AAPM Task Group Report 290: Respiratory motion management for particle therapy.

Dose uncertainty induced by respiratory motion remains a major concern for treating thoracic and abdominal lesions using particle beams. This Task Group report reviews the impact of tumor motion and dosimetric considerations in particle radiotherapy, current motion-management techniques, and limitations for different particle-beam delivery modes (i.e., passive scattering, uniform scanning, and pencil-beam scanning). Furthermore, the report provides guidance and risk analysis for quality assurance of the motion-management procedures to ensure consistency and accuracy, and discusses future development and emerging motion-management strategies. This report supplements previously published AAPM report TG76, and considers aspects of motion management that are crucial to the accurate and safe delivery of particle-beam therapy. To that end, this report produces general recommendations for commissioning and facility-specific dosimetric characterization, motion assessment, treatment planning, active and passive motion-management techniques, image guidance and related decision-making, monitoring throughout therapy, and recommendations for vendors. Key among these recommendations are that: (1) facilities should perform thorough planning studies (using retrospective data) and develop standard operating procedures that address all aspects of therapy for any treatment site involving respiratory motion; (2) a risk-based methodology should be adopted for quality management and ongoing process improvement.

3-D fiducial motion tracking using limited MV projections in arc therapy.

PURPOSE: In-treatment fiducial tracking has recently received attention as a method for improving treatment accuracy, dose conformity, and sparing of healthy tissue. 3-D fiducial localization in arc-radiotherapy remains challenging due to the motion of targets and the complexity of arc deliveries. We propose a novel statistical method for estimating 3-D fiducial motion using limited 2-D megavoltage (MV) projections. METHODS: 3-D fiducial motion was estimated by a maximum a posteriori (MAP) approach to integrating information of fiducial projections with prior knowledge of target motion. To obtain the imaging geometries, short sequences of MV projections were selected in which fiducials were continuously visible. The MAP algorithm estimated the 3-D motion by maximizing the probability of displacement of fiducials in the sequences. Prior knowledge of target motion from a large statistical sample was built into the model to enhance the accuracy of estimation. In the case that a motion prior was unavailable, the algorithm can be simplified to the maximum likelihood (ML) approach. To compare tracking performance, a multiprojection geometric method was also presented by extending the typical two-project ion geometric estimation approach. The algorithms were evaluated using clinical prostate motion traces, and the performance was measured in quality indices and statistical evaluation. RESULTS: The results showed that the MAP method significantly outperforms the geometric method in all measures. In our simulations, the MAP method achieved an accuracy of less than 1 mm RMS error using only five continuous projections, whereas the geometric method required 15 projections to achieve a similar result. CONCLUSIONS: The approach presented can accurately estimate tumor motion using a limited number of continuous projections. The MAP motion estimation is superior to both the ML and geometric estimation methods.

Characterizing a novel scintillating glass for application to megavoltage cone-beam computed tomography.

PURPOSE: The purpose of this study was to evaluate the performance of a prototype electric portal imaging device (EPID) with a high detective quantum efficiency (DQE) scintillator, LKH-5. Specifically, image quality in context of both planar and megavoltage (MV) cone-beam computed tomography (CBCT) is analyzed. METHODS: Planar image quality in terms of modulation transfer function (MTF), noise power spectrum (NPS), and DQE are measured and compared to an existing EPID (AS-1200) using the 6 MV beamline for a Varian TrueBeam linac. Imager performance is contextualized for three-dimensional (3D), MV-CBCT performance by measuring imager lag and analyzing the expected degradation of the DQE as a function of dose. Finally, comparisons between reconstructed images of the Catphan phantom in terms of qualitative quality and signal-difference-to-noise ratio (SDNR) are made for 6 MV images using both conventional and LKH-5 EPIDs as well as for the kilovoltage (kV) on-board imager (OBI). RESULTS: Analysis of the NPS reveals linearity at all measured doses using the prototype LKH-5 detector. While the first zero of the MTF is much lower for the LKH-5 detector than the conventional EPID (0.6 cycles/mm vs 1.6 cycles/mm), the normalized NPS (NNPS) multiplied by total quanta (qNNPS) of the LKH-5 detector is roughly a factor of seven to eight times lower, yielding a DQE(0) of approximately 8%. First, second, and third frame lag were measured at approximately 23%, 5%, and 1%, respectively, although no noticeable image artifacts were apparent in reconstructed volumes. Analysis of low-dose performance reveals that DQE(0) remains at 80% of its maximum value at a dose as low as 7.5 × 10-6  MU. For a 400 projection technique, this represents a total scan dose of 0.0030 MU, suggesting that if imaging doses are increased to a value typical of kV-CBCT scans (~2.7 cGy), the LKH-5 detector will retain quantum noise limited performance. Finally, comparing Catphan scans, the prototype detector exhibits much lower image noise than the conventional EPID, resulting in improved small object representation. Furthermore, SDNR of H2 O and polystyrene cylinders improved from -1.95 and 2.94 to -15 and 18.7, respectively. CONCLUSIONS: Imaging performance of the prototype LKH-5 detector was measured and analyzed for both planar and 3D contexts. Improving noise transfer of the detector results in concurrent improvement of DQE(0). For 3D imaging, temporal characteristics were adequate for artifact-free performance and at relevant doses, the detector retained quantum noise limited performance. Although quantitative MTF measurements suggest poorer resolution, small object representation of the prototype imager is qualitatively improved over the conventional detector due to the measured reduction in noise.

