Measurements and Computational Modeling of Cerebrospinal Fluid Flow in Humans Brian Sweetman, PhD Candidate Laboratory for Product and Process Design Department of Bioengineering University of Illinois at Chicago
The Craniospinal System Cranium Spinal canal Medical Image Mathematical Model
Diseases of the Central Nervous System Arteriosclerosis Hydrocephalus Thrombosis Meningitis Parkinson’s Aneurysms Hypertension Alzheimer’s Epilepsy Cancer Subarachnoid hemorrhage
Hydrocephalus Normal Hydrocephalic
Hydrocephalus Treatment Current treatments Pressure shunt and catheter Third ventriculostomy • Problems • $1 billion annually in the US • Numerous revisions necessary • Effective for NPH patients?
CSF Flow Dynamics Can we understand the flow field? What causes it to flow? Why is it pulsatile? • Can we predict the flow field? • Do the basic laws of mass and momentum conservation apply?
Ventricular Volume Sensor Model Development Device Parameters Tested Sensor Fabrication 1mm • Reference: Linninger/Basati/Dawe/Penn. Med Eng Phys, 2009. 31(7):838-45. 8 of 68
Intracranial Pressure and Hydrocephalus: Humans 3551 Pa 1875 Pa 502 Pa Flow Pressure 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, 2009. 37(7): p. 1434-47. Linninger, A.A., et al. Pulsatile cerebrospinal fluid dynamics in the human brain. TBME, 2005. 52(4): p. 557-65.
From Medical Imaging to Computational Modeling Medical Imaging 1st Principles: Math/Physics Computer Science
Measured and Predicted CSF Flow Third ventricle 3rd ventricle Aqueduct 4th ventricle Pontine cistern
CSF Flow Dynamics mm/s 3rd ventricle Aqueduct 4th ventricle Pontine cistern
CSF Pressure Dynamics Definition of Symbols/Abbreviations LV: lateral ventricle SAS: subarachnoid space V4: fourth ventricle CCJ: cranio-cervical junction
CSF Dynamics: Big Ideas Pressure gradients in the brain remain small (<1mmHg) Blood flow and vasculature expansion driving force for pulsatile CSF motion
Future Directions Vasculature drives the CSF Can we improve our representation of the cerebral vasculature Will an improved vasculature model improve our model of hydrocephalus? Link between arteriosclerosis and hydrocephalus How is the blood flow affected by ventricular enlargement?
Acknowledgements • Director • Prof. Andreas Linninger • LPPD members • Dr. Andrej Mošať, Post-doctorate Fellow • Dr. Madhawa Hettiarachchi, Post-doctorate Fellow • Dr. Michalis Xenos, Post-doctorate Fellow • Sukhraaj S. Basati, PhD Candidate • Seon Kim, PhD Candidate • Eric Lueshen, PhD Candidate • Nikhil Sindhwani, MS Candidate • Undergraduate researchers • Nicholas Vaičaitis, Ying Hsu, Cierra Hall, Tim Harris, Brian Henry, Nabiha Shamsi, Laura Zitella
References • 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. • 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. • 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. • 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. • 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. • 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. • 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. • 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.