Quantification of Brown Adipose Tissue by MRI in Children and Teenagers

描述（由申请人提供）：本提案的目的是开发和验证化学位移脂肪-水MRI方法，用于检测和定量人类代谢活性和非活性棕色脂肪组织（BAT）。虽然目前BAT成像的金标准模式是融合正电子发射和计算机断层扫描（PET/CT），但该方法有一些局限性。PET/CT只能通过摄取外源性放射性核素示踪剂来识别代谢活性BAT，限制了其适用性。此外，PET/CT价格昂贵，不广泛使用，并且由于示踪剂的摄取高度依赖于环境因素，因此不精确。相比之下，MRI是非电离和非侵入性的，使其适用于更大比例的人群，甚至适用于健康受试者的前瞻性纵向研究。此外，化学位移脂肪-水MRI能够在成像体积中以体素为单位对组织的脂肪部分进行非常敏感的测量。由于BAT的细胞学结构与白色脂肪组织（WAT）不同，我们假设BAT的脂肪部分是由化学位移MRI唯一代表的，并且它明显低于富含脂质的WAT。除MRI外，我们还将确定独立CT是否也能够区分BAT和WAT，该CT测量的是豪斯菲尔德单位（HUs）的x射线衰减。我们推测，由于BAT含有更多的细胞内水，其HUs明显高于WAT。拟议的工作将在洛杉矶儿童医院实施。提出了两项研究。首先，一项涉及90例患者的横断面研究将用于验证独立CT和MRI在评估代谢活性BAT中的作用。这些患者将接受常规PET/CT成像作为其医疗护理的一部分，并将活性BAT的PET/CT值与独立CT和MRI进行比较。一项验证研究将在20具尸体中进行，以评估MRI和CT测量的特异性和可重复性，以定位和量化BAT。为此，将体积、溶血酶和脂肪分数测量结果与组织学分析进行比较和关联。本研究的另一个目的是研究儿童和青少年的BAT与年龄、体重、体重、身体肥胖和肌肉组织之间的关系。MRI技术量化BAT的发展将为纵向研究影响不同人群BAT的遗传和环境因素（如饮食、温度、运动等）提供更简单、更容易获得的方法。

DESCRIPTION (provided by applicant): The objective of this proposal is to develop and validate chemical-shift fat-water MRI methods for the detection and quantification of both metabolically active and inactive brown adipose tissue (BAT) in humans. While the current gold-standard modality for BAT imaging is fusion positron emission and computed tomography (PET/CT), the approach has several limitations. PET/CT can only identify metabolically active BAT through the uptake of exogenous radionuclide tracers, limiting its applicability. Additionally, PET/CT is expensive, not widely available, and is imprecise since the uptake of a tracer is highly dependent on environmental factors. In contrast, MRI is non-ionizing and non-invasive, making it applicable to a larger proportion of the population even for prospective longitudinal studies in healthy subjects. Furthermore, chemical-shift fat-water MRI is capable of yielding very sensitive measures of a tissue's fat fraction on a voxel- wise basis in the imaging volume. Due to BAT's cytological structure differences from white adipose tissue (WAT), we hypothesized that the fat fraction of BAT is uniquely represented by chemical-shift MRI, and that it is significantly lower than that of lipid-rich WAT. In addition to MRI, we will also determine whether standalone CT, which measures X-ray attenuation in Hounsefield Units (HUs), is also capable of differentiating BAT and WAT. It is hypothesized that since BAT contains more intracellular water, its HUs are significantly more positive than that of WAT. The proposed work will be implemented at Childrens Hospital of Los Angeles. Two studies are proposed. First, a cross-sectional study involving 90 patients will be used to validate standalone CT and MRI in the assessment of metabolically active BAT. These patients will undergo routine PET/CT imaging as part of their medical care, and PET/CT values for active BAT will be compared to standalone CT and MRI. A validation study will be conducted in 20 cadavers to assess the specificity and reproducibility of MRI and CT measurements to locate and quantify BAT. To this end, volume, HUs, and fat fraction measurements will be compared and correlated to histological analysis. Another aim of this study is to examine the relationships between BAT and age, weight, body mass, body adiposity, and musculature in children and teenagers. The development of MRI techniques to quantify BAT will provide simpler, more accessible approaches to longitudinally study the genetic and environmental factors (e.g. diet, temperature, exercise, etc.) that influence BAT in different populations. PUBLIC HEALTH RELEVANCE: Brown adipose tissue is of great research interest since by increasing energy expenditure through thermogenesis, it can potentially counteract weight gain and development of obesity. This proposal investigates the utilization of advanced imaging methods in computed tomography and more importantly, magnetic resonance imaging to safely and non-invasively measure brown adipose tissue in humans. In addition, the proposal will study how brown adipose tissue quantity varies with age, gender, and body composition, particularly in children and adolescents.