Peter B. Greer

Dosimetric properties of an amorphous silicon electronic portal imaging device for verification of dynamic intensity modulated radiation therapy

Dosimetric properties of an amorphous silicon electronic portal imaging device (EPID) for verification of dynamic intensity modulated radiation therapy (IMRT) delivery were investigated. The EPID was utilized with continuous frame-averaging during the beam delivery. Properties studied included effect of buildup, dose linearity, field size response, sampling of rapid multileaf collimator (MLC) leaf speeds, response to dose-rate fluctuations, memory effect, and reproducibility. The dependence of response on EPID calibration and a dead time in image frame acquisition occurring every 64 frames were measured. EPID measurements were also compared to ion chamber and film for open and wedged static fields and IMRT fields. The EPID was linear with dose and dose rate, and response to MLC leaf speeds up to 2.5 cm s(-1) was found to be linear. A field size dependent response of up to 5% relative to dmax ion-chamber measurement was found. Reproducibility was within 0.8% (1 standard deviation) for an IMRT delivery recorded at intervals over a period of one month. The dead time in frame acquisition resulted in errors in the EPID that increased with leaf speed and were over 20% for a 1 cm leaf gap moving at 1.0 cm s(-1). The EPID measurements were also found to depend on the input beam profile utilized for EPID flood-field calibration. The EPID shows promise as a device for verification of IMRT, the major limitation currently being due to dead-time in frame acquisition.

An Atlas-Based Electron Density Mapping Method for Magnetic Resonance Imaging (MRI)-Alone Treatment Planning and Adaptive MRI-Based Prostate Radiation Therapy

PURPOSE Prostate radiation therapy dose planning directly on magnetic resonance imaging (MRI) scans would reduce costs and uncertainties due to multimodality image registration. Adaptive planning using a combined MRI-linear accelerator approach will also require dose calculations to be performed using MRI data. The aim of this work was to develop an atlas-based method to map realistic electron densities to MRI scans for dose calculations and digitally reconstructed radiograph (DRR) generation. METHODS AND MATERIALS Whole-pelvis MRI and CT scan data were collected from 39 prostate patients. Scans from 2 patients showed significantly different anatomy from that of the remaining patient population, and these patients were excluded. A whole-pelvis MRI atlas was generated based on the manually delineated MRI scans. In addition, a conjugate electron-density atlas was generated from the coregistered computed tomography (CT)-MRI scans. Pseudo-CT scans for each patient were automatically generated by global and nonrigid registration of the MRI atlas to the patient MRI scan, followed by application of the same transformations to the electron-density atlas. Comparisons were made between organ segmentations by using the Dice similarity coefficient (DSC) and point dose calculations for 26 patients on planning CT and pseudo-CT scans. RESULTS The agreement between pseudo-CT and planning CT was quantified by differences in the point dose at isocenter and distance to agreement in corresponding voxels. Dose differences were found to be less than 2%. Chi-squared values indicated that the planning CT and pseudo-CT dose distributions were equivalent. No significant differences (p > 0.9) were found between CT and pseudo-CT Hounsfield units for organs of interest. Mean ± standard deviation DSC scores for the atlas-based segmentation of the pelvic bones were 0.79 ± 0.12, 0.70 ± 0.14 for the prostate, 0.64 ± 0.16 for the bladder, and 0.63 ± 0.16 for the rectum. CONCLUSIONS The electron-density atlas method provides the ability to automatically define organs and map realistic electron densities to MRI scans for radiotherapy dose planning and DRR generation. This method provides the necessary tools for MRI-alone treatment planning and adaptive MRI-based prostate radiation therapy.

MRI-guided prostate radiation therapy planning: Investigation of dosimetric accuracy of MRI-based dose planning

