Evaluation of the organs at risk doses for lung tumors in gated and conventional radiotherapy.

PURPOSE: The purpose of this study was to evaluate the organs at risk (OARs) doses for lung tumors in gated radiotherapy (RT) compared to conventional RT using the four-dimensional extended cardiac-torso (4D-XCAT) digital phantom in a simulation study. MATERIALS AND METHODS: 4D-XCAT digital phantom was used to create 32 digital phantom datasets of different tumor diameters of 3 and 4 cm, and motion ranges (MRs) of 2, 2.5, 3, and 3.5 cm and each tumor was placed in four different lung locations (right lower lobe, right upper lobe, left lower lobe, and left upper lobe). XCAT raw binary images were converted to the digital imaging and communication in medicine format using an in-house MATLAB-based program and were imported to treatment planning system (TPS). For each dataset, gated and conventional treatment plans were prepared using Planning Computerized RadioTherapy-three dimensional (PCRT-3D) TPS with superposition computational algorithm. Dose differences between gated and conventional plans were evaluated and compared (as a function of 3D motion and tumor volume and its location) with respect to the dose-volume histograms of different organs-at-risk. RESULTS: There are statistically significant differences in dosimetric parameters among gated and conventional RT, especially for the tumors near the diaphragm (P < 0.05). The maximum reduction in the mean dose of the lung, heart, and liver were 6.11 Gy, 1.51 Gy, and 10.49 Gy, respectively, using gated RT. CONCLUSIONS: Dosimetric comparison between gated and conventional RT showed that gated RT provides relevant dosimetric improvements to lung normal tissue and the other OARs, especially for the tumors near the diaphragm. In addition, dosimetric differences between gated and conventional RT did generally increase with increasing tumor motion and decreasing tumor volume.

Assessment of range uncertainty in lung-like tissue using a porcine lung phantom and proton radiography.

Thoracic tumours are increasingly considered indications for pencil beam scanned proton therapy (PBS-PT) treatments. Conservative robustness settings have been suggested due to potential range straggling effects caused by the lung micro-structure. Using proton radiography (PR) and a 4D porcine lung phantom, we experimentally assess range errors to be considered in robust treatment planning for thoracic indications. A human-chest-size 4D phantom hosting inflatable porcine lungs and corresponding 4D computed tomography (4DCT) were used. Five PR frames were planned to intersect the phantom at various positions. Integral depth-dose curves (IDDs) per proton spot were measured using a multi-layer ionisation chamber (MLIC). Each PR frame consisted of 81 spots with an assigned energy of 210 MeV (full width at half maximum (FWHM) 8.2 mm). Each frame was delivered five times while simultaneously acquiring the breathing signal of the 4D phantom, using an ANZAI load cell. The synchronised ANZAI and delivery log file information was used to retrospectively sort spots into their corresponding breathing phase. Based on this information, IDDs were simulated by the treatment planning system (TPS) Monte Carlo dose engine on a dose grid of 1 mm. In addition to the time-resolved TPS calculations on the 4DCT phases, IDDs were calculated on the average CT. Measured IDDs were compared with simulated ones, calculating the range error for each individual spot. In total, 2025 proton spots were individually measured and analysed. The range error of a specific spot is reported relative to its water equivalent path length (WEPL). The mean relative range error was 1.2% (1.5 SD 2.3 %) for the comparison with the time-resolved TPS calculations, and 1.0% (1.5 SD 2.2 %) when comparing to TPS calculations on the average CT. The determined mean relative range errors justify the use of 3% range uncertainty for robust treatment planning in a clinical setting for thoracic indications.

Consistent and invertible deformation vector fields for a breathing anthropomorphic phantom: a post-processing framework for the XCAT phantom.

