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PHYSIOLOGICAL FLOW NETWORK Funded by the EPSRC Imaging and Modelling for Interventional Planning University of Oxford, Department of Engineering 18-19 April 2006 Organisers: Yiannis Ventikos Stephen Payne (The University of Oxford) (The University of Oxford) Network Coordinators: Spencer Sherwin (Imperial College London), Sarah Waters (Nottingham) Page 1 PhysioloficalFlowNet\DelegatePack Contents Page Welcome ....................................................................................................................................................... 3 Funding ......................................................................................................................................................... 3 Acknowledgements ..................................................................................................................................... 3 Meeting and Accommodation Location....................................................................................................... 4 Computer access .......................................................................................................................................... 6 Poster competition ....................................................................................................................................... 6 Dates for your diary ..................................................................................................................................... 6 Programme .................................................................................................................................................. 7 List of Participants and Accommodation .................................................................................................... 8 Abstracts for invited speakers .................................................................................................................... 10 Abstracts for posters ................................................................................................................................... 23 The STEP Project .......................................................................................................................................... 35 Page 2 PhysioloficalFlowNet\DelegatePack Welcome Welcome to the Department of Engineering Science, University of Oxford, for the third meeting of the EPSRC network in Physiological Flow Modelling. The network is led by Spencer Sherwin (Imperial College) and Sarah Waters (Nottingham) and aims to promote interactions between scientists involved in physiological flow modelling in both the physical and life sciences, to explore the potential impact of emerging areas, and to provide a basic teaching function. We have plenary presentations from Daniel Rüfenacht, Geneva, David Steinman, Toronto, and Aaron Fogelson, Utah, as well as a number of leading UK experts. The presentations are grouped in the areas of imaging, modelling for disease and treatment, and CSF flow. We again have a number of posters, which we hope will lead to much informal discussion and intellectual stimulation. The historic city and University of Oxford is only a few minutes walk away, and we hope that you will have time to enjoy both the conference and the city. Yiannis Ventikos and Stephen Payne Funding We gratefully acknowledge funding from the EPSRC without whose financial support the meeting could not take place. We would also like to thank the National E-Science Centre for hosting the workshop. Acknowledgements The network coordinators would like to thank the local organising committee and in particular Dr Yiannis Ventikos for their considerable effort in arranging the meeting. We would also like to acknowledge and Karen Clarke for her secretarial assistance. Page 3 PhysioloficalFlowNet\DelegatePack Location The meeting is being held at the Thom building, Department of Engineering, University of Oxford. Details of which are shown in the following map: Page 4 PhysioloficalFlowNet\DelegatePack For resident participants your accommodation will be at the college given in the participants section on page 9. For participants staying at Keble, Wadham or Mansifled the following map shows the location of the college. Keble is number 14; Wadham is number 43 and Mansfield is number 20. The University Club is opposite Mansfield. Page 5 PhysioloficalFlowNet\DelegatePack Computer Access There is a computing room set aside for people to use. It is located on the 5 th floor of the Thom building. The computers are ready for use and the password is teach2050 A wireless network can also accessed by completing a form available from Stephen Payne at the registration desk. Poster Competition OXFORD UNIVERSITY PRESS Oxford University Press is pleased to sponsor the Third Physiological Flow Meeting Prize for the Best Poster presented by a PhD Student. The winner will receive a £100 Book Voucher from Oxford University Press. There are also 2 runner up prizes of £50 worth of Book Vouchers to be won. Winners will be announced at the Third Physiological Flow Meeting: Imaging and Modelling for Interventional Planning before the final plenary Seminar Dates for your Diary The next meeting of the Physiological Flow Network is: " Respiratory Biomechanics and Physiological Fluid-Structure Interactions Problems " Manchester University 1-3 April 2007 Organisers: Mathias Heil. Paul Dark Page 6 PhysioloficalFlowNet\DelegatePack PHYSIOLOGICAL FLOW NETWORK 18-19 April 2006 Programme TUESDAY 18th April 09.30-10.25 Registration and coffee 10.25-10.30 Welcome Session 1 (Chairperson Y. Ventikos). Clinical Challenges in Modelling and Imaging 10.30-11.30 Keynote Lecture: Daniel Rufenacht, Geneva. “Role of flow in cerebral aneurysm pathophysiology and treatment” 11.30-12.00 Paul Dark, Manchester. “Clinical and engineering challenges in cardiovascular imaging and modeling: the intensive care setting” 12.00-13.30 LUNCH AND POSTER SESSION Session 2 (Chairperson A. Noble). Advanced Imaging Techniques 13.30-14.00 David Firmin, Imperial College, London. “Vascular Imaging and Blood Flow measurement by MRI” 14.00-14.30 Alan Jackson, Manchester. “Microvascular Flow in the Brain” 14.30-15.00 David Larkman, Imperial College, London. “Partially Parallel Imaging: New developments in MRI using multiple receiver coils” 15.00-15.30 TEA BREAK AND POSTER SESSION Session 3 (Chairperson ?) Imaging in Cardiovascular Disease 15.30-16.00 Saul Myerson, JR, Oxford. “Cardiovascular magnetic resonance – the gold standard?” 16.00-16.30 Panicos Kyriacou, City University, London. “Non invasive optical monitoring for medical diagnosis” 16.30-17.00 Robert Dickinson, Imperial College, London. “Catheter-based ultrasound devices for directing vascular intervention” 17.00-17.05 Announcements, closing the first day 18.45-? Pre-dinner drinks and reception at Wadham College (see location section for directions) Page 7 PhysioloficalFlowNet\DelegatePack WEDNESDAY 19th April Session 4-I (Chairperson S. Sherwin) Modelling for Disease and Treatment 9.00-10.30 Keynote Lecture: David Steinman, Toronoto “On the finer points of simulating cerebral aneurysm interventions using CFD” 10.30-11.00 Yun Xu, Imperial College, London. “Patient-specific studies of thoracoabdominal and abdominal aortic aneurysms” 11.00-11.30 COFFEE BREAK AND POSTER SESSION Session 4-II (Chairperson S. Sherwin) Modelling for Disease and Treatment 11.30-12.00 Sarah Waters, Nottingham. “Fluid flow in the stented ureter” 12.00-12.30 Rod Hose, Sheffield “Dynamic anatomy, haemodynamics and the sparing of the superior mesenteric artery” 12.00-13.30 LUNCH AND POSTER SESSIONS Session 5 (Chairperson P. Summers) Modelling and Measurements for the CSF Environment 13.30-14.00 Ian Sobey, Oxford. “Poroelastic modeling for evolution and treatment for hydrocephalus” 14.00-14.30 Peter Carpenter, Warwick. “Modelling the dynamics of the spinal CSF system: the pathogenesis of syringomyelia” 14.30-15.00 Bob Marchbanks, Southampton. “Mechanics of the cerebrospinal fluid system and the clinical importance of inner ear fluid interactions” 15.00-15.30 Stephen Payne, Oxford. “Combined modeling and measurement of CSF pulsatility” 15.30-16.00 TEA BREAK AND POSTER SESSION 16.00-16.10 Poster competition announcement 16.10-17.10 Keynote Lecture: Aaron Fogelson, Utah. “Computational modeling of blood clotting” Chairs Yiannis Ventikos 17.10-17.20 Closing remarks List of Participants & Accommodation Name Mark Atherton Jordi Alastruey Leah Band Stefan Bernhard Tony Birch Jarl Blijd Organisation Brunel University Imperial College London Nottingham University Universitat Gottingen Southampton University Philips Medical Systems e-mail address mark.atherton@brunel.ac.uk jordi.alastruey-arimon@imperial.ac.uk pmxlrb@nottingham.ac.uk stefan@bernhard-professional.de tony.birch@suht.swest.nhs.uk jarl.Blijd@philips.com Page 8 PhysioloficalFlowNet\DelegatePack Accommodation University Club Wadham Mansfield Andrew Bond Tim Bowker Neil Bressloff Bindi Brook Tom Bruijns Peter Carpenter Michael Chappell Duanduan Chen Andrew Cookson Paul Dark Diganta Das Robert Dickenson Denis Doorly William Easson Carles Falcon David Firmin Aaron Fogelson Katherine Fraser Constantinos Hadjissou Matthias Heil Rod Hose Peter Hoskins Alan Jackson Clare Jackson Oliver Jenson Stathis Kaliviotis Asimina Kazakidi Andreas Kempf Panos Kyriacou David Larkman William Lee Rachel Levy Prashanta Kumar Mandal Bob Marchbanks Aristotelis Mitsos Keri Moyle Saul Myerson Stephen Payne Joaquim Peiro Stefan Piechnik Matthew Robson Daniel Rufenacht Spencer Sherwin Jennifer Siggers Ian Sobey David Steinman Pavel Stroev Paul Summers Raoul Van Loon Yiannis Ventikos Peter Vincent Sarah Waters Yun Xu Yufeng Yao Imperial College London Oxford University Southampton University Nottingham University Philipss Medical Systems Warwick University Oxford University Oxford University Imperial College London Manchester University/Hope Hospital Oxford University Imperial College London Imperial College London Edinburgh University IDIBAPS-Hospital Clinic de Barcelona Imperial College University of Utah Edinburgh University Oxford University Manchester University Sheffield University Edinburgh University Manchester University Oxford University Nottingham University King’s College London Imperial College London Imperial College London City University Imperial College London Edinburgh University Duke University Oxford University Southampton University Oxford University Oxford University Oxford University Oxford University Imperial College London Oxford University Oxford University Geneva, Switzerland Imperial College Nottingham University Oxford University Toronto, Canada Edinburgh University Oxford University Imperial College London Oxford University Imperial College London Nottingham University Imperial College London Kingston University andrew.bond@imperial.ac.uk timothy.bowker@ox.ac.uk n.w.bressloff@soton.ac.uk bindi.brook@nottingham.ac.uk tom.bruijns@philips.com pwc@eng.warwick.ac.uk michael.chappell@eng.ox.ac.uk duanduan.chen@ox.ac.uk a.cookson@imperial.ac.uk mdssspmd@manchester.ac.uk diganta.das@eng.ox.ac.uk robert.dickinson@imperial.ac.uk d.doorly@imperial.ac.uk bill.easson@ed.ac.uk cfalcon@ub.edu d.firmin@imperial.ac.uk fogelson@math.utah.edu kate.fraser@ed.ac.uk constantinos.hadjistassou@eng.ox.ac.uk M.Heil@maths.man.ac.uk d.r.hose@sheffield.ac.uk p.hoskins@ed.ac.uk alan.jackson@manchester.ac.uk clare.jackson@cardiov.ox.ac.uk oliver.jensen@nottingham.ac.uk efstathios.kaliviotis@kcl.ac.uk