A Monte Carlo study of the impact of phosphor optical properties on EPID imaging performance.

We have developed a Monte Carlo computational model of a clinically employed electronic portal imaging device (EPID), and demonstrated the impact of phosphor optical properties on the imaging performance. The EPID model was built with Geant4 application for tomographic emission. Both radiative and optical transport were included in the model. Modulation transfer function (MTF), normalized noise-power spectrum times the incident x-ray fluence (qNNPS), and detective quantum efficiency (DQE) were calculated for simulated and measured data, and their agreement was quantified by the normalized root-mean-square error (NRMSE). MTF was computed using a 100 µm wide slit tilted by 1.5° and qNNPS was estimated using the Fujita-Lubberts-Swank method. DQE was calculated from MTF and qNNPS data. The NRMSE value was 0.0467 for MTF, 0.0217 for qNNPS, and 0.0885 for DQE, showing good agreement between measurement and simulation. Five major optical properties, phosphor grain size, phosphor thickness, phosphor refractive index, binder refractive index, and packing ratio were tested for their influence on the qNNPS, MTF, and DQE(0) of the model. Generally, the effect on the qNNPS is greater than MTF, and no impact on DQE(0), except from phosphor thickness, was observed. Multiple applications, such as imager design optimization and investigations of the dosimetric performance, are expected to benefit from the validated model.

Leveraging multi-layer imager detector design to improve low-dose performance for megavoltage cone-beam computed tomography.

While megavoltage cone-beam computed tomography (CBCT) using an electronic portal imaging device (EPID) provides many advantages over kilovoltage (kV) CBCT, clinical adoption is limited by its high doses. Multi-layer imager (MLI) EPIDs increase DQE(0) while maintaining high resolution. However, even well-designed, high-performance MLIs suffer from increased electronic noise from each readout, degrading low-dose image quality. To improve low-dose performance, shift-and-bin addition (ShiBA) imaging is proposed, leveraging the unique architecture of the MLI. ShiBA combines hardware readout-binning and super-resolution concepts, reducing electronic noise while maintaining native image sampling. The imaging performance of full-resolution (FR); standard, aligned binned (BIN); and ShiBA images in terms of noise power spectrum (NPS), electronic NPS, modulation transfer function (MTF), and the ideal observer signal-to-noise ratio (SNR)-the detectability index (d')-are compared. The FR 4-layer readout of the prototype MLI exhibits an electronic NPS magnitude 6-times higher than a state-of-the-art single layer (SLI) EPID. Although the MLI is built on the same readout platform as the SLI, with each layer exhibiting equivalent electronic noise, the multi-stage readout of the MLI results in electronic noise 50% higher than simple summation. Electronic noise is mitigated in both BIN and ShiBA imaging, reducing its total by ~12 times. ShiBA further reduces the NPS, effectively upsampling the image, resulting in a multiplication by a sinc2 function. Normalized NPS show that neither ShiBA nor BIN otherwise affects image noise. The LSF shows that ShiBA removes the pixilation artifact of BIN images and mitigates the effect of detector shift, but does not quantifiably improve the MTF. ShiBA provides a pre-sampled representation of the images, mitigating phase dependence. Hardware binning strategies lower the quantum noise floor, with 2 × 2 implementation reducing the dose at which DQE(0) degrades by 10% from 0.01 MU to 0.004 MU, representing 20% improvement in d'.

