maxillofacial bone models accurate for 3D printing

Clinically relevant investigation of flattening filter-free skin dose

As flattening filter-free (FFF) photon beams become readily available for treatment delivery in techniques such as SBRT, thorough investigation of skin dose from FFF photon beams is necessary under clinically relevant conditions. Using a parallel-plate PTW Markus chamber placed in a custom water-equivalent phantom, surface-dose measurements were taken at 2 × 2, 3 × 3, 4 × 4, 6 × 6, 8 × 8, 10 × 10, 20 × 20, and 30 × 30 cm2 field sizes, at 80, 90, and 100 cm source-to-surface distances (SSDs), and with fields defined by jaws and multileaf collimator (MLC) using multiple beam energies (6X, 6XFFF, 10X, and 10XFFF). The same set of measurements was repeated with the chamber at a reference depth of 10 cm. Each surface measurement was normalized by its corresponding reference depth measurement for analysis. The FFF surface doses at 100 cm SSD were higher than flattened surface doses by 45% at 2 × 2 cm2 to 13% at 20 × 20 cm2 for 6 MV energy. These surface dose differences varied to a greater degree as energy increased, ranging from +63% at 2 × 2 cm2 to -2% at 20 × 20 cm2 for 10 MV. At small field sizes, higher energy increased FFF surface dose relative to flattened surface dose; while at larger field sizes, relative FFF surface dose was higher for lower energies. At both energies investigated, decreasing SSD caused a decrease in the ratios of FFF-to-flattened surface dose. Variability with SSD of FFF-to flattened surface dose differences increased with field size and ranged from 0% to 6%. The field size at which FFF and flattened beams gave the same skin dose increased with decreasing beam energy. Surface dose was higher with MLC fields compared to jaw fields under most conditions, with the difference reaching its maximum at a field size between 4 × 4 cm2 and 6 × 6 cm2 for a given energy and SSD. This study conveyed the magnitude of surface dose in a clinically meaningful manner by reporting results normalized to 10 cm depth dose instead of depth of dose maximum

Nothing Besides Remains: Preserving the Scientific and Cultural Value of Paleontological Resources in the United States

Receptor occupancy assessed by Positron Emission Tomography (PET) can provide important translational information to help bridge information from one drug to another or from animal to man. The aim of this thesis was to develop nonlinear mixed effects methods for estimation of the relationship between drug exposure and receptor occupancy for the two mGluR5 antagonists AZD9272 and AZD2066 and for the 5HT1B receptor antagonist AZD3783. Also the optimal design for improved estimation of the relationship between drug exposure and receptor occupancy as well as for improved dose finding in neuropathic pain treatment, was investigated. Different modeling approaches were applied. For AZD9272, the radioligand kinetics and receptor occupancy was simultaneously estimated using arterial concentrations as input function and including two brain regions of interest. For AZD2066, a model was developed where brain/plasma partition coefficients from ten different brain regions were included simultaneously as observations. For AZD3783, the simplified reference tissue model was extended to allow different non-specific binding in the reference region and brain regions of interest and the possibility of using white matter as reference was also evaluated. The optimal dose-selection for improved precision of receptor occupancy as well as for improved precision of the minimum effective dose of a neuropathic pain treatment was assessed, using the D-optimal as well as the Ds-optimal criteria. Simultaneous modelling of radioligand and occupancy provided a means to avoid simplifications or approximations and provided the possibility to tests or to relax assumptions. Inclusion of several brain regions of different receptor density simultaneously in the analysis, markedly improved the precision of the affinity parameter. Higher precision was achieved in relevant parameters with designs based on the Ds compared to the D-optimal criterion. The optimal design for improved precision of the relationship between dose and receptor occupancy depended on the number of brain regions and the receptor density of these regions. In conclusion, this thesis presents novel non-linear mixed effects models estimating the relationship between drug exposure and receptor occupancy, providing useful translational information, allowing for a better informed drug-development

