Deep learning models for organ contouring in radiotherapy are poised for clinical usage, but currently, there exist few tools for automated quality assessment (QA) of the predicted contours. Bayesian models and their associated uncertainty, can potentially automate the process of detecting inaccurate predictions. We investigate two Bayesian models for auto-contouring, DropOut and FlipOut, using a quantitative measure – expected calibration error (ECE) and a qualitative measure – region-based accuracy-vs-uncertainty (R-AvU) graphs. It is well understood that a model should have low ECE to be considered trustworthy. However, in a QA context, a model should also have high uncertainty in inaccurate regions and low uncertainty in accurate regions. Such behaviour could direct visual attention of expert users to potentially inaccurate regions, leading to a speed-up in the QA process. Using R-AvU graphs, we qualitatively compare the behaviour of different models in accurate and inaccurate regions. Experiments are conducted on the MICCAI2015 Head and Neck Segmentation Challenge and on the DeepMindTCIA CT dataset using three models: DropOut-DICE, Dropout-CE (Cross Entropy) and FlipOut-CE. Quantitative results show that DropOut-DICE has the highest ECE, while Dropout-CE and FlipOut-CE have the lowest ECE. To better understand the difference between DropOut-CE and FlipOut-CE, we use the R-AvU graph which shows that FlipOut-CE has better uncertainty coverage in inaccurate regions than DropOut-CE. Such a combination of quantitative and qualitative metrics explores a new approach that helps to select which model can be deployed as a QA tool in clinical settings. @en

Bayesian Neural Nets (BNN) are increasingly used for robust organ auto-contouring. Uncertainty heatmaps extracted from BNNs have been shown to correspond to inaccurate regions. To help speed up the mandatory quality assessment (QA) of contours in radiotherapy, these heatmaps could be used as stimuli to direct visual attention of clinicians to potential inaccuracies. In practice, this is non-trivial to achieve since many accurate regions also exhibit uncertainty. To influence the output uncertainty of a BNN, we propose a modified accuracy-versus-uncertainty (AvU) metric as an additional objective during model training that penalizes both accurate regions exhibiting uncertainty as well as inaccurate regions exhibiting certainty. For evaluation, we use an uncertainty-ROC curve that can help differentiate between Bayesian models by comparing the probability of uncertainty in inaccurate versus accurate regions. We train and evaluate a FlipOut BNN model on the MICCAI2015 Head and Neck Segmentation challenge dataset and on the DeepMind-TCIA dataset, and observed an increase in the AUC of uncertainty-ROC curves by 5.6% and 5.9%, respectively, when using the AvU objective. The AvU objective primarily reduced false positives regions (uncertain and accurate), drawing less visual attention to these regions, thereby potentially improving the speed of error detection.@en

Ensembles of contours arise in various applications like simulation, computer-aided design, and semantic segmentation. Uncovering ensemble patterns and analyzing individual members is a challenging task that suffers from clutter. Ensemble statistical summarization can alleviate this issue by permitting analyzing ensembles' distributional components like the mean and median, confidence intervals, and outliers. Contour boxplots, powered by Contour Band Depth (CBD), are a popular non-parametric ensemble summarization method that benefits from CBD's generality, robustness, and theoretical properties. In this work, we introduce Inclusion Depth (ID), a new notion of contour depth with three defining characteristics. First, ID is a generalization of functional Half-Region Depth, which offers several theoretical guarantees. Second, ID relies on a simple principle: the inside/outside relationships between contours. This facilitates implementing ID and understanding its results. Third, the computational complexity of ID scales quadratically in the number of members of the ensemble, improving CBD's cubic complexity. This also in practice speeds up the computation enabling the use of ID for exploring large contour ensembles or in contexts requiring multiple depth evaluations like clustering. In a series of experiments on synthetic data and case studies with meteorological and segmentation data, we evaluate ID's performance and demonstrate its capabilities for the visual analysis of contour ensembles.@en