Breathing motion is challenging for radiotherapy planning and delivery. This requires advanced four-dimensional (4D) imaging and motion mitigation strategies and associated validation tools with known deformations. Numerical phantoms such as the XCAT provide reproducible and realistic data for simulation-based validation. However, the XCAT generates partially inconsistent and non-invertible deformations where tumours remain rigid and structures can move through each other. We address these limitations by post-processing the XCAT deformation vector fields (DVF) to generate a breathing phantom with realistic motion and quantifiable deformation. An open-source post-processing framework was developed that corrects and inverts the XCAT-DVFs while preserving sliding motion between organs. Those post-processed DVFs are used to warp the first XCAT-generated image to consecutive time points providing a 4D phantom with a tumour that moves consistently with the anatomy, the ability to scale lung density as well as consistent and invertible DVFs. For a regularly breathing case, the inverse consistency of the DVFs was verified and the tumour motion was compared to the original XCAT. The generated phantom and DVFs were used to validate a motion-including dose reconstruction (MIDR) method using isocenter shifts to emulate rigid motion. Differences between the reconstructed doses with and without lung density scaling were evaluated. The post-processing framework produced DVFs with a maximum [Formula: see text]-percentile inverse-consistency error of 0.02 mm. The generated phantom preserved the dominant sliding motion between the chest wall and inner organs. The tumour of the original XCAT phantom preserved its trajectory while deforming consistently with the underlying tissue. The MIDR was compared to the ground truth dose reconstruction illustrating its limitations. MIDR with and without lung density scaling resulted in small dose differences up to 1 Gy (prescription 54 Gy). The proposed open-source post-processing framework overcomes important limitations of the original XCAT phantom and makes it applicable to a wider range of validation applications within radiotherapy.

Development of realistic multi-contrast textured XCAT (MT-XCAT) phantoms using a dual-discriminator conditional-generative adversarial network (D-CGAN).

Develop a machine learning-based method to generate multi-contrast anatomical textures in the 4D extended cardiac-torso (XCAT) phantom for more realistic imaging simulations. As a pilot study, we synthesize CT and CBCT textures in the chest region. For training purposes, major organs and gross tumor volumes (GTVs) in chest region were segmented from real patient images and assigned to different HU values to generate organ maps, which resemble the XCAT images. A dual-discriminator conditional-generative adversarial network (D-CGAN) was developed to synthesize anatomical textures in the corresponding organ maps. The D-CGAN was uniquely designed with two discriminators, one trained for the body and the other for the tumor. Various XCAT phantoms were input to the D-CGAN to generate textured XCAT phantoms. The D-CGAN model was trained separately using 62 CT and 63 CBCT images from lung SBRT patients to generate multi-contrast textured XCAT (MT-XCAT). The MT-XCAT phantoms were evaluated by comparing the intensity histograms and radiomic features with those from real patient images using Wilcoxon rank-sum test. The visual examination demonstrated that the MT-XCAT phantoms presented similar general contrast and anatomical textures as CT and CBCT images. The mean HU of the MT-XCAT-CT and MT-XCAT-CBCT were [Formula: see text] and [Formula: see text], compared with that of real CT ([Formula: see text]) and CBCT ([Formula: see text]). The majority of radiomic features from the MT-XCAT phantoms followed the same distribution as the real images according to the Wilcoxon rank-sum test, except for limited second-order features. The study demonstrated the feasibility of generating realistic MT-XCAT phantoms using D-CGAN. The MT-XCAT phantoms can be further expanded to include other modalities (MRI, PET, ultrasound, etc) under the same scheme. This crucial development greatly enhances the value of the phantom for various clinical applications, including testing and optimizing novel imaging techniques, validation of radiomics analysis methods, and virtual clinical trials.

Real-time direct diaphragm tracking using kV imaging on a standard linear accelerator.

PURPOSE: As the predominant driver of respiratory motion, the diaphragm represents a key surrogate for motion management during the irradiation of thoracic cancers. Existing approaches to diaphragm tracking often produce phase-based estimates, suffer from lateral side failures or are not executable in real-time. In this paper, we present an algorithm that continuously produces real-time estimates of three-dimensional (3D) diaphragm position using kV images acquired on a standard linear accelerator. METHODS: Patient-specific 3D diaphragm models were generated via automatic segmentation on end-exhale four-dimensional-computed tomography (4D-CT) images. The estimated trajectory of diaphragmatic motion, referred to as the principal motion vector, was obtained by registering end-exhale to end-inhale 4D-CT images. Two-dimensional (2D) diaphragm masks were generated by forward-projecting 3D models over the complement of angles spanned during kV image acquisition. For each kV image, diaphragm position was determined by shifting angle-matched 2D masks along the principal motion vector and selecting the position of highest contrast on a vertical difference image. Retrospective analysis was performed using 22 cone beam CT (CBCT) image sequences for six lung cancer patients across two datasets. Given the current lack of objective ground truth for diaphragm position, our algorithm was evaluated by examining its ability to track implanted markers. Simple linear regression was used to construct 3D marker motion models and estimation errors were computed as the difference between estimated and ground truth marker positions. Additionally, Pearson correlation coefficients were used to characterize diaphragm-marker correlation. RESULTS: The mean ± standard deviation of the estimation errors across all image sequences was -0.1 ± 0.7 mm, -0.1 ± 1.8 mm and 0.2 ± 1.4 mm in the LR, SI, and AP directions respectively. The 95th percentile of the absolute errors ranged over 0.5-3.1 mm, 1.6-6.7 mm, and 1.2-4.0 mm in the LR, SI, and AP directions, respectively. The mean ± standard deviation of diaphragm-marker correlations over all image sequences was -0.07 ± 0.57, 0.67 ± 0.49, and 0.29 ± 0.52 in the LR, SI, and AP directions, respectively. Diaphragm-marker correlation was observed to be highly dependent on marker position. Mean correlation along the SI axis ranged over 0.91-0.93 for markers situated in the lower lobes of the lung, while correlations ranging over -0.51-0.79 were observed for markers situated in the upper and middle lobes. CONCLUSION: This work advances a new approach to real-time direct diaphragm tracking in realistic treatment scenarios. By achieving continuous estimates of diaphragmatic motion, the proposed method has applications for both markerless tumor tracking and respiratory binning in 4D-CBCT.

