Script-based implementation of automatic grid placement for lattice stereotactic body radiation therapy.

Background and purpose: Spatially fractionated radiation therapy (SFRT) has demonstrated promising clinical response in treating large tumors with heterogeneous dose distributions. Lattice stereotactic body radiation therapy (SBRT) is an SFRT technique that leverages inverse optimization to precisely localize regions of high and lose dose within disease. The aim of this study was to evaluate an automated heuristic approach to sphere placement in lattice SBRT treatment planning. Materials and methods: A script-based algorithm for sphere placement in lattice SBRT based on rules described by protocol was implemented within a treatment planning system. The script was applied to 22 treated cases and sphere distributions were compared with manually placed spheres in terms of number of spheres, number of protocol violations, and time required to place spheres. All cases were re-planned using script-generated spheres and plan quality was compared with clinical plans. Results: The mean number of spheres placed excluding those that violate rules was greater using the script (13.8) than that obtained by either dosimetrist (10.8 and 12.0, p < 0.001 and p = 0.003) or physicist (12.7, p = 0.061). The mean time required to generate spheres was significantly less using the script (2.5 min) compared to manual placement by dosimetrists (25.0 and 29.9 min) and physicist (19.3 min). Plan quality indices were similar in all cases with no significant differences, and OAR constraints remained met on all plans except two. Conclusion: A script placed spheres for lattice SBRT according to institutional protocol rules. The script-produced placement was superior to that of manually-specified spheres, as characterized by sphere number and rule violations.

Inter-fractional portability of deep learning models for lung target tracking on cine imaging acquired in MRI-guided radiotherapy.

MRI-guided radiotherapy systems enable beam gating by tracking the target on planar, two-dimensional cine images acquired during treatment. This study aims to evaluate how deep-learning (DL) models for target tracking that are trained on data from one fraction can be translated to subsequent fractions. Cine images were acquired for six patients treated on an MRI-guided radiotherapy platform (MRIdian, Viewray Inc.) with an onboard 0.35 T MRI scanner. Three DL models (U-net, attention U-net and nested U-net) for target tracking were trained using two training strategies: (1) uniform training using data obtained only from the first fraction with testing performed on data from subsequent fractions and (2) adaptive training in which training was updated each fraction by adding 20 samples from the current fraction with testing performed on the remaining images from that fraction. Tracking performance was compared between algorithms, models and training strategies by evaluating the Dice similarity coefficient (DSC) and 95% Hausdorff Distance (HD95) between automatically generated and manually specified contours. The mean DSC for all six patients in comparing manual contours and contours generated by the onboard algorithm (OBT) were 0.68 ± 0.16. Compared to OBT, the DSC values improved 17.0 - 19.3% for the three DL models with uniform training, and 24.7 - 25.7% for the models based on adaptive training. The HD95 values improved 50.6 - 54.5% for the models based on adaptive training. DL-based techniques achieved better tracking performance than the onboard, registration-based tracking approach. DL-based tracking performance improved when implementing an adaptive strategy that augments training data fraction-by-fraction.

Simulation study of a novel small animal FLASH irradiator (SAFI) with integrated inverse-geometry CT based on circularly distributed kV X-ray sources.

Ultra-high dose rate (UHDR) radiotherapy (RT) or FLASH-RT can potentially reduce normal tissue toxicity. A small animal irradiator that can deliver FLASH-RT treatments similar to clinical RT treatments is needed for pre-clinical studies of FLASH-RT. We designed and simulated a novel small animal FLASH irradiator (SAFI) based on distributed x-ray source technology. The SAFI system comprises a distributed x-ray source with 51 focal spots equally distributed on a 20 cm diameter ring, which are used for both FLASH-RT and onboard micro-CT imaging. Monte Carlo simulation was performed to estimate the dosimetric characteristics of the SAFI treatment beams. The maximum dose rate, which is limited by the power density of the tungsten target, was estimated based on finite-element analysis (FEA). The maximum DC electron beam current density is 2.6 mA/mm2, limited by the tungsten target's linear focal spot power density. At 160 kVp, 51 focal spots, each with a dimension of [Formula: see text] mm2 and 10° anode angle, can produce up to 120 Gy/s maximum DC irradiation at the center of a cylindrical water phantom. We further demonstrate forward and inverse FLASH-RT planning, as well as inverse-geometry micro-CT with circular source array imaging via numerical simulations.

An atlas-guided automatic planning approach for rectal cancer intensity-modulated radiotherapy.

