Novel Magnetic Resonance Approach to Detect BAT Distribution and Temperature

检测 BAT 分布和温度的新型磁共振方法

• 批准号: 8145186
• 负责人: Rosa Tamara Branca
• 金额: $ 3.22万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2012-07-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8145186
• 关键词: Accounting; Adipose tissue; Adult; Animals; Biomedical Technology; Body Weight; Brown Fat; Characteristics; Clinical; Clinical Trials; Collaborations; Complex; Contrast Media; Data; Detection; Development; Drug or chemical Tissue Distribution; Energy Metabolism; Fatty acid glycerol esters; Frequencies; Goals; Grant; Health Care Costs; Histology; Histopathology; Human; Image; Imaging Device; Imaging Techniques; Imaging technology; In Vitro; Incidence; Individual; Laboratories; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Methodology; Methods; Microscopy; Molecular; Monitor; Mus; Non-Invasive Cancer Detection; Obesity; PET/CT scan; Paper; Pharmaceutical Preparations; Physiology; Play; Positron-Emission Tomography; Process; Protons; Public Health; Radiation; Regulation; Research; Research Personnel; Resources; Rodent; Role; Scanning; Screening procedure; Signal Transduction; Staging; Structure; Techniques; Technology; Temperature; Testing; Time; Tissues; Translating; Translations; United States National Institutes of Health; Universities; Validation; Water; Work; base; combat; drug development; efficacy testing; energy balance; imaging modality; in vivo; innovation; novel; obesity treatment; pre-clinical; programs; public health relevance; quantum; therapeutic target; tool; uptake

DESCRIPTION (provided by applicant): The recent detection of brown adipose tissue (BAT) in humans suggests a radically different strategy for obesity control, if BAT can play the same role in humans that it plays in animals for regulation of body weight. Arguably the largest obstacle to answering this question is the lack of a non-invasive means to detect BAT presence and activity in humans. The only technology currently available to detect human BAT (18FDG- PET) is prone to false negatives, is subject to high scan-rescan variability, and causes significant radiation exposure, which limits repeated studies on the same subject necessary to test the efficacy of new drugs. The long-term goal of the proposed research is to develop a non-invasive MRI based method that allows the detection of both BAT presence and BAT activity in humans. The objective of this application is to develop and optimize this method pre-clinically and then to validate it through comparison with histology and more established 18FDG-PET scans. The proposed approach uses a novel proton Magnetic Resonance Imaging (MRI) method (detection of intermolecular zero-quantum coherences, or iZQCs) which exploits structural differences between BAT and White Adipose Tissue (WAT). The central hypothesis is that the proposed method is sensitive to tissue microstructure and can differentiate BAT depots from WAT. Moreover, since this method is sensitive to BAT temperature it can be used to monitor tissue activity. This hypothesis has been formulated on the basis of preliminary results from the investigator's laboratory, which identify a marker for BAT in the NMR spectra that arises from the iZQC signal between spins that are 100 microns apart. Guided by strong preliminary data, the research will test the central hypothesis by pursuing two Specific Aims: 1) Develop, optimize, and validate this method for BAT localization in vivo in mice; and 2) Optimize and accelerate BAT temperature measurement to monitor BAT activity in mice. The proposed approach is innovative because it exploits the unique sensitivity of iZQC to tissue structure to detect the presence of small BAT depots that are mixed with other tissues and its sensitivity to temperature to monitor BAT activity. The proposed research is significant because increasing the ability to measure BAT mass and BAT activity in humans in vivo will allow for a better understanding of BAT's role in physiology and its potential as a therapeutic target in the treatment of obesity. The approach is noninvasive; the signal is intrinsic, and does not even require contrast agent administration. It thus allows repeated scanning on the same subject, which is critical to test the efficacy of new drugs that are developed to increase BAT tissue mass or to boost BAT activity. PUBLIC HEALTH RELEVANCE: The proposed study will develop an MRI-based imaging technique to detect Brown Adipose Tissue (BAT) in vivo and to monitor its metabolic state. Such a technique will provide an invaluable tool to study the occurrence of BAT in humans and monitor its metabolic state over time. The proposed research has relevance to public health because new tools for non-invasive detection of BAT will show the connection between BAT occurrence and obesity and ultimately accelerate the process of developing better treatments for obesity.

描述（由申请人提供）：人类最近发现棕色脂肪组织（BAT）的发现表明，如果BAT可以在人类中发挥相同的作用，则在人类中起着与动物相同的作用，以调节体重的大部分策略。可以说，回答这个问题的最大障碍是缺乏检测人类蝙蝠存在和活动的非侵入性手段。目前可用于检测人类蝙蝠（18fdg- PET）的唯一技术容易出现虚假负面因素，受到高扫描剂的可变性，并引起重大的辐射暴露，这限制了对测试新药有效性所必需的相同主题的重复研究。拟议研究的长期目标是开发一种基于非侵入性MRI的方法，该方法允许检测人类的蝙蝠存在和蝙蝠活性。该应用程序的目的是在链式链接情况下开发和优化此方法，然后通过与组织学和更建立的18FDG-PET扫描进行比较来验证它。 所提出的方法使用一种新型的质子磁共振成像（MRI）方法（检测分子间零量器相干或IZQCS），从而利用了BAT和白脂肪组织（WAT）之间的结构差异。中心假设是所提出的方法对组织微观结构敏感，并且可以将BAT库与WAT区分开。此外，由于该方法对BAT温度很敏感，因此可以用于监测组织活动。该假设是根据研究者实验室的初步结果提出的，该实验室确定了NMR光谱中BAT的标记，该射频是由100微米分开的自旋之间的IZQC信号引起的。在强大的初步数据的指导下，该研究将通过追求两个具体的目的来检验中心假设：1）在小鼠中开发，优化和验证这种在​​体内蝙蝠定位的方法； 2）优化和加速蝙蝠温度测量以监测小鼠的蝙蝠活动。提出的方法具有创新性，因为它利用了IZQC对组织结构的独特灵敏度，以检测与其他组织混合的小蝙蝠库的存在及其对温度的敏感性以监测蝙蝠活性。拟议的研究非常重要，因为增强体内人类蝙蝠质量和蝙蝠活性的能力将可以更好地了解BAT在生理学中的作用及其作为治疗肥胖症治疗靶标的潜力。这种方法是无创的。该信号是固有的，甚至不需要对比剂给药。因此，它允许对同一受试者进行重复扫描，这对于测试为增加蝙蝠组织质量或增强蝙蝠活性而开发的新药的功效至关重要。 公共卫生相关性：拟议的研究将开发一种基于MRI的成像技术，以检测体内棕色脂肪组织（BAT）并监测其代谢状态。这样的技术将为研究人类的蝙蝠出现并随着时间的流逝而监测其代谢状态的宝贵工具。拟议的研究与公共卫生有关，因为非侵入性检测的新工具将显示出蝙蝠发生与肥胖之间的联系，并最终加速开发更好的肥胖治疗方法。