Continuous generation of volumetric images during stereotactic body radiation therapy using periodic kV imaging and an external respiratory surrogate.

We present a technique for continuous generation of volumetric images during SBRT using periodic kV imaging and an external respiratory surrogate signal to drive a patient-specific PCA motion model. Using the on-board imager, kV radiographs are acquired every 3 s and used to fit the parameters of a motion model so that it matches observed changes in internal patient anatomy. A multi-dimensional correlation model is established between the motion model parameters and the external surrogate position and velocity, enabling volumetric image reconstruction between kV imaging time points. Performance of the algorithm was evaluated using 10 realistic eXtended CArdiac-Torso (XCAT) digital phantoms including 3D anatomical respiratory deformation programmed with 3D tumor positions measured with orthogonal kV imaging of implanted fiducial gold markers. The clinically measured ground truth 3D tumor positions provided a dataset with realistic breathing irregularities, and the combination of periodic on-board kV imaging with recorded external respiratory surrogate signal was used for correlation modeling to account for any changes in internal-external correlation. The three-dimensional tumor positions are reconstructed with an average root mean square error (RMSE) of 1.47 mm, and an average 95th percentile 3D positional error of 2.80 mm compared with the clinically measured ground truth 3D tumor positions. This technique enables continuous 3D anatomical image generation based on periodic kV imaging of internal anatomy without the additional dose of continuous kV imaging. The 3D anatomical images produced using this method can be used for treatment verification and delivered dose computation in the presence of irregular respiratory motion.

Basic evaluation of a novel 4D target and human body phantom.

Stereotactic body radiation therapy (SBRT) is usually verified with a dynamic phantom or solid phantom, but there is a demand for phantoms that can accurately simulate tumor dynamics within an individual that would allow customized validation in every patient. We developed a new 4D dynamic target phantom (multi-cell 4D phantom) that allows simulation of tumor movement in patients. The basic quality and dynamic reproducibility of this new phantom was verified in this investigation. The newly developed multi-cell 4D phantom comprises four main components: soft tissue, bones, lungs, and tumor (target). The phantom structure was based on computed tomography (CT) data of a male. In this study, we investigated the basic performance of a multi-cell 4D phantom. All the CT numbers of the phantom were very close to those of human data. The geometric maximum amplitudes were 4.57 mm in the lateral direction, 4.59 mm in the ventrodorsal direction, and 3.68 mm in the cranio-caudal direction. Geometric errors were 0.84, 0.58, and 0.40 mm, respectively. Movements of the abdominal surface were stable for 60 s. Repeated measurements show no actual differences in target movements between multiple measurements and indicated high reproducibility (r > 0.97). End-to-end tests using Gafchromic film revealed a gamma pass rate of 98% or above (2 mm/3%). Although our phantom performed limited reproducibility in the movement of the patient tumor at present, a satisfactory level of precision was confirmed in general. This is a very promising device for use in the verification of radiation therapy for moving targets.

4D digital tomosynthesis image reconstruction using brute force-based adaptive total variation (BF-ATV) in a prototype LINAC system.