We try to develop an atlas-guided automatic planning (AGAP) approach and evaluate its feasibility and performance in rectal cancer intensity-modulated radiotherapy. The developed AGAP approach consisted of four independent modules: patient atlas, similar patient retrieval, beam morphing (BM), and plan fine-tuning (PFT) modules. The atlas was setup using anatomy and plan data from Pinnacle auto-planning (P-auto) plans. Given a new patient, the retrieval function searched the top similar patient by a generic Fourier descriptor algorithm and retrieved its plan information. The BM function generated an initial plan for the new patient by morphing the beam aperture from the top similar patient plan. The beam aperture and calculated dose of the initial plan were used to guide the new plan optimization in the PFT function. The AGAP approach was tested on 96 patients by the leave-one-out validation and plan quality was compared with the P-auto plans. The AGAP and P-auto plans had no statistical difference for target coverage and dose homogeneity in terms ofV100%(p = 0.76) and homogeneity index (p = 0.073), respectively. The CI index showed they had a statistically significant difference. But the ΔCI was both 0.02 compared to the perfect CI index of 1. The AGAP approach reduced the bladder mean dose by 152.1 cGy (p < 0.05) andV50by 0.9% (p < 0.05), and slightly increased the left and right femoral head mean dose by 70.1 cGy (p < 0.05) and 69.7 cGy (p < 0.05), respectively. This work developed an efficient and automatic approach that could fully automate the IMRT planning process in rectal cancer radiotherapy. It reduced the plan quality dependence on the planner experience and maintained the comparable plan quality with P-auto plans.

Development of a storage phosphor imaging system for proton pencil beam spot profile determination.

PURPOSE: Accurate two-dimensional (2D) profile measurements at submillimeter precision are necessary for proton beam commissioning and periodic quality assurance (QA) purposes and are currently performed at our institution with a commercial scintillation detector (Lynx PT) with limited means for independent checks. The purpose of this work was to create an independent dosimetry system consisting of an in-house optical scanner and a BaFBrI:Eu2+ storage phosphor dosimeter by: (a) determining the optimal settings for the optical scanner, (b) measuring 2D proton spot profiles with the storage phosphors, and (c) comparing them to similar measurements using a commercial scintillation detector. METHODS: An in-house 2D laboratory optical scanner was constructed and spatially calibrated for accurate 2D photostimulated luminescence (PSL) dosimetry. Square 5 × 5 cm2 BaFBrI:Eu2+ dosimeter samples were uniformly irradiated with line scans performed to determine the physical and electronic scanner settings resulting in the highest signal-to-noise ratios (SNR) at a sub-millimeter spatial resolution. The resultant spatial resolution of the scanner was then quantitatively assessed by measuring (a) line pairs on a standard X-ray lead bar phantom and (b) modulation transfer functions. Following this, 2D proton spot profiles from a Mevion S250i Hyperscan proton unit were obtained at 1, 10, 20, 30, 40, and 50 monitor unit (MU) settings at maximum energy (E0  = 227.1 MeV) and compared to baseline profiles from a commercial scintillation detector, where 1 MU is calibrated to deliver 1 Gy absolute proton dose-to-water under reference conditions, that is, 41 × 41 proton spots uniformly spaced by 0.25 cm within a 10 × 10 cm2 square field size at maximum energy (227.1 MeV) in water at depth of 5 cm at isocenter. The dosimetric system's sensitivities to (a) ±1 mm positional shifts and (b) ±0.3 mm beam lateral spread changes were quantitatively evaluated through a Gaussian fitting of the crossline and inline plots of the respective artificially shifted beam profiles. RESULTS: The physical scanner settings of (a) Δτ = 27 ms time interval between data samples, (b) vx  = 1.235 cm/s scanning speed, (c) 1% laser transmission (0.02 mW power) and (d) (Δx, Δy) = (0.33, 0.50 mm) pixel sizes with electronic settings of (a) 300 microseconds time constant, (b) normal dynamic reserve, (c) 24 dB/oct low pass filter slope, and (d) 160 Hz chopping frequency resulted in the highest SNR while maintaining sub-millimeter spatial resolution. The BaFBr0.85 I0.15 :Eu2+ storage phosphor dosimeters were linear from 1 to 50 MU and their profiles did not saturate up to 150 MU. The scanner was able to detect lateral displacements of ±1 mm in both the crossline and inline directions and ±0.3 mm beam spread changes that were artificially introduced by varying the incident proton energy. Specific to our proton unit, proton energy changes of ±1 MeV can also be detected indirectly via beam spread measurements. CONCLUSION: Our combined dosimetric system including an in-house laboratory optical scanner and reusable BaFBr0.85 I0.15 :Eu2+ storage phosphors demonstrated a sufficient spatial resolution and dosimetric accuracy to support its use as an independent proton spot measurement dosimeter system. Its wide dynamic range allows for other versatile applications such as proton halo measurements.

Characterization of Dosimetric Differences in Strut-Adjusted Volume Implant Treatment Plans Calculated With TG-43 Formalism and a Model-Based Dose Calculation Algorithm.