Physics considerations in MV-CBCT multi-layer imager design.

Megavoltage (MV) cone-beam computed tomography (CBCT) using an electronic portal imaging (EPID) offers advantageous features, including 3D mapping, treatment beam registration, high-z artifact suppression, and direct radiation dose calculation. Adoption has been slowed by image quality limitations and concerns about imaging dose. Developments in imager design, including pixelated scintillators, structured phosphors, inexpensive scintillation materials, and multi-layer imager (MLI) architecture have been explored to improve EPID image quality and reduce imaging dose. The present study employs a hybrid Monte Carlo and linear systems model to determine the effect of detector design elements, such as multi-layer architecture and scintillation materials. We follow metrics of image quality including modulation transfer function (MTF) and noise power spectrum (NPS) from projection images to 3D reconstructions to in-plane slices and apply a task based figure-of-merit, the ideal observer signal-to-noise ratio (d') to determine the effect of detector design on object detectability. Generally, detectability was limited by detector noise performance. Deploying an MLI imager with a single scintillation material for all layers yields improvement in noise performance and d' linear with the number of layers. In general, improving x-ray absorption using thicker scintillators results in improved DQE(0). However, if light yield is low, performance will be affected by electronic noise at relatively high doses, resulting in rapid image quality degradation. Maximizing image quality in a heterogenous MLI detector (i.e. multiple different scintillation materials) is most affected by limiting total noise. However, while a second-order effect, maximizing total spatial resolution of the MLI detector is a balance between the intensity contribution of each layer against its individual MTF. So, while a thinner scintillator may yield a maximal individual-layer MTF, its quantum efficiency will be relatively low in comparison to a thicker scintillator and thus, intensity contribution may be insufficient to noticeably improve the total detector MTF.

Super-resolution imaging in a multiple layer EPID.

A new portal imager consisting of four vertically stacked conventional electronic portal imaging device (EPID) layers has been constructed in pursuit of improved detective quantum efficiency (DQE). We hypothesize that super-resolution (SR) imaging can also be achieved in such a system by shifting each layer laterally by half a pixel relative to the layer above. Super-resolution imaging will improve resolution and contrast-to-noise ratio (CNR) in megavoltage (MV) planar and cone beam computed tomography (MV-CBCT) applications. Simulations are carried out to test this hypothesis with digital phantoms. To assess planar resolution, 2 mm long iron rods with 0.3 × 0.3 mm2 square cross-section are arranged in a grid pattern at the center of a 1 cm thick solid water. For measuring CNR in MV-CBCT, a 20 cm diameter digital phantom with 8 inserts of different electron densities is used. For measuring resolution in MV-CBCT, a digital phantom featuring a bar pattern similar to the Gammex™ phantom is used. A 6 MV beam is attenuated through each phantom and detected by each of the four detector layers. Fill factor of the detector is explicitly considered. Projections are blurred with an estimated point spread function (PSF) before super-resolution reconstruction. When projections from multiple shifted layers are used in SR reconstruction, even a simple shift-add fusion can significantly improve the resolution in reconstructed images. In the reconstructed planar image, the grid pattern becomes visually clearer. In MV-CBCT, combining projections from multiple layers results in increased CNR and resolution. The inclusion of two, three and four layers increases CNR by 40%, 70% and 99%, respectively. Shifting adjacent layers by half a pixel almost doubles resolution. In comparison, using four perfectly aligned layers does not improve resolution relative to a single layer.

Online Combination of EPID & Cherenkov Imaging for 3-D Dosimetry in a Liquid Phantom.

Online acquisition of Cherenkov and portal imaging data was combined with a reconstruction scheme called EC3-D, providing a full 3-D dosimetry of megavoltage X-ray beams in a water tank. The methodology was demonstrated and quantified in a single static beam. Furthermore, the dynamics and visualization of the 3-D dose reconstruction were demonstrated with a volumetric modulated arc therapy plan for TG-119 C-Shape geometry. The developed algorithm combines depth dose information, provided by Cherenkov images, with the lateral dose distribution, provided by the electronic portal imaging device. The strength of our approach lies in the acquisition of both imaging data streams with sub-millimeter theoretical resolution at 5-Hz frame-rate, which can be concurrently processed by the fast Fourier transform-based analysis, thus providing means for an efficient real-time 3-D dosimetry.

