Ultra-fast molecular MRI of human adipose tissue with hyperpolarized xenon-129 contrast agent

Vanderbilt University Medical Center, Nashville TN

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Abstract

? DESCRIPTION (provided by applicant): The potential involvement of brown adipose tissue (BAT) in adult humans with blood lipid metabolism, glucose homeostasis, and weight maintenance has gathered significant scientific attention. Until recently, the persistence of BAT from childhood into adulthood was thought to not occur. Prior research linking the presence of BAT inversely to development of metabolic syndromes was performed in animal models (chiefly mice and rats). Little, however, has been determined clearly regarding the function of BAT in humans (hBAT). This limitation could be due in part to a lack of techniques permitting longitudinal study of the function of hBAT with excellent temporal resolution. Despite the recent advent of MRI-based imaging techniques quantifying BAT mass and detecting activation by thermometry, the primary technique used to date has been 18F-FDG-PET/CT. In addition to its radiation exposure risk, the technique has come under scrutiny for its likelihood in underreporting the prevalence of hBAT: Glucose uptake by BAT is not the preferred energy substrate. Recent report of the detection of BAT in mice using lipophilic hyperpolarized (HP) natural abundance xenon-129 gas dissolved in the blood compared favorably with 18F-FDG-PET/CT for detecting BAT activity and thermogenesis. However, xenon imaging of BAT has not been performed to date in humans. Therefore, in our work we will have subjects inhale hyperpolarized xenon-129 gas to obtain sub-second acquisition of MRI images of BAT activation in an upright posture 0.05 T clinical multi-nuclear imaging system. In addition to the primary goal of successful detection of hBAT activity by HP 129Xe, our study will examine differences in activation after hBAT thermogenesis stimulation of lean and obese adult humans selected for age, gender, and body mass index. In pursuit of these goals, in this study we will pursue the following three Specific Aims: [1] Construct 129Xe radiofrequency detection coils for a 0.05 T clinical imaging system interfaced to a clinical 129Xe hyperpolarizer; [2] Develop 129Xe imaging protocols for the 0.05 T MR scanner; [3] Detect brown adipose tissue response to thermogenesis stimulation in adult humans. Impact: Molecular imaging of hBAT by highly polarized (>50%), low-cost (<$20/dose), natural abundance 129Xe will provide an efficient and sensitive means for conducting longitudinal intervention studies seeking to counteract metabolic diseases including obesity and diabetes by enabling therapeutic enhancement of hBAT activity.