PURPOSE: To comprehensively characterize dosimetric differences between calculations with a commercial model-based dose calculation algorithm (MBDCA) and the TG-43 formalism in application to accelerated partial breast irradiation (APBI) with the strut-adjusted volume implant (SAVI) applicator. METHODS: Dose for 100 patients treated with the SAVI applicator was recalculated with an MBDCA for comparison to dose calculated via TG-43. For every pair of dose calculations, dose-volume histogram (DVH) metrics including V90%, V95%, V100%, V150%, and V200% for the PTV_EVAL were compared. Features were defined for each case including (1) applicator size, (2) ratio between PTV_EVAL contour and 1-cm rind surrounding SAVI applicator, (3) ratio between dwell time in central catheter and total dwell time, and (4) mean computed tomography (CT) number within the lumpectomy cavity. Wilcoxon rank sum tests were performed to test whether treatment plans could be stratified according to feature values into groups with statistically significant dosimetry differences between MBDCA and TG-43. RESULTS: For all DVH metrics, differences between TG-43 and MBDCA calculations were statistically significant (P < .05). Minimum (maximum) relative percent differences between the MBDCA and TG-43 for V90%, V95%, and V100% were -2.1% (0.1%), -3.1% (-0.1%), and -5.0% (-0.5%), respectively. The median relative percent difference in mean PTV_EVAL dose between the MBDCA and TG-43 was -3.9%, with minimum (maximum) difference of -6.5% (-1.8%). For V90%, V95%, and V100%, plan quality worsened beyond defined thresholds in 26, 23, and 31 cases with no instances of coverage improvement. Features 1, 2, and 4 were shown to be able to stratify treatment plans into groups with statistically significant differences in dosimetry metrics between MBDCA and TG-43. CONCLUSIONS: Investigated dose metrics for SAVI treatments were found to be systematically lower with MBDCA calculation in comparison to TG-43. Plans could be stratified according to several features by the magnitude of dosimetric differences between these calculations.

Dual-storage phosphor proton therapy dosimetry: Simultaneous quantification of dose and linear energy transfer.

PURPOSE: To investigate the feasibility of using the high Zeff storage phosphor material BaFBrI:Eu2+ in conjunction with the low Zeff storage phosphor material KCl:Eu2+ for simultaneous proton dose and linear energy transfer (LET) measurements by (a) measuring the fundamental optical and dosimetric properties of BaFBrI:Eu2+ , (b) evaluating its compatibility in being readout simultaneously with KCl:Eu2+ dosimeters, and (c) modeling and validating its LET dependence under elevated proton LET irradiation. METHODS: A commercial BaFBrI:Eu2+ storage phosphor detector (Model ST-VI, Fujifilm) was characterized with energy dispersive x-ray spectroscopy (EDS) analysis to obtain its elemental composition. The dosimeters were irradiated using both a Mevion S250 proton therapy unit (at the center of a spread-out Bragg peak, SOBP) and a Varian Clinac iX linear accelerator with the latter being a low LET irradiation. The photostimulated luminescence (PSL) emission spectra, excitation spectra, and luminescent lifetimes of the detector were measured after proton and photon irradiations. Dosimetric properties including dose linearity, dose rate dependence, radiation hardness, temporal, and readout stabilities were studied using a laboratory optical reader after proton irradiations. In addition, its proton energy dependence was analytically modeled and experimentally validated by irradiating the detectors at various depths within the SOBP (Range: 15.0 g/cm2 , Modulation: 10.0 g/cm2 ). RESULTS: The active detector composition for the high Zeff storage phosphor detector was found to be BaFBr0.85 I0.15 :Eu2+ . The BaFBr0.85 I0.15 :Eu2+ material's excitation and emission spectra were in agreement under proton and photon irradiations, with peaks of 586 ± 1 nm and 400 ± 1 nm, respectively, with a full width at half maximum (FWHM) of 119 ± 3 nm and 30 ± 2 nm, respectively. As dosimeter response under photon irradiation is generally believed to be free from LET effect, these results suggest LET independence of charge storage center types resulted from ionizing radiations. There is sufficient spectral overlaps with KCl:Eu2+ dosimeters allowing both dosimeters to be readout under equivalent readout conditions, that is, 594 nm stimulation and 420 nm detection wavelengths. Its PSL characteristic lifetime was found to be less than 5 microseconds which would make it suitable for fast 2D readout post irradiation. Its 420 nm emission band intensity was found to be linear up to 10 Gy absolute proton dose under the same irradiation conditions, dose rate independent, stable in time and under multiple readouts, and with high radiation hardness under cumulative proton dose histories up to 200 Gy as tested in this study. BaFBr0.85 I0.15 :Eu2+ showed significant proton energy-dependent dose under-response in regions of high LET which could be modeled by stopping power ratio calculations with an accuracy of 3% in low LET regions and a distance-to-agreement (DTA) of 1 mm in high LET regions (>5 keV/µm). CONCLUSION: We have proven the feasibility of dual-storage phosphor proton dosimetry for simultaneous proton dose and LET measurements. BaFBr0.85 I0.15 :Eu2+ has shown equally excellent dosimetry performance as its low Zeff complement KCl:Eu2+ with distinctive LET dependence merely as a result of its higher Zeff . These promising results pave the way for future studies involving simultaneous proton dose and LET measurements using this novel approach.

Technical Note: Cumulative dose modeling for organ motion management in MRI-guided radiation therapy.

