Sarntinoranont Malisa, Banerjee Rupak K, Lonser Russell R, Morrison Paul F
Division of Bioengineering and Physical Science ORS, National Institutes of Health, Bethesda, MD 20892, USA.
Ann Biomed Eng. 2003 Apr;31(4):448-61. doi: 10.1114/1.1558032.
Convection-enhanced interstitial infusion can deliver macromolecular drugs to large tissue volumes of the central nervous system. To characterize infusion into the spinal cord, an image-based three-dimensional finite element model of the rat spinal cord was developed. The model incorporated convection and diffusion through white and gray matter, including anisotropic transport due to alignment of white matter tracts. Spatial and temporal distribution of the marker substance albumin within the interstitial space was determined. Consistent with previous experiments, predicted distribution was highly anisotropic. Infusing into the dorsal column, albumin was primarily confined to, white matter with limited penetration into adjacent gray matter. Distribution was determined primarily by the ratio of fiber-parallel to fiber-perpendicular hydraulic conductivity tensor components (k(wm-z)/k(wm-x)), the ratio of transverse white and gray matter hydraulic conductivity (k(wm-x)/k(gm)), and tissue porosity. Fits to previous experimental measures of axial and transverse spread, distribution volume, and protein recovery yielded an optimum k(wm-z)/k(wm-x) of approximately 20 at 0.1 microl/min. k(wm-x)/k(gm) of 100 was sufficient to match experimental transverse distribution data. Best fits to data at 0.1 microl/min were achieved by porosities characteristic of moderate edema (e.g., 0.26). Distribution also varied with catheter placement with more medial placement resulting in greater distribution volumes.
对流增强型间质输注可将大分子药物输送至中枢神经系统的大组织区域。为了描述向脊髓的输注情况，构建了基于图像的大鼠脊髓三维有限元模型。该模型纳入了通过白质和灰质的对流与扩散，包括由于白质束排列导致的各向异性传输。确定了标记物质白蛋白在间质空间内的时空分布。与先前的实验一致，预测的分布具有高度各向异性。向背柱输注时，白蛋白主要局限于白质，对相邻灰质的渗透有限。分布主要由纤维平行方向与纤维垂直方向水力传导率张量分量的比值（k(wm-z)/k(wm-x)）、横向白质与灰质水力传导率的比值（k(wm-x)/k(gm)）以及组织孔隙率决定。与先前关于轴向和横向扩散、分布体积以及蛋白质回收率的实验测量结果拟合，得出在0.1微升/分钟时k(wm-z)/k(wm-x)的最佳值约为20。k(wm-x)/k(gm)为100足以匹配实验横向分布数据。以中度水肿的孔隙率特征（例如0.26）可实现与0.1微升/分钟数据的最佳拟合。分布也随导管位置而变化，更偏向内侧放置会导致更大的分布体积。
