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

摘要 晚期肺气肿的主要特征是慢性炎症，小气道阻塞，以及 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。药物治疗已被证明对咳嗽和短促等症状有效。 减少呼吸，也有助于预防急性加重，但对提高死亡率或恢复原状几乎无济于事 功能丧失。虽然肺减容手术(LVRS)已经证明了改善肺功能的能力， 在某些经过严格挑选的患者中，它与生活质量和死亡率显著增加有关 围手术期和短期并发症，仍然是一种未得到充分利用的治疗方法。 2018年，Zephar EBV治疗成为第一个支气管镜下肺体积 减量技术获得FDA批准。通过导管插入瓣膜以封堵目标。 肺气肿叶，导致部分或完全肺叶不张，减少残气量，减少 恶性充气和改善呼吸力学和肺功能与LVRS相似，发病率有所改善 和死亡率。尽管许多研究表明，在临床上有显著的平均改善，在各种 然而，功能和解剖学结果指标，目前仍有相当数量的EBV 因此，未能体验到有意义的生活质量福利的受助者。 为了解决这一差异，拟议的项目将使用超极化氙气-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，以 更全面地了解EBV放置扰乱和 改变了肺部。我们假设，这主要是由通风和灌流的重新分配组成的 更健康的肺部以及局部和全身炎症负担的减少--而且敏感地 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治疗疗效的定量和定性评估之间的差异。 使用之前开发的多呼吸超极化129Xe聚集/洗出序列，结合 测量信号强度，以生成分钟通气量和功能的定量图 对于剩余容量，我们将在肺叶或节段性水平上量化通气量再分布和残余量。 将这些地图与呼吸道疾病的注册和分段CT测量结果进行比较 肺气肿。接下来，我们将使用HP 129Xe溶解相成像来量化红血球对气体的摄取 肺中的细胞-这一测量与血液氧合的关系比测量 并研究动态气流成像在区分临床重要侧支循环病例中的应用。 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，如活化的巨噬细胞和CD8+T细胞，它们的存在 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.