PURPOSE: To develop a method for continuous online dose accumulation during irradiation in MRI-guided radiation therapy (MRgRT) and to demonstrate its application in evaluating the impact of internal organ motion on cumulative dose. METHODS: An intensity-modulated radiation therapy (IMRT) treatment plan is partitioned into its unique apertures. Dose for each planned aperture is calculated using Monte Carlo dose simulation on each phase of a four-dimensional computed tomography (4D-CT) dataset. Deformable image registration is then performed both (a) between each frame of a cine-MRI acquisition obtained during treatment and a reference frame, and (b) between each volume of the 4D-CT phases and a reference phase. These registrations are used to associate each cine image with a 4D-CT phase. Additionally, for each 4D-CT phase, the deformation vector field (DVF) is used to warp the pre-calculated dose volumes per aperture onto the reference CT dataset. To estimate the dose volume delivered during each frame of the cine-MRI acquisition, we retrieve the pre-calculated warped dose volume for the delivered aperture on the associated 4D-CT phase and adjust it by a rigid translation to account for baseline drift and instances where motion on the cine image exceeds the amplitude observed between 4D-CT phases. RESULTS: The proposed dose accumulation method is retrospectively applied to a liver cancer case previously treated on an MRgRT platform. Cumulative dose estimated for free-breathing and respiration-gated delivery is compared against dose calculated on static anatomy. In this sample case, the target minimum dose and D 98 varied by as much as 5% and 7%, respectively. CONCLUSION: We demonstrate a technique suitable for continuous online dose accumulation during MRgRT. In contrast to other approaches, dose is pre-calculated per aperture and phase and then retrieved based on a mapping scheme between cine MRI and 4D-CT datasets, aiming at reducing the computational burden for potential real-time applications.

Quantitative proton radiation therapy dosimetry using the storage phosphor europium-doped potassium chloride.

PURPOSE: To (a) characterize the fundamental optical and dosimetric properties of the storage phosphor europium-doped potassium chloride for quantitative proton dosimetry, and (b) investigate if its dose radiation response can be described by an analytic radiation transport model. METHODS: Cylindrical KCl:Eu2+ dosimeters with dimensions of 6 mm diameter and 1 mm thickness were fabricated in-house. The dosimeters were irradiated using both a Mevion S250 passive scattering proton therapy system and a Varian Clinac iX linear accelerator. Photostimulated luminescence (PSL) emission spectra, excitation spectra, and luminescence lifetimes were measured for both proton and photon irradiations. Dosimetric properties including radiation hardness, dose linearity, signal stabilization, dose rate sensitivity, and energy dependence were studied using a laboratory optical reader after irradiations. The dosimeters were modeled using physical quantities including mass stopping powers in the storage phosphor and water for a given proton beam, and mass energy absorption coefficients and massing stopping powers in detector and water for a given photon beam. RESULTS: KCl:Eu2+ exhibited optical emission and stimulation peaks at 421 and 560 nm, respectively, for both proton and photon irradiations, enabling postirradiation readouts using a visible light source while detecting the PSL using a photomultiplier tube. KCl:Eu2+ showed a linear response from 0 to 8 Gy absorbed dose-to-water, a large dynamic range up to 60 Gy, dose-rate independence measured from 83 to 500 MU/min, and a PSL lifetime of <5 ms that is sufficiently short for supporting rapid scanning in a two-dimensional geometry. KCl:Eu2+ was highly reusable with only a slight signal decrease of ~3% at accumulated doses over 100 Gy, which could be managed by a periodic recalibration. The detected PSL signal strength of the dosimeter in the proton field had been calculated accurately to a maximum discrepancy of 2% using known physical quantities along with its prior signal strength as measured in a photon field at the same dose-to-water. This discrepancy might be attributed to an under-response due to linear energy transfer (LET) effect. However, comparisons of depth-dose measurements in a spread-out Bragg peak (SOBP) field with a parallel-plate ionization chamber showed no clear evidence of LET effects. Furthermore, range measurements agreed with ionization chamber measurements to within 1 mm. CONCLUSIONS: KCl:Eu2+ showed linear response over a large dynamic range for proton irradiations and reliably reproduced SOBP measurements as measured by ionization chambers. Its relatively low atomic number of 18 and near LET independence make it suited for quantitative proton dosimetry. In addition, its high radiation hardness means that it can be reused numerous times. Any potential measurement artifacts encountered in complex irradiation conditions should be able to be corrected for using known physical quantities.

Automated and robust beam data validation of a preconfigured ring gantry linear accelerator using a 1D tank with synchronized beam delivery and couch motions.

PURPOSE: To develop an efficient and automated methodology for beam data validation for a preconfigured ring gantry linear accelerator using scripting and a one-dimensional (1D) tank with automated couch motions. MATERIALS AND METHODS: Using an application programming interface, a program was developed to allow the user to choose a set of beam data to validate with measurement. Once selected the program generates a set of instructions for radiation delivery with synchronized couch motions for the linear accelerator in the form of an extensible markup language (XML) file to be delivered on the ring gantry linear accelerator. The user then delivers these beams while measuring with the 1D tank and data logging electrometer. The program also automatically calculates this set of beams on the measurement geometry within the treatment planning system (TPS) and extracts the corresponding calculated dosimetric data for comparison to measurement. Once completed the program then returns a comparison of the measurement to the predicted result from the TPS to the user and prints a report. In this work lateral, longitudinal, and diagonal profiles were taken for fields sizes of 6 × 6, 8 × 8, 10 × 10, 20 × 20, and 28 × 28 cm2 at depths of 1.3, 5, 10, 20, and 30 cm. Depth dose profiles were taken for all field sizes. RESULTS: Using this methodology, the TPS was validated to agree with measurement. All compared points yielded a gamma value less than 1 for a 1.5%/1.5 mm criteria (100% passing rate). Off axis profiles had >98.5% of data points producing a gamma value <1 with a 1%/1 mm criteria. All depth profiles produced 100% of data points with a gamma value <1 with a 1%/1 mm criteria. All data points measured were within 1.5% or 2 mm distance to agreement. CONCLUSIONS: This methodology allows for an increase in automation in the beam data validation process. Leveraging the application program interface allows the user to use a single system to create the measurement files, predict the result, and then compare to actual measurement increasing efficiency and reducing the chance for user input errors.

