Measuring Human BAT Volume and Activity by Quantitative and Functional MRI

描述（由申请人提供）：肥胖在美国已经成为一种流行病。超过三分之一的美国成年人（35.7%）肥胖，超过三分之一的儿童和青少年超重或肥胖。肥胖影响所有器官系统，增加糖尿病、心血管疾病、癌症、脂肪肝疾病和其他合并症的发病率。肥胖是能量摄入和消耗不平衡的结果。探索脂肪组织在调节能量平衡中的作用，对于理解和治疗肥胖至关重要。哺乳动物有两种功能不同的脂肪组织：白色脂肪组织（WAT）和棕色脂肪组织（BAT）。WAT是能量储存的主要部位，而BAT是一种适应性产热器官，通过能量消耗产生热量。最近的研究表明，活跃的人体BAT诱导的能量消耗可能在适应体重减轻中起重要作用。瘦人的BAT活性明显高于肥胖者，能量消耗似乎与BAT活性成比例地增加。总的来说，BAT激活有望成为肥胖干预的潜在目标。利用18-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET/CT）计算机断层扫描（FDG-PET/CT）通过监测葡萄糖代谢来鉴定冷暴露后的BAT，从而发现成人体内存在代谢活跃的BAT。然而，由于FDG-PET/CT对各种身体和环境条件的敏感性，缺乏细胞水平的组织特征，以及电离辐射暴露阻碍了纵向和儿科研究，FDG-PET/CT在人类BAT成像中的应用受到限制。磁共振成像（MRI）提供了一种非电离辐射成像方式，目前在评估身体脂肪组织方面处于最前沿。目前的MRI技术主要集中在鉴别WAT和BAT；然而，缺乏对个体内BAT组织特性的表征，以及对BAT激活后组织特性变化的检测。我们的目标是开发用于BAT组织表征和组织类型分类的多参数定量MRI方法。我们将首次在热中性和冷刺激条件下对人体BAT进行定量MRI成像，研究冷激活对人体BAT微结构组织特性的影响。此外，将开发功能性血氧水平依赖（BOLD） MRI方法来研究急性冷暴露后组织的生理变化。冷刺激BAT激活图将通过定量和功能mri生成。这些新的MRI方法将提供结构和质量以外的信息，以功能测量可能揭示BAT的代谢和生理功能。

DESCRIPTION (provided by applicant): Obesity has become an epidemic in the United States. More than one-third of U.S. adults (35.7%) are obese, and more than one third of children and adolescents are overweight or obese. Obesity affects all organ systems, increasing the incidence of diabetes, cardiovascular disease, cancer, fatty liver disease, and other co-morbidities. Obesity results from an imbalance between energy intake and expenditure. Exploring the role of adipose tissues in regulating energy balance is essential for understanding and treatment of obesity. There are two functionally different types of adipose tissues in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is the primary site for energy storage, whereas BAT is an adaptive thermogenesis organ that generates heat by energy expenditure. Recent research suggests that energy expenditure induced by active human BAT may play an important role in the adaption to weight loss. BAT activity is significantly higher in lean than obese individuals and the energy expenditure appears to increase in proportion to the amount of BAT activity. Overall, BAT activation is expected to serve as a potential target for obesity interventions. Identification of BAT after cold exposure with 18-Fluoro-deoxyglucose positron emission tomography computed tomography (FDG-PET/CT) imaging by monitoring glucose metabolism led to the discovery of the existence of metabolically active BAT in adult humans. Nevertheless, the utility of FDG-PET/CT for imaging human BAT is limited mainly due to its sensitivity to various body and environmental conditions, lack of tissue characterization in a cellular level and ionizing radiation exposure impeding longitudinal and pediatric studies. Magnetic Resonance Imaging (MRI) provides a non-ionizing radiation imaging modality that is now at the forefront in the assessment of body adipose tissues. Current MRI techniques are focused on differentiation between WAT and BAT; however, there is a lack of the characterization of BAT tissue properties within individuals, and the detection of tissue property changes secondary to BAT activation. Our goal is to develop multi-parametric quantitative MRI methods for BAT tissue characterization and tissue type classification. For the first time, we will implement quantitative MRI BAT imaging in both thermoneutral and cold-stimulated conditions to investigate the BAT microstructural tissue property changes due to cold activation in human. Furthermore, functional blood oxygenation level dependent (BOLD) MRI methods will be developed to investigate the tissue physiological changes in response to acute cold exposure. Cold-stimulated BAT activation map will be generated by both quantitative and functional MRIs. These novel MRI methods will provide information beyond structure and mass to functional measures that may reveal the metabolic and physiological functions of BAT.