Respiratory-correlated cone-beam CT (CBCT) not only inhibits rapid scanning due to the slow speed of the LINAC head gantry rotation, but its implementation for routine patient imaging is impractical because of the high radiation dose delivered during the process. Digital tomosynthesis (DTS) is a potentially faster technique that delivers a much lower radiation dose by reducing the number of projections in a limited angular range. Unfortunately, 4D-DTS introduces strong aliasing artifacts in the reconstructed images due to the sparsely sampled projections in each respiratory phase bin. The authors hereby suggest a novel low-dose 4D-DTS image reconstruction method that achieves a compromise between the occurrence of aliasing artifacts and image smoothing using a brute force-based adaptive weighting parameter searching technique. We used a prototype LINAC system mounted with a flat-panel detector to acquire tomosynthesis projections of respiratory motion in a phantom in the anterior-posterior (AP) and lateral views. Three different 4D-DTS image reconstruction schemes that included conventional filtered back-projection (FBP), adaptive steepest descent projection onto convex sets (ASD-POCS), and the proposed brute force-based adaptive total variation (BF-ATV) were implemented in four different respiratory phase bins for both AP and lateral views. All reconstructions were accelerated using a single GPU card to reduce the computation time. To study the performance of the algorithm under various sparse conditions, we operated the prototype system in three different gantry sweep modes. The results indicate that the proposed BF-ATV method yields the largest structural similarities in the differenced image between the ground-truth dataset acquired using the slow gantry sweep mode and the sparse dataset from both moderate and fast sweep modes. In addition, the proposed method maintained the object sharpness with less streaking lines and small loss of sharpness compared to the conventional FBP and ASD-POCS methods. In conclusion, the proposed low-dose 4D-DTS reconstruction scheme may provide better performance due in part to its rapid scanning. Therefore, it is potentially applicable to practical 4D imaging for radiotherapy.

Feasibility of 4DCBCT-based proton dose calculation: An ex vivo porcine lung phantom study.

Inter-fractional variations of breathing pattern and patient anatomy introduce dose uncertainties in proton therapy. One approach to monitor these variations is to utilize the cone-beam computed tomography (CT, CBCT) scans routinely taken for patient positioning, reconstruct them as 4DCBCTs, and generate 'virtual CTs' (vCTs), combining the accurate CT numbers of the diagnostic 4DCT and the geometry of the daily 4DCBCT by using deformable image registration (DIR). In this study different algorithms for 4DCBCT reconstruction and DIR were evaluated. For this purpose, CBCT scans of a moving ex vivo porcine lung phantom with 663 and 2350 projections respectively were acquired, accompanied by an additional 4DCT as reference. The CBCT projections were sorted in 10 phase bins with the Amsterdam-shroud method and reconstructed phase-by-phase using first a FDK reconstruction from the Reconstruction Toolkit (RTK) and again an iterative reconstruction algorithm implemented in the Gadgetron Toolkit. The resulting 4DCBCTs were corrected by DIR of the corresponding 4DCT phases, using both a morphons algorithm from REGGUI and a b-spline deformation from Plastimatch. The resulting 4DvCTs were compared to the 4DCT by visual inspection and by calculating water equivalent thickness (WET) maps from the phantom's surface to the distal edge of a target from various angles. The optimized procedure was successfully repeated with mismatched input phases and on a clinical patient dataset. Proton treatment plans were simulated on the 4DvCTs and the dose distributions compared to the reference based on the 4DCT via gamma pass rate analysis. A combination of iterative reconstruction and morphons DIR yielded the most accurate 4DvCTs, with median WET differences under 2mm and 3%/3mm gamma pass rates per phase between 89% and 99%. These results suggest that image correction of iteratively reconstructed 4DCBCTs with a morphons DIR of the planning CT may yield sufficiently accurate 4DvCTs for daily time resolved proton dose calculations.

Cine 4DCT imaging artifacts: Quantification and correlations with scanning parameters and target kinetics.

To study temporal resolved computed tomography imaging (4-Dimensional Computed Tomography: 4DCT) artifacts correlations with scanning parameters and target kinetics and to assess uncertainty introduced by 4DCT in radiotherapy treatment planning. In this work we classified 4DCT artifacts as finite gantry rotation speed related (FGS) and finite sampling frequency related (FSF). We studied FGS artifacts using a respiratory phantom and FSF artifacts using a Monte Carlo simulation of acquisition timing. From our analysis FGS localization error is comparable with image resolution determined by voxel dimensions. Remaining FGS artifacts are correlated with gantry rotation time (Trot), target velocity (v) and their interaction. FSF artifacts occurrence is correlated with sampling ratio (SR), i.e. the ratio of patient respiratory period (Tresp) and sampling time (Ts). In the studied velocity range (0-2 cm/s), using a Trot of 0,5s and a SR higher than 15, FGS and FSF artifacts became comparable with other sources of uncertainty. Our considerations are valid for "ideal" breathing pattern only. When variations from periodical breathing, high target velocity (more than 2 cm/s) or high peak to peak amplitude (more than 2 cm) are present, patient specific images artifacts analysis is recommended.

