CNS wide simulation of flow resistance and drug transport due to spinal microanatomy
CNS wide simulation of flow resistance and drug transport due to spinal microanatomy
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DOI：
10.1016/j.jbiomech.2015.02.018
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发表时间：
2015-07-16
影响因子：
2.4
通讯作者：
Linninger, Andreas A.
中科院分区：
文献类型：
--
作者：
Tangen, Kevin M.;Hsu, Ying;Linninger, Andreas A.
已知脊髓微结构会显著影响脑脊液模式，但其对流动阻力的实际影响尚未量化。由于显微解剖方面的长度尺度低于医学图像分辨率，因此难以通过实验观察它们对流动的影响。使用计算流体力学的方法，我们能够量化的脑脊液（CSF）的流动模式和流动阻力在整个中枢神经系统（CNS）的微观解剖方面的贡献。根据人类成像数据重建了颅骨和脊髓CSF填充隔室;人工添加低于图像检测阈值的显微小梁。神经根和小梁被发现诱导微循环的区域，其位置，大小和涡度沿着脊柱的特点。我们的CFD模拟基于在正常人类受试者中使用电影相位对比MRI获得的体积流速，表明主要由于蛛网膜小梁导致压降增加2-2.5倍。还计算了脑脊液压力和速度波沿椎管沿着的时间和相位滞后，并创建了编码CSF体积流速和压力的完整时空图。通过微解剖诱导的涡流周围的脉动流，嘴侧药物分散的速度急剧加快。探索在超级计算机上的大规模并行化，证明了计算药物转运研究的可行性。CNS范围内的鞘内给药模拟可以成为计算机设计，物种间缩放和优化实验药物试验的实用工具。(C)2015爱思唯尔有限公司版权所有。
Spinal microstructures are known to substantially affect cerebrospinal fluid patterns, yet their actual impact on flow resistance has not been quantified. Because the length scale of microanatomical aspects is below medical image resolution, their effect on flow is difficult to observe experimentally. Using a computational fluid mechanics approach, we were able to quantify the contribution of micro-anatomical aspects on cerebrospinal fluid (CSF) flow patterns and flow resistance within the entire central nervous system (CNS). Cranial and spinal CSF filled compartments were reconstructed from human imaging data; microscopic trabeculae below the image detection threshold were added artificially. Nerve roots and trabeculae were found to induce regions of microcirculation, whose location, size and vorticity along the spine were characterized. Our CFD simulations based on volumetric flow rates acquired with Cine Phase Contrast MRI in a normal human subject suggest a 2-2.5 fold increase in pressure drop mainly due to arachnoid trabeculae. The timing and phase lag of the CSF pressure and velocity waves along the spinal canal were also computed, and a complete spatio-temporal map encoding CSF volumetric flow rates and pressure was created.Micro-anatomy induced fluid patterns were found responsible for the rapid caudo-cranial spread of an intrathecally administered drug. The speed of rostral drug dispersion is drastically accelerated through pulsatile flow around microanatomy induced vortices. Exploring massive parallelization on a supercomputer, the feasibility of computational drug transport studies was demonstrated. CNS-wide simulations of intrathecal drugs administration can become a practical tool for in silico design, interspecies scaling and optimization of experimental drug trials. (C) 2015 Elsevier Ltd. All rights reserved.