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

A multiscale model for collagen alignment in wound healing

It is thought that collagen alignment plays a significant part in scar tissue formation during dermal wound healing. We present a multiscale model for collagen deposition and alignment during this process. We consider fibroblasts as discrete units moving within an extracellular matrix of collagen and fibrin modelled as continua. Our model includes flux induced alignment of collagen by fibroblasts, and contact guidance of fibroblasts by collagen fibres. We can use the model to predict the effects of certain manipulations, such as varying fibroblast speed, or placing an aligned piece of tissue in the wound. We also simulate experiments which alter the TGF-β concentrations in a healing dermal wound and use the model to offer an explanation of the observed influence of this growth factor on scarring

Cancer modelling: Getting to the heart of the problem

Paradoxically, improvements in healthcare that have enhanced the life expectancy of humans in the Western world have, indirectly, increased the prevalence of certain types of cancer such as prostate and breast. It remains unclear whether this phenomenon should be attributed to the ageing process itself or the cumulative effect of prolonged exposure to harmful environmental stimuli such as ultraviolet light, radiation and carcinogens (Franks and Teich, 1988). Equally, there is also compelling evidence that certain genetic abnormalities can predispose individuals to specific cancers (Ilyas et al., 1999). The variety of factors that have been implicated in the development of solid tumours stems, to a large extent, from the fact that ‘cancer’ is a generic term, often used to characterize a series of disorders that share common features. At this generic level of description, cancer may be viewed as a cellular disease in which controls that usually regulate growth and maintain homeostasis are disrupted. Cancer is typically initiated by genetic mutations that lead to enhanced mitosis of a cell lineage and the formation of an avascular tumour. Since it receives nutrients by diffusion from the surrounding tissue, the size of an avascular tumour is limited to several millimeters in diameter. Further growth relies on the tumour acquiring the ability to stimulate the ingrowth of a new, circulating blood supply from the host vasculature via a process termed angiogenesis (Folkman, 1974). Once vascularised, the tumour has access to a vast nutrient source and rapid growth ensues. Further, tumour fragments that break away from the primary tumour, on entering the vasculature, may be transported to other organs in which they may establish secondary tumours or metastases that further compromise the host. Invasion is another key feature of solid tumours whereby contact with the tissue stimulates the production of enzymes that digest the tissue, liberating space into which the tumour cells migrate. Thus, cancer is a complex, multiscale process. The spatial scales of interest range from the subcellular level, to the cellular and macroscopic (or tissue) levels while the timescales may vary from seconds (or less) for signal transduction pathways to months for tumour doubling times The variety of phenomena involved, the range of spatial and temporal scales over which they act and the complex way in which they are inter-related mean that the development of realistic theoretical models of solid tumour growth is extremely challenging. While there is now a large literature focused on modelling solid tumour growth (for a review, see, for example, Preziosi, 2003), existing models typically focus on a single spatial scale and, as a result, are unable to address the fundamental problem of how phenomena at different scales are coupled or to combine, in a systematic manner, data from the various scales. In this article, a theoretical framework will be presented that is capable of integrating a hierarchy of processes occurring at different scales into a detailed model of solid tumour growth (Alarcon et al., 2004). The model is formulated as a hybrid cellular automaton and contains interlinked elements that describe processes at each spatial scale: progress through the cell cycle and the production of proteins that stimulate angiogenesis are accounted for at the subcellular level; cell-cell interactions are treated at the cellular level; and, at the tissue scale, attention focuses on the vascular network whose structure adapts in response to blood flow and angiogenic factors produced at the subcellular level. Further coupling between the different spatial scales arises from the transport of blood-borne oxygen into the tissue and its uptake at the cellular level. Model simulations will be presented to illustrate the effect that spatial heterogeneity induced by blood flow through the vascular network has on the tumour’s growth dynamics and explain how the model may be used to compare the efficacy of different anti-cancer treatment protocols

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Context-awareness for mobile sensing: a survey and future directions

The evolution of smartphones together with increasing computational power have empowered developers to create innovative context-aware applications for recognizing user related social and cognitive activities in any situation and at any location. The existence and awareness of the context provides the capability of being conscious of physical environments or situations around mobile device users. This allows network services to respond proactively and intelligently based on such awareness. The key idea behind context-aware applications is to encourage users to collect, analyze and share local sensory knowledge in the purpose for a large scale community use by creating a smart network. The desired network is capable of making autonomous logical decisions to actuate environmental objects, and also assist individuals. However, many open challenges remain, which are mostly arisen due to the middleware services provided in mobile devices have limited resources in terms of power, memory and bandwidth. Thus, it becomes critically important to study how the drawbacks can be elaborated and resolved, and at the same time better understand the opportunities for the research community to contribute to the context-awareness. To this end, this paper surveys the literature over the period of 1991-2014 from the emerging concepts to applications of context-awareness in mobile platforms by providing up-to-date research and future research directions. Moreover, it points out the challenges faced in this regard and enlighten them by proposing possible solutions

