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）：详细了解肺部气溶胶的命运对于了解暴露于空气中颗粒物 (PM) 和传染性病原体的影响以及评估吸入药物治疗的功效至关重要。对人类外周气溶胶沉积（DE）进行详细且非侵入性的研究几乎是不可能的。因此，了解气溶胶在肺部的命运需要使用可以使用更具侵入性技术的动物模型和/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的主要成像方式，并已成功应用于各种肺部研究。最近还表明，使用具有非常高空间分辨率（50-100 5m）的 MRI 扫描仪，可以直接测量组织中单微米大小的氧化铁颗粒的位置。该研究的两个主要目标是 1) 改进我们的 MRI 技术来测量大鼠模型中的气溶胶 DE 模式； 2) 应用该技术来表征肺气肿对气溶胶 DE 模式的影响。我们首先将雾化的荧光标记氧化铁颗粒递送给健康的麻醉大鼠。使用高分辨率 MRI，我们将描述整个大鼠肺部的气溶胶 DE 模式，并确定从肺叶到亚肺叶大小不同的肺部分区的相对 DE。我们还将通过荧光测定法表征同一动物的气溶胶 DE 模式，以验证 MRI 数据。利用这种新颖的 MRI 技术，我们将研究肺气肿对气溶胶 DE 的影响。在气溶胶暴露前六周，通过气管内滴注胰腺弹性蛋白酶在 Wistar 大鼠中诱导肺气肿。然后，在受控呼吸模式下，用雾化氧化铁颗粒（1 和 3 微米）对健康和肺气肿大鼠进行气管通气。动物将通过 MRI 成像以生成气溶胶 DE 区域图。肺气肿的影响将通过分析变异系数并比较在健康和肺气肿大鼠中获得的DE图来确定。拟议的研究将提供肺部气溶胶 DE 模式的详细定量描述，涉及三个主要领域：1）暴露于空气中的 PM，2）肺气肿疾病和 3）气溶胶吸入治疗的改进。越来越多的证据表明，暴露于环境 PM 会增加易感人群的心肺发病率和死亡率。了解颗粒物的 DE 模式不仅可以对气溶胶 DE 进行定量评估，还可以为表征 PM 暴露引起的宿主免疫反应提供深入的信息。更好地了解气溶胶在肺部的命运也将有利于气溶胶药物治疗，因为它将允许药物更好地靶向其预期作用部位。最后，肺气肿是 45 岁以上人群最常见的慢性疾病之一，它会改变肺部气流，从而改变吸入颗粒在肺部的渗透和随后的 DE。 MRI 技术的验证将为阐明肺气肿对气溶胶 DE 的影响提供重要工具。这种验证还将使得未来能够对多种不同的肺部疾病模型进行 MRI 研究。项目叙述：我们建议通过磁共振成像（MRI）定量评估大鼠肺部因气溶胶暴露而产生的沉积颗粒的分布。拟议的研究与公共卫生相关，因为 1) 它将为表征颗粒物暴露导致的宿主免疫反应提供富有洞察力的信息，2) 将有益于气溶胶药物治疗，因为它将允许药物更好地靶向肺部的所需区域，3) 将阐明肺气肿对气溶胶沉积的影响。拟议研究中开发的技术还将支持未来对多种不同肺部疾病模型的 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