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
• 负责人: CHANTAL DARQUENNE
• 金额: $ 15.74万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-04 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7536031
• 关键词: Aerosol Drug Therapy; Aerosols; Affect; Age-Years; Air Pollution; Airborne Particulate Matter; Alveolar; Animal Model; Animals; Area; Biological Sciences; Biological Warfare; Breathing; Caliber; Cardiopulmonary; Characteristics; Chronic Disease; Clinical Medicine; Computer Simulation; Data; Databases; Deposition; Detection; Dimensions; Disease; Disease model; Drug Delivery Systems; Environmental air flow; Exposure to; Fluorometry; Future; Gases; Health; Human; Image; Imaging Techniques; Immune response; Infectious Agent; Knowledge; Label; Link; Liquid substance; Lobar; Location; Lung; Lung diseases; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medical; Methods; Modeling; Morbidity - disease rate; Pancreatic Elastase; Particle Size; Particulate Matter; Pattern; Penetration; Peripheral; Pharmaceutical Preparations; Pharmacotherapy; Population; Public Health; Pulmonary Emphysema; Rattus; Relative (related person); Research; Resolution; Respiratory Mechanics; Site; Structure; Techniques; Tissues; Validation; Variant; Wistar Rats; aerosolized; airway obstruction; base; imaging modality; improved; iron oxide; lung volume; mortality; novel; particle; tool

DESCRIPTION (provided by applicant): Detailed knowledge of the fate of aerosols in the lung is essential in understanding the effect of exposure to airborne particulate matter (PM) and infectious agents as well as in assessing the efficacy of inhaled drug therapy. Detailed yet non-invasive studies of peripheral aerosol deposition (DE) are almost impossible in humans. Thus, understanding the fate of aerosols in the lung requires the use of animal models in which more invasive techniques can be used and/or computational models. In the last decade, Magnetic Resonance Imaging (MRI) has become a major imaging modality both in clinical medicine and in life science research, and has been successfully used in various lung studies. Recently it has also been shown that, using MRI scanners with very high spatial resolutions (50-100 5m), it is possible to directly measure the location of single micron-sized particles of iron oxide in tissue. The two main objectives of the study are 1) to improve our MRI technique to measure aerosol DE patterns in a rat model; and 2) apply this technique to characterize the effects of emphysema on aerosol DE patterns. We will first deliver aerosolized fluorescent-labeled iron oxide particles to healthy anesthetized rats. Using high-resolution MRI, we will characterize the aerosol DE patterns for the entire rat lung and determine the relative DE in subregions of the lung varying in size from lobar to sub-lobar. We will also characterize the aerosol DE patterns in the same animals by fluorometry to validate the MRI data. Using this novel MRI technique, we will then study the effect of emphysema on aerosol DE. Six weeks prior to aerosol exposure, emphysema will be induced in Wistar rats by intratracheal instillation of pancreatic elastase. Healthy and emphysematous rats will then be tracheally ventilated with aerosolized iron oxide particles (1 and 3 micron) under controlled breathing patterns. Animals will be imaged by MRI to produce regional maps of aerosol DE. The effect of emphysema will be determined by analysis of coefficients of variation and by comparison between DE maps obtained in healthy and emphysematous rats. The proposed study, that will provide a detailed quantitative description of aerosol DE patterns in the lung, is relevant to three main areas: 1) exposure to airborne PM, 2) the disease of emphysema and 3) the improvement of therapy by aerosol inhalation. There is ongoing growing evidence that exposure to ambient PM increases cardiopulmonary morbidity and mortality in susceptible subpopulations. Knowledge of the DE patterns of particles will not only provide quantitative assessment of aerosol DE but also insightful information for the characterization of host immune responses resulting for PM exposure. A better understanding of the fate of aerosols in the lung will also be beneficial in aerosol drug therapy as it will allow for better targeting of the drugs to their intended site of action. Finally, emphysema, one of the most common chronic illnesses of the population over 45 years of age, alters pulmonary gas flow and therefore the penetration and subsequent DE of inhaled particles in the lung. The validation of the MRI technique will provide an important tool in elucidating the effect of emphysema on aerosol DE. Such validation will also enable future MRI studies of numerous different lung disease models. Project Narrative: We propose to quantitatively assess by Magnetic Resonance Imaging (MRI) the distribution of deposited particles resulting from aerosol exposure in a rat lung. The proposed research is relevant to public health as 1) it will provide insightful information for the characterization of host immune responses resulting for particulate matter exposure, 2) will be beneficial in aerosol drug therapy as it will allow for better targeting of the drugs to desired regions of the lung and 3) will elucidate the effect of emphysema on aerosol deposition. The technique developed in the proposed research will also enable future MRI studies of numerous different lung disease models.

