Convective Drug Transport in the Spinal Cord

脊髓中的对流药物转运

• 批准号: 7093671
• 负责人: Malisa Sarntinoranont
• 金额: $ 15.15万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7093671
• 关键词: birth; diffusion; fluid; interstitial; model; spinal cord; tissues

DESCRIPTION (provided by applicant): With the development of promising therapeutic agents for chronic pain, spinal injury, and other neurodegenerative diseases, local drug delivery methods are increasingly being considered as a solution to overcoming transport barriers encountered by macromolecular, slow-diffusing drugs. Intelligent design of regional therapy will require new tools to evaluate drug transport issues specific to nervous tissue physiology. Recently, the PI has presented a method for predicting the local tissue distribution of an injected macromolecule in the spinal cord. Medical image-based computational models are created to determine interstitial (extracellular) fluid flow and convective and diffusive transport in white and gray matter regions. Further research is warranted to develop this approach for intraneural infusion and convective transport at nerve entry into the spinal cord. The PI plans to implement a novel application of diffusion weighted imaging (DWI) technology which will use the effective water diffusion tensor to predict preferential interstitial transport directions along white matter tracts. Computational fluid dynamic (CFD) models will integrate DWI data with porous media transport analysis to create 3D models of direct nerve infusion into spinal cord tissue targeted as an alternative, less invasive delivery site. Concurrently, a pressure sensor system will be developed to measure interstitial fluid pressure gradients and characterize hydraulic conductivity. The relationship between transport properties and infusion mechanics will be validated and further improved by fitting predicted distributions to macromolecular tracer data obtained in rat spinal cord studies. Successful physiologically-based drug delivery models can be used for feasibility studies and improved drug protocols. Ultimately, image-based drug transport modeling provides the first step toward computer-aided chemical surgery and patient-specific therapeutic treatment. This will enable customized medical care for patients that inherently factors in physiological differences due to age, gender, and/or disease progression.

描述（由申请人提供）：随着有望用于慢性疼痛，脊柱损伤和其他神经退行性疾病的有希望的治疗剂，越来越多地将局部药物输送方法视为克服大分子分子慢速，缓慢降低药物遇到的运输障碍的解决方案。区域治疗的智能设计将需要新工具来评估特定于神经组织生理学的药物运输问题。最近，PI提出了一种预测脊髓中注射大分子的局部组织分布的方法。创建基于医学图像的计算模型是为了确定白色和灰质区域中的间隙（细胞外）流体流动以及对流和扩散运输。有必要进一步研究在神经进入脊髓时开发这种方法，以进行内部输注和对流运输。 PI计划实施扩散加权成像（DWI）技术的新应用，该技术将使用有效的水扩散张量来预测沿白质区域的优先间隙运输方向。计算流体动力学（CFD）模型将将DWI数据与多孔介质传输分析整合在一起，以创建直接神经输注的3D模型，该模型以替代性，侵入性较低的递送位点为目标。同时，将开发一个压力传感器系统来测量间隙流体压力梯度并表征液压电导率。通过将预测的分布拟合到大鼠脊髓研究中获得的大分子示踪剂数据，将验证运输特性与输注力学之间的关系。成功基于生理的药物输送模型可用于可行性研究和改善药物方案。最终，基于图像的药物运输建模为计算机辅助化学手术和患者特异性治疗提供了第一步。这将为患者提供定制的医疗护理，这些患者固有地因年龄，性别和/或疾病进展而引起的生理差异。