Integrating formal methods into medical software development : the ASM approach

Medical devices are safety-critical systems since their malfunctions can seriously compromise human safety. Correct operation of a medical device depends upon the controlling software, whose development should adhere to certification standards. However, these standards provide general descriptions of common software engineering activities without any indication regarding particular methods and techniques to assure safety and reliability. This paper discusses how to integrate the use of a formal approach into the current normative for the medical software development. The rigorous process is based on the Abstract State Machine (ASM) formal method, its refinement principle, and model analysis approaches the method supports. The hemodialysis machine case study is used to show how the ASM-based design process covers most of the engineering activities required by the related standards, and provides rigorous approaches for medical software validation and verification

Vessel tractography using an intensity based tensor model with branch detection

In this paper, we present a tubular structure seg- mentation method that utilizes a second order tensor constructed from directional intensity measurements, which is inspired from diffusion tensor image (DTI) modeling. The constructed anisotropic tensor which is fit inside a vessel drives the segmen- tation analogously to a tractography approach in DTI. Our model is initialized at a single seed point and is capable of capturing whole vessel trees by an automatic branch detection algorithm developed in the same framework. The centerline of the vessel as well as its thickness is extracted. Performance results within the Rotterdam Coronary Artery Algorithm Evaluation framework are provided for comparison with existing techniques. 96.4% average overlap with ground truth delineated by experts is obtained in addition to other measures reported in the paper. Moreover, we demonstrate further quantitative results over synthetic vascular datasets, and we provide quantitative experiments for branch detection on patient Computed Tomography Angiography (CTA) volumes, as well as qualitative evaluations on the same CTA datasets, from visual scores by a cardiologist expert

Grid simulation services for the medical community

The first part of this paper presents a selection of medical simulation applications, including image reconstruction, near real-time registration for neuro-surgery, enhanced dose distribution calculation for radio-therapy, inhaled drug delivery prediction, plastic surgery planning and cardio-vascular system simulation. The latter two topics are discussed in some detail. In the second part, we show how such services can be made available to the clinical practitioner using Grid technology. We discuss the developments and experience made during the EU project GEMSS, which provides reliable, efficient, secure and lawful medical Grid services

Drugst.One -- A plug-and-play solution for online systems medicine and network-based drug repurposing

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.Comment: 45 pages, 6 figures, 7 table

Adaptive Segmentation Of Cardiovascular Vessels

Coronary collateral vessels may contribute to survival after myocardial infarction by providing blood to the cardiac muscle after coronary arterial occlusion. However, these vessels are not present in all people and can develop after infarction and in some cases they develop prior to infarction for reasons not fully understood. The goal of this thesis is to investigate the segmentation of coronary collateral vessels from micro-computed tomography (microCT) images of a mouse's heart. A problem limiting study of collateral vessels is the exceedingly small size and correspondingly low blood flow of these vessels, making the regions of interest (ROI) below the resolution of most imaging modalities. Segmentation of vessels is a challenge for all imaging modalities and organs. There is no standard algorithm or method that works for all images, therefore, a combination of multiple approaches were used to address this problem

Distributed computing practice for large-scale science and engineering applications

It is generally accepted that the ability to develop large-scale distributed applications has lagged seriously behind other developments in cyberinfrastructure. In this paper, we provide insight into how such applications have been developed and an understanding of why developing applications for distributed infrastructure is hard. Our approach is unique in the sense that it is centered around half a dozen existing scientific applications; we posit that these scientific applications are representative of the characteristics, requirements, as well as the challenges of the bulk of current distributed applications on production cyberinfrastructure (such as the US TeraGrid). We provide a novel and comprehensive analysis of such distributed scientific applications. Specifically, we survey existing models and methods for large-scale distributed applications and identify commonalities, recurring structures, patterns and abstractions. We find that there are many ad hoc solutions employed to develop and execute distributed applications, which result in a lack of generality and the inability of distributed applications to be extensible and independent of infrastructure details. In our analysis, we introduce the notion of application vectors: a novel way of understanding the structure of distributed applications. Important contributions of this paper include identifying patterns that are derived from a wide range of real distributed applications, as well as an integrated approach to analyzing applications, programming systems and patterns, resulting in the ability to provide a critical assessment of the current practice of developing, deploying and executing distributed applications. Gaps and omissions in the state of the art are identified, and directions for future research are outlined

