Quantification of Brown Adipose Tissue by MRI in Children and Teenagers

通过 MRI 对儿童和青少年棕色脂肪组织进行定量

• 批准号: 8150960
• 负责人: VICENTE GILSANZ
• 金额: $ 18.11万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8150960
• 关键词: Address; Adipocytes; Adipose tissue; Adolescent; Age; Anthropometry; Body Composition; Body Weight; Brown Fat; Cadaver; Caring; Chemicals; Child; Childhood; Cross-Sectional Studies; Detection; Development; Diet; Emission-Computed Tomography; Energy Metabolism; Environmental Risk Factor; Exercise; Exposure to; Fatty acid glycerol esters; Food Energy; Gender; Genetic; Gold; Growth; Heating; Histology; Hospitals; Human; Image; Imaging Techniques; Ionizing radiation; Least-Squares Analysis; Lipids; Location; Longitudinal Studies; Los Angeles; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical; Methods; Mitochondria; Modality; Muscle Development; Muscle Fibers; Obesity; Oxidative Phosphorylation; PET/CT scan; Patients; Population; Positron; Prevalence; Radioisotopes; Reproducibility; Research; Roentgen Rays; Sensitivity and Specificity; Signal Transduction; Specificity; Structure; Techniques; Teenagers; Temperature; Testing; Thermogenesis; Tissues; Tracer; Translating; Triglycerides; Vascularization; Visceral; Water; Weight Gain; Weights and Measures; Work; X-Ray Computed Tomography; attenuation; base; imaging modality; in vivo; interest; novel; progenitor; prospective; public health relevance; subcutaneous; uptake; validation studies

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.

描述（由申请方提供）：本提案的目的是开发和验证用于检测和定量人体代谢活性和非活性棕色脂肪组织（BAT）的化学位移脂肪-水MRI方法。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性BAT，限制了其适用性。此外，PET/CT是昂贵的，不是广泛可用的，并且是不精确的，因为示踪剂的摄取高度依赖于环境因素。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，即使是健康受试者的前瞻性纵向研究。此外，化学位移脂肪-水MRI能够在成像体积中的逐体素基础上产生组织的脂肪分数的非常灵敏的测量。由于BAT的细胞学结构与白色脂肪组织（WAT）的差异，我们假设BAT的脂肪部分是唯一的化学位移MRI代表，它是显着低于富含脂质的WAT。除了MRI之外，我们还将确定独立CT（以Hounsefield单位（HU）测量X射线衰减）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，其HU比WAT显着更积极。 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，将使用一项涉及90名患者的横断面研究来验证独立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，并将活动BAT的PET/CT值与独立CT和MRI进行比较。将在20具尸体中进行确认研究，以评估MRI和CT测量的特异性和再现性，以定位和量化BAT。为此，将比较体积、HU和脂肪分数测量值，并将其与组织学分析相关联。本研究的另一个目的是研究BAT与儿童和青少年的年龄，体重，体重，身体肥胖和肌肉组织之间的关系。 MRI技术量化BAT的发展将提供更简单，更容易获得的方法来纵向研究遗传和环境因素（例如饮食，温度，运动等）。影响不同人群的BAT。 公共卫生相关性：棕色脂肪组织具有很大的研究兴趣，因为通过产热增加能量消耗，它可以潜在地抵消体重增加和肥胖的发展。该提案研究了利用先进的成像方法在计算机断层扫描，更重要的是，磁共振成像安全和非侵入性地测量人类棕色脂肪组织。此外，该提案还将研究棕色脂肪组织的数量如何随年龄、性别和身体成分而变化，特别是在儿童和青少年中。

项目成果

Changes in brown adipose tissue in boys and girls during childhood and puberty.

• DOI: 10.1016/j.jpeds.2011.09.035
• 发表时间: 2012-04
• 期刊: JOURNAL OF PEDIATRICS
• 影响因子: 5.1
• 作者: Gilsanz, Vicente;Smith, Michelle L.;Goodarzian, Fariba;Kim, Mimi;Wren, Tishya A. L.;Hu, Houchun H.
• 通讯作者: Hu, Houchun H.

Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI.

• DOI: 10.1002/jmri.24053
• 发表时间: 2013-10
• 期刊: JOURNAL OF MAGNETIC RESONANCE IMAGING
• 影响因子: 4.4
• 作者: Hu, Houchun H.;Yin, Larry;Aggabao, Patricia C.;Perkins, Thomas G.;Chia, Jonathan M.;Gilsanz, Vicente
• 通讯作者: Gilsanz, Vicente

MRI detection of brown adipose tissue with low fat content in newborns with hypothermia.

• DOI: 10.1016/j.mri.2013.10.003
• 发表时间: 2014-02
• 期刊: MAGNETIC RESONANCE IMAGING
• 影响因子: 2.5
• 作者: Hu, Houchun H.;Wu, Tai-Wei;Yin, Larry;Kim, Mimi S.;Chia, Jonathan M.;Perkins, Thomas G.;Gilsanz, Vicente
• 通讯作者: Gilsanz, Vicente

Unequivocal identification of brown adipose tissue in a human infant.

• DOI: 10.1002/jmri.23531
• 发表时间: 2012-04
• 期刊: JOURNAL OF MAGNETIC RESONANCE IMAGING
• 影响因子: 4.4
• 作者: Hu, Houchun H.;Tovar, Jason P.;Pavlova, Zdena;Smith, Michelle L.;Gilsanz, Vicente
• 通讯作者: Gilsanz, Vicente

Characterization of human brown adipose tissue by chemical-shift water-fat MRI.

• DOI: 10.2214/ajr.12.8996
• 发表时间: 2013-01
• 期刊: AJR. American journal of roentgenology
• 作者: Hu HH;Perkins TG;Chia JM;Gilsanz V
• 通讯作者: Gilsanz V