A novel multilayer MV imager computational model for component optimization.

PURPOSE: A novel Megavoltage (MV) multilayer imager (MLI) design featuring higher detective quantum efficiency and lower noise than current conventional MV imagers in clinical use has been recently reported. Optimization of the MLI design for multiple applications including tumor tracking, MV-CBCT and portal dosimetry requires a computational model that will provide insight into the physics processes that affect the overall and individual components' performance. The purpose of the current work was to develop and validate a comprehensive computational model that can be used for MLI optimization. METHODS: The MLI model was built using the Geant4 Application for Tomographic Emission (GATE) application. The model includes x-ray and charged-particle interactions as well as the optical transfer within the phosphor. A first prototype MLI device featuring a stack of four detection layers was used for model validation. Each layer of the prototype contains a copper buildup plate, a phosphor screen and photodiode array. The model was validated against measured data of Modulation Transfer Function (MTF), Noise-Power Spectrum (NPS), and Detective Quantum Efficiency (DQE). MTF was computed using a slanted slit with 2.3° angle and 0.1 mm width. NPS was obtained using the autocorrelation function technique. DQE was calculated from MTF and NPS data. The comparison metrics between simulated and measured data were the Pearson's correlation coefficient (r) and the normalized root-mean-square error (NRMSE). RESULTS: Good agreement between measured and simulated MTF and NPS values was observed. Pearson's correlation coefficient for the combined signal from all layers of the MLI was equal to 0.9991 for MTF and 0.9992 for NPS; NRMSE was 0.0121 for MTF and 0.0194 for NPS. Similarly, the DQE correlation coefficient for the combined signal was 0.9888 and the NRMSE was 0.0686. CONCLUSIONS: A comprehensive model of the novel MLI design was developed using the GATE toolkit and validated against measured MTF, NPS, and DQE data acquired with a prototype device featuring four layers. This model will be used for further optimization of the imager components and configuration for clinical radiotherapy applications.

Technical Note: Combination of multiple EPID imager layers improves image quality and tracking performance of low contrast-to-noise objects.

PURPOSE: We hypothesized that combining multiple amorphous silicon flat panel layers increases photon detection efficiency in an electronic portal imaging device (EPID), improving image quality and tracking accuracy of low-contrast targets during radiotherapy. METHODS: The prototype imager evaluated in this study contained four individually programmable layers each with a copper converter layer, Gd2 O2 S scintillator, and active-matrix flat panel imager (AMFPI). The imager was placed on a Varian TrueBeam linac and a Las Vegas phantom programmed with sinusoidal motion (peak-to-peak amplitude = 20 mm, period = 3.5 s) was imaged at a frame rate of 10 Hz with one to four layers activated. Number of visible circles and CNR of least visible circle (depth = 0.5 mm, diameter = 7 mm) was computed to assess the image quality of single and multiple layers. A previously validated tracking algorithm was employed for auto-tracking. Tracking error was defined as the difference between the programmed and tracked positions of the circle. Pearson correlation coefficient (R) of CNR and tracking errors was computed. RESULTS: Motion-induced blurring significantly reduced circle visibility. During four cycles of phantom motion, the number of visible circles varied from 11-23, 13-24, 15-25, and 16-26 for one-, two-, three-, and four-layer imagers, respectively. Compared with using only a single layer, combining two, three, and four layers increased the median CNR by factors of 1.19, 1.42, and 1.71, respectively and reduced the average tracking error from 3.32 mm to 1.67 mm to 1.47 mm, and 0.74 mm, respectively. Significant correlations (P~10-9 ) were found between the tracking error and CNR. CONCLUSION: Combination of four conventional EPID layers significantly improves the EPID image quality and tracking accuracy for a poorly visible object which is moving with a frequency and amplitude similar to respiratory motion.

A novel method for quantification of beam's-eye-view tumor tracking performance.

