Focal delivery during direct infusion to brain: role of flow rate, catheter diameter, and tissue mechanics
Focal delivery during direct infusion to brain: role of flow rate, catheter diameter, and tissue mechanics
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DOI：
10.1152/ajpregu.1999.277.4.r1218
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发表时间：
1999-10-01
影响因子：
2.8
通讯作者：
Oldfield, EH
中科院分区：
文献类型：
--
作者：
Morrison, PF;Chen, MY;Oldfield, EH
直接间质输注是一种能够在小尺寸和大尺寸的脑组织上递送药剂的技术。然而，在足够高的体积流入速率下，可能发生沿着导管轴的回流并损害输送。根据基于斯托克斯流、多孔介质中的达西流和脑组织的弹性变形的数学模型，确定了纯灰质中沿该导管的有限回流距离沿着的比例关系（x（m））：x（m）=常数Q（o）（3）R（4）r（c）（4）G（-3）mu（-1）（Q（o）=体积流入速率，R =组织液压阻力，r（c）=导管半径，G =剪切模量，mu =粘度）。这意味着通过使用小直径导管可以最大限度地减少回流，并且可以通过用导管半径的类似减小来抵消流速的增加来维持固定（最小）回流距离。一般来说，回流是避免在大鼠灰质与32号导管低于0.5 μ l/min。扩展的比例关系，包括大脑大小的阻力项导致的发现，绝对回流距离获得与一个给定的导管和流入率是微弱的影响导管尖端位置的深度，因此，大脑的大小。最后，模型的扩展描述了导管在终止于灰色之前通过白色物质层的情况，这已被证明可以解释在一定体积流入率范围内向大鼠纹状体输注4 μ l化合物后胼胝体中观察到的白蛋白百分比。
Direct interstitial infusion is a technique capable of delivering agents over both small and large dimensions of brain tissue. However, at a sufficiently high volumetric inflow rate, backflow along the catheter shaft may occur and compromise delivery. A scaling relationship for the finite backflow distance along this catheter in pure gray matter (x(m)) has been determined from a mathematical model based on Stokes flow, Darcy flow in porous media, and elastic deformation of the brain tissue: x(m) = constant Q(o)(3)R(4)r(c)(4)G(-3)mu(-1) (Q(o) = volumetric inflow rate, R = tissue hydraulic resistance, r(c) = catheter radius, G = shear modulus, and mu = viscosity). This implies that backflow is minimized by the use of small diameter catheters and that a fixed (minimal) backflow distance may be maintained by offsetting an increase in flow rate with a similar decrease in catheter radius. Generally, backflow is avoided in rat gray matter with a 32-gauge catheter operating below 0.5 mu l/min. An extension of the scaling relationship to include brain size in the resistance term leads to the finding that absolute backflow distance obtained with a given catheter and inflow rate is weakly affected by the depth of catheter tip placement and, thus, brain size. Finally, an extension of the model to describe catheter passage through a white matter layer before terminating in the gray has been shown to account for observed percentages of albumin in the col pus callosum after a 4-mu l infusion of the compound to rat striatum over a range of volumetric inflow rates.