Quasi-static imaged-based immersed boundary-finite element model of human left ventricle in diastole

SUMMARY: Finite stress and strain analyses of the heart provide insight into the biomechanics of myocardial function and dysfunction. Herein, we describe progress toward dynamic patient-specific models of the left ventricle using an immersed boundary (IB) method with a finite element (FE) structural mechanics model. We use a structure-based hyperelastic strain-energy function to describe the passive mechanics of the ventricular myocardium, a realistic anatomical geometry reconstructed from clinical magnetic resonance images of a healthy human heart, and a rule-based fiber architecture. Numerical predictions of this IB/FE model are compared with results obtained by a commercial FE solver. We demonstrate that the IB/FE model yields results that are in good agreement with those of the conventional FE model under diastolic loading conditions, and the predictions of the LV model using either numerical method are shown to be consistent with previous computational and experimental data. These results are among the first to analyze the stress and strain predictions of IB models of ventricular mechanics, and they serve both to verify the IB/FE simulation framework and to validate the IB/FE model. Moreover, this work represents an important step toward using such models for fully dynamic fluid–structure interaction simulations of the heart

User-centered visual analysis using a hybrid reasoning architecture for intensive care units

One problem pertaining to Intensive Care Unit information systems is that, in some cases, a very dense display of data can result. To ensure the overview and readability of the increasing volumes of data, some special features are required (e.g., data prioritization, clustering, and selection mechanisms) with the application of analytical methods (e.g., temporal data abstraction, principal component analysis, and detection of events). This paper addresses the problem of improving the integration of the visual and analytical methods applied to medical monitoring systems. We present a knowledge- and machine learning-based approach to support the knowledge discovery process with appropriate analytical and visual methods. Its potential benefit to the development of user interfaces for intelligent monitors that can assist with the detection and explanation of new, potentially threatening medical events. The proposed hybrid reasoning architecture provides an interactive graphical user interface to adjust the parameters of the analytical methods based on the users' task at hand. The action sequences performed on the graphical user interface by the user are consolidated in a dynamic knowledge base with specific hybrid reasoning that integrates symbolic and connectionist approaches. These sequences of expert knowledge acquisition can be very efficient for making easier knowledge emergence during a similar experience and positively impact the monitoring of critical situations. The provided graphical user interface incorporating a user-centered visual analysis is exploited to facilitate the natural and effective representation of clinical information for patient care

Current Trends and New Challenges of Databases and Web Applications for Systems Driven Biological Research

Dynamic and rapidly evolving nature of systems driven research imposes special requirements on the technology, approach, design and architecture of computational infrastructure including database and Web application. Several solutions have been proposed to meet the expectations and novel methods have been developed to address the persisting problems of data integration. It is important for researchers to understand different technologies and approaches. Having familiarized with the pros and cons of the existing technologies, researchers can exploit its capabilities to the maximum potential for integrating data. In this review we discuss the architecture, design and key technologies underlying some of the prominent databases and Web applications. We will mention their roles in integration of biological data and investigate some of the emerging design concepts and computational technologies that are likely to have a key role in the future of systems driven biomedical research

Dynamic finite-strain modelling of the human left ventricle in health and disease using an immersed boundary-finite element method

Detailed models of the biomechanics of the heart are important both for developing improved interventions for patients with heart disease and also for patient risk stratification and treatment planning. For instance, stress distributions in the heart affect cardiac remodelling, but such distributions are not presently accessible in patients. Biomechanical models of the heart offer detailed three-dimensional deformation, stress and strain fields that can supplement conventional clinical data. In this work, we introduce dynamic computational models of the human left ventricle (LV) that are derived from clinical imaging data obtained from a healthy subject and from a patient with a myocardial infarction (MI). Both models incorporate a detailed invariant-based orthotropic description of the passive elasticity of the ventricular myocardium along with a detailed biophysical model of active tension generation in the ventricular muscle. These constitutive models are employed within a dynamic simulation framework that accounts for the inertia of the ventricular muscle and the blood that is based on an immersed boundary (IB) method with a finite element description of the structural mechanics. The geometry of the models is based on data obtained non-invasively by cardiac magnetic resonance (CMR). CMR imaging data are also used to estimate the parameters of the passive and active constitutive models, which are determined so that the simulated end-diastolic and end-systolic volumes agree with the corresponding volumes determined from the CMR imaging studies. Using these models, we simulate LV dynamics from end-diastole to end-systole. The results of our simulations are shown to be in good agreement with subject-specific CMR-derived strain measurements and also with earlier clinical studies on human LV strain distributions