Abstract 16795: Detection of Brown Adipose Tissue Activation and Mass Using Contrast Ultrasound

Abstract

Obesity is an increasingly frequent condition and a risk factor for cardiovascular diseases. Brown adipose tissue (BAT), located mostly in the paravertebral and supraclavicular space in humans and between the scapulae in rodents, consumes lipids and glucose to produce heat when it is activated by norepinephrine (NE) or cold. Increasing metabolic activity and/or mass of BAT could open new therapeutic avenues to treat obesity. Currently,18F-fluorodeoxyglucose Positron Emission Tomography is the only imaging technique detecting BAT and its activation in humans. Since increased BAT blood flow is associated with BAT activation, we hypothesized that BAT contrast ultrasound (CU) could estimate the degree of BAT activation and BAT mass, both in mice and humans. To validate the ability of CU to estimate BAT perfusion, the BAT and kidney of C57BL6 wild type mice were imaged with a 14 MHz linear transducer during continuous infusion of DefinityTM microbubble contrast. The time intensity curves of the contrast were quantified and blood flow was estimated by the product of the curve plateau A and slope ß. The BAT/kidney blood flow ratio obtained with CU was compared to that measured with fluorescent microspheres. In another experiment, to validate the ability of CU to estimate BAT mass, the maximal area of perfusion of BAT was compared to the BAT weight, in mice. Finally, the BAT vascular response to activation was assessed in 6 mice before and after infusing 1µg/kg/min NE and in 7 young and lean human volunteers before and after cold exposure (16°C for 2 hours).The BAT/kidney blood flow ratio obtained by CU in mice correlated with microsphere measurements (R2=0.85, p<0.05). The maximal area of BAT measured by CU correlated with BAT weight (R2=0.58, p<0.002). Mice demonstrated a 10-fold increase in BAT perfusion after infusion of NE (Aß 0.6±0.1 vs. 5.5±0.9 dB/s, p<0.05) while kidney perfusion decreased. Similarly, BAT perfusion increased in humans after cold exposure (Aß 0.1±0.0 vs. 1.0±0.4 dB/s,p<0.05). In conclusion, contrast ultrasound imaging can be used to estimate BAT activation and its mass. This noninvasive technique free of ionizing radiation offers a method for serial evaluation and monitoring of therapies designed to activate BAT or augment its mass.