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

• 批准号: 10470825
• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10470825
• 关键词: Acid-Base Equilibrium; Affect; Analgesics; Anatomy; Bathing; Blood Circulation; Brain; Cerebrospinal Fluid; Characteristics; Clinical; Cognition Disorders; Convection; Development; Diffuse; Diffusion; Drug Delivery Systems; Drug Kinetics; Drug Transport; Electrolyte Balance; Excision; Formulation; Heart; Hormones; In Vitro; Injections; Intracranial Pressure; Investigation; Light; Liquid substance; Location; Lymphatic System; Malignant neoplasm of central nervous system; Measurement; Metabolism; Methodology; Modeling; Molecular; Motion; Neuraxis; Neuroglia; Neurons; Neuropeptides; Neurotransmitters; Nutrient; Outcome; Pathology; Patients; Pharmaceutical Preparations; Physiological; Plasma; Positioning Attribute; Posture; Procedures; Protocol Compliance; Protocols documentation; Radiology Specialty; Research; Rotation; Spinal; Spinal Canal; Spinal Cord; Stream; Subarachnoid Space; Surface; Time; Validation; Variant; Waste Products; bulk motion; cerebrospinal fluid flow; chemotherapy; chronic pain; density; experience; in vivo; mathematical model; multidisciplinary; nervous system disorder; neurotransmitter release; novel; particle; patient response; release factor; respiratory; solute

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.

开发患者特定的溶质分子在体内运输的数学模型 沿椎管的脑脊液 (CSF) 项目概要/摘要 脑脊液（CSF）主要由血浆分泌，并持续沐浴和 围绕大脑和脊髓的外表面循环。它维持电解平衡 中枢神经系统（CNS），作为向神经元和神经胶质细胞供应营养的媒介 清除细胞新陈代谢的废物。它还运输激素、神经递质和其他 神经肽遍布中枢神经系统。脑脊液循环的放松管制可能会损害这些物质的运输 中枢神经系统的溶质和正常生理功能有助于某些认知和功能的发展 神经系统疾病。 CSF 还提供了向患者输送强效镇痛药和化疗的渠道。 CNS，一种药物输送程序，通常称为鞘内或椎管内药物输送 (ITDD)。迄今为止，有 没有能够预测患者特定的脑脊液和脑脊液的长期运动的综合方法 溶质分子沿椎管的运输。因此，本提案的主要目标是制定一个 能够预测溶质分子沿管道的长期运输的综合建模方法 每个患者的椎管都有特定的解剖结构和生理条件。该建模方法结合了 使用两个时间尺度渐近分析椎管内脑脊液的欧拉速度场 通过患者特定的放射学测量进行实验和详细的体内验证。拟议的 该方法适用于广泛的分子扩散性，并解释了脑脊液的对流效应， 包括“剪切增强扩散”、“稳流”和“斯托克斯漂移”，以确定长时拉格朗日 溶质在椎管蛛网膜下腔 (SAS) 中的运输。拟议的预期成果 研究有双重意义：1）它将提供对调节所有物质运输的机制的详细了解。 对中枢神经系统功能至关重要的重要分子，2）它还将提供必要的方法 优化 ITDD 协议。