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: 9371094
• 负责人: Laura Lee Walkup
• 金额: $ 11.1万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9371094
• 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; Environmental air flow; Ethics; Exposure to; Foundations; Funding; Future; Gases; Gold; Hematology; Hospitalization; Image; Imagery; 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; 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; Writing; X-Ray Computed Tomography; airway obstruction; base; career; career development; clinical care; clinical imaging; follow-up; functional decline; imaging modality; improved; improved outcome; lung imaging; mortality; novel; oncology; outcome forecast; patient population; pulmonary function; pulmonary function decline; respiratory; screening; secondary outcome; skills; symposium; tool

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 支气管炎闭塞综合征（BOS）是由组合引起的不可逆的阻塞性肺部疾病 炎症和免疫反应表现为永久性肺功能下降。 BOS是一个 肺部和骨髓移植（BMT）受体的肺部并发症的重要来源，以及 尽管它的盛行和急剧的临床过程，但缺乏常规监视的临床工具 BOS移植后。 BOS的监视很大程度上仅限于肺活量法，这在年轻人中可能不可靠 儿童对早期气道异议和计算机断层扫描不敏感。在BMT患者中，常规 由于连续电离辐射暴露和通过肺活量测定法进行筛查，避免通过CT进行筛查通常更少 通常比肺移植者接受者。结果，该人群中的肺并发症可能会陷入困境 诊断出，BMT患者通常仅在明显的肺功能性后才转介肺医生 下降，这限制了改善患者预后的介入选择。 新兴的磁共振成像（MRI）技术被毒化为彻底改变肺成像和 确实，已经开始对诸如囊性纤维化，COPD和哮喘等疾病产生影响。极端主义者- 现在的可视化和数量，较短的回声时间（UTE）MRI方法可能会危险 实质病理学和单个超极化129xE的单一呼吸可以揭示通风定义，这是 是由于气道异议而无法正确通风的肺部区域。这个职业的核心假设 - 开发建议是一种组合的UTE和129XE基于MRI的方法对早期肺更敏感 BMT患者的结构和功能变化比传统的临床随访以及将来的结构变化（AIM 3， 将UTE和129XE MRI与一系列常规肺功能相结合的临床算法桥梁桥梁） 测试将改善BMT患者的预后。强大的初步数据支持定量的应用 UTE和129XE MRI在该人群中。 辛辛那提儿童是小儿骨髓移植，肺部医学领域的世界领导者 和放射学，是进行拟议研究和PI开发拟议研究的理想环境 成为转化科学独立研究者的成功职业的基本技能。 pi 已经确定了一个心理团队，合作者和非正式顾问，以支持和指导和指导 研究项目及其职业发展，后者的重点是培养强大的科学 通过正式演示和出版物，网络和教育机会进行交流 国家和国际会议，研究道德行为方面的正式和非正式培训以及 协作赠款提案写作。