Assessment of lung function in neonates and infants

新生儿和婴儿肺功能评估

• 批准号: 8531345
• 负责人: Iulian Constantin Ruset
• 金额: $ 24.17万
• 依托单位: XEMED, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8531345
• 关键词: 2 year old; 6 year old; Acute; Adult; Age; Air; Alveolar; Asthma; Biological Markers; Bolus Infusion; Boxing; Breathing; Bronchopulmonary Dysplasia; Caring; Chest; Child; Childhood; Chronic Disease; Chronic lung disease; Clinical; Clinical Treatment; Clinical Trials; Communities; Cystic Fibrosis; Development; Devices; Diagnosis; Diagnostic; Diagnostic Imaging; Diffusion; Diffusion weighted imaging; Dimensions; Disease; Dose; Early Diagnosis; Elements; Engineering; Environmental air flow; Event; Exposure to; Functional Magnetic Resonance Imaging; Gases; Helium; Hypoxia; Image; Imaging Device; Imaging Techniques; Infant; Infant Care; Injury; Institutional Review Boards; Intubation; Ionizing radiation; Length; Lung; Lung diseases; Magnetic Resonance Imaging; Maps; Measurement; Mechanical Ventilators; Medical; Methods; Monitor; Morbidity - disease rate; Motion; Neonatal Intensive Care; Neonatal Intensive Care Units; Noble Gases; Outcome; Outcome Measure; Patient Care; Patients; Pattern; Perinatal; Phase; Physiologic pulse; Pneumonia; Premature Infant; Protocols documentation; Pulmonary function tests; Quantitative Evaluations; Reporting; Research; Research Infrastructure; Research Personnel; Resolution; Respiratory physiology; Risk; Safety; Sedation procedure; Severities; Severity of illness; Simulate; Solutions; Spirometry; Structure; Symptoms; System; Techniques; Technology; Testing; Tissues; Toddler; Tracer; Trees; Ventilator; Very Low Birth Weight Infant; Weaning; Work; X-Ray Computed Tomography; Xenon; age group; base; cost; design; early cystic fibrosis; imaging modality; infrastructure development; injured; lung imaging; neonate; novel; premature; success

DESCRIPTION (provided by applicant): Assessment of lung function in neonates and infants Lung disease is the most common chronic disease of childhood, but methods for assessing lung disease such as spirometry cannot be performed by young children. Thus clinicians have only parental reports of patient symptoms upon which to base treatment decisions. Further, clinical trials of treatments for lung disease are difficult to perform in the absence of a quantitative outcome. Therefore many treatments for lung disease have not been tested in young children. Hyperpolarized (HP) noble gas magnetic resonance imaging is a technique for imaging the lung functional microstructure that provides a quantitative evaluation of lung disease severity in three-dimensions with high resolution. Ventilation imaging depicts regional patency of the airway tree, even down to the smallest airways. Ventilation abnormalities reveal the earliest signs of obstructive disease, such as cystic fibrosis and asthma. Diffusion weighted imaging quantifies the Brownian-motion length-scale of gas atoms. By mapping out acinar dimension regionally, diffusion weighted imaging is exquisitely sensitive to underdeveloped or injured alveolar tissues. Since hyperpolarized gas MRI does not use ionizing radiation, it is well-suited for use in children and infants. What is needed are safe and effective devices and methods for administering and imaging hyperpolarized noble gas in neonates and infants. We propose to develop a simple and elegant method for administering hyperpolarized helium-3 (HHe) to neonates and infants. New MR-compatible gas flow technologies will be developed, compared, and incorporated into a novel pass-though junction box which can substitute a small bolus of HHe for an equal amount of air. Its mostly passive and intrinsically safe design features will allow its use with either fre- breathing infants or with neonates on a mechanical ventilator. We will test the device by imaging free-breathing healthy adults while they are simulating the breathing volumes and patterns of infants. We further propose to adapt our 32-element chest coil which we successfully employed for accelerated structure-function imaging in adults. First we down-size it for subjects 13kg and under, and in year 2 optimize a second chest coil design for neonates under 4.5kg. We will submit IRB filings for these devices as non-significant medical risk devices. Working with our academic collaborators, we will first acquire accelerated hyperpolarized helium-3 images in free-breathing 1-2 year old infants, five who are healthy normals and two with chronic lung disease of prematurity (bronchopulmonary dysplasia, BPD). We will compare accelerated spiral and Cartesian imaging protocols exploiting the parallel coil. After regulatory review, we will proceed to imaging two neonates on ventilators just before they are extubated. One subject will be a neonate born prematurely who has early BPD. The second subject will be a neonate under care due to an hypoxic ischemic event. This subject's lungs should be structurally normal.

描述（由申请人提供）：新生儿和婴儿肺功能的评估 肺病是儿童期最常见的慢性疾病，但幼儿无法进行评估肺病的方法，例如肺活量测定。因此，临床医生只有患者症状的父母报告才能做出治疗决定。此外，在缺乏定量结果的情况下，肺病治疗的临床试验很难进行。因此，许多肺部疾病的治疗方法尚未在幼儿中进行过测试。超极化 (HP) 稀有气体磁共振成像是一种对肺功能微观结构进行成像的技术，可在三维空间中以高分辨率定量评估肺部疾病的严重程度。通气成像描绘了气道树的区域通畅性，甚至​​是最小的气道。通气异常揭示了阻塞性疾病的最早迹象，例如囊性纤维化和哮喘。扩散加权成像量化了气体原子的布朗运动长度尺度。通过局部绘制腺泡尺寸，弥散加权成像对发育不全或受损的肺泡组织非常敏感。由于超极化气体 MRI 不使用电离辐射，因此非常适合儿童使用 和婴儿。需要的是用于对新生儿和婴儿进行超极化惰性气体管理和成像的安全且有效的装置和方法。我们建议开发一种简单而优雅的方法来对新生儿和婴儿施用超极化氦 3 (HHe)。我们将开发、比较新的 MR 兼容气流技术，并将其纳入新型直通接线盒中，该接线盒可以用少量 HHe 代替等量的空气。其主要被动和本质安全的设计特点将允许其用于呼吸自由的婴儿或使用机械呼吸机的新生儿。我们将通过对自由呼吸的健康成年人进行成像来测试该设备，同时模拟婴儿的呼吸量和模式。我们进一步建议改造我们的 32 元件胸部线圈，我们已成功地将其用于成人的加速结构功能成像。首先，我们针对 13 公斤及以下的受试者缩小了其尺寸，并在第二年针对 4.5 公斤以下的新生儿优化了第二个胸部线圈设计。我们将把这些设备作为非重大医疗风险设备提交 IRB 备案。我们将与我们的学术合作者合作，首先获取自由呼吸的 1-2 岁婴儿的加速超极化氦 3 图像，其中 5 名健康正常，两名患有早产儿慢性肺病（支气管肺发育不良，BPD）。我们将比较利用并行线圈的加速螺旋成像协议和笛卡尔成像协议。经过监管审查后，我们将在两名使用呼吸机的新生儿拔管之前对其进行成像。一名受试者是患有早期 BPD 的早产新生儿。第二个受试者是一名因缺氧缺血事件而接受护理的新生儿。该对象的肺部结构应该正常。