330 Interactions of Brain, Blood, and CSF: A Novel Mathematical Model of Cerebral Edema

Abstract

INTRODUCTION: Previous models of intracranial pressure (ICP) dynamics have not included flow of cerebral interstitial fluid (ISF) and changes in resistance to its flow when brain swelling occurs. METHODS: We developed a lumped parameter model which includes a representation of cerebral ISF flow within brain tissue and its interactions with CSF flow and CBF. The model is based on an electrical analog circuit with four intracranial compartments: the (1) subarachnoid space, (2) brain, (3) ventricles and (4) cerebral vasculature. We determined changes in pressure and volume within cerebral compartments at steady-state and simulated perturbations: Rapid injection into the intracranial space, hyper-and hypoventilation. We simulated changes in resistance to flow or absorption of CSF and cerebral ISF to model hydrocephalus and cerebral edema. RESULTS: The model accurately replicates features of intracranial physiology including the pressure–volume curve, increased ICP pulse pressure with rising ICP, hydrocephalus from increased resistance to CSF outflow, and changes associated with ventilation. Importantly, modeling edema with increased resistance to ISF flow mimics key features of brain swelling including elevated ICP, increased brain volume, effaced ventricles, and a contracted subarachnoid space. Similarly, decreased resistance to flow of fluid across the BBB leads to an exponential-like rise in ICP and ventricular collapse. CONCLUSIONS: The model accurately depicts the complex interactions that occur between pressure, volume, and resistances to flow in the different intracranial compartments under specific pathophysiological conditions. In modelling resistance to bulk flow of cerebral ISF, it may serve as a platform for improved modelling of cerebral edema and blood–brain barrier disruption that occur following brain injury.