Pulsatile cerebral paraarterial flow by peristalsis, pressure and directional resistance

Abstract

Background: A glymphatic system has been proposed that comprises flow that enters along cerebral paraarterial channels between the artery wall and the surrounding glial layer, continues through the parenchyma, and then exits along similar paravenous channels. The mechanism driving flow through this system is unclear. The pulsatile (oscillatory plus mean) flow measured in the space surrounding the middle cerebral artery (MCA) suggests that peristalsis created by intravascular blood pressure pulses is a candidate for the paraarterial flow in the subarachnoid spaces. However, peristalsis is ineffective in driving significant mean flow when the amplitude of channel wall motion is small, as has been observed in the MCA artery wall. In this paper, peristalsis in combination with two additional mechanisms, a longitudinal pressure gradient and directional flow resistance, is evaluated to match the measured MCA paraarterial oscillatory and mean flows.

Methods: Two analytical models are used that simplify the paraarterial branched network to a long continuous channel with a traveling wave in order to maximize the potential effect of peristalsis on the mean flow. The two models have parallel-plate and annulus geometries, respectively, with and without an added longitudinal pressure gradient. The effect of directional flow resistors was also evaluated for the parallel-plate geometry.

Results: For these models, the measured amplitude of arterial wall motion is too large to cause the small measured amplitude of oscillatory velocity, indicating that the outer wall must also move. At a combined motion matching the measured oscillatory velocity, peristalsis is incapable of driving enough mean flow. Directional flow resistance elements augment the mean flow, but not enough to provide a match. With a steady longitudinal pressure gradient, both oscillatory and mean flows can be matched to the measurements.

Conclusions: These results suggest that peristalsis drives the oscillatory flow in the subarachnoid paraarterial space, but is incapable of driving the mean flow. The effect of directional flow resistors is insufficient to produce a match, but a small longitudinal pressure gradient is capable of creating the mean flow. Additional experiments are needed to confirm whether the outer wall also moves, as well as to validate the pressure gradient.

Keywords: Brain; Glymphatic flow; Paravascular; Peristaltic flow; Perivascular.

Fig. 1

Geometric parameters of the peristalitc wall motion

Fig. 2

Orientation of cylinders to promote flow in the left to right direction. Left—cylinder orientation for zero flow. Middle—left to right flow flexes the cylinder so that it is oriented tangential to the flow. Right—right to left flow flexes the cylinder towards normal orientation. For simplicity, only one cylinder is shown, and it is attached to the wall, but in the solution in this section, cylinders are distributed throughout the channel. (From [17])

Fig. 3

Mean flow rate normalized by the maximum peristaltic mean flow rate versus wall-amplitude-to-gap-height ratio

Fig. 4

Ratio of oscillatory to mean velocities versus wall-amplitude-to-gap-height ratio for all models. This ratio is 0.66 for the Mestre, et al. [7] measurements