Example-Based Urban Modeling

The manual modeling of virtual cities or suburban regions is an extremely time-consuming task, which expects expert knowledge of different fields. Existing modeling tool-sets have a steep learning curve and may need special education skills to work with them productively. Existing automatic methods rely on rule sets and grammars to generate urban structures; however, their expressiveness is limited by the rule-sets. Expert skills are necessary to typeset rule sets successfully and, in many cases, new rule-sets need to be defined for every new building style or street network style. To enable non-expert users, the possibility to construct urban structures for individual experiments, this work proposes a portfolio of novel example-based synthesis algorithms and applications for the controlled generation of virtual urban environments. The notion example-based denotes here that new virtual urban environments are created by computer programs that re-use existing digitized real-world data serving as templates. The data, i.e., street networks, topography, layouts of building footprints, or even 3D building models, necessary to realize the envisioned task is already publicly available via online services. To enable the reuse of existing urban datasets, novel algorithms need to be developed by encapsulating expert knowledge and thus allow the controlled generation of virtual urban structures from sparse user input. The focus of this work is the automatic generation of three fundamental structures that are common in urban environments: road networks, city block, and individual buildings. In order to achieve this goal, the thesis proposes a portfolio of algorithms that are briefly summarized next. In a theoretical chapter, we propose a general optimization technique that allows formulating example-based synthesis as a general resource-constrained k-shortest path (RCKSP) problem. From an abstract problem specification and a database of exemplars carrying resource attributes, we construct an intermediate graph and employ a path-search optimization technique. This allows determining either the best or the k-best solutions. The resulting algorithm has a reduced complexity for the single constraint case when compared to other graph search-based techniques. For the generation of road networks, two different techniques are proposed. The first algorithm synthesizes a novel road network from user input, i.e., a desired arterial street skeleton, topography map, and a collection of hierarchical fragments extracted from real-world road networks. The algorithm recursively constructs a novel road network reusing these fragments. Candidate fragments are inserted into the current state of the road network, while shape differences will be compensated by warping. The second algorithm synthesizes road networks using generative adversarial networks (GANs), a recently introduced deep learning technique. A pre- and postprocessing pipeline allows using GANs for the generation of road networks. An in-depth evaluation shows that GANs faithfully learn the road structure present in the example network and that graph measures such as area, aspect ratio, and compactness, are maintained within the virtual road networks. To fill empty city blocks in road networks we propose two novel techniques. The first algorithm re-uses real-world city blocks and synthesizes building footprint layouts into empty city blocks by retrieving viable candidate blocks from a database. We evaluate the algorithm and synthesize a multitude of city block layouts reusing real-world building footprint arrangements from European and US-cities. In addition, we increase the realism of the synthesized layouts by performing example-based placement of 3D building models. This technique is evaluated by placing buildings onto challenging footprint layouts using different example building databases. The second algorithm computes a city block layout, resembling the style of a real-world city block. The original footprint layout is deformed to construct a textit{guidance map}, i.e., the original layout is transferred to a target city block using warping. This guidance map and the original footprints are used by an optimization technique that computes a novel footprint layout along the city block edges. We perform a detailed evaluation and show that using the guidance map allows transferring of the original layout, locally as well as globally, even when the source and target shapes drastically differ. To synthesize individual buildings, we use the general optimization technique described first and formulate the building generation process as a resource-constrained optimization problem. From an input database of annotated building parts, an abstract description of the building shape, and the specification of resource constraints such as length, area, or a number of architectural elements, a novel building is synthesized. We evaluate the technique by synthesizing a multitude of challenging buildings fulfilling several global and local resource constraints. Finally, we show how this technique can even be used to synthesize buildings having the shape of city blocks and might also be used to fill empty city blocks in virtual street networks. All algorithms presented in this work were developed to work with a small amount of user input. In most cases, simple sketches and the definition of constraints are enough to produce plausible results. Manual work is necessary to set up the building part databases and to download example data from mapping services available on the Internet

Hybrid visibility compositing and masking for illustrative rendering

In this paper, we introduce a novel framework for the compositing of interactively rendered 3D layers tailored to the needs of scientific illustration. Currently, traditional scientific illustrations are produced in a series of composition stages, combining different pictorial elements using 2D digital layering. Our approach extends the layer metaphor into 3D without giving up the advantages of 2D methods. The new compositing approach allows for effects such as selective transparency, occlusion overrides, and soft depth buffering. Furthermore, we show how common manipulation techniques such as masking can be integrated into this concept. These tools behave just like in 2D, but their influence extends beyond a single viewpoint. Since the presented approach makes no assumptions about the underlying rendering algorithms, layers can be generated based on polygonal geometry, volumetric data, point-based representations, or others. Our implementation exploits current graphics hardware and permits real-time interaction and rendering.publishedVersio