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Convolutional neural networks have achieved excellent results in automatic medical image segmentation. In this study, we proposed a novel 3D multi-path DenseNet for generating the accurate glioblastoma (GBM) tumor contour from four multi-modal pre-operative MR images. We hypothesized that the multi-path architecture could achieve more accurate segmentation than a single-path architecture. 258 GBM patients were included in this study. Each patient had four MR images (T1-weighted, contrast-enhanced T1-weighted, T2-weighted, and FLAIR) and the manually segmented tumor contour. We built a 3D multi-path DenseNet that could be trained to generate the corresponding GBM tumor contour from the four MR images. A 3D single-path DenseNet was also built for comparison. Both DenseNets were based on the encoder-decoder architecture. All four images were concatenated and fed into a single encoder path in the single-path DenseNet, while each input image had its own encoder path in the multi-path DenseNet. The patient cohort was randomly split into a training set of 180 patients, a validation set of 39 patients, and a testing set of 39 patients. Model performance was evaluated using the Dice similarity coefficient (DSC), average surface distance (ASD), and 95% Hausdorff distance (HD95%). Wilcoxon signed-rank tests were conducted to examine the model differences. The single-path DenseNet achieved a DSC of 0.911$\pm$0.060, ASD of 1.3$\pm$0.7 mm, and HD95% of 5.2$\pm$7.1 mm, while the multi-path DenseNet achieved a DSC of 0.922$\pm$0.041, ASD of 1.1$\pm$0.5 mm, and HD95% of 3.9$\pm$3.3 mm. The p-values of all Wilcoxon signed-rank tests were less than 0.05. Both 3D DenseNets generated GBM tumor contours in good agreement with the manually segmented contours from multi-modal MR images. The multi-path DenseNet achieved more accurate tumor segmentation than the single-path DenseNet., Comment: 15 pages, 6 figures, review in progress

We proposed a fully automatic workflow for glioblastoma (GBM) survival prediction using deep learning (DL) methods. 285 glioma (210 GBM, 75 low-grade glioma) patients were included. 163 of the GBM patients had overall survival (OS) data. Every patient had four pre-operative MR scans and manually drawn tumor contours. For automatic tumor segmentation, a 3D convolutional neural network (CNN) was trained and validated using 122 glioma patients. The trained model was applied to the remaining 163 GBM patients to generate tumor contours. The handcrafted and DL-based radiomic features were extracted from auto-contours using explicitly designed algorithms and a pre-trained CNN respectively. 163 GBM patients were randomly split into training (n=122) and testing (n=41) sets for survival analysis. Cox regression models with regularization techniques were trained to construct the handcrafted and DL-based signatures. The prognostic power of the two signatures was evaluated and compared. The 3D CNN achieved an average Dice coefficient of 0.85 across 163 GBM patients for tumor segmentation. The handcrafted signature achieved a C-index of 0.64 (95% CI: 0.55-0.73), while the DL-based signature achieved a C-index of 0.67 (95% CI: 0.57-0.77). Unlike the handcrafted signature, the DL-based signature successfully stratified testing patients into two prognostically distinct groups (p-value<0.01, HR=2.80, 95% CI: 1.26-6.24). The proposed 3D CNN generated accurate GBM tumor contours from four MR images. The DL-based signature resulted in better GBM survival prediction, in terms of higher C-index and significant patient stratification, than the handcrafted signature. The proposed automatic radiomic workflow demonstrated the potential of improving patient stratification and survival prediction in GBM patients.

Electron density maps must be accurately estimated to achieve valid dose calculation in MR-only radiotherapy. The goal of this study is to assess whether two deep learning models, the conditional generative adversarial network (cGAN) and the cycle-consistent generative adversarial network (cycleGAN), can generate accurate abdominal synthetic CT (sCT) images from 0.35T MR images for MR-only liver radiotherapy. A retrospective study was performed using CT images and 0.35T MR images of 12 patients with liver (n=8) and non-liver abdominal (n=4) cancer. CT images were deformably registered to the corresponding MR images to generate deformed CT (dCT) images for treatment planning. Both cGAN and cycleGAN were trained using MR and dCT transverse slices. Four-fold cross-validation testing was conducted to generate sCT images for all patients. The HU prediction accuracy was evaluated by voxel-wise similarity metric between each dCT and sCT image for all 12 patients. dCT-based and sCT-based dose distributions were compared using gamma and dose-volume histogram (DVH) metric analysis for 8 liver patients. sCTcycleGAN achieved the average mean absolute error (MAE) of 94.1 HU, while sCTcGAN achieved 89.8 HU. In both models, the average gamma passing rates within all volumes of interest were higher than 95% using a 2%, 2 mm criterion, and 99% using a 3%, 3 mm criterion. The average differences in the mean dose and DVH metrics were within +/-0.6% for the planning target volume and within +/-0.15% for evaluated organs in both models. Results demonstrated that abdominal sCT images generated by both cGAN and cycleGAN achieved accurate dose calculation for 8 liver radiotherapy plans. sCTcGAN images had smaller average MAE and achieved better dose calculation accuracy than sCTcyleGAN images. More abdominal patients will be enrolled in the future to further evaluate two models., Comment: Review in progress

