![Clinical background
Aneurysmal SAH major cause of morbidity and mortality with high
rates of case fatality (40-50%) [1,2]
Management of unruptured IAs remains controversial topic in
Neurosurgery
Most aneurysms do not rupture [2], etiological/pathological factors
responsible for rupture remain poorly understood
Morbidity and mortality from operative/endovascular
treatment, prompts need for better management protocol
Evidence from literature suggests an emerging role of
haemodynamics, shape and tissue stress/strain in aneurysmal
pathogenesis [3,4]
(1) Inagawa
Stroke 2001, (2) ISUIA N Eng J Med 1998, (3) Sekhar et al. Neurosurgery 1981, (4) Ujiie et al.
Neurosurgery 1999](https://image.slidesharecdn.com/beaumont0v6-111128051905-phpapp01/85/Computer-Modelling-of-Flow-Shape-and-Tissue-Stress-Strain-in-Intracranial-Aneurysm-5-320.jpg)
![Role of haemodynamics
Wall Shear Stress (WSS)
WSS definition: frictional tangential force exerted by blood flow on
endothelial layer
Supra- and infra-physiological values of WSS have been
associated to endothelial damage, aneurysm formation and
rupture [1]
normal WSS infra-physiological WSS
(1) Malek et al JAMA 1999](https://image.slidesharecdn.com/beaumont0v6-111128051905-phpapp01/85/Computer-Modelling-of-Flow-Shape-and-Tissue-Stress-Strain-in-Intracranial-Aneurysm-6-320.jpg)
![@neurIST technology:
shape measurements
non-sphericity-index (NSI): quantifies difference between
aneurysm shape and a perfect circumscribed sphere
Aspect ratio: ratio between aneurysm depth and neck max width.
It has been correlated with aneurysm rupture [1]
non-sphericity-index aspect ratio
a
b
(1) Raghavan et al J Neurosurg 2005](https://image.slidesharecdn.com/beaumont0v6-111128051905-phpapp01/85/Computer-Modelling-of-Flow-Shape-and-Tissue-Stress-Strain-in-Intracranial-Aneurysm-11-320.jpg)
![APPENDIX Computational Fluid Dynamics –
•pressure waveform
The engineering trick
• pressure [mmHg]
•t [s]
•flowrate waveform
• flow rate [ml s-1]
•t [s] 39
@neurIST Confidential Copyright © 2006-2008](https://image.slidesharecdn.com/beaumont0v6-111128051905-phpapp01/85/Computer-Modelling-of-Flow-Shape-and-Tissue-Stress-Strain-in-Intracranial-Aneurysm-39-320.jpg)
Computer Modelling of Flow, Shape and Tissue Stress/Strain in Intracranial Aneurysm
- 1. Computer Modelling of Flow, Shape and Tissue Stress/Strain in Intracranial Aneurysm Alberto Marzo, Derek Sweeney, Martin Murphy
- 2. Demonstration layout IDAC company background IAs clinical background role of haemodynamics in IAs @neurIST technology demonstration of unstented case demonstration of stented case SBNS study what next
- 3. IDAC company background CAE Consultants, established in 1997 5 Employees Derek Sweeney Dr. Paul Fanning Bob Moore Barbara Leichtenstern Dr Alberto Marzo In collaboration with partners in 3 successful European projects, we have developed a range of web-enabled simulation applications aimed at Medical Device Manufacturers and Clinical Researchers @neurIST (European Project) finished in March 2010. We are now trying to market the tools developed. We supported Martin Murphy in his Research work (poster won a best in section prize at the SBNS meeting) Purpose of this meeting is to show you what can be done and then explore possibility of Research projects etc
- 4. @neurIST Multidisciplinary European initiative funded by the EU* 4-year project, budget 17 million € Neurosurgeons, neuroradiologists, epidemiologists, engineers, biologi sts and computer scientists from 32 EU institutions Industrial, academic and medical institutions Aim: improve current management of intracranial aneurysms Members of the consortium
