Very-short-time diffusion MRI of hyperpolarized gases

描述（由申请人提供）：本研究的主要目的是开发利用超极化惰性气体磁共振成像（MRI）在肺泡长度尺度上评估肺部微观结构的新方法。非放射性稀有气体同位素氦-3 （3He）和氙-129 （129Xe）在20世纪90年代中期被引入MRI作为吸入造影剂，此后显示出巨大的潜力，可以提供肺气肿和哮喘等肺部疾病的医学相关信息，达到其他成像方式无法达到的程度。特别是，吸入的超极化气体的扩散MRI比高分辨率计算机断层扫描（CT）或标准肺功能检查更早地发现与疾病相关的肺微观结构变化。扩散核磁共振成像的优势在于，它允许人们探测比传统成像像素小得多的长度尺度；该技术的有效“分辨率”取决于测量扩散效应的时间。非常短的时间尺度，相当于肺的肺泡尺寸，使用现有的超极化气体扩散MRI方法很难达到。因此，到目前为止，绝大多数体内超极化气体扩散研究都是在与肺泡簇或腺泡大小相对应的较长时间尺度上进行的。本研究的基本前提是，在非常短的时间尺度上进行弥散测量，将对肺腺泡下水平上早期和渐进式疾病相关的肺微结构变化更加敏感。具体的研究目的是开发、测试和优化新的MRI脉冲序列策略，用于测量吸入超极化气体的极短时间扩散；建立优化技术在模型系统肺泡长度尺度上进行定量结构测量的能力；并将新技术应用于正常和患病动物的肺中，以评估其在肺泡水平检测肺微结构微小变化的潜力，包括腺泡空气空间表面与体积比的变化。这些目标的成功完成将为临床医生和科学家研究肺部疾病的病理生理学、监测疾病进展和开发有效的治疗方法开辟令人兴奋的新途径。

DESCRIPTION (provided by applicant): The principal objective of this research is to develop new methods for assessing lung microstructure at alveolar length scales, using hyperpolarized noble-gas magnetic resonance imaging (MRI). The non- radioactive noble-gas isotopes helium-3 (3He) and xenon-129 (129Xe) were introduced in the mid-1990s as inhaled contrast agents for MRI, and have since shown substantial potential for providing medically relevant information about lung diseases such as emphysema and asthma, to a degree inaccessible by other imaging modalities. In particular, diffusion MRI of the inhaled hyperpolarized gas shows promise for detecting disease- related changes in lung microstructure earlier than high-resolution computed tomography (CT) or standard pulmonary function tests. The advantage of diffusion MRI is that it allows one to probe length scales that are much smaller than a conventional imaging pixel; the effective "resolution" of the technique depends on the time over which diffusion effects are measured. Very-short time scales, corresponding to alveolar dimensions in the lung, are very challenging to reach using existing hyperpolarized-gas diffusion MRI methods. Accordingly, the vast majority of in-vivo hyperpolarized-gas diffusion studies to date have been performed at longer time scales corresponding to the size of alveolar clusters, or acini. The basic premise of the proposed research is that diffusion measurements at very short time scales will be significantly more sensitive to early and incremental disease- related changes in lung microstructure at the sub-acinar level. The specific research aims are to develop, test, and optimize new MRI pulse-sequence strategies for measuring very-short-time diffusion of inhaled hyperpolarized gas; to establish the ability of the optimized techniques to make quantitative structural measurements at alveolar length scales in model systems; and to apply the new techniques in normal and diseased animal lungs to evaluate their potential for detecting small changes in lung microstructure at the alveolar level, including alterations in the surface-to-volume ratio of acinar air spaces. Successful completion of these aims will open up exciting new avenues for clinicians and scientists to investigate the pathophysiology of lung disease, monitor disease progression, and develop effective treatments. PUBLIC HEALTH RELEVANCE: The principal objective of the proposed research is to develop methods for non-invasively measuring details of microscopic lung structure using magnetic resonance imaging. Application of these methods may be used for early detection of serious lung diseases such as emphysema and will provide a tool for medical researchers to better investigate the causes and potential treatments of lung disease.