Tumors are heterogeneous tissues consisting of multiple regions with distinct characteristics. Characterization of these intra-tumor regions can improve patient diagnosis and enable a better targeted treatment. Ideally, tissue characterization could be performed non-invasively, using medical imaging data, to derive per voxel a number of features, indicative of tissue properties. However, the high dimensionality and complexity of this imaging-derived feature space is prohibiting for easy exploration and analysis -especially when clinical researchers require to associate observations from the feature space to other reference data, e.g., features derived from histopathological data. Currently, the exploratory approach used in clinical research consists of juxtaposing these data, visually comparing them and mentally reconstructing their relationships. This is a time consuming and tedious process, from which it is difficult to obtain the required insight. We propose a visual tool for: (1) easy exploration and visual analysis of the feature space of imaging-derived tissue characteristics and (2) knowledge discovery and hypothesis generation and confirmation, with respect to reference data used in clinical research. We employ, as central view, a 2D embedding of the imaging-derived features. Multiple linked interactive views provide functionality for the exploration and analysis of the local structure of the feature space, enabling linking to patient anatomy and clinical reference data. We performed an initial evaluation with ten clinical researchers. All participants agreed that, unlike current practice, the proposed visual tool enables them to identify, explore and analyze heterogeneous intra-tumor regions and particularly, to generate and confirm hypotheses, with respect to clinical reference data.the derivation of tumor tissue characteristics from imaging data is based on -more or less-complex mathematical models [SB13]. Different modeling approaches make different assumptions, resulting in features with different distributions. A priori, it is not known whether different alternatives in modeling present significant differences or which option leads to better results. Additionally, all modeling approaches introduce model-fitting inaccuracy in the derived features. Exploring variability and incorporating inaccuracy induced by different modeling approaches, with respect to anatomical or clinical reference data, can have significant impact on the final clinical decision and treatment.However, the high dimensionality and complexity of the imaging-derived feature space, along with model-induced variability and inaccuracy, is prohibiting for easy exploration. The structure of this feature space is also not fully comprehended and, in the state-of-the-art clinical research workflow, there is no easy and insightful way to link observations from histopathology or clinical reference to features derived from imaging.

In radiotherapy, tumors are irradiated with a high dose, while surrounding healthy tissues are spared. To quantify the probability that a tumor is effectively treated with a given dose, statistical models were built and employed in clinical research. These are called tumor control probability (TCP) models. Recently, TCP models started incorporating additional information from imaging modalities. In this way, patient-specific properties of tumor tissues are included, improving the radiobiological accuracy of models. Yet, the employed imaging modalities are subject to uncertainties with significant impact on the modeling outcome, while the models are sensitive to a number of parameter assumptions. Currently, uncertainty and parameter sensitivity are not incorporated in the analysis, due to time and resource constraints. To this end, we propose a visual tool that enables clinical researchers working on TCP modeling, to explore the information provided by their models, to discover new knowledge and to confirm or generate hypotheses within their data. Our approach incorporates the following four main components: (1) It supports the exploration of uncertainty and its effect on TCP models; (2) It facilitates parameter sensitivity analysis to common assumptions; (3) It enables the identification of inter-patient response variability; (4) It allows starting the analysis from the desired treatment outcome, to identify treatment strategies that achieve it. We conducted an evaluation with nine clinical researchers. All participants agreed that the proposed visual tool provides better understanding and new opportunities for the exploration and analysis of TCP modeling.

Parallel Coordinate Plots (PCPs) is one of the most powerful techniques for the visualization of multivariate data. However, for large datasets, the representation suffers from clutter due to overplotting. In this case, discerning the underlying data information and selecting specific interesting patterns can become difficult. We propose a new and simple technique to improve the display of PCPs by emphasizing the underlying data structure. Our Orientation-enhanced Parallel Coordinate Plots (OPCPs) improve pattern and outlier discernibility by visually enhancing parts of each PCP polyline with respect to its slope. This enhancement also allows us to introduce a novel and efficient selection method, the Orientation-enhanced Brushing (O-Brushing). Our solution is particularly useful when multiple patterns are present or when the view on certain patterns is obstructed by noise. We present the results of our approach with several synthetic and real-world datasets. Finally, we conducted a user evaluation, which verifies the advantages of the OPCPs in terms of discernibility of information in complex data. It also confirms that O-Brushing eases the selection of data patterns in PCPs and reduces the amount of necessary user interactions compared to state-of-the-art brushing techniques.

We present the Bladder Runner, a novel tool to enable detailed visual exploration and analysis of the impact of bladder shape variation on the accuracy of dose delivery, during the course of prostate cancer radiotherapy (RT). Our tool enables the investigation of individual patients and cohorts through the entire treatment process, and it can give indications of RT-induced complications for the patient. In prostate cancer RT treatment, despite the design of an initial plan prior to dose administration, bladder toxicity remains very common. The main reason is that the dose is delivered in multiple fractions over a period of weeks, during which, the anatomical variation of the bladder -due to differences in urinary filling -causes deviations between planned and delivered doses. Clinical researchers want to correlate bladder shape variations to dose deviations and toxicity risk through cohort studies, to understand which specific bladder shape characteristics are more prone to side effects. This is currently done with Dose-Volume Histograms (DVHs), which provide limited, qualitative insight. The effect of bladder variation on dose delivery and the resulting toxicity cannot be currently examined with the DVHs. To address this need, we designed and implemented the Bladder Runner, which incorporates visualization strategies in a highly interactive environment with multiple linked views. Individual patients can be explored and analyzed through the entire treatment period, while inter-patient and temporal exploration, analysis and comparison are also supported. We demonstrate the applicability of our presented tool with a usage scenario, employing a dataset of 29 patients followed through the course of the treatment, across 13 time points. We conducted an evaluation with three clinical researchers working on the investigation of RT-induced bladder toxicity. All participants agreed that Bladder Runner provides better understanding and new opportunities for the exploration and analysis of the involved cohort data.