Ensembles of contours arise in various applications like simulation, computer-aided design, and semantic segmentation. Uncovering ensemble patterns and analyzing individual members is a challenging task that suffers from clutter. Ensemble statistical summarization can alleviate this issue by permitting analyzing ensembles' distributional components like the mean and median, confidence intervals, and outliers. Contour boxplots, powered by Contour Band Depth (CBD), are a popular non-parametric ensemble summarization method that benefits from CBD's generality, robustness, and theoretical properties. In this work, we introduce Inclusion Depth (ID), a new notion of contour depth with three defining characteristics. First, ID is a generalization of functional Half-Region Depth, which offers several theoretical guarantees. Second, ID relies on a simple principle: the inside/outside relationships between contours. This facilitates implementing ID and understanding its results. Third, the computational complexity of ID scales quadratically in the number of members of the ensemble, improving CBD's cubic complexity. This also in practice speeds up the computation enabling the use of ID for exploring large contour ensembles or in contexts requiring multiple depth evaluations like clustering. In a series of experiments on synthetic data and case studies with meteorological and segmentation data, we evaluate ID's performance and demonstrate its capabilities for the visual analysis of contour ensembles.@en

Background and purpose: Retrospective dose evaluation for organ-at-risk auto-contours has previously used small cohorts due to additional manual effort required for treatment planning on auto-contours. We aimed to do this at large scale, by a) proposing and assessing an automated plan optimization workflow that used existing clinical plan parameters and b) using it for head-and-neck auto-contour dose evaluation. Materials and methods: Our automated workflow emulated our clinic's treatment planning protocol and reused existing clinical plan optimization parameters. This workflow recreated the original clinical plan (POG) with manual contours (PMC) and evaluated the dose effect (POG-PMC) on 70 photon and 30 proton plans of head-and-neck patients. As a use-case, the same workflow (and parameters) created a plan using auto-contours (PAC) of eight head-and-neck organs-at-risk from a commercial tool and evaluated their dose effect (PMC-PAC). Results: For plan recreation (POG-PMC), our workflow had a median impact of 1.0% and 1.5% across dose metrics of auto-contours, for photon and proton respectively. Computer time of automated planning was 25% (photon) and 42% (proton) of manual planning time. For auto-contour evaluation (PMC-PAC), we noticed an impact of 2.0% and 2.6% for photon and proton radiotherapy. All evaluations had a median ΔNTCP (Normal Tissue Complication Probability) less than 0.3%. Conclusions: The plan replication capability of our automated program provides a blueprint for other clinics to perform auto-contour dose evaluation with large patient cohorts. Finally, despite geometric differences, auto-contours had a minimal median dose impact, hence inspiring confidence in their utility and facilitating their clinical adoption.@en

Background and purpose: Retrospective dose evaluation for organ-at-risk auto-contours has previously used small cohorts due to additional manual effort required for treatment planning on auto-contours. We aimed to do this at large scale, by a) proposing and assessing an automated plan optimization workflow that used existing clinical plan parameters and b) using it for head-and-neck auto-contour dose evaluation. Materials and methods: Our automated workflow emulated our clinic's treatment planning protocol and reused existing clinical plan optimization parameters. This workflow recreated the original clinical plan (POG) with manual contours (PMC) and evaluated the dose effect (POG-PMC) on 70 photon and 30 proton plans of head-and-neck patients. As a use-case, the same workflow (and parameters) created a plan using auto-contours (PAC) of eight head-and-neck organs-at-risk from a commercial tool and evaluated their dose effect (PMC-PAC). Results: For plan recreation (POG-PMC), our workflow had a median impact of 1.0% and 1.5% across dose metrics of auto-contours, for photon and proton respectively. Computer time of automated planning was 25% (photon) and 42% (proton) of manual planning time. For auto-contour evaluation (PMC-PAC), we noticed an impact of 2.0% and 2.6% for photon and proton radiotherapy. All evaluations had a median ΔNTCP (Normal Tissue Complication Probability) less than 0.3%. Conclusions: The plan replication capability of our automated program provides a blueprint for other clinics to perform auto-contour dose evaluation with large patient cohorts. Finally, despite geometric differences, auto-contours had a minimal median dose impact, hence inspiring confidence in their utility and facilitating their clinical adoption.@en

