Disorders of intracranial pressure, including traumatic brain injury and hydrocephalus, can cause significant morbidity and mortality. There is increasing evidence that many of our """"""""standard"""""""" theories explaining the pathophysiology of these disorders should be reconsidered. In this proposal, a novel theory describing the pathophysiology of elevated intracranial pressure and hydrocephalus is studied using a combination of bioengineering modeling methods and laboratory experimental investigations. The theory, which we termed the hemodynamic theory, is based on an interrelationship between intracranial compliance, cerebral blood flow impedance, and intracranial pressure. Our preliminary studies using a small animal model have demonstrated a strong correlation between compliance and disturbances in blood flow. The overall objective of this project is to construct and validate a transmission-line circuit that models intracranial pressure changes in relationship to altered hemodynamics. In order to enhance the accuracy of the model, the individual circuit parameters will be estimated from in vitro experiments. In addition, an in vivo model of acute hydrocephalus will be used to test the theoretical basis supporting the circuit model. Finally, the computer simulations of the new circuit model will be compared to the actual physiological data derived from the animal experiments. The long-term goal of this project is to establish a comprehensive, unifying theory of intracranial pressure pathophysiology that accurately represents and predicts the various clinical disorders affected by altered intracranial pressure. The use of bioengineering modeling techniques provides a powerful method to test hypotheses by simulating complex physiologic phenomenon. An improved understanding of these disorders will offer new and better treatment modalities for millions of affected patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS040122-03
Application #
6531123
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (03))
Program Officer
Pancrazio, Joseph J
Project Start
2000-04-20
Project End
2004-02-29
Budget Start
2002-03-01
Budget End
2004-02-29
Support Year
3
Fiscal Year
2002
Total Cost
$102,604
Indirect Cost
Name
University of California Los Angeles
Department
Surgery
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Hu, Xiao; Xu, Peng; Asgari, Shadnaz et al. (2010) Forecasting ICP elevation based on prescient changes of intracranial pressure waveform morphology. IEEE Trans Biomed Eng 57:1070-8
Hu, Xiao; Glenn, Thomas; Scalzo, Fabien et al. (2010) Intracranial pressure pulse morphological features improved detection of decreased cerebral blood flow. Physiol Meas 31:679-95
Hu, Xiao; Alwan, Abeer A; Rubinstein, Eduardo H et al. (2006) Reduction of compartment compliance increases venous flow pulsatility and lowers apparent vascular compliance: implications for cerebral blood flow hemodynamics. Med Eng Phys 28:304-14