Mechanistic-mathematical modeling of intracranial pressure (ICP) profiles over a single heart cycle. The fundament of the ICP curve form.

The intracranial pressure (ICP) curve with its different peaks has been comprehensively studied, but the exact physiological mechanisms behind its morphology has not been revealed. If the pathophysiology behind deviations from the normal ICP curve form could be identified, it could be vital information to diagnose and treat each single patient. A mathematical model of the hydrodynamics in the intracranial cavity over single heart cycles was developed. A Windkessel model approach was generalized but the unsteady Bernoulli equation was utilized for blood flow and CSF flow. This is a modification of earlier models using the extended and simplified classical Windkessel analogies to a model that is based on mechanisms rooted in the laws of physics. The improved model was calibrated with patient data for cerebral arterial inflow, venous outflow, cerebrospinal fluid (CSF), and ICP over one heart cycle from 10 neuro-intensive care unit patients. A priori model parameter values were obtained by considering patient data and values taken from earlier studies. These values were used as an initial guess for an iterated constrained-ODE (ordinary differential equation) optimization problem with cerebral arterial inflow data as input into the system of ODEs. The optimization routine found patient-specific model parameter values that produced model ICP curves that showed excellent agreement with clinical measurements while model venous and CSF flow were within a physiologically acceptable range. The improved model and the automated optimization routine gave better model calibration results compared to previous studies. Moreover, patient-specific values of physiologically important parameters like intracranial compliance, arterial and venous elastance, and venous outflow resistance were determined. The model was used to simulate intracranial hydrodynamics and to explain the underlying mechanisms of the ICP curve morphology. Sensitivity analysis showed that the order of the three main peaks of the ICP curve was affected by a decrease in arterial elastance, a large increase in resistance to arteriovenous flow, an increase in venous elastance, or a decrease in resistance to CSF flow in the foramen magnum; and the frequency of oscillations were notably affected by intracranial elastance. In particular, certain pathological peak patterns were caused by these changes in physiological parameters. To the best of our knowledge, there are no other mechanism-based models associating the pathological peak patterns to variation of the physiological parameters.