Quantification of Brown Adipose Tissue by MRI in Children and Teenagers

描述(申请人提供)：这项建议的目标是开发和验证化学位移脂肪-水磁共振方法，用于检测和量化人类代谢活跃和不活跃的棕色脂肪组织(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)，但该方法有几个局限性。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跃的BAT，限制了其适用性。此外，由于示踪剂的摄取高度依赖于环境因素，PET/CT价格昂贵，不能广泛获得，而且不准确。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，化学位移脂肪水磁共振成像能够在成像体积中以体素为基础产生非常敏感的组织脂肪分数的测量结果。由于BAT的细胞学结构与白色脂肪组织(WAT)不同，我们假设BAT的脂肪部分是化学位移磁共振唯一的代表，并且显著低于富含脂肪的WAT。除了MRI，我们还将确定独立CT是否也能够区分BAT和WAT。据推测，由于BAT含有更多的细胞内水分，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名患者的横断面研究将用于验证独立的CT和MRI在评估代谢活跃的BAT中的作用。这些患者将接受常规的PET/CT成像，作为其医疗护理的一部分，活动BAT的PET/CT值将与独立的CT和MRI进行比较。将对20具身体进行验证性研究，以评估MRI和CT测量定位和量化BAT的特异性和重复性。为此，将比较体积、HUS和脂肪分数的测量结果，并将其与组织学分析相关联。这项研究的另一个目的是研究蝙蝠与儿童和青少年的年龄、体重、体重、身体肥胖和肌肉发达之间的关系。量化BAT的MRI技术的发展将为纵向研究遗传和环境因素(如饮食、温度、运动等)提供更简单、更容易的方法。这会影响不同种群的蝙蝠。 与公共健康相关：棕色脂肪组织是非常有研究意义的，因为它通过产热增加能量消耗，潜在地可以抵消体重增加和肥胖的发展。这项建议研究了先进的成像方法在计算机断层扫描中的应用，更重要的是，磁共振成像可以安全和非侵入性地测量人类的棕色脂肪组织。此外，该提案还将研究棕色脂肪组织的数量如何随年龄、性别和身体成分的变化而变化，特别是在儿童和青少年中。

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.