Early detection of pulmonary complications of hematopoietic stem-cell transplantation in children using hyperpolarized xenon MRI

超极化氙MRI早期发现儿童造血干细胞移植肺部并发症

基本信息

批准号：
10563271
负责人：
Laura Lee Walkup
金额：
$ 65.32万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-15 至 2027-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10563271
关键词：
18 year old 5 year old Age Awareness Blood Vessels Cessation of life Characteristics Child Childhood Childhood Injury Clinical Clinical Management Contrast Media Data Defect Diagnosis Diagnostic Diffusion Disease Early Diagnosis Early Intervention Ensure Erythrocytes Etiology Evaluation Functional disorder Gases Goals Hematopoietic Stem Cell Transplantation Heterogeneity Image Imaging Techniques Impairment Individual Inhalation Lung Lung Transplantation Lung diseases MRI Scans Magnetic Resonance Imaging Malignant - descriptor Measures Monitor Morbidity - disease rate Neonatal Non-Malignant Nursery Schools Obstruction Outcome Patient-Focused Outcomes Patients Phenotype Physiological Population Process Pulmonary function tests Research Resolution Risk Sampling Scanning School-Age Population Sedation procedure Signal Transduction Source Spirometry Techniques Testing Therapeutic Three-Dimensional Imaging Tissues Toddler Translating Transplant Recipients Work X-Ray Computed Tomography Xenon chest computed tomography clinical application clinical care clinical risk diagnostic strategy experience imaging modality improved improved outcome innovation interstitial lung injury microvascular pathology mortality neonate novel personalized management personalized therapeutic pulmonary agents pulmonary function pulmonary function decline risk stratification success targeted treatment treatment response vascular abnormality vascular factor ventilation volunteer

项目摘要

PROJECT SUMMARY/ABSTRACT Late-onset, non-infectious pulmonary complications following hematopoietic stem-cell transplant (HSCT) occur in up to half of all patients, are heterogeneous in etiology and in clinical course, and are deadly. Spirometry is the cornerstone of surveillance, yet half of the pediatric HSCT population are unable to perform spirometry. As a result, post-HSCT lung injury in children often is diagnosed in an advanced stage, where therapeutic options are limited, damage is irreversible, and mortality is high. Early detection of lung injury after HSCT is our best opportunity to intervene, stabilize lung-function decline, and improve outcomes, and there is an urgent need for better diagnostics for young HSCT patients—especially for those who are unable to perform spirometry. To this end, we have developed inhaled hyperpolarized xenon-129 (129Xe) ventilation and gas-exchange magnetic resonance imaging (MRI) techniques to spatially resolve, differentiate, and quantify small airway, interstitial, and microvascular abnormalities. The long-term goal of this project is to lower pulmonary-related morbidity in the pediatric HSCT population via the clinical application of 129Xe MRI as an imaging-based, lung-function diagnostic. The central hypothesis of this proposal is that 129Xe MRI is feasible in very young children who are unable to perform PFTs and will detect early lung involvement post-HSCT. Our approach is based on three Specific Aims: (1) develop 129Xe gas-exchange MRI in children by imaging healthy-control volunteers and patients with diagnosed gas-exchange impairment ages 6-18 years old; (2) phenotype post-HSCT pulmonary involvement using 129Xe ventilation and gas-exchange MRI in children ages 6-18 years old who have received HSCT, with longitudinal MRI and PFTs at ~100 days and 1-year post-HSCT; (3) optimize strategies for rapid 129Xe MRI in HSCT patients ages 2-5 years old. This approach is supported by our previous work and experience showing 129Xe MRI is feasible in neonates, in young children who are unable to perform spirometry, and in sedated patients. This approach is innovative because 129Xe gas-exchange MRI is novel to any pediatric population, and imaging children with diagnosed gas-exchange impairment will build a conceptual bridge between better-understood disease pathophysiology and 129Xe gas-exchange MRI findings, which will enhance the clinical interpretation of 129Xe MRI and diagnosis of gas-exchange impairment in the HSCT population. Preliminary data in pediatric HSCT patients revealed diffusion-barrier and RBC-transfer abnormalities, suggesting a clinically-under-recognized, non-obstructive phenotype. This project will revolutionize clinical care for young HSCT patients with pulmonary complications. Longitudinal trajectories of ventilation, interstitial, and microvascular changes from 129Xe MRI post-HSCT will help in clinical risk stratification. 129Xe MRI will enable surveillance and early detection in asymptomatic patients, phenotyping to personalize clinical management and therapeutic approach, and robust assessment of lung function in very young children.

项目概要/摘要造血干细胞移植 (HSCT) 后出现迟发性非感染性肺部并发症多达一半的患者在病因学和临床过程中存在异质性，并且肺活量测定是致命的。监测的基石，但一半的儿科 HSCT 人群无法进行肺活量测定。因此，儿童造血干细胞移植后肺损伤通常在晚期才被诊断出来，此时需要采取治疗方案 HSCT 后早期发现肺损伤是我们最好的选择。干预、稳定肺功能衰退和改善预后的机会，并且迫切需要为年轻的 HSCT 患者提供更好的诊断，尤其是那些无法进行肺活量测定的患者。最后，我们开发了吸入式超极化氙129（129Xe）通气和气体交换磁力磁共振成像 (MRI) 技术可在空间上解析、区分和量化小气道、间质和该项目的长期目标是降低肺部相关的发病率。通过 129Xe MRI 的临床应用作为基于成像的肺功能评估儿童 HSCT 人群该提案的中心假设是 129Xe MRI 对于年幼的儿童是可行的。无法进行 PFT 并能检测 HSCT 后的早期肺部受累情况我们的方法基于以下三个方面。具体目标：(1) 由健康的成像控制志愿者开发儿童 129Xe 气体交换 MRI 年龄 6-18 岁诊断出气体交换障碍的患者 (2) HSCT 后肺部表型；使用 129Xe 通气和气体交换 MRI 对接受过治疗的 6-18 岁儿童进行干预 HSCT，在 HSCT 后约 100 天和 1 年进行纵向 MRI 和 PFT (3) 优化快速策略； 2-5 岁 HSCT 患者的 129Xe MRI 这种方法得到了我们之前的工作和支持。经验表明 129Xe MRI 可用于新生儿、无法进行肺活量测定的幼儿、这种方法对于使用镇静剂的患者来说是创新的，因为 129Xe 气体交换 MRI 对于任何儿科来说都是新颖的。人群，并对诊断出气体交换障碍的儿童进行成像将建立一座概念桥梁更好地理解疾病病理生理学和 129Xe 气体交换 MRI 结果之间的关系，这将增强 129Xe MRI 的临床解释和 HSCT 人群气体交换障碍的诊断。儿科 HSCT 患者的初步数据显示扩散屏障和红细胞转移异常，表明临床上未被充分认识的非阻塞性表型该项目将彻底改变临床护理。适用于患有肺部并发症的年轻 HSCT 患者的通气、间质和呼吸的纵向轨迹。 HSCT 后 129Xe MRI 的微血管变化将有助于临床风险分层。对无症状患者进行监测和早期发现，进行表型分析以个性化临床管理和治疗方法以及对幼儿肺功能的稳健评估。