The objective of this proposal is to develop and validate chemical-shift fat-water MRI methods for the detection and quantification of both metabolically active and inactive brown adipose tissue (BAT) in humans. While the current gold-standard modality for BAT imaging is fusion positron emission and computed tomography (PET/CT), the approach has several limitations. PET/CT can only identify metabolically active BAT through the uptake of exogenous radionuclide tracers, limiting its applicability. Additionally, PET/CT is expensive, not widely available, and is imprecise since the uptake of a tracer is highly dependent on environmental factors. In contrast, MRI is non-ionizing and non-invasive, making it applicable to a larger proportion of the population even for prospective longitudinal studies in healthy subjects. Furthermore, chemical-shift fat-water MRI is capable of yielding very sensitive measures of a tissue's fat fraction on a voxel- wise basis in the imaging volume. Due to BAT's cytological structure differences from white adipose tissue (WAT), we hypothesized that the fat fraction of BAT is uniquely represented by chemical-shift MRI, and that it is significantly lower than that of lipid-rich WAT. In addition to MRI, we will also determine whether standalone CT, which measures X-ray attenuation in Hounsefield Units (HUs), is also capable of differentiating BAT and WAT. It is hypothesized that since BAT contains more intracellular water, its HUs are significantly more positive than that of WAT. The proposed work will be implemented at Childrens Hospital of Los Angeles. Two studies are proposed. First, a cross-sectional study involving 90 patients will be used to validate standalone CT and MRI in the assessment of metabolically active BAT. These patients will undergo routine PET/CT imaging as part of their medical care, and PET/CT values for active BAT will be compared to standalone CT and MRI. A validation study will be conducted in 20 cadavers to assess the specificity and reproducibility of MRI and CT measurements to locate and quantify BAT. To this end, volume, HUs, and fat fraction measurements will be compared and correlated to histological analysis. Another aim of this study is to examine the relationships between BAT and age, weight, body mass, body adiposity, and musculature in children and teenagers. The development of MRI techniques to quantify BAT will provide simpler, more accessible approaches to longitudinally study the genetic and environmental factors (e.g. diet, temperature, exercise, etc.) that influence BAT in different populations.

Public Health Relevance

Brown adipose tissue is of great research interest since by increasing energy expenditure through thermogenesis, it can potentially counteract weight gain and development of obesity. This proposal investigates the utilization of advanced imaging methods in computed tomography and more importantly, magnetic resonance imaging to safely and non-invasively measure brown adipose tissue in humans. In addition, the proposal will study how brown adipose tissue quantity varies with age, gender, and body composition, particularly in children and adolescents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DK090778-02
Application #
8150960
Study Section
Special Emphasis Panel (ZDK1-GRB-W (OS))
Program Officer
Laughlin, Maren R
Project Start
2010-09-30
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2011
Total Cost
$181,145
Indirect Cost
Name
Children's Hospital of Los Angeles
Department
Type
DUNS #
052277936
City
Los Angeles
State
CA
Country
United States
Zip Code
90027
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Hu, Houchun H; Tovar, Jason P; Pavlova, Zdena et al. (2012) Unequivocal identification of brown adipose tissue in a human infant. J Magn Reson Imaging 35:938-42

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