Repeated deep-inspiration breath-hold CT scans at planning underestimate the actual motion between breath-holds at treatment for lung cancer and lymphoma patients.

PURPOSE/OBJECTIVE: Deep-inspiration breath-hold (DIBH) during radiotherapy may reduce dose to the lungs and heart compared to treatment in free breathing. However, intra-fractional target shifts between several breath-holds may decrease target coverage. We compared target shifts between four DIBHs at the planning-CT session with those measured on CBCT-scans obtained pre- and post-DIBH treatments. MATERIAL/METHODS: Twenty-nine lung cancer and nine lymphoma patients were treated in DIBH. An external gating block was used as surrogate for the DIBH-level with a window of 2 mm. Four DIBH CT-scans were acquired: one for planning (CTDIBH3) and three additional (CTDIBH1,2,4) to assess the intra-DIBH target shifts at scanning by registration to CTDIBH3. During treatment, pre-treatment (CBCTpre) and post-treatment (CBCTpost) scans were acquired. For each pair of CBCTpre/post, the target intra-DIBH shift was determined. For lung cancer, tumour (GTV-Tlung) and lymph nodes (GTV-Nlung) were analysed separately. Group mean (GM), systematic and random errors, and GM for the absolute maximum shifts (GMmax) were calculated for the shifts between CTDIBH1,2,3,4 and between CBCTpre/post. RESULTS: For GTV-Tlung, GMmax was larger at CBCT than CT in all directions. GMmax in cranio-caudal direction was 3.3 mm (CT)and 6.1 mm (CBCT). The standard deviations of the shifts in the left-right and cranio-caudal directions were larger at CBCT than CT. For GTV-Nlung and CTVlymphoma, no difference was found in GMmax or SD. CONCLUSION: Intra-DIBH shifts at planning-CT session are generally smaller than intra-DIBH shifts observed at CBCTpre/post and therefore underestimate the intra-fractional DIBH uncertainty during treatment. Lung tumours show larger intra-fractional variations than lymph nodes and lymphoma targets.

Beam characterization and feasibility study for a small animal irradiation platform at clinical proton therapy facilities.

A deeper understanding of biological mechanisms to promote more efficient treatment strategies in proton therapy demands advances in preclinical radiation research. However this is often limited by insufficient availability of adequate infrastructures for precision image guided small animal proton irradiation. The project SIRMIO aims at filling this gap by developing a portable image-guided research platform for small animal irradiation, to be used at clinical facilities and allowing for a precision similar to a clinical treatment, when scaled down to the small animal size. This work investigates the achievable dosimetric properties of different lowest energy clinical proton therapy beams, manipulated by a dedicated portable beamline including active focusing after initial beam energy degradation and collimation. By measuring the lateral beam size in air close to the beam nozzle exit and the laterally integrated depth dose in water, an analytical beam model based on the beam parameters of the clinical beam at the Rinecker Proton Therapy Center was created for the lowest available clinical beam energy. The same approach was then applied to estimate the lowest energy beam model of different proton therapy facilities, Paul Scherrer Institute, Centre Antoine Lacassagne, Trento Proton Therapy Centre and the Danish Centre for Particle Therapy, based on their available beam commissioning data. This comparison indicated similar beam properties for all investigated sites, with emittance values of a few tens of mm·mrad. Finally, starting from these beam models, we simulated propagation through a novel beamline designed to manipulate the beam energy and size for precise small animal irradiation, and evaluated the resulting dosimetric properties in water. For all investigated initial clinical beams, similar dosimetric results suitable for small animal irradiation were found. This work supports the feasibility of the proposed SIRMIO beamline, promising suitable beam characteristics to allow for precise preclinical irradiation at clinical treatment facilities.

Fully automatic segmentation of arbitrarily shaped fiducial markers in cone-beam CT projections.

