Detection of Brown Adipose Tissue Using Contrast Ultrasound

使用对比超声检测棕色脂肪组织

• 批准号: 8308374
• 负责人: MARIELLE SCHERRER-CROSBIE
• 金额: $ 20.44万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8308374
• 关键词: Acute; Adipocytes; Adipose tissue; Adult; Aging; Animals; Area; Blood; Blood Vessels; Blood Volume; Blood flow; Body Weight decreased; Brown Fat; Cardiac; Chronic; Color; Coupled; Data; Data Reporting; Detection; Dietary Intervention; Disease; Energy Intake; Energy Metabolism; Fatty Acids; Fatty acid glycerol esters; Foundations; Glucose; Growth; Health; Heating; Human; Human Volunteers; Imagery; Individual; Infant; Intravenous infusion procedures; Left; Lipids; Malignant Neoplasms; Measures; Mediating; Metabolic; Metabolism; Methods; Microbubbles; Monitor; Mus; Neurodegenerative Disorders; Nonesterified Fatty Acids; Norepinephrine; Nutrient; Obese Mice; Obesity; Organ; Overweight; Oxygen; Perfusion; Population Intervention; Positron-Emission Tomography; Procedures; Radiation; Radioactivity; Reporting; Research; Research Personnel; Rodent; Sensitivity and Specificity; Stem cells; Structure; Supraclavicular; Sympathetic Nervous System; Techniques; Technology; Temperature; Thermogenesis; Tissue Differentiation; Tissues; Ultrasonography; Validation; Ventricular; X-Ray Computed Tomography; age effect; age related; base; design; feeding; fluorodeoxyglucose positron emission tomography; in vivo; interest; intravenous injection; mitochondrial uncoupling protein; mouse model; obesity treatment; oxidation; research study; scapula; sugar; tumor; uptake; volunteer

DESCRIPTION (provided by applicant): As obesity is becoming a major health concern worldwide, the search for therapies targeted towards decreasing overweight attracts unprecedented interest. Treatments for obesity involve decreasing energy uptake and/or increasing energy expenditure. When activated by cold and sympathetic nervous system stimulation, brown adipose tissue (BAT) increases energy expenditure by using fatty acids and glucose to produce heat. The thermogenic ability of BAT has been reported for decades in rodents. Until recently, it was assumed that functional BAT existed only in human infants and disappeared thereafter. As BAT has recently been found in adult humans, interest in increasing the amount and activity of BAT has grown, as a possible approach to increase energy expenditure and decrease obesity. There are however difficulties associated with studying BAT in vivo. 18F-fluorodeoxyglucose positron emission tomography coupled with CT scan (18F-FDG PET-CT) is currently the only technology available to detect human BAT in vivo, but these machines are rare, the experiments expensive, and because of radiation exposure it is not possible to do repeated studies in an individual under various conditions. The present proposal is based on the fact that activation of BAT is accompanied by an increase in BAT blood flow. This increase in blood flow is thought to deliver additional substrates and oxygen to the BAT and is necessary for BAT-induced thermogenesis. Contrast-enhanced ultrasound involves the intravenous infusion of echogenic microbubbles during the ultrasound procedure, allowing the estimation of tissue blood flow. We propose to use contrast-enhanced ultrasound (CEU) to detect and monitor functional BAT in mice and humans. In preliminary data, we report that CEU detects blood flow in mice and human BAT, before and after BAT stimulation. We propose to 1.characterize BAT perfusion in mice. 2. Validate CEU in the detection of BAT in humans. In mice, after validation of CEU-estimated BAT blood flow and volume, the effect of aging or obesity on BAT perfusion, volume and thermogenesis will be investigated. In humans, the relationship between CEU-derived BAT blood flow and the metabolic activity of BAT will be characterized. For this purpose, 20 human volunteers will undergo CEU before and after cold exposure and 18F-FDG PET-CT after cold exposure. The CEU-estimated blood flow in BAT (and white adipose tissue) will be compared to the metabolic activity detected by PET. The CEU-calculated supraclavicular BAT volume will be compared to that calculated by PET. Contrast-enhanced ultrasound is noninvasive, easily available, and affordable. If the proposal is successful, CEU may be a non irradiating, widely available technique to detect BAT and monitor potential therapies that increase functional BAT.

