Deformation Driven Seq2Seq Longitudinal Tumor and Organs-at-Risk Prediction for Radiotherapy

Purpose: Radiotherapy presents unique challenges and clinical requirements for longitudinal tumor and organ-at-risk (OAR) prediction during treatment. The challenges include tumor inflammation/edema and radiation-induced changes in organ geometry, whereas the clinical requirements demand flexibility in input/output sequence timepoints to update the predictions on rolling basis and the grounding of all predictions in relationship to the pre-treatment imaging information for response and toxicity assessment in adaptive radiotherapy. Methods: To deal with the aforementioned challenges and to comply with the clinical requirements, we present a novel 3D sequence-to-sequence model based on Convolution Long Short Term Memory (ConvLSTM) that makes use of series of deformation vector fields (DVF) between individual timepoints and reference pre-treatment/planning CTs to predict future anatomical deformations and changes in gross tumor volume as well as critical OARs. High-quality DVF training data is created by employing hyper-parameter optimization on the subset of the training data with DICE coefficient and mutual information metric. We validated our model on two radiotherapy datasets: a publicly available head-and-neck dataset (28 patients with manually contoured pre-, mid-, and post-treatment CTs), and an internal non-small cell lung cancer dataset (63 patients with manually contoured planning CT and 6 weekly CBCTs). Results: The use of DVF representation and skip connections overcomes the blurring issue of ConvLSTM prediction with the traditional image representation. The mean and standard deviation of DICE for predictions of lung GTV at week 4, 5, and 6 were 0.83$\pm$0.09, 0.82$\pm$0.08, and 0.81$\pm$0.10, respectively, and for post-treatment ipsilateral and contralateral parotids, were 0.81$\pm$0.06 and 0.85$\pm$0.02.

Deep cross-modality (MR-CT) educed distillation learning for cone beam CT lung tumor segmentation

Despite the widespread availability of in-treatment room cone beam computed tomography (CBCT) imaging, due to the lack of reliable segmentation methods, CBCT is only used for gross set up corrections in lung radiotherapies. Accurate and reliable auto-segmentation tools could potentiate volumetric response assessment and geometry-guided adaptive radiation therapies. Therefore, we developed a new deep learning CBCT lung tumor segmentation method. Methods: The key idea of our approach called cross modality educed distillation (CMEDL) is to use magnetic resonance imaging (MRI) to guide a CBCT segmentation network training to extract more informative features during training. We accomplish this by training an end-to-end network comprised of unpaired domain adaptation (UDA) and cross-domain segmentation distillation networks (SDN) using unpaired CBCT and MRI datasets. Feature distillation regularizes the student network to extract CBCT features that match the statistical distribution of MRI features extracted by the teacher network and obtain better differentiation of tumor from background.} We also compared against an alternative framework that used UDA with MR segmentation network, whereby segmentation was done on the synthesized pseudo MRI representation. All networks were trained with 216 weekly CBCTs and 82 T2-weighted turbo spin echo MRI acquired from different patient cohorts. Validation was done on 20 weekly CBCTs from patients not used in training. Independent testing was done on 38 weekly CBCTs from patients not used in training or validation. Segmentation accuracy was measured using surface Dice similarity coefficient (SDSC) and Hausdroff distance at 95th percentile (HD95) metrics.

Nested-block self-attention for robust radiotherapy planning segmentation

Although deep convolutional networks have been widely studied for head and neck (HN) organs at risk (OAR) segmentation, their use for routine clinical treatment planning is limited by a lack of robustness to imaging artifacts, low soft tissue contrast on CT, and the presence of abnormal anatomy. In order to address these challenges, we developed a computationally efficient nested block self-attention (NBSA) method that can be combined with any convolutional network. Our method achieves computational efficiency by performing non-local calculations within memory blocks of fixed spatial extent. Contextual dependencies are captured by passing information in a raster scan order between blocks, as well as through a second attention layer that causes bi-directional attention flow. We implemented our approach on three different networks to demonstrate feasibility. Following training using 200 cases, we performed comprehensive evaluations using conventional and clinical metrics on a separate set of 172 test scans sourced from external and internal institution datasets without any exclusion criteria. NBSA required a similar number of computations (15.7 gflops) as the most efficient criss-cross attention (CCA) method and generated significantly more accurate segmentations for brain stem (Dice of 0.89 vs. 0.86) and parotid glands (0.86 vs. 0.84) than CCA. NBSA's segmentations were less variable than multiple 3D methods, including for small organs with low soft-tissue contrast such as the submandibular glands (surface Dice of 0.90).

Unified cross-modality feature disentangler for unsupervised multi-domain MRI abdomen organs segmentation

Our contribution is a unified cross-modality feature disentagling approach for multi-domain image translation and multiple organ segmentation. Using CT as the labeled source domain, our approach learns to segment multi-modal (T1-weighted and T2-weighted) MRI having no labeled data. Our approach uses a variational auto-encoder (VAE) to disentangle the image content from style. The VAE constrains the style feature encoding to match a universal prior (Gaussian) that is assumed to span the styles of all the source and target modalities. The extracted image style is converted into a latent style scaling code, which modulates the generator to produce multi-modality images according to the target domain code from the image content features. Finally, we introduce a joint distribution matching discriminator that combines the translated images with task-relevant segmentation probability maps to further constrain and regularize image-to-image (I2I) translations. We performed extensive comparisons to multiple state-of-the-art I2I translation and segmentation methods. Our approach resulted in the lowest average multi-domain image reconstruction error of 1.34$\pm$0.04. Our approach produced an average Dice similarity coefficient (DSC) of 0.85 for T1w and 0.90 for T2w MRI for multi-organ segmentation, which was highly comparable to a fully supervised MRI multi-organ segmentation network (DSC of 0.86 for T1w and 0.90 for T2w MRI).

PSIGAN: Joint probabilistic segmentation and image distribution matching for unpaired cross-modality adaptation based MRI segmentation

We developed a new joint probabilistic segmentation and image distribution matching generative adversarial network (PSIGAN) for unsupervised domain adaptation (UDA) and multi-organ segmentation from magnetic resonance (MRI) images. Our UDA approach models the co-dependency between images and their segmentation as a joint probability distribution using a new structure discriminator. The structure discriminator computes structure of interest focused adversarial loss by combining the generated pseudo MRI with probabilistic segmentations produced by a simultaneously trained segmentation sub-network. The segmentation sub-network is trained using the pseudo MRI produced by the generator sub-network. This leads to a cyclical optimization of both the generator and segmentation sub-networks that are jointly trained as part of an end-to-end network. Extensive experiments and comparisons against multiple state-of-the-art methods were done on four different MRI sequences totalling 257 scans for generating multi-organ and tumor segmentation. The experiments included, (a) 20 T1-weighted (T1w) in-phase mdixon and (b) 20 T2-weighted (T2w) abdominal MRI for segmenting liver, spleen, left and right kidneys, (c) 162 T2-weighted fat suppressed head and neck MRI (T2wFS) for parotid gland segmentation, and (d) 75 T2w MRI for lung tumor segmentation. Our method achieved an overall average DSC of 0.87 on T1w and 0.90 on T2w for the abdominal organs, 0.82 on T2wFS for the parotid glands, and 0.77 on T2w MRI for lung tumors.

Multiple resolution residual network for automatic thoracic organs-at-risk segmentation from CT

We implemented and evaluated a multiple resolution residual network (MRRN) for multiple normal organs-at-risk (OAR) segmentation from computed tomography (CT) images for thoracic radiotherapy treatment (RT) planning. Our approach simultaneously combines feature streams computed at multiple image resolutions and feature levels through residual connections. The feature streams at each level are updated as the images are passed through various feature levels. We trained our approach using 206 thoracic CT scans of lung cancer patients with 35 scans held out for validation to segment the left and right lungs, heart, esophagus, and spinal cord. This approach was tested on 60 CT scans from the open-source AAPM Thoracic Auto-Segmentation Challenge dataset. Performance was measured using the Dice Similarity Coefficient (DSC). Our approach outperformed the best-performing method in the grand challenge for hard-to-segment structures like the esophagus and achieved comparable results for all other structures. Median DSC using our method was 0.97 (interquartile range [IQR]: 0.97-0.98) for the left and right lungs, 0.93 (IQR: 0.93-0.95) for the heart, 0.78 (IQR: 0.76-0.80) for the esophagus, and 0.88 (IQR: 0.86-0.89) for the spinal cord.

Local block-wise self attention for normal organ segmentation

We developed a new and computationally simple local block-wise self attention based normal structures segmentation approach applied to head and neck computed tomography (CT) images. Our method uses the insight that normal organs exhibit regularity in their spatial location and inter-relation within images, which can be leveraged to simplify the computations required to aggregate feature information. We accomplish this by using local self attention blocks that pass information between each other to derive the attention map. We show that adding additional attention layers increases the contextual field and captures focused attention from relevant structures. We developed our approach using U-net and compared it against multiple state-of-the-art self attention methods. All models were trained on 48 internal headneck CT scans and tested on 48 CT scans from the external public domain database of computational anatomy dataset. Our method achieved the highest Dice similarity coefficient segmentation accuracy of 0.85$\pm$0.04, 0.86$\pm$0.04 for left and right parotid glands, 0.79$\pm$0.07 and 0.77$\pm$0.05 for left and right submandibular glands, 0.93$\pm$0.01 for mandible and 0.88$\pm$0.02 for the brain stem with the lowest increase of 66.7\% computing time per image and 0.15\% increase in model parameters compared with standard U-net. The best state-of-the-art method called point-wise spatial attention, achieved \textcolor{black}{comparable accuracy but with 516.7\% increase in computing time and 8.14\% increase in parameters compared with standard U-net.} Finally, we performed ablation tests and studied the impact of attention block size, overlap of the attention blocks, additional attention layers, and attention block placement on segmentation performance.

Integrating cross-modality hallucinated MRI with CT to aid mediastinal lung tumor segmentation

Lung tumors, especially those located close to or surrounded by soft tissues like the mediastinum, are difficult to segment due to the low soft tissue contrast on computed tomography images. Magnetic resonance images contain superior soft-tissue contrast information that can be leveraged if both modalities were available for training. Therefore, we developed a cross-modality educed learning approach where MR information that is educed from CT is used to hallucinate MRI and improve CT segmentation. Our approach, called cross-modality educed deep learning segmentation (CMEDL) combines CT and pseudo MR produced from CT by aligning their features to obtain segmentation on CT. Features computed in the last two layers of parallelly trained CT and MR segmentation networks are aligned. We implemented this approach on U-net and dense fully convolutional networks (dense-FCN). Our networks were trained on unrelated cohorts from open-source the Cancer Imaging Archive CT images (N=377), an internal archive T2-weighted MR (N=81), and evaluated using separate validation (N=304) and testing (N=333) CT-delineated tumors. Our approach using both networks were significantly more accurate (U-net $P <0.001$; denseFCN $P <0.001$) than CT-only networks and achieved an accuracy (Dice similarity coefficient) of 0.71$\pm$0.15 (U-net), 0.74$\pm$0.12 (denseFCN) on validation and 0.72$\pm$0.14 (U-net), 0.73$\pm$0.12 (denseFCN) on the testing sets. Our novel approach demonstrated that educing cross-modality information through learned priors enhances CT segmentation performance

Cross-modality (CT-MRI) prior augmented deep learning for robust lung tumor segmentation from small MR datasets

Lack of large expert annotated MR datasets makes training deep learning models difficult. Therefore, a cross-modality (MR-CT) deep learning segmentation approach that augments training data using pseudo MR images produced by transforming expert-segmented CT images was developed. Eighty-One T2-weighted MRI scans from 28 patients with non-small cell lung cancers were analyzed. Cross-modality prior encoding the transformation of CT to pseudo MR images resembling T2w MRI was learned as a generative adversarial deep learning model. This model augmented training data arising from 6 expert-segmented T2w MR patient scans with 377 pseudo MRI from non-small cell lung cancer CT patient scans with obtained from the Cancer Imaging Archive. A two-dimensional Unet implemented with batch normalization was trained to segment the tumors from T2w MRI. This method was benchmarked against (a) standard data augmentation and two state-of-the art cross-modality pseudo MR-based augmentation and (b) two segmentation networks. Segmentation accuracy was computed using Dice similarity coefficient (DSC), Hausdroff distance metrics, and volume ratio. The proposed approach produced the lowest statistical variability in the intensity distribution between pseudo and T2w MR images measured as Kullback-Leibler divergence of 0.069. This method produced the highest segmentation accuracy with a DSC of 0.75 and the lowest Hausdroff distance on the test dataset. This approach produced highly similar estimations of tumor growth as an expert (P = 0.37). A novel deep learning MR segmentation was developed that overcomes the limitation of learning robust models from small datasets by leveraging learned cross-modality priors to augment training. The results show the feasibility of the approach and the corresponding improvement over the state-of-the-art methods.

Comparison of Patch-Based Conditional Generative Adversarial Neural Net Models with Emphasis on Model Robustness for Use in Head and Neck Cases for MR-Only planning

A total of twenty paired CT and MR images were used in this study to investigate two conditional generative adversarial networks, Pix2Pix, and Cycle GAN, for generating synthetic CT images for Headand Neck cancer cases. Ten of the patient cases were used for training and included such common artifacts as dental implants; the remaining ten testing cases were used for testing and included a larger range of image features commonly found in clinical head and neck cases. These features included strong metal artifacts from dental implants, one case with a metal implant, and one case with abnormal anatomy. The original CT images were deformably registered to the mDixon FFE MR images to minimize the effects of processing the MR images. The sCT generation accuracy and robustness were evaluated using Mean Absolute Error (MAE) based on the Hounsfield Units (HU) for three regions (whole body, bone, and air within the body), Mean Error (ME) to observe systematic average offset errors in the sCT generation, and dosimetric evaluation of all clinically relevant structures. For the test set the MAE for the Pix2Pix and Cycle GAN models were 92.4 $\pm$ 13.5 HU, and 100.7 $\pm$ 14.6 HU, respectively, for the body region, 166.3 $\pm$ 31.8 HU, and 184 $\pm$ 31.9 HU, respectively, for the bone region, and 183.7 $\pm$ 41.3 HU and 185.4 $\pm$ 37.9 HU for the air regions. The ME for Pix2Pix and Cycle GAN were 21.0 $\pm$ 11.8 HU and 37.5 $\pm$ 14.9 HU, respectively. Absolute Percent Mean/Max Dose Errors were less than 2% for the PTV and all critical structures for both models, and DRRs generated from these models looked qualitatively similar to CT generated DRRs showing these methods are promising for MR-only planning.