Early detection of regional BOS in BMT patients using UTE and 129Xe MRI

项目总结 闭塞性细支气管炎综合征(BOS)是一种不可逆转的阻塞性肺疾病，由 炎症和免疫反应，表现为永久性肺功能下降。BOS是一家 肺和骨髓移植(BMT)受者肺部并发症的重要来源，以及 尽管其发病率和临床病程陡峭，但缺乏常规监测的临床工具。 BOS移植后。对BOS的监测在很大程度上仅限于肺活量测定，这在年轻人中可能不可靠 儿童对早期呼吸道阻塞不敏感，并进行计算机断层扫描。在骨髓移植患者中，常规 由于连续的电离辐射暴露，避免了通过CT进行筛查，而通过肺活量测定进行筛查的情况往往较少 比肺移植受者更频繁。因此，这一人群中的肺部并发症可能会 确诊后，骨髓移植患者通常只有在肺功能显著后才被转介给肺部医生。 下降，这限制了改善患者预后的干预选择。 新兴的磁共振成像(MRI)技术将彻底改变肺部成像和 确实已经开始对囊性纤维化、慢性阻塞性肺病和哮喘等疾病产生影响。超强的 短回声时间(UTE)MRI方法在区域肺的显示和量化方面现在可与CT相媲美 实质病理和单次超极化129Xe屏气可以揭示换气障碍，这 肺部区域是否由于呼吸道阻塞而不能正常通风。这份职业的核心假设是- 开发建议是基于UTE和129Xe MRI的联合方法对早期肺更敏感 骨髓移植患者的结构和功能变化比传统的临床随访和未来的(目标3， Bridge to R01)，这是一种将UTE和129Xe MRI与一组常规肺功能相结合的临床算法 测试，将改善骨髓移植患者的预后。强劲的初步数据支持量化宽松的应用 UTE和129Xe磁共振在这一人群中的应用。 辛辛那提儿童医院在儿童骨髓移植、肺医学、 和放射学，是进行拟议研究和私人投资发展的理想环境 作为一名翻译科学领域的独立研究人员，拥有成功职业生涯的基本技能。《少年派》 已经确定了一个指导团队、合作者和非正式顾问，以支持和指导 研究项目和她的职业发展，后者侧重于培养强大的科学能力 通过正式演示文稿和出版物、网络和教育机会进行交流 国家和国际会议，研究道德行为的正式和非正式培训，以及 协作性拨款提案撰写。

PROJECT SUMMARY Bronchiolitis obliterans syndrome (BOS) is an irreversible, obstructive lung condition resulting from a combination of inflammation and immune response which manifests as permanent pulmonary function decline. BOS is a significant source of pulmonary complications for both lung and bone-marrow transplant (BMT) recipients, and despite its prevalence and precipitous clinical course, there is a lack of clinical tools for routine surveillance for BOS post-transplantation. Surveillance for BOS is largely limited to spirometry, which can be unreliable in young children and insensitive to early airway obstruction, and computed tomography. In BMT patients, routine screening via CT is avoided due to serial ionizing radiation exposure and screening via spirometry is often less frequent than lung-transplant recipients. As a result, pulmonary complications in this population can go under diagnosed, and BMT patients often are referred to pulmonary physicians only after significant lung functional decline, which limits interventional options to improve patient outcomes. Emerging magnetic resonance imaging (MRI) techniques are poised to revolutionize pulmonary imaging and indeed have already begun to have an impact on diseases such as cystic fibrosis, COPD, and asthma. Ultra- short echo time (UTE) MRI methods now rival CT in the visualization and quantification of regional lung parenchymal pathology, and a single breath-hold of hyperpolarized 129Xe can reveal ventilation deficits, which are regions of the lung not properly ventilated due to airway obstruction. The central hypothesis of this career- development proposal is that a combined UTE and 129Xe MRI-based approach is more sensitive to early lung structural and functional changes in BMT patients than traditional clinical follow-up, and that in the future (Aim 3, Bridge to R01), a clinical algorithm that combines UTE and 129Xe MRI with a battery of routine pulmonary function tests, will improve outcomes for BMT patients. Strong preliminary data support the application of quantitative UTE and 129Xe MRI in this population. Cincinnati Children’s is a world-leader in the fields of pediatric bone marrow transplantation, pulmonary medicine, and radiology, and is the ideal environment to conduct the proposed research and for the PI to develop the essential skills to have a successful career as an independent investigator in the translational sciences. The PI has identified a mentoring team, collaborators, and informal advisors to support and guide aspects of the research project and her career development, the latter of which focuses on cultivating strong scientific communication through formal presentations and publications, networking and educational opportunities at national and international conferences, formal and informal training in the ethical conduct of research, and collaborative grant proposal writing.