描述（由申请人提供）：随着肥胖成为全球主要的健康问题，寻找针对减少超重的治疗方法引起了前所未有的兴趣。肥胖的治疗包括减少能量摄取和/或增加能量消耗。当被寒冷和交感神经系统刺激激活时，棕色脂肪组织（BAT）通过使用脂肪酸和葡萄糖产生热量来增加能量消耗。在啮齿动物中，BAT的产热能力已经报道了几十年。直到最近，人们还认为功能性BAT只存在于人类婴儿中，此后就消失了。由于最近在成年人中发现了BAT，人们对增加BAT的数量和活性的兴趣越来越大，这可能是增加能量消耗和减少肥胖的一种方法。然而，在体内研究BAT存在困难。18f -氟脱氧葡萄糖正电子发射断层扫描与CT扫描（18F-FDG PET-CT）是目前唯一可用于检测体内人类BAT的技术，但这些机器很少，实验费用昂贵，并且由于辐射暴露，不可能在各种条件下对个体进行重复研究。目前的建议是基于BAT的激活伴随着BAT血流的增加这一事实。这种血流量的增加被认为向BAT输送了额外的底物和氧气，这对于BAT诱导的产热是必要的。对比增强超声包括超声过程中静脉输注回声微泡，允许估计组织血流量。我们建议使用对比增强超声（CEU）检测和监测小鼠和人类的功能性BAT。在初步数据中，我们报告了CEU在BAT刺激前后检测小鼠和人类BAT的血流。我们提议……表征小鼠BAT灌注。2. 验证CEU在人类BAT检测中的应用。在小鼠中，在验证ceu估计的BAT血流量和体积后，将研究衰老或肥胖对BAT灌注、体积和产热的影响。在人类中，ceu衍生的BAT血流量与BAT代谢活性之间的关系将被表征。为此，20名人类志愿者将在冷暴露前后进行CEU检查，并在冷暴露后进行18F-FDG PET-CT检查。ceu估计的BAT（和白色脂肪组织）的血流量将与PET检测的代谢活性进行比较。将ceu计算的锁骨上BAT体积与PET计算的BAT体积进行比较。对比增强超声是非侵入性的，容易获得，并且负担得起。如果该建议成功，CEU可能是一种非辐照的、广泛可用的技术，用于检测BAT和监测增加功能性BAT的潜在疗法。

项目成果

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.

• DOI: 10.1016/j.yjmcc.2015.05.002
• 发表时间: 2015-07
• 期刊: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
• 影响因子: 5
• 作者: Thoonen, Robrecht;Ernande, Laura;Cheng, Juan;Nagasaka, Yasuko;Yao, Vincent;Miranda-Bezerra, Alexandre;Chen, Chan;Chao, Wei;Panagia, Marcello;Sosnovik, David E.;Puppala, Dheeraj;Armoundas, Antonis A.;Hindle, Allyson;Bloch, Kenneth D.;Buys, Emmanuel S.;Scherrer-Crosbie, Marielle
• 通讯作者: Scherrer-Crosbie, Marielle

Assessing the Cardiac Toxicity of Chemotherapeutic Agents: Role of Echocardiography.

评估化疗药物的心脏毒性：超声心动图的作用。

• DOI: 10.1007/s12410-012-9163-3
• 发表时间: 2012
• 期刊: Current cardiovascular imaging reports
• 影响因子: 0.9
• 作者: Tan,TimothyC;Scherrer-Crosbie,Marielle
• 通讯作者: Scherrer-Crosbie,Marielle

Cardiac complications of chemotherapy: role of imaging.

• DOI: 10.1007/s11936-014-0296-3
• 发表时间: 2014-04-01
• 期刊: Current treatment options in cardiovascular medicine
• 作者: Tan, Timothy C;Scherrer-Crosbie, Marielle
• 通讯作者: Scherrer-Crosbie, Marielle

In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice.

• DOI: 10.1161/circimaging.112.975607
• 发表时间: 2012-09-01
• 期刊: Circulation. Cardiovascular imaging
• 作者: Baron DM;Clerte M;Brouckaert P;Raher MJ;Flynn AW;Zhang H;Carter EA;Picard MH;Bloch KD;Buys ES;Scherrer-Crosbie M
• 通讯作者: Scherrer-Crosbie M

Brown adipose tissue blood flow and mass in obesity: a contrast ultrasound study in mice.

• DOI: 10.1016/j.echo.2013.07.015
• 发表时间: 2013-12
• 期刊: JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
• 影响因子: 6.5
• 作者: Clerte, Maeva;Baron, David M.;Brouckaert, Peter;Ernande, Laura;Raher, Michael J.;Flynn, Aidan W.;Picard, Michael H.;Bloch, Kenneth D.;Buys, Emmanuel S.;Scherrer-Crosbie, Marielle
• 通讯作者: Scherrer-Crosbie, Marielle