1 dept. of mechanical engineering, university of washington 2 dept. of neurosurgery, university of...
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1 Dept. of Mechanical Engineering, University of Washington
2 Dept. of Neurosurgery, University of Washington3 Dept. of Aeronautics, Imperial College London
Towards a Multi-scale Model of Cerebral Aneurysm Evolution
Michael C Barbour1,3, Michael R. Levitt2, Spencer J. Sherwin3
Alberto Aliseda1
Whitaker Enrichment Seminar
April 27th – May 1st 2015Budapest, Hungary
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Background• Cerebral aneurysms (CAs) are
found in 5-8% of the population
• 1-3% of aneurysms rupture per year
• Rupture leads to subarachnoid hemorrhaging • Mortality rates of 30-40%• Significant impairment to
survivors• Hospitalization costs - $750
million per year
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Endovascular Treatment Options
• Designed to occlude flow into the aneurysm sac causing thrombosis
• Risks of associated morbidity and mortality
• Treatment is not straightforward
Coil Embolization Pipeline Embolization
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Treatment Assessment Will the Aneurysm Grow to Rupture or Stabilize?
• Current prediction praxis:• Largely subjective and based on clinical experience • Size is the main determining factor (>7mm)• Inadequate - many small aneurysms rupture and large
aneurysms remain dormant
• Need more accurate and comprehensive prediction criteria
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Aneurysm Pathophysiology
• Multifactorial Process• Models exist in isolation – need for coupling
H. Meng et al, AJRN, 2014
• Rupture occurs when the vascular wall can no longer withstand hemodynamic loads
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Objectives
• Develop a multi-scale/multi-physics model of CA initiation and growth • Couple hemodynamics with cell dynamics• Validate model with longitudinal patient-specific data• Initiation growth
• Improve rupture prediction• Understand the processes that govern CA genesis, growth
and rupture• Simulate patient-specific progression of a CA from
genesis to rupture or stabilization
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Nektar++Open source, high-order spectral/hp element framework
• Convergence and accuracy characteristics of spectral method
• Geometric flexibility of traditional finite element method
• Biomedical applications
• Efficient & highly parallelized (C++ & MPI)
• Designed for simple new model development and communication between solvers
• www.nektar.info
Vascular Wall Permeability
Aortic arch flow
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Hemodynamic Model (CFD)• 3D reconstruction of vessel from rotational angiography
• Incompressible Navier-Stokes
• Time-dependent Womerlsey velocity profile at inlet
• Post-processing routines:
• Wall shear stress (WSS), oscillatory shear index (OSI), wall shear stress gradient (WSSG)
Vessel segmentation
Time-averaged WSS (Pa) and velocity streamlines
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SB3C CFD Challenge• Predict rupture outcome of 5 MCA aneurysms
• High vs. Low WSS debate• Cebral JR et al. AJNR, 2011 & Xiang J et al. Stoke,
2011• Contradictory conclusions & predictions
• Hemodynamics alone are not sufficient• Need to understand the progression
Case 1 Case 2
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Endothelial Cell (EC) Sensing
• WSS – mechanical stimulus for multiple vascular tone regulation pathways• Maintain vascular homeostasis
• Un-physiological WSS values lead to:• Matrix metalloproteinase activation• Smooth muscle cell apoptosis• Extracellular matrix degradation• Pro-inflammatory responses
Plata A., ICL, 2011
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EC Model• WSS signaling pathways:
• Direct – activate cation channel• Indirect – release stored Ca2+
• 4 ODE’s: • 4th order Runge-Kutta• WSS and ATP dependent
Advection-Diffusion • Agonist concentration field -
Plank et al. Progress in Biophys. and Mol. Bio. 2006
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EC – Hemodynamic Pipelinei. Reconstruct “healthy” vesselii. Run hemodynamic model— solve for velocity and WSSiii. Plug velocity field into advection-diffusion model — solve
for ATP concentration iv. Plug ATP and WSS into EC model
Diseased Vessel “Healthy” Vessel
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Single Cell Results
Plank et al.
Elevated WSS and basal ATP
Elevated ATP and basal WSS
Solid: Dashed:
Nektar++Nektar++
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Preliminary 3D Results
Time-averaged WSS (Pa)
eNOS[·]
• Direct transduction only
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Conclusions/Moving Forward
• To date:• Developed new boundary conditions and post-processing
routines for hemodynamic model
• Coupled EC sensing model with hemodynamic and advection-
diffusion models
• Moving Forward:• Investigate possible correlation between eNOS concentration
and CA initiation location
• Extend cell model to include SMC apoptosis/matrix
degradation
• Solid Mechanics: Nektar++ or FEBio?
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Acknowledgements
• Whitaker International Fellowship (IIE)• Sherwin Lab, Imperial College London• Dr. Spencer Sherwin• Dr. Andrew Comerford• Yumnah Mohamied• Entire Nektar++ Team
Thanks for listening!
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References
• Meng H, Tutino VM, Xiang J and Siddiqui A. “High WSS or Low WSS? Complex
Interactions of Hemodynamics with Intracranial Aneurysm Initiation, Growth and
Rupture: Towards a Unifying Hypothesis.” AJNR 2014
• Plank MJ, Wall DJN and David T, “Atherosclerosis and calcium signaling in endothelial
cells.” Biophys. and Mol. Bio. 2006
• Cantwell CD, Moxey D and Sherwin SJ. “Nektar++: An open-source spectral/hp
element framework.” Computer Physics Communication 2015
• Xiang J and Menh H. “Hemodynamic-Morphologic Discriminants for Intracranial
Aneurysm Rupture.” Stroke 2011
• Cerbal JR, Mut F, Weir J, and Putman CM. “Association of Hemodynamic
Characteristics and Cerebral Aneurysm Rupture.” AJNR 2011