asimina.kazakidi@imperial.ac.uk a.kempf@imperial.ac.uk p.kyriacou@city.ac.uk david.larkman@imperial.ac.uk william.lee@ed.ac.uk rachel.levy@gmail.com pkmind02@yahoo.co.uk rob@marchbanks.co.uk Aristotelis.mitsos@wolfson.ox.ac.uk keri.moyle@eng.ox.ac.uk saul.myerson@cardiov.ox.ac.uk stephen.payne@eng.ox.ac.uk j.peiro@imperial.ac.uk stefanp@fmrib.ox.ac.uk Matthew.robson@cardiov.ox.ac.uk daniel.rufenacht@sim.hcuge.ch s.sherwin@imperial.ac.uk jennifer.siggers@nottingham.ac.uk ian.sobey@comlab.ox.ac.uk steinman@mie.utoronto.ca pavel.stroev@ed.ac.uk paul.summers@nds.ox.ac.uk r.v.loon@imperial.ac.uk yiannis.ventikos@ox.ac.uk peter.vincent@imperial.ac.uk sarah.walters@nottingham.ac.uk yun.xu@ic.ac.uk y.yao@kingston.ac.uk Page 9 PhysioloficalFlowNet\DelegatePack Wadham Mansfield University Club Wadham University Club Mansfield Mansfield University Club Keble Mansfield Mansfield University Club Keble University Club Wadham Wadham Mansfield University Club University Club Mansfield Mansfield University Club Mansfield Keble University Club Mansfield Mansfield Wadham Wadham ABSTRACTS FOR INVITED SPEAKERS (Alphabetical order by first author) Modelling the dynamics of the spinal CSF system: The pathogenesis of syringomyelia Peter Carpenter Warwick University The aim of our work is to develop a biomechanical theoretical model for pressure propagation in the intraspinal cerebrospinal-fluid system. Our motivation is to elucidate the pathogenesis of syringomyelia. This is a serious disease characterized by the appearance of longitudinal cavities within the spinal cord. Its causes are unknown, but pressure propagation is probably implicated. Our current theoretical model of the spinal cord assumes that it is axisymmetric comprising of a poro-elastic cylinder (the spinal cord), surrounded by a thin, relatively stiff, membrane (the pia mater), this is surrounded in turn by a rigid-walled cylindrical tube (the sub-arachnoid space) filled with a fluid (the cerebrospinal fluid). The mechanics of the pia mater is represented by a conventional tube law. The whole system forms a non-linear system that supports propagating waves. On the basis of our theoretical model we investigate the mechanisms proposed recently by medical researchers for the origins of syringomyelia. All these proposed mechanisms are found to have serious shortcomings. We then go on to propose a novel mechanism of our own which involves the generation of pressure pulses in the spinal system due to actions such as coughing and sneezing. Owing to the nonlinear nature of the wave propagation the leading edge of the pressure pulses tend to steepen to form shock-like elastic jumps. The reflection of such an elastic jump at a stenosis is found to generate a substantial transient pressure rise within the spinal cord in the vicinity of the stenosis. Typically the stenosis would be due to the hindbrain tonsil associated with the Arnold-Chiari malformation. The proposed mechanism seems to be consistent with the available empirical and clinical data. ***** Clinical and engineering challenges in cardiovascular imaging and modelling: the intensive care setting Paul Dark Manchester University Intensive care is the general term for specialist treatment given to critically ill patients. Patients who are in a life-threatening condition because of a major infection, an accident, or because they are recovering from a major operation will need intensive care. A major function of intensive care is to monitor and support every organ system during otherwise overwhelming tissue injury or infection, such that appropriate therapeutic decisions and interventions can occur in a time-critical fashion. The cardiovascular or circulatory system is central to the body’s responses to injury/infection and is a key organ system that has to be monitored and supported continuously during the provision of intensive care. My talk will describe the current international debate surrounding how circulatory acute patho-physiology should be monitored in this healthcare setting, concentrating on the established physical Page 10 PhysioloficalFlowNet\DelegatePack biomarkers of cardiovascular status, including their utility, validity and clinical effectiveness. I will then describe the development of newer, minimally invasive technologies and overview my own recent work on the development of a transoesophageal Doppler ultrasound technique that has depended on a better understanding of pulsatile blood flow characteristics in man during extreme perturbation. Dr Dark's collaborative research work in Manchester focuses on developing an understanding of how humans respond biologically to severe injury and infection, and developing new therapeutic approaches to help people survive and recover from intensive care. ***** Catheter-based ultrasound devices for directing vascular intervention R.J.Dickinson1 , R.I.Kitney1 and A.Jain2 1. Department of Bioengineering, Imperial College, London 2. Department of Cardiac Research, London Chest Hospital, London Catheter-based ultrasound can be used to diagnose and guide treatment of diseased coronary arteries. Interventional ultrasound imaging probes must be sufficiently small to gain access to the surgical site, and any rigid portion must be limited in length to permit adequate flexibility. In practice this means the ultrasound probes have to operate at high frequency and constructing high-frequency sub-miniature probes presents a number of technical challenges, in particular relating to interconnects and packaging. It is now possible to build a 1mm diameter intravascular imaging probe which can used to characterise the stenosis, and monitor the correct deployment of stents. A new application is to guide the creation of an anastomosis between the coronary artery and vein, where alignment of the crossing needle is crucial. This can be achieved with two catheters each with a single ultrasound transducers; the ‘arterial’ catheter emits a narrow beam of ultrasound. Detection of the ultrasound beam by the ‘venous’ catheter confirms alignment and a nitinol crossing needle makes a channel from artery to vein. An accuracy of 1mm is confirmed by in vitro and in vivo trials. ***** Vascular Imaging and Blood Flow measurement by MRI David Firmin Imperial College, London This presentation will discuss the MR tools that available to study the cardiovascular system with emphasis on the current status including limitation and the future potential. As well as the numerous techniques for measuring function, morphology and characterising cardiac tissues, MR is showing considerable potential for studying the vasculature of the body along with the blood that is flowing through it. One of the most important developments has been in the area of imaging the arterial wall. Studies have involved numerous vessels including the aorta and the coronaries, however, the majority of effort has gone into imaging of the carotid arterial wall. The reasons for this are that it is reasonably large and close to the surface, it moves relatively little and the carotid bifurcation is a relatively common site of disease. Techniques have been developed to characterise the different atheromatous tissue types and these have been assessed by comparison with histology on endarterectomy specimens following surgical removal. Results have been mixed and although there Page 11 PhysioloficalFlowNet\DelegatePack have been examples of multiple components of atheromatous plaque the methods are far from routine. One of the issues is that the best methods of imaging the carotid vessel wall are single slice and require a significant acquisition time of several minutes. Volume methods are possible but are susceptible to motion problems and retention of signals from slowly flowing and re-circulating blood that can easily be mistaken for plaque. In other vessels although the issues of blood signals may be less of a problem, signal to noise ratios and motion become more difficult. MR also has potential to measure some functional aspects of the vessel wall. Vessel wall imaging methods can be timed at end systole or end diastole to give a measure of distensibility; alternatively cine imaging methods can be used to image the vessel cross-section throughout the heart-cycle. Methods have also been described to enable regional strain measurements although these are as yet far from established. Of course to measure vascular compliance from the distensibility requires either an invasive measurement or an estimation of the pressure in the vessel being imaged. The other aspect that MR has to offer in this area is the measurement of blood flow. A single slice measurement can be achieved with relatively high spatial and temporal resolution with components of velocity measured in three orthogonal directions all with an acquisition time of a minute or less. However, to measure the flow in a 3D volume would take considerably longer. MR flow can now be acquired with a high enough temporal resolution (~4ms) simultaneously in two slices to give a measure of pulse wave velocity which can again be used to derive the vascular compliance. One issue that is common for vascular function and for blood flow measurement is that for a reasonable resolution image the acquisition takes a period a minute or more and this time scale can make it difficult to follow controlled changes or physiological variations to the flow or function. Some methods have been developed to speed up the acquisition; however, a compromise will always have to be made to another aspect of the measurement. In summary MR has much to offer in the study of the vascular system, methods enable registered images to characterise disease and measure functional and blood flow aspects. It has the advantage of being non-invasive and without hazardous radiation which enables longitudinal studies and studies involving normal subjects. There are, however, limitations and compromises that have to be made, often between imaging time, signal to noise and resolutions and there is no doubt that the information is best combined with other imaging and /or modelling methods. ***** Computational Modeling of Blood Clotting Aaron Fogelson Utah (USA) Intravascular hemostasis and thrombosis occur under flow and this can profoundly influence the progress of clot formation. This talk will focus on two different aspects of our efforts to model and probe the interactions of flow and clotting. One involves the biochemistry of the coagulation enzyme network and how the behavior of this system is affected by flow-mediated platelet deposition on aninjury and by flow-mediated transport of the enzymes and their precursors. The other involves a continuum model that describes platelet thrombosis initiated by a ruptured atherosclerotic plaque in a coronary-artery-sized vessel. This model includes full treatment of the fluid dynamics, and the aggregation of platelets in response to the plaque rupture and further chemical signals. Among the behaviors seen with this model are the growth of wall-adherent Page 12 PhysioloficalFlowNet\DelegatePack platelet thrombi to occlude the vessel and stop the flow, and the transient growth and subsequent embolization of thrombi leaving behind a passivated injured surface. ***** Dynamic anatomy, haemodynamics and the sparing of the superior mesenteric artery Rod Hose Sheffield University The abdominal aorta and its branches are common sites of atherosclerotic lesions. In contrast to the surrounding vasculature, primary atherosclerosis of the superior mesenteric artery (sma) is rare. This presentation will focus on the anatomy and the