Ultra-fast molecular MRI of human adipose tissue with hyperpolarized xenon-129 contrast agent

 描述（由申请人提供）：棕色脂肪组织（BAT）在成年人中与血脂代谢、葡萄糖稳态和体重维持的潜在参与已经引起了重大的科学关注。直到最近，BAT从儿童到成年的持久性被认为是不存在的。先前将BAT的存在与代谢综合征的发展反向联系起来的研究是在动物模型（主要是小鼠和大鼠）中进行的。然而，关于BAT在人类中的功能（hBAT），几乎没有明确的确定。这种限制可能部分是由于缺乏技术允许纵向研究的功能hBAT具有良好的时间分辨率。尽管最近出现了基于MRI的成像技术，可以量化BAT质量并通过测温检测激活，但迄今为止使用的主要技术是18F-FDG-PET/CT。除了辐射暴露风险外，该技术还因其可能低估hBAT的流行率而受到审查：BAT的葡萄糖摄取不是首选的能量底物。最近的报告使用溶解在血液中的亲脂性超极化（HP）天然丰度氙-129气体检测小鼠中的BAT，与用于检测BAT活性和产热的18F-FDG-PET/CT相比是有利的。然而，迄今为止，BAT的氙成像尚未在人类中进行。因此，在我们的工作中，我们将有科目吸入超极化氙-129气体，以获得亚秒级收购的BAT激活的MRI图像在直立姿势0.05 T的临床多核成像系统。除了通过HP 129 β成功检测hBAT活性的主要目标之外，我们的研究还将检查根据年龄、性别和体重指数选择的瘦和肥胖成年人在hBAT产热刺激后激活的差异。为了实现这些目标，在本研究中，我们将追求以下三个具体目标：[1]构建用于0.05 T临床成像系统的129射频检测线圈，该线圈与临床129超极化器连接; [2]开发用于0.05 T MR扫描仪的129成像协议; [3]检测成人棕色脂肪组织对产热刺激的反应。影响力：通过高极化（>50%）、低成本（<20美元/剂）、天然丰度的129 Xe对hBAT进行分子成像，将为进行纵向干预研究提供一种有效且灵敏的手段，旨在通过治疗增强hBAT活性来对抗包括肥胖和糖尿病在内的代谢疾病。

 DESCRIPTION (provided by applicant): The potential involvement of brown adipose tissue (BAT) in adult humans with blood lipid metabolism, glucose homeostasis, and weight maintenance has gathered significant scientific attention. Until recently, the persistence of BAT from childhood into adulthood was thought to not occur. Prior research linking the presence of BAT inversely to development of metabolic syndromes was performed in animal models (chiefly mice and rats). Little, however, has been determined clearly regarding the function of BAT in humans (hBAT). This limitation could be due in part to a lack of techniques permitting longitudinal study of the function of hBAT with excellent temporal resolution. Despite the recent advent of MRI-based imaging techniques quantifying BAT mass and detecting activation by thermometry, the primary technique used to date has been 18F-FDG-PET/CT. In addition to its radiation exposure risk, the technique has come under scrutiny for its likelihood in underreporting the prevalence of hBAT: Glucose uptake by BAT is not the preferred energy substrate. Recent report of the detection of BAT in mice using lipophilic hyperpolarized (HP) natural abundance xenon-129 gas dissolved in the blood compared favorably with 18F-FDG-PET/CT for detecting BAT activity and thermogenesis. However, xenon imaging of BAT has not been performed to date in humans. Therefore, in our work we will have subjects inhale hyperpolarized xenon-129 gas to obtain sub-second acquisition of MRI images of BAT activation in an upright posture 0.05 T clinical multi-nuclear imaging system. In addition to the primary goal of successful detection of hBAT activity by HP 129Xe, our study will examine differences in activation after hBAT thermogenesis stimulation of lean and obese adult humans selected for age, gender, and body mass index. In pursuit of these goals, in this study we will pursue the following three Specific Aims: [1] Construct 129Xe radiofrequency detection coils for a 0.05 T clinical imaging system interfaced to a clinical 129Xe hyperpolarizer; [2] Develop 129Xe imaging protocols for the 0.05 T MR scanner; [3] Detect brown adipose tissue response to thermogenesis stimulation in adult humans. Impact: Molecular imaging of hBAT by highly polarized (>50%), low-cost (<$20/dose), natural abundance 129Xe will provide an efficient and sensitive means for conducting longitudinal intervention studies seeking to counteract metabolic diseases including obesity and diabetes by enabling therapeutic enhancement of hBAT activity.