Development of a deformable phantom for experimental verification of 4D Monte Carlo simulations in a deforming anatomy.

PURPOSE: To verify the accuracy of 4D Monte Carlo (MC) simulations, using the 4DdefDOSXYZnrc user code, in a deforming anatomy. We developed a tissue-equivalent and reproducible deformable lung phantom and evaluated 4D simulations of delivered dose to the phantom by comparing calculations against measurements. METHODS: A novel deformable phantom consisting of flexible foam, emulating lung tissue, inside a Lucite external body was constructed. A removable plug, containing an elastic tumor that can hold film and other dosimeters, was inserted in the phantom. Point dose and position measurements were performed inside and outside the tumor using RADPOS 4D dosimetry system. The phantom was irradiated on an Elekta Infinity linac in both stationary and moving states. The dose delivery was simulated using delivery log files and the phantom motion recorded with RADPOS. RESULTS: Reproducibility of the phantom motion was determined to be within 1 mm. The phantom motion presented realistic features like hysteresis. MC calculations and measurements agreed within 2% at the center of tumor. Outside the tumor agreements were better than 5% which were within the positional/dose reading uncertainties at the measurement points. More than 94% of dose points from MC simulations agreed within 2%/2 mm compared to film measurements. CONCLUSION: The deformable lung phantom presented realistic and reproducible motion characteristics and its use for verification of 4D dose calculations was demonstrated. Our 4DMC method is capable of accurate calculations of the realistic dose delivered to a moving and deforming anatomy during static and dynamic beam delivery techniques.

Evaluation of normal lung tissue complication probability in gated and conventional radiotherapy using the 4D XCAT digital phantom.

PURPOSE: The present study was conducted to investigate normal lung tissue complication probability in gated and conventional radiotherapy (RT) as a function of diaphragm motion, lesion size, and its location using 4D-XCAT digital phantom in a simulation study. MATERIALS AND METHODS: Different time series of 3D-CT images were generated using the 4D-XCAT digital phantom. The binary data obtained from this phantom were then converted to the digital imaging and communication in medicine (DICOM) format using an in-house MATLAB-based program to be compatible with our treatment planning system (TPS). The 3D-TPS with superposition computational algorithm was used to generate conventional and gated plans. Treatment plans were generated for 36 different XCAT phantom configurations. These included four diaphragm motions of 20, 25, 30 and 35 mm, three lesion sizes of 3, 4, and 5 cm in diameter and each tumor was placed in four different lung locations (right lower lobe, right upper lobe, left lower lobe and left upper lobe). The complication of normal lung tissue was assessed in terms of mean lung dose (MLD), the lung volume receiving ≥20 Gy (V20), and normal tissue complication probability (NTCP). RESULTS: The results showed that the gated RT yields superior outcomes in terms of normal tissue complication compared to the conventional RT. For all cases, the gated radiation therapy technique reduced the mean dose, V20, and NTCP of lung tissue by up to 5.53 Gy, 13.38%, and 23.89%, respectively. CONCLUSIONS: The results of this study showed that the gated RT provides significant advantages in terms of the normal lung tissue complication, compared to the conventional RT, especially for the lesions near the diaphragm.

A CBCT study of the gravity-induced movement in rotating rabbits.

Fixed-beam radiotherapy systems with subjects rotating about a longitudinal (horizontal) axis are subject to gravity-induced motion. Limited reports on the degree of this motion, and any deformation, has been reported previously. The purpose of this study is to quantify the degree of anatomical motion caused by rotating a subject around a longitudinal axis, using cone-beam CT (CBCT). In the current study, a purpose-made longitudinal rotating was aligned to a Varian TrueBeam kV imaging system. CBCT images of three live rabbits were acquired at fixed rotational offsets of the cradle. Rigid and deformable image registrations back to the original position were used to quantify the motion experienced by the subjects under rotation. In the rotation offset CBCTs, the mean magnitude of rigid translations was 5.7 ± 2.7 mm across all rabbits and all rotations. The translation motion was reproducible between multiple rotations within 2.1 mm, 1.1 mm, and 2.8 mm difference for rabbit 1, 2, and 3, respectively. The magnitude of the mean and absolute maximum deformation vectors were 0.2 ± 0.1 mm and 5.4 ± 2.0 mm respectively, indicating small residual deformations after rigid registration. In the non-rotated rabbit 4DCBCT, respiratory diaphragm motion up to 5 mm was observed, and the variation in respiratory motion as measured from a series of 4DCBCT scans acquired at each rotation position was small. The principle motion of the rotated subjects was rigid translational motion. The deformation of the anatomy under rotation was found to be similar in scale to normal respiratory motion. This indicates imaging and treatment of rotated subjects with fixed-beam systems can use rigid registration as the primary mode of motion estimation. While the scaling of deformation from rabbits to humans is uncertain, these proof-of-principle results indicate promise for fixed-beam treatment systems.