PURPOSE: In-treatment imaging using an electronic portal imaging device (EPID) can be used to confirm patient and tumor positioning. Real-time tumor tracking performance using current digital megavolt (MV) imagers is hindered by poor image quality. Novel EPID designs may help to improve quantum noise response, while also preserving the high spatial resolution of the current clinical detector. Recently investigated EPID design improvements include but are not limited to multi-layer imager (MLI) architecture, thick crystalline and amorphous scintillators, and phosphor pixilation and focusing. The goal of the present study was to provide a method of quantitating improvement in tracking performance as well as to reveal the physical underpinnings of detector design that impact tracking quality. The study employs a generalizable ideal observer methodology for the quantification of tumor tracking performance. The analysis is applied to study both the effect of increasing scintillator thickness on a standard, single-layer imager (SLI) design as well as the effect of MLI architecture on tracking performance. METHODS: The present study uses the ideal observer signal-to-noise ratio (d') as a surrogate for tracking performance. We employ functions which model clinically relevant tasks and generalized frequency-domain imaging metrics to connect image quality with tumor tracking. A detection task for relevant Cartesian shapes (i.e., spheres and cylinders) was used to quantitate trackability of cases employing fiducial markers. Automated lung tumor tracking algorithms often leverage the differences in benign and malignant lung tissue textures. These types of algorithms (e.g., soft-tissue localization - STiL) were simulated by designing a discrimination task, which quantifies the differentiation of tissue textures, measured experimentally and fit as a power-law in trend (with exponent ß) using a cohort of MV images of patient lungs. The modeled MTF and NPS were used to investigate the effect of scintillator thickness and MLI architecture on tumor tracking performance. RESULTS: Quantification of MV images of lung tissue as an inverse power-law with respect to frequency yields exponent values of ß = 3.11 and 3.29 for benign and malignant tissues, respectively. Tracking performance with and without fiducials was found to be generally limited by quantum noise, a factor dominated by quantum detective efficiency (QDE). For generic SLI construction, increasing the scintillator thickness (gadolinium oxysulfide - GOS) from a standard 290 µm to 1720 µm reduces noise to about 10%. However, 81% of this reduction is appreciated between 290 and 1000 µm. In comparing MLI and SLI detectors of equivalent individual GOS layer thickness, the improvement in noise is equal to the number of layers in the detector (i.e., 4) with almost no difference in MTF. Further, improvement in tracking performance was slightly less than the square-root of the reduction in noise, approximately 84-90%. In comparing an MLI detector with an SLI with a GOS scintillator of equivalent total thickness, improvement in object detectability is approximately 34-39%. CONCLUSIONS: We have presented a novel method for quantification of tumor tracking quality and have applied this model to evaluate the performance of SLI and MLI EPID designs. We showed that improved tracking quality is primarily limited by improvements in NPS. When compared to very thick scintillator SLI, employing MLI architecture exhibits the same gains in QDE, but by mitigating the effect of optical Swank noise, results in more dramatic improvements in tracking performance.

Spectral imaging using clinical megavoltage beams and a novel multi-layer imager.

We assess the feasibility of clinical megavoltage (MV) spectral imaging for material and bone separation with a novel multi-layer imager (MLI) prototype. The MLI provides higher detective quantum efficiency and lower noise than conventional electronic portal imagers. Simulated experiments were performed using a validated Monte Carlo model of the MLI to estimate energy absorption and energy separation between the MLI components. Material separation was evaluated experimentally using solid water and aluminum (Al), copper (Cu) and gold (Au) for 2.5 MV, 6 MV and 6 MV flattening filter free (FFF) clinical photon beams. An anthropomorphic phantom with implanted gold fiducials was utilized to further demonstrate bone/gold separation. Weighted subtraction imaging was employed for material and bone separation. The weighting factor (w) was iteratively estimated, with the optimal w value determined by minimization of the relative signal difference ([Formula: see text]) and signal-difference-to-noise ratio (SDNR) between material (or bone) and the background. Energy separation between layers of the MLI was mainly the result of beam hardening between components with an average energy separation between 34 and 47 keV depending on the x-ray beam energy. The minimum average energy of the detected spectrum in the phosphor layer was 123 keV in the top layer of the MLI with the 2.5 MV beam. The w values that minimized [Formula: see text] and SDNR for Al, Cu and Au were 0.89, 0.76 and 0.64 for 2.5 MV; for 6 MV FFF, w was 0.98, 0.93 and 0.77 respectively. Bone suppression in the anthropomorphic phantom resulted in improved visibility of the gold fiducials with the 2.5 MV beam. Optimization of the MLI design is required to achieve optimal separation at clinical MV beam energies.

