1. The role of blood flow in aneurysm pathophysiology and treatment - @neurIST, Physiome - voxel, pixel, phyxel, bioxel - flow in aneurysms - flow in the intracranial compartment - homeostasis, allostasis daniel.rufenacht@sim.hcuge.ch www.neuroimaging.ch STEP 15 / 16.5.2006 - a strategy for the EUORPHYSIOME - FP7

2. Pixel Picture (Pics, Pix) and element Voxel Volume and pixel (spatial aspects) Bioxel (biological element) integration of all biological and physical parameters allowing for modelling of life in a virtual environment to understand homeostasic and allostasic mechanisms of biological systems Phyxel (physical element) 4D - pixel (temporal aspects) Real Human Virtual Replica of Human Converging technologies

3. Mission statement: @neurIST will develop an IT infrastructure for the management and processing of heterogeneous data associated with the diagnosis and treatment of cerebral aneurysm and subarachnoid haemorrhage. The data span all length scales, from molecular, through cellular to tissue, organ and patient representations. These data are increasingly heterogeneous in form, including textual, image and other symbolic structures, and are also diverse in context, from global guidelines based on the broadest epidemiological studies, through knowledge gained from disease-specific scientific studies, to patient-specific data from electronic health records. New methods are required to manage, integrate and interrogate the breadth of data and to present it in a form that is accessible to the end user. FP6 http://aneurist.org

4. Initiation Growth Rupture Humphrey JD Cardiovascular solid mechanics 2001 2-4% 2000-4000/100K 10/100K/y Humphrey JD Cardiovascular solid mechanics 2001

5. Humphrey JD Cardiovascular solid mechanics 2001 oscillatory shear stress

6. @neuEndo WCE – ANSYS IDAC – ASD @neuRisk INF - PMS How will the results precisely impact on the targeted groups? Improve decision making processes in the management of unruptured aneurysms by providing a score that integrates all the available information for identifying at-risk patients and reducing current over treatment Support computational design processes towards a next generation of smart flow- correcting implants to treat ruptured aneurysms and reduce current treatment costs, side effects and recurrence. Support the knowledge discovery for linking genetics to disease, vasospasm and blood clotting after cerebral hemorrhage @neurIST Systems Support the integration of modeling, simulation and visualization of multimodal data @neuCompute/Info NEC – GS – ANSYS Support integration of data and computing resources. @neuFuse B3C – PMS Support Tools Enabling IT @neuLink SCAI (Roche, Actelion)

7. Balloon Aneurysm Filling Coil Aneurysm Filling Stent-Assisted Coiling Flow Diversion Vessel Repair 1985 1990 2005 2010 Cebral JR, Putman C - G. Mason Univ., Fairfax, VA

8. Image guided minimal invasive treatment methods: Endovascular repair of cerebral arteries based on 3D imaging data: Converging Technologies Medical Imaging 3D dataset DSA,MR,CT Patient database Treatment control Medical Informatics, Flow-/ Wall- Biomech. Simulation - Validation (numeric, in-vitro, …) CFD PIV / LDV Flow- correction Rupture risk assessment; Stent design CAD Medical Device Stent material Stent delivery Stent Treatment

9. outsidewallinside perianeurismal environment tissue, shape, biomechanics blood flow rheology Weir B

10. Wiebers DO, et al. NER Symposium, ASNR’03

12. Autoregulation: Flow in collapsible veins - CBF 1.Increased ICP increases outflow obstruction 2.The vascular resistance of the microvascular bed decreases at increased ICP (within certain limits) Venous autoregulation of global CBF D Greitz: Int J Neurorad 1997 1. 2.

13. Autoregulation of CBF and CSF (Homeostasis) 1.Homeostasis (“stability through constancy”) of brain and CSF circulation can adapt to parameter changes in a limited range. 2.Under pathological conditions such as Trauma, Hemorrhage, Thrombosis, Ischemia, etc. the homeostatic mechanisms are unable to cope with the demands placed on them (acutely, chronically). 3.Allostasis (“stability through change”) allows for reaching conditions of a new balance in such pathological conditions (“fitness under natural selection”). 4.Only numerical simulation may help to understand such complex conditions and suggest ways of medical therapy, i.e. corrections that may lead to a new equilibrium for a system in trouble. P Sterling: Principles of allostasis, 2004