Enhanced in vitro model of the CSF dynamics

Anne Benninghaus*, Olivier Balédent, Armelle Lokossou, Carlos Castelar, Steffen Leonhardt, Klaus Radermacher

*Korrespondierende/r Autor/-in für diese Arbeit
24 Zitate (Scopus)


Background: Fluid dynamics of the craniospinal system are complex and still not completely understood. In vivo flow and pressure measurements of the cerebrospinal fluid (CSF) are limited. Whereas in silico modeling can be an adequate pathway for parameter studies, in vitro modeling of the craniospinal system is essential for testing and evaluation of therapeutic measures associated with innovative implants relating to, for example, normal pressure hydrocephalus and other fluid disorders. Previously-reported in vitro models focused on the investigation of only one hypothesis of the fluid dynamics rather than developing a modular set-up to allow changes in focus of the investigation. The aim of this study is to present an enhanced and validated in vitro model of the CSF system which enables the future embedding of implants, the validation of in silico models or phase-contrast magnetic resonance imaging (PC-MRI) measurements and a variety of sensitivity analyses regarding pathological behavior, such as reduced CSF compliances, higher resistances or altered blood dynamics. Methods: The in vitro model consists of a ventricular system which is connected via the aqueduct to the cranial and spinal subarachnoid spaces. Two compliance chambers are integrated to cushion the arteriovenous blood flow generated by a cam plate unit enabling the modeling of patient specific flow dynamics. The CSF dynamics are monitored using three cranial pressure sensors and a spinal ultrasound flow meter. Measurements of the in vitro spinal flow were compared to cervical flow data recorded with PC-MRI from nine healthy young volunteers, and pressure measurements were compared to the literature values reported for intracranial pressure (ICP) to validate the newly developed in vitro model. Results: The maximum spinal CSF flow recorded in the in vitro simulation was 133.60 ml/min in the caudal direction and 68.01 ml/min in the cranial direction, whereas the PC-MRI flow data of the subjects showed 122.82 ml/min in the caudal and 77.86 ml/min in the cranial direction. In addition, the mean ICP (in vitro) was 12.68 mmHg and the pressure wave amplitude, 4.86 mmHg, which is in the physiological range. Conclusions: The in vitro pressure values were in the physiological range. The amplitudes of the flow results were in good agreement with PC-MRI data of young and healthy volunteers. However, the maximum cranial flow in the in vitro model occurred earlier than in the PC-MRI data, which might be due to a lack of an in vitro dynamic compliance. Implementing dynamic compliances and related sensitivity analyses are major aspects of our ongoing research.

ZeitschriftFluids and Barriers of the CNS
PublikationsstatusVeröffentlicht - 29.04.2019