Multiscale Modeling of Lung Disease-Influenced Aerosol Dosimetry
肺部疾病影响的气溶胶剂量测定的多尺度建模
基本信息
- 批准号:9768482
- 负责人:
- 金额:$ 65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:3-Dimensional4D ImagingAerosolsAffectAir PollutionAlgorithmsAsthmaBiologicalBreathingCaliberCause of DeathChemicalsChronic Obstructive Airway DiseaseComputer SimulationCoupledCouplingDataDatabasesDepositionDevelopmentDimensionsDiseaseDoseDrug Delivery SystemsDustEnvironmental HealthEnvironmental air flowExposure toFutureGoalsHealthHeterogeneityHumanHuman VolunteersImageIndividualIndoor Air PollutionInhalationIrritantsLinkLiquid substanceLungLung diseasesMeasurementMechanicsMethodsModelingNoseOccupationalOral cavityOutcomePerformancePharmaceutical PreparationsPharmacologic SubstancePropertyPublished DatabasePublishingQuality of lifeRattusResearchResearch PersonnelResolutionRespiratory SystemRiskRisk AssessmentRouteSiteStandardizationTherapeuticTherapeutic InterventionThree-Dimensional ImagingTissuesWorkWorkplaceX-Ray Computed Tomographybasecigarette smokecohortdata submissiondosimetryenvironmental toxicologyimprovedmodel developmentmulti-scale modelingmultimodalitynovelnovel strategiesparticlepathogen exposurephysical propertypredictive modelingrespiratoryvolunteer
项目摘要
Abstract
The overall goal of this proposal is to develop multiscale computational models that can predict the deposition
of inhaled aerosols in all regions of the respiratory system of individuals that are either healthy or suffering
from respiratory diseases such as COPD (chronic obstructive pulmonary disease). COPD is generally associated
with exposure to toxic/irritant aerosols (e.g. cigarette smoke, occupational dusts/fumes, environmental PM2.5
air pollution, etc.) and adversely affects the quality of life for millions of susceptible individuals. Along with
asthma, COPD is the third leading disease-based cause of death in the U.S. In addition, the respiratory system
has been exploited as a potential route for local and systemic delivery of therapeutic aerosols for COPD,
asthma, or other diseases where drugs may not be as effective by other routes of administration. As a result, the
development of predictive aerosol dosimetry models has been a major focus of environmental toxicology and
pharmaceutical health research for decades. To date, the challenge of predicting the deposition of inhaled
aerosols under disease conditions has been largely unmet. We propose to utilize advancements our established
team of investigators and others have made in imaging, aerosol exposure and measurement, and
computational modeling to develop, experimentally evaluate, and refine multiscale models that predict site-
and region-specific deposition of aerosols throughout the respiratory system and to study how deposition is
influenced by disease. Our proposed models will be developed by a step-wise, modular integration of 3D
computational fluid dynamic (CFD) airflow and aerosol tracking models that extend from the nose and mouth
to the conducting airways of the lung with each 3D pulmonary airway bi-directionally coupled with lower
dimensional airflow, aerosol transport, and tissue mechanics models to describe aerosol transport and
deposition over the full respiratory system and throughout the complete breathing cycle (Aim 1). Models will
initially be developed for healthy individuals (Aim 2) followed by disease (Aim 3) using published airway and
tissue mechanics data and, where data do not exist for humans, extracted from our 4D imaging and aerosol
deposition data in healthy and diseased rats. Our modular approach to multiscale linkages will allow users to
substitute individual model components as new advances are made. The multiscale models will be evaluated
and further refined using a rich database of multi-modal 3D imaging and aerosol deposition measurements in
human volunteers that include both healthy and COPD cohorts. The expected outcome of our work will be a
suite of modular, multiscale models and standardized approaches for new model development that can be used
by researchers, risk assessors, or clinicians to predict aerosol deposition in the respiratory systems of humans
under healthy and disease conditions in addition to the underlying algorithms and framework for effective
linking of user-defined, personalized aerosol dosimetry models in the future.
