Enabling accurate identification and quantification of brown adipose tissue mass by xenon enhanced computed tomography

通过氙增强计算机断层扫描能够准确识别和量化棕色脂肪组织块

• 批准号: 10052750
• 负责人: Rosa Tamara Branca
• 金额: $ 49.32万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10052750
• 关键词: Address; Adipose tissue; Adopted; Adult; Affect; Animal Model; Biopsy; Blood flow; Brown Fat; Cardiovascular Diseases; Clinical; Computational Technique; Contrast Media; Coupled; Detection; Development; Diabetes Mellitus; Dose; Energy Intake; Energy Metabolism; Epidemic; Epidemiology; Evolution; Gases; Goals; Gold; Growth; Health Care Costs; Histology; Human; Human Biology; Hydration status; Hypertrophy; Imaging Techniques; Inhalation; Insulin; Insulin Resistance; Intervention; Knowledge; Lead; Longitudinal Studies; Measurement; Measures; Methods; Monitor; Morphology; National Institute of Diabetes and Digestive and Kidney Diseases; Needle biopsy procedure; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Overweight; PET/CT scan; Pathogenesis; Phenotype; Play; Population; Positron-Emission Tomography; Prevalence; Protocols documentation; Publishing; Radiation exposure; Reproducibility; Research Personnel; Research Project Grants; Research Proposals; Research Subjects; Risk Factors; Role; Sensitivity and Specificity; Specificity; Stimulus; Target Populations; Techniques; Therapeutic Intervention; Thermogenesis; Thinness; Tissue Differentiation; Tissues; Translating; Validation; Work; X-Ray Computed Tomography; Xenon; base; blood glucose regulation; diabetes mellitus therapy; energy balance; fluorodeoxyglucose; glucose uptake; head-to-head comparison; imaging approach; insight; lipophilicity; low dose computed tomography; new therapeutic target; nonhuman primate; novel strategies; novel therapeutic intervention; novel therapeutics; obesity treatment; phantom model; pre-clinical; reconstruction; research study; response; sex; targeted treatment; tomography; tool; uptake; Address; Adipose tissue; Adopted; Adult; Affect; Animal Model; Biopsy; Blood flow; Brown Fat; Cardiovascular Diseases; Clinical; Computational Technique; Contrast Media; Coupled; Detection; Development; Diabetes Mellitus; Dose; Energy Intake; Energy Metabolism; Epidemic; Epidemiology; Evolution; Gases; Goals; Gold; Growth; Health Care Costs; Histology; Human; Human Biology; Hydration status; Hypertrophy; Imaging Techniques; Inhalation; Insulin; Insulin Resistance; Intervention; Knowledge; Lead; Longitudinal Studies; Measurement; Measures; Methods; Monitor; Morphology; National Institute of Diabetes and Digestive and Kidney Diseases; Needle biopsy procedure; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Overweight; PET/CT scan; Pathogenesis; Phenotype; Play; Population; Positron-Emission Tomography; Prevalence; Protocols documentation; Publishing; Radiation exposure; Reproducibility; Research Personnel; Research Project Grants; Research Proposals; Research Subjects; Risk Factors; Role; Sensitivity and Specificity; Specificity; Stimulus; Target Populations; Techniques; Therapeutic Intervention; Thermogenesis; Thinness; Tissue Differentiation; Tissues; Translating; Validation; Work; X-Ray Computed Tomography; Xenon; base; blood glucose regulation; diabetes mellitus therapy; energy balance; fluorodeoxyglucose; glucose uptake; head-to-head comparison; imaging approach; insight; lipophilicity; low dose computed tomography; new therapeutic target; nonhuman primate; novel strategies; novel therapeutic intervention; novel therapeutics; obesity treatment; phantom model; pre-clinical; reconstruction; research study; response; sex; targeted treatment; tomography; tool; uptake

