A New Approach for the Assessment of Pulmonary Inflammation

 描述（由申请人提供）：作为对损伤的基本身体反应，炎症是许多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已经开发出用于评估与肺部炎症相关的结构和功能改变的参数。然而，这些方法无法评估这些改变之前和背后的代谢变化。鉴于这一知识差距，拟议的研究旨在优化碳-13 MR代谢成像方法，并将其与结构和功能数据相结合，以改善肺部炎症的临床管理。碳-13 MR作为代谢成像模式具有重要的前景，因为它能够检测炎症肺的不同能量需求。但由于缺乏丙酮酸以外的超极化生物探针，其潜力受到限制。因此，我们的研究的第一阶段提出实施一种将超极化丙酮酸盐转化为超极化碳酸氢盐、二氧化碳和乙酸盐的技术。这些新的探针将支持区域性肺部炎症的新生化标志物的开发。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部进行非侵入性的局部pH标测。这种方法的优化将使我们能够在许多炎症性肺部疾病改变肺结构和功能之前灵敏地检测与它们相关的酸化。由于炎症在肺部疾病中的普遍存在，这些技术可用于研究许多不同的临床问题。在这里提出的研究中，我们将解决一个长期存在的临床问题：肺损伤患者的机械通气管理。这些患者通常会发生呼吸机诱导的肺损伤（VILI），这是肺部炎症的传播和恶化。由于结构和功能数据与各种呼吸机方法之间的关系不明确，因此不存在广泛接受的用于校准呼吸机设置以限制炎症扩散的协议。在应用碳-13 MR来解决这个问题时，我们希望开发一种更直接和敏感的方法来评估炎症进展，以设计适当的呼吸机策略。这项研究的高度跨学科性质-它包含物理学，化学，放射学，肺病学和麻醉学的元素-使其研究结果可能对不同的科学家和临床医生产生影响。我们在这里开发的特殊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的代谢成像研究，包括大脑，心脏，肾脏和肝脏。

 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.