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

Area of Science:

• Neuroimaging
• Biophysics
• Medical Physics

Background:

• Water exchange between brain tissue and cerebrospinal fluid (CSF) is crucial for waste clearance and homeostasis.
• Perivascular spaces (PVS) are key pathways for this exchange, potentially linked to glymphatic function.
• Quantifying tissue-CSF water exchange non-invasively remains a challenge.

Purpose of the Study:

• To apply Magnetization Transfer Indirect Spin Labeling (MISL) MRI for quantifying human brain tissue-CSF water exchange.
• To evaluate MISL's utility in assessing tissue-CSF exchange within PVS.
• To characterize altered water exchange dynamics in pathologic conditions.

Main Methods:

• MISL MRI at 3T utilized off-resonance magnetization transfer to label parenchymal water.
• Long-TE 3D-TSE readout captured CSF exchange, suppressing parenchymal signals.
• Atlas-based segmentation enabled CSF-region-specific quantification in healthy subjects and a brain tumor patient.

Main Results:

• MISL demonstrated widespread, heterogeneous tissue-CSF exchange, strongest in PVS and near the choroid plexus.
• Tissue-to-CSF flow (TCF) was estimated at 100-300 mL/100 mL/min, with higher MISL signals (~8.4%) in PVS.
• Age-dependent TCF declines were observed, and elevated water exchange was detected in a tumor patient even without overt FLAIR hyperintensity.

Conclusions:

• MISL enables robust, non-invasive mapping of tissue-CSF exchange with high sensitivity and spatial resolution.
• MISL offers a unique window into PVS tissue-CSF exchange, potentially reflecting glymphatic function.
• This technique can characterize altered water exchange in disease states.