title: Brown adipose tissue blood flow and mass in obesity: a contrast ultrasound study in mice.
abstract: BACKGROUND
  When activated by the sympathetic nervous system, brown adipose tissue (BAT) increases energy expenditure to produce heat. Augmenting BAT mass or increasing BAT activation could potentially be used to decrease obesity. Noninvasive methods to detect and monitor BAT mass are needed. Contrast ultrasound can estimate BAT blood flow and is able to measure the perfused volume of an organ and thus its mass. The objective of this study was to evaluate whether contrast ultrasound could characterize BAT mass in two mouse models of obesity: wild-type mice fed a high-fat diet and mutant db/db mice.
  
  
  METHODS
  Contrast ultrasound of BAT (Definity 2 μL/min; 14-MHz linear probe) was performed before and after stimulation of BAT with norepinephrine (NE). BAT replenishment curves were obtained, and blood flow was estimated by the product of the curve's plateau and slope. Additionally, consecutive two-dimensional images of perfused BAT were acquired at 1-mm intervals after stimulation with NE and used to assess BAT volume and mass.
  
  
  RESULTS
  BAT blood flow increased after NE infusion in all mice studied. Blood flow response to NE was similar in wild-type mice fed either a low-fat diet or a high-fat diet. BAT blood flow was lower in db/db mice than in wild-type mice (P = .02). Contrast ultrasound-derived BAT mass was correlated with BAT mass obtained at necropsy (R(2) = 0.83, P < .001). BAT mass was higher in mice fed a high-fat diet than in those fed a low-fat diet.
  
  
  CONCLUSIONS
  Contrast ultrasound can be used to estimate BAT mass in mice when BAT vascularization is not significantly impaired. This noninvasive technique may potentially allow the serial evaluation of therapies designed to augment BAT mass.
authors.affiliation: Cardiac Ultrasound Laboratory, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Maëva
authors.initials: M
authors.lastname: Clerte
authors.forename: David M
authors.initials: DM
authors.lastname: Baron
authors.forename: Peter
authors.initials: P
authors.lastname: Brouckaert
authors.forename: Laura
authors.initials: L
authors.lastname: Ernande
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Raher
authors.forename: Aidan W
authors.initials: AW
authors.lastname: Flynn
authors.forename: Michael H
authors.initials: MH
authors.lastname: Picard
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Buys
authors.forename: Marielle
authors.initials: M
authors.lastname: Scherrer-Crosbie
mesh_terms: D002001:Adipose Tissue, Brown / Q000098:blood supply* / Q000000981:diagnostic imaging*; D000818:Animals; D001783:Blood Flow Velocity; D003287:Contrast Media; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009765:Obesity / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D009929:Organ Size; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014463:Ultrasonography / Q000379:methods*
chemical_list: D003287:Contrast Media
keywords: (18)F-fluorodeoxyglucose; BAT; Brown adipose tissue; CU; Contrast ultrasound; FDG; HFD; High-fat diet; Imaging; LFD; Low-fat diet; NE; Norepinephrine; Obesity; PET; Positron emission tomography; UCP1; Uncoupling protein 1; WT; Wild-type; db/db mