Non‐Contrast Ultrasound Perfusion Imaging of Human Brown Adipose Tissue

Abstract

Brown adipose tissue (BAT) is a highly vascularized tissue that uptakes and oxidizes fatty acids from the circulation in response to a cold stimulus, resulting in thermogenesis. Tissue perfusion has been proposed as an approach to understand BAT metabolism, but current imaging techniques require invasive contrast or ionizing radiation. Power Doppler ultrasound imaging enables sensitive, high temporal resolution measures of the movement of blood as it perfuses a tissue without the need for contrast injections. The purpose of this study was to explore the utility of non‐contrast ultrasound perfusion imaging of human BAT during personalized cooling. Five healthy subjects [4 men; age: 31.8 ± 5.6 yrs.; body mass index: 22.5 ± 3.3 kg/m2; total body fat % (dual‐energy x‐ray absorptiometry scan): 22.9 ±7.0 %] underwent an individualized, perception‐based cooling protocol to stimulate BAT. Infrared thermography, a surrogate measure of BAT activity, and power Doppler ultrasound images were acquired over the right and left supraclavicular space, respectively, every five minutes in thermoneutrality (TN; duration: 15 min) and during cold exposure (CE) to the participant’s shiver threshold (duration: 58.3 ± 10.8 min; cooling dose: 319.7 ± 140.4 °C*min). Ultrasound images were post‐processed with a block‐wise, independent component analysis filter to analyze signal changes related to perfusion. BAT regions of interest were defined, and TN and CE conditions were compared as the mean ± standard deviation of the difference in the 95th percentile skin temperatures (infrared thermography) and the mean power Doppler signal (ultrasound). Supraclavicular skin temperature increased by 0.56 ± −0.21 °C (95% bootstrap confidence interval (CI): −0.57 to 1.72 °C), indicating a potential thermogenic response of BAT to individualized cooling (TN: 33.8 ± 1.1 °C vs. CE: 34.3 ± 0.9 °C). Similarly, the mean power Doppler signal increased by 11.6 ± 3.8 dB (95% CI: 3.2 to 19.4 dB) following cold exposure (TN: 46.8 ± 5.3 dB vs. CE: 58.3 ± 9.1 dB). These preliminary data demonstrate the feasibility of non‐contrast ultrasound perfusion imaging to detect the microvascular response of BAT to a cold stimulus in healthy adults. Power Doppler ultrasound imaging could prove useful when combined with existing noninvasive modalities (e.g. magnetic resonance imaging) to assess both the perfusion and metabolic substrate uptake response of BAT to potential obesity‐targeted therapies.Support or Funding InformationNIDDK/NIH R01‐DK‐105371, NCATS/NIH UL1‐TR000445