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Objective. Cone-beam CT (CBCT) in modern pre-clinical small-animal radiation research platforms provides volumetric images for image guidance and experiment planning purposes. In this work, we implemented multi-energy element-resolved (MEER) CBCT using three scans with different kVps on a SmART platform (Precision x-ray Inc.) to determine images of relative electron density (rED) and elemental composition (EC) that are needed for Monte Carlo-based radiation dose calculation. Approach. We performed comprehensive calibration tasks to achieve sufficient accuracy for this quantitative imaging purpose. For geometry calibration, we scanned a ball bearing phantom and used an analytical method together with an optimization approach to derive gantry angle specific geometry parameters. Intensity calibration and correction included the corrections for detector lag, glare, and beam hardening. The corrected CBCT projection images acquired at 30, 40, and 60 kVp in multiple scans were used to reconstruct CBCT images using the Feldkamp–Davis–Kress reconstruction algorithm. After that, an optimization problem was solved to determine images of rED and EC. We demonstrated the effectiveness of our CBCT calibration steps by showing improvements in image quality and successful material decomposition in cases with a small animal CT calibration phantom and a plastinated mouse phantom. Main results. It was found that artifacts induced by geometry inaccuracy, detector lag, glare, and beam hardening were visually reduced. CT number mean errors were reduced from 19% to 5%. In the CT calibration phantom case, median errors in H, O, and Ca fractions for all the inserts were below 1%, 2%, and 4% respectively, and median error in rED was less than 5%. Compared to the standard approach deriving material type and rED via CT number conversion, our approach improved Monte Carlo simulation-based dose calculation accuracy in bone regions. Mean dose error was reduced from 47.5% to 10.9%. Significance. The MEER-CBCT implemented on an existing CBCT system of a small animal irradiation platform achieved accurate material decomposition and significantly improved Monte Carlo dose calculation accuracy. more...

PURPOSE: We have previously proposed an intelligent automatic treatment planning (IATP) framework that builds a virtual treatment planner network (VTPN) to operate a treatment planning system (TPS) to generate high-quality radiation therapy (RT) treatment plans. While the potential of IATP in automating RT treatment planning has been demonstrated, its poor scalability caused by an almost linear growth of network size with the number of treatment planning parameters (TPPs) is a bottleneck, preventing its application in complicate, but clinically relevant treatment planning problems. The decision-making behavior of the trained network is hard to understand. Motivated by the decision-making process of a human planner, this study proposes a hierarchical IATP framework. METHODS AND MATERIALS: The hierarchical VTPN (HieVTPN) consists of three networks, i.e. Structure-Net, Parameter-Net, and Action-Net. When interacting with a TPS, the networks are employed in a sequential order in each step to decide the structure to adjust, the TPP to adjust for the selected structure, and the specific adjustment manner for the parameter, respectively. We developed an end-to-end hierarchical deep reinforcement learning (DRL) scheme to simultaneously train the three networks. We then evaluated the effectiveness of the proposed framework in the treatment planning problems for prostate cancer intensity modulated RT (IMRT) and stereotactic body RT (SBRT). We benchmarked the performance of our approach by comparing plans made by VTPN of a parallel architecture, and the human plans submitted for competition in the 2016 American Association of Medical Dosimetrist (AAMD)/Radiosurgery Society (RSS) Plan Study. We analyzed scalability of the network size with respect to the number of TPPs. Numerical experiments were also performed to understand the rationale of the decision-making behaviors of the trained HieVTPN. RESULTS: Both HieVTPNs for prostate IMRT and SBRT were trained successfully using 10 training patient cases and 5 validation cases. For IMRT, HieVTPN was able to generate high-quality plans for 59 testing patient cases that were not included in training process, achieving an average plan score of 8.62 (±0.83), with 9 being the maximal score. The score was comparable to that of the VTPN, 8.45 (±0.48). For SBRT planning, HieVTPN achieved an average plan score of 139.07 on five testing patient cases compared to the score of 132.21 averaged over the human plans summited for competition in AAMD/RSS plan study. Different from VTPN with network size linearly scaling with the number of TPPs, the network size of HieVTPN is almost independent of the number of TPPs. It was also observed that the decision-making behaviors of HieVTPN were understandable and generally agreed with the human experience. CONCLUSIONS: With the scalability and explainability, the hierarchical IATP framework is more favorable than the previous framework in terms of handling treatment planning problems involving a large number of TPPs. more...

Purpose. Needle catheter positions critically affect the quality of treatment plans in prostate cancer high-dose-rate (HDR) brachytherapy. The current standard needle positioning approach is based on human intuition, which cannot guarantee a high-quality plan. This study proposed a method to simultaneously select needle catheter positions and determine dwell time for preplanning of HDR brachytherapy of prostate cancer. Methods. We formulated the needle catheter selection problem and inverse dwell time optimization problem in a unified framework. In addition to the dose objectives of the planning target volume (PTV) and organs at risk (OARs), the objective function incorporated a group-sparsity term with a needle-specific adaptive weighting scheme to generate high-quality plans with the minimal number of needle catheters. The optimization problem was solved by a fast-iterative shrinkage-thresholding algorithm. For validation purposes, we tested the proposed algorithm on 10 patient cases previously treated at our institution and compared the resulting plans with plans generated using needle catheters selected manually. Results. Compared to the plan with manually selected needle catheters, when normalizing both plans to the same PTV coverage V 100% = 95%, the plans generated by the proposed algorithm reduced median V 125% from 65% to 64%, but increased median V 150% from 35% to 38%, and V 200% from 14% to 16%. All planning objectives were met. All clinically important dosimetric parameters of OARs were reduced. D 1cc of bladder and rectum were reduced from 8.57 Gy to 8.50 Gy and from 7.24 Gy to 6.80 Gy, respectively. D max of urethra was reduced from 15.85 Gy to 15.77 Gy. The median number of selected needle catheters was reduced by two. The computational time for solving the proposed optimization problem was ∼90 s using MATLAB. Conclusion. The proposed algorithm was able to generate plans for prostate cancer HDR brachytherapy preplanning with increased median conformity index (0.73–0.77) and slightly lower median homogeneity index (0.64–0.62) with the number of selected needles reduced by two compared to the manual needle selection approach. more...

