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: 10386772
• 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/10386772
• 关键词: Address; Algorithms; Antibiotics; Applications Grants; Asthma; Bone Marrow Transplantation; Bronchiolitis Obliterans; Cessation of life; Child; Childhood; Chronic Obstructive Pulmonary 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; Prevention; Prognosis; 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; 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; 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.

项目概要 闭塞性细支气管炎综合征 (BOS) 是一种不可逆的阻塞性肺部疾病，由多种因素共同导致 表现为永久性肺功能下降的炎症和免疫反应是一种BOS。 肺和骨髓移植（BMT）受者肺部并发症的重要来源，以及 尽管其普遍存在且临床病程急速，但仍缺乏常规监测的临床工具 BOS 移植后的监测主要限于肺活量测定，这对于年轻人来说可能不可靠。 儿童和对早期气道阻塞不敏感的患者，常规进行计算机断层扫描。 由于连续电离辐射暴露，避免通过 CT 筛查，而通过肺活量测定法筛查通常较少 因此，该人群的肺部并发症可能会比肺移植受者更常见。 确诊后，BMT 患者通常只有在肺功能显着改善后才会转诊至肺科医师处 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) 技术有望彻底改变肺部成像和 事实上，它们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。 短回波时间 (UTE) MRI 方法现在在局部肺部的可视化和量化方面可与 CT 相媲美 实质病理学和单次屏气超极化 129Xe 可以揭示通气缺陷，这 是由于气道阻塞而导致肺部无法正常通气的区域。 开发建议是基于 UTE 和 129Xe MRI 的组合方法对早期肺更敏感 与传统临床随访相比，BMT 患者的结构和功能变化以及未来的变化（目标 3， Bridge to R01），一种将 UTE 和 129Xe MRI 与一系列常规肺功能相结合的临床算法 强有力的初步数据支持定量的应用。 该人群中的 UTE 和 129Xe MRI。 辛辛那提儿童医院在儿科骨髓移植、肺科、 和放射学，并且是进行拟议研究和 PI 开发 作为转化科学领域的独立研究者，拥有成功职业生涯的基本技能 已经确定了一个指导团队、合作者和非正式顾问来支持和指导项目的各个方面 研究项目和她的职业发展，后者的重点是培养强大的科学能力 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、研究道德行为方面的正式和非正式培训，以及 协作资助提案撰写。

项目成果

Modern Lung Magnetic Resonance Imaging to Screen for Pulmonary Complications in Patients with Dyskeratosis Congenita.

现代肺磁共振成像筛查先天性角化不良患者的肺部并发症。

• 发表时间: 2021-12-01
• 影响因子: 24.7
• 作者: Walkup, Laura L;Myers, Kasiani C;Willmering, Matthew M;Mehta, Parinda A;Nelson, Adam S;Fleck, Robert J;Woods, Jason C;Davies, Stella M;Towe, Christopher T
• 通讯作者: Towe, Christopher T