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The @neurIST project: towards understanding cerebral aneurysms

Alejandro Frangi, David R. Hose, and Daniel A. Ruefenacht By providing an integrated approach to alleviate the current fragmentation of relevant information, a novel data management system will have a major impact on the treatment of cerebral aneurisms. As for almost every form of knowledge, the volume of data describing human disease processes, including our understanding, diagnosis, and management of them, is growing exponentially. The data is also increasingly heterogeneous in form as text, images, and other symbolic formats. The data is also extremely diverse in context. For instance, it ranges from global guidelines based on the broadest epidemiological studies, through knowledge gained from disease-specic scientic studies, both in vitro and in vivo, to individual patient-specic data. In addition, the data also scales from the molecular to the cellular sizes, and from tissue or organ to patient representations. The recent breakthroughs in the description of the human genome and in our understanding of its connection to disease processes have also contributed more data through functional genomics studies. This phenomenal volume of fragmented information and its growth rate represent an unprecedented data-management challenge. In particular, it is often impossible for an individual whether a clinician responsible for patient management, or a physicist or engineer developing new imaging or interventional devicesto understand and assimilate this knowledge. The result is that it has become increasingly evident that new methods are required to manage, integrate and search data so that it becomes accessible to the end user. The @neurIST project was designed to address this issue.1 Scalable and reusable concepts The current fragmentation of relevant data effectively compromises disease treatment. This is why the @neurIST project rst aims to achieve vertical integration across data structures and across length scales. It also seeks to take into account the

Figure 1. @neurIST subject-specic computational uid dynamics (CFD) models of cerebral aneurysms are used to understand the role of blood ow in the rupture process. The pictures show simulations (colorcoded by ow velocity magnitude) in four subjects (1-4) with mirror aneurysms in the Circle of Willis (i.e. aneurysms symmetrically placed in the cerebral circulation). In each subject, the aneurysms are comparable in shape, type and location, with identical genetic and systemic factors. However, one of them ruptures (a) while the other does not (b). The complex processing chain developed in the project will help to understand whether ow conditions differ and how they can be used to dene surrogates of risk of rupture in a patient-specic context. Images are a courtesy of Alessandro Radaelli from the University of Pompeu Fabra and were produced in collaboration with Neuroangiograa Terapeutica SE (NAT/HGC), the Hospital Clinic i Provincial de Barcelona (HCPB) and George Mason University, using the ANSYS CFD solver.

horizontal integration that is present at every level of abstraction, from access to information sources, evidence processing, knowledge representation, structuring, and fusion. While the project is only focused on one carefully selected disease, cerebral aneurysm (see Figure 1), our overall goal is to create an integrative approach, scalable and reusable for other disease processes. Continued on next page

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Although important due to its impact on public health, cerebral aneurysm also has a number of interesting challenges that make it attractive as a proof of concept for our data management approach. Additionally, we believe that such a level of focus is necessary to credibly address the expected vertical integration and to identify clear exploitation paths. The latter are operative in industrial contexts, for instance in decision-support systems and in the advanced design of medical devices, and also in medical contexts, where they support further research and discovery, such as linking the molecular level understanding of a disease with the disease process itself. Management of cerebral aneurysm information The current understanding of cerebrovascular aneurysm disease combined with modern imaging technology can increasingly reveal silent lesions of the type found during clinical exams. With a prevalence of 2-3% and a rupture risk of the order of 1/10,000 people annually, treatment of this disease would benet significantly from an integrated approach and the development of a personalized risk-assessment strategy. The integration of multiple clinical data and the use of grid-based information technology (IT) systems may provide the required platform. This will reduce health care costs by optimally targeting the relevant patient population, thus avoiding unnecessary and potentially risky interventions while improving methods for minimally invasive treatment. Currently, the @neurIST project involves work at several different levels. The overall goal is to develop a novel IT-enabled system for cerebral aneurysm management.2 This requires identifying and collecting all publicly-available, relevant, and strategically important data from scientic studies.35 It also entails delivering a rich, multiscale information-processing chain to provide new diagnostic indexes and insights into the process of aneurysm formation and rupture.613 Another work area is the development of a set of scalable and reusable integrative suites and the demonstration of their value for understanding and managing the disease.1 Finally, ongoing efforts are directed at providing an information and communication technology system for developing, integrating and sharing relevant biomedical knowledge as required by the integrative suites. The @neurIST infrastructure will not only support computationally demanding tasks, such as complex modelling and simulation, but will also enable access to public and protected health databases all over the world.14 This capacity will no doubt promote the development of corresponding systems for other disease processes by demonstrating the personal and economic impact of IT-enabled information integration in the context of cerebral aneurysm management.