haemodynamics of the sma and will explore the question of whether either has unique features that might in some way contribute to the relative sparing of this vessel from the disease process. A methodology will be described for automatic segmentation of the region of the branching of the superior mesenteric artery from the aorta, over the cardiac cycle, by image registration. The facility for generation of a computationally efficient mesh using the same process will be discussed. Vessel geometry is obtained from cardiacgated magnetic resonance imaging, with flow boundary conditions from a phase contrast sequence. Dynamic and haemodynamic characteristics of the artery will be described, including measures of wall shear and oscillatory shear index. The effects of the motion of the artery on the computed haemodynamic characteristics will also be discussed. ***** Microvascular Flow in the Brain Alan Jackson Manchester University Every medical student is taught that the most important aspect of brain bloodflow is that the delivery of nutrients, particularly oxygen, is kept above a critical threshold value. We have specific autoregulatory mechanisms to protect mean arterial blood pressure in the brain in the face of physiological challenge and if those mechanisms fail then the brain rapidly experiences ischaemic injury and eventually stroke. This is an admirable example of the grossly over simplistic models that we feed our medical students and which form the basis on which they eventually make therapeutic interventions. The beauty of such models is that they work if they are used in the right context. For instance in patients with acute thrombotic stroke the main risk is of permanent ischaemic damage which can be avoided only by recanalizing vessels and restoring cerebral blood flow within a critical time period. Sometimes these models can be easily extended to fit admirably with observations from disease states. Let us considered two examples: 1) large decreases in cerebral blood flow are seen in patients with hydrocephalus despite maintenance of arterial blood pressure. This is easily explained by the increase in interstitial pressure which accompanies hydrocephalus and reduces cerebral perfusion pressure (arterial pressure minus venous pressure/interstitial pressure). Shunting the patient (ie draining CSF from the ventricles) reverses the elevation in intracranial pressure and the blood flow Page 13 PhysioloficalFlowNet\DelegatePack returns to near normal values. 2) the presence of extensive areas of white matter damage, known as Deep White Matter Hyperintensities (DWMH) due to their characteristic high signal on MRI, is common in old age and many age-related disease states. DWMH is most commonly attributed to local ischaemia due to microvascular disease and radiological reports commonly state that "these appearances are typical of microvascular disease". Unfortunately there is clear evidence that in some forms of hydrocephalus large decreases in cerebral bloodflow occurred despite normal intracranial pressure whilst histological examination of the microvessels causing "microvascular disease" shows that there is no evidence of abnormality in up to 35%. Furthermore, since histological vascular abnormalities and DWMH both show a strong age correlation the evidence for a causative relationship is much weaker than it first appears. The aim of this long preamble is to demonstrate our amazing reliance on simple fundamental models of physiological behaviour and, our tendency to use these models to explain new findings even when there is clear evidence that invalidates one or more of the basic assumptions on which the model is based. Remember if the only tool you have is a hammer, you tend to see every problem as a nail (Abraham Maslow). So what is needed? Do we abandon models in favour of hypothesis driven, condition specific experimentation or do we develop more complex models? Although the answer to this question seems self-evident (to me) it does deserve serious consideration. We can easily develop hypothesis driven constructs for individual diseases which may well serve well as the basis for decision support in the management of disease states. However, the need for separate disease-specific models simply reflects a lack of understanding of the pathogenetic mechanisms involved. Furthermore, it leads to the potential construction of multiple parallel hypotheses, probably based on a series of basic assumptions which fundamentally disagree. Alternatively the development of the more complex models allows for a unified framework against which to test experimental and clinical observations. Diagnostic treatment decision mechanisms can be robustly based on an efficient model and, such models should massively increase our understanding of the pathophysiology. So effectively it is no contest! Unfortunately, the very reason for extending our model is that the system we are attempting to understand is so complex that it does not respond to simplistic attempts at interpretation. We should therefore expect the model to be complex and, more importantly, to change with time in order to incorporate new observations. This means that the model could become extremely complex and certainly far too complex for junior doctors to carry around in their head and apply at the bedside. However, complexity should not invalidate our efforts to develop such a model. The purpose of the model is to remove as many layers of complexity is possible not to oversimplify the point where the model becomes ineffective. So where to start? In this lecture I am going to attempt to review the experimental and clinical evidence which has accumulated over the past 10 to 15 years about the effects of arterial pressure pulsatility on cerebral bloodflow. Although the exact effects of the systolic pulse wave within the skull remain the subject of research there is now a general consensus as to the mechanism in normal subjects. Teleologically this mechanism can be seen as a necessary evolutionary development to protect the brain from constant mechanical stresses which would be imposed by repeated systolic expansions of intracerebral vessels by large variations in intraluminal pressure. In normal healthy individuals systolic expansion of the basal arteries occurs proximal to the pial arteriolar resistance vessels responsible for autoregulatory control of cerebral blood flow [1, 2]. Arterial pulsatility produces a pressure wave within the subarachnoid CSF which causes an outflow of CSF through the foramen magnum into the compliant spinal CSF space, equivalent to approximately Page 14 PhysioloficalFlowNet\DelegatePack 50% of the increase in intracerebral blood volume [1]. The pressure wave is also transmitted to the major dural venous sinuses, a mechanism apparently mediated by systolic expansion of the arachnoid granulations [3, 4]. The effect of this is that the energy in the arterial pressure wave entering the cranial cavity is dissipated into the formation of CSF and venous pulsatility and largely bypasses the cerebral circulation. In addition, the elastic properties of expanding arterial walls absorb part of the energy of the systolic pulse wave which is then released in diastole. This has the effect of further flattening the arteriolar pressure profile to which the intracerebral circulation is exposed. Constancy of cerebral perfusion pressure is also maintained by transient systolic increases in venous backpressure within the brain due to direct compression of cortical surface veins by the systolic pulse wave in the subarachnoid CSF space. This combination of processes maintains a constant perfusion pressure and flow in the cerebral capillary bed despite the major pressure changes seen between systole and diastole. The major importance in the elucidation of these complex autoregulatory mechanisms is the increasing recognition that they are deranged in a wide range of cerebral diseases. This has led to a reappraisal of the pathogenetic mechanisms behind a wide range of diseases including communicating hydrocephalus [2] normal pressure hydrocephalus (NPH)[5, 6] , idiopathic intracranial hypertension (IIH) [7, 8], secondary intracranial hypertension (SIH) [7], the ischaemic white matter change known as leukoariaosis (LA) [1], neurodegenerative and mixed dementias and other cerebral atrophic disorders [9, 10]. For example: modern theories of hydrocephalus identify a chronic form of communicating hydrocephalus which is believed to result from decreased compliance in basal arteries which gives rise to break down of the windkessel mechanism causing increased pulsatility in cerebral arterioles and capillaries. This causes an intermittent trans-mantle pressure differential leading to progressive ventricular dilation until a new physiological balance is reached [2]. Many other pathogenetic mechanisms mediated by a breakdown in this autoregulatory system have been postulated including decreased arteriolar resistance with a resultant increase in cerebral blood flow (IIH) [8], increased venous resistance due to partial outflow of destruction (SIH) [7], focal reductions in venular compliance (LA) [1], and reduced venous compliance due to abnormally large transmission of the systolic CSF pressure wave to the venous sinuses causing superficial cortical vein compression ( NPH) [5]. Modelling such a complex mechanism is difficult although not impossible and several authors have attempted to present electrical equivalence models which describe the interplay of vascular and CSF fluid flow is that occurs during the cardiac cycle. The problem with these models is that they are effectively impossible to test against reallife data where the range of measurements which can be obtained is restricted. I will present a basic simplified example of such a model and showed how it can be tested against data obtained from normal volunteers. I will then discuss the potential problems in expanding the model to become a true descriptive basis for data analysis in disease states. ”Everything you've learned in school as "obvious" becomes a less and less obvious as you begin to study the universe. For example, there are no solids in the universe. There's not even a suggestion of a solid. There are no absolute continuums. There are no surfaces. There are no straight lines. " R Buckminster Fuller (inventor of the geophysical dome) References 1. Bateman, G.A., Pulse-wave encephalopathy: a comparative study of the hydrodynamics of leukoaraiosis and normal-pressure hydrocephalus. Neuroradiology, 2002. 44(9): p. 740-8. Page 15 PhysioloficalFlowNet\DelegatePack 2. Greitz, D., Radiological assessment of hydrocephalus: new theories and implications for therapy. Neurosurg Rev, 2004. 27(3): p. 145-65. 3. Stolz, E., et al., Transcranial color-coded duplex sonography of intracranial veins and sinuses in adults. Reference data from 130 volunteers. Stroke, 1999. 30(5): p. 1070-5. 4. Greitz, D., T. Greitz, and T. Hindmarsh, A new view on the CSF-circulation with the potential for pharmacological treatment of childhood hydrocephalus. Acta Paediatr, 1997. 86(2): p. 125-32. 5. Bateman, G.A., Vascular compliance in normal pressure hydrocephalus. AJNR Am J Neuroradiol, 2000. 21(9): p. 1574-85. 6. Bateman, G.A., The reversibility of reduced cortical vein compliance in normalpressure hydrocephalus following shunt insertion. Neuroradiology, 2003. 45(2): p. 6570. 7. Bateman, G.A., Vascular hydraulics associated with idiopathic and secondary intracranial hypertension. AJNR Am J Neuroradiol, 2002. 23(7): p. 1180-6. 