BACKGROUND AND PURPOSE Dose planning requires a CT scan which provides the electron density distribution for dose calculation. MR provides superior soft tissue contrast compared to CT and the use of MR-alone for prostate planning would provide further benefits such as lower cost to the patient. This study compares the accuracy of MR-alone based dose calculations with bulk electron density assignment to CT-based dose calculations for prostate radiotherapy. MATERIALS AND METHODS CT and whole pelvis MR images were contoured for 39 prostate patients. Plans with uniform density and plans with bulk density values assigned to bone and tissue were compared to the patients gold standard full density CT plan. The optimal bulk density for bone was calculated using effective depth measurements. The plans were evaluated using ICRU point doses, dose volume histograms, and Chi comparisons. Differences in spatial uniformity were investigated for the CT and MR scans. RESULTS The calculated dose for CT bulk bone and tissue density plans was 0.1±0.6% (mean±1 SD) higher than the corresponding full density CT plan. MR bulk bone and tissue density plans were 1.3±0.8% lower than the full density CT plan. CT uniform density plans and MR uniform density plans were 1.4±0.9% and 2.6±0.9% lower, respectively. Paired t-tests performed on specific points on the DVH graphs showed that points on DVHs for all bulk electron density plans were equivalent with two exceptions. There was no significant difference between doses calculated on Pinnacle and Eclipse. The dose distributions of six patients produced Chi values outside the acceptable range of values when MR-based plans were compared to the full density plan. CONCLUSIONS MR-alone bulk density planning is feasible provided bone is assigned a density, however, manual segmentation of bone on MR images will have to be replaced with automatic methods. The major dose differences for MR bulk density plans are due to differences in patient external contours introduced by the MR couch-top and pelvic coil.

Cone beam computerized tomography: the effect of calibration of the Hounsfield unit number to electron density on dose calculation accuracy for adaptive radiation therapy

The availability of cone beam computerized tomography (CBCT) images at the time of treatment has opened possibilities for dose calculations representing the delivered dose for adaptive radiation therapy. A significant component in the accuracy of dose calculation is the calibration of the Hounsfield unit (HU) number to electron density (ED). The aim of this work is to assess the impact of HU to ED calibration phantom insert composition and phantom volume on dose calculation accuracy for CBCT. CBCT HU to ED calibration curves for different commercial phantoms were measured and compared. The effect of the scattering volume of the phantom on the HU to ED calibration was examined as a function of phantom length and radial diameter. The resulting calibration curves were used at the treatment planning system to calculate doses for geometrically simple phantoms and a pelvic anatomical phantom to compare against measured doses. Three-dimensional dose distributions for the pelvis phantom were calculated using the HU to ED curves and compared using Chi comparisons. The HU to ED calibration curves for the commercial phantoms diverge at densities greater than that of water, depending on the elemental composition of the phantom insert. The effect of adding scatter material longitudinally, increasing the phantom length from 5 cm to 26 cm, was found to be up to 260 HU numbers for the high-density insert. The change in the HU value, by increasing the diameter of the phantom from 18 to 40 cm, was found to be up to 1200 HU for the high-density insert. The effect of phantom diameter on the HU to ED curve can lead to dose differences for 6 MV and 18 MV x-rays under bone inhomogeneities of up to 20% in extreme cases. These results show significant dosimetric differences when using a calibration phantom with materials which are not tissue equivalent. More importantly, the amount of scattering material used with the HU to ED calibration phantom has a significant effect on the dosimetric accuracy, particularly in the radial direction.

Evaluation of an algorithm for the assessment of the MTF using an edge method

An algorithm to calculate the presampling modulation transfer function (MTF) of an imaging system from an angled edge image has its own inherent transfer function. Factors such as the angle of the sampling aperture to the edge, registration of edge function profiles using the determined edge angle, differentiation, smoothing, and folding all combine to produce the frequency response of the algorithm. In this work, the profile registration transfer function accounting for an error in the determined edge angle has been derived. This has been incorporated with other, previously reported, algorithm component transfer functions to fully characterize the MTF calculation algorithm. When registering profiles, small errors in the edge angle determination were found to result in large errors in the MTF, as the misalignment errors increase with the number of profiles. For example, registering 50 profiles a 0.07 degree error in a 7 degree edge angle (1% error) produces a 36% error in the MTF at the system cutoff frequency f=f(c) when profiles are oversampled at a frequency f(s)=8f(c)(f(c) is defined as the maximum frequency reproducible without aliasing when sampling at the limiting system Nyquist frequency f(s) = 2f(c)). These results highlight the importance of quantifying the transfer function of the algorithm used to determine an imaging system modulation transfer function. The MTF calculation algorithm and the transfer function analysis have been incorporated into a Windows-based software program to be made available for general use.