PROJECT SUMMARY / ABSTRACT In the US, more than 36% of the population is obese and 9.4% has diabetes, most of which is type-2 diabetes driven by obesity-associated insulin resistance. Current anti-obesity strategies have been proven to be largely inadequate, and new-targeted therapies are desperately needed to stop this epidemic. At the fundamental level, obesity results from the imbalance between energy intake and energy expenditure. The latter can be regulated by the activity of brown adipose tissue (BAT), a tissue that plays a regulatory role not only in energy balance, but also in glucose homeostasis. As a result, new therapeutic approaches are now being devised to target BAT for the treatment of obesity and diabetes. However, a major roadblock to the development of such therapies is the ability to detect and quantify BAT mass accurately. Current techniques are either too insensitive, or lack the necessary specificity to differentiate this tissue from white adipose tissue. This is especially true in overweight/obese subjects - the target population for interventional therapies targeting BAT. The goal of the proposed research project is to develop a new imaging approach based on low-dose, xenon- enhanced CT (XECT) that can detect BAT and yield accurate measurements of its mass, independently of its activity. This proposal builds upon our preliminary results, in which we had shown that the inert and lipophilic gas xenon can be used as a CT contrast agent to detect and quantify BAT mass. Regardless of the tissue's thermogenic capacity, hydration status, and glucose uptake capacity, upon stimulation of thermogenic activity, xenon accumulates into BAT at a concentration high enough to significantly change the radiodensity of this tissue, making BAT visible in CT images. Our objectives in this application are: a) to characterize xenon uptake dynamics in BAT as a function of tissue hydration and thermogenic potency in lean and obese non human primates animal models; b) to characterize and optimize low-dose XECT protocols for use in longitudinal studies in humans; and c) to establish that low- dose XECT can correctly identify BAT with greater sensitivity and specificity than 18F-FDG-PET/CT, the most widely used technique for measurement of BAT volume, using biopsy as ground truth. XECT will enable accurate quantification of BAT mass in the general adult human population, while providing new insights into the morphological changes that occur in this tissue during the onset of obesity. This project is expected to have a high impact; this novel approach can be easily implemented on standard PET/CT platforms and combined with other functional measures of BAT to increase their accuracy by reducing partial volume effects. Accurate quantification of BAT mass and activity is expected to lead to a better understanding of the growth, evolution, and remodeling of this tissue resulting from various stimuli and conditions.

项目摘要 /摘要 在美国，超过36％的人口是肥胖的，有9.4％的人患有糖尿病，其中大多数是2型糖尿病 由肥胖相关胰岛素抵抗驱动。当前的抗肥胖策略已被证明很大程度上是 迫切需要制止这种流行病，因此迫切需要不足和新靶向的疗法。在基本 水平，肥胖是由于能量摄入和能量消耗之间的不平衡而导致的。后者可以是 受棕色脂肪组织（BAT）的活性调节，该组织不仅在能量中起着调节作用 平衡，但也处于葡萄糖稳态。结果，现在正在设计新的治疗方法 目标蝙蝠治疗肥胖和糖尿病。但是，这是这种发展的主要障碍 疗法是准确检测和量化蝙蝠质量的能力。当前的技术也是 不敏感，或缺乏将这种组织与白色脂肪组织区分开的必要特异性。这是 在超重/肥胖的受试者中尤其如此 - 针对蝙蝠的介入疗法的目标人群。 拟议的研究项目的目的是开发一种基于低剂量Xenon-的新成像方法 增强的CT（XECT）可以检测BAT并产生其质量的准确测量，而与其质量无关 活动。该提议建立在我们的初步结果的基础上，我们证明了惰性和亲脂性 气体氙可以用作检测和量化蝙蝠质量的CT对比剂。无论组织如何 热能力，水合状态和葡萄糖摄取能力，刺激热活动， Xenon以足够高的浓度积聚成BAT，以显着改变其放射线 组织，使蝙蝠在CT图像中可见。 我们在此应用程序中的目标是：a）表征蝙蝠中的氙气吸收动力学作为组织的函数 瘦肉和肥胖的非人类灵长类动物模型中的水合和热效力； b）表征 并优化低剂量晶体方案，用于在人类的纵向研究中使用； c）确定低 - 剂量晶体可以比18F-fdg-pet/ct正确识别具有更高灵敏度和特异性的蝙蝠，这是最多的 使用活检作为地面真理，广泛使用的技术用于测量蝙蝠体积。 CYT将在成年人人口中准确量化蝙蝠质量，同时提供 肥胖发作期间在该组织中发生的形态变化的新见解。这个项目是 预计会产生很大的影响；这种新颖的方法可以轻松在标准PET/CT平台上实施 并与其他功能性量度相结合，以通过减少部分体积来提高其准确性 效果。预计蝙蝠质量和活动的准确量化将使人们更好地理解 由各种刺激和条件引起的该组织的生长，进化和重塑。