Ratner Vadim, Gao Yi, Lee Hedok, Elkin Rena, Nedergaard Maiken, Benveniste Helene, Tannenbaum Allen
Department of Computer Science, Stony Brook University, Stony Brook, NY 11790, USA.
Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY 11790, USA.
Neuroimage. 2017 May 15;152:530-537. doi: 10.1016/j.neuroimage.2017.03.021. Epub 2017 Mar 18.
The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns. Here we have applied an alternative mathematical analysis approach to a dynamic time series of MRI images acquired every 4min over ∼3h in anesthetized rats, following administration of a small molecular weight paramagnetic tracer into the CSF reservoir of the cisterna magna. We use Optimal Mass Transport (OMT) to model the glymphatic flow vector field, and then analyze the flow to find the network of CSF-ISF flow channels. We use 3D visualization computational tools to visualize the OMT defined network of CSF-ISF flow channels in relation to anatomical and vascular key landmarks from the live rodent brain. The resulting OMT model of the glymphatic transport network agrees largely with the current understanding of the glymphatic transport patterns defined by dynamic contrast-enhanced MRI revealing key CSF transport pathways along the ventral surface of the brain with a trajectory towards the pineal gland, cerebellum, hypothalamus and olfactory bulb. In addition, the OMT analysis also revealed some interesting previously unnoticed behaviors regarding CSF transport involving parenchymal streamlines moving from ventral reservoirs towards the surface of the brain, olfactory bulb and large central veins.
类淋巴途径是一个促进脑脊液（CSF）和组织间液（ISF）持续交换的系统，在清除啮齿动物大脑中的废物方面发挥着关键作用。类淋巴途径功能障碍可能与阿尔茨海默病的病理生理学有关。有趣的是，类淋巴系统在深波睡眠全身麻醉期间最为活跃。通过将顺磁性示踪剂注入啮齿动物的脑脊液中，我们之前展示了MRI在描绘类淋巴运输的宏观全脑视图方面的效用，但我们尚未定义和可视化具体的流动模式。在此，我们应用了一种替代的数学分析方法，对在麻醉大鼠中，于延髓池的脑脊液储库中注入小分子量顺磁性示踪剂后，在约3小时内每隔4分钟采集一次的MRI图像动态时间序列进行分析。我们使用最优质量传输（OMT）对类淋巴流矢量场进行建模，然后分析流动以找到脑脊液 - 组织间液流动通道网络。我们使用三维可视化计算工具来可视化由OMT定义的脑脊液 - 组织间液流动通道网络与活体啮齿动物大脑的解剖和血管关键标志的关系。所得的类淋巴运输网络的OMT模型在很大程度上与目前对由动态对比增强MRI定义的类淋巴运输模式的理解一致，揭示了沿脑腹侧表面朝向松果体、小脑、下丘脑和嗅球的关键脑脊液运输途径。此外，OMT分析还揭示了一些关于脑脊液运输的有趣的、以前未被注意到的行为，包括实质流线从腹侧储库向脑表面、嗅球和大的中央静脉移动。
