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

• 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
• 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

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.

项目摘要/摘要 造血干细胞移植（HSCT）后发生迟发性非感染性肺部并发症 在多达一半的所有患者中，在病因学和临床过程中是异质的，并且是致命的。肺活量测定 尽管这是监测的基石，但一半的儿科HSCT人群无法进行肺量测定。作为 因此，儿童HSCT后肺损伤通常在晚期才被诊断出来， 是有限的，损害是不可逆转的，死亡率很高。HSCT后早期发现肺损伤是我们的最佳选择 有机会进行干预，稳定肺功能下降，并改善结果，迫切需要 为年轻的HSCT患者提供更好的诊断，特别是那些无法进行肺量测定的患者。本 最后，我们开发了吸入超极化氙-129（129）通气和气体交换磁 磁共振成像（MRI）技术在空间上分辨、区分和量化小气道、间质和 微血管异常该项目的长期目标是降低 通过临床应用129 MRI作为基于成像的肺功能检查， 诊断该建议的中心假设是，129 μ M MRI在年龄很小的儿童中是可行的， 无法进行PFT，并将检测HSCT后的早期肺部受累。我们的方法基于三个 具体目的：（1）通过对健康对照志愿者进行成像， 诊断为气体交换障碍的患者，年龄6-18岁;（2）HSCT后肺表型 在6-18岁儿童中使用129 mmHg通气和气体交换MRI， HSCT，在HSCT后约100天和1年时进行纵向MRI和PFT;（3）优化快速 2-5岁HSCT患者的129例MRI。这种方法得到了我们以前工作的支持， 经验表明，129 MRI在新生儿、无法进行肺量测定的幼儿中是可行的， 以及镇静剂患者。这种方法是创新的，因为129 mA气体交换MRI对于任何儿科患者都是新颖的。 人口，和成像儿童诊断气体交换障碍将建立一个概念的桥梁 更好地了解疾病的病理生理学和129个气体交换MRI结果之间的关系，这将增强 HSCT人群中129 MRI的临床解释和气体交换损伤的诊断。 儿科HSCT患者的初步数据显示扩散屏障和RBC转移异常， 提示其为临床上未充分认识的非阻塞性表型。这个项目将彻底改变临床护理 有肺部并发症的年轻HSCT患者。通气、间质和 HSCT后129 MRI的微血管变化将有助于临床风险分层。129英寸MRI将使 无症状患者的监测和早期发现，表型分析以个性化临床管理， 治疗方法，并在非常年幼的儿童肺功能的稳健评估。