Using Auto-Segmentation to Reduce Contouring and Dose Inconsistency in Clinical Trials: The Simulated Impact on RTOG 0617.

PURPOSE: Contouring inconsistencies are known but understudied in clinical radiation therapy trials. We applied auto-contouring to the Radiation Therapy Oncology Group (RTOG) 0617 dose escalation trial data. We hypothesized that the trial heart doses were higher than reported due to inconsistent and insufficient heart segmentation. We tested our hypothesis by comparing doses between deep-learning (DL) segmented hearts and trial hearts. METHODS AND MATERIALS: The RTOG 0617 data were downloaded from The Cancer Imaging Archive; the 442 patients with trial hearts and dose distributions were included. All hearts were resegmented using our DL pipeline and quality assured to meet the requirements for clinical implementation. Dose (V5%, V30%, and mean heart dose) was compared between the 2 sets of hearts (Wilcoxon signed-rank test). Each dose metric was associated with overall survival (Cox proportional hazards). Lastly, 18 volume similarity metrics were assessed for the hearts and correlated with |DoseDL - DoseRTOG0617| (linear regression; significance: P ≤ .0028; corrected for 18 tests). RESULTS: Dose metrics were significantly higher for DL hearts compared with trial hearts (eg, mean heart dose: 15 Gy vs 12 Gy; P = 5.8E-16). All 3 DL heart dose metrics were stronger overall survival predictors than those of the trial hearts (median, P = 2.8E-5 vs 2.0E-4). Thirteen similarity metrics explained |DoseDL - DoseRTOG0617|; the axial distance between the 2 centers of mass was the strongest predictor (CENTAxial; median, R2 = 0.47; P = 6.1E-62). CENTAxial agreed with the qualitatively identified inconsistencies in the superior direction. The trial's qualitative heart contouring score was not correlated with |DoseDL - DoseRTOG0617| (median, R2 = 0.01; P = .02) or with any of the similarity metrics (median, Rs = 0.13 [range, -0.22 to 0.31]). CONCLUSIONS: Using a coherent heart definition, as enabled through our open-source DL algorithm, the trial heart doses in RTOG 0617 were found to be significantly higher than previously reported, which may have led to an even more rapid mortality accumulation. Auto-segmentation is likely to reduce contouring and dose inconsistencies and increase the quality of clinical RT trials.

Library of deep-learning image segmentation and outcomes model-implementations.

An open-source library of implementations for deep-learning-based image segmentation and outcomes models based on radiotherapy and radiomics is presented. As oncology treatment planning becomes increasingly driven by automation, such a library of model implementations is crucial to (i) validate existing models on datasets collected at different institutions, (ii) automate segmentation, (iii) create ensembles for improving performance and (iv) incorporate validated models in the clinical workflow. Inclusion of deep-learning-based image segmentation and outcomes models in the same library provides a fully automated and reproduceable pipeline to estimate prognosis. The library was developed with the Computational Environment for Radiological Research (CERR) software platform. Centralizing model implementations in CERR builds upon its rich set of radiotherapy and radiomics tools and caters to the world-wide user base. CERR provides well-validated feature extraction pipelines for radiotherapy dosimetry and radiomics with fine control over the calculation settings, allowing users to select appropriate parameters used in model derivation. Models for automatic image segmentation are distributed via containers, allowing them to be deployed with a variety of scientific computing architectures. The library includes implementations of popular DVH-based models outlined in the Quantitative Analysis of Normal Tissue Effects in the Clinic effort and recently published literature. Radiomics models include features from the Image Biomarker Standardization Initiative and application-specific features found to be relevant across multiple sites and image modalities. The library is distributed as a module within CERR at https://www.github.com/cerr/CERR under the GNU-GPL copyleft with additional restrictions on clinical and commercial use and provision to dual license in future.

Deformable multisurface segmentation of the spine for orthopedic surgery planning and simulation.

Purpose: We describe a shape-aware multisurface simplex deformable model for the segmentation of healthy as well as pathological lumbar spine in medical image data. Approach: This model provides an accurate and robust segmentation scheme for the identification of intervertebral disc pathologies to enable the minimally supervised planning and patient-specific simulation of spine surgery, in a manner that combines multisurface and shape statistics-based variants of the deformable simplex model. Statistical shape variation within the dataset has been captured by application of principal component analysis and incorporated during the segmentation process to refine results. In the case where shape statistics hinder detection of the pathological region, user assistance is allowed to disable the prior shape influence during deformation. Results: Results demonstrate validation against user-assisted expert segmentation, showing excellent boundary agreement and prevention of spatial overlap between neighboring surfaces. This section also plots the characteristics of the statistical shape model, such as compactness, generalizability and specificity, as a function of the number of modes used to represent the family of shapes. Final results demonstrate a proof-of-concept deformation application based on the open-source surgery simulation Simulation Open Framework Architecture toolkit. Conclusions: To summarize, we present a deformable multisurface model that embeds a shape statistics force, with applications to surgery planning and simulation.

Cardio-pulmonary substructure segmentation of radiotherapy computed tomography images using convolutional neural networks for clinical outcomes analysis.