8. Mathew, N.T., J.S. Meyer, and E.O. Ott, Increased cerebral blood volume in benign intracranial hypertension. Neurology, 1975. 25(7): p. 646-9. 9. Bateman, G.A., Pulse wave encephalopathy: a spectrum hypothesis incorporating Alzheimer's disease, vascular dementia and normal pressure hydrocephalus. Med Hypotheses, 2004. 62(2): p. 182-7. 10. Naish, J., et al., Abnormalities of CSF flow patterns in the cerebral aqueduct in treatment resistant late life depression: a potential biomarker of microvascular angiopathy. MRM. Mag Reson Med, (In Press). ***** Optical Sensors in Physiological Measurements Panos Kyriacou City University Throughout human history, light has played an important role in medicine. New optical technologies, many involving light emitting diodes, laser diodes, lasers, fibre optics or nanotechnologies providing sensitive and compact electronic like devices are revolutionising many fields. Applications of new optical technologies to medicine might be described as in an adolescent stage, where their power and potential can be recognised but are still developing rapidly, and much is yet to come. Pulse oximetry has been one of the most significant technological advances in clinical monitoring in the last two decades. Pulse oximetry is a non-invasive photometric technique that provides information about the arterial blood oxygen saturation (SpO2) and heart rate, and has widespread clinical applications. When peripheral perfusion is poor, as in states of hypovolaemia, hypothermia and vasoconstriction, oxygenation readings become unreliable or cease. The problem arises because conventional pulse oximetry sensors must be attached to the most peripheral parts of the body, such as finger, ear or toe, where pulsatile flow is most easily compromised. This presentation describes the development of new electro-optical sensors used for the investigation of patients with compromised perfusion. The basic physics, technology and clinical applications of such a technology are described. ***** Page 16 PhysioloficalFlowNet\DelegatePack Partially Parallel Imaging: New developments in MRI using multiple receiver coils David Larkman Imperial College, London The advent of partially parallel imaging (PPI) has had a wide ranging impact on MRI. At its simplest it enables us to image faster. This has obvious benefits for the study of dynamic physiological processes. PPI has benefited dynamic contrast uptake studies, angiography, arterial spin labeling, cardiac imaging and many other applications where reducing the sample time increases the diagnostic content of the images. Newer research into the use of PPI has revealed that speed up is just the starting point for PPI. The use of multiple coils allows us to perform consistency checks on our data and where inconsistencies are found, apply motion models to improve consistency and correct flow (and other) artifacts. Such approaches result not only in images with reduced artifacts but also potentially allow us to learn something about the source of those artifacts. This talk will cover the basics principles of PPI and then discuss how these principles can be used to identify and correct images corrupted by flow. It will also review the use of PPI in the more challenging MRI applications and finally discuss the limitations of the approaches presented. ***** Mechanics of the interactions cerebrospinal fluid system and the clinical importance of inner ear fluid interactions Robert Marchbanks Southampton University Fluid flow within the cerebrospinal fluid (CSF) system may be considered at several different timescales. Firstly, there is the relatively slow fluid exchange that occurs throughout the CSF system several times each day. Secondly, there are oscillatory flows that are linked to cerebral blood volume changes with cardiovascular activity and respiration or slow vasogenic waves such as linked to changes in the systemic blood pressure. Finally, transitory CSF flows occur due to hydrostatic pressure changes with posture and impulsive transitions such as due to coughing/sneezing/yawning or trauma (i.e. head percussion injuries). Many of these flows occur in terms of a redistribution of the CSF volume between the cerebral and lumbar regions due to changes in CSF pressure. The dynamics of CSF system can be studied using techniques such as functional MRI to visualise flows directly, surgically implanted or non-invasive transducers to measure pressure, or compliance of the CSF system can be measured or derived. In Southampton we use a technique known as the ‘MMS-11 Cerebral and Cochlear Fluid Pressure (CCFP) Analyser’ that is also referred to as the ‘Tympanic Membrane Displacement (TMD)’ Analyser. As the name suggests, this technique indirectly measures intracranial pressure waves in terms of tympanic membrane displacement and this is possible because most people have an open fluid channel between the CSF and the inner ear. Since the TMD technique is non-invasive, it provides a ‘window’ onto real-time CSF dynamics that promise to greatly expand the utility of CSF dynamics in clinical practice. Not only does this technique promise commonplace measurements for Page 17 PhysioloficalFlowNet\DelegatePack patients with neurological disorders, but also certain balance and hearing disorders are found to have abnormal CSF dynamics that disturb the usual intracranial-inner ear fluid interactions. Methods of measurement, the principles of the CSF dynamics and changes as a consequence of neurological disorders will be discussed. Clinical data will be presented from patients suffering various neurological disorders that both support current theories but also question our limited understanding of CSF dynamics. It is apparent that the full clinical benefit of CSF models will only be achieved in combination with the new non-invasive physiological measurement techniques that enable working hypothesis to be readily tested. ***** Cardiovascular magnetic resonance – the gold standard? Saul Myerson Oxford University Cardiovascular magnetic resonance (CMR) is an excellent non-invasive imaging tool which is capable of visualizing in-vivo vascular structures in any plane, and also flow visualization and quantification. The talk will focus on what CMR can do and what advantages this particular technique brings in assessing human flow systems. Clinical examples of normal and disease states will be used to illustrate the capabilities of CMR. ***** Combined modelling and measurement of CSF pulsatility Stephen Payne Oxford University The role of CerebroSpinal Fluid (CSF) in both normal and pathological conditions is not yet well understood, particularly over the short time scales involved in the cardiac cycle. It is thought that abnormal CSF behaviour is due to a number of changes in different parameters. Flow-sensitive MR images acquired by colleagues at Manchester University show the pulsatile nature of intracranial CSF flow, being driven by the arterial blood flow into the brain. An electrical circuit equivalent model of intracranial pulsatility, relating cerebral blood flow and CSF flows, has been developed, simplified and verified using flow data obtained from MR images of 24 normal subjects. A set of model parameters from a subset of the normal subjects has also been obtained, which can help to understand the nature of pulsatile intracranial flows. ***** Page 18 PhysioloficalFlowNet\DelegatePack Role of flow in cerebral aneurysm pathophysiology and treatment Daniel Rüfenacht Geneva, Switzerland To study the role of blood flow in cerebral aneurysm pathophysiology and for minimal invasive treatment is of growing interest in view of possibilities provided by converging information obtained through medical imaging and image analysis with medical device design. Initiation, growth and rupture encompass the life cycle of cerebral aneurysms, a disease with a high prevalence (2-4%) but expressing rarely with rupture hemorrhage, an event that is presenting under catastrophic circumstances and with a serious prognosis. The parameters influencing the different parts of this life cycle are multiple and exhibit a complex relationship. These parameters might be grouped, and here we propose to do this according to location, such as parameters governing the inside of the vessel, the vessel wall or the outside of the vessel. To evaluate the respective role of these different parameters, several methods may provide ways to weigh the relative importance of each parameter considered. The group of parameters that may be influenced by minimally invasive endovascular treatment methods is the group with location inside the vessel. Of this group, blood flow could be considered a key parameter, and therefore there is reason to outline its potential role in the different parts of the aneurysm life cycle, and to design ways endovascular devices may correct for pathological flow conditions. Although, there may be a whole range of other parameters with importance to an aneurysm life, it may be enough to understand and correct for pathological blood flow conditions, when it comes to addressing not just the symptom but a decisive element in the chain of causes leading to a dangerous aneurysm evolution. The role of flow in: a. Initiation. Most cerebral aneurysms develop at vessel bifurcations. Initiation of such aneurysms may in part be related to the stress bifurcations are exposed to by blood flow. Before reaching the two branches, blood flow is impinging on the vessel wall at bifurcations producing areas of increased shear stress. Such areas could be a likely primary force leading to vessel wall weakening and thus to initiation of a cerebral aneurysm. b. Growth. The growth matrix of aneurysms is considered to be mostly at the inflow zone, where high shear stresses apply – flow seems for these reasons to constitute a key factor of aneurysm growth. c. Rupture. Although the highest shear stress appears to be produced at the aneurysm inflow zone, the shear stress at the aneurysm dome wall is responsible for mechanical induction of wall weakening through biological changes. Once unevenly weakened, the aneurysm wall may be exposed to oscillatory shear stresses sufficient to induce rupture. Depending on sizes and geometrical disposition of the adjacent parent vessels, the vessel defect and the aneurysm shape, there will be flow directed to the aneurysm dome impinging on the weak aneurysm wall. Such flow can produce larger or smaller areas of impingement what could translate in variable risk of rupture. Page 19 PhysioloficalFlowNet\DelegatePack Flow correction in minimally invasive endovascular treatment: a. Role of coils. Coils within an aneurismal cavity disturb the blood flow and will lead to slowing of blood flow leading to increased blood viscosity. The sudden clotting of aneurysm after coil introduction corresponding to 20-30% of the aneurismal volume may be explained by such flow changes inducing mainly rheological changes. However, coil treatment does not change significantly the flow conditions in the parent vessel, what may constitute the reason for recurrence. Coil treatment may therefore be considered not as causative but symptomatic treatment. b. Role of stents. A stent may act as a scaffold outlining the parent vessel wall and correcting at the same time the pathological flow conditions. Such flow diversion might reduce immediately the shear stress at the aneurysm dome wall alleviating from rupture risk. Further, if a flow reduction in the aneurismal cavity can be achieved, clotting may result. The flow changes at the growth matrix may be such, that no further growth is stimulated – the stent carries the potential of a causative treatment. In summary, the role of blood flow in aneurysm pathophysiology may constitute a key factor and correction for pathological local flow conditions by means of a flow diverting device such as a stent, may provide remedy treating one of the main causes leading to initiation, growth and rupture. Simulation and understanding of individual flow conditions including rheological aspects may lead to customized choice or even manufacture of new generation medical implants used for minimally invasive endovascular treatment of cerebral aneurysms. ***** Poroelastic modelling for evolution and treatment of hydrocephalus Ian Sobey University of Oxford An integral part of the brain is a fluid flow system that is separate from brain tissue and the cerebral blood flow system: cerebrospinal fluid (CSF) is produced near the centre of the brain, flows out and around the brain, including around the spinal cord and is absorbed primarily in a region between the brain tissue and the skull. Hydrocephalus covers a broad range of anomalous flow and pressure situations: the normal flow path can become blocked, other problems can occur which result in abnormal tissue deformation or pressure changes. I will describe work which treats the brain tissue as a poroelastic matrix through which the CSF can flow, producing tissue deformation and pressure changes or which can respond to slow changes in pressure or material properties. We have a number of models, the simplest treating the brain and CSF flow as having spherical symmetry and ranging to more complex, fully three-dimensional computations. At present the modelling is restricted to slow events over a long time scale and allows some evaluation of the effect of intervention such as shunting; work is in progress to extend the model to shorter, more clinically relevant time scales. ***** Page 20 PhysioloficalFlowNet\DelegatePack On the finer points of simulating cerebral aneurysm interventions using CFD David Steinmann Toronto, Canada Building on our experience with image-based CFD modelling of carotid bifurcation hemodynamics, five years ago we set about to simulate cerebral aneurysm interventions in a patient-specific manner. At the time we identified two key challenges: how to trust the fine, let alone coarse, flow dynamics available from these compellingly detailed simulations; and how to resolve flow around order-of-magnitude finer stent and coil wires. In this context I will review our work on the development of virtual angiography, which serves to validate the coarse hemodynamic predictions against routine clinical data. I will then focus on our more recent work using particle image velocimetry to validate the complex vortex dynamics predicted in patientspecific carotid artery and basilar tip aneurysm CFD models. Time permitting, I will also present preliminary data regarding the effects of non-Newtonian rheology on the CFD predictions. Finally, I will review our efforts to provide robust and objective tools to embed endovascukar devices into CFD models. ***** Fluid flow in the stented ureter Sarah Waters University of Nottingham Vesicorenal reflux is a major complication in patients with ureteric stents. Typically the bladder pressure is fairly low, but during bladder twitches or voiding it rises, driving reflux (or back flow) of urine up the ureter and into the renal pelvis, which, in turn, may lead to infections or scarring in the renal pelvis. We develop a mathematical model to examine urine flow in a stented ureter. We treat the ureter as a long, thin, vertical, axisymmetric tube, and model its wall as a membrane with nonlinear elastic properties. The stent is modelled as a rigid, permeable, hollow circular cylinder lying coaxially inside the ureter. The renal pelvis is treated as an elastic bag, whose volume increases in response to increased internal pressure. Fluid enters the renal pelvis from the kidney with a prescribed flux. The stent, ureter and renal pelvis are filled with urine, which is assumed to be an incompressible Newtonian fluid, and the pressure in the bladder is prescribed. We use the model to calculate the total volume of reflux generated during voiding and twitches, and investigate how it is affected by the stent and ureter properties. Finally we discuss the implications of our results for the optimisation of stent design to minimise reflux. This work is joint with JH Siggers, LJ Cummings and JAD Wattis and is funded by the BBSRC. ***** Page 21 PhysioloficalFlowNet\DelegatePack Patient-specific studies of thoracic and abdominal aortic aneurysms X. Y. Xu Imperial College London An aneurysm is an abnormal widening of a portion of an artery, related to weakness in the vessel wall. The underlying causes for the formation of aortic aneurysms can be either inherited or acquired, with risk factors including smoking, hypertension and atherosclerosis. Surgical interventions are usually recommended for aneurysms reaching the critical diameters (6-7 cm for thoracic and 5.5 cm for abdominal aortic aneurysms). However, smaller aneurysms are also known to rupture and the associated mortality rate is particularly high. We have been working on patient-specific modelling of thoracic and adnominal aortic aneurysms (TAA and AAA) in collaboration with the CMR Unit at the Royal Brompton Hospital and Vascular Surgery, Radiology and ICCH at the St Mary’s Hospital, with an aim to understand the role of biomechanical forces in the development and rupture of aortic aneurysms. Patients with aortic aneurysms of different sizes were scanned using CT or MRI, and realistic models were constructed from in vivo data. The presence of intraluminal thrombus was taken into account and fully-coupled fluid-solid interaction simulations were performed to obtain flow patterns, wall shear stress as well as wall mechanical stress. Effects of thrombus and aneurysm expansion rate on predicted stress patterns were investigated. Examples of TAA and AAA models will be presented, including models of ruptured aneurysms. The results were obtained by research students Alessandro Borghi (for TAA) and James Leung (for AAA). These studies are sponsored by the British Heart Foundation. ***** Page 22 PhysioloficalFlowNet\DelegatePack ABSTRACTS FOR POSTERS MODELLING THE CIRCLE OF WILLIS TO ASSESS THE EFFECTS OF ANATOMIC VARIATIONS AND OCCLUSIONS ON CEREBRAL FLOWS J. Alastruey, K.H. Parker, J. Peiro and S.J.Sherwin Imperial College London Blood flow in the circle of Willis (CoW) is modelled using the one-dimensional equations of pressure and flow wave propagation in compliant vessels. The model starts at the left ventricle and includes the larger arteries that supply the CoW. Based on published physiological data, it is able to capture and explain the main features of wave propagation along the aorta, at the brachiocephalic bifurcation and throughout the cerebral arteries. The model is used to assess the collateral ability of the complete CoW and its most frequent anatomic variations in normal conditions and after occlusion of a carotid or vertebral artery. Our results suggest that the system does not require collateral pathways through the communicating arteries to adequately perfuse the brain of normal subjects. The communicating arteries become important in cases of missing or occluded vessels, the anterior communicating artery (ACoA) being a more critical collateral pathway than the posterior communicating arteries (PCoAs) if the internal carotid artery (ICA) is occluded. Occlusions of the vertebral arteries proved to be far less critical than occlusions of the ICAs. The worst scenario in terms of reduction of the mean cerebral outflows is a CoW without the first segment of an anterior cerebral artery combined with an occlusion of the contralateral ICA. We also show that in patients without any severe occlusion of a carotid or vertebral artery, the direction of the flow measured at the communicating arteries indicates the side of the CoW with an occluded artery. Finally, we show the effect of partial occlusions of the communicating arteries on the cerebral flows, which again confirms that the ACoA is a more important collateral pathway than the PCoAs if the ICA is occluded. Our model is a fast and powerful research tool to enhance our understanding of blood flow patterns and distributions throughout the brain within a prescribed geometry. If used in conjunction with patient-specific geometry, it can predict the haemodynamic effect of clinical interventions such as carotid endarterectomy, angioplasty and stenting. It has the potential to simulate local flows in detail if coupled to a 3-D simulation of a local area of the cerebral circulation, which, in turn, can be used to investigate, for instance, the flow patterns that lead to increased probability of formation of atherosclerosis or intracraneal aneurysms. ***** Performance measures for robust design development of vascular stents, Atherton & Collins Mark Atherton Brunel University A quantitative measure of spatially distributed WSS values is preferred in driving a design optimisation algorithm. We have used time-averaged WSS and developed 'Dissipated Power' as performance measures with some success but they lose information on whether WSS values lie outside the 'healthy' limits of 1 Pa to 4 Pa. Therefore, in this poster we show how statistical measures make very interesting distinctions between two proprietry stent designs that are supported by clinical evidence. ***** Mathematical modelling of eccentric arterial plaque growth L.R. Band, D. S. Riley and S. L. Waters Leah Band University of Nottingham An atherosclerotic plaque is a region of fibrous tissue and cholesterol within an arterial wall. Plaque growth may lead to positive remodelling in which the artery wall grows outwards preserving the lumen size. Although the mechanisms for remodelling are unclear, biological studies suggest positive remodelling is more frequent in eccentric soft plaques. Positive remodelling is thought to be associated with plaque rupture which can lead to heart attacks or strokes. To gain insight into the underlying mechanisms by which the artery wall remodels in response to its changing mechanical properties, we develop a mathematical model for the cross-section of an atherosclerotic artery. The appropriate viscoelastic model for the plaque remains unresolved; we assume here that the long-time behaviour is Page 23 PhysioloficalFlowNet\DelegatePack viscous as may be appropriate for soft plaques. The plaque is modelled as an annulus of viscous fluid; this viscous fluid layer lines a rigid tube which represents both the healthy outer layer of the artery wall and the surrounding perivascular tissue. The fluid in the lumen is taken to be inviscid, as appropriate for modelling blood in the large arteries. Variations in the wall's mechanical properties are captured by specifying a variable tension at the interface between the viscous fluid layer and the lumenal fluid. A novel nonlinear evolution equation for the width of the fluid layer is derived using thin-film asymptotics. With constant interfacial tension infinitely many neutrally-stable steady solutions exist. However, when the interfacial tension varies azimuthally we identify one centred (i.e. no dry patch) steady-state profile. The linear stability of this steady state is examined and compared with numerical solutions. For all variable tensions there exists an unstable perturbation to the centred steady state, in sharp contrast to the constant tension case. We consider the growth and