Department of Chemical and Biological Engineering, Montana State University, Bozeman, USA.
Advanced Imaging Research Center, Oregon Health and Sciences University, Portland, USA.
Fluids Barriers CNS. 2021 Dec 7;18(1):55. doi: 10.1186/s12987-021-00290-z.
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.
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 ([Formula: see text]), a transport parameter combining all mechanisms of transport, that best represent the experimental data are determined and compared to apparent diffusivity ([Formula: see text]), the known rate of diffusion through brain tissue, to draw conclusions about dominant transport mechanisms in each region.
In the perivascular regions of major arteries, [Formula: see text] for gadoteridol (550 Da) was over 10,000 times greater than [Formula: see text]. In the brain tissue, constituting interstitial space and the perivascular space of smaller blood vessels, [Formula: see text] was 10-25 times greater than [Formula: see text].
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.
了解大脑中的分子转运对于神经疾病和损伤的护理和预防至关重要。一个关键问题是转运是否主要通过扩散发生，还是也通过对流或弥散发生。动态对比增强（DCE-MRI）实验长期以来报告了大脑中的溶质转运，其速度似乎比单独的扩散快，但这种转运速率尚未量化为可与已知示踪剂扩散速率相比较的物理相关值。
在这项工作中，使用基于个体的有限元模型对 DCE-MRI 实验数据进行分析，以量化整个小鼠大脑不同解剖区域的转运。确定了一组区域有效扩散率（[Formula: see text]），这是一个结合了所有转运机制的转运参数，该参数最能代表实验数据，并与表观扩散率（[Formula: see text]）进行比较，即已知的脑组织扩散速率，以得出关于每个区域主要转运机制的结论。
在主要动脉的血管周围区域，对于钆喷酸葡胺（550 Da），[Formula: see text]比[Formula: see text]大 10,000 多倍。在脑组织中，构成间质空间和较小血管的血管周围空间，[Formula: see text]比[Formula: see text]大 10-25 倍。
分析得出结论，对流存在于整个大脑中。对流在主要表面和分支动脉的血管周围空间占主导地位（Pe>1000），并且对于较小血管的间质空间和血管周围空间中的大分子量物质（未通过 DCE-MRI 解决）很重要。重要的是，这项工作支持了沿穿透血管的血管周围对流。