BACKGROUND AND PURPOSE: Radiation dose to the cardio-pulmonary system is critical for radiotherapy-induced mortality in non-small cell lung cancer. Our goal was to automatically segment substructures of the cardio-pulmonary system for use in outcomes analyses for thoracic cancers. We built and validated a multi-label Deep Learning Segmentation (DLS) model for accurate auto-segmentation of twelve cardio-pulmonary substructures. MATERIALS AND METHODS: The DLS model utilized a convolutional neural network for segmenting substructures from 217 thoracic radiotherapy Computed Tomography (CT) scans. The model was built in the presence of variable image characteristics such as the absence/presence of contrast. We quantitatively evaluated the final model against expert contours for a hold-out dataset of 24 CT scans using Dice Similarity Coefficient (DSC), 95th Percentile of Hausdorff Distance and Dose-volume Histograms (DVH). DLS contours of an additional 25 scans were qualitatively evaluated by a radiation oncologist to determine their clinical acceptability. RESULTS: The DLS model reduced segmentation time per patient from about one hour to 10 s. Quantitatively, the highest accuracy was observed for the Heart (median DSC = (0.96 (0.95-0.97)). The median DSC for the remaining structures was between 0.81 and 0.93. No statistically significant difference was found between DVH metrics of the auto-generated and manual contours (p-value ⩾ 0.69). The expert judged that, on average, 85% of contours were qualitatively equivalent to state-of-the-art manual contouring. CONCLUSION: The cardio-pulmonary DLS model performed well both quantitatively and qualitatively for all structures. This model has been incorporated into an open-source tool for the community to use for treatment planning and clinical outcomes analysis.

Dynamic multiatlas selection-based consensus segmentation of head and neck structures from CT images.

PURPOSE: Manual delineation of head and neck (H&N) organ-at-risk (OAR) structures for radiation therapy planning is time consuming and highly variable. Therefore, we developed a dynamic multiatlas selection-based approach for fast and reproducible segmentation. METHODS: Our approach dynamically selects and weights the appropriate number of atlases for weighted label fusion and generates segmentations and consensus maps indicating voxel-wise agreement between different atlases. Atlases were selected for a target as those exceeding an alignment weight called dynamic atlas attention index. Alignment weights were computed at the image level and called global weighted voting (GWV) or at the structure level and called structure weighted voting (SWV) by using a normalized metric computed as the sum of squared distances of computed tomography (CT)-radiodensity and modality-independent neighborhood descriptors (extracting edge information). Performance comparisons were performed using 77 H&N CT images from an internal Memorial Sloan-Kettering Cancer Center dataset (N = 45) and an external dataset (N = 32) using Dice similarity coefficient (DSC), Hausdorff distance (HD), 95th percentile of HD, median of maximum surface distance, and volume ratio error against expert delineation. Pairwise DSC accuracy comparisons of proposed (GWV, SWV) vs single best atlas (BA) or majority voting (MV) methods were performed using Wilcoxon rank-sum tests. RESULTS: Both SWV and GWV methods produced significantly better segmentation accuracy than BA (P < 0.001) and MV (P < 0.001) for all OARs within both datasets. SWV generated the most accurate segmentations with DSC of: 0.88 for oral cavity, 0.85 for mandible, 0.84 for cord, 0.76 for brainstem and parotids, 0.71 for larynx, and 0.60 for submandibular glands. SWV's accuracy exceeded GWV's for submandibular glands (DSC = 0.60 vs 0.52, P = 0.019). CONCLUSIONS: The contributed SWV and GWV methods generated more accurate automated segmentations than the other two multiatlas-based segmentation techniques. The consensus maps could be combined with segmentations to visualize voxel-wise consensus between atlases within OARs during manual review.

3D lumbar spine intervertebral disc segmentation and compression simulation from MRI using shape-aware models.

PURPOSE: More accurate and robust image segmentations are needed for identification of spine pathologies and to assist with spine surgery planning and simulation. A framework for 3D segmentation of healthy and herniated intervertebral discs from T2-weighted magnetic resonance imaging was developed that exploits weak shape priors encoded in simplex mesh active surface models. METHODS: Weak shape priors inherent in simplex mesh deformable models have been exploited to automatically segment intervertebral discs. An ellipsoidal simplex template mesh was initialized within the disc image boundary through affine landmark-based registration and was allowed to deform according to image gradient forces. Coarse-to-fine multi-resolution approach was adopted in conjunction with decreasing shape memory forces to accurately capture the disc boundary. User intervention is allowed to turn off the shape feature and guide model deformation when the internal simplex shape memory influence hinders detection of pathology. A resulting surface mesh was utilized for disc compression simulation under gravitational and weight loads using Simulation Open Framework Architecture. For testing, 16 healthy discs were automatically segmented, and five pathological discs were segmented with minimal supervision. RESULTS: Segmentation results were validated against expert guided segmentation and demonstrate mean absolute shape distance error of <1 mm. Healthy intervertebral disc compression simulation resulted in a bulging disc under vertical pressure of 100 N/cm(2). CONCLUSION: This study presents the application of a simplex active surface model featuring weak shape priors for 3D segmentation of healthy as well as herniated discs. A framework was developed that enables the application of shape priors in the healthy part of disc anatomy, with user intervention when the priors were inapplicable. The surface-mesh-based segmentation method is part of a processing pipeline for anatomical modelling to support interactive surgery simulation.