EXPANDING THE APPLICATION OF MRI FOR BODY FAT STUDIES IN HUMANS

描述（由申请人提供）：拟议的为期四年的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无创磁共振成像（MRI）方法，以便在一年级期间准确表征和量化人体脂肪，以及(2)将开发的MRI技术应用于2 - 4年级西班牙儿童和青少年的肥胖和2型糖尿病病因学研究。该提案的总体目标是验证MRI作为脂肪量化的可靠和准确的工具，并扩大其目前在身体脂肪研究中的应用，而不仅仅是对皮下和内脏脂肪组织库的简单体积测量。在这项工作中使用的主要技术是单体素磁共振光谱（MRS）和称为IDEAL（回声不对称和最小二乘估计的迭代分解）的稳健脂肪-水MRI方法。MRS和IDEAL-MRI都能准确估计体内脂肪与水氢的比例（脂肪分数）。在这项工作中，研究了3特斯拉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量化和表征中的多功能性。该项目的目的是设计和验证一种用于脂肪研究的单一全面的IDEAL-MRI方案，该方案可常规用于肥胖研究，而对操作员专业知识的依赖最小。结果将显著扩展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的独特代谢谱的细节，他们有发展为2型糖尿病和肥胖的倾向。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前沿。首席研究员将在Michael I. Goran博士和Krishna S. Nayak博士的指导下，Michael I. Goran博士是著名的儿童肥胖研究者，Krishna S. Nayak博士是电子工程教授，在MRI脉冲序列开发和快速成像技术方面具有专业知识。南加州大学是开展这项工作的理想地点，因为它致力于识别和预防影响公众健康的疾病，包括癌症、2型糖尿病和肥胖。此外，更大的洛杉矶人口提供了一个队列池，可以很容易地从中招募有2型糖尿病和肥胖风险的西班牙裔人。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. 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.