Quantitative analysis of macroscopic solute transport in the murine brain
Autor: | Martin M. Pike, Lori Ray, Matthew J. Simon, Jeffrey J. Iliff, Jeffrey J. Heys |
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Rok vydání: | 2021 |
Předmět: |
Male
Perivascular transport Brain transport Interstitial transport Convection Biotransport Mice Cellular and Molecular Neuroscience Murine brain Glymphatic Developmental Neuroscience Animals RC346-429 Chemistry Research Brain Biological Transport General Medicine Models Theoretical Magnetic Resonance Imaging Mice Inbred C57BL Dynamic contrast-enhanced MRI Neurology Biophysics Female Neurology. Diseases of the nervous system Quantitative analysis (chemistry) Glymphatic System |
Zdroj: | Fluids and Barriers of the CNS, Vol 18, Iss 1, Pp 1-19 (2021) Fluids and Barriers of the CNS |
ISSN: | 2045-8118 |
Popis: | Background Understanding molecular transport in the brain is critical to care and prevention of neurological disease and injury. A key question is whether transport occurs primarily by diffusion, or also by convection or dispersion. Dynamic contrast-enhanced (DCE-MRI) experiments have long reported solute transport in the brain that appears to be faster than diffusion alone, but this transport rate has not been quantified to a physically relevant value that can be compared to known diffusive rates of tracers. Methods In this work, DCE-MRI experimental data is analyzed using subject-specific finite-element models to quantify transport in different anatomical regions across the whole mouse brain. The set of regional effective diffusivities ($$D_{eff}$$ D eff ), a transport parameter combining all mechanisms of transport, that best represent the experimental data are determined and compared to apparent diffusivity ($$D_{app}$$ D app ), the known rate of diffusion through brain tissue, to draw conclusions about dominant transport mechanisms in each region. Results In the perivascular regions of major arteries, $$D_{eff}$$ D eff for gadoteridol (550 Da) was over 10,000 times greater than $$D_{app}$$ D app . In the brain tissue, constituting interstitial space and the perivascular space of smaller blood vessels, $$D_{eff}$$ D eff was 10–25 times greater than $$D_{app}$$ D app . Conclusions The analysis concludes that convection is present throughout the brain. Convection is dominant in the perivascular space of major surface and branching arteries (Pe > 1000) and significant to large molecules (> 1 kDa) in the combined interstitial space and perivascular space of smaller vessels (not resolved by DCE-MRI). Importantly, this work supports perivascular convection along penetrating blood vessels. |
Databáze: | OpenAIRE |
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