The overall objective of the proposed research is to develop and validate methods for volumetric quantification and metabolic activation detection of brown adipose tissue (BAT) using magnetic resonance imaging (MRI). BAT is a thermogenic tissue known to be present in human infants. BAT was believed to diminish with age to be essentially undetectable in adults. However, recent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) studies suggest that small but metabolically significant amounts of BAT persist into adulthood. These studies further suggest an inverse relationship between BAT and obesity, although it remains unclear whether reduced BAT amount and/or activity promotes or results from obesity. Therefore, reliable identification and spatial mapping methods that can distinguish BAT from white adipose tissue (WAT) would provide investigators with a powerful tool with which to study BAT's influence on body metabolism and composition. We hypothesize that in human adult subjects, BAT will be detectable and quantifiable separately from WAT and non-adipose background tissues using MRI approaches that enable quantitative measurement of MR properties of water and lipid protons. To achieve these goals, we will pursue the following specific aims: [1] Develop and optimize MRI measurements of fat signal fraction (FSF), water longitudinal magnetization relaxation rate (T1_H2O), water apparent diffusion coefficient (ADC_H2O), water phenomenological transverse relaxation rate (T2*_H2O), and proton resonance frequency (PRF) shift thermometry for the volumetric quantification and metabolic activation detection of BAT in lean athletic adult human subjects who are screened with conventional FWMRI and identified to have conspicuous adipose depots in the anatomical locations typical for BAT. Location(s), volume, and metabolic activity of BAT will be confirmed using cold- activated 18F-FDG PET. [2] Validate MRI measurements of FSF, T1_H2O, ADC_H2O, T2*_H2O and PRF shift thermometry for prospective volumetric quantification and metabolic activation detection of BAT in adult human subjects who have body weights in the normal to obese range and significant WAT depots. Location(s), volume, and metabolic activity of BAT will be confirmed using cold-activated 18F-FDG PET. Impact: MRI-based volumetric quantification and metabolic activation detection of BAT in adult humans will enable many novel endocrinology studies of BAT's connection to body composition and obesity and may lead to clinical investigations of positive effects of BAT activity (and its enhancement) for counteracting obesity.
Enhancing the volume or activity of brown adipose tissue (BAT) could impact the clinical management of obesity, but such studies will require a safe, non-invasive method for BAT quantification that can be applied repeatedly in a broad range of human subjects. The ability to identify and quantify BAT using MRI will have a positive impact on clinical endocrinology and the pursuit of new avenues of obesity research and treatment.