Delineation of tumours and organs-at-risk permits detecting and correcting changes in the patients' anatomy throughout the treatment, making it a core step of adaptive external beam radiotherapy. Although auto-contouring technologies have sped up this process, the time needed to perform the quality assessment of the generated contours remains a bottleneck, taking clinicians between several minutes and an hour to complete. The authors of this article conducted several interviews and an observational study at two treatment centres in the Netherlands to identify challenges and opportunities for speeding up the delineation process in adaptive therapies. The study revealed three contextual variables that influence contouring performance: usable additional information, applicable domain-specific knowledge, and available editing capabilities in contouring software. In practice, clinicians leverage these variables to accelerate contouring in two ways. First, they use domain-specific knowledge and relevant clinical features such as the proximity of the organs-at-risk to the tumour to enable targeted inspection of the delineation. Second, clinicians modulate editing precision depending on the effect they anticipate the edit will have on the patient outcome. By implementing these acceleration strategies in guidelines and contouring tools, developers and workflow builders could increase contouring efficiency and consistency without affecting the patient outcome.@en

Post-translational modifications (PTMs) affecting a protein's residues (amino acids) can disturb its function, leading to illness. Whether or not a PTM is pathogenic depends on its type and the status of neighboring residues. In this paper, we present the ProtoFold Neighborhood Inspector (PFNI), a visualization system for analyzing residues neighborhoods. The main contribution is a visualization idiom, the Residue Constellation (RC), for identifying and comparing three-dimensional neighborhoods based on per-residue features and spatial characteristics. The RC leverages two-dimensional representations of the protein's three-dimensional structure to overcome problems like occlusion, easing the analysis of neighborhoods that often have complicated spatial arrangements. Using the PFNI, we explored proteins' structural PTM data, which allowed us to identify patterns in the distribution and quantity of per-neighborhood PTMs that might be related to their pathogenic status. In the following, we define the tasks that guided the development of the PFNI and describe the data sources we derived and used. Then, we introduce the PFNI and illustrate its usage through an example of an analysis workflow. We conclude by reflecting on preliminary findings obtained while using the tool on the provided data and future directions concerning the development of the PFNI.@en

Artificial Intelligence (AI)-based auto-delineation technologies rapidly delineate multiple structures of interest like organs-at-risk and tumors in 3D medical images, reducing personnel load and facilitating time-critical therapies. Despite its accuracy, the AI may produce flawed delineations, requiring clinician attention. Quality assessment (QA) of these delineations is laborious and demanding. Delineation error detection systems aim to aid QA, yet questions linger about clinician adoption, challenges, and time-saving potential. In this study, we address these queries in two stages. First, we investigate the error detection workflow of a radiotherapy technologist and a radiation oncologist from Holland Proton Therapy Center, a Dutch cancer treatment center. The user study revealed which information sources clinicians prefer to use for the error prioritization task and elucidated clinicians' slice-based navigation workflows with and without system assistance. Based on the findings from the user study, we developed a simulation model of the QA process, which we used to assess different error detection workflows on a retrospective cohort of 42 head and neck cancer patients. The simulation study results indicate potential time savings through error and dose information, contingent on per-slice analysis time remaining near the current baseline. Our findings encourage the development of user-centric delineation error detection systems and provide a new way to model and evaluate these systems' potential clinical value.@en