@neurIST and the virtual physiological human Although this integrated project is primarily concerned with the vertical integration of biomedical data, many of the developed concepts have obvious implications and applications within the framework of the STEP (A Strategy Towards the Europhysiome) roadmap initiative,15 funded as a concerted action with @neurIST. In particular, it provides a platform for demonstrating the benets and viability of the in silico model of a human being, by merging a top-down approach starting from models of body parts and organs with a bottom-up approach that models molecular interactions, pathways and cells. We believe that @neurIST is a pragmatic and concrete example of the virtual physiological human16 concept as well as a transitional project of tremendous signicance for the biomedical community. Author Information Alejandro Frangi Universitat Pompeu Fabra Barcelona, Spain David R. Hose University of Shefeld Shefeld, United Kingdom Daniel A. Ruefenacht University of Geneva Geneva, Switzerland
References 1. @neurIST: European initiative to integrate biomedical informatics in the management of cerebral aneurysms. http://www.aneurist.org 2. A. Arbona, S. Benkner, J. Fingberg, A. F. Frangi, M. Hofmann, D. R. Hose, G Lonsdale, D. A. Ruefenacht, and M. Viceconti, Outlook for grid service technologies within the @neurIST eHealth environment, Stud. Health Technol. Inform. 120, pp. 401404, 2006. 3. C. M. Friedrich, M. Zimmermann, and M. Hofmann, Grid Computing - An opportunity for biomedical and statistical computing p. 5, Statistical Computing 2006, 2006. Schloss Reisenburg; Germany. 4. J. Bonis, L. I. Furlong, and F. Sanz, OSIRIS: a tool for retrieving literature about sequence variants, Bioinformatics 22 (20), pp. 25672569, 2006. doi:10.1093/bioinformatics/btl421 5. L. I. Furlong, H. Dach, M. Hofmann-Apitius, and F. Sanz, Towards a development of a text-mining system for genes, sequence variants and phenotypes: integration of OSIRIS with ProMiner, Spanish Symp. Bioinformatics and Computational Bio., 2006. 6. J. R. Cebral, A. G. Radaelli, A. F. Frangi, and C. M. Putman, Hemodynamics before and after bleb formation in cerebral aneurysms, Proc. SPIE 6511, p. 65112C, 2007. doi:10.1117/12.709240 7. E. Oubel, M. de Craene, C. M. Putman, J. R. Cebral, and A. F. Frangi, Analysis of intracranial aneurysm wall motion and its effects on hemodynamic patterns, Proc. SPIE 6511, p. 65112A, 2007. doi:10.1117/12.708937 8. A. G. Radaelli, T. Sola, E. Vivas, X. Mellado, L. Guimaraens, J. R. Cebral, and A. F. Frangi, Combined clinical and computational information in complex cerebral aneurysms: application to mirror cerebral aneurysms, Proc. SPIE 6511, p. 65111F, 2007.

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9. D. San Millan Ruiz, H. Yilmaz, A. R. Dehdashti, A. Alimenti, N. de Tribolet, and D. A. Rufenacht, The perianeurysmal environment: inuence on saccular aneurysm shape and rupture, Am. J. Neuroradiol. 27 (3), pp. 504512, 2006. 10. D. Mill n, L. Dempere, J. M. Pozo, J. R. Cebral, and A. F. Frangi, Morphologia cal characterization of intracranial aneurysms using 3D moment invariants, IEEE Trans. Med. Imaging, 2007. accepted 11. M. Hernandez and A. F. Frangi, Non-parametric geodesic active regions: Method and evaluation for cerebral aneurysms segmentation in 3DRA and CTA, Med. Image Anal. 11 (3), pp. 207324, 2007. doi:10.1016/j.media.2007.01.002 12. S. E. Harrison, S. M. Smith, J. Bernsdorf, D. R. Hose, and P. V. Lawford, Application and validation of the lattice Boltzmann method for modelling ow-related clotting, J. Biomech., 2007. in press, doi:10.1016/j.jbiomech.2007.01.026 13. D. Wanga, P. Lammersb, and J. Bernsdorf, Lattice Boltzmann simulations of steady shear thinnining blood ow with a Carreau-Yasuda model Intl. Conf. Parallel Computational Fluid Dynamics , May 21-24, 2007. 14. K. Kumpf, A. Woehrer, S. Benkner, G. Engelbrecht, and J. Fingberg, A semantic mediation architecture for a clinical Data Grid, ch. 12, Wiley & Sons, 2007. 15. STEP: A strategy towards the EuroPhysiome is a coordination action that aims to provide a roadmap to the development of the Virtual Physiological Human. http://www.europhysiome.org 16. Towards virtual physiological human: multilevel modelling and simulation of the human anatomy and physiology, S. Nrager, I. Iakovidis, M. Cabr era, and R. Ozcivelek (eds.), White Paper DG INFSO & DG JRC, 2005. http://ec.europa.eu/information society/activities/health/docs/events/ barcelona2005/ec-vph-white-paper2005nov.pdf

c 2007 SPIEThe International Society for Optical Engineering