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Updated: Oct 8, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Age-dependent cerebrospinal fluid-tissue water exchange detected by magnetization transfer indirect spin labeling MRI
Anna M Li1, Lin Chen1,2,3, Hongshuai Liu4
1F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, Maryland, USA.
Purpose:
A non-invasive magnetization transfer indirect spin labeling (MISL) MRI method is developed to quantify the water exchange between cerebrospinal fluid (CSF) and other tissues in the brain and to examine the age-dependence of water exchange.
Method:
In the pulsed MISL, we implemented a short selective pulse followed by a post-labeling delay before an MRI acquisition with a long echo time; in the continuous MISL, a train of saturation pulses was applied. MISL signal (∆Z) was obtained by the subtraction of the label MRI at -3.5 ppm from the control MRI at 200 ppm. CSF was extracted from the mouse ventricles for the MISL optimization and validation. Comparison between wild type (WT) and aquaporin-4 knockout (AQP4-/- ) mice was performed to examine the contributions of CSF water exchange, whereas its age-dependence was investigated by comparing the adult and young WT mice.
Results:
The pulsed MISL method observed that the MISL signal reached the maximum at 1.5 s. The continuous MISL method showed the highest MISL signal in the fourth ventricle (∆Z = 13.5% ± 1.4%), whereas the third ventricle and the lateral ventricles had similar MISL ∆Z values (∆Z = 12.0% ± 1.8%). Additionally, significantly lower ∆Z (9.3%-18.7% reduction) was found in all ventricles for the adult mice than those of the young mice (p < 0.02). For the AQP4-/- mice, the ∆Z values were 5.9%-8.3% smaller than those of the age-matched WT mice in the lateral and fourth ventricles, but were not significant.
Conclusion:
The MISL method has a great potential to study CSF water exchange with the surrounding tissues in brain.
Insights
Magnetization transfer indirect spin labeling (MISL) MRI quantifies brain water exchange between cerebrospinal fluid (CSF) and tissues. This method reveals age-dependent changes and aquaporin-4
Area of Science:
- Neuroimaging
- Biophysics
- Physiology
Background:
- Cerebrospinal fluid (CSF) dynamics are crucial for brain health.
- Quantifying water exchange between CSF and brain tissues is challenging.
- Age-related changes in brain physiology may affect CSF dynamics.
Purpose of the Study:
- To develop and validate a non-invasive Magnetization Transfer Indirect Spin Labeling (MISL) MRI technique.
- To quantify water exchange between CSF and brain tissues using MISL.
- To investigate the age-dependence of CSF-tissue water exchange.
Main Methods:
- Implementation of pulsed and continuous MISL MRI sequences.
- Acquisition of labeled and control MRI scans for signal difference (ΔZ) calculation.
- Validation in wild-type (WT) and aquaporin-4 knockout (AQP4-/-) mice, comparing young and adult groups.
Main Results:
- Continuous MISL demonstrated highest signal in the fourth ventricle (13.5% ± 1.4%).
- Adult mice showed significantly reduced ΔZ values (9.3%-18.7% decrease) compared to young mice.
- AQP4-/- mice exhibited non-significant trends towards lower ΔZ values compared to WT mice.
Conclusions:
- The MISL MRI technique is effective for quantifying CSF-tissue water exchange.
- Water exchange between CSF and brain tissues exhibits age-dependent alterations.
- MISL MRI holds significant potential for studying brain water dynamics in vivo.