Radio-opaque fiducial markers of different shapes are often implanted in or near abdominal or thoracic tumors to act as surrogates for the tumor position during radiotherapy. They can be used for real-time treatment adaptation, but this requires a robust, automatic segmentation method able to handle arbitrarily shaped markers in a rotational imaging geometry such as cone-beam computed tomography (CBCT) projection images and intra-treatment images. In this study, we propose a fully automatic dynamic programming (DP) assisted template-based (TB) segmentation method. Based on an initial DP segmentation, the DPTB algorithm generates and uses a 3D marker model to create 2D templates at any projection angle. The 2D templates are used to segment the marker position as the position with highest normalized cross-correlation in a search area centered at the DP segmented position. The accuracy of the DP algorithm and the new DPTB algorithm was quantified as the 2D segmentation error (pixels) compared to a manual ground truth segmentation for 97 markers in the projection images of CBCT scans of 40 patients. Also the fraction of wrong segmentations, defined as 2D errors larger than 5 pixels, was calculated. The mean 2D segmentation error of DP was reduced from 4.1 pixels to 3.0 pixels by DPTB, while the fraction of wrong segmentations was reduced from 17.4% to 6.8%. DPTB allowed rejection of uncertain segmentations as deemed by a low normalized cross-correlation coefficient and contrast-to-noise ratio. For a rejection rate of 9.97%, the sensitivity in detecting wrong segmentations was 67% and the specificity was 94%. The accepted segmentations had a mean segmentation error of 1.8 pixels and 2.5% wrong segmentations.

Determining the mechanical properties of a radiochromic silicone-based 3D dosimeter.

New treatment modalities in radiotherapy (RT) enable delivery of highly conformal dose distributions in patients. This creates a need for precise dose verification in three dimensions (3D). A radiochromic silicone-based 3D dosimetry system has recently been developed. Such a dosimeter can be used for dose verification in deformed geometries, which requires knowledge of the dosimeter's mechanical properties. In this study we have characterized the dosimeter's elastic behaviour under tensile and compressive stress. In addition, the dose response under strain was determined. It was found that the dosimeter behaved as an incompressible hyperelastic material with a non-linear stress/strain curve and with no observable hysteresis or plastic deformation even at high strains. The volume was found to be constant within a 2% margin at deformations up to 60%. Furthermore, it was observed that the dosimeter returned to its original geometry within a 2% margin when irradiated under stress, and that the change in optical density per centimeter was constant regardless of the strain during irradiation. In conclusion, we have shown that this radiochromic silicone-based dosimeter's mechanical properties make it a viable candidate for dose verification in deformable 3D geometries.

An interdimensional correlation framework for real-time estimation of six degree of freedom target motion using a single x-ray imager during radiotherapy.

Increasing evidence suggests that intrafraction tumour motion monitoring needs to include both 3D translations and 3D rotations. Presently, methods to estimate the rotation motion require the 3D translation of the target to be known first. However, ideally, translation and rotation should be estimated concurrently. We present the first method to directly estimate six-degree-of-freedom (6DoF) motion from the target's projection on a single rotating x-ray imager in real-time. This novel method is based on the linear correlations between the superior-inferior translations and the motion in the other five degrees-of-freedom. The accuracy of the method was evaluated in silico with 81 liver tumour motion traces from 19 patients with three implanted markers. The ground-truth motion was estimated using the current gold standard method where each marker's 3D position was first estimated using a Gaussian probability method, and the 6DoF motion was then estimated from the 3D positions using an iterative method. The 3D position of each marker was projected onto a gantry-mounted imager with an imaging rate of 11 Hz. After an initial 110° gantry rotation (200 images), a correlation model between the superior-inferior translations and the five other DoFs was built using a least square method. The correlation model was then updated after each subsequent frame to estimate 6DoF motion in real-time. The proposed algorithm had an accuracy (±precision) of -0.03 ± 0.32 mm, -0.01 ± 0.13 mm and 0.03 ± 0.52 mm for translations in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions respectively; and, 0.07 ± 1.18°, 0.07 ± 1.00° and 0.06 ± 1.32° for rotations around the LR, SI and AP axes respectively on the dataset. The first method to directly estimate real-time 6DoF target motion from segmented marker positions on a 2D imager was devised. The algorithm was evaluated using 81 motion traces from 19 liver patients and was found to have sub-mm and sub-degree accuracy.