Image quality of four-dimensional cone-beam computed tomography obtained at various gantry rotation speeds for liver stereotactic body radiation therapy with fiducial markers.

In this study, qualities of 4D cone-beam CT (CBCT) images obtained using various gantry rotation speeds (GRSs) for liver stereotactic body radiation therapy (SBRT) with fiducial markers were quantitatively evaluated. Abdominal phantom containing a fiducial marker was moved along a sinusoidal waveform, and 4D-CBCT images were acquired with GRSs of 50-200°â€¯min-1. We obtained the 4D-CBCT projection data from six patients who underwent liver SBRT and generated 4D-CBCT images at GRSs of 67-200°â€¯min-1, by varying the number of projection data points. The image quality was evaluated based on the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and structural similarity index (SSIM). The fiducial marker positions with different GRSs were compared with the setup values and a reference position in the phantom and clinical studies, respectively. The root mean square errors (RMSEs) were calculated relative to the reference positions. In the phantom study, the mean SNR, CNR, and SSIM decreased from 37.6 to 10.1, from 39.8 to 10.1, and from 0.9 to 0.7, respectively, as the GRS increased from 50 to 200°â€¯min-1. The fiducial marker positions were within 2.0 mm at all GRSs. Similarly, in the clinical study, the mean SNR, CNR, and SSIM decreased from 50.4 to 13.7, from 24.2 to 6.0, and from 0.92 to 0.73, respectively. The mean RMSEs were 2.0, 2.1, and 3.6 mm for the GRSs of 67, 100, and 200°â€¯min-1, respectively. We conclude that GRSs of 67 and 85°â€¯min-1 yield images of acceptable quality for 4D-CBCT in liver SBRT with fiducial markers.

Multi-GPU configuration of 4D intensity modulated radiation therapy inverse planning using global optimization.

We report on the design, implementation and characterization of a multi-graphic processing unit (GPU) computational platform for higher-order optimization in radiotherapy treatment planning. In collaboration with a commercial vendor (Varian Medical Systems, Palo Alto, CA), a research prototype GPU-enabled Eclipse (V13.6) workstation was configured. The hardware consisted of dual 8-core Xeon processors, 256 GB RAM and four NVIDIA Tesla K80 general purpose GPUs. We demonstrate the utility of this platform for large radiotherapy optimization problems through the development and characterization of a parallelized particle swarm optimization (PSO) four dimensional (4D) intensity modulated radiation therapy (IMRT) technique. The PSO engine was coupled to the Eclipse treatment planning system via a vendor-provided scripting interface. Specific challenges addressed in this implementation were (i) data management and (ii) non-uniform memory access (NUMA). For the former, we alternated between parameters over which the computation process was parallelized. For the latter, we reduced the amount of data required to be transferred over the NUMA bridge. The datasets examined in this study were approximately 300 GB in size, including 4D computed tomography images, anatomical structure contours and dose deposition matrices. For evaluation, we created a 4D-IMRT treatment plan for one lung cancer patient and analyzed computation speed while varying several parameters (number of respiratory phases, GPUs, PSO particles, and data matrix sizes). The optimized 4D-IMRT plan enhanced sparing of organs at risk by an average reduction of [Formula: see text] in maximum dose, compared to the clinical optimized IMRT plan, where the internal target volume was used. We validated our computation time analyses in two additional cases. The computation speed in our implementation did not monotonically increase with the number of GPUs. The optimal number of GPUs (five, in our study) is directly related to the hardware specifications. The optimization process took 35 min using 50 PSO particles, 25 iterations and 5 GPUs.

Optical computed tomography for spatially isotropic four-dimensional imaging of live single cells.

