Abstract
BACKGROUND: The cerebrospinal fluid filling the ventricles of the brain moves with a cyclic velocity driven by the transmantle pressure, or instantaneous pressure difference between the lateral ventricles and the cerebral subarachnoid space. This dynamic phenomenon is of particular interest for understanding ventriculomegaly in cases of normal pressure hydrocephalus (NPH). The magnitude of the transmantle pressure is small, on the order of a few Pascals, thereby hindering direct in vivo measurements. To complement previous computational efforts, we perform here, for the first time, in vitro experiments involving an MRI-informed experimental model of the cerebral aqueduct flow. METHODS: Dimensional analysis is used in designing a scaled-up model of the aqueduct flow, with physical similarity maintained by adjusting the flow frequency and the properties of the working fluid. High-resolution MRI images are used to generate a 3D-printed anatomically correct aqueduct model. A programmable pump is used to generate a pulsatile flow rate signal measured from phase-contrast MRI. Extensive experiments are performed to investigate the relation between the cyclic fluctuations of the aqueduct flow rate and the transmantle pressure fluctuation over the range of flow conditions commonly encountered in healthy subjects. The time-dependent pressure measurements are validated through comparisons with predictions obtained with a previously derived computational model. RESULTS: Parametric dependences of the pressure-fluctuation amplitude and its phase lag relative to the flow rate are delineated. The results indicate, for example, that the phase lag is nearly independent on the stroke volume. A simple expression relating the mean amplitude of the interventricular pressure difference (between third and fourth ventricle) with the stroke volume of the oscillatory flow is established. CONCLUSIONS: MRI-informed in-vitro experiments using an anatomically correct model of the cerebral aqueduct and a realistic flow rate have been used to characterize transmantle pressure. The quantitative results can be useful in enabling quick clinical assessments of transmantle pressure to be made from noninvasive phase contrast MRI measurements of aqueduct flow rates. The scaled-up experimental facility provides the ability to conduct future experiments specifically aimed at investigating altered CSF flow and associated transmantle pressure, as needed in connection with NPH studies.