Characterization of image quality and image-guidance performance of a preclinical microirradiator.

PURPOSE: To assess image quality and image-guidance capabilities of a cone-beam CT based small-animal image-guided irradiation unit (micro-IGRT). METHODS: A micro-IGRT system has been developed in collaboration with the authors' laboratory as a means to study the radiobiological effects of conformal radiation dose distributions in small animals. The system, the X-Rad 225Cx, consists of a 225 kVp x-ray tube and a flat-panel amorphous silicon detector mounted on a rotational C-arm gantry and is capable of both fluoroscopic x-ray and cone-beam CT imaging, as well as image-guided placement of the radiation beams. Image quality (voxel noise, modulation transfer, CT number accuracy, and geometric accuracy characteristics) was assessed using water cylinder and micro-CT test phantoms. Image guidance was tested by analyzing the dose delivered to radiochromic films fixed to BB's through the end-to-end process of imaging, targeting the center of the BB, and irradiation of the film/BB in order to compare the offset between the center of the field and the center of the BB. Image quality and geometric studies were repeated over a 5-7 month period to assess stability. RESULTS: CT numbers reported were found to be linear (R2 0.998) and the noise for images of homogeneous water phantom was 30 HU at imaging doses of approximately 1 cGy (to water). The presampled MTF at 50% and 10% reached 0.64 and 1.35 mm(-1), respectively. Targeting accuracy by means of film irradiations was shown to have a mean displacement error of [deltax, deltay, deltaz] = [-0.12, -0.05, -0.02] mm, with standard deviations of [0.02, 0.20, 0.17] mm. The system has proven to be stable over time, with both the image quality and image-guidance performance being reproducible for the duration of the studies. CONCLUSIONS: The micro-IGRT unit provides soft-tissue imaging of small-animal anatomy at acceptable imaging doses (< or =1 cGy). The geometric accuracy and targeting systems permit dose placement with submillimeter accuracy and precision. The system has proven itself to be stable over 2 yr of routine laboratory use (>1800 irradiations) and provides a platform for the exploration of targeted radiation effects in small-animal models.

Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose-volume outcome relationships.

Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

A comparison of Monte Carlo dose calculation denoising techniques.

Recent studies have demonstrated that Monte Carlo (MC) denoising techniques can reduce MC radiotherapy dose computation time significantly by preferentially eliminating statistical fluctuations ('noise') through smoothing. In this study, we compare new and previously published approaches to MC denoising, including 3D wavelet threshold denoising with sub-band adaptive thresholding, content adaptive mean-median-hybrid (CAMH) filtering, locally adaptive Savitzky-Golay curve-fitting (LASG), anisotropic diffusion (AD) and an iterative reduction of noise (IRON) method formulated as an optimization problem. Several challenging phantom and computed-tomography-based MC dose distributions with varying levels of noise formed the test set. Denoising effectiveness was measured in three ways: by improvements in the mean-square-error (MSE) with respect to a reference (low noise) dose distribution; by the maximum difference from the reference distribution and by the 'Van Dyk' pass/fail criteria of either adequate agreement with the reference image in low-gradient regions (within 2% in our case) or, in high-gradient regions, a distance-to-agreement-within-2% of less than 2 mm. Results varied significantly based on the dose test case: greater reductions in MSE were observed for the relatively smoother phantom-based dose distribution (up to a factor of 16 for the LASG algorithm); smaller reductions were seen for an intensity modulated radiation therapy (IMRT) head and neck case (typically, factors of 2-4). Although several algorithms reduced statistical noise for all test geometries, the LASG method had the best MSE reduction for three of the four test geometries, and performed the best for the Van Dyk criteria. However, the wavelet thresholding method performed better for the head and neck IMRT geometry and also decreased the maximum error more effectively than LASG. In almost all cases, the evaluated methods provided acceleration of MC results towards statistically more accurate results.

The influence of brachytherapy dose heterogeneity on estimates of alpha/beta for prostate cancer.

The sensitivity of estimates of alpha/beta for prostate tumours to dose heterogeneity in 125I brachytherapy implants, as well as to variation in selected radiobiological parameters, is analysed. The tumour control probabilities of brachytherapy and external beam radiotherapy are equated for ranges of alpha, Tpot, RBE and external beam dose. For each combination of parameters, the equality is used to derive the value of alpha/beta. Different clinical (non-uniform) brachytherapy dose distributions, and three uniform brachytherapy dose distributions (120, 144 and 160 Gy) are used. For 'nominal' input parameter values of Tpot = 45 days, alpha = 0.2 Gy(-1), RBE = 1.4, and an external beam dose of 70 Gy, the values obtained for alpha/beta ranged between 2.1 and 12.3 Gy for all of the clinical DVHs, between 2.1 and 3.8 Gy for the better quality clinical implants and between 1.0 and 1.8 Gy for the uniform brachytherapy doses. When only 2% of the volume receiving the lowest dose is omitted from the clinical DVHs, the estimated alpha/beta values ranged between 1.4 and 2.1 Gy. When ranges of input parameters were also considered, the overall range of alpha/beta values for the clinical brachytherapy dose distributions lay between 1.1 and 12.3 Gy for the three best clinical implants, and between 0.7 and 6.3 Gy for uniform doses. We conclude that estimation of alpha/beta without taking into account dose heterogeneity and inter-patient variation may underestimate the actual value alpha/beta.

Multi-institutional dosimetric and geometric commissioning of image-guided small animal irradiators.

PURPOSE: To compare the dosimetric and geometric properties of a commercial x-ray based image-guided small animal irradiation system, installed at three institutions and to establish a complete and broadly accessible commissioning procedure. METHODS: The system consists of a 225 kVp x-ray tube with fixed field size collimators ranging from 1 to 44 mm equivalent diameter. The x-ray tube is mounted opposite a flat-panel imaging detector, on a C-arm gantry with 360° coplanar rotation. Each institution performed a full commissioning of their system, including half-value layer, absolute dosimetry, relative dosimetry (profiles, percent depth dose, and relative output factors), and characterization of the system geometry and mechanical flex of the x-ray tube and detector. Dosimetric measurements were made using Farmer-type ionization chambers, small volume air and liquid ionization chambers, and radiochromic film. The results between the three institutions were compared. RESULTS: At 225 kVp, with 0.3 mm Cu added filtration, the first half value layer ranged from 0.9 to 1.0 mm Cu. The dose-rate in-air for a 40 × 40 mm(2) field size, at a source-to-axis distance of 30 cm, ranged from 3.5 to 3.9 Gy/min between the three institutions. For field sizes between 2.5 mm diameter and 40 × 40 mm(2), the differences between percent depth dose curves up to depths of 3.5 cm were between 1% and 4% on average, with the maximum difference being 7%. The profiles agreed very well for fields >5 mm diameter. The relative output factors differed by up to 6% for fields larger than 10 mm diameter, but differed by up to 49% for fields ≤5 mm diameter. The mechanical characteristics of the system (source-to-axis and source-to-detector distances) were consistent between all three institutions. There were substantial differences in the flex of each system. CONCLUSIONS: With the exception of the half-value layer, and mechanical properties, there were significant differences between the dosimetric and geometric properties of the three systems. This underscores the need for careful commissioning of each individual system for use in radiobiological experiments.