Prediction of convection-enhanced drug delivery to the human brain
Prediction of convection-enhanced drug delivery to the human brain
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DOI：
10.1016/j.jtbi.2007.09.009
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发表时间：
2008-01-07
影响因子：
2
通讯作者：
Zhang, Libin
中科院分区：
文献类型：
--
作者：
Linninger, Andreas A.;Somayaji, Mahadevabharath R.;Zhang, Libin
中枢神经系统（CNS）的许多神经退行性疾病的治疗涉及向大脑递送大分子量药物。然而，血脑屏障阻止许多治疗分子进入CNS。尽管在动物模型中研究药物分散方面做了很多努力，但在人体中准确的药物靶向仍然是一个挑战。本文提出了全工程方法的系统设计，靶向药物输送到人脑。所提出的方法预测可实现的治疗剂的分布体积的基础上的第一原则运输和化学动力学模型，以及准确的重建从患者特定的扩散张量磁共振成像的脑几何形状。该方法的预测能力将被证明为侵入性脑实质内给药。一个系统的程序，以确定最佳的输注和导管设计参数，以最大限度地提高渗透深度和体积的分布在目标区域将进行讨论。计算结果与琼脂糖凝胶体模实验进行了验证。该方法集成了医学成像和工程的跨学科专业知识。这种方法将允许医生和科学家以系统的方式设计和优化药物管理。(C)2007爱思唯尔有限公司保留所有权利。
The treatment for many neurodegenerative diseases of the central nervous system (CNS) involves the delivery of large molecular weight drugs to the brain. The blood brain barrier, however, prevents many therapeutic molecules from entering the CNS. Despite much effort in studying drug dispersion with animal models, accurate drug targeting in humans remains a challenge. This article proposes all engineering approach for the systematic design of targeted drug delivery into the human brain. The proposed method predicts achievable volumes of distribution for therapeutic agents based on first principles transport and chemical kinetics models as well as accurate reconstruction of the brain geometry from patient-specific diffusion tensor magnetic resonance imaging. The predictive capabilities of the methodology will be demonstrated for invasive intraparenchymal drug administration. A systematic procedure to determine the optimal infusion and catheter design parameters to maximize penetration depth and volumes of distribution in the target area will be discussed. The computational results are validated with agarose gel phantom experiments. The methodology integrates interdisciplinary expertise from medical imaging and engineering. This approach will allow physicians and scientists to design and optimize drug administration in a systematic fashion. (C) 2007 Elsevier Ltd. All rights reserved.