CT Automated Exposure Control Using A Generalized Detectability Index

Purpose Identifying an appropriate tube current setting can be challenging when using iterative reconstruction due to the varying relationship between spatial resolution, contrast, noise, and dose across different algorithms. This study developed and investigated the application of a generalized detectability index (d\u27gen) to determine the noise parameter to input to existing automated exposure control (AEC) systems to provide consistent image quality (IQ) across different reconstruction approaches. Methods This study proposes a task‐based automated exposure control (AEC) method using a generalized detectability index (d\u27gen). The proposed method leverages existing AEC methods that are based on a prescribed noise level. The generalized d\u27gen metric is calculated using lookup tables of task‐based modulation transfer function (MTF) and noise power spectrum (NPS). To generate the lookup tables, the American College of Radiology CT accreditation phantom was scanned on a multidetector CT scanner (Revolution CT, GE Healthcare) at 120 kV and tube current varied manually from 20 to 240 mAs. Images were reconstructed using a reference reconstruction algorithm and four levels of an in‐house iterative reconstruction algorithm with different regularization strengths (IR1–IR4). The task‐based MTF and NPS were estimated from the measured images to create lookup tables of scaling factors that convert between d\u27gen and noise standard deviation. The performance of the proposed d\u27gen‐AEC method in providing a desired IQ level over a range of iterative reconstruction algorithms was evaluated using the American College of Radiology (ACR) phantom with elliptical shell and using a human reader evaluation on anthropomorphic phantom images. Results The study of the ACR phantom with elliptical shell demonstrated reasonable agreement between the d\u27gen predicted by the lookup table and d\u27 measured in the images, with a mean absolute error of 15% across all dose levels and maximum error of 45% at the lowest dose level with the elliptical shell. For the anthropomorphic phantom study, the mean reader scores for images resulting from the d\u27gen‐AEC method were 3.3 (reference image), 3.5 (IR1), 3.6 (IR2), 3.5 (IR3), and 2.2 (IR4). When using the d\u27gen‐AEC method, the observers’ IQ scores for the reference reconstruction were statistical equivalent to the scores for IR1, IR2, and IR3 iterative reconstructions (P \u3e 0.35). The d\u27gen‐AEC method achieved this equivalent IQ at lower dose for the IR scans compared to the reference scans. Conclusions A novel AEC method, based on a generalized detectability index, was investigated. The proposed method can be used with some existing AEC systems to derive the tube current profile for iterative reconstruction algorithms. The results provide preliminary evidence that the proposed d\u27gen‐AEC can produce similar IQ across different iterative reconstruction approaches at different dose levels

Stochastic Approximation and Modern Model-Based Designs for Dose-Finding Clinical Trials

In 1951 Robbins and Monro published the seminal article on stochastic approximation and made a specific reference to its application to the "estimation of a quantal using response, nonresponse data." Since the 1990s, statistical methodology for dose-finding studies has grown into an active area of research. The dose-finding problem is at its core a percentile estimation problem and is in line with what the Robbins--Monro method sets out to solve. In this light, it is quite surprising that the dose-finding literature has developed rather independently of the older stochastic approximation literature. The fact that stochastic approximation has seldom been used in actual clinical studies stands in stark contrast with its constant application in engineering and finance. In this article, I explore similarities and differences between the dose-finding and the stochastic approximation literatures. This review also sheds light on the present and future relevance of stochastic approximation to dose-finding clinical trials. Such connections will in turn steer dose-finding methodology on a rigorous course and extend its ability to handle increasingly complex clinical situations.Comment: Published in at http://dx.doi.org/10.1214/10-STS334 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

A Database for Estimating Organ Dose for Chest and Head CT Scans for Arbitrary Spectra and Angular Tube Current Modulation

