Multiscale Interaction of Pulmonary Gas Flow and Lung Tissue Mechanics
肺气流与肺组织力学的多尺度相互作用
基本信息
- 批准号:8451894
- 负责人:
- 金额:$ 33.19万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-04-01 至 2015-03-31
- 项目状态:已结题
- 来源:
- 关键词:AbdomenAdenosineAdenosine TriphosphateAdoptedArchivesAsthmaAutomobile DrivingBacteriaBiochemicalBiologicalBiological ModelsBiomedical EngineeringBreathingCalcium SignalingCalcium ionCell Culture TechniquesCell modelCellsCellular biologyCharacteristicsChronic Obstructive Airway DiseaseClinicalCommunitiesConfocal MicroscopyCyclic AMPCystic FibrosisDataDatabasesDaughterEpithelial CellsFailureFundingGasesGenerationsGrantHeatingHeightHomeostasisHumanHuman VolunteersHumidityImageIn VitroIonsIrritantsLinkLiquid substanceLobeLungLung diseasesMapsMeasurementMeasuresMechanicsMediatingMedical ImagingMetabolismModelingMotionMotivationMucociliary ClearanceMucous body substanceNucleotidesOrganParticulatePathologic ProcessesPathway interactionsPhysiologicalPhysiologyProcessProductionPulmonary EmphysemaRegulationResearchResearch ProposalsResistanceRespiratory DiaphragmRespiratory physiologyRoleSignal TransductionSimulateSmokerSolidSpottingsStressStructureStructure of parenchyma of lungSurfaceSystemSystems BiologyTechniquesTechnologyTemperatureTestingThermodynamicsTissuesToxinTranslationsTreesUnited States National Institutes of HealthValidationWaterWorkX-Ray Computed Tomographyairway remodelingbasedetectorevent cycleexperienceimage registrationinnovationlung imaginglung pressuremeetingsmen who have sex with menmultidisciplinarynon-smokernucleotide metabolismprogramspublic health relevancereceptorrepositoryresearch studyresponserib bone structureshear stress
项目摘要
DESCRIPTION (provided by applicant): The broad objective of this research is to apply the image-based fluid-structure interaction (FSI) technique to study the mechanical force resulting from the multiscale interactions between pulmonary gas flow and lung tissue mechanics, and its role in the distribution and progression of lung disease. A biological hypothesis motivating this work is that lung diseases alter mechanical force, which then alters stress-mediated adenosine triphosphate nucleotide release, disturbs periciliary liquid (PCL) water homeostasis, and weakens the integrated airway defense system, forming a vicious cycle of events. In a multidisciplinary effort, this proposal seeks to adopt an innovative systems biology approach that integrates mechanics and cell models to model transmittal of mechanical force from macro to micro scales, and further translation to biochemical responses at cellular level to maintain the PCL volume for mucociliary clearance. To achieve the objective and test the hypothesis, we propose the following specific aims. (1) Study the distributions of airflow-induced shear stress and airway-wall tissue stress in the central 6 generations of airways where the maximum resistance occurs. The emphasis will be placed on alteration of stresses due to airway rigidity, airway narrowing, and tissue stiffness, especially near the bifurcations in both upper and lower lobes as assessed in normal, asthmatic and emphysema subjects. (2) Study the biochemical responses of bronchial epithelial cells to the alteration of stresses in terms of the regional distributions of PCL water level and calcium ion concentration together with thermodynamics for heat and moisture in the human lung. The emphasis will be placed on deviation from PCL water homeostasis due to depletion or over-production of PCL volume near the bifurcations in both upper and lower lobes, and assess its implication on mucociliary transport. (3) Share the databases and models developed for this project with research and clinical communities via our medical image file archive system and model repository. To achieve these aims, we will extend our existing flow model to include lung tissue mechanics via image-registration-assisted FSI to simulate transmittal of mechanical force between airflow and tissue. We will also incorporate a stress-dependent nucleotide model into our existing model for calcium signaling and transmembrane ion and water fluxes in the ciliated epithelial cell. The fluid-structure (organ- tissue) mechanics model and the epithelial cell model will be integrated with regionally distributed airway thermodynamics to predict dynamic changes in the depth of the PCL layer and calcium ion concentration in the healthy and diseased airways. Both multi-detector row computed tomography (MDCT) experiments and cell culture experiments will be performed for model refinement and validation.
