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:8112016
- 负责人:
- 金额:$ 29.55万
- 依托单位:
- 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:
- 关键词:AccountingAdverse effectsAffectAgonistAgreementAlbuminsAmygdaloid structureAnatomyAnimalsAnisotropyAnticonvulsantsAntiepileptic AgentsAtrophicAutomobile DrivingAwarenessBio-BaseBiological ModelsBiological ProductsBlood - brain barrier anatomyBolus InfusionBrainBrain regionBypassCalcium Channel BlockersCannulasChronicCicatrixCollaborationsComplexComputer SimulationConvectionCoupledCyclophosphamideCystDataData SetDependenceDevelopmentDiffusionDiffusion Magnetic Resonance ImagingDiseaseDisease ProgressionDrug TransportEpilepsyExperimental ModelsExtracellular FluidExtracellular SpaceFamilyFiberFocal SeizureFutureGABA-A ReceptorGadoliniumGliosisGoalsHealthHippocampus (Brain)HumanImageImaging technologyIndividualInfusion proceduresInjection of therapeutic agentKindling (Neurology)KnowledgeLabelLeadLifeLiquid substanceLocationMagnetic ResonanceMagnetic Resonance ImagingMalignant NeoplasmsMapsMeasurementMeasuresMechanicsMedicalMethodsModelingMuscimolN-Type Calcium ChannelsNatureNeedlesNerve TissueNeurotransmittersOperative Surgical ProceduresParkinson DiseasePartial EpilepsiesPathway interactionsPatientsPatternPharmaceutical PreparationsPopulationPrimatesPropertyRattusRecurrenceRefractoryResearchResearch PersonnelResistanceResolutionRiskRodentRoleScanningSeizuresSignal TransductionSiteSliceStructureSwellingSystemTechniquesTechnologyTemporal Lobe EpilepsyTestingTherapeuticTherapeutic AgentsTimeTissuesToxic effectTracerUnited StatesUnited States National Institutes of HealthValidationVariantWaterWorkbasebrain tissueeffective therapyexperienceextracellularfluid flowgadolinium oxidegray matterimaging modalityimplanted sensorin vivolocal drug deliverymembernervous system disordernovel strategiesnovel therapeutic interventionpressureresearch studysensorsuccesstissue fixingtooltreatment planningwhite 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):局部药物递送方法,例如对流增强递送(CED),用于绕过血脑屏障并将血脑屏障不可渗透的治疗剂分配到大范围内的选定体积内。中枢神经系统。 在这项研究中,我们的目标是提供对 CED 将化合物转运至海马体以治疗颞叶癫痫 (TLE) 的基本了解。 我们将使用耦合建模和实验 CED 方法来选择性地针对大量海马体。 研究将集中于量化正常和病理条件下的细胞外流量和大分子示踪剂分布。 将测试不同的递送部位、输注速率和控制条件。 为了进行计算,组织将被建模为多孔介质,并使用高分辨率和扩散张量磁共振成像技术来解释现实的解剖边界、流体-组织相互作用和各向异性传输。 将使用压力传感器系统和显微压痕测试来测量细胞外运输特性。 相应的体内磁共振成像研究将量化啮齿类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)。 此前尚未进行过如此全面的研究,以量化 TLE 海马系统内的 CED 转运。 这项研究还将提供量化生物转运和通过 CED 测量体内转运的基本工具和技术。 该研究将阐明细胞外流、组织各向异性、病理变化、组织肿胀和回流的作用。 基于磁共振的生物转运工具为患者特异性治疗迈出了重要一步,因为它们解释了疾病引起的解剖和结构变化。 公共健康相关性:在这项研究中,我们的目标是提供对将化合物进入海马体的对流增强递送 (CED) 以治疗颞叶癫痫的基本了解。 体内高分辨率磁共振和扩散张量成像测量将指导三维计算模型的开发,该模型将用于确定解剖边界、流体-组织相互作用和组织结构对细胞外 CED 传输的影响。
项目成果
期刊论文数量(0)
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Malisa Sarntinoranont其他文献
Malisa Sarntinoranont的其他文献
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{{ truncateString('Malisa Sarntinoranont', 18)}}的其他基金
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
- 批准号:
8304295 - 财政年份:2008
- 资助金额:
$ 29.55万 - 项目类别:
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
- 批准号:
7591503 - 财政年份:2008
- 资助金额:
$ 29.55万 - 项目类别:
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
- 批准号:
7693686 - 财政年份:2008
- 资助金额:
$ 29.55万 - 项目类别:
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