描述（由申请人提供）：对肺中气溶胶命运的详细知识对于理解暴露于空气中的颗粒物（PM）和感染剂的影响以及评估吸入药物治疗的功效至关重要。人类几乎不可能对周围气溶胶沉积（DE）进行详细但无创的研究。因此，了解肺中气溶胶的命运需要使用动物模型，其中可以使用更多的侵入性技术和/或计算模型。在过去的十年中，磁共振成像（MRI）已成为临床医学和生命科学研究中的主要成像方式，并已成功用于各种肺部研究。最近还显示，使用具有很高空间分辨率的MRI扫描仪（50-100 5m），可以直接测量单个微米大小的氧化铁在组织中的位置。研究的两个主要目标是1）改进我们的MRI技术，以测量大鼠模型中的气溶胶DE模式； 2）应用此技术来表征肺气肿对气溶胶DE模式的影响。我们将首先将雾化的荧光标记氧化铁颗粒传递到健康的麻醉大鼠中。使用高分辨率MRI，我们将表征整个大鼠肺的气溶胶DE模式，并确定肺部的相对DE的大小从Lobar到亚叶片变化。我们还将通过荧光测定法以验证MRI数据来表征同一动物中的​​气溶胶DE模式。使用这种新颖的MRI技术，我们将研究肺气肿对气溶胶DE的影响。气溶胶暴露前六周，气管内胰腺弹性酶将在Wistar大鼠中诱导肺气肿。然后，在受控的呼吸模式下，将用氧化铁颗粒（1和3微米）对健康和过滤大鼠进行气管通风。动物将由MRI成像以生成气溶胶DE的区域地图。肺气肿的效果将通过分析变异系数的分析以及在健康和过滤大鼠中获得的DE地图之间的比较。拟议的研究将对肺中的气溶胶DE模式提供详细的定量描述，与三个主要领域有关：1）暴露于空气中的PM，2）肺气肿疾病和3）气溶胶吸入的治疗改善。越来越多的证据表明，暴露于环境PM会增加易感亚群中的心肺发病率和死亡率。了解颗粒模式的知识不仅将提供对气溶胶DE的定量评估，而且还将提供有见地的信息，以表征导致PM暴露的宿主免疫反应。更好地了解肺中气溶胶的命运也将在气溶胶药物治疗中有益，因为这将使药物更好地靶向其预期的作用部位。最后，肺气肿是45岁以上人群中最常见的慢性疾病之一，改变了肺气流量，因此肺部的渗透和随后的DE肺中吸入了肺中的颗粒。 MRI技术的验证将为阐明肺气肿对气溶胶DE的影响提供重要的工具。这种验证还将实现对许多不同肺部疾病模型的未来MRI研究。项目叙述：我们建议通过磁共振成像（MRI）定量评估大鼠肺中气溶胶暴露导致的沉积颗粒的分布。拟议的研究与公共卫生相关，因为1）它将提供深刻的信息，以表征导致颗粒物暴露的宿主免疫反应，2）将对气溶胶药物治疗有益，因为它将允许更好地靶向肺部所需区域的药物和3）将阐明肺气肿对气溶胶降低的作用。拟议的研究中开发的技术还将实现对许多不同肺部疾病模型的未来MRI研究。

项目成果

Airflow and particle deposition simulations in health and emphysema: from in vivo to in silico animal experiments.

• DOI: 10.1007/s10439-013-0954-8
• 发表时间: 2014-04
• 期刊: ANNALS OF BIOMEDICAL ENGINEERING
• 影响因子: 3.8
• 作者: Oakes, Jessica M.;Marsden, Alison L.;Grandmont, Celine;Shadden, Shawn C.;Darquenne, Chantal;Vignon-Clementel, Irene E.
• 通讯作者: Vignon-Clementel, Irene E.

Distribution of aerosolized particles in healthy and emphysematous rat lungs: comparison between experimental and numerical studies.

• DOI: 10.1016/j.jbiomech.2015.01.004
• 发表时间: 2015-04-13
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: Oakes JM;Marsden AL;Grandmont C;Darquenne C;Vignon-Clementel IE
• 通讯作者: Vignon-Clementel IE