描述(由申请人提供):本研究的主要目标是应用基于图像的流固耦合(FSI)技术来研究肺气流与肺组织力学之间多尺度相互作用产生的机械力及其作用肺部疾病的分布和进展。推动这项工作的生物学假设是,肺部疾病改变了机械力,从而改变了应激介导的三磷酸腺苷核苷酸的释放,扰乱了纤毛周围液体(PCL)水稳态,并削弱了综合气道防御系统,形成了事件的恶性循环。在多学科的努力中,该提案寻求采用一种创新的系统生物学方法,该方法将力学和细胞模型相结合,以模拟机械力从宏观到微观尺度的传递,并进一步转化为细胞水平的生化反应,以维持粘膜纤毛清除的 PCL 体积。为了实现目标并检验假设,我们提出以下具体目标。 (1)研究最大阻力处中央6代气道中气流引起的剪应力和气道壁组织应力的分布。重点将放在由于气道刚性、气道狭窄和组织僵硬引起的压力变化上,特别是在正常、哮喘和肺气肿受试者中评估的上叶和下叶分叉处附近。 (2)根据PCL水位和钙离子浓度的区域分布以及人肺中热量和水分的热力学研究支气管上皮细胞对应激变化的生化反应。重点将放在上叶和下叶分叉处附近由于 PCL 体积耗尽或过量产生而导致 PCL 水稳态的偏差,并评估其对粘液纤毛运输的影响。 (3) 通过我们的医学图像文件存档系统和模型存储库与研究和临床社区共享为此项目开发的数据库和模型。为了实现这些目标,我们将通过图像配准辅助 FSI 扩展现有的流动模型,将肺组织力学纳入其中,以模拟气流和组织之间的机械力传递。我们还将把应激依赖性核苷酸模型纳入我们现有的纤毛上皮细胞中钙信号传导、跨膜离子和水通量模型中。流体-结构(器官-组织)力学模型和上皮细胞模型将与区域分布的气道热力学相结合,以预测健康和患病气道中PCL层深度和钙离子浓度的动态变化。将进行多探测器行计算机断层扫描(MDCT)实验和细胞培养实验以进行模型细化和验证。
项目成果
期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A 4DCT imaging-based breathing lung model with relative hysteresis.
具有相对滞后的基于 4DCT 成像的呼吸肺模型。
- DOI:10.1016/j.jcp.2016.08.039
- 发表时间:2016
- 期刊:
- 影响因子:4.1
- 作者:Miyawaki,Shinjiro;Choi,Sanghun;Hoffman,EricA;Lin,Ching-Long
- 通讯作者:Lin,Ching-Long
A PERFECT MATCH CONDITION FOR POINT-SET MATCHING PROBLEMS USING THE OPTIMAL MASS TRANSPORT APPROACH.
- DOI:10.1137/12086443x
- 发表时间:2013-04-03
- 期刊:
- 影响因子:2.1
- 作者:Chen P;Lin CL;Chern IL
- 通讯作者:Chern IL
Multiscale image-based modeling and simulation of gas flow and particle transport in the human lungs.
- DOI:10.1002/wsbm.1234
- 发表时间:2013-09
- 期刊:
- 影响因子:7.9
- 作者:Lin, Ching-Long;Tawhai, Merryn H.;Hoffman, Eric A.
- 通讯作者:Hoffman, Eric A.
Efficient methods for implementation of multi-level nonrigid mass-preserving image registration on GPUs and multi-threaded CPUs.
- DOI:10.1016/j.cmpb.2015.12.018
- 发表时间:2016-04
- 期刊:
- 影响因子:6.1
- 作者:Ellingwood ND;Yin Y;Smith M;Lin CL
- 通讯作者:Lin CL
A Numerical Study of Water Loss Rate Distributions in MDCT-Based Human Airway Models.
- DOI:10.1007/s10439-015-1318-3
- 发表时间:2015-11
- 期刊:
- 影响因子:3.8
- 作者:Wu D;Miyawaki S;Tawhai MH;Hoffman EA;Lin CL
- 通讯作者:Lin CL
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CHING-LONG LIN其他文献
CHING-LONG LIN的其他文献
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{{ truncateString('CHING-LONG LIN', 18)}}的其他基金
Deep Learning and Subtyping of Post-COVID-19 Lung Progression Phenotypes
COVID-19 后肺部进展表型的深度学习和亚型分析
- 批准号:
10634998 - 财政年份:2023
- 资助金额:
$ 33.19万 - 项目类别:
An integrative statistics-guided image-based multi-scale lung model
综合统计引导的基于图像的多尺度肺模型
- 批准号:
8850481 - 财政年份:2013
- 资助金额:
$ 33.19万 - 项目类别:
An integrative statistics-guided image-based multi-scale lung model
综合统计引导的基于图像的多尺度肺模型
- 批准号:
9283608 - 财政年份:2013
- 资助金额:
$ 33.19万 - 项目类别:
An integrative statistics-guided image-based multi-scale lung model
综合统计引导的基于图像的多尺度肺模型
- 批准号:
8714034 - 财政年份:2013
- 资助金额:
$ 33.19万 - 项目类别:
An integrative statistics-guided image-based multi-scale lung model
综合统计引导的基于图像的多尺度肺模型
- 批准号:
8554276 - 财政年份:2013
- 资助金额:
$ 33.19万 - 项目类别:
An integrative statistics-guided image-based multi-scale lung model
综合统计引导的基于图像的多尺度肺模型
- 批准号:
9066766 - 财政年份:2013
- 资助金额:
$ 33.19万 - 项目类别:
Multiscale Interaction of Pulmonary Gas Flow and Lung Tissue Mechanics
肺气流与肺组织力学的多尺度相互作用
- 批准号:
8242729 - 财政年份:2010
- 资助金额:
$ 33.19万 - 项目类别:
Multiscale Interaction of Pulmonary Gas Flow and Lung Tissue Mechanics
肺气流与肺组织力学的多尺度相互作用
- 批准号:
7758994 - 财政年份:2010
- 资助金额:
$ 33.19万 - 项目类别:
Multiscale Interaction of Pulmonary Gas Flow and Lung Tissue Mechanics
肺气流与肺组织力学的多尺度相互作用
- 批准号:
8043553 - 财政年份:2010
- 资助金额:
$ 33.19万 - 项目类别:
Large-Scale Computing and Visualization for Cardiopulmonary Imaging
心肺成像的大规模计算和可视化
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7388316 - 财政年份:2008
- 资助金额:
$ 33.19万 - 项目类别:
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