Purpose: The purpose of this study was to develop a database for estimating organ dose in a voxelized patient model for coronary angiography and brain perfusion CT acquisitions with any spectra and angular tube current modulation setting. The database enables organ dose estimation for existing and novel acquisition techniques without requiring Monte Carlo simulations. Methods: The study simulated transport of monoenergetic photons between 5 and 150 keV for 1000 projections over 360◦ through anthropomorphic voxelized female chest and head (0◦ and 30◦ tilt) phantoms and standard head and body CTDI dosimetry cylinders. The simulations resulted in tables of normalized dose deposition for several radiosensitive organs quantifying the organ dose per emitted photon for each incident photon energy and projection angle for coronary angiography and brain perfusion acquisitions. The values in a table can be multiplied by an incident spectrum and number of photons at each projection angle and then summed across all energies and angles to estimate total organ dose. Scanner-specific organ dose may be approximated by normalizing the database-estimated organ dose by the database-estimated CTDIvol and multiplying by a physical CTDIvol measurement. Two examples are provided demonstrating how to use the tables to estimate relative organ dose. In the first, the change in breast and lung dose during coronary angiography CT scans is calculated for reduced kVp, angular tube current modulation, and partial angle scanning protocols relative to a reference protocol. In the second example, the change in dose to the eye lens is calculated for a brain perfusion CT acquisition in which the gantry is tilted 30◦ relative to a nontilted scan. Results: Our database provides tables of normalized dose deposition for several radiosensitive organs irradiated during coronary angiography and brain perfusion CT scans. Validation results indicate total organ doses calculated using our database are within 1% of those calculated using Monte Carlo simulations with the same geometry and scan parameters for all organs except red bone marrow (within 6%), and within 23% of published estimates for different voxelized phantoms. Results from the example of using the database to estimate organ dose for coronary angiography CT acquisitions show 2.1%, 1.1%, and −32% change in breast dose and 2.1%, −0.74%, and 4.7% change in lung dose for reduced kVp, tube current modulated, and partial angle protocols, respectively, relative to the reference protocol. Results show −19.2% difference in dose to eye lens for a tilted scan relative to a nontilted scan. The reported relative changes in organ doses are presented without quantification of image quality and are for the sole purpose of demonstrating the use of the proposed database. Conclusions: The proposed database and calculation method enable the estimation of organ dose for coronary angiography and brain perfusion CT scans utilizing any spectral shape and angular tube current modulation scheme by taking advantage of the precalculated Monte Carlo simulation results. The database can be used in conjunction with image quality studies to develop optimized acquisition techniques and may be particularly beneficial for optimizing dual kVp acquisitions for which numerous kV, mA, and filtration combinations may be investigated. © 2012 American Association of Physicists in Medicine

Optimization of spatiotemporally fractionated radiotherapy treatments with bounds on the achievable benefit

Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, may lower treatment side effects without compromising tumor control. This is achieved by hypofractionating parts of the tumor while delivering approximately uniformly fractionated doses to the healthy tissue. Optimization of such treatments is based on biologically effective dose (BED), which leads to computationally challenging nonconvex optimization problems. Current optimization methods yield only locally optimal plans, and it has been unclear whether these are close to the global optimum. We present an optimization model to compute rigorous bounds on the normal tissue BED reduction achievable by such plans. The approach is demonstrated on liver tumors, where the primary goal is to reduce mean liver BED without compromising other treatment objectives. First a uniformly fractionated reference plan is computed using convex optimization. Then a nonconvex quadratically constrained quadratic programming model is solved to local optimality to compute a spatiotemporally fractionated plan that minimizes mean liver BED subject to the constraints that the plan is no worse than the reference plan with respect to all other planning goals. Finally, we derive a convex relaxation of the second model in the form of a semidefinite programming problem, which provides a lower bound on the lowest achievable mean liver BED. The method is presented on 5 cases with distinct geometries. The computed spatiotemporal plans achieve 12-35% mean liver BED reduction over the reference plans, which corresponds to 79-97% of the gap between the reference mean liver BEDs and our lower bounds. This indicates that spatiotemporal treatments can achieve substantial reduction in normal tissue BED, and that local optimization provides plans that are close to realizing the maximum potential benefit

Novel X-ray imaging technology enables significant patient dose reduction in interventional cardiology while maintaining diagnostic image quality

Objectives: The purpose of this study was to quantify the reduction in patient radiation dose during coronary angiography (CA) by a new X-ray technology, and to assess its impact on diagnostic image quality. Background: Recently, a novel X-ray imaging technology has become available for interventional cardiology, using advanced image processing and an optimized acquisition chain for radiation dose reduction. Methods: 70 adult patients were randomly assigned to a reference X-ray system or the novel X-ray system. Patient demographics were registered and exposure parameters were recorded for each radiation event. Clinical image quality was assessed for both patient groups. Results: With the same angiographic technique and a comparable patient population, the new imaging technology was associated with a 75% reduction in total kerma-area product (KAP) value (decrease from 47 Gycm(2) to 12 Gycm(2), P<0.001). Clinical image quality showed an equivalent detail and contrast for both imaging systems. On the other hand, the subjective appreciation of noise was more apparent in images of the new image processing system, acquired at lower doses, compared to the reference system. However, the higher noise content did not affect the overall image quality score, which was adequate for diagnosis in both systems. Conclusions: For the first time, we present a new X-ray imaging technology, combining advanced noise reduction algorithms and an optimized acquisition chain, which reduces patient radiation dose in CA drastically (75%), while maintaining diagnostic image quality. Use of this technology may further improve the radiation safety of cardiac angiography and interventions