- 5. Clinical background Aneurysmal SAH major cause of morbidity and mortality with high rates of case fatality (40-50%) [1,2] Management of unruptured IAs remains controversial topic in Neurosurgery Most aneurysms do not rupture [2], etiological/pathological factors responsible for rupture remain poorly understood Morbidity and mortality from operative/endovascular treatment, prompts need for better management protocol Evidence from literature suggests an emerging role of haemodynamics, shape and tissue stress/strain in aneurysmal pathogenesis [3,4] (1) Inagawa Stroke 2001, (2) ISUIA N Eng J Med 1998, (3) Sekhar et al. Neurosurgery 1981, (4) Ujiie et al. Neurosurgery 1999
- 6. Role of haemodynamics Wall Shear Stress (WSS) WSS definition: frictional tangential force exerted by blood flow on endothelial layer Supra- and infra-physiological values of WSS have been associated to endothelial damage, aneurysm formation and rupture [1] normal WSS infra-physiological WSS (1) Malek et al JAMA 1999
- 7. Role of haemodynamics Hemodynamic Intracranial Aneurysm Proposed mechanism(s) References factors Initiation Growth Rupture Dynamic Wall Shear Stress High Low Low Increased WSS increases the production of Gao et al (2008), Fukuda et al (2000), (WSS) MMP-13 which in turn leads to vessel wall Meng et al (2007), Shojima et al damage (2004), Jou et al (2008), Malek et al (1999), Ujie et al (1999), Boussel et al Decreased WSS increases iNOS synthesis- (2008), NO induced damage to vessel wall Low WSS increases endothelial proliferation and apoptosis Oscillatory Shear High/Low High High Degenerative changes in endothelium Mantha et al (2006), Glor et al (2004), Index (OSI) Goubergrits et al (2008) Jet of Blood Stream Impingement Impingement Impingement Localized endothelial cell injury Foutrakis et al (1999), Cebral et al (2005), Cebral et al (2008) Flow Pattern - - Complex Statistical association Cebral et al (2005), Cebral et al (2008) Hydrostatic Pressure High High High Passive yield/ water hammer effect Inci and Spetzler (2000), Morimoto et al (2002), Steiger et al (1989) NB: WSS; wall shear stress, MMP-13; matrixmetalloproteneases-13, iNOS; inducible-nitric oxide synthase, NO; nitric oxide, OSI; oscillatory shear index Singh PK, Marzo A et al Comput Intell Neurosci 2009
- 8. @neurIST technology medical image surface reconstruction 1 surface reconstruction 2 Click Here for Video surface reconstruction 3 computer model flow prediction Click Here for Video
- 9. @neurIST technology: CFD Detailed in-vivo measurements of relevant flow variables in regions affected are currently impossible Motivated by its success in other disciplines scientists started using CFD to predict blood flows in IAs Sports Engineering Automotive Aerospace
- 10. @neurIST technology: haemodynamic predictions inflow jet and pressure wall shear stress
- 11. @neurIST technology: shape measurements non-sphericity-index (NSI): quantifies difference between aneurysm shape and a perfect circumscribed sphere Aspect ratio: ratio between aneurysm depth and neck max width. It has been correlated with aneurysm rupture [1] non-sphericity-index aspect ratio a b (1) Raghavan et al J Neurosurg 2005
- 12. @neurIST technology: stress/strain predictions it is likely that the event of rupture occurs when the tissue stress or strain exceeds some sustainable level tissue stress tissue strain
- 13. Live Demo Unstented Case Click Above for Demo
- 14. Analysis computation IDAC EASA web-based computing power @neuFuse files can be uploaded on the web to run analyses using web-based computing power (IDAC EASA) user interface file uploading