A novel EPID design for enhanced contrast and detective quantum efficiency.

Beams-eye-view imaging applications such as real-time soft-tissue motion estimation are hindered by the inherently low image contrast of electronic portal imaging devices (EPID) currently available for clinical use. We introduce and characterize a novel EPID design that provides substantially increased detective quantum efficiency (DQE), contrast-to-noise ratio (CNR) and sensitivity without degradation in spatial resolution. The prototype design features a stack of four conventional EPID layers combined with low noise integrated readout electronics. Each layer consists of a copper plate, a scintillator ([Formula: see text]) and a photodiode/TFT-switch (aSi:H). We characterize the prototype's signal response to a 6 MV photon beam in terms of modulation transfer function (MTF), DQE and CNR. The presampled MTF is estimated using a slanted slit technique, the DQE is calculated from measured normalized noise power spectra (nNPS) and the MTF and CNR is estimated using a Las Vegas contrast phantom. The prototype has been designed and built to be interchangeable with the current clinical EPID on the Varian TrueBeam platform (AS-1200) in terms of size and data output specifications. Performance evaluation is conducted in absolute values as well as in relative terms using the Varian AS-1200 EPID as a reference detector. A fivefold increase of DQE(0) to about 6.7% was observed by using the four-layered design versus the AS-1200 reference detector. No substantial differences are observed between each layer's individual MTF and the one for all four layers operating combined indicating that defocusing due to beam divergence is negligible. Also, using four layers instead of one increases the signal to noise ratio by a factor of 1.7.

Beam's-eye-view imaging during non-coplanar lung SBRT.

PURPOSE: Beam's-eye-view (BEV) imaging with an electronic portal imaging device (EPID) can be performed during lung stereotactic body radiation therapy (SBRT) to monitor the tumor location in real-time. Image quality for each patient and treatment field depends on several factors including the patient anatomy and the gantry and couch angles. The authors investigated the angular dependence of automatic tumor localization during non-coplanar lung SBRT delivery. METHODS: All images were acquired at a frame rate of 12 Hz with an amorphous silicon EPID. A previously validated markerless lung tumor localization algorithm was employed with manual localization as the reference. From ten SBRT patients, 12 987 image frames of 123 image sequences acquired at 48 different gantry-couch rotations were analyzed. δ was defined by the position difference of the automatic and manual localization. RESULTS: Regardless of the couch angle, the best tracking performance was found in image sequences with a gantry angle within 20° of 250° (δ = 1.40 mm). Image sequences acquired with gantry angles of 150°, 210°, and 350° also led to good tracking performances with δ = 1.77-2.00 mm. Overall, the couch angle was not correlated with the tracking results. Among all the gantry-couch combinations, image sequences acquired at (θ = 30°, ϕ = 330°), (θ = 210°, ϕ = 10°), and (θ = 250°, ϕ = 30°) led to the best tracking results with δ = 1.19-1.82 mm. The worst performing combinations were (θ = 90° and 230°, ϕ = 10°) and (θ = 270°, ϕ = 30°) with δ > 3.5 mm. However, 35% (17/48) of the gantry-couch rotations demonstrated substantial variability in tracking performances between patients. For example, the field angle (θ = 70°, ϕ = 10°) was acquired for five patients. While the tracking errors were ≤1.98 mm for three patients, poor performance was found for the other two patients with δ ≥ 2.18 mm, leading to average tracking error of 2.70 mm. Only one image sequence was acquired for all other gantry-couch rotations (δ = 1.18-10.29 mm). CONCLUSIONS: Non-coplanar beams with gantry-couch rotation of (θ = 30°, ϕ = 330°), (θ = 210°, ϕ = 10°), and (θ = 250°, ϕ = 30°) have the highest accuracy for BEV lung tumor localization. Additionally, gantry angles of 150°, 210°, 250°, and 350° also offer good tracking performance. The beam geometries (θ = 90° and 230°, ϕ = 10°) and (θ = 270°, ϕ = 30°) are associated with substantial automatic localization errors. Overall, lung tumor visibility and tracking performance were patient dependent for a substantial number of the gantry-couch angle combinations studied.

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.

Generation of fluoroscopic 3D images with a respiratory motion model based on an external surrogate signal.

