Abstract
There is a major resurgence of interest in brown adipose tissue (BAT) biology, particularly regarding its determinants and consequences in newborns and infants. Reliable methods for non-invasive BAT measurement in human infants have yet to be demonstrated. The current study first validates methods for quantitative BAT imaging of rodents post mortem followed by BAT excision and re-imaging of excised tissues. Identical methods are then employed in a cohort of in vivo infants to establish the reliability of these measures and provide normative statistics for BAT depot volume and fat fraction. Using multi-echo water-fat MRI, fat- and water-based images of rodents and neonates were acquired and ratios of fat to the combined signal from fat and water (fat signal fraction) were calculated. Neonatal scans (n = 22) were acquired during natural sleep to quantify BAT and WAT deposits for depot volume and fat fraction. Acquisition repeatability was assessed based on multiple scans from the same neonate. Intra- and inter-rater measures of reliability in regional BAT depot volume and fat fraction quantification were determined based on multiple segmentations by two raters. Rodent BAT was characterized as having significantly higher water content than WAT in both in situ as well as ex vivo imaging assessments. Human neonate deposits indicative of bilateral BAT in spinal, supraclavicular and axillary regions were observed. Pairwise, WAT fat fraction was significantly greater than BAT fat fraction throughout the sample (ΔWAT-BAT = 38%, p<10−4). Repeated scans demonstrated a high voxelwise correlation for fat fraction (Rall = 0.99). BAT depot volume and fat fraction measurements showed high intra-rater (ICCBAT,VOL = 0.93, ICCBAT,FF = 0.93) and inter-rater reliability (ICCBAT,VOL = 0.86, ICCBAT,FF = 0.93). This study demonstrates the reliability of using multi-echo water-fat MRI in human neonates for quantification throughout the torso of BAT depot volume and fat fraction measurements.
Highlights
There is a major resurgence of interest in brown adipose tissue (BAT) biology consequent to relatively recent discoveries that BAT persists into adulthood and appears to play a protective role against obesity/adiposity risk and metabolic dysfunction [1,2,3]
This study examined the reliability of a non-invasive method for infant BAT imaging based on imaging in rodents and a relatively large cohort of neonates
Previous findings were replicated by demonstrating that multi-echo water-fat magnetic resonance imaging (MRI)-based BAT fat fraction (FF) is significantly lower than white adipose tissue (WAT) FF in both rodents (DWAT-BAT 30%) and neonates (DWAT-BAT 38%)
Summary
There is a major resurgence of interest in brown adipose tissue (BAT) biology consequent to relatively recent discoveries that BAT persists into adulthood and appears to play a protective role against obesity/adiposity risk and metabolic dysfunction [1,2,3]. Very little is known about BAT characteristics in early life such as amount, activity, change over time, as well as its immediate and long-term implications for obesity/adiposity and metabolic function. These questions require the development of reliable and valid non-invasive methods to perform quantitative BAT imaging in newborns, infants and children. The predominant imaging modality for BAT has been positron emission coupled with computed tomography (PET/CT) due to it’s ability to image active BAT metabolism alongside composition using Hounsefield unit attenuation. Despite it’s ability to only morphologically characterize BAT, magnetic resonance imaging (MRI) has been identified as the ‘‘ major advancement’’ in imaging BAT, in pediatrics [4]. The ratio of water to fat is greater in BAT relative to WAT, making it ideally suited for multiecho water-fat MRI techniques
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