To achieve magnetic resonance (MR)-only radiotherapy, a method needs to be employed to estimate a synthetic CT (sCT) for generating electron density maps and patient positioning reference images. We investigated 2D and 3D convolutional neural network (CNN) methods to generate a male pelvic sCT using a T1-weighted MR image. A retrospective study was performed using CTs and T1-weighted MR images of 20 prostate cancer patients. The proposed 2D CNN model, which contained 27 convolutional layers, was modified from the SegNet for better performance. 3D version of the CNN model was also developed. Both CNN models were trained from scratch to map intensities of T1-weighted MR images to CT Hounsfield Unit (HU) values. Each sCT was generated in a five-fold-cross-validation framework and compared with the corresponding CT using voxel-wise mean absolute error (MAE), and dice similarity coefficient (DSC), recall, and precision for bony structures. Wilcoxon signed-rank tests were performed to evaluate the differences between the both models. The MAE averaged across all patients were 40.5 $\pm$ 5.4 HU and 37.6 $\pm$ 5.1 HU for the 2D and 3D CNN models, respectively. The DSC, recall, and precision of the bony structures were 0.81 $\pm$ 0.04, 0.85 $\pm$ 0.04, and 0.77 $\pm$ 0.09 for the 2D CNN model, and 0.82 $\pm$ 0.04, 0.84 $\pm$ 0.04, and 0.80 $\pm$ 0.08 for the 3D CNN model, respectively. P values of the Wilcoxon signed-rank tests were less than 0.05 except for recall, which was 0.6. The 2D and 3D CNN models generated accurate pelvic sCTs for the 20 patients using T1-weighted MR images. The evaluation metrics and statistical tests indicated that the 3D model was able to generate sCTs with better MAE, bone DSC, and bone precision. The accuracy of the dose calculation and patient positioning using generated sCTs will be tested and compared for the two models in the future., Comment: Medical Physics 2019

The XCAT phantom is a realistic 4D digital torso phantom that is widely used in imaging and therapy research. However, lung mass is not conserved between respiratory phases of the phantom, making detailed dosimetric simulations and dose accumulation unphysical. A framework is developed to correct this issue by enforcing local mass conservation in the XCAT lung. Dose calculations are performed to assess the implications of neglecting mass conservation, and to demonstrate an application of the phantom to calculate the accumulated delivered dose in an irregularly breathing patient. Monte Carlo methods are used to simulate conventional and SBRT treatment delivery. The spatial distribution of the lung dose was qualitatively changed by the use of mass conservation; however the corresponding DVH did not change significantly. Comparison of the delivered dose with 4DCT-based predictions shows similar lung metric results, however dose differences of 10% can be seen in some spatial regions. Using this tool to simulate patient treatments reveals differences between the planned dose and the calculated delivered dose for the full treatment. The software is freely available from the authors., Comment: 18 pages, 10 figures. Accepted for publication in Medical Physics

Recently we have developed an algorithm for reconstructing volumetric images and extracting 3D tumor motion information from a single x-ray projection. We have demonstrated its feasibility using a digital respiratory phantom with regular breathing patterns. In this work, we present a detailed description and a comprehensive evaluation of the improved algorithm. The algorithm was improved by incorporating respiratory motion prediction. The accuracy and efficiency were then evaluated on 1) a digital respiratory phantom, 2) a physical respiratory phantom, and 3) five lung cancer patients. These evaluation cases include both regular and irregular breathing patterns that are different from the training dataset. For the digital respiratory phantom with regular and irregular breathing, the average 3D tumor localization error is less than 1 mm. On an NVIDIA Tesla C1060 GPU card, the average computation time for 3D tumor localization from each projection ranges between 0.19 and 0.26 seconds, for both regular and irregular breathing, which is about a 10% improvement over previously reported results. For the physical respiratory phantom, an average tumor localization error below 1 mm was achieved with an average computation time of 0.13 and 0.16 seconds on the same GPU card, for regular and irregular breathing, respectively. For the five lung cancer patients, the average tumor localization error is below 2 mm in both the axial and tangential directions. The average computation time on the same GPU card ranges between 0.26 and 0.34 seconds.

Purpose: To develop an algorithm for real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy. Methods: Given a set of volumetric images of a patient at N breathing phases as the training data, we perform deformable image registration between a reference phase and the other N-1 phases, resulting in N-1 deformation vector fields (DVFs). These DVFs can be represented efficiently by a few eigenvectors and coefficients obtained from principal component analysis (PCA). By varying the PCA coefficients, we can generate new DVFs, which, when applied on the reference image, lead to new volumetric images. We then can reconstruct a volumetric image from a single projection image by optimizing the PCA coefficients such that its computed projection matches the measured one. The 3D location of the tumor can be derived by applying the inverted DVF on its position in the reference image. Our algorithm was implemented on graphics processing units (GPUs) to achieve real-time efficiency. We generated the training data using a realistic and dynamic mathematical phantom with 10 breathing phases. The testing data were 360 cone beam projections corresponding to one gantry rotation, simulated using the same phantom with a 50% increase in breathing amplitude. Results: The average relative image intensity error of the reconstructed volumetric images is 6.9% +/- 2.4%. The average 3D tumor localization error is 0.8 mm +/- 0.5 mm. On an NVIDIA Tesla C1060 GPU card, the average computation time for reconstructing a volumetric image from each projection is 0.24 seconds (range: 0.17 and 0.35 seconds). Conclusions: We have shown the feasibility of reconstructing volumetric images and localizing tumor positions in 3D in near real-time from a single x-ray image., Comment: 8 pages, 3 figures, submitted to Medical Physics Letter