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Development of Patient-Specific Mathematical Models for the Transport of Solute Molecules in the Cerebrospinal Fluid (CSF) Along the Spinal Canal

开发针对脑脊液 (CSF) 中溶质分子沿椎管运输的患者特定数学模型

基本信息

批准号：
10680419
负责人：
Antonio Luis Sanchez
金额：
$ 46.92万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-08-31
项目状态：
未结题

项目摘要

Development of patient-specific mathematical models for the transport of solute molecules in the cerebrospinal fluid (CSF) along the spinal canal PROJECT SUMMARY / ABSTRACT The cerebrospinal fluid (CSF) is predominantly secreted from the blood plasma and continuously bathes and circulates around the external surfaces of the brain and spinal cord. It maintains the electrolytic balance of the central nervous system (CNS), and serves as a medium for the supply of nutrients to neuronal and glial cells and the removal of waste products of cellular metabolism. It also transports hormones, neurotransmitters, and other neuropeptides throughout the CNS. The deregulation of the CSF circulation may compromise the transport of these solutes and the normal physiologic functions of the CNS contributing to the development of some cognitive and neurological diseases. CSF also provides a conduit for the delivery of potent analgesics and chemotherapy to the CNS, a drug delivery procedure often referred to as intrathecal or intraspinal drug delivery (ITDD). To date, there is no comprehensive methodology capable of predicting the patient-specific, long-term, motion of the CSF and the transport of solute molecules along the spinal canal. Thus, the main objective of this proposal is to develop a comprehensive modeling methodology capable of predicting the long-term transport of solute molecules along the spinal canal in each patient-specific anatomy and physiological conditions. The modeling approach combines the use of two time-scales asymptotic analysis of the Eulerian velocity field of the CSF in the spinal canal with in-vitro experimentation and detailed in-vivo validation with patient-specific radiological measurements. The proposed methodology is valid for a wide range of molecular diffusivities and accounts for convective effects of the CSF, including “shear-enhanced diffusion”, “steady-streaming”, and “Stokes drift”, to determine the long-time Lagrangian transport of the solute in the subarachnoid space (SAS) of the spinal canal. The expected outcomes of the proposed research are twofold: 1) it will provide a detailed understanding of the mechanisms regulating the transport of all important molecules key to the functioning of the CNS and 2) it will also provide the methodology necessary to optimize ITDD protocols.

患者特有的溶质分子输运数学模型的研究进展沿椎管的脑脊液(CSF) 项目摘要/摘要脑脊液(CSF)主要从血浆中分泌，并持续地沐浴和在大脑和脊髓的外表面循环。它维持着体内的电解质平衡。中枢神经系统(CNS)，作为向神经元和神经胶质细胞供应营养物质的介质清除细胞新陈代谢的废物。它还运输荷尔蒙、神经递质和其他中枢神经系统中的神经肽。放松对脑脊液循环的管制可能会损害这些物质的运输溶质和中枢神经的正常生理功能有助于某些认知功能的发展和神经系统疾病。脑脊液还提供了一条管道，将有效的止痛药和化疗输送到中枢神经系统，一种通常被称为鞘内或椎管内给药(ITDD)的给药程序。到目前为止，有没有一种全面的方法能够预测患者特有的、长期的脑脊液和脑脊液运动溶质分子沿椎管的运输。因此，这项提案的主要目标是制定一项能够预测溶质分子沿河流长期运移的综合模拟方法椎管内有每个患者特定的解剖和生理条件。该建模方法结合了双时间尺度渐近分析椎管内脑脊液的欧拉速度场实验和详细的体内验证与患者特定的放射测量。建议数方法学对大范围的分子扩散是有效的，并考虑了CSF的对流效应，包括“剪切增强扩散”、“定常流动”和“斯托克斯漂移”，以确定长时间拉格朗日量溶质在椎管的蛛网膜下腔(SAS)的运输。拟议方案的预期结果研究有两个方面：1)它将提供对所有对中枢神经系统功能至关重要的重要分子和2)它还将提供必要的方法学优化ITDD协议。