Quantitative analysis of macroscopic solute transport in the murine brain

Abstract

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 (Deff), a transport parameter combining all mechanisms of transport, that best represent the experimental data are determined and compared to apparent diffusivity (Dapp), 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, Deff for gadoteridol (550 Da) was over 10,000 times greater than Dapp. In the brain tissue, constituting interstitial space and the perivascular space of smaller blood vessels, Deff was 10–25 times greater than Dapp. 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.