- 15. Analysis computation IDAC EASA web-based computing power Analysis status can be monitored and results (e.g. tabulated indices, WSS plots) accessed once analyses are completed analysis status results post-processing
- 16. Validation it is likely that the event of rupture occurs when the tissue stress or strain exceeds some sustainable level Virtual Angio Real Angio Click Here for Video Click Here for Video
- 17. Stented Case Click Above for Demo
- 18. @neurEndo Virtual Endovascular Treatment The stent is represented by a deformable model expanding into the vascular lumen The stent deformation is constrained with information on the stent design (strut length, angle between struts) Time consumption: approximately 1 minute
- 19. @neurEndo Virtual Endovascular Treatment Stent deployed Haemodynamics
- 20. Physical Characterisation of Cerebral Aneurysms and Identification of Factors Suggestive of Imminent Rupture TM Murphy1,3, A Marzo2, DR Rawluk1, C Bolger1,4 1 Department of Neurosurgery, Beaumont Hospital, Dublin. 2 Department of Cardiovascular Engineering, Royal Hallamshire Hospital, Sheffield 3 Department of Vascular Research Engineering, University College Dublin 4 Department of Neurosciences, Royal College of Surgeons of Ireland, Dublin
- 21. Updated ISUIA (2003) <7 <7 7-12 13-24 ≥25 Group 1 Group 2 Cavernous 0 0 0 3% 6.4% carotid AC/MC/IC 0 1.5% 2.6% 14.5% 40% Post-P comm 2.5% 3.4% 14.5% 18.4 % 50% Wiebers DO et al. Lancet 2003
- 22. Materials and methods Retrospective pilot study investigating role of haemodynamic indices in subarachnoid haemorrhage 10 patients from Beaumont Hospital recruited Ethical approval 3D rotational acquisitions (3DRA) images were processed with @neuFuse Case Age Urgency? Location Size 1 59 Elective Basilar 4 2 59 SAH R P Comm 3 3 53 SAH R P Comm 2 4 35 Elective R P Comm 3 5 42 SAH Basilar 10 6 35 SAH R ICA 3 7 66 SAH L P Comm 10 8 67 SAH L P Comm 6 9 57 SAH R P Comm 10 10 60 Elective L P Comm 7
- 23. Haemodynamic Results Infra-physiological time-ave Wall Shear Stress (<0.4 Pa) Case Number Age Ruptured? Location Size Area WSS<0.4Pa (mm2) % WSS<0.4Pa 1 59 Elective Basilar 4 0 0 2 59 SAH R P Comm 3 7.5 11.4 3 53 SAH R P Comm 2 0 0 4 35 Elective R P Comm 3 0 0 5 42 SAH Basilar 10 76.6 59.4 6 35 SAH R ICA 3 0 0 7 66 SAH L P Comm 10 16.9 7.4 8 67 SAH L P Comm 6 4.7 5.6 9 57 SAH R P Comm 10 0 0 10 60 Elective L P Comm 7 0 0 Aneurysm 2 Aneurysm 5 Aneurysm 7 WSS<0.4 Pa
- 24. Haemodynamic Results Jet impingement at peak systole Case Number Age Ruptured/Elective Location Size (mm) Maximum Pressure (mmHg) Area Pressure Elevated (%) 1 59 Elective Basilar 4 100.8 0.2 2 59 SAH R P Comm 3 110.5 0.6 3 53 SAH R P Comm 2 114.3 3.2 4 35 Elective R P Comm 3 118 16.5 5 42 SAH Basilar 10 119.5 0.2 6 35 SAH R ICA 3 109 8 7 66 SAH L P Comm 10 103 2.6 8 67 SAH L P Comm 6 106 6.4 9 57 SAH R P Comm 10 141 3 10 60 Elective L P Comm 7 110.5 52 Aneurysm 4 Aneurysm 5 pressure jet
- 25. Haemodynamic Results Oscillatory Shear Index Area Elevated OSI Case Number Age Ruptured/Elective Location Size Maximum OSI (%) 1 59 Elective Basilar 4 0.32 0.7 2 59 SAH R P Comm 3 0.47 7.7 3 53 SAH R P Comm 2 0.38 4.5 4 35 Elective R P Comm 3 0.28 0.9 5 42 SAH Basilar 10 0.44 4 6 35 SAH R ICA 3 0.48 24.1 7 66 SAH L P Comm 10 0.41 3.4 8 67 SAH L P Comm 6 0.42 1.2 9 57 SAH R P Comm 10 0.44 3.0 10 60 Elective L P Comm 7 0.38 8.9 Aneurysm 5 Aneurysm 6 Aneurysm 7 OSI
- 26. Morphological Results Shape indices automatically extracted from @neuFuse Case Number Age Ruptured/Elective Location Size Aspect Ratio Non-sphericity index Size ratio 1 59 Elective Basilar 4 0.92 0.09 1.5 2 59 SAH R P Comm 3 1.38 0.2 1.71 3 53 SAH R P Comm 2 0.81 0.12 0.86 4 35 Elective R P Comm 3 0.92 0.09 1.63 a 5 42 SAH Basilar 10 2.09 0.29 2.36 6 35 SAH R ICA 3 1.27 0.15 1.25 7 66 SAH L P Comm 10 2.59 0.26 2.49 b 8 67 SAH L P Comm 6 1.83 0.25 1.81 9 57 SAH R P Comm 10 1.88 0.29 3.09 10 60 Elective L P Comm 7 0.87 0.21 0.83 Aneurysm 1 Aneurysm 2 Aneurysm 3 Aneurysm 4 Aneurysm 5 Aneurysm 6 Aneurysm 7 Aneurysm 8 Aneurysm 9 Aneurysm 10
