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

使用 UTE 和 129Xe MRI 早期检测 BMT 患者的局部 BOS

• 批准号: 10118604
• 负责人: Laura Lee Walkup
• 金额: $ 24.9万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10118604
• 关键词: Address; Algorithms; Antibiotics; Applications Grants; Asthma; Bone Marrow Transplantation; Bronchiolitis Obliterans; Cessation of life; Child; Childhood; Chronic Obstructive Airway Disease; Clinic; Clinical; Communication; Cystic Fibrosis; Data; Death Rate; Diagnosis; Disease; Disease Progression; Early Diagnosis; Early Intervention; Emergency department visit; Environment; Ethics; Exposure to; Foundations; Funding; Future; Gases; Gold; Hematology; Hospitalization; Image; Imaging Techniques; Immune response; Incidence; Inflammation; Interdisciplinary Study; International; Intervention; Ionizing radiation; Lead; Lung; Lung Transplantation; Lung diseases; Magnetic Resonance Imaging; Measures; Mentors; Methods; Monitor; Morbidity - disease rate; Obstruction; Obstructive Lung Diseases; Oncology; Outcome; Pathology; Patient-Focused Outcomes; Patients; Pediatrics; Physicians; Physiologic pulse; Population; Prevalence; Preventive Intervention; Publications; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary function tests; Pulmonology; Radiation exposure; Radiology Specialty; Regimen; Research; Research Personnel; Research Project Grants; Respiratory Tract Infections; Respiratory physiology; Source; Spirometry; Structural defect; Structure; Syndrome; Time; Training; Translational Research; Transplant Recipients; Transplantation; Variant; Visualization; Writing; X-Ray Computed Tomography; airway obstruction; career; career development; clinical care; clinical imaging; follow-up; functional decline; imaging approach; imaging modality; improved; improved outcome; lung imaging; mortality; novel imaging technique; outcome forecast; patient population; post-transplant; pulmonary function; pulmonary function decline; respiratory; routine screening; screening; secondary outcome; skills; symposium; tool; ventilation

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.

项目摘要 闭塞性细支气管炎综合征（BOS）是一种不可逆的阻塞性肺病， 炎症和免疫反应，表现为永久性肺功能下降。BOS是一个 肺和骨髓移植（BMT）受者肺部并发症的重要来源，以及 尽管它的流行和陡峭的临床过程中，有缺乏常规监测的临床工具， 移植后BOS。对BOS的监测主要限于肺量测定法，这在年轻人中可能不可靠。 儿童和不敏感的早期气道阻塞，和计算机断层扫描。在BMT患者中， 由于连续的电离辐射暴露，避免了通过CT进行筛查，而通过肺量计进行筛查通常较少 比肺移植受者更常见因此，这一人群的肺部并发症可能低于 BMT患者通常只有在肺功能显著改善后才被转诊给肺科医生。 下降，这限制了改善患者结局的干预选择。 新兴的磁共振成像（MRI）技术有望彻底改变肺部成像， 事实上，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- 短回波时间（UTE）MRI方法现在在局部肺的可视化和定量方面与CT相媲美 实质病理学，超极化129 Ω的单次屏气可以显示通气缺陷， 是由于气道阻塞而无法正常通气的肺部区域。这一职业的核心假设是- 一项开发建议是，基于UTE和129 MRI的联合方法对早期肺栓塞更敏感。 BMT患者的结构和功能变化比传统的临床随访，并在未来（目的3， 桥接至R 01），一种将UTE和129 MRI与常规肺功能组合的临床算法 测试，将改善BMT患者的结果。强有力的初步数据支持应用定量 UTE和129 MRI。 辛辛那提儿童医院是儿科骨髓移植、肺内科、 和放射学，是进行拟议研究和PI开发 基本技能，有一个成功的职业生涯作为一个独立的研究人员在翻译科学。的PI 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，后者的重点是培养强大的科学 通过正式演讲和出版物、网络和教育机会进行交流， 国家和国际会议，研究伦理行为方面的正式和非正式培训，以及 协作式赠款提案写作。