DRUG TRANSPORT IN BRAIN

该项目关注的是表征和改进交付 药物和诊断剂的剂量。 先前 发展了基于多孔介质中流动的微输注理论， 微血管运输和脑代谢被用来预测大 组织的渗透和相对均匀的剂量， 大分子的微量输注。 我们确认了 猫脑中白色物质的大分子渗透， 放射自显影，以及平坦的浓度曲线和预期 在老鼠的灰质中传播 我们进行了SPECT研究， 灵长类动物和幻影，从而证明了这种技术的能力， 监测输送并表征组织扩散、清除和效应 对血流的影响 调用模型计算来筛选 可用造影剂（碘帕醇和Gd-DTPA-白蛋白）跟踪 大分子药物在正常和肿瘤脑中的作用。 基于多孔 介质流动和变形理论，回流的数学模型， 沿着导管轴的输注物被开发为流速的函数， 导管直径和组织参数。 这包括发展 一个新的无量纲标量，用于选择最佳的 导管直径和流速组合。 为了确定最佳 帕金森病的兴奋性毒素苍白球毁损术的输注参数， 我们还开发了一个数学模型， 小的灰质核。

This project is concerned with characterizing and improving the delivery of pharmacologic and diagnostic agents to the brain. A previously developed theory of microinfusion based on flow in porous media, microvascular transport, and brain metabolism was used to predict large penetration and relatively even dosing of tissue for high-flow microinfusion of macromolecules. We confirmed multi-centimeter macromolecular penetration of white matter in the cat brain via autoradiography, as well as flat concentration profiles and expected spread in the gray matter of rats. We performed a SPECT study in primates and phantoms, thus demonstrating this technique's ability to monitor delivery and characterize tissue spread, clearance, and effects on blood flow. Model computations were invoked to screen the ability of available contrast agents (iopamidol and Gd-DTPA-albumin) to track macromolecular agents in normal and tumorous brain. Based on porous media flow and deformation theory, a mathematical model of backflow of infusate along catheter shafts was developed as a function of flow rate, catheter diameter, and tissue parameters. This included the development of a new nondimensional scalar that is useful for selecting optimal catheter diameter and flow-rate combinations. To ascertain optimal infusion parameters for excitotoxin pallidotomy of Parkinson's disease, we also developed a mathematical model of quinolinic acid infusion into small gray matter nuclei.