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

总结 晚期肺气肿的主要特征是慢性炎症，小气道阻塞， 实质破坏导致过度充气，损害呼吸力学， 功能衰退医学疗法已被证明对治疗咳嗽和气短等症状有效 也可以帮助预防急性加重，但对改善死亡率或恢复几乎没有帮助。 失去功能。虽然肺减容手术（LVRS）已经证明了改善肺功能的能力， 在某些严格选择的患者中，它与生活质量和死亡率的显著增加有关。 围手术期和短期发病率，仍然是一种未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量 减少技术获得FDA批准。通过导管插入瓣膜，以封堵目标 肺气肿性肺叶，引起部分或完全肺叶肺不张，残余容量减少， 与LVRS相似，过度充气和改善呼吸力学和肺功能，并改善发病率 and mortality.尽管许多研究表明，在各种疾病中， 然而，功能和解剖结局指标，目前仍有大量的EBV 因此无法享受有意义的生活质量福利的受助人。 为了解决这一矛盾，拟议的项目将使用超极化氙-129磁共振成像的独特能力， 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放置干扰和 改变了肺部我们假设这主要包括通气和灌注的重新分配， 更健康的肺以及局部和全身炎症负荷的减少， 评估这些变化的存在/不存在，以及它们的程度，将有助于解释频繁的 EBV治疗效果的定量和定性评估之间的差异。 使用先前开发的多呼吸超极化129 μ m建立/洗脱序列，结合 测量信号强度建立，以生成每分钟通气量和功能的定量图 剩余容量，我们将在叶或节段水平上量化通风再分布和剩余容量。 将这些图与气道疾病的配准和分段CT衍生测量结果进行比较， 肺气肿接下来，我们将使用HP 129 Xe溶解相成像来量化红血的气体吸收 肺中的细胞-这是一种与血氧比测量更密切相关的测量， 灌注，并探讨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，以及炎性细胞，如活化的巨噬细胞和CD8 + T细胞，其存在 我们将尝试与治疗后的主观生活质量评估相关联。

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.