Ultra-long-TE arterial spin labeling reveals rapid and brain-wide blood-to-CSF water transport in humans
Leonie Petitclerc,
Lydiane Hirschler,
Jack A. Wells,
David L. Thomas,
Marianne A.A. van Walderveen,
Mark A. van Buchem,
Matthias J.P. van Osch
Affiliations
Leonie Petitclerc
C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, Netherlands; Corresponding author at: Leids Universitair Medisch Centrum, C.J. Gorter Center for high field MRI, Room J0-56, Albinusdreef 2, 2333 ZA Leiden, Netherlands.
Lydiane Hirschler
C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
Jack A. Wells
UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, United Kingdom
David L. Thomas
Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom
Marianne A.A. van Walderveen
Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
Mark A. van Buchem
C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
Matthias J.P. van Osch
C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center, Leiden, Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden, Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
The study of brain clearance mechanisms is an active area of research. While we know that the cerebrospinal fluid (CSF) plays a central role in one of the main existing clearance pathways, the exact processes for the secretion of CSF and the removal of waste products from tissue are under debate. CSF is thought to be created by the exchange of water and ions from the blood, which is believed to mainly occur in the choroid plexus. This exchange has not been thoroughly studied in vivo.We propose a modified arterial spin labeling (ASL) MRI sequence and image analysis to track blood water as it is transported to the CSF, and to characterize its exchange from blood to CSF. We acquired six pseudo-continuous ASL sequences with varying labeling duration (LD) and post-labeling delay (PLD) and a segmented 3D-GRASE readout with a long echo train (8 echo times (TE)) which allowed separation of the very long-T2 CSF signal. ASL signal was observed at long TEs (793 ms and higher), indicating presence of labeled water transported from blood to CSF. This signal appeared both in the CSF proximal to the choroid plexus and in the subarachnoid space surrounding the cortex. ASL signal was separated into its blood, gray matter and CSF components by fitting a triexponential function with T2s taken from literature. A two-compartment dynamic model was introduced to describe the exchange of water through time and TE. From this, a water exchange time from the blood to the CSF (Tbl->CSF) was mapped, with an order of magnitude of approximately 60 s.