long time-scale behaviour of the unstable perturbation; the perturbation grows until the film reaches another steady state featuring a novel dry patch region. Our results suggest that soft plaques may naturally move to an eccentric position within the arterial tissues; this may have implications for the remodelling process. ***** Transient integral boundary layer method to calculate the pressure drop in a time dependent vessel geometry applied to myocardial bridges Stefan Bernhard Universität Göttingen Background: The pressure-flow relations in arteries, particularly the losses associated in laminar flow through stenosis and the sites where atherosclerosis develops have motivated many researchers the last decades. The most vulnerable regions are found at places where the vessel is curved, bifurcates or shows a sudden change in flow geometry. These flows mostly involve flow separation and secondary motions which are difficult to calculate and analyse. The pathophysiological situation present in myocardial bridges further involves externally forced vessel deformation caused by cardiac muscles overlying an intramural segment of the coronary artery. Methods: Because a three dimensional description of the hemodynamic conditions in myocardial bridges is not feasible we present a boundary layer model for the calculation of the pressure drop and flow separation. The approach is based on the assumption that the flow can be sufficiently well described by the interaction of an inviscid core and a viscous boundary layer. Under the assumption that the idealised flow through a constriction is given by near-equilibrium velocity profiles of the Falkner-Skan-Cooke (FSC) family, the evolution of the boundary layer is obtained by the simultaneous solution of the Falkner-Skan equation and the transient von-Karman integral momentum equation. Results: The model was used to investigate the relative importance of several physical parameters present in myocardial bridges. Results have been obtained for steady and unsteady flow through vessels with 0-85% deformation stenosis. The fractional flow reserve (FFR) for fixed and dynamic stenosis has shown that the flow is less affected in dynamic lesions, because the distal pressure partially recovers during re-opening of the vessel in diastole. We have further calculated the wall shear stress distributions in addition to the location and length of the flow reversal zones in dependence on the severity of the disease. Conclusions: The results indicate that the FFR of myocardial bridges with diameter deformations greater than 55 % in fixed and 67% in dynamic environment, fall below the critical cut-off value of 0.75 and that the FFR calculated under the assumption of Hagen-Poiseuille flow is overestimated. Earlier models are supplemented by the effects of prescribed temporal wall motion in quasi three-dimensional vessel geometries. ***** Page 24 PhysioloficalFlowNet\DelegatePack Use of endothelial morphometry to determine blood flow patterns near rabbit aortic branches Andrew Bond Imperial College, London Haemodynamic shear stresses exerted on the arterial wall by the flow of blood determine endothelial phenotype, properties of the underlying wall, and possibly arterial disease patterns. We have previously mapped patterns of wall permeability and disease around aortic branch points in mature rabbits. (Both patterns differ from the classical ones observed in immature rabbits.) Here we investigate whether these patterns can be explained by shear stress variations; endothelial cells and their nuclei align with the dominant flow direction and elongate with elevated shear, providing a natural array of shear sensors. Aortas of male New Zealand White rabbits (Harlan, >38wks, n=5) were fixed at physiological pressure in situ after the animals had been given heparin (2184USP units iv) and an overdose of pentobarbitone (0.8ml/kg, iv). Sheets of endothelium were isolated using a modified Häutchen technique, stained with propidium iodide and imaged by fluorescence microscopy. Nuclear length-to-width ratios (L/W) and orientations were determined with image processing software. They significantly depended on location around aortic branch mouths (p<0.05, 2-way ANOVA). L/W indicated highest shears upstream and at the sides of branches. Orientations suggested secondary flows down the aorta and entry into the branch from its lateral margins. These flow patterns contrast with earlier data for immature rabbits, and may account for the observed patterns of wall permeability and lipid deposition. ***** A computational model combining vascular biology and haemodynamics for coil-induced thrombosis prediction in anatomically accurate cerebral vessels T Bowker, AS Bedekar, K Pant, S Sundaram, JV Byrne, P Summers, Y Ventikos University of Oxford The prevalence of cerebral aneurysms in the general population is estimated at between 2 and 5%. A large proportion of such aneurysms are asymptomatic, but rupture does occur and the consequences are severe. The use of detachable coils for preventative or post-rupture treatment is now considered to be more effective than surgical clipping. The detachable coils are delivered endovascularly from a catheter into the lumen of the aneurysm in order to induce a stable clot. Ideally this will eventually lead to permanent occlusion of the diseased vasculature through neovascularisation of the lumen and endothelial re-growth at the aneurysm neck. The formation of a thrombus or clot in vivo is initiated through the expression of tissue factor. The traditional view is that coagulation then proceeds through a cascade of proteolytic reactions that culminates in the production of fibrin. Recently, this view has been refined to include the important role that tissue factor bearing cells and platelets play in providing a surface for the procoagulant reactions. We present a model of coagulation that couples the effect of a growing thrombus on the flow field. In brief, platelets first undergo adsorption to the coil surface and then to one another resulting in the formation of a platelet aggregate. The thrombus-haemodynamic coupling is mediated through locally variable porosity which is calculated with respect to the platelet concentration. The model is applied to patient specific geometries, derived from magnetic resonance angiography. Blood is considered to be Newtonian and pulsatile conditions are applied at the inlet boundary. We focus our attention on the rate of thrombus growth within the aneurysm sac and the subsequent flow division leading to stable occlusion of the diseased geometry. ***** Page 25 PhysioloficalFlowNet\DelegatePack Do decompression induced bubbles inhibit blood flow? Michael Chappell University of Oxford Bubbles are known to arise in the body under decompression. These cause a range of symptoms identified as Decompression Sickness (DCS) and more commonly known as ‘the bends’. Bubbles form both within the body tissues and in the blood, and it is the latter which have been associated with the various neurological symptoms of DCS. It is likely that these blood bubbles grow from nuclei present on the walls of blood vessels and this process has previously been studied using dynamic models. However, the emergence of these bubbles into the blood has not been accurately simulated. A model was derived which considered a bubble interface, at a circular opening into the bloodstream, which grows due to a continuous influx of gas into the bubble from the local tissue. Initially the shape of the bubble interface is deformed by the blood flow, before sliding along the vessel wall and subsequently detaching into the bloodstream. The continued growth of this detached free bubble, due to gas diffusion from the blood, is then simulated to establish whether it may grow to a size similar to that of a capillary, which would have the potential to result in vessel blockage. It was found that under typical decompression conditions it is possible for a bubble, which has detached from a nucleation site in the blood, to grow such that it can block a capillary vessel before it has traversed the whole length of the vessel. Such blockages may cause a disruption to the local oxygen supply of the body tissues and hence lead to a number of the more serious symptoms associated with DCS. ***** Investigation of the fluid dynamical properties of helical pipes from a mixing perspective Andrew Cookson, Denis Doorly, Spencer Sherwin Imperial College, London Cardiovascular disease is responsible for the majority of deaths in developed countries, and of these most are associated with abnormalities in arterial blood flow. Atherogenesis often results in an arterial stenosis that is treated by the surgical insertion of a bypass graft. Unfortunately, over 50% of coronary artery bypass grafts fail within 10 years due to the development of neo-intimal hyperplasia. Computational studies suggest that the three-dimensional geometry of nonplanar grafts introduces a physiologically more favourable flow environment (reduced shear extrema, lower particle residence times and increased mixing) [1], however preservation of this geometry post surgery is difficult. Caro et al. [2] have proposed that small amplitude helical tubes will achieve the same fluid dynamical properties as a non-planar graft, but with the benefit of mechanical robustness. A preliminary in-vivo study comparing the small amplitude helical pipes with cylindrical pipes for use as shunts found that after eight weeks the conventional technology was fully occluded, but completely clear for the helical shunt. This work aims to investigate the fluid dynamical properties of the flow through helical pipes, so that the mechanisms behind their success as bypass grafts and shunts can be understood. It is known qualitatively that there is substantial in-plane mixing in a helical pipe, due to the swirl induced by the geometry. Previous work on helical pipes has generally focused on the primitive variables such as velocity profiles, whereas this paper will examine the flow from a mixing perspective using entropic measures, Lyapunov exponents and particle residence times to quantify the degree of mixing, and then relate this to geometric parameters of the helix. References: 1. Sherwin et al., 2000, The influence of out-of-plane geometry on the flow within a distal end-to-side anastomosis, ASME J. Biomech. 122. 