Characterization of a prototype rapid kilovoltage x-ray image guidance system designed for a ring shape radiation therapy unit.

PURPOSE: This study aims to characterize the performance of a prototype rapid kilovoltage (kV) x-ray image guidance system onboard the newly released Halcyon 2.0 linear accelerator (Varian Medical Systems, Palo Alto, CA) by use of conventional and innovatively designed testing procedures. METHODS: Basic imaging system performance tests and radiation dose measurements were performed for all eleven kV-cone beam computed tomography (CBCT) imaging protocols available on a preclinical Halcyon 2.0 LINAC. Both conventional CBCT reconstruction using the Feldkamp-Davis-Kress (FDK) algorithm and a novel, advanced iterative reconstruction (iCBCT) available on this platform were evaluated. Standard image quality metrics, including slice thickness accuracy, high-contrast resolution, low-contrast resolution, regional uniformity and noise, and CT Hounsfield unit (HU) number accuracy and linearity were evaluated using a manufacturer-supplied QUART phantom (GmbH, Zorneding, Germany) and an independent image quality phantom (Catphan 500, The Phantom Laboratory, New York, NY). Due to the simplified design of the QUART phantom, we developed surrogate and clinically feasible strategies for measuring slice thickness and high- and low-contrast resolution. Imaging dose delivered by these eleven protocols was measured using a computed tomography dose index phantom and pencil chamber with commonly accepted methods and procedures. A subset of measurements were repeated on a conventional C-arm LINAC (TrueBeam and Trilogy, Varian Medical System) for comparison. Clinical patient images of pelvic and abdominal regions are also presented for qualitative assessment as part of a feasibility study for clinical implementation. RESULTS: Image acquisition time was 17-42 s on the Halcyon system compared with 60 s on the C-arm LINAC systems. The kV imager projection offset, imaging and treatment isocenter coincidence and the couch three-dimensional match movement all achieved less than1 mm mechanical accuracy. All major image quality metrics were within either the national guideline or vendor-recommended tolerances. The designed surrogate approach with the QUART phantom showed a range of 0.24-0.35 cycles/mm for spatial resolution, a contrast-to-noise ratio (CNR) of 2-20 for FDK reconstruction and a tolerance of 0.5 mm for slice thickness. Other metrics derived from the Catphan images obtained on the Halcyon and C-arm LINACs showed comparable values for the FDK reconstruction. The iterative reconstruction tended to reduce noise, as evidenced by a higher CNR ratio. The fast scan pelvis protocols for Halcyon resulted in 50% lower dose compared to the standard scans, and the thorax fast protocol similarly delivered 10% lower dose than the standard thoracic scan. Preliminary patient images indicated that rapid kV CBCT with breath-hold is feasible, with improved imaging quality compared to free-breathing scans. CONCLUSION: Independent and comprehensive characterization of the kV imaging guidance system on the Halcyon 2.0 system demonstrated acceptable image quality for clinical use. The imaging unit onboard the Halcyon meets vendor specifications and satisfies requirements for routine clinical use. The fast kV imaging system enables the potential for volumetric CBCT acquisition during a single breath-hold and the iterative reconstruction tends to reduce the noise therefore has the potential to improve the CNR for normal size patient.

Treatment Outcome Prediction for Cancer Patients based on Radiomics and Belief Function Theory.

In this study, we proposed a new radiomics-based treatment outcome prediction model for cancer patients. The prediction model is developed based on belief function theory (BFT) and sparsity learning to address the challenges of redundancy, heterogeneity, and uncertainty of radiomic features, and relatively small-sized and unbalanced training samples. The model first selects the most predictive feature subsets from relatively large amounts of radiomic features extracted from pre- and/or in-treatment positron emission tomography (PET) images and available clinical and demographic features. Then an evidential k-nearest neighbor (EK-NN) classifier is proposed to utilize the selected features for treatment outcome prediction. Twenty-five stage II-III lung, 36 esophagus, 63 stage II-III cervix, and 45 lymphoma cancer patient cases were included in this retrospective study. Performance and robustness of the proposed model were assessed with measures of feature selection stability, outcome prediction accuracy, and receiver operating characteristics (ROC) analysis. Comparison with other methods were conducted to demonstrate the feasibility and superior performance of the proposed model.

A novel MRI segmentation method using CNN-based correction network for MRI-guided adaptive radiotherapy.