Time to biochemical failure and prostate-specific antigen doubling time as surrogates for prostate cancer-specific mortality : evidence from the TROG 96.01 randomised controlled trial

BACKGROUND Surrogate endpoints for prostate cancer-specific mortality after curative primary treatment are not well established. We sought to assess time to biochemical failure (TTBF) and prostate-specific antigen doubling time (PSADT) after failure of curative treatment as candidates for this endpoint. METHODS PSA and survival data from the Trans-Tasman Radiation Oncology Group (TROG) 96.01 trial were used to assess surrogate candidates. Between June 28, 1996, and Feb 16, 2000, 802 eligible men with locally advanced prostate cancer were randomly allocated to prostatic irradiation alone, or to 3 or 6 months of maximum short-term androgen deprivation (STAD) before and during radiation. Successful surrogates were required to satisfy the Prentice criteria and to predict the trial finding. The TROG 96.01 trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482. FINDINGS 6 months of STAD was shown to significantly decrease prostate cancer-specific mortality compared with radiation alone, but 3 months of STAD did not result in a decrease. Relative to radiation alone, the hazard ratio of prostate cancer-specific mortality from randomisation was 0.95 (95% CI 0.63-1.41; p=0.79) in the 3-month STAD treatment arm and 0.56 (0.36-0.88; p=0.01) in the 6-month arm. PSADT predicted the trial finding and satisfied all four Prentice criteria at the cutpoints of less than 12 months and less than 15 months, with proportion of treatment effect ratios between 0.36 and 0.56. Time to biochemical failure was better than PSADT at predicting the trial finding and satisfying all four Prentice criteria at cutpoints of less than 1.5, less than 2, and less than 2.5 years, with proportion of treatment effect ratios between 0.45 and 0.64. INTERPRETATION This study provides proof of principle that TTBF and PSADT can be useful as surrogate endpoints for prostate cancer-specific mortality and offer potential to substantially reduce follow up in clinical trials. These endpoints now require assessment in multi-trial meta-analyses before use in clinical trials.

Does the planning dose–volume histogram represent treatment doses in image-guided prostate radiation therapy? Assessment with cone-beam computerised tomography scans

PURPOSE To assess the accuracy of the initial CT plan dose-volume histograms (DVHs) for prostate, rectum and bladder by comparison to delivered doses determined from cone beam CT (CBCT) scans acquired during image-guided treatment. MATERIALS AND METHODS Twelve prostate patients were treated using daily implanted fiducial guidance and following local protocol for bladder and rectal preparation. CBCT scans were acquired twice weekly and contoured for prostate, rectum and bladder. The planned beams were applied to all CBCT scans to determine the delivered doses. Prostate dose coverage was assessed by the proportion of the CTV fully encompassed by the 95% and 98% isodose lines. Rectal and bladder volumes receiving 40 Gy, 60 Gy and 70 Gy at treatment were compared to the initial plan, with significance determined using the one-sample t-test. RESULTS Four patients showed marginally compromised CTV coverage by the 95% isodose at all CBCT plans. For nine patients the initial plan rectal DVH was significantly outside the range of the treatment DVHs. CONCLUSIONS Dose coverage of the prostate was not achieved for all patients. Observed rectal and bladder doses were higher than predicted. The initial treatment plan cannot be assumed to represent accurate normal tissue doses.

Measurement and modeling of the effect of support arm backscatter on dosimetry with a varian EPID.

PURPOSE Amorphous silicon EPIDs have been used for planar dose verification in IMRT treatments for many years. The support arm used to attach some types of EPIDs to linear accelerators can introduce inaccuracies to dosimetry measurements due to the presence of metallic parts in their structures. It is demonstrated that this uncertainty may be as large as approximately 6% of maximum image signal for large fields. In this study, a method has been described to quantify, model and correct for the effect of backscattered radiation from the EPID support arm (E-Arm type, Varian Medical Systems). METHODS Measurements of a support arm backscatter kernel were made using several 1 x 1 cm2 6 MV pencil beam irradiations at a sample of positions over the sensitive area of the EPID in standard clinical setup and repeated with the EPID removed from the support arm but at the same positions. A curve-fit to the subtraction of EPID response obtained on and off the arm was used to define the backscatter kernel. The measured kernel was compared with a backscatter kernel obtained by Monte Carlo simulations with EGS/BEAM code. A backscatter dose prediction using the measured backscatter kernel was added to an existing EPID dose prediction model. The improvement in the agreement of the modified model predictions with EPID measurements for a number of open fields and IMRT beams were investigated by comparison to the original model results. RESULTS Considering all functions tested to find the best functional fit to the data points, a broad Gaussian curve proved to be the optimum fit to the backscatter data. The best fit through the Monte Carlo simulated backscatter kernel was also found to be a Gaussian curve. The maximum decrease in normalized root mean squared deviation of the measured and modeled EPID image profiles for open fields was 13.7% for a 15 x 15 cm2 field with no decrease observed for a 3 x 3 cm2 (the smallest) field as it was not affected by the arm backscatter. Gamma evaluation (2%, 2 mm criteria) showed the improvement in agreement between the model and measurement results when the backscatter was incorporated. The average increase in Gamma pass rate was 2% for head and neck and 1.3% for prostate IMRT fields investigated in this study. CONCLUSIONS The application of the backscatter kernel determined in this study improved the accuracy of dosimetry using a Varian EPID with E-arm for open fields of different sizes: Eight head and neck and seven prostate IMRT fields. Further improvement in the agreement between the model predictions and EPID measurements requires more sophisticated modeling of the backscatter.

