Assessment of lung function in neonates and infants

新生儿和婴儿肺功能评估

• 批准号: 9110299
• 负责人: Talissa A Altes
• 金额: $ 50万
• 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 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9110299
• 关键词: 3 year old; Age; Air; Alveolar; Asthma; Award; Bolus Infusion; Breathing; Bronchopulmonary Dysplasia; Chest; Child; Childhood; Chronic Disease; Chronic lung disease; Clinical; Clinical Research; Clinical Trials; Communities; Computer software; Cystic Fibrosis; Data Analyses; Development; Devices; Diagnosis; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Dimensions; Disease; Dose; Drug Approval; Drug Labeling; Early Diagnosis; Engineering; Environmental air flow; Exposure to; Functional Imaging; Funding; Gases; Gestational Age; Hand; Helium; Image; Infant; Injury; Ionizing radiation; Language; Length; Lung; Lung diseases; Magnetic Resonance Imaging; Manuals; Mechanics; Methods; Modality; Monitor; Morbidity - disease rate; Neonatal; Noble Gases; Obstructive Lung Diseases; Outcome Measure; Patient Care; Pharmaceutical Preparations; Phase; Philanthropic Fund; Physiologic pulse; Population; Premature Infant; Rare Diseases; Recruitment Activity; Reporting; Research Infrastructure; Research Personnel; Resolution; Respiratory physiology; Risk; Sequence Analysis; Severities; Severity of illness; Small Business Innovation Research Grant; Spirometry; Structure; Technology; Testing; Tracer; Voice; X-Ray Computed Tomography; base; chest computed tomography; cohort; cystic fibrosis patients; imaging biomarker; imaging modality; lung imaging; neonate; new technology; novel therapeutics; premature; public health relevance

 DESCRIPTION (provided by applicant): Although lung disease is a major cause of morbidity in children, the forced breathing maneuvers required for assessing disease, spirometry, cannot be performed by young children. Thus, characterizing the activity or monitoring the severity of pediatric lung disease in younger children is primarily qualitative, based upon parental reports, with little quantitative information upon which to base treatment decisions. Equally important, it is difficult to perform clinical trials in young children with lung disease in the absence of a quantifiable outcome measure. Hyperpolarized helium-3 (HHe) magnetic resonance imaging (MRI) is an exquisitely sensitive, versatile, and quantitative modality for tomographic (3D) mapping of pulmonary functional microstructure with excellent resolution. The Apparent Diffusion Coefficient (ADC), an imaging biomarker for alveolar length-scales, can determine the stage of prematurity and/or assess injury to septal walls associated with chronic lung disease of prematurity, also known as bronchopulmonary dysplasia (BPD). Because HHe MRI is non-ionizing, infants and children stand the most to benefit from this newly emerging diagnostic modality. During Phase I we developed and demonstrated new devices, methods, and technology and acquired HHe MRI images from eleven free-breathing, unsedated infants between the ages of nine months and three years, establishing feasibility for imaging without voice inhalation and breath-hold commands. For Phase II we propose clinical studies, technical refinements, and regulatory filings that will advance HHe MRI towards a New Drug Application. In Aim#1 we will conduct a simple longitudinal trial, recruiting eight preterm infants with BPD. We will perform the first imaging session in the NICU and image again at six months corrected gestational age. We will also recruit a cohort of eight full-term infants, and image at one and six months. This second cohort will serve as an age-matched comparator for normal development of alveolar dimension. We will investigate the hypothesis that HHe MRI diffusion-sensitive imaging is a sensitive and specific assessment of alveolar dimension in neonates, distinguishing abnormal from normal and stratifying severity. In Aim#2 we will refine the infrastructure technology and establish a final specification for all essential components and methods required for neonatal lung function assessments including the HHe polarizer, gas administration device(s), neonatal-sized chest coil, fast spiral imaging pulse sequences, and data analysis software. In Aim#3 we will submit regulatory filings for FDA advancement of HHe as a diagnostic drug agent for assessments of lung functional microstructure in neonates. We will also submit regulatory filings to advance the case for FDA approval of our devices for the NICU. BPD is considered an orphan disease, which eases the regulatory burden for approval of HHe as a New Drug for this disease population.

 描述（由申请人提供）：尽管肺部疾病是儿童发病的主要原因，但评估疾病所需的用力呼吸动作（肺量测定）不能由幼儿进行。因此，根据父母的报告，描述年幼儿童的活动或监测儿科肺部疾病的严重程度主要是定性的，很少有定量信息作为治疗决策的基础。同样重要的是，在缺乏可量化的结果测量的情况下，很难在患有肺部疾病的幼儿中进行临床试验。超极化氦-3（HHe）磁共振成像（MRI）是一种灵敏、多功能和定量的方法，可用于肺功能微结构的断层扫描（3D）成像，具有出色的分辨率。表观扩散系数（ADC）是肺泡长度尺度的成像生物标志物，可以确定早产儿的阶段和/或评估与早产儿慢性肺病（也称为支气管肺发育不良（BPD））相关的间隔壁损伤。由于HHe MRI是非电离的，因此婴儿和儿童最能从这种新兴的诊断方式中受益。在第一阶段，我们开发并展示了新的设备，方法和技术，并从11名9个月至3岁的自由呼吸，未镇静的婴儿中获得了HHe MRI图像，建立了无需语音吸气和屏气命令的成像可行性。对于第二阶段，我们提出了临床研究，技术改进和监管备案，这将推动HHe MRI向新药申请。在目标1中，我们将进行一项简单的纵向试验，招募8名患有BPD的早产儿。我们将在新生儿重症监护室进行第一次成像，并在校正胎龄6个月时再次成像。我们还将招募一组8名足月婴儿，分别在1岁和6岁时进行成像。 个月这第二个队列将作为年龄匹配的比较正常发育的肺泡尺寸。我们将调查的假设，HHe MRI扩散敏感成像是一个敏感和具体的评估肺泡尺寸在新生儿，区分异常正常和分层的严重程度。在目标2中，我们将完善基础设施技术，并为新生儿肺功能评估所需的所有基本组件和方法建立最终规范，包括HHe偏振器、气体管理设备、胸部尺寸的胸部线圈、快速螺旋成像脉冲序列和数据分析软件。在目标3中，我们将提交FDA推进HHe作为诊断药物用于评估新生儿肺功能微观结构的监管文件。我们还将提交监管文件，以推动FDA批准我们的NICU设备。BPD被认为是一种孤儿病，这减轻了批准HHe作为该疾病人群新药的监管负担。