PURPOSE: The purpose of this study was to expedite the contouring process for MRI-guided adaptive radiotherapy (MR-IGART), a convolutional neural network (CNN) deep-learning (DL) model is proposed to accurately segment the liver, kidneys, stomach, bowel and duodenum in 3D MR images. METHODS: Images and structure contours for 120 patients were collected retrospectively. Treatment sites included pancreas, liver, stomach, adrenal gland, and prostate. The proposed DL model contains a voxel-wise label prediction CNN and a correction network which consists of two sub-networks. The prediction CNN and sub-networks in the correction network each includes a dense block which consists of twelve densely connected convolutional layers. The correction network was designed to improve the voxel-wise labeling accuracy of a CNN by learning and enforcing implicit anatomical constraints in the segmentation process. Its sub-networks learn to fix the erroneous classification of its previous network by taking as input both the original images and the softmax probability maps generated from its previous sub-network. The parameters of each sub-network were trained independently using piecewise training. The model was trained on 100 datasets, validated on 10 datasets and tested on the remaining 10 datasets. Dice coefficient, Hausdorff distance (HD) were calculated to evaluate the segmentation accuracy. RESULTS: The proposed DL model was able to segment the organs with good accuracy. The correction network outperformed the conditional random field (CRF), a most comparable method that is usually applied as a post-processing step. For the 10 testing patients, the average Dice coefficients were 95.3 ± 0.73, 93.1 ± 2.22, 85.0 ± 3.75, 86.6 ± 2.69, and 65.5 ± 8.90 for liver, kidneys, stomach, bowel, and duodenum, respectively. The mean Hausdorff Distance (HD) were 5.41 ± 2.34, 6.23 ± 4.59, 6.88 ± 4.89, 5.90 ± 4.05, and 7.99 ± 6.84 mm, respectively. Manual contouring, as to correct the automatic segmentation results, was four times as fast as manual contouring from scratch. CONCLUSION: The proposed method can automatically segment the liver, kidneys, stomach, bowel, and duodenum in 3D MR images with good accuracy. It is useful to expedite the manual contouring for MR-IGART.

A rapid, computational approach for assessing interfraction esophageal motion for use in stereotactic body radiation therapy planning.

PURPOSE: We present a rapid computational method for quantifying interfraction motion of the esophagus in patients undergoing stereotactic body radiation therapy on a magnetic resonance (MR) guided radiation therapy system. METHODS AND MATERIALS: Patients who underwent stereotactic body radiation therapy had simulation computed tomography (CT) and on-treatment MR scans performed. The esophagus was contoured on each scan. CT contours were transferred to MR volumes via rigid registration. Digital Imaging and Communications in Medicine files containing contour points were exported to MATLAB. In-plane CT and MR contour points were spline interpolated, yielding boundaries with centroid positions, CCT and CMR. MR contour points lying outside of the CT contour were extracted. For each such point, BMR(j), a segment from CCT intersecting BMR(j), was produced; its intersection with the CT contour, BCT(i), was calculated. The length of the segment Sij, between BCT(i) and BMR(j), was found. The orientation θ was calculated from Sij vector components:θ = arctan[(Sij)y / (Sij)x]A set of segments {Sij} was produced for each slice and binned by quadrant with 0° < θ ≤ 90°, 90° < θ ≤ 180°, 180° < θ ≤ 270°, and 270° < θ ≤ 360° for the left anterior, right anterior, right posterior, and left posterior quadrants, respectively. Slices were binned into upper, middle, and lower esophageal (LE) segments. RESULTS: Seven patients, each having 3 MR scans, were evaluated, yielding 1629 axial slices and 84,716 measurements. The LE segment exhibited the greatest magnitude of motion. The mean LE measurements in the left anterior, left posterior, right anterior, and right posterior were 5.2 ± 0.07 mm, 6.0 ± 0.09 mm, 4.8 ± 0.08 mm, and 5.1 ± 0.08 mm, respectively. There was considerable interpatient variability. CONCLUSIONS: The LE segment exhibited the greatest magnitude of mobility compared with the middle and upper esophageal segments. A novel computational method enables personalized, nonuniform esophageal margins to be tailored to individual patients.

A deep Boltzmann machine-driven level set method for heart motion tracking using cine MRI images.

Heart motion tracking for radiation therapy treatment planning can result in effective motion management strategies to minimize radiation-induced cardiotoxicity. However, automatic heart motion tracking is challenging due to factors that include the complex spatial relationship between the heart and its neighboring structures, dynamic changes in heart shape, and limited image contrast, resolution, and volume coverage. In this study, we developed and evaluated a deep generative shape model-driven level set method to address these challenges. The proposed heart motion tracking method makes use of a heart shape model that characterizes the statistical variations in heart shapes present in a training data set. This heart shape model was established by training a three-layered deep Boltzmann machine (DBM) in order to characterize both local and global heart shape variations. During the tracking phase, a distance regularized level-set evolution (DRLSE) method was applied to delineate the heart contour on each frame of a cine MRI image sequence. The trained shape model was embedded into the DRLSE method as a shape prior term to constrain an evolutional shape to reach the desired heart boundary. Frame-by-frame heart motion tracking was achieved by iteratively mapping the obtained heart contour for each frame to the next frame as a reliable initialization, and performing a level-set evolution. The performance of the proposed motion tracking method was demonstrated using thirty-eight coronal cine MRI image sequences.