Robustness is an important aspect when evaluating a method of medical image analysis. In this study, we investigated the robustness of a deep learning (DL)-based lung-nodule classification model for CT images with respect to noise perturbations. A deep neural network (DNN) was established to classify 3D CT images of lung nodules into malignant or benign groups. The established DNN was able to predict malignancy rate of lung nodules based on CT images, achieving the area under the curve of 0.91 for the testing dataset in a tenfold cross validation as compared to radiologists’ prediction. We then evaluated its robustness against noise perturbations. We added to the input CT images noise signals generated randomly or via an optimization scheme using a realistic noise model based on a noise power spectrum for a given mAs level, and monitored the DNN’s output. The results showed that the CT noise was able to affect the prediction results of the established DNN model. With random noise perturbations at 100 mAs, DNN’s predictions for 11.2% of training data and 17.4% of testing data were successfully altered by at least once. The percentage increased to 23.4% and 34.3%, respectively, for optimization-based perturbations. We further evaluated robustness of models with different architectures, parameters, number of output labels, etc, and robustness concern was found in these models to different degrees. To improve model robustness, we empirically proposed an adaptive training scheme. It fine-tuned the DNN model by including perturbations in the training dataset that successfully altered the DNN’s perturbations. The adaptive scheme was repeatedly performed to gradually improve DNN’s robustness. The numbers of perturbations at 100 mAs affecting DNN’s predictions were reduced to 10.8% for training and 21.1% for testing by the adaptive training scheme after two iterations. Our study illustrated that robustness may potentially be a concern for an exemplary DL-based lung-nodule classification model for CT images, indicating the needs for evaluating and ensuring model robustness when developing similar models. The proposed adaptive training scheme may be able to improve model robustness. more...

Complex intra-fractional motion and deformation of the liver significantly impacts the accuracy of delivered dose in radiotherapy, and limits margin reduction, dose escalation and normal tissue sparing. A critical component of motion management is to accurately reconstruct tumor motion. In this study, we developed a Six Degree of Freedom Projection Marker Matching method (6-DoF PM3) to reconstruct translational and rotational liver tumor motion in a rotational treatment delivery, such as volumetric modulated arc therapy (VMAT). Specifically, we modeled the use of two gold markers implanted in a linear form. The four endpoints of the two gold linear markers were used as tracking surrogates. During delivery, kV x-ray projection images were acquired. A method was developed to automatically identify the 2D marker-endpoints on the projection images. 3D marker positions were determined by solving an optimization problem with the objective function penalizing the distance from the reconstructed 3D position of each fiducial marker endpoint to the corresponding straight line defined by the kV x-ray projection of the endpoints. We performed a series of tests to evaluate different components of the method. For 2D marker endpoints identification, 99.9% of the marker endpoints were identified with an error ≤0.338 mm (1 pixel) along both u and v directions. For 3D reconstruction of motion in simulation studies, error of rotational angle was (0.5 ± 6.5) × 10(−3) degree without considering the 2D marker identification error. The rotational angle error was relatively sensitive to the accuracy of 2D marker identification. When the error raised from 0.22mm to 0.776 mm, the error of 3D rotational angle increased from 0.5 degree to 2.5 degree. In the experimental end-to-end tests, the mean root-mean square error of the 3D reconstructed marker positions was 0.75 mm and the mean error of rotational angle was within 1.7°. Our method can accurately determine intra-fractional liver tumor motion in rotational radiotherapy using kV projections of only two linear fiducial markers. more...

Digitization of interstitial needles is a complicated and tedious process for the treatment planning of 3D CT image based interstitial high dose-rate brachytherapy (HDRBT) of gynecological cancer. We developed a deep-learning assisted auto-digitization method for interstitial needles. The digitization method consisted of two steps. The first step used a deep neural network with a U-net structure to segment all needles from CT images. The second step simultaneously clustered the segmented voxels into different needle groups and generated the needle central trajectories by solving an optimization problem. We evaluated the effectiveness of the developed method in ten interstitial HDRBT patient cases that were not used in the training of the U-net. Average number of needles per case was 20.7. For the segmentation step, average Dice similarity coefficient between automatic and manual segmentation was 0.93. For the digitization step, Hausdorff distance between needle trajectories determined by our method and manually by qualified medical physicists was ~0.71 mm on average and mean difference of tip positions was ~0.63 mm, which were considered acceptable for HDRBT treatment planning. It took ~5 min to complete the digitization process of an interstitial HDRBT case. The achieved accuracy and efficiency made our method clinically attractive. more...