Quantitative three-dimensional (3D) computed tomography (CT) imaging of living single cells enables orientation-independent morphometric analysis of the intricacies of cellular physiology. Since its invention, x-ray CT has become indispensable in the clinic for diagnostic and prognostic purposes due to its quantitative absorption-based imaging in true 3D that allows objects of interest to be viewed and measured from any orientation. However, x-ray CT has not been useful at the level of single cells because there is insufficient contrast to form an image. Recently, optical CT has been developed successfully for fixed cells, but this technology called Cell-CT is incompatible with live-cell imaging due to the use of stains, such as hematoxylin, that are not compatible with cell viability. We present a novel development of optical CT for quantitative, multispectral functional 4D (three spatial + one spectral dimension) imaging of living single cells. The method applied to immune system cells offers truly isotropic 3D spatial resolution and enables time-resolved imaging studies of cells suspended in aqueous medium. Using live-cell optical CT, we found a heterogeneous response to mitochondrial fission inhibition in mouse macrophages and differential basal remodeling of small (0.1 to 1 fl) and large (1 to 20 fl) nuclear and mitochondrial structures on a 20- to 30-s time scale in human myelogenous leukemia cells. Because of its robust 3D measurement capabilities, live-cell optical CT represents a powerful new tool in the biomedical research field.

Contour propagation for lung tumor delineation in 4D-CT using tensor-product surface of uniform and non-uniform closed cubic B-splines.

A robust contour propagation method is proposed to help physicians delineate lung tumors on all phase images of four-dimensional computed tomography (4D-CT) by only manually delineating the contours on a reference phase. The proposed method models the trajectory surface swept by a contour in a respiratory cycle as a tensor-product surface of two closed cubic B-spline curves: a non-uniform B-spline curve which models the contour and a uniform B-spline curve which models the trajectory of a point on the contour. The surface is treated as a deformable entity, and is optimized from an initial surface by moving its control vertices such that the sum of the intensity similarities between the sampling points on the manually delineated contour and their corresponding ones on different phases is maximized. The initial surface is constructed by fitting the manually delineated contour on the reference phase with a closed B-spline curve. In this way, the proposed method can focus the registration on the contour instead of the entire image to prevent the deformation of the contour from being smoothed by its surrounding tissues, and greatly reduce the time consumption while keeping the accuracy of the contour propagation as well as the temporal consistency of the estimated respiratory motions across all phases in 4D-CT. Eighteen 4D-CT cases with 235 gross tumor volume (GTV) contours on the maximal inhale phase and 209 GTV contours on the maximal exhale phase are manually delineated slice by slice. The maximal inhale phase is used as the reference phase, which provides the initial contours. On the maximal exhale phase, the Jaccard similarity coefficient between the propagated GTV and the manually delineated GTV is 0.881 [Formula: see text] 0.026, and the Hausdorff distance is 3.07 [Formula: see text] 1.08 mm. The time for propagating the GTV to all phases is 5.55 [Formula: see text] 6.21 min. The results are better than those of the fast adaptive stochastic gradient descent B-spline method, the 3D + t B-spline method and the diffeomorphic demons method. The proposed method is useful for helping physicians delineate target volumes efficiently and accurately.

A novel 3D-printed phantom insert for 4D PET/CT imaging and simultaneous integrated boost radiotherapy.

PURPOSE: To construct a 3D-printed phantom insert designed to mimic the variable PET tracer uptake seen in lung tumor volumes and a matching dosimetric insert to be used in simultaneous integrated boost (SIB) phantom studies, and to evaluate the design through end-to-end tests. METHODS: A set of phantom inserts was designed and manufactured for a realistic representation of gated radiotherapy steps from 4D PET/CT scanning to dose delivery. A cylindrical phantom (φ80 × 120 mm) holds inserts for PET/CT scanning. The novel 3D printed insert dedicated to 4D PET/CT mimics high PET tracer uptake in the core and low uptake in the periphery. This insert is a variable density porous cylinder (φ44.5 × 70.0 mm), ABS-P430 thermoplastic, 3D printed by fused deposition modeling an inner (φ11 × 42 mm) cylindrical void. The square pores (1.8 × 1.8 mm2 each) fill 50% of outer volume, resulting in a 2:1 PET tracer concentration ratio in the void volume with respect to porous volume. A matching cylindrical phantom insert is dedicated to validate gated radiotherapy. It contains eight peripheral holes and one central hole, matching the location of the porous part and the void part of the 3D printed insert, respectively. These holes accommodate adaptors for Farmer-type ion chamber and cells vials. End-to-end tests were designed for imaging, planning, and dose measurements. RESULTS: End-to-end test were performed from 4D PET/CT scanning to transferring data to the planning system, target volume delineation, and dose measurements. 4D PET/CT scans were acquired of the phantom at different respiratory motion patterns and gating windows. A measured 2:1 18F-FDG concentration ratio between inner void and outer porous volume matched the 3D printed design. Measured dose in the dosimetric insert agreed well with planned dose on the imaging insert, within 3% for the static phantom and within 5% for most breathing patterns. CONCLUSIONS: The novel 3D printed phantom insert mimics variable PET tracer uptake typical of tumors. Obtained 4D PET/CT scans are suitable for segmentation and treatment planning and delivery in SIB gated treatments. Our experiments demonstrate the feasibility of this set of phantom inserts serving as end-to-end quality-assurance phantoms of SIB radiotherapy.

