Choroid plexus perfusion and bulk cerebrospinal fluid flow across the adult lifespan

Abstract

The choroid plexus (ChP) comprises a collection of modified ependymal cells that play an important role in the production of brain cerebrospinal fluid (CSF), and ChP perfusion aberrations have been implicated in a range of cerebrovascular and neurodegenerative disorders. To provide an exemplar for the growing interest in ChP activity, we evaluated ChP perfusion and bulk CSF flow cross-sectionally across the healthy adult lifespan. Participants (n = 77; age range = 21–86 years) were scanned at 3T using T1-weighted, T2-weighted-FLAIR, perfusion-weighted pCASL, and phase contrast MRI to calculate ChP anatomy, perfusion, and aqueductal CSF flow, respectively. Regression models were applied to evaluate aging effects on ChP volume and ChP perfusion in the lateral ventricles, as well as CSF flow. ChP volume (mean ± std = 2.81 ± 1.1 cm3) increased (p < 0.001), ChP perfusion (36.3 ± 8.6 mL/100 g/min) decreased (p = 0.0078), and ChP total blood flow (1.13 ± 0.34 mL/min) increased (p < 0.001) with age. Cranial-to-caudal net CSF flow (0.245 ± 0.20 mL/min) decreased, absolute CSF flow (4.86 ± 2.96 mL/min) increased, and CSF regurgitant fraction (0.87 ± 0.126) increased with age (all: p < 0.001). ChP perfusion was directly related to net cranial-to-caudal CSF flow through the aqueduct (p = 0.033). The implications of these findings are discussed in the context of the growing literature on CSF circulatory dysfunction in neurodegeneration and cerebrovascular disease.

Parasagittal dural space hypertrophy and amyloid-β deposition in Alzheimer’s disease

“…We have previously shown age-related reductions in ChP perfusion and net CSF flow through the aqueduct of Sylvius in healthy adults, and further demonstrated a positive relationship between these two measures. 20 These findings provided support that CSF production from the ChP can be detected downstream in the CSF flow pathway and allowed us to establish surrogate markers of choroidal CSF production. In the present study, we did not observe relationships with global Aβ accumulation and either of the two measures, which may indicate that choroidal CSF production is not involved in the clearance of Aβ.…”

“…We have recently reported on novel MRI methods to quantify these measurements in humans in vivo and non-invasively. 19 , 20 In previous work, we observed age-related hypertrophy of both the ChP and PSD. We also observed decreases in ChP perfusion and caudal CSF flow through the aqueduct of Sylvius with increasing age.…”

“…For this scan, an equilibrium magnetization (M 0 ) scan was sequentially acquired with identical geometry and scanner gain, but with pseudo-continuous arterial spin labelling preparation removed and TR = 15 000 ms. A phase-contrast angiography acquisition (2D gradient echo; TR = 12.0 ms, TE = 7.8 ms, spatial resolution = 0.59 × 0.59 × 4.0 mm 3 , velocity encoding = 12 cm/s) was adapted to quantify net CSF flow draining from the lateral and third ventricles at the level of the aqueduct of Sylvius. 20 …”

“…ChP perfusion was calculated using a previously published deep-learning segmentation pipeline. 20 Briefly, participants’ T 1 -weighted and T 2 -weighted FLAIR images were transformed to 1 mm3 isotropic MNI152 space using the Advanced Normalization Tools non-linear registration tool. 29 The ChP was then automatically segmented using a fully convolutional neural network (F-CNN) based on a 3D U-Net architecture adapted from Zhao et al .…”

“…The net flow parameter represents the net volume of CSF that flows out of the third ventricle and through the aqueduct of Sylvius per minute. 20 …”