Imaging the functional response of the lung to bronchoscopic lung volume reduction

成像肺对支气管镜肺减容的功能反应

• 批准号: 10528137
• 负责人: RAHIM R RIZI
• 金额: $ 68.08万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-10 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10528137
• 关键词: Acute; Address; Aftercare; Air Movements; Airway Disease; Anatomy; Atelectasis; Biological Markers; Blood; CD8-Positive T-Lymphocytes; Catheters; Cells; Chronic; Clinical; Coughing; Erythrocytes; Extravasation; Functional Residual Capacity; Gases; Human Herpesvirus 4; Image; Inflammation; Inflammatory; Lobar; Lobe; Lung; Lung Volume Reductions; Lung volume reduction surgery; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medical; Morbidity - disease rate; Outcome Measure; Patients; Perfusion; Perioperative; Phase; Pulmonary Emphysema; Quality of life; Quality-of-Life Assessment; Residual volume; Respiratory Mechanics; Shortness of Breath; Signal Transduction; Techniques; Treatment Efficacy; Xenon; airway obstruction; clinically significant; experience; functional decline; functional restoration; improved; macrophage; mortality; prevent; pulmonary function; response; symptom treatment; uptake; ventilation

Summary Advanced emphysema is primarily characterized by chronic inflammation, small airways obstruction, and parenchymal destruction leading to hyperinflation, compromised respiratory mechanics, and progressive functional decline. Medical therapy has proven effective in treating symptoms such as coughing and shortness of breath, and can also help to prevent acute exacerbations, but does little to improve either mortality or restore lost function. While lung volume reduction surgery (LVRS) has demonstrated the ability to improve lung function, quality of life and mortality in certain, rigorously selected patients, it is associated with a significant increase in perioperative and short-term morbidity and remains an underutilized treatment. In 2018, treatment with Zephyr Endobronchial Valves (Zephyr EBV) became the first bronchoscopic lung volume reduction technique to receive FDA approval. Valves are inserted via catheter in order to occlude a target emphysematous lobe, causing partial or complete lobar atelectasis, decreasing residual volume, reducing hyperinflation and improving breathing mechanics and lung function similarly to LVRS with improved morbidity and mortality. Despite numerous studies demonstrating clinically significant average improvements in various functional and anatomical outcome measures, however, there currently remain a significant number of EBV recipients who fail to experience meaningful quality of life benefits as a result. In order to address this discrepancy, the proposed project will use hyperpolarized xenon-129 MRI's unique ability to measure regional lung function, in combination with the assessment of systemic inflammatory biomarkers, to attain a more comprehensive understanding of the mechanisms through which EBV placement perturbs and alters the lung. We hypothesize that this consists primarily of a redistribution of both ventilation and perfusion to the healthier lung as well as a decrease in both local and systemic inflammatory burden—and that sensitively assessing the presence/absence of these changes, as well as their degree, will help to explain the frequent divergence between quantitative and qualitative assessments of EBV treatment efficacy. Using a previously developed multi-breath hyperpolarized 129Xe buildup/washout sequence, combined with a measurement of signal intensity buildup, to produce quantitative maps of minute ventilation and functional residual capacity, we will quantify ventilation redistribution and residual volume at a lobar or segmental level. These maps are compared to registered and segmented CT-derived measurements of airways disease and emphysema. Next, we will employ HP 129Xe dissolved-phase imaging to quantify gas uptake by the red blood cells in the lung—a measurement that relates more closely to blood oxygenation than measurements of perfusion, and investigate the use of dynamic airflow imaging to distinguish clinically important cases of collateral ventilation and leakage around the valve. Finally, we will evaluate a number of systemic inflammatory biomarkers, as well as inflammatory cells such as activated macrophages and CD8+ T cells, whose presence we will attempt to correlate with subjectively quality of life assessments post-treatment.

概括 晚期肺气肿的主要特征是慢性炎症、小气道阻塞和 实质破坏导致恶性通货膨胀、呼吸力学受损和进行性 功能衰退。药物治疗已被证明可以有效治疗咳嗽和气短等症状 呼吸，也可以帮助预防急性加重，但对降低死亡率或恢复生命几乎没有作用 失去功能。虽然肺减容手术 (LVRS) 已被证明能够改善肺功能， 在某些经过严格挑选的患者中，生活质量和死亡率的显着增加与 围手术期和短期发病率较高，并且仍然是一种未得到充分利用的治疗方法。 2018 年，Zephyr 支气管内瓣膜 (Zephyr EBV) 治疗成为第一个支气管镜肺容积治疗 减少技术获得 FDA 批准。通过导管插入瓣膜以封闭目标 肺叶气肿，引起部分或完全性肺叶不张，减少残气量，减少 与 LVRS 类似，可抑制过度通货膨胀并改善呼吸力学和肺功能，并改善发病率 和死亡率。尽管大量研究表明临床上各种方面的平均改善显着 然而，功能和解剖结果测量目前仍存在大量 EBV 结果，受益者无法体验到有意义的生活质量益处。 为了解决这一差异，拟议项目将利用超极化氙 129 MRI 的独特能力 测量局部肺功能，结合全身炎症生物标志物的评估， 更全面地了解 EBV 放置扰乱和影响的机制 改变肺部。我们假设这主要包括通气和灌注的重新分配 肺部更健康，局部和全身炎症负担减少——而且敏感 评估这些变化的存在/不存在及其程度，将有助于解释频繁出现的情况 EBV 治疗效果的定量和定性评估之间存在差异。 使用先前开发的多呼吸超极化 129Xe 构建/冲洗序列，并结合 测量信号强度积累，以生成每分钟通气量和功能的定量图 剩余容量，我们将量化肺叶或节段水平的通气重新分配和剩余容量。 这些图与气道疾病的注册和分段 CT 测量值进行比较 气肿。接下来，我们将采用 HP 129Xe 溶解相成像来量化红血的气体吸收 肺细胞——这种测量与血氧合作关系比测量更密切 灌注，并研究使用动态气流成像来区分临床上重要的侧支循环病例 阀门周围的通风和泄漏。最后，我们将评估一些全身性炎症 生物标志物以及炎症细胞，例如活化的巨噬细胞和 CD8+ T 细胞，其存在 我们将尝试将治疗后的主观生活质量评估联系起来。