2. Caro C. G., Cheshire N. J., Watkins N., 2005, Preliminary comparative study of small amplitude helical and conventional ePTFE arteriovenous shunts in pigs, J. R. Soc. Interface, 2. ***** Page 26 PhysioloficalFlowNet\DelegatePack ***** Page 27 PhysioloficalFlowNet\DelegatePack Mapping Multi–Scale Oxygen Flux in a Capillary–Tissue Cerebral System Hadjistassou C. K., Moyle K., Ventikos Y. University of Oxford Although fMRI is based on the Blood Oxygenation Level Dependent effect, the underlying physiological mechanism behind this phenomenon is insufficiently understood. To elucidate the BOLD idiosyncrasy, we consider the multi–scale efflux of oxygen from erythrocytes into plasma and eventually into cerebral tissue. We address the multi–scale nature of the problem (diffusion/dissociation scale – erythrocyte scale – capillary/system scale) by considering transport at the cell and capillary level. The model consists of an idealised cerebral capillary, 8ìm in diameter by 160ìm in length, surrounded by a coaxial tissue compartment 25ìm in thickness. Extraction rates for oxy/deoxyhaemoglobin and oxygen are determined for neuron inactivity–to–activity transitions. Microscopic modelling focuses on oxygen flux from a single (or up to three) erythrocyte into the plasma and tissue. A single file of equidistantly arranged erythrocytes, which measure 7.2ìm by 3.25ìm, with a distinct and separate membrane 20nm in thickness, is studied. Macroscopically, both the radial and axial oxygen transport rate and magnitude decrease in an exponential fashion as oxygen is advected downstream. Microscopically, we demonstrate coupling of erythrocyte shape deformation (estimated by solving the relevant fluid–structure interaction problem) with oxygen diffusion and the haemoglobin–oxygen dissociation process. ***** On the time-dependence of red blood cell aggregation E. Kaliviotis, E. and M. Yianneskis, Department of Mechanical Engineering, King's College London, UK Blood flow in the complex human circulatory system presents a number of problems and challenges common to many engineering fluid mechanics topics and has received much attention and scientific interest to date. It has been recognised that red blood cell (RBC) deformability and aggregability, is responsible for many aspects of the complex behaviour of blood flow. The aggregation process, at stasis, starts when the distance between erythrocytes is sufficiently small; cells at random orientation approach each other, align and/or slide over each other until their centres coincide. Flow has a double effect on the aggregation process; at low shear rates (0.1 s-1 to 1 s-1) the aggregation process is accelerated mainly due to the cell-to-cell interactions induced by the hydrodynamic conditions. However, as the shear rate is increased further, the aggregation extent decreases due to the higher shear stresses developed within the fluid and acting on the cells. Factors affecting aggregation include the hematocrit or/and the biochemistry of the suspension; plasma macromolecules (mainly fibrinogen) and their concentration, have a pronounced effect on aggregation. Intrinsic properties of the RBC (electromechanical), which are mainly attributed to membrane properties, may influence aggregation independently of the suspension biochemistry. The mechanisms responsible for the aggregate (rouleaux) formation are still not clear; plasma macromolecules accumulate on the cell membrane suggesting that aggregation may result from forces acting on neighbouring cells due to the absorption of the same macromolecules (bridging model) (Chien and Jan, 1973). Another theory that contradicts the bridging mechanism stems from experiments on membrane-membrane attraction, which have shown an increase in adhesive energy between the membranes with a decrease in polymer accumulation near the membranes (depletion model) (Evans and Needham, 1988). The time-dependent aggregative properties of the RBCs affect the bulk fluid mechanical properties; relaxation and different shear rate gradients in rheometric measurements may significantly affect the results in the low shear rate regime (Snabre and Mills, 1996). Moreover, aggregation enhances the tendency of the cells to move away form their geometric boundaries (wall slip) (Picart etal. 1999) as a result problems like torque decay and decrease in apparent viscosity appear even at a high roughness degree walls. In addition there is little direct data on the behaviour of aggregates in the microcirculation or in unsteady flows at physiological RBC concentrations. In view of the above considerations the present work focuses in the investigation of different aspects of the aggregation phenomenon at normal hematocrits and at different flow conditions; extent of aggregation, size and shape of the aggregates, red cell constitution of aggregates, aggregate orientation and the time evolution of the aggregation process are studied in dynamic flow conditions and in different flow configurations. In addition, inter-aggregate branch characteristics are examined in order to clarify their role in various aspects of the flow. For the quantification of aggregation parameters direct techniques, including high resolution light microscopy and image analysis in a plate-plate shearing system, are used in combination with rheometrical measurements. Page 28 PhysioloficalFlowNet\DelegatePack References: Chien, S. and K. M. Jan (1973). Ultrastructural basis of the mechanism of rouleaux formation. Microvascular Research 5, 155–166. Evans, E. and D. Needham (1988). Attraction between lipid bilayer membranes in concentrated solutions of on absorbing polymers: Comparison of mean-field theory with measurements of adhesion energy. Macromolecules 64, 1822–1831. Snabre, P. and P. Mills (1996). Rheology of weakly flocculated suspensions of viscoelastic particles. Journal De Physique III 6, 1835–1855. Picart, C., J.-M. Piau, H. Galliard, and P. Carpentier (1998). Blood low shear rate rheometry: influence of fibrinogen level and hematocrit on slip and migrational effects. Biorheology 35 (4,5), 335–353. ***** Shear Stresses and Flow Fields in Patient Specific Abdominal Aortic Aneurysms A Kazakidi (1-2), S J Sherwin (1), P D Weinberg (2), M A McAteer (3), J E Schneider (3), R P Choudhury (3), K M Channon (3) Departments of (1) Aeronautics and (2) Bioengineering, Imperial College London (3) Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford Atherosclerosis is the most common disease of large and medium-sized systemic arteries and may cause ischemia, heart attack or stroke. Depending on species, and/or age, atheromata develop non-uniformly in the arterial wall in curved regions and at branch points. At the outer wall of the origin of the brachiocephalic artery, which is the first branch of the aortic arch, ÒvulnerableÓ atherosclerotic plaques are known to develop in ApoE-/- mice [J L Johnson, C L Jackson. Athorosclerotic plaque rupture in the apolipoprotein E knockout mouse. Atherosclerosis 2001;154(2):399-406]. It has been suggested that haemodynamic factors strongly influence lesion development and that wall shear stress (WSS) therefore correlates with lesion location and growth. The current study attempts to examine the validity of this view by computing blood flow and WSS patterns within a realistic geometry of the proximal mouse aorta. The three-dimensional geometry of the wall of the aortic arch and proximal arteries of a wild-type mouse were reconstructed from highresolution magnetic resonance (MR) images using in-house reconstruction tools. Blood flow is computed within reconstructed geometries and, for initial work, by making the assumptions of rigid walls, steady flow, uniform inlet velocity profile and approximate branch flow splits. In preliminary experiments, WSS was found to be highly nonuniform along the aorta with the lowest shears occurring on the walls opposite the flow dividers of the main branches. The outer wall of the brachiocephalic artery, a region prone to disease, was identified as a low-shear region. Future work will consider diseased animals in order to enhance our understanding of the effect of haemodynamics on atherosclerosis and, more specifically, on the progression from initial lesions to advanced, rupture-prone vulnerable plaques. (Funded by IBME, Imperial College, and Al S Onassis Foundation.) ***** Thin film equations for fluid motion driven by surfactants Rachel Levy Duke University In the lubrication approximation, the motion of a thin liquid film is described by a single fourth-order partial differential equation (PDE) that models the evolution of the height of the film. When the fluid is driven by a Marangoni force generated by a distribution of insoluble surfactant, the thin film equation is coupled to an equation for the concentration of surfactant. Such films have been studied in the context of surfactant replacement therapy for the lungs of premature infants. Analysis of the PDEs and numerical simulations reveal a wide array of wave-like structures in the film, which persist when capillarity and surface diffusion are neglected. We explain the structures for the reduced system as a combination of traveling waves with discontinuities, and reveal a critical threshold at which the type of solution changes dramatically. PDE simulations and a dynamical systems approach help us understand the behavior of the solutions and how they change as higher order terms are returned to the system. ***** Page 29 PhysioloficalFlowNet\DelegatePack Blood flow and volume in cerebral circulation – from simple tube to a hierarchical model Stefan Piechnik University of Oxford Knowledge of cerebral blood flow and vascular volume are of major interest in mapping cerebral activity using modern functional imaging techniques. We aim to better understand the governing relationship between relative changes in cerebrovascular volume and flow (v(f))with the help of three models of cerebral circulation: M1 is a tube with reactive diameter changes distributed uniformly along its length. 3-compartmental M2 contains additional constant resistive inflow and voluminous outflow (respectively á, â of total resistance and volume at rest). M3 is a multilevel hierarchical network with distributed reactivity dependent on vessel-size and type. We find that the model choice changes the shape of the v(f) relationship from that of a simple power function used by Grubb (v=f^0.4), which was designed as a scaled version of M1 (v=f^0.5). However, within the experimentally relevant range of changes the relation closely approaches linear and can be described just by a slope k, roughly equivalent to the Grubbs exponent. K depends strongly on the ratio of regulating to non-regulating vessels in the volume of interest. In M3, the microvascular compartment has the steepest, and venous compartments have the flattest v(f) curve. This systematic variability of v(f) coupling constitutes a significant confounding factor for the interpretation of focal metabolic findings from high resolution imaging such as magnetic resonance imaging where measurements of flow and volume may be weighted towards different cerebrovascular compartments. ***** Aggregation of Blood Components on a Surface J. Leon Shohet University of Wisconsin-Madison The aggregation of blood components on blood vessels is known to be generated by sheared flow activation of blood components which themselves are greatly influenced by flow patterns. This is particularly important in the case of small-diameter (< 5mm) blood vessels. A numerical simulation was conducted to evaluate the flow patterns in a microminiature blood circulation loop to determine those flow factors that promote the aggregation of blood components and their potential deposition on the lumenal surface. The local geometry of the system was found to be the most important factor that affects the evolution of the flow field. Based on these results, the predicted locations of blood component aggregation for the circulating loop were compared with experimental results. Page 30 PhysioloficalFlowNet\DelegatePack Page 31 PhysioloficalFlowNet\DelegatePack ***** Page 32 PhysioloficalFlowNet\DelegatePack A method for patient-specific adjustment of the multi-branched model estimating hemodynamic parameters in the human arterial system Pavel V. Stroev (1), Salikh S. Zakirov (2) , Peter R. Hoskins (3) , William J. Easson (1) (1) School of Engineering and Electronics, The University of Edinburgh, The King’s Buildings, Edinburgh, EH9 3JL (2) Intel, 14 Bolshoy Savvinsky, Moscow, 119435, Russia (3) Medical Physics Section, The University of Edinburgh, Chancellors Buildings, 49 Little France Crescent, Edinburgh, EH16 4SB Background: It remains practically possible to model computationally the full 3D equations for