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BMES Annual Meeting, October 6 - 9, 2010 Austin, TX

Measurements and Computational Modeling of Cerebrospinal Fluid Flow in Humans. BMES Annual Meeting, October 6 - 9, 2010 Austin, TX Track: Systems Biology, Bioinformatics and Computational Biology. Brian Sweetman, Richard Penn, and Andreas A. Linninger

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BMES Annual Meeting, October 6 - 9, 2010 Austin, TX

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  1. Measurements and Computational Modeling of Cerebrospinal Fluid Flow in Humans BMES Annual Meeting, October 6 - 9, 2010 Austin, TX Track: Systems Biology, Bioinformatics and Computational Biology Brian Sweetman, Richard Penn, and Andreas A. Linninger Laboratory for Product and Process Design Department of Bioengineering University of Illinois at Chicago (UIC)

  2. Specific Research Questions Why does the cerebrospinal fluid (CSF) pulsate? What is the CSF pressure? How does hydrocephalus occur?

  3. Hydrocephalus Healthy Hydrocephalic

  4. Specific Research Questions Why does the cerebrospinal fluid (CSF) pulsate? What is the CSF pressure? How does hydrocephalus occur?

  5. From Medical Imaging to Computational Modeling Medical Imaging 1st Principles: Math/Physics Computer Science

  6. Blood Flow Drives the CSF Motion

  7. Blood Flow Drives the CSF Motion

  8. Specific Research Questions Why does the cerebrospinal fluid (CSF) pulsate? What is the CSF pressure? How does hydrocephalus occur?

  9. We Calculate the CSF Pressure Field Early systole (86% cc) Mid systole (15% cc) Late systole (24% cc) Diastole (60% cc) Mass balance; incompressible fluid Momentum balance

  10. Specific Research Questions Why does the cerebrospinal fluid (CSF) pulsate? What is the CSF pressure? How does hydrocephalus occur?

  11. Ventricular Enlargement: Hakim’s Theory A large pressure difference must exist between the lateral ventricles and the subarachnoid space Cranial vault Dura mater Subdural space (vacuum) Arachnoid membrane Arachnoidal strands Subarachnoid space Piaglial membrane Lateral ventricle S. Hakim, et al. Surg Neurol. 5 (1976) 187-210.

  12. Intracranial Pressure and Hydrocephalus: Dogs

  13. 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.

  14. Conclusions Large pressure gradients are not needed to induce hydrocephalus Blood flow drives CSF motion The Navier-Stokes equations allow us to calculate the pressure gradients in the brain

  15. Acknowledgements • Director • Prof. Andreas Linninger • LPPD members • Dr. Andrej Mošať, Post-doctorate Fellow • Dr. Madhawa Hettiarachchi, 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

  16. 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.

  17. Research Objectives Supplement experimental data with first principles mathematical analysis Quantify the mechanical interaction between major components of the central nervous system Advance our understanding of central nervous system physics

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