A New Approach for the Assessment of Pulmonary Inflammation

评估肺部炎症的新方法

• 批准号: 9010971
• 负责人: RAHIM R RIZI
• 金额: $ 74.92万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-06 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9010971
• 关键词: Acetates; Acute Lung Injury; Alveolar; Anesthesiology; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Asthma; Atelectasis; Bicarbonates; Biochemical Markers; Biological; Brain; Calibration; Carbon; Carbon Dioxide; Cereals; Chemical Shift Imaging; Chemicals; Chemistry; Chronic Obstructive Airway Disease; Clinical; Clinical Management; Cystic Fibrosis; Data; Detection; Development; Disease; Edema; Elements; Environmental air flow; Family suidae; Gases; Goals; Grant; Health; Heart; Hydrogen Peroxide; Image; Imaging Techniques; Individual; Infiltration; Inflammation; Inflammatory; Intervention; Investigation; Kidney; Knowledge; Light; Liver; Lung; Lung Inflammation; Lung diseases; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mechanical ventilation; Medical; Metabolic; Metabolism; Methods; Modeling; Molecular; Nature; Organ; Patients; Pharmacologic Substance; Physics; Plant Roots; Population Heterogeneity; Production; Protocols documentation; Publishing; Pulmonary Inflammation; Pulmonology; Pyruvate; Radiology Specialty; Rattus; Research; Resolution; Scientist; Staging; Stretching; Structure; Techniques; Technology; Time; Tissues; Ventilator; Ventilator-induced lung injury; Work; X-Ray Computed Tomography; imaging modality; improved; in vivo; inflammatory marker; injured; lung injury; mortality; novel; novel strategies; pathogen; pre-clinical; protective effect; response

 DESCRIPTION (provided by applicant): As a fundamental bodily response to insult, inflammation is at the root of a multitude of serious lung disorders. Research using hyperpolarized gas magnetic resonance imaging (HP gas MRI), computed tomography (CT), and other imaging techniques has developed parameters for the assessment of the structural and functional alterations correlated with pulmonary inflammation. However, these approaches are unable to assess the metabolic changes that precede and underlie these alterations. In light of this knowledge gap, the proposed research seeks to optimize the carbon-13 MR approach to metabolic imaging and synthesize it with structural and functional data in order to improve the clinical management of pulmonary inflammation. Carbon-13 MR has significant promise as a metabolic imaging modality due to its ability to detect the different energy needs of inflamed lung. But its potential has been limited by a lack of hyperpolarized bio-probes other than pyruvate. The first stage of our research thus proposes to implement a technique for converting hyperpolarized pyruvate into hyperpolarized bicarbonate, carbon dioxide, and acetate. These novel probes will support the development of new biochemical markers of regional lung inflammation. Here, we will utilize hyperpolarized bicarbonate and carbon dioxide to carry out non-invasive, regional pH mapping in animal lungs. Optimization of this method will allow us to sensitively detect the acidification associated with many inflammatory pulmonary diseases before they alter lung structure and function. Because of inflammation's ubiquity in lung disorders, these techniques could be used to investigate a number of different clinical problems. In the research proposed here, we will tackle a specific longstanding clinical issue: the management of mechanical ventilation in patients with lung injury. These patients often develop ventilator-induced lung injury (VILI), a propagation and worsening of pulmonary inflammation. There exists no widely accepted protocol for the calibration of ventilator settings in order to limt the spread of inflammation, as the relationship between structural and functional data and various ventilator approaches is nebulous. In applying carbon-13 MR to this problem, we hope to develop a more direct and sensitive means of assessing inflammatory progression in order to devise appropriate ventilator strategies. The highly interdisciplinary nature of this research-it contains elements of physics, chemistry, radiology, pulmonology, and anesthesiology-make its findings potentially impactful for a diverse population of scientists and clinicians. The particula techniques we develop here can be used to investigate many inflammatory lung disorders, including asthma, COPD, and cystic fibrosis. More broadly, the availability of new hyperpolarized substrates will facilitate metabolic imaging research on several other organs, including the brain, heart, kidney, and liver.

 描述（由适用提供）：作为对侮辱的基本身体反应，感染是多种严重肺部疾病的根源。使用超极化气体磁共振成像（HP气体MRI），计算机断层扫描（CT）和其他成像技术的研究开发了用于评估与肺部注入相关的结构和功能变化的参数。但是，这些方法无法评估和基础这些改变之前的代谢变化。鉴于这种知识差距，拟议的研究旨在优化碳13 MR方法的代谢成像，并将其与结构和功能数据合成，以改善肺部感染的临床管理。碳13 MR由于能够检测发炎肺的不同能量需求的能力，因此作为代谢成像方式具有巨大的希望。但是，由于丙酮酸以外的其他生物探测，其潜力受到限制。我们的研究的第一阶段因此，提出了一种将超极化丙酮酸转化为超极化碳酸氢盐，二氧化碳和乙酸盐的技术。这些新的问题将支持区域肺部感染的新生化标志物的发展。在这里，我们将利用超极化的碳酸氢盐和二氧化碳在动物肺中进行无创的区域pH映射。这种方法的优化将使我们能够在改变肺结构和功能之前敏感地检测与许多感染肺部疾病相关的酸化。由于感染在肺部疾病中无处不在，这些技术可用于研究许多不同的临床问题。在此处提出的研究中，我们将解决一个特定的长期临床问题：肺损伤患者机械通气的管理。这些患者经常出现通风引起的肺损伤（VILI），这是肺部感染的传播和担忧。没有广泛接受的通风设置校准的方案以限制感染的扩散，因为结构和功能数据与各种呼吸机方法之间的关系是模糊的。在将碳13 MR应用于此问题时，我们希望开发一种评估炎症进展的更直接和敏感的方法，以设计适当的呼吸机策略。这项研究的高度跨学科性质包含物理，化学，放射学，肺病学和麻醉学的要素，其发现可能对科学家和临床医生的多样性人群有可能影响。我们在这里开发的颗粒技术可用于研究许多炎症性肺部疾病，包括哮喘，COPD和囊性纤维化。更广泛地说，新的超极化底物的可用性将促进对其他几个器官，包括大脑，心脏，肾脏和肝脏的代谢成像研究。