Rapid Tissue-CSF Water Exchange in the Human Brain Revealed by Magnetization Transfer Indirect Spin Labeling

To apply the Magnetization Transfer Indirect Spin Labeling (MISL) MRI technique for quantifying tissue-CSF water exchange in the human brain, and to investigate its utility in (1) evaluating tissue-CSF water exchange within perivascular spaces (PVS), and (2) characterizing altered water exchange dynamics in pathologic conditions.

MISL was implemented on a 3 T MRI using off-resonance magnetization transfer to label parenchymal water. The resulting exchange with CSF was captured via long-TE 3D-TSE readout to suppress parenchymal signals. CSF-region-specific quantification was achieved by atlas-based segmentation. Studies were conducted in healthy subjects across age groups and in patient with metastatic brain tumor.

MISL revealed widespread and regionally heterogeneous tissue-CSF exchange, with the strongest signals observed in the PVS and areas adjacent to the choroid plexus. MISL signals were typically 2%-3% in the ventricles and subarachnoid space, and reached 3% in the cerebellar regions, suggesting tissue-to-CSF flow (TCF) in the range of 100-300 mL/100 mL/min. The high MISL signals observed in the PVS (∼8.4%) indicated active tissue-CSF water exchange, providing functional information of the PVS that conventional T2w imaging cannot capture. Significant age-dependent declines in TCF were observed across most brain regions, except for the third and fourth ventricles. In the tumor patient, MISL revealed elevated water exchange, even where no overt FLAIR hyperintensity was present.

MISL enables robust, non-invasive mapping of tissue-CSF exchange with high sensitivity and spatial resolution. MISL provides a unique window into tissue-CSF exchange within PVS, which may reflect glymphatic function.