- 27. Morphological Results Shape indices automatically extracted from @neuFuse Case Number Age Ruptured/Elective Location Size Aspect Ratio Non-sphericity index Size ratio 1 59 Elective Basilar 4 0.92 0.09 1.5 2 59 SAH R P Comm 3 1.38 0.2 1.71 3 53 SAH R P Comm 2 0.81 0.12 0.86 4 35 Elective R P Comm 3 0.92 0.09 1.63 5 42 SAH Basilar 10 2.09 0.29 2.36 6 35 SAH R ICA 3 1.27 0.15 1.25 7 66 SAH L P Comm 10 2.59 0.26 2.49 8 67 SAH L P Comm 6 1.83 0.25 1.81 9 57 SAH R P Comm 10 1.88 0.29 3.09 10 60 Elective L P Comm 7 0.87 0.21 0.83 Aneurysm 1 Aneurysm 2 Aneurysm 3 Aneurysm 4 Aneurysm 5 Aneurysm 6 Aneurysm 7 Aneurysm 8 Aneurysm 9 Aneurysm 10
- 28. Qualitative comparison case 1 – wall shear stress Martin Alberto
- 29. Qualitative comparison case 8 – wall shear stress Martin Alberto
- 30. Results Summary Accepted “wisdom” Predicted the SAH patients? Size matters (7mm) 3/7 Proposed indices Aspect ratio (1.6) 5/7 Size ratio (3) 1/7 WSS 4/7 Oscillatory shear index (0.40) 6/7 Non-sphericity index (0.183) 6/7 The software is easy to use by clinicians Results were interchangeable with Dr Marzo’s within 5 cases. 45 minutes clinician time + 2-3 hours computation
- 31. Conclusions Size is not the best predictor of aneurysm’s rupture potential Haemodynamic and shape indices may have greater influence on rupture potential Strongest correlations found for Oscillatory Shear Index and Non-sphericity index
- 32. Dissemination The software has been exposed and used by clinicians at several venues with positive feedback Feedback was collected and used to improve the software Location: Boston, USA Location: Bertinoro, Italy Conference: WFNS 2009 Conference: ICCB 2009 Exposure: Workshop Exposure: Workshop Participants: 38 Participants: 13 biomedical neurosurgeons engineers Feedback: Overall Feedback: Engineering impression positive, audience community showed great showed great interest interest and positive @neurIST feedback Location: Lisbon, Portugal Location: Nagoya, Japan Conference: ESMINT 2008 Conference: ICCVS 2009 Exposure: Workshop Exposure: Presentation Participants: 36 Participants: 50+ neuroradiologists, neurosurgeons neurosurgeons, engineers Feedback: Audience showed Feedback: Very positive great enthusiasm Location: Santiago, Chile Location: Barcelona, Spain Conference: SILK- Conference: ESMINT 2009 Workshop 2009 Exposure: Workshop Exposure: Workshop Participants: 104 Participants: 22 neuroradiologists, epidemiolo Endovascular gists, engineers, neurosurgeo Neuroradiologists ns Feedback: Very Feedback: Positive positive, GUI needs improvement Published in Computational Intelligence and Neuroscience 2009
- 33. What next? • We can offer tools and services to support the following activities: o Research into cerebral aneurysms o Research into other vascular diseases o Patient specific CFD study* • Typical cost for a 100 Case Research Project would be €10,000. This includes o Initial training in use of software and interpretation of results o Tailoring of report and output data o Ongoing support and training o Use of @neuFuse and @neuEndo software • Typical cost for a single patient CFD study would be € 400. This includes o Transient CFD study o Interactive discussion with clinician on results o Presentation of results in summary report • Open Forum o Feedback o Interest in further collaboration o Can we identify a funded research project?