blood flow only in the small sections of arterial system, so considerable efforts have been put into developing ID models to simulate flow in large sections or even the entire circulatory system. If 1D models are coupled with 3D models and employed to provide boundary conditions at the edges of the 3D computational domain, the estimated flow waveforms may in turn influence the 3D flow patterns predicted by a CFD model, possibly leading to different results regarding both flow and wall shear stress. For 1D models used in clinical practice some method for patient-specific tuning is also desirable, as anatomical parameters of the arterial system, cardiac output, whole blood viscosity, and disease development vary for different subjects. Method: We used a transmission line model of the human arterial system to generate pressure and flow waveforms in the common carotid, brachial and popliteal arteries to obtain load impedances at these sites. These data could be measured in patients non-invasively and, along with the pulse wave velocities (PWV) in the arteries, fully determine transmission properties of the model. Taking in turns pressure from each of these sites as the input to the model and assuming there were errors in measurement of pressure and flow waveforms, PWV, lengths of the arteries, and their diameters, we reconstructed pressure and flow waveforms in the abdominal aorta and compared the output with that given by the reference model in order to study the impact of the measurement errors on the reconstructed waveforms. Conclusions: It is possible to reconstruct pressure and flow waveforms in the arteries with an accuracy about 10-20% fitting the multibranched model of the human arterial system to data, which can be measured during routine diagnostic ultrasonography and applanation tonometry. Keywords: Systemic Circulation, Blood Flow, Mathematical Model ***** Fluid-Structure interaction of the aortic heart valve Raoul Van Loon Imperial College The motion of a native or prosthetic aortic valve is a difficult problem to computationally tackle. The slender leaflets are very flexible not impeding the flow during systole but are sufficiently stiff to withstand a diastolic pressure gradient. A fictitious domain method is presented that describes the solid motion/deformation of the valve induced by the pulsatile flow. In order to enhance the accuracy in the vicinity of the leaflets the method is extended with an adaptive meshing scheme. As a result these methods are applied to a 3D geometry of an aortic heart valve. ***** Page 33 PhysioloficalFlowNet\DelegatePack 2D Computational Study of Cellular Scale Variations in LDL Concentration at an Endothelium with Physiologically Realistic Inter-Cellular Cleft Dimensions P. Vincent1, S. Sherwin1, P. Weinberg2 Department of Aeronautics1 and Department of BioEngineering2, Imperial College London Previous cellular scale computational investigations† into Low Density Lipoprotein (LDL) build up at the endothelium have incorporated unrealistically large cell cleft dimensions. In the study presented here a simple two-dimensional model of LDL transport through the endothelium is developed. The model incorporates smaller, more realistic cleft dimensions (30nm width), along with a consequently increased inter-cellular transmural velocity; in order to maintain total transmural flux through the endothelium. Results from the study are compared with those from previous investigations† using identical vascular scale flow conditions (fully developed Poiseuille Flow in a 0.6cm diameter vessel with a peak velocity of 5cm/s). The model presented predicts an almost 60% increase in LDL concentration at cell clefts (relative to the bulk flow). This is compared with an approximately 7% concentration increase at clefts, predicted by previous studies that used unrealistically large cleft widths†. The results indicate the importance of using physiologically accurate cleft dimensions in future cellular scale models of the endothelium. † S. Wada and T. Karino, Prediction of LDL Concentration at the Luminal Surface of a Vascular Endothelium, Biorheology 39 (2002) 331-336 ****** Mathematical modelling of coronary artery blood flow SL Waters, JH Siggers School of Mathematical Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK The most common arterial disease, atherosclerosis, is particularly prevalent in the coronary arteries. The distribution of atherosclerotic plaques, which characterise the disease, is correlated with regions of low mean wall shear stress (WSS) and regions where the WSS changes direction during the cardiac cycle. The coronary arteries are situated on the surface of the beating heart or penetrate the muscular heart wall and hence their geometry, represented by the curvature and torsion of the vessels centreline, as well as its diameter and length, varies substantially with time as the heart beats. This study addresses the effect that the coronary artery curvature and motion have on the WSS distribution and the development of atherosclerosis. We develop and solve an idealized mathematical model, in which the artery is modelled as a pipe with constant circular cross-section of radius a, having a centreline lying on an arc of a circle of radius R. The curvature is finite, in contrast to many previous studies that assumed it to be asymptotically small, and varies sinusoidally with time. The blood is modelled as a Newtonian viscous fluid driven by a pulsatile axial pressure gradient. The frequency of the pressure gradient and the curvature oscillations are equal. The model solution indicates that in certain parameter regimes, curved pipes with finite, time-dependent curvature exhibit a qualitatively different solution structure from curved pipes with asymptotically small time-dependent curvature. Furthermore, differences in curvature can lead to substantial quantitative differences in the WSS distribution. The physiological implications of these results to coronary artery blood flow will be discussed. Page 34 PhysioloficalFlowNet\DelegatePack The STEP Project STEP: A Strategy for the EuroPhysiome January 2006 – March 2007 Scientific Coordinator: Marco Viceconti Project Coordinator: Gordon Clapworthy STEP is funded by the European Commission under the Information Society Technologies Programme. The term EuroPhysiome has been coined to indicate a coherent, integrated European approach to the multiscale modelling of the human physiome. STEP is currently orchestrating consensus building within the relevant European communities – academic, industrial, clinical – to create a sound base on which the EuroPhysiome can be established. It will deliver a roadmap in early 2007 that will define the way in which European work should proceed ultimately to deliver the Virtual Physiological Human – the in silico human. To this end a conference “Towards the Virtual Physiological Human” will be held in Brussels (further details available from Dr S.L. Waters). The conference will be preceded by Internet-based discussions, open to all, in which the major issues will be identified so that the discussions at the conference can proceed swiftly. The philosophy of the STEP project is to be as inclusive as possible, and participation of all interested parties is encouraged, subject to the physical limits of the conference accommodation. The conference will provide an opportunity for the community at large to join fully in the discussions related to that strategy and to influence the course that the development will ultimately take. The STEP project concentrates mainly on those sub-systems of the human body for which the interpretation mechanisms employ physics-based modeling. These include the cardiovascular, respiratory, musculoskeletal, and digestive apparti, together with the skin, through which the human body exchanges forces with the external environment. But it excludes, for example, the brain and all the perceptual and cognitive aspects of the sensorial appartus. Considering the Physiome as a whole would be highly complex. So to enable fruitful discussion, STEP has defined a number of Strands within which discussions can take place. One of these is the Fluids Strand which rd is particularly relevant to the audience here at the 3 Physiological Flows Network Meeting. The discussions that are ongoing within this strand have been categorized into a number of topics that are open to debate. The following gives a flavour of the topics along with questions that could be addressed within each topic. 1. • • • • Validation: Is this the single most important topic? What approaches to validation should be used? Within any funded project what proportion of the funding should be devoted to validation? What is the relationship between in vivo and in vitro validation? Should this be addressed specifically? 2. Translation of ideas (time-to-market): • One of the key factors for the EC is the lack of products that are usable by industry and clinicians from past spending. How can this be addressed? • What impact does model/simulation have on industry/clinical practice/further model development • What are the applications for any physiome-related model/simulation? Industry? Clinical practice? Education? Increase in knowledge? • How are the models/simulations exploited? • Is the fundamental science translatable into useful application (in time). How long would it/should it take? • What are the industrial/clinical viewpoints? 3. Scope and Gaps: • What should the scope of the modelling be? What should be included and what should be excluded? For example : blood, breath, lymph, urine, cerebrospinal fluid, rheology… • How should multilevel models be coupled (1D, 2D, 3D, spatially averaged) • What about multiscale models (temporal/spatial)? • What about coupling of fluids models with other models (for example systems biology models)? • To what extent should multiphase models be developed – what materials should be included?= • What is missing from current developments? Effect of nervous/control systems? Endocrine system? Chemical reactions? • What data sources are needed? Of what quality should these be? • What about inter-subject variablility; how should this be addressed? Page 35 PhysioloficalFlowNet\DelegatePack 3. Technical and scientific challenges: • What are the true grand challenges? • Flow characteristics: low Re and transitional flow; turbulence, measures of recirculation? Methods of computation? data decimation? Characterisation and parameterization? Identification of boundary conditions? Coupling techniques (and standards)? Coupling to sources of excitation. Mesh generation? Subject variation? • How should uncertainties and sensitivities be incorporated into the modelling process? 4. Standards: • Compared with the aerospace industry (for instance) few standards exist. How much effort should be put into generating rules/standards within which to develop models? • Would industry-like standards be useful in cases where there are two-way links between disciplines, coupling interfaces, to enable compatibility between products/techniques ? • Who should drive the process? 5. • • • • Transverse items (across all strands): Do you have a view on the ethics of data use? Who should control access to data? How should data be maintained? How should relationships with other modelling centres/initiatives be fostered? Finally, of the main topics listed above, what do you think are the most important main topics the fluids strand should discuss? Do you think there are important topics missing from this list? Page 36 PhysioloficalFlowNet\DelegatePack