抽象的
该提案的总体目标是开发可以预测沉积的多尺度计算模型
健康或患病个体呼吸系统所有区域吸入的气溶胶
患有慢性阻塞性肺疾病(COPD)等呼吸系统疾病。 COPD 通常与
暴露于有毒/刺激性气溶胶(例如香烟烟雾、职业粉尘/烟雾、环境 PM2.5
空气污染等)并对数百万易感人群的生活质量产生不利影响。连同
哮喘、慢性阻塞性肺病是美国第三大疾病死亡原因。此外,呼吸系统
已被开发为慢性阻塞性肺病治疗气雾剂局部和全身输送的潜在途径,
哮喘或其他疾病,药物通过其他给药途径可能效果不佳。结果,
预测气溶胶剂量测定模型的开发一直是环境毒理学和
数十年的药物健康研究。迄今为止,预测吸入物沉积的挑战
疾病条件下的气溶胶基本上没有得到满足。我们建议利用我们已建立的进步
研究人员和其他人的团队在成像、气溶胶暴露和测量方面取得了进展,并且
计算建模来开发、实验评估和完善预测站点的多尺度模型
和整个呼吸系统中气溶胶的特定区域沉积,并研究沉积是如何发生的
受疾病影响。我们提出的模型将通过 3D 的逐步模块化集成来开发
从鼻子和嘴巴延伸的计算流体动力学 (CFD) 气流和气溶胶跟踪模型
到肺部的传导气道,每个 3D 肺气道与下部气道双向耦合
三维气流、气溶胶输送和组织力学模型来描述气溶胶输送和
沉积在整个呼吸系统和整个呼吸周期(目标 1)。模型将
最初针对健康个体(目标 2)开发,然后使用已发布的气道和疾病(目标 3)开发
组织力学数据,如果没有人类数据,则从我们的 4D 成像和气溶胶中提取
健康和患病大鼠的沉积数据。我们的多尺度联系的模块化方法将允许用户
随着新进展的出现,替换单个模型组件。将评估多尺度模型
并使用丰富的多模态 3D 成像和气溶胶沉积测量数据库进一步完善
人类志愿者,包括健康人群和慢性阻塞性肺病人群。我们工作的预期成果将是
一套模块化、多尺度模型和标准化方法,可用于新模型开发
由研究人员、风险评估人员或临床医生预测人类呼吸系统中的气溶胶沉积
除了底层算法和框架之外,在健康和疾病条件下也能有效
未来连接用户定义的个性化气溶胶剂量测定模型。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
专利数量(0)
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CHANTAL DARQUENNE其他文献
CHANTAL DARQUENNE的其他文献
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{{ truncateString('CHANTAL DARQUENNE', 18)}}的其他基金
Multiscale Modeling of Lung Disease-Influenced Aerosol Dosimetry
肺部疾病影响的气溶胶剂量测定的多尺度建模
- 批准号:
10200811 - 财政年份:2018
- 资助金额:
$ 65万 - 项目类别:
Multiscale Modeling of Lung Disease-Influenced Aerosol Dosimetry
肺部疾病影响的气溶胶剂量测定的多尺度建模
- 批准号:
10436278 - 财政年份:2018
- 资助金额:
$ 65万 - 项目类别:
MR Imaging of Upper Airway Dynamics in Obstructive Sleep Apnea
阻塞性睡眠呼吸暂停上气道动力学的 MR 成像
- 批准号:
8913765 - 财政年份:2014
- 资助金额:
$ 65万 - 项目类别:
MR Imaging of Upper Airway Dynamics in Obstructive Sleep Apnea
阻塞性睡眠呼吸暂停上气道动力学的 MR 成像
- 批准号:
8771245 - 财政年份:2014
- 资助金额:
$ 65万 - 项目类别:
Quantitative MRI-based Assessment of Aerosol Deposition in the Lung
基于 MRI 的肺部气溶胶沉积定量评估
- 批准号:
7387104 - 财政年份:2007
- 资助金额:
$ 65万 - 项目类别:
Quantitative MRI-based Assessment of Aerosol Deposition in the Lung
基于 MRI 的肺部气溶胶沉积定量评估
- 批准号:
7536031 - 财政年份:2007
- 资助金额:
$ 65万 - 项目类别:
Modeling of Aerosol Transport in Alveolated Airways
肺泡气道中气溶胶传输的建模
- 批准号:
7385997 - 财政年份:2001
- 资助金额:
$ 65万 - 项目类别:
Modeling of Aerosol Transport in Alveolated Airways
肺泡气道中气溶胶传输的建模
- 批准号:
7212251 - 财政年份:2001
- 资助金额:
$ 65万 - 项目类别:
Modeling of Aerosol Transport in Alveolated Airways
肺泡气道中气溶胶传输的建模
- 批准号:
7070575 - 财政年份:2001
- 资助金额:
$ 65万 - 项目类别:
Modeling of Aerosol Transport in Alveolated Airways
肺泡气道中气溶胶传输的建模
- 批准号:
6914718 - 财政年份:2001
- 资助金额:
$ 65万 - 项目类别:
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