- 34. APPENDIX Computational Fluid Dynamics - What is it? CFD is the science of predicting fluid flow, heat and mass transfer and it’s based on the physical principles that govern any fluid flow: Conservation of Mass Conservation of Momentum (Newton’s Second Law) Conservation of Energy (First Law of Thermodynamics) 34 @neurIST Confidential Copyright © 2006-2008
- 35. APPENDIX Computational Fluid Dynamics - What is it? CFD is the science of predicting fluid flow, heat and mass transfer and it’s based on the physical principles that govern any fluid flow: Conservation of Mass Conservation of Momentum (Newton’s Second Law) Conservation of Energy (First Law of Thermodynamics) What goes in … … must go out … … for an incompressible fluid Fluid Control Volume 35 @neurIST Confidential Copyright © 2006-2008
- 36. APPENDIX Computational Fluid Dynamics - What is it? CFD is the science of predicting fluid flow, heat and mass transfer and it’s based on the physical principles that govern any fluid flow: Conservation of Mass Conservation of Momentum (Newton’s Second Law) Conservation of Energy (First Law of Thermodynamics) τ pressure pressure g τ Fluid Control Volume 36 @neurIST Confidential Copyright © 2006-2008
- 37. APPENDIX Computational Fluid Dynamics - What is it? CFD is the science of predicting fluid flow, heat and mass transfer and it’s based on the physical principles that govern any fluid flow: Conservation of Mass Conservation of Momentum (Newton’s Second Law) Conservation of Energy (First Law of Thermodynamics) Fluid Control Volume 37 @neurIST Confidential Copyright © 2006-2008
- 38. APPENDIX Computational Fluid Dynamics - Navier-Stokes Equations Analytical or closed solution currently impossible for complex physical problems Designated as Millenium Problem by Clay Mathematics Institute in Cambridge, MA, USA. Solution worth 1M $ 38 @neurIST Confidential Copyright © 2006-2008
- 39. APPENDIX Computational Fluid Dynamics – •pressure waveform The engineering trick • pressure [mmHg] •t [s] •flowrate waveform • flow rate [ml s-1] •t [s] 39 @neurIST Confidential Copyright © 2006-2008
Editor's Notes
- #24: Blue areas area areas of the aneurysm wall exposed to wall shear stress (time-averaged along the cardiac cycle) below 0.4 Pa. This a threshold found to be deleterious for endothelial cells by Malek (see ref before)
- #25: Narrow jet and localised pressure elevation (aneurysm 5) correlated with rupture (Cebral AJNR 2005). Interestingly aneurysm 5 has high pressure over a small area (0.2% of aneurysm surface) and is ruptured. Aneurysm 4 shows high pressure too but distributed of a larger area (16.5 % of aneurysm area) and interestingly this is unruptured.
- #26: Disturbed/turbulent (high OSI) flow has been associated with endothelial cell disruption. Interestingly in this cohort aneurysms with high OSI (>0.4), i.e. aneurysms 5,6,7,8 are ruptured. On the contrary unruptured aneurysm show a smaller OSI.
- #27: Average aspect ratio, non-sphericitiy index, and size ratio is higher in ruptured than unruptured aneurysm. In particular non-sphericity index is quite low (0.09, almost spherical) for elective aneurysms (aneurysm 1 and 4). Whereas the same index is high for SAH aneurysms (e.g. aneurysms 5, 7 ,8, 9)
- #28: Average aspect ratio, non-sphericitiy index, and size ratio is higher in ruptured than unruptured aneurysm. In particular non-sphericity index is quite low (0.09, almost spherical) for elective aneurysms (aneurysm 1 and 4). Whereas the same index is high for SAH aneurysms (e.g. aneurysms 5, 7 ,8, 9)