Department of Neurology, Henry Ford Health System, Detroit, MI, USA; Department of Radiology, Henry Ford Health System, Detroit, MI, USA.
Department of Neurology, Henry Ford Health System, Detroit, MI, USA.
Neuroimage. 2019 Mar;188:616-627. doi: 10.1016/j.neuroimage.2018.12.039. Epub 2018 Dec 19.
The glymphatic system is functional waste clearance path from the brain parenchyma through dynamic exchange of cerebrospinal fluid (CSF) with interstitial fluid (ISF). Impairment of glymphatic waste clearance is involved in the development of neurodegenerative conditions. Despite many recent studies investigating the glymphatic system, few studies have tried to use a mathematical model to describe this system, quantitatively. In this study, we aim to model the glymphatic system from the kinetics of Gd-DTPA tracer measured using MRI in order to: 1) map the glymphatic system path, 2) derive kinetic parameters of the glymphatic system, and 3) provide quantitative maps of the structure and function of this system. In the proposed model, the brain is clustered to similar regions with respect to the profile of contrast agent (CA) density measured by MRI. Then, each region is described as a two-compartment kinetic model 'derived from' or 'clears to' its neighbors with local input function. We thus fit our model to the local cerebral regions rather than to the averaged time signal curve (TSC) of the whole brain. The estimated parameters showed distinctive differences between diabetes mellitus (DM) and control rats. The results suggest that in a typical DM brain the CSF bulk speed in the para-vasculature network is low. In addition, the resulting maps indicate that there may be increased binding and decreased absorbing of large molecules in a diabetic compared with a non-diabetic brain. The important contribution of this work was to fit the model to the local regions rather than to the averaged time signal curve (TSC) of the whole brain. This enabled us to derive quantitative maps of the glymphatic system from MRI.
脑淋巴系统是大脑实质通过脑脊液（CSF）与细胞间液（ISF）的动态交换来实现废物清除的功能途径。脑淋巴清除功能障碍与神经退行性疾病的发展有关。尽管最近有许多研究探讨了脑淋巴系统，但很少有研究试图使用数学模型来对其进行定量描述。在这项研究中，我们旨在通过 MRI 测量的 Gd-DTPA 示踪剂的动力学来模拟脑淋巴系统，以：1）描绘脑淋巴系统路径，2）得出脑淋巴系统的动力学参数，3）提供该系统结构和功能的定量图谱。在提出的模型中，大脑根据 MRI 测量的对比剂（CA）密度分布聚类为类似的区域。然后，每个区域都被描述为一个两室动力学模型，该模型是“源自”或“清除”其邻居的局部输入函数。因此，我们将模型拟合到局部脑区，而不是整个大脑的平均时间信号曲线（TSC）。估计的参数在糖尿病（DM）和对照大鼠之间显示出明显的差异。结果表明，在典型的 DM 大脑中，脑脊液在血管周围网络中的整体速度较低。此外，所得图谱表明，与非糖尿病大脑相比，糖尿病大脑中可能会增加大分子的结合和减少吸收。这项工作的一个重要贡献是将模型拟合到局部区域，而不是整个大脑的平均时间信号曲线（TSC）。这使我们能够从 MRI 得出脑淋巴系统的定量图谱。