Quantitative FDG-PET/CT predicts local recurrence and survival for squamous cell carcinoma of the anus.

PURPOSE: 18F-fluorodeoxyglucose (FDG) positron emission tomography-(PET)/computed tomography (CT) imaging is used for staging and treatment planning of patients with anal cancer. Quantitative pre- and posttreatment metrics that are predictive of recurrence are unknown. We evaluated the association between pre- and posttreatment FDG-PET/CT parameters and outcomes for patients with squamous cell carcinoma of the anus (SCCA). METHODS AND MATERIALS: The records of 110 patients treated between 2003 and 2013 with definitive radiation therapy for SCCA were reviewed under an institutional review board-approved protocol. The median radiation therapy dose was 50.4 Gy (range, 35-60 Gy). Concurrent chemotherapy was administered for 109 of 110 patients and generally consisted of 5-fluorouracil and mitomycin C (n = 94). All patients underwent pretreatment FDG-PET/CT and 101 of 110 underwent posttreatment FDG-PET/CT 3 months after completion of radiation therapy. The maximum standard uptake value (SUVmax) was analyzed, in addition to multiple patient and treatment factors, by univariate and multivariate Cox regression for correlation with local recurrence (LR) and overall survival (OS). RESULTS: The median follow-up was 28.6 months. LR occurred in 1 of 15 (6.7%), 5 of 47 (10.6%), and 6 of 48 (12.5%) patients with stage I, II, and III disease, respectively. On univariate analysis, a significant association was observed between reduced LR and posttreatment SUVmax <6.1 (P = .0095) and between increased OS and posttreatment SUVmax <6.1 (P = .0086). On multivariate analysis, a significant association was observed between reduced LR and posttreatment SUVmax <6.1 (P = .0013) and the use of intensity modulated radiation therapy (P < .001). A significant multivariate association was observed between increased OS and posttreatment SUVmax <6.1 (P = .0373) and the use of 5-fluorouracil/mitomycin C chemotherapy (P = .001). CONCLUSION: Posttreatment SUVmax <6.1 is associated with reduced LR and increased OS after chemoradiation therapy for SCCA independent of T and N stage on multivariate analysis. Greater follow-up is required to confirm this association with late patterns of failure.

Development of a fast Monte Carlo dose calculation system for online adaptive radiation therapy quality assurance.

Online adaptive radiation therapy (ART) based on real-time magnetic resonance imaging represents a paradigm-changing treatment scheme. However, conventional quality assurance (QA) methods based on phantom measurements are not feasible with the patient on the treatment couch. The purpose of this work is to develop a fast Monte Carlo system for validating online re-optimized tri-60Co IMRT adaptive plans with both high accuracy and speed. The Monte Carlo system is based on dose planning method (DPM) code with further simplification of electron transport and consideration of external magnetic fields. A vendor-provided head model was incorporated into the code. Both GPU acceleration and variance reduction were implemented. Additionally, to facilitate real-time decision support, a C++ GUI was developed for visualizing 3D dose distributions and performing various analyses in an online adaptive setting. A thoroughly validated Monte Carlo code (gPENELOPE) was used to benchmark the new system, named GPU-accelerated DPM with variance reduction (gDPMvr). The comparison using 15 clinical IMRT plans demonstrated that gDPMvr typically runs 43 times faster with only 0.5% loss in accuracy. Moreover, gDPMvr reached 1% local dose uncertainty within 2.3 min on average, and thus is well-suited for ART QA.

A method to reconstruct and apply 3D primary fluence for treatment delivery verification.

MOTIVATION: In this study, a method is reported to perform IMRT and VMAT treatment delivery verification using 3D volumetric primary beam fluences reconstructed directly from planned beam parameters and treatment delivery records. The goals of this paper are to demonstrate that 1) 3D beam fluences can be reconstructed efficiently, 2) quality assurance (QA) based on the reconstructed 3D fluences is capable of detecting additional treatment delivery errors, particularly for VMAT plans, beyond those identifiable by other existing treatment delivery verification methods, and 3) QA results based on 3D fluence calculation (3DFC) are correlated with QA results based on physical phantom measurements and radiation dose recalculations. METHODS: Using beam parameters extracted from DICOM plan files and treatment delivery log files, 3D volumetric primary fluences are reconstructed by forward-projecting the beam apertures, defined by the MLC leaf positions and modulated by beam MU values, at all gantry angles using first-order ray tracing. Treatment delivery verifications are performed by comparing 3D fluences reconstructed using beam parameters in delivery log files against those reconstructed from treatment plans. Passing rates are then determined using both voxel intensity differences and a 3D gamma analysis. QA sensitivity to various sources of errors is defined as the observed differences in passing rates. Correlations between passing rates obtained from QA derived from both 3D fluence calculations and physical measurements are investigated prospectively using 20 clinical treatment plans with artificially introduced machine delivery errors. RESULTS: Studies with artificially introduced errors show that common treatment delivery problems including gantry angle errors, MU errors, jaw position errors, collimator rotation errors, and MLC leaf position errors were detectable at less than normal machine tolerances. The reported 3DFC QA method has greater sensitivity than measurement-based QA methods. Statistical analysis-based Spearman's correlations shows that the 3DFC QA passing rates are significantly correlated with passing rates of physical phantom measurement-based QA methods. CONCLUSION: Among measurement-less treatment delivery verification methods, the reported 3DFC method is less demanding than those based on full dose re-calculations, and more comprehensive than those that solely checks beam parameters in treatment log files. With QA passing rates correlating to measurement-based passing rates, the 3DFC QA results could be useful for complementing the physical phantom measurements, or verifying treatment deliveries when physical measurements are not available. For the past 4+ years, the reported method has been implemented at authors' institution 1) as a complementary metric to physical phantom measurements for pretreatment, patient-specific QA of IMRT and VMAT plans, and 2) as an important part of the log file-based automated verification of daily patient treatment deliveries. It has been demonstrated to be useful in catching both treatment plan data transfer errors and treatment delivery problems.

