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In Vivo Imaging of Cerebrospinal Fluid Transport through the Intact Mouse Skull using Fluorescence Macroscopy
Published on: July 29, 2019
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Apparent diffusion coefficient estimates based on 24 hours tracer movement support glymphatic transport in human
Lars Magnus Valnes1, Sebastian K Mitusch2, Geir Ringstad3
1Department of Mathematics, University of Oslo, Oslo, Norway.
Scientific Reports
|June 10, 2020
Summary
The study suggests bulk flow aids brain waste clearance, potentially impacting Alzheimer's disease. MRI findings indicate bulk flow complements diffusion in cerebrospinal fluid transport over days.
Area of Science:
- Neuroscience
- Biophysics
- Medical Imaging
Background:
- The glymphatic system, a proposed brain waste clearance pathway, is debated, with micro-level studies questioning its bulk flow mechanism.
- Macro-level experimental data and novel MRI findings suggest bulk flow plays a role in cerebrospinal fluid (CSF) transport.
- Understanding brain waste clearance is crucial for neurodegenerative diseases like Alzheimer's disease.
Purpose of the Study:
- To investigate if observed CSF tracer distributions over hours and days via MRI support bulk flow as a significant transport mechanism in the brain.
- To quantify the contribution of bulk flow to solute transport in the brain's complex geometry and heterogeneous flow environment.
- To reconcile conflicting evidence regarding the glymphatic system's bulk flow hypothesis.
Main Methods:
- Utilized partial differential constrained optimization to model CSF tracer movement over days.
- Integrated complex brain geometry and heterogeneous CSF flow into the biomechanical model.
- Identified the apparent diffusion coefficient (ADC) that best fits novel magnetic resonance imaging (MRI) findings.
Main Results:
- Computed apparent diffusion coefficients (ADC) in cortical grey matter were 5-26% higher than those estimated using diffusion tensor imaging (DTI).
- The findings indicate that diffusion alone may not fully explain the observed tracer distributions.
- The results support the inclusion of bulk flow as a complementary transport mechanism to diffusion in the brain.
Conclusions:
- The study provides quantitative evidence supporting bulk flow as a significant component of CSF transport in the brain.
- The findings challenge the notion that diffusion is the sole mechanism for solute movement in the brain's interstitial space.
- This research contributes to the ongoing debate on the glymphatic system and its role in brain health and disease, such as Alzheimer's.
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