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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
5K25DK087931-05
Application #
8447051
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Podskalny, Judith M,
Project Start
2010-04-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
5
Fiscal Year
2013
Total Cost
$144,115
Indirect Cost
$10,675
Name
Children's Hospital of Los Angeles
Department
Type
DUNS #
052277936
City
Los Angeles
State
CA
Country
United States
Zip Code
90027
Hu, Houchun H; Wu, Tai-Wei; Yin, Larry et al. (2014) MRI detection of brown adipose tissue with low fat content in newborns with hypothermia. Magn Reson Imaging 32:107-17
Kim, Mimi S; Hu, Houchun H; Aggabao, Patricia C et al. (2014) Presence of brown adipose tissue in an adolescent with severe primary hypothyroidism. J Clin Endocrinol Metab 99:E1686-90
Hu, Houchun H; Perkins, Thomas G; Chia, Jonathan M et al. (2013) Characterization of human brown adipose tissue by chemical-shift water-fat MRI. AJR Am J Roentgenol 200:177-83
Joshi, Anand A; Hu, Houchun H; Leahy, Richard M et al. (2013) Automatic intra-subject registration-based segmentation of abdominal fat from water-fat MRI. J Magn Reson Imaging 37:423-30
Sharma, Samir D; Hu, Houchun H; Nayak, Krishna S (2013) Chemical shift encoded water-fat separation using parallel imaging and compressed sensing. Magn Reson Med 69:456-66
Yang, Yongbin; Smith Jr, Daniel L; Hu, Houchun H et al. (2013) Chemical-shift water-fat MRI of white adipose depots: inability to resolve cell size differences. Int J Body Compos Res 11:9-16
Hu, Houchun H; Hines, Catherine D G; Smith Jr, Daniel L et al. (2012) Variations in T(2)* and fat content of murine brown and white adipose tissues by chemical-shift MRI. Magn Reson Imaging 30:323-9
Casazza, K; Hanks, L J; Hidalgo, B et al. (2012) Short-term physical activity intervention decreases femoral bone marrow adipose tissue in young children: a pilot study. Bone 50:23-7
Chalfant, James S; Smith, Michelle L; Hu, Houchun H et al. (2012) Inverse association between brown adipose tissue activation and white adipose tissue accumulation in successfully treated pediatric malignancy. Am J Clin Nutr 95:1144-9
Sharma, Samir D; Hu, Houchun H; Nayak, Krishna S (2012) Accelerated water-fat imaging using restricted subspace field map estimation and compressed sensing. Magn Reson Med 67:650-9

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