Visual Analysis of Tumor Control Models for Prediction of Radiotherapy Response

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.     

Visualization of myocardial perfusion derived from coronary anatomy

Visually assessing the effect of the coronary artery anatomy on the perfusion of the heart muscle in patients with coronary artery disease remains a challenging task. We explore the feasibility of visualizing this effect on perfusion using a numerical approach. We perform a computational simulation of the way blood is perfused throughout the myocardium purely based on information from a three-dimensional anatomical tomographic scan. The results are subsequently visualized using both three-dimensional visualizations and bull's eye plots, partially inspired by approaches currently common in medical practice. Our approach results in a comprehensive visualization of the coronary anatomy that compares well to visualizations commonly used for other scanning technologies. We demonstrate techniques giving detailed insight in blood supply, coronary territories and feeding coronary arteries of a selected region. We demonstrate the advantages of our approach through visualizations that show information which commonly cannot be directly observed in scanning data, such as a separate visualization of the supply from each coronary artery. We thus show that the results of a computational simulation can be effectively visualized and facilitate visually correlating these results to for example perfusion data.     

Data compression systems for home-use digital video recording

The authors focus on image data compression techniques for digital recording. Image coding for storage equipment covers a large variety of systems because the applications differ considerably in nature. Video coding systems suitable for digital TV and HDTV recording and digital electronic still picture storage are considered. In addition, attention is paid to picture coding for interactive systems, such as the compact-disc interactive system. The relation between the recording system boundary conditions and the applied coding techniques is outlined. The main emphasis is on picture coding techniques for digital consumer recording     

The EASI project-improving the effectiveness and quality ofimage-guided surgery

In recent years, advances in computer technology and a significant increase in the accuracy of medical imaging have made it possible to develop systems that can assist the clinician in diagnosis, planning, and treatment. This paper deals with an area that is generally referred to as computer-assisted surgery, image-directed surgery, or image-guided surgery. We report the research, development, and clinical validation performed since January 1996 in the European Applications in Surgical Interventions (EASI) project, which is funded by the European Commission in their “4th Framework Telematics Applications for Health” program. The goal of this project is the improvement of the effectiveness and quality of image-guided neurosurgery of the brain and image-guided vascular surgery of abdominal aortic aneurysms, while at the same time reducing patient risks and overall cost. We have developed advanced prototype systems for preoperative surgical planning and intraoperative surgical navigation, and we have extensively clinically validated these systems. The prototype systems and the clinical validation results are described in this paper     

Interactive virtual probing of 4D MRI blood-flow

Better understanding of hemodynamics conceivably leads to improved diagnosis and prognosis of cardiovascular diseases. Therefore, an elaborate analysis of the blood-flow in heart and thoracic arteries is essential. Contemporary MRI techniques enable acquisition of quantitative time-resolved flow information, resulting in 4D velocity fields that capture the blood-flow behavior. Visual exploration of these fields provides comprehensive insight into the unsteady blood-flow behavior, and precedes a quantitative analysis of additional blood-flow parameters. The complete inspection requires accurate segmentation of anatomical structures, encompassing a time-consuming and hard-to-automate process, especially for malformed morphologies. We present a way to avoid the laborious segmentation process in case of qualitative inspection, by introducing an interactive virtual probe. This probe is positioned semi-automatically within the blood-flow field, and serves as a navigational object for visual exploration. The difficult task of determining position and orientation along the view-direction is automated by a fitting approach, aligning the probe with the orientations of the velocity field. The aligned probe provides an interactive seeding basis for various flow visualization approaches. We demonstrate illustration-inspired particles, integral lines and integral surfaces, conveying distinct characteristics of the unsteady blood-flow. Lastly, we present the results of an evaluation with domain experts, valuing the practical use of our probe and flow visualization techniques.     

Exploration of 4D MRI blood flow using stylistic visualization

Insight into the dynamics of blood-flow considerably improves the understanding of the complex cardiovascular system and its pathologies. Advances in MRI technology enable acquisition of 4D blood-flow data, providing quantitative blood-flow velocities over time. The currently typical slice-by-slice analysis requires a full mental reconstruction of the unsteady blood-flow field, which is a tedious and highly challenging task, even for skilled physicians. We endeavor to alleviate this task by means of comprehensive visualization and interaction techniques. In this paper we present a framework for pre-clinical cardiovascular research, providing tools to both interactively explore the 4D blood-flow data and depict the essential blood-flow characteristics. The framework encompasses a variety of visualization styles, comprising illustrative techniques as well as improved methods from the established field of flow visualization. Each of the incorporated styles, including exploded planar reformats, flow-direction highlights, and arrow-trails, locally captures the blood-flow dynamics and may be initiated by an interactively probed vessel cross-section. Additionally, we present the results of an evaluation with domain experts, measuring the value of each of the visualization styles and related rendering parameters.     

