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Asymmetric Ensemble of Asymmetric U-Net Models for Brain Tumor Segmentation With Uncertainty Estimation

ABSTRACT: Accurate brain tumor segmentation is crucial for clinical assessment, follow-up, and subsequent treatment of gliomas. While convolutional neural networks (CNN) have become state of the art in this task, most proposed models either use 2D architectures ignoring 3D contextual information or 3D models requiring large memory capacity and extensive learning databases. In this study, an ensemble of two kinds of U-Net-like models based on both 3D and 2.5D convolutions is proposed to segment multimodal magnetic resonance images (MRI). The 3D model uses concatenated data in a modified U-Net architecture. In contrast, the 2.5D model is based on a multi-input strategy to extract low-level features from each modality independently and on a new 2.5D Multi-View Inception block that aims to merge features from different views of a 3D image aggregating multi-scale features. The Asymmetric Ensemble of Asymmetric U-Net (AE AU-Net) based on both is designed to find a balance between increasing multi-scale and 3D contextual information extraction and keeping memory consumption low. Experiments on 2019 dataset show that our model improves enhancing tumor sub-region segmentation. Overall, performance is comparable with state-of-the-art results, although with less learning data or memory requirements. In addition, we provide voxel-wise and structure-wise uncertainties of the segmentation results, and we have established qualitative and quantitative relationships between uncertainty and prediction errors. Dice similarity coefficient for the whole tumor, tumor core, and tumor enhancing regions on BraTS 2019 validation dataset were 0.902, 0.815, and 0.773. We also applied our method in BraTS 2018 with corresponding Dice score values of 0.908, 0.838, and 0.800.

SUBMITTER: Rosas-Gonzalez S

PROVIDER: S-EPMC8515181 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Problem. Image biomarker analysis, also known as radiomics, is a tool for tissue characterization and treatment prognosis that relies on routinely acquired clinical images and delineations. Due to the uncertainty in image acquisition, processing, and segmentation (delineation) protocols, radiomics often lack reproducibility. Radiomics harmonization techniques have been proposed as a solution to reduce these sources of uncertainty and/or their influence on the prognostic model performance. A relevant question is how to estimate the protocol-induced uncertainty of a specific image biomarker, what the effect is on the model performance, and how to optimize the model given the uncertainty. Methods. Two non-small cell lung cancer (NSCLC) cohorts, composed of 421 and 240 patients, respectively, were used for training and testing. Per patient, a Monte Carlo algorithm was used to generate three hundred synthetic contours with a surface dice tolerance measure of less than 1.18 mm with respect to the original GTV. These contours were subsequently used to derive 104 radiomic features, which were ranked on their relative sensitivity to contour perturbation, expressed in the parameter η. The top four (low η) and the bottom four (high η) features were selected for two models based on the Cox proportional hazards model. To investigate the influence of segmentation uncertainty on the prognostic model, we trained and tested the setup in 5000 augmented realizations (using a Monte Carlo sampling method); the log-rank test was used to assess the stratification performance and stability of segmentation uncertainty. Results. Although both low and high η setup showed significant testing set log-rank p-values (p = 0.01) in the original GTV delineations (without segmentation uncertainty introduced), in the model with high uncertainty, to effect ratio, only around 30% of the augmented realizations resulted in model performance with p < 0.05 in the test set. In contrast, the low η setup performed with a log-rank p < 0.05 in 90% of the augmented realizations. Moreover, the high η setup classification was uncertain in its predictions for 50% of the subjects in the testing set (for 80% agreement rate), whereas the low η setup was uncertain only in 10% of the cases. Discussion. Estimating image biomarker model performance based only on the original GTV segmentation, without considering segmentation, uncertainty may be deceiving. The model might result in a significant stratification performance, but can be unstable for delineation variations, which are inherent to manual segmentation. Simulating segmentation uncertainty using the method described allows for more stable image biomarker estimation, selection, and model development. The segmentation uncertainty estimation method described here is universal and can be extended to estimate other protocol uncertainties (such as image acquisition and pre-processing).

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Asymmetric Ensemble of Asymmetric U-Net Models for Brain Tumor Segmentation With Uncertainty Estimation

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