EXPANDING THE APPLICATION OF MRI FOR BODY FAT STUDIES IN HUMANS

描述（由申请人提供）：拟议的四年研究项目的目的有两个方面：（1）在第一年期间开发和验证基于化学位移原理的无创磁共振成像（MRI）方法，以准确表征和量化人体脂肪，以及（2）将已开发的MRI技术应用于2 - 4年级西班牙裔儿童和青少年的肥胖和2型糖尿病病因的研究。该提案的总体目标是验证MRI作为脂肪定量的可靠和准确的工具，并将其目前在体脂研究中的应用扩展到皮下和内脏脂肪组织库的简单体积测量之外。在这项工作中使用的主要技术是单体素磁共振波谱（MRS）和一个强大的脂肪水磁共振成像方法称为理想（迭代分解与回波不对称性和最小二乘估计）。MRS和IDEAL-MRI都可以准确估计体内脂肪与水氢的比例（脂肪分数）。在这项工作中，在3特斯拉的脂肪分数成像的多功能性研究异位器官和肌肉脂肪，脂肪细胞大小的白色脂肪细胞，棕色脂肪组织的量化和表征。该项目的终点是为脂肪研究设计和验证一个单一的综合IDEAL-MRI方案，该方案可常规用于肥胖研究，对操作员专业知识的依赖性最小。结果将显着扩大我们对脂肪沉积和脂质代谢机制的理解，并提供西班牙裔儿童和青少年中有发展2型糖尿病和肥胖倾向的独特代谢特征的详细信息。这个职业发展应用程序结合了南加州大学（USC）凯克医学院和维特比工程学院的科学家和临床医生的专业知识，他们处于转化成像和肥胖研究的最前沿。主要研究者将接受Michael I博士的指导。Goran博士和Krishna S. Nayak博士是一位电气工程教授，擅长MRI脉冲序列开发和快速成像技术。南加州大学是拟议工作的理想地点，因为它致力于识别和预防影响公共健康的疾病，包括癌症，2型糖尿病和肥胖症。此外，更大的洛杉矶人口提供了一个队列池，可以很容易地招募有2型糖尿病和肥胖风险的西班牙裔。大学医院、（洛杉矶县）LAC-USC医院和南加州大学-洛杉矶儿童医院为实施计划项目提供必要的基础设施和资源。该奖项将为研究提供受保护的时间，促进跨学科合作的机会，培养导师和学习，并为首席研究员过渡到独立研究员建立路线图。

DESCRIPTION (provided by applicant): The purpose of the proposed four-year research project is two fold: (1) to develop and validate noninvasive magnetic resonance imaging (MRI) methods based on chemical-shift principles for accurate characterization and quantification of human body fat during Year 1, and (2) to apply the developed MRI techniques in the study of obesity and the etiology of type 2 diabetes in Hispanic children and adolescents during Years 2 - 4. The overall goal of the proposal is to validate MRI as a reliable and accurate tool for fat quantification, and to expand its current application in body fat studies beyond simple volume measurements of subcutaneous and visceral adipose tissue depots. The primary techniques used in this work are single-voxel MR spectroscopy (MRS) and a robust fat-water MRI approach called IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation). Both MRS and IDEAL-MRI can yield accurate estimates of the ratio of fat to water hydrogens (fat fraction) in vivo. In this work, the versatility of fat fraction imaging at 3 Tesla is investigated in the quantification and characterization of ectopic organ and muscle fat, fat cell size of white adipocytes, and brown adipose tissue. The endpoint of the project is the design and validation of a single comprehensive IDEAL-MRI protocol for fat studies that can be routinely used in obesity research with minimal dependence on operator expertise. Results will significantly expand our understanding of the mechanisms of fat deposition and lipid metabolism, and provide details on the unique metabolic profiles in Hispanic children and adolescents who have a propensity for developing type 2 diabetes and obesity. This career development application combines the expertise of scientists and clinicians from the Keck School of Medicine and the Viterbi School of Engineering at the University of Southern California (USC) who are at the forefront of translational imaging and obesity research. The Principal Investigator will be under the mentorship of Dr. Michael I. Goran, a renowned investigator in pediatric obesity, and Dr. Krishna S. Nayak, an electrical engineering professor with expertise in MRI pulse sequence development and rapid imaging techniques. USC is an ideal location for the proposed work, as it is dedicated to the identification and prevention of diseases that impact public health, including cancer, type 2 diabetes, and obesity. Furthermore, the greater Los Angeles population provides a cohort pool from which Hispanics at risk of type 2 diabetes and obesity can be easily recruited. The ensemble of University Hospital, (Los Angeles County) LAC-USC Hospital, and USC-Children's Hospital of Los Angeles provides the necessary infrastructure and resources to implement the planned projects. The award will provide protected time for research, foster opportunities of interdisciplinary collaboration, cultivate mentorship and learning, and establish a roadmap for the Principal Investigator to transition into an independent researcher.