Computational Transport Models for Convection-Enhanced CNS Delivery

对流增强中枢神经系统输送的计算传输模型

基本信息

批准号：
7693686
负责人：
Malisa Sarntinoranont
金额：
$ 30.25万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-29 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7693686
关键词：
Accounting Adverse effects Affect Agonist Agreement Albumins Amygdaloid structure Anatomy Animals Anisotropy Anticonvulsants Antiepileptic Agents Atrophic Automobile Driving Awareness Bio-Base Biological Models Biological Products Blood - brain barrier anatomy Bolus Infusion Brain Brain region Bypass Calcium Channel Blockers Cannulas Chronic Cicatrix Collaborations Complex Computer Simulation Convection Coupled Cyst Data Data Set Dependence Development Diffusion Diffusion Magnetic Resonance Imaging Disease Disease Progression Drug Transport Epilepsy Experimental Models Extracellular Fluid Extracellular Space Family Fiber Focal Seizure Future GABA-A Receptor Gadolinium Gliosis Goals Health Hippocampus (Brain)Human Image Imaging technology Individual Infusion procedures Injection of therapeutic agent Kindling (Neurology)Knowledge Label Lead Life Liquid substance Location Magnetic Resonance Magnetic Resonance Imaging Malignant Neoplasms Maps Measurement Measures Mechanics Medical Methods Modeling Muscimol N-Type Calcium Channels Nature Needles Nerve Tissue Neurotransmitters Operative Surgical Procedures Parkinson Disease Partial Epilepsies Pathway interactions Patients Pattern Pharmaceutical Preparations Population Primates Property Rattus Recurrence Refractory Research Research Personnel Resistance Resolution Risk Rodent Role Scanning Seizures Signal Transduction Site Slice Structure Swelling System Techniques Technology Temporal Lobe Epilepsy Testing Therapeutic Therapeutic Agents Time Tissues Toxic effect Tracer United States United States National Institutes of Health Validation Variant Water Work base brain tissue effective therapy experience extracellular fluid flow gray matter imaging modality implanted sensor in vivo local drug delivery member nervous system disorder novel strategies novel therapeutic intervention pressure public health relevance research study sensor success tissue fixing tool treatment planning white matter

项目摘要

DESCRIPTION (provided by applicant): Local drug delivery methods, such as convection-enhanced delivery (CED), are being used to circumvent the blood-brain-barrier and to distribute blood-brain-barrier-impermeable therapeutic agents over large selected volumes within the CNS. In this study, our goal is to provide fundamental understanding of CED transport of compounds into the hippocampus for the treatment of temporal lobe epilepsy (TLE). We will use a coupled modeling-and-experimental CED approach to selectively target a large volume of the hippocampus. Studies will concentrate on quantifying extracellular flows and macromolecular tracer distributions under both normal and pathological conditions. Varying delivery sites, infusion rates, and control conditions will be tested. For computations, tissues will be modeled as porous media and will account for realistic anatomical boundaries, fluid-tissue interactions, and anisotropic transport using high resolution and diffusion tensor magnetic resonance imaging technologies. Extracellular transport properties will be measured using pressure sensor systems and microindentation testing. Corresponding in vivo magnetic resonance imaging studies will quantify spatial concentrations following CED in rodent and primate brains (primate studies will be done in collaboration with researchers at the NIH). Such a comprehensive study, to quantify CED transport within the TLE hippocampal system, has not been previously conducted. This study will also provide fundamental tools and techniques to quantify bio- transport and measure in vivo transport by CED. The study will clarify the roles of extracellular flow, tissue anisotropy, pathological changes, tissue swelling, and backflow. MR-based bio-transport tools provide an important step towards patient-specific treatment since they account for anatomical and structural changes with disease. PUBLIC HEALTH RELEVANCE: In this study, our goal is to provide a fundamental understanding of convection enhanced delivery (CED) of compounds into the hippocampus for the treatment of temporal lobe epilepsy. High-resolution magnetic resonance and diffusion tensor imaging measurements in vivo will guide the development of a three- dimensional computational model that will be used to determine the effects of anatomical boundaries, fluid- tissue interactions, and tissue structure on extracellular CED transport.

描述（由申请人提供）：局部药物输送方法，例如对流增强的递送（CED），用于绕过血脑 - 脑屏障，并在CNS内的大型选定体积上分配可侵化的血脑屏障 - 可耐受性治疗剂。在这项研究中，我们的目标是提供对化合物进入海马的CED转运的基本理解，以治疗颞叶癫痫（TLE）。我们将使用耦合的建模和实验性CED方法来选择性地靶向大量海马。研究将集中于在正常和病理条件下量化细胞外流和大分子示踪剂分布。将测试不同的输送地点，输注率和控制条件。对于计算，组织将建模为多孔介质，并使用高分辨率和扩散张量磁共振成像技术来说明逼真的解剖边界，流体组织相互作用以及各向异性转运。细胞外运输特性将使用压力传感器系统和显微标记测试进行测量。相应的体内磁共振成像研究将量化啮齿动物和灵长类动物大脑中CED后的空间浓度（灵长类动物研究将与NIH的研究人员合作进行）。以前没有进行过这样的全面研究，以量化海马系统内的CED运输。这项研究还将提供基本的工具和技术，以量化CED生物运输和测量体内运输的生物运输。该研究将阐明细胞外流动，组织各向异性，病理变化，组织肿胀和背流的作用。基于MR的生物传播工具为患者特定治疗提供了重要的一步，因为它们解释了疾病的解剖学和结构变化。公共卫生相关性：在这项研究中，我们的目标是对对流的增强（CED）的基本了解（CED）进入海马，以治疗颞叶癫痫病。高分辨率的磁共振和体内的扩散张量成像测量将指导三维计算模型的发展，该模型将用于确定解剖学边界，流体组织相互作用以及组织结构对细胞外CED转运的影响。