ANSYS FLUENT Application: Intracranial dynamics Velocity [m/s] Pressure [Pa] Normal Linninger, A.A., M. Xenos, D.C. Zhu, M.R. Somayaji, S. Kondapalli, and R.D. Penn. Cerebrospinal fluid flow in the normal and hydrocephalic human brain. IEEE Trans. Biomed. Eng. 54:291-302, 2007.
ANSYS FLUENT Application: Intracranial dynamics LV: lateral ventricleSAS: subarachnoid space V4: fourth ventricleCCJ: cranio-cervical junction Definition of Symbols/Abbreviations
ANSYS FLUENT Application: Intracranial dynamics— Conclusions Pressure gradients in the brain remain small (<1mmHg) Blood flow and vasculature expansion driving force for pulsatile CSF motion
ANSYS FLUENT for Brain ResearchApplication Drug Delivery
ANSYS FLUENT Application: Drug delivery to the human brain Motivation: Validate invasive techniques for clinical practice Geometrical Challenge: Reconstruction of brain anatomy from images Physiological Challenge: Quantify brain anisotropy and heterogeneity from DTI Drug Transport Challenge: Predict spatio-temporal drug distribution in 3d Treatment Challenge: Propose optimal catheter positioning and CED parameters Apparent water diffusion tensor in human brain from diffusion tensor imaging (DTI) Axial view Drug transport—porous brain parenchyma Effective Diffusion Tensor of Growth Factor (GDNF) near the Putamen Diffusion flux in anisotropic tissue:
ANSYS FLUENT Application: Drug delivery to the human brain
Axial slices high low Molecular weight = 27,000 kg/kmol; Flow rate = 4µl/min ; X 0 = 3.7·10 -3 mol/l, no reaction
ANSYS FLUENT for Brain Research Drug Delivery Additional Applications
ANSYS FLUENT Application: Drug distribution & catheter placement Week #1Week #4 Thalamus injection Injection into gray matter A. Linninger, M.R. Somayaji, L. Zhang, M.S. Hariharan and R. Penn. Rigorous Mathematical Modeling Techniques for Optimal Delivery of Macromolecules to the Brain. IEEE Transaction on Biomedical Engineering, 55 (9): 2303-2313, 2008. GDNF (neurotrophic factor) concentration field over time mol/l Week #2 Week #1Week #4Week #2 mol/l Internal capsule injection Injection into white matter
ANSYS FLUENT Application: Drug distribution & catheter design Concentration field over time lowhigh Flow direction at week 3 Week #1Week #3Week #2
ANSYS FLUENT Application: References 1.Linninger, A.A., M.R. Somayaji, T. Erickson, X. Guo, and R.D. Penn. Computational methods for predicting drug transport in anisotropic and heterogeneous brain tissue. Journal of Biomechanics. 41:2176-2187, 2008. 2.Linninger, A.A., M.R. Somayaji, M. Mekarski, and L. Zhang. Prediction of convection-enhanced drug delivery to the human brain. J Theor Biol. 250:125-138, 2008. 3.Linninger, A.A., M.R. Somayaji, L. Zhang, M.S. Hariharan, and R.D. Penn. Rigorous Mathematical Modeling Techniques for Optimal Delivery of Macromolecules to the Brain. Biomedical Engineering, IEEE Transactions on. 55:2303-2313, 2008. 4.Linninger, A.A., B. Sweetman, and R. Penn. Normal and hydrocephalic brain dynamics: the role of reduced cerebrospinal fluid reabsorption in ventricular enlargement. Ann. Biomed. Eng. 37:1434- 47, 2009. 5.Linninger, A.A., M. Xenos, B. Sweetman, S. Ponkshe, X. Guo, and R. Penn. A mathematical model of blood, cerebrospinal fluid and brain dynamics. J. Math. Biol. 59:729-59, 2009. 6.Linninger, A.A., M. Xenos, D.C. Zhu, M.R. Somayaji, S. Kondapalli, and R.D. Penn. Cerebrospinal fluid flow in the normal and hydrocephalic human brain. IEEE Trans. Biomed. Eng. 54:291-302, 2007. 7.Morrison, P.F., R.R. Lonser and E.H. Oldfield, “Convective delivery of glial cell line-derived neurotrophic factor in the human putamen”, J Neurosurg, vol.107, pp. 74-83, Jul, 2007. 8.Salvatore, M.F., Y. Ai, B. Fischer, A.M. Zhang, R.C. Grondin, Z. Zhang, G.A. Gerhardt, D.M. Gash, “Point source concentration of GDNF may explain failure of phase II clinical trial”, Experimental Neurology, vol. 202, pp. 497-505, 2006.