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：(1)开发和验证基于化学位移原理的非侵入性磁共振成像(MRI)方法，以便在第一年准确地描述和量化人体脂肪；(2)在第二至第四年，将开发的MRI技术应用于西班牙裔儿童和青少年肥胖和2型糖尿病的病因研究。建议的总体目标是验证MRI作为一种可靠和准确的脂肪量化工具，并扩大其目前在体脂研究中的应用，超越简单的皮下和内脏脂肪组织堆积的体积测量。在这项工作中使用的主要技术是单体素磁共振波谱(MRS)和一种称为理想(带有回声不对称和最小二乘估计的迭代分解)的稳健的脂肪-水磁共振方法。MRS和Idea-MRI都可以准确地估计体内脂肪与水氢的比率(脂肪比例)。在这项工作中，研究了3特斯拉的脂肪分数成像在异位器官和肌肉脂肪、白色脂肪细胞和棕色脂肪组织的脂肪细胞大小的定量和表征方面的多功能性。该项目的终点是设计和验证用于脂肪研究的单一综合理想-MRI方案，该方案可以常规用于肥胖研究，最大限度地减少对操作员专业知识的依赖。研究结果将极大地扩展我们对脂肪沉积和脂肪代谢机制的理解，并提供有患2型糖尿病和肥胖倾向的西班牙裔儿童和青少年独特的代谢特征的细节。这一职业发展申请结合了南加州大学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，他们处于翻译成像和肥胖研究的前沿。首席调查员将在迈克尔·I·戈兰博士和克里希纳·S·纳亚克博士的指导下工作，前者是一位著名的儿科肥胖研究员，后者是一位电气工程教授，在核磁共振脉冲序列开发和快速成像技术方面拥有专业知识。南加州大学是这项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，可以很容易地招募到有2型糖尿病和肥胖症风险的拉美裔美国人。大学医院、(洛杉矶县)LAC-USC医院和洛杉矶-南加州大学儿童医院为实施计划中的项目提供了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，培养指导和学习，并为首席研究员转变为独立研究人员确立路线图。 公共卫生相关性：肥胖在美国是一种日益严重的流行病，影响着儿童、青少年和成年人，并且仍然是一个主要的健康和社会问题。脂肪在人体内的积累是肥胖的主要组成部分，并导致心血管疾病、2型糖尿病和几种癌症的健康风险增加。该项目将贡献新的和非侵入性的磁共振成像技术，以准确和可靠地研究整个人体的脂肪。

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. PUBLIC HEALTH RELEVANCE: Obesity is a growing epidemic in the United States, affecting children, adolescents, and adults, and remains a major health and social problem. The accumulation of fat in the human body is the main component of obesity, and is responsible for increased health risks in cardiovascular diseases, type 2 diabetes, and several cancers. This project will contribute novel and non-invasive magnetic resonance imaging techniques to accurately and reliably study fat across the entire human body.