Technical Note: A method to evaluate dosimetric effects on organs-at-risk for treatment delivery systematic uncertainties.

PURPOSE: The aim of this study is to provide a practical method to quantify the dosimetric effects on organs-at-risk (OARs) due to systematic uncertainties in linear accelerator treatment delivery in order to aid external beam treatment planning and raise warnings about additional risks to critical OARs. METHODS: A dose approximation method, based on geometrical transformations, was developed to automatically estimate perturbations to dose volumes arising from five important potential uncertainties at the time of treatment delivery, including (a) systematic isocenter misalignment between image guidance and beam delivery systems, and systematic errors in, (b) collimator, (c) gantry, (d) couch table, and (e) multi-leaf collimator (MLC) leaf bank positions. The agreement between the estimated dose volume using the dose approximation method and the re-calculated dose volume obtained from the treatment planning system (TPS) was verified using a dose difference test (2% threshold and 0 mm distance-to-agreement). For each type of uncertainty, the worst-case maximal dose values to the most critical OARs (brainstem, chiasm, optic nerves, and spinal cord) were quantitatively evaluated, and compared with the maximal dose values to the corresponding OARs from clinical plans. RESULTS: Six brain and six T-spine IMRT plans were used for evaluation. The average passing rates of 2% dose difference test were calculated to be 98.9% ± 1.3% for the uncertainties considered in this paper. The average time per patient to automatically analyze the dosimetric effects of all systematic uncertainties is 5.8 s. The worst-case scenarios for each plan, i.e., the largest changes in maximal doses to the OARs, were identified and confirmed to be in agreement with those calculated using the TPS. CONCLUSION: For a given external beam plan, the proposed dose approximation method allows efficient evaluation of the dosimetric effects of potential patient positioning uncertainties and systematic machine delivery errors on maximal dose to critical OARs. While the same uncertainties can be manually analyzed using the TPS, the proposed method is automatic and computationally inexpensive, and therefore significantly more practical. The proposed method could be useful to provide insights about otherwise unquantified risks and plan robustness during the stage of treatment planning.

Magnetic Resonance Image Guided Radiation Therapy for External Beam Accelerated Partial-Breast Irradiation: Evaluation of Delivered Dose and Intrafractional Cavity Motion.

PURPOSE: To use magnetic resonance image guided radiation therapy (MR-IGRT) for accelerated partial-breast irradiation (APBI) to (1) determine intrafractional motion of the breast surgical cavity; and (2) assess delivered dose versus planned dose. METHODS AND MATERIALS: Thirty women with breast cancer (stages 0-I) who underwent breast-conserving surgery were enrolled in a prospective registry evaluating APBI using a 0.35-T MR-IGRT system. Clinical target volume was defined as the surgical cavity plus a 1-cm margin (excluding chest wall, pectoral muscles, and 5 mm from skin). No additional margin was added for the planning target volume (PTV). A volumetric MR image was acquired before each fraction, and patients were set up to the surgical cavity as visualized on MR imaging. To determine the delivered dose for each fraction, the electron density map and contours from the computed tomography simulation were transferred to the pretreatment MR image via rigid registration. Intrafractional motion of the surgical cavity was determined by applying a tracking algorithm to the cavity contour as visualized on cine MR. RESULTS: Median PTV volume was reduced by 52% when using no PTV margin compared with a 1-cm PTV margin used conventionally. The mean (± standard deviation) difference between planned and delivered dose to the PTV (V95) was 0.6% ± 0.1%. The mean cavity displacement in the anterior-posterior and superior-inferior directions was 0.6 ± 0.4 mm and 0.6 ± 0.3 mm, respectively. The mean margin required for at least 90% of the cavity to be contained by the margin for 90% of the time was 0.7 mm (5th-95th percentile: 0-2.7 mm). CONCLUSION: Minimal intrafractional motion was observed, and the mean difference between planned and delivered dose was less than 1%. Assessment of efficacy and cosmesis of this MR-guided APBI approach is under way.