Selection of fluorescent probes for flow cytometric viability assessment of Listeria monocytogenes exposed to membrane-active and oxidizing disinfectants

The aim of this study was to select fluorescence methods for use as alternatives to plate counting to assess the viability of Listeria monocytogenes cells exposed to benzalkonium chloride (BAC) and hydrogen peroxide, two disinfectants with different mechanisms of action. A further aim of this study was to determine whether growth phase influences fluorescence labeling and whether it is possible to predict whether a probe will be a good viability indicator for cells exposed to a certain disinfectant on the basis of the mechanism of action of the disinfectant and the target of the fluorescent probe. The fluorescence methods used were labeling with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC; dehydrogenase activity), labeling with TOTO-1 iodide (TOTO; membrane-impermeant probe), and assessment of pH gradient maintenance in a low-pH buffer after labeling with the pH-sensitive probe 5-(and 6)-carboxyfluorescein succinimidyl ester (CFSE) (the pH(in) method). Growth phase influenced fluorescent labeling. However, the cutoff value for distinction between viable and nonviable cells was the same for both growth phases. The viability (determined by plate counts) of BAC-exposed cells correlated well with CTC labeling and TOTO exclusion. For both BAC-exposed and hydrogen peroxide-exposed cells, the pH(in) method gave a good qualitative indication of viability, sublethal damage, and cell death. CTC labeling and TOTO exclusion did not correlate with the viability of hydrogen peroxide-exposed cells. Our results demonstrate that even if the mechanism of action of a disinfectant is known, in some cases it is still difficult to predict whether a certain fluorescent probe is suitable for viability assessment. Thus, the proper selection of fluorescent probes for the assessment of the efficacy of antimicrobial agents is essential.     

Automatic contour propagation in cine cardiac magnetic resonance images

We have developed a method for automatic contour propagation in cine cardiac magnetic resonance images. The method consists of a new active contour model that tries to maintain a constant contour environment by matching gray values in profiles perpendicular to the contour. Consequently, the contours should maintain a constant position with respect to neighboring anatomical structures, such that the resulting contours reflect the preferences of the user. This is particularly important in cine cardiac magnetic resonance images because local image features do not describe the desired contours near the papillary muscle. The accuracy of the propagation result is influenced by several parameters. Because the optimal setting of these parameters is application dependent, we describe how to use full factorial experiments to optimize the parameter setting. We have applied our method to cine cardiac magnetic resonance image sequences from the long axis two-chamber view, the long axis four-chamber view, and the short axis view. We performed our optimization procedure for each contour in each view. Next, we performed an extensive clinical validation of our method on 69 short axis data sets and 38 long axis data sets. In the optimal parameter setting, our propagation method proved to be fast, robust, and accurate. The resulting cardiac contours are positioned within the interobserver ranges of manual segmentation. Consequently, the resulting contours can be used to accurately determine physiological parameters such as stroke volume and ejection fraction.     

Assessment of viability of microorganisms employing fluorescence techniques

Viability assessment of microorganisms is relevant for a wide variety of applications in industry, including evaluation of inactivation treatments and quality assessment of starter cultures for beer, wine, and yoghurt production. Usually, the ability of microbial cells to reproduce is considered as the benchmark method for determination of cell viability, and this is most commonly determined by the plate count method. The time needed to form visible colonies, however, is relatively long. Therefore, there is an increasing interest in rapid methods which exploit criteria other than reproduction. In this review the applications of fluorescent probes for, e.g., determination of membrane integrity, enzyme activities, respiration, membrane potential and intracellular pH, are discussed in detail.     

Biofilm formation, extracellular polysaccharide production, and cell-to-cell signaling in various Enterobacter sakazakii strains: aspects promoting environmental persistence

Enterobacter sakazakii is considered an opportunistic pathogen and has been implicated in food-associated cases of meningitis or enteritis, especially in neonates and infants. The organism has been detected in various types of food and in food production units, but so far only powdered infant formula has been linked to outbreaks of disease. Survival and persistence in such environments requires the ability to adapt to high osmotic potentials and/or dry conditions. Fifty-six E. sakazakii strains were evaluated for several features important for persistence and survival: (i) biofilm formation and the putative production of cellulose as one of the components of the extracellular matrix, (ii) adherence to hydrophilic and hydrophobic surfaces, (iii) the production of extracellular polysaccharides, and (iv) the ability of E. sakazakii to produce cell-to-cell signaling molecules. Pellicle and flock formation was observed in 21 of the strains grown in Luria-Bertani broth and in 44 of the strains grown in brain heart infusion broth. Calcofluor-stained fibrils, observed microscopically in every (fragile or rigid) pellicle, suggested the presence of cellulose as an extracellular compound in this type of biofilm. Twelve isolates did not form any pellicle or flocks under either condition. Twenty-three of the isolates exhibited the potential to adhere to glass surfaces in shaken cultures, and 33 strains showed biofilm formation at the air-solid interface of polyvinyl chloride microtiter wells. Sixteen isolates adhered to both surfaces. Twenty-four of the isolates tested produced a milky, viscous mass, considered as extracellular polysaccharide. High-performance liquid chromatography analysis of the polysaccharide revealed the presence of glucose, galactose, fucose, and glucuronic acid. Thin-layer chromatography analyses performed on ethyl acetate extracts of cell-free supernatants of the 56 strains indicated the presence of two different types of acylated homoserine lactones (3-oxo-C6-HSL and 3-oxo-C8-HSL). These findings illustrate the ability of E. sakazakii to produce cell-to-cell signaling molecules.