Determining appropriate imaging parameters for kilovoltage intrafraction monitoring: an experimental phantom study.

Kilovoltage intrafraction monitoring (KIM) utilises the kV imager during treatment for real-time tracking of prostate fiducial markers. However, its effectiveness relies on sufficient image quality for the fiducial tracking task. To guide the performance characterisation of KIM under different clinically relevant conditions, the effect of different kV parameters and patient size on image quality, and quantification of MV scatter from the patient to the kV detector panel were investigated in this study. Image quality was determined for a range of kV acquisition frame rates, kV exposure, MV dose rates and patient sizes. Two methods were used to determine image quality; the ratio of kV signal through the patient to the MV scatter from the patient incident on the kilovoltage detector, and the signal-to-noise ratio (SNR). The effect of patient size and frame rate on MV scatter was evaluated in a homogeneous CIRS pelvis phantom and marker segmentation was determined utilising the Rando phantom with embedded markers. MV scatter incident on the detector was shown to be dependent on patient thickness and frame rate. The segmentation code was shown to be successful for all frame rates above 3 Hz for the Rando phantom corresponding to a kV to MV ratio of 0.16 and an SNR of 1.67. For a maximum patient dimension less than 36.4 cm the conservative kV parameters of 5 Hz at 1 mAs can be used to reduce dose while retaining image quality, where the current baseline kV parameters of 10 Hz at 1 mAs is shown to be adequate for marker segmentation up to a patient dimension of 40 cm. In conclusion, the MV scatter component of image quality noise for KIM has been quantified. For most prostate patients, use of KIM with 10 Hz imaging at 1 mAs is adequate however image quality can be maintained and imaging dose reduced by altering existing acquisition parameters.

Real-time segmentation of multiple implanted cylindrical liver markers in kilovoltage and megavoltage x-ray images.

Gold markers implanted in or near a tumor can be used as x-ray visible landmarks for image based tumor localization. The aim of this study was to develop and demonstrate fast and reliable real-time segmentation of multiple liver tumor markers in intra-treatment kV and MV images and in cone-beam CT (CBCT) projections, for real-time motion management. Thirteen patients treated with conformal stereotactic body radiation therapy in three fractions had 2-3 cylindrical gold markers implanted in the liver prior to treatment. At each fraction, the projection images of a pre-treatment CBCT scan were used for automatic generation of a 3D marker model that consisted of the size, orientation, and estimated 3D trajectory of each marker during the CBCT scan. The 3D marker model was used for real-time template based segmentation in subsequent x-ray images by projecting each marker's 3D shape and likely 3D motion range onto the imager plane. The segmentation was performed in intra-treatment kV images (526 marker traces, 92,097 marker projections) and MV images (88 marker traces, 22,382 marker projections), and in post-treatment CBCT projections (42 CBCT scans, 71,381 marker projections). 227 kV marker traces with low mean contrast-to-noise ratio were excluded as markers were not visible due to MV scatter. Online segmentation times measured for a limited dataset were used for estimating real-time segmentation times for all images. The percentage of detected markers was 94.8% (kV), 96.1% (MV), and 98.6% (CBCT). For the detected markers, the real-time segmentation was erroneous in 0.2-0.31% of the cases. The mean segmentation time per marker was 5.6 ms [2.1-12 ms] (kV), 5.5 ms [1.6-13 ms] (MV), and 6.5 ms [1.8-15 ms] (CBCT). Fast and reliable real-time segmentation of multiple liver tumor markers in intra-treatment kV and MV images and in CBCT projections was demonstrated for a large dataset.

Quality assurance for the clinical implementation of kilovoltage intrafraction monitoring for prostate cancer VMAT.

PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a real-time 3D tumor monitoring system for cancer radiotherapy. KIM uses the commonly available gantry-mounted x-ray imager as input, making this method potentially more widely available than dedicated real-time 3D tumor monitoring systems. KIM is being piloted in a clinical trial for prostate cancer patients treated with VMAT (NCT01742403). The purpose of this work was to develop clinical process and quality assurance (QA) practices for the clinical implementation of KIM. METHODS: Informed by and adapting existing guideline documents from other real-time monitoring systems, KIM-specific QA practices were developed. The following five KIM-specific QA tests were included: (1) static localization accuracy, (2) dynamic localization accuracy, (3) treatment interruption accuracy, (4) latency measurement, and (5) clinical conditions accuracy. Tests (1)-(4) were performed using KIM to measure static and representative patient-derived prostate motion trajectories using a 3D programmable motion stage supporting an anthropomorphic phantom with implanted gold markers to represent the clinical treatment scenario. The threshold for system tolerable latency is <1 s. The tolerances for all other tests are that both the mean and standard deviation of the difference between the programmed trajectory and the measured data are <1 mm. The (5) clinical conditions accuracy test compared the KIM measured positions with those measured by kV/megavoltage (MV) triangulation from five treatment fractions acquired in a previous pilot study. RESULTS: For the (1) static localization, (2) dynamic localization, and (3) treatment interruption accuracy tests, the mean and standard deviation of the difference are <1.0 mm. (4) The measured latency is 350 ms. (5) For the tests with previously acquired patient data, the mean and standard deviation of the difference between KIM and kV/MV triangulation are <1.0 mm. CONCLUSIONS: Clinical process and QA practices for the safe clinical implementation of KIM, a novel real-time monitoring system using commonly available equipment, have been developed and implemented for prostate cancer VMAT.

DMLC tracking and gating can improve dose coverage for prostate VMAT.

PURPOSE: To assess and compare the dosimetric impact of dynamic multileaf collimator (DMLC) tracking and gating as motion correction strategies to account for intrafraction motion during conventionally fractionated prostate radiotherapy. METHODS: A dose reconstruction method was used to retrospectively assess the dose distributions delivered without motion correction during volumetric modulated arc therapy fractions for 20 fractions of five prostate cancer patients who received conventionally fractionated radiotherapy. These delivered dose distributions were compared with the dose distributions which would have been delivered had DMLC tracking or gating motion correction strategies been implemented. The delivered dose distributions were constructed by incorporating the observed prostate motion with the patient's original treatment plan to simulate the treatment delivery. The DMLC tracking dose distributions were constructed using the same dose reconstruction method with the addition of MLC positions from Linac log files obtained during DMLC tracking simulations with the observed prostate motions input to the DMLC tracking software. The gating dose distributions were constructed by altering the prostate motion to simulate the application of a gating threshold of 3 mm for 5 s. RESULTS: The delivered dose distributions showed that dosimetric effects of intrafraction prostate motion could be substantial for some fractions, with an estimated dose decrease of more than 19% and 34% from the planned CTVD99% and PTV D95% values, respectively, for one fraction. Evaluation of dose distributions for DMLC tracking and gating deliveries showed that both interventions were effective in improving the CTV D99% for all of the selected fractions to within 4% of planned value for all fractions. For the delivered dose distributions the difference in rectum V65% for the individual fractions from planned ranged from -44% to 101% and for the bladder V65% the range was -61% to 26% from planned. The application of tracking decreased the maximum rectum and bladder V65% difference to 6% and 4%, respectively. CONCLUSIONS: For the first time, the dosimetric impact of DMLC tracking and gating to account for intrafraction motion during prostate radiotherapy has been assessed and compared with no motion correction. Without motion correction intrafraction prostate motion can result in a significant decrease in target dose coverage for a small number of individual fractions. This is unlikely to effect the overall treatment for most patients undergoing conventionally fractionated treatments. Both DMLC tracking and gating demonstrate dose distributions for all assessed fractions that are robust to intrafraction motion.