Artificial Intelligence (AI)-based auto-delineation technologies rapidly delineate multiple structures of interest like organs-at-risk and tumors in 3D medical images, reducing personnel load and facilitating time-critical therapies. Despite its accuracy, the AI may produce flawed delineations, requiring clinician attention. Quality assessment (QA) of these delineations is laborious and demanding. Delineation error detection systems aim to aid QA, yet questions linger about clinician adoption, challenges, and time-saving potential. In this study, we address these queries in two stages. First, we investigate the error detection workflow of a radiotherapy technologist and a radiation oncologist from Holland Proton Therapy Center, a Dutch cancer treatment center. The user study revealed which information sources clinicians prefer to use for the error prioritization task and elucidated clinicians' slice-based navigation workflows with and without system assistance. Based on the findings from the user study, we developed a simulation model of the QA process, which we used to assess different error detection workflows on a retrospective cohort of 42 head and neck cancer patients. The simulation study results indicate potential time savings through error and dose information, contingent on per-slice analysis time remaining near the current baseline. Our findings encourage the development of user-centric delineation error detection systems and provide a new way to model and evaluate these systems' potential clinical value.@en

Delineation of tumors and organs-at-risk permits detecting and correcting changes in the patients' anatomy throughout the treatment, making it a core step of adaptive proton therapy (APT). Although AI-based auto-contouring technologies have sped up this process, the time needed to perform the quality assessment (QA) of the generated contours remains a bottleneck, taking clinicians between several minutes up to an hour to complete. This paper introduces a fast contouring workflow suitable for time-critical APT, enabling detection of anatomical changes in shorter time frames and with a lower demand of clinical resources. The proposed AI-infused workflow follows two principles uncovered after reviewing the APT literature and conducting several interviews and an observational study in two radiotherapy centers in the Netherlands. First, enable targeted inspection of the generated contours by leveraging AI uncertainty and clinically-relevant features such as the proximity of the organs-at-risk to the tumor. Second, minimize the number of interactions needed to edit faulty delineations with redundancy-aware editing tools that provide the user a sense of predictability and control. We use a proof of concept that we validated with clinicians to demonstrate how current and upcoming AI capabilities support the workflow and how it would fit into clinical practice.@en

Delineation of tumors and organs-at-risk permits detecting and correcting changes in the patients' anatomy throughout the treatment, making it a core step of adaptive proton therapy (APT). Although AI-based auto-contouring technologies have sped up this process, the time needed to perform the quality assessment (QA) of the generated contours remains a bottleneck, taking clinicians between several minutes up to an hour to complete. This paper introduces a fast contouring workflow suitable for time-critical APT, enabling detection of anatomical changes in shorter time frames and with a lower demand of clinical resources. The proposed AI-infused workflow follows two principles uncovered after reviewing the APT literature and conducting several interviews and an observational study in two radiotherapy centers in the Netherlands. First, enable targeted inspection of the generated contours by leveraging AI uncertainty and clinically-relevant features such as the proximity of the organs-at-risk to the tumor. Second, minimize the number of interactions needed to edit faulty delineations with redundancy-aware editing tools that provide the user a sense of predictability and control. We use a proof of concept that we validated with clinicians to demonstrate how current and upcoming AI capabilities support the workflow and how it would fit into clinical practice.@en

Delineation of tumors and organs-at-risk permits detecting and correcting changes in the patients' anatomy throughout the treatment, making it a core step of adaptive proton therapy (APT). Although AI-based auto-contouring technologies have sped up this process, the time needed to perform the quality assessment (QA) of the generated contours remains a bottleneck, taking clinicians between several minutes up to an hour to complete. This paper introduces a fast contouring workflow suitable for time-critical APT, enabling detection of anatomical changes in shorter time frames and with a lower demand of clinical resources. The proposed AI-infused workflow follows two principles uncovered after reviewing the APT literature and conducting several interviews and an observational study in two radiotherapy centers in the Netherlands. First, enable targeted inspection of the generated contours by leveraging AI uncertainty and clinically-relevant features such as the proximity of the organs-at-risk to the tumor. Second, minimize the number of interactions needed to edit faulty delineations with redundancy-aware editing tools that provide the user a sense of predictability and control. We use a proof of concept that we validated with clinicians to demonstrate how current and upcoming AI capabilities support the workflow and how it would fit into clinical practice.@en