Reducing 4DCBCT imaging time and dose: the first implementation of variable gantry speed 4DCBCT on a linear accelerator.

Four dimensional cone beam computed tomography (4DCBCT) uses a constant gantry speed and imaging frequency that are independent of the patient's breathing rate. Using a technique called respiratory motion guided 4DCBCT (RMG-4DCBCT), we have previously demonstrated that by varying the gantry speed and imaging frequency, in response to changes in the patient's real-time respiratory signal, the imaging dose can be reduced by 50-70%. RMG-4DCBCT optimally computes a patient specific gantry trajectory to eliminate streaking artefacts and projection clustering that is inherent in 4DCBCT imaging. The gantry trajectory is continuously updated as projection data is acquired and the patient's breathing changes. The aim of this study was to realise RMG-4DCBCT for the first time on a linear accelerator. To change the gantry speed in real-time a potentiometer under microcontroller control was used to adjust the current supplied to an Elekta Synergy's gantry motor. A real-time feedback loop was developed on the microcontroller to modulate the gantry speed and projection acquisition in response to the real-time respiratory signal so that either 40, RMG-4DCBCT40, or 60, RMG-4DCBCT60, uniformly spaced projections were acquired in 10 phase bins. Images of the CIRS dynamic Thorax phantom were acquired with sinusoidal breathing periods ranging from 2 s to 8 s together with two breathing traces from lung cancer patients. Image quality was assessed using the contrast to noise ratio (CNR) and edge response width (ERW). For the average patient, with a 3.8 s breathing period, the imaging time and image dose were reduced by 37% and 70% respectively. Across all respiratory rates, RMG-4DCBCT40 had a CNR in the range of 6.5 to 7.5, and RMG-4DCBCT60 had a CNR between 8.7 and 9.7, indicating that RMG-4DCBCT allows consistent and controllable CNR. In comparison, the CNR for conventional 4DCBCT drops from 20.4 to 6.2 as the breathing rate increases from 2 s to 8 s. With RMG-4DCBCT, the ERW in the direction of motion of the imaging insert decreases from 2.1 mm to 1.1 mm as the breathing rate increases from 2 s to 8 s while for conventional 4DCBCT the ERW increases from 1.9 mm to 2.5 mm. Image quality can be controlled during 4DCBCT acquisition by varying the gantry speed and the projection acquisition in response to the patient's real-time respiratory signal. However, although the image sharpness, i.e. ERW, is improved with RMG-4DCBCT, the ERW depends on the patient's breathing rate and breathing regularity.

Development of a four-dimensional Monte Carlo dose calculation system for real-time tumor-tracking irradiation with a gimbaled X-ray head.

PURPOSE: To develop a four-dimensional (4D) dose calculation system for real-time tumor tracking (RTTT) irradiation by the Vero4DRT. METHODS: First, a 6-MV photon beam delivered by the Vero4DRT was simulated using EGSnrc. A moving phantom position was directly measured by a laser displacement gauge. The pan and tilt angles, monitor units, and the indexing time indicating the phantom position were also extracted from a log file. Next, phase space data at any angle were created from both the log file and particle data under the dynamic multileaf collimator. Irradiation both with and without RTTT, with the phantom moving, were simulated using several treatment field sizes. Each was compared with the corresponding measurement using films. Finally, dose calculation for each computed tomography dataset of 10 respiratory phases with the X-ray head rotated was performed to simulate the RTTT irradiation (4D plan) for lung, liver, and pancreatic cancer patients. Dose-volume histograms of the 4D plan were compared with those calculated on the single reference respiratory phase without the gimbal rotation [three-dimensional (3D) plan]. RESULTS: Differences between the simulated and measured doses were less than 3% for RTTT irradiation in most areas, except the high-dose gradient. For clinical cases, the target coverage in 4D plans was almost identical to that of the 3D plans. However, the doses to organs at risk in the 4D plans varied at intermediate- and low-dose levels. CONCLUSIONS: Our proposed system has acceptable accuracy for RTTT irradiation in the Vero4DRT and is capable of simulating clinical RTTT plans.