Regional Quantification of Lung Function in Cystic Fibrosis using Xe129 MRI

使用 Xe129 MRI 对囊性纤维化肺功能进行区域量化

• 批准号: 8420003
• 负责人: Jaime Mata
• 金额: $ 33.25万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8420003
• 关键词: 12 year old; 3-Dimensional; Address; Age; Alveolar; Alveolus; Breeding; Caucasians; Caucasoid Race; Chemical Shift Imaging; Childhood; Chloride Channels; Clinical; Clinical Trials; Complex; Cystic Fibrosis; Data; Development; Diagnosis; Disease; Enrollment; Environmental air flow; Erythrocytes; FDA approved; Fibrosis; Future; Gases; Genes; Genotype; Goals; Human; Infection; Inflammation; Ionizing radiation; Lung; Lung diseases; Magnetic Resonance Imaging; Measurement; Measures; Methods; Molecular; Morphologic artifacts; Mucous body substance; Noise; Obstruction; Patients; Performance; Phase; Physiologic pulse; Physiological; Physiology; Population; Predisposition; Pulmonary Cystic Fibrosis; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary function tests; Radioactive; Resolution; Respiratory physiology; Safety; Severity of illness; Signal Transduction; Single-Gene Defect; Speed; Spirometry; Staging; Structure of parenchyma of lung; Study Subject; Supportive care; Techniques; Testing; Thick; Tissues; Treatment Efficacy; Work; base; cost; cystic fibrosis patients; improved; infancy; insight; magnetic resonance spectroscopic imaging; nutrition; prevent; public health relevance; response; tool; uptake

DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is the most common, fatal, single gene defect in the Caucasian population. The gene encodes a chloride channel that, when defective, causes the lungs to produce unusually thick and viscous mucus that clogs the airways. This leads to poor lung ventilation and creates an ideal breeding ground for lung infections. Current treatments for CF are aimed at improving airway clearance, and preventing or curing infection that is to improve ventilation and decrease inflammation. CF is typically diagnosed in early infancy, and the current median age of survival is approximately 37 years. There are many required daily supportive therapies including specialized (and costly) treatments to alleviate mucus obstruction, control lung infections, and maximize nutrition. Exciting new treatments under development are aimed at the molecular basis of the disease. Such treatments are likely to be quite expensive, like the recently FDA approved Kalydeco (VX770, Vertex, MA) with an estimated annual cost of more than $250,000/patient, and will be tested in only the most common genotypes. The purpose of the proposed work is to optimize and evaluate a new method capable to provide new insights into pulmonary CF and assess the efficacy of treatments for CF. Currently a clinical method does not exist for non-invasively assessing regional inflammation or gas exchange in the lung. A method recently pioneered by our group, based on hyperpolarized Xe-129 gas (hp Xe-129) and magnetic resonance spectroscopic imaging (MRSI), and termed Single Breath-hold Chemical Shift Imaging (3D SB-CSI), is capable of non-invasively assessing, in a single breath hold (less than 15 seconds), regional lung ventilation, inflammation, and gas exchange-uptake without the use of radioactive substances or ionizing radiation. Our promising preliminary results let us hypothesize that this technique will provide new insights into pulmonary CF and its response to treatment. The first aim of this project is to implement, optimize, and validate improvements to our current 3D SB-CSI technique to increase both the speed and resolution of the acquisition, to improve our ability to separate the tissue and red-blood-cell (RBC) contributions, and to improve the signal- to-noise ratio (SNR). The second aim is two-fold: 1) we propose to characterize gas exchange among lung compartments by measuring regional Xe-129 uptake from the alveoli into lung tissue and RBCs. These measurements will be conducted in 15 healthy subjects (ages 12 years-old and up) and will be age matched to the CF subjects studied under the second part of this aim; and 2) perform an exploratory study in 30 subjects with CF (15 subjects with mild-moderate pulmonary disease and 15 subjects with severe pulmonary disease). Since this is a pediatric disease, we propose enrolling subjects as young as 12 years old and up. This will allow us to characterize regional Xe-129 gas uptake into tissue and into RBCs as a function of disease severity. All subjects under this aim will also receive full pulmonary function tests (PFTs) to evaluate the degree of disease severity and to correlate with the results from 3D SB-CSI.

描述（由申请人提供）：囊性纤维化（CF）是高加索人群中最常见的，致命的单基因缺陷。该基因编码一个氯化物通道，当缺陷时，该通道会导致肺部产生异常厚和粘性的粘液，使气道堵塞。这导致肺通风不良，并为肺部感染创造了理想的繁殖地。当前对CF的治疗旨在改善气道间隙，并防止或治愈感染，这是为了改善通风和减少炎症。 CF通常在婴儿早期诊断出，当前生存年龄大约为37岁。有许多需要的日常支持疗法，包括专门的（和昂贵）治疗，以减轻粘液阻塞，控制肺部感染和最大化营养。令人兴奋的开发新疗法针对该疾病的分子基础。此类处理可能会非常昂贵，例如最近获得FDA批准的Kalydeco（VX770，VERTEX，MA），估计年费用超过250,000美元/患者，并且将仅以最常见的基因型进行测试。拟议工作的目的是优化和评估一种能够为肺CF提供新见解的新方法，并评估CF治疗的功效。目前，对于非侵入性评估肺部的区域炎症或气体交换尚不存在临床方法。我们小组最近基于超极化的XE-129气体（HP XE-129）和磁共振光谱成像（MRSI）（MRSI）并被称为单呼吸含量化学移位成像（3D SB-CSI）的一种方法，在不相处评估的情况下，没有超过15秒的速度，并将其称为单一呼吸含量的化学偏移成像（3D SB-CSI），并将其称为单个呼吸化学偏移成像（3D SB-CSI），并且能够进行较少的频率（较小的秒数）。放射性物质或电离辐射。我们有希望的初步结果使我们假设该技术将为肺CF提供新的见解及其对治疗的反应。该项目的第一个目的是实施，优化和验证我们当前3D SB-CSI技术的改进，以提高采集的速度和分辨率，以提高我们分离组织和红血球（RBC）贡献的能力，并提高信号比率（SNR）。第二个目标是两个方面：1）我们建议通过测量从肺泡进入肺组织和RBC的区域XE-129摄取区域XE-129来表征肺部室之间的气体交换。这些测量将在15名健康受试者（12岁及以上）中进行，并将与该目标第二部分研究的CF受试者相匹配； 2）对30名患有CF的受试者（15名患有轻度肺疾病的受试者和15名患有严重肺部疾病的受试者）进行探索性研究。由于这是一种儿科疾病，我们建议入学到12岁及以上的受试者。这将使我们能够将XE-129 XE-129气体吸收到组织和RBC中的特征，这是疾病严重程度的函数。此目标下的所有受试者还将接受完整的肺功能测试（PFT），以评估疾病严重程度并与3D SB-CSI的结果相关。