Sickle cell anemia and pediatric strokes: Computational fluid dynamics analysis in the middle cerebral artery

Children with sickle cell anemia (SCA) have a high incidence of strokes, and transcranial Doppler (TCD) identifies at-risk patients by measuring blood velocities in large intracerebral arteries; time-averaged mean velocities greater than 200 cm/s confer high stroke risk and warrant therapeutic intervention with blood transfusions. Our objective was to use computational fluid dynamics to alter fluid and artery wall properties, to simulate scenarios causative of significantly elevated arterial blood velocities. Two-dimensional simulations were created and increasing percent stenoses were created in silico, with their locations varied among middle cerebral artery (MCA), internal carotid artery (ICA), and anterior cerebral artery (ACA). Stenoses placed in the MCA, ICA, or ACA generated local increases in velocity, but not sufficient to reach magnitudes > 200 cm/s, even up to 75% stenosis. Three-dimensional reconstructions of the MCA, ICA, and ACA from children with SCA were generated from magnetic resonance angiograms. Using finite element method, blood flow was simulated with realistic velocity waveforms to the ICA inlet. Three-dimensional reconstructions revealed an uneven, internal arterial wall surface in children with SCA and higher mean velocities in the MCA up to 145 cm/s compared to non-SCA reconstructions. There were also greater areas of flow recirculation and larger regions of low wall shear stress. Taken together, these bumps on the internal wall of the cerebral arteries could create local flow disturbances that, in aggregate, could elevate blood velocities in SCA. Identifying cellular causes of these microstructures as adhered blood cells or luminal narrowing due to endothelial hyperplasia induced by disturbed flow would provide new targets to treat children with SCA. The preliminary qualitative results provided here point out the critical role of 3D reconstruction of patient-specific vascular geometries and provide qualitative insight to complex interplay between vascular geometry and rheological properties possibly altered by SCA.