Patient Specific Prostate Segmentation in 3-D Magnetic Resonance Images

Accurate localization of the prostate and its surrounding tissue is essential in the treatment of prostate cancer. This paper presents a novel approach to fully automatically segment the prostate, including its seminal vesicles, within a few minutes of a magnetic resonance (MR) scan acquired without an endorectal coil. Such MR images are important in external beam radiation therapy, where using an endorectal coil is highly undesirable. The segmentation is obtained using a deformable model that is trained on-the-fly so that it is specific to the patients scan. This case specific deformable model consists of a patient specific initialized triangulated surface and image feature model that are trained during its initialization. The image feature model is used to deform the initialized surface by template matching image features (via normalized cross-correlation) to the features of the scan. The resulting deformations are regularized over the surface via well established simple surface smoothing algorithms, which is then made anatomically valid via an optimized shape model. Mean and median Dices similarity coefficients (DSCs) of 0.85 and 0.87 were achieved when segmenting 3T MR clinical scans of 50 patients. The median DSC result was equal to the inter-rater DSC and had a mean absolute surface error of 1.85 mm. The approach is showed to perform well near the apex and seminal vesicles of the prostate.

Detection and correction for EPID and gantry sag during arc delivery using cine EPID imaging

PURPOSE Electronic portal imaging devices (EPIDs) have been studied and used for pretreatment and in-vivo dosimetry applications for many years. The application of EPIDs for dosimetry in arc treatments requires accurate characterization of the mechanical sag of the EPID and gantry during rotation. Several studies have investigated the effects of gravity on the sag of these systems but each have limitations. In this study, an easy experiment setup and accurate algorithm have been introduced to characterize and correct for the effect of EPID and gantry sag during arc delivery. METHODS Three metallic ball bearings were used as markers in the beam: two of them fixed to the gantry head and the third positioned at the isocenter. EPID images were acquired during a 360° gantry rotation in cine imaging mode. The markers were tracked in EPID images and a robust in-house developed MATLAB code was used to analyse the images and find the EPID sag in three directions as well as the EPID + gantry sag by comparison to the reference gantry zero image. The algorithm results were then tested against independent methods. The method was applied to compare the effect in clockwise and counter clockwise gantry rotations and different source-to-detector distances (SDDs). The results were monitored for one linear accelerator over a course of 15 months and six other linear-accelerators from two treatment centers were also investigated using this method. The generalized shift patterns were derived from the data and used in an image registration algorithm to correct for the effect of the mechanical sag in the system. The Gamma evaluation (3%, 3 mm) technique was used to investigate the improvement in alignment of cine EPID images of a fixed field, by comparing both individual images and the sum of images in a series with the reference gantry zero image. RESULTS The mechanical sag during gantry rotation was dependent on the gantry angle and was larger in the in-plane direction, although the patterns were not identical for various linear-accelerators. The reproducibility of measurements was within 0.2 mm over a period of 15 months. The direction of gantry rotation and SDD did not affect the results by more than 0.3 mm. Results of independent tests agreed with the algorithm within the accuracy of the measurement tools. When comparing summed images, the percentage of points with Gamma index <1 increased from 85.4% to 94.1% after correcting for the EPID sag, and to 99.3% after correction for gantry + EPID sag. CONCLUSIONS The measurement method and algorithms introduced in this study use cine-images, are highly accurate, simple, fast, and reproducible. It tests all gantry angles and provides a suitable automatic analysis and correction tool to improve EPID dosimetry and perform comprehensive linac QA for arc treatments.