Respiratory motion during radiotherapy can cause uncertainties in definition of the target volume and in estimation of the dose delivered to the target and healthy tissue. In this paper, we generate volumetric images of the internal patient anatomy during treatment using only the motion of a surrogate signal. Pre-treatment four-dimensional CT imaging is used to create a patient-specific model correlating internal respiratory motion with the trajectory of an external surrogate placed on the chest. The performance of this model is assessed with digital and physical phantoms reproducing measured irregular patient breathing patterns. Ten patient breathing patterns are incorporated in a digital phantom. For each patient breathing pattern, the model is used to generate images over the course of thirty seconds. The tumor position predicted by the model is compared to ground truth information from the digital phantom. Over the ten patient breathing patterns, the average absolute error in the tumor centroid position predicted by the motion model is 1.4 mm. The corresponding error for one patient breathing pattern implemented in an anthropomorphic physical phantom was 0.6 mm. The global voxel intensity error was used to compare the full image to the ground truth and demonstrates good agreement between predicted and true images. The model also generates accurate predictions for breathing patterns with irregular phases or amplitudes.

Using an external surrogate for predictor model training in real-time motion management of lung tumors.

PURPOSE: Precise prediction of respiratory motion is a prerequisite for real-time motion compensation techniques such as beam, dynamic couch, or dynamic multileaf collimator tracking. Collection of tumor motion data to train the prediction model is required for most algorithms. To avoid exposure of patients to additional dose from imaging during this procedure, the feasibility of training a linear respiratory motion prediction model with an external surrogate signal is investigated and its performance benchmarked against training the model with tumor positions directly. METHODS: The authors implement a lung tumor motion prediction algorithm based on linear ridge regression that is suitable to overcome system latencies up to about 300 ms. Its performance is investigated on a data set of 91 patient breathing trajectories recorded from fiducial marker tracking during radiotherapy delivery to the lung of ten patients. The expected 3D geometric error is quantified as a function of predictor lookahead time, signal sampling frequency and history vector length. Additionally, adaptive model retraining is evaluated, i.e., repeatedly updating the prediction model after initial training. Training length for this is gradually increased with incoming (internal) data availability. To assess practical feasibility model calculation times as well as various minimum data lengths for retraining are evaluated. Relative performance of model training with external surrogate motion data versus tumor motion data is evaluated. However, an internal-external motion correlation model is not utilized, i.e., prediction is solely driven by internal motion in both cases. RESULTS: Similar prediction performance was achieved for training the model with external surrogate data versus internal (tumor motion) data. Adaptive model retraining can substantially boost performance in the case of external surrogate training while it has little impact for training with internal motion data. A minimum adaptive retraining data length of 8 s and history vector length of 3 s achieve maximal performance. Sampling frequency appears to have little impact on performance confirming previously published work. By using the linear predictor, a relative geometric 3D error reduction of about 50% was achieved (using adaptive retraining, a history vector length of 3 s and with results averaged over all investigated lookahead times and signal sampling frequencies). The absolute mean error could be reduced from (2.0 ± 1.6) mm when using no prediction at all to (0.9 ± 0.8) mm and (1.0 ± 0.9) mm when using the predictor trained with internal tumor motion training data and external surrogate motion training data, respectively (for a typical lookahead time of 250 ms and sampling frequency of 15 Hz). CONCLUSIONS: A linear prediction model can reduce latency induced tracking errors by an average of about 50% in real-time image guided radiotherapy systems with system latencies of up to 300 ms. Training a linear model for lung tumor motion prediction with an external surrogate signal alone is feasible and results in similar performance as training with (internal) tumor motion. Particularly for scenarios where motion data are extracted from fluoroscopic imaging with ionizing radiation, this may alleviate the need for additional imaging dose during the collection of model training data.

The impact of cine EPID image acquisition frame rate on markerless soft-tissue tracking.

PURPOSE: Although reduction of the cine electronic portal imaging device (EPID) acquisition frame rate through multiple frame averaging may reduce hardware memory burden and decrease image noise, it can hinder the continuity of soft-tissue motion leading to poor autotracking results. The impact of motion blurring and image noise on the tracking performance was investigated. METHODS: Phantom and patient images were acquired at a frame rate of 12.87 Hz with an amorphous silicon portal imager (AS1000, Varian Medical Systems, Palo Alto, CA). The maximum frame rate of 12.87 Hz is imposed by the EPID. Low frame rate images were obtained by continuous frame averaging. A previously validated tracking algorithm was employed for autotracking. The difference between the programmed and autotracked positions of a Las Vegas phantom moving in the superior-inferior direction defined the tracking error (δ). Motion blurring was assessed by measuring the area change of the circle with the greatest depth. Additionally, lung tumors on 1747 frames acquired at 11 field angles from four radiotherapy patients are manually and automatically tracked with varying frame averaging. δ was defined by the position difference of the two tracking methods. Image noise was defined as the standard deviation of the background intensity. Motion blurring and image noise are correlated with δ using Pearson correlation coefficient (R). RESULTS: For both phantom and patient studies, the autotracking errors increased at frame rates lower than 4.29 Hz. Above 4.29 Hz, changes in errors were negligible withδ < 1.60 mm. Motion blurring and image noise were observed to increase and decrease with frame averaging, respectively. Motion blurring and tracking errors were significantly correlated for the phantom (R = 0.94) and patient studies (R = 0.72). Moderate to poor correlation was found between image noise and tracking error with R -0.58 and -0.19 for both studies, respectively. CONCLUSIONS: Cine EPID image acquisition at the frame rate of at least 4.29 Hz is recommended. Motion blurring in the images with frame rates below 4.29 Hz can significantly reduce the accuracy of autotracking.

Cine EPID evaluation of two non-commercial techniques for DIBH.

PURPOSE: To evaluate the efficacy of two noncommercial techniques for deep inspiration breathhold (DIBH) treatment of left-sided breast cancer (LSBC) using cine electronic portal imaging device (EPID) images. METHODS: 23,875 EPID images of 65 patients treated for LSBC at two different cancer treatment centers were retrieved. At the Milford Regional Cancer Center, DIBH stability was maintained by visual alignment of inroom lasers and patient skin tattoos (TAT). At the South Shore Hospital, a distance-measuring laser device (RTSSD) was implemented. For both centers,cine EPID images were acquired at least once per week during beam-on. Chest wall position relative to image boundary was measured and tracked over the course of treatment for every patient and treatment fraction for which data were acquired. RESULTS: Median intrabeam chest motion was 0.31 mm for the TAT method and 0.37 mm for the RTSSD method. The maximum excursions exceeded our treatment protocol threshold of 3 mm in 0.3% of cases (TAT) and 1.2% of cases (RTSSD). The authors did not observe a clinically significant difference between the two datasets. CONCLUSIONS: Both noncommercial techniques for monitoring the DIBH location provided DIBH stability within the predetermined treatment protocol parameters (<3 mm). The intreatment imaging offered by the EPID operating in cine mode facilitates retrospective analysis and validation of both techniques.

Registration of clinical volumes to beams-eye-view images for real-time tracking.

PURPOSE: The authors combine the registration of 2D beam's eye view (BEV) images and 3D planning computed tomography (CT) images, with relative, markerless tumor tracking to provide automatic absolute tracking of physician defined volumes such as the gross tumor volume (GTV). METHODS: During treatment of lung SBRT cases, BEV images were continuously acquired with an electronic portal imaging device (EPID) operating in cine mode. For absolute registration of physician-defined volumes, an intensity based 2D/3D registration to the planning CT was performed using the end-of-exhale (EoE) phase of the four dimensional computed tomography (4DCT). The volume was converted from Hounsfield units into electron density by a calibration curve and digitally reconstructed radiographs (DRRs) were generated for each beam geometry. Using normalized cross correlation between the DRR and an EoE BEV image, the best in-plane rigid transformation was found. The transformation was applied to physician-defined contours in the planning CT, mapping them into the EPID image domain. A robust multiregion method of relative markerless lung tumor tracking quantified deviations from the EoE position. RESULTS: The success of 2D/3D registration was demonstrated at the EoE breathing phase. By registering at this phase and then employing a separate technique for relative tracking, the authors are able to successfully track target volumes in the BEV images throughout the entire treatment delivery. CONCLUSIONS: Through the combination of EPID/4DCT registration and relative tracking, a necessary step toward the clinical implementation of BEV tracking has been completed. The knowledge of tumor volumes relative to the treatment field is important for future applications like real-time motion management, adaptive radiotherapy, and delivered dose calculations.