Institute for Computational and Mathematical Engineering (ICME), Center for Turbulence Research, Stanford University, Stanford, CA, 94305-3024, USA.
Scientific IT & Application Support (SCITAS), Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Fluids Barriers CNS. 2024 Feb 28;21(1):20. doi: 10.1186/s12987-024-00518-8.
Impaired cerebrospinal fluid (CSF) dynamics is involved in the pathophysiology of neurodegenerative diseases of the central nervous system and the optic nerve (ON), including Alzheimer's and Parkinson's disease, as well as frontotemporal dementia. The smallness and intricate architecture of the optic nerve subarachnoid space (ONSAS) hamper accurate measurements of CSF dynamics in this space, and effects of geometrical changes due to pathophysiological processes remain unclear. The aim of this study is to investigate CSF dynamics and its response to structural alterations of the ONSAS, from first principles, with supercomputers.
Large-scale in-silico investigations were performed by means of computational fluid dynamics (CFD) analysis. High-order direct numerical simulations (DNS) have been carried out on ONSAS geometry at a resolution of 1.625 μm/pixel. Morphological changes on the ONSAS microstructure have been examined in relation to CSF pressure gradient (CSFPG) and wall strain rate, a quantitative proxy for mass transfer of solutes.
A physiological flow speed of 0.5 mm/s is achieved by imposing a hydrostatic pressure gradient of 0.37-0.67 Pa/mm across the ONSAS structure. At constant volumetric rate, the relationship between pressure gradient and CSF-accessible volume is well captured by an exponential curve. The ONSAS microstructure exhibits superior mass transfer compared to other geometrical shapes considered. An ONSAS featuring no microstructure displays a threefold smaller surface area, and a 17-fold decrease in mass transfer rate. Moreover, ONSAS trabeculae seem key players in mass transfer.
The present analysis suggests that a pressure drop of 0.1-0.2 mmHg over 4 cm is sufficient to steadily drive CSF through the entire subarachnoid space. Despite low hydraulic resistance, great heterogeneity in flow speeds puts certain areas of the ONSAS at risk of stagnation. Alterations of the ONSAS architecture aimed at mimicking pathological conditions highlight direct relationships between CSF volume and drainage capability. Compared to the morphological manipulations considered herein, the original ONSAS architecture seems optimized towards providing maximum mass transfer across a wide range of pressure gradients and volumetric rates, with emphasis on trabecular structures. This might shed light on pathophysiological processes leading to damage associated with insufficient CSF flow in patients with optic nerve compartment syndrome.
脑脊液（CSF）动力学的障碍与中枢神经系统和视神经（ON）的神经退行性疾病的病理生理学有关，包括阿尔茨海默病和帕金森病以及额颞叶痴呆。视神经蛛网膜下腔（ONSAS）的微小和复杂结构阻碍了对该空间内 CSF 动力学的准确测量，并且由于病理生理过程引起的几何变化的影响尚不清楚。本研究的目的是从第一性原理出发，利用超级计算机研究 CSF 动力学及其对 ONSAS 结构变化的响应。
通过计算流体动力学（CFD）分析进行了大规模的计算机模拟。在 1.625μm/pixel 的分辨率下对 ONSAS 几何形状进行了高阶直接数值模拟（DNS）。研究了 CSF 压力梯度（CSFPG）和壁应变速率与 ONSAS 微观结构形态变化之间的关系，壁应变速率是溶质质量传递的定量代理。
通过在 ONSAS 结构上施加 0.37-0.67 Pa/mm 的静压梯度，实现了 0.5mm/s 的生理流速。在恒定容积速率下，压力梯度与 CSF 可及体积之间的关系由指数曲线很好地捕获。与所考虑的其他几何形状相比，ONSAS 微观结构表现出优异的质量传递性能。没有微观结构的 ONSAS 显示出的表面积小三倍，质量传递速率低 17 倍。此外，ONSAS 小梁似乎是质量传递的关键因素。
本分析表明，在 4cm 上产生 0.1-0.2mmHg 的压降足以稳定地将 CSF 驱动通过整个蛛网膜下腔。尽管水力阻力低，但流速的高度异质性使 ONSAS 的某些区域有停滞的风险。旨在模拟病理条件的 ONSAS 结构的改变突出了 CSF 体积与排水能力之间的直接关系。与本文考虑的形态操作相比，原始的 ONSAS 结构似乎针对在广泛的压力梯度和容积速率范围内提供最大的质量传递进行了优化，重点是小梁结构。这可能有助于阐明与视神经间隙综合征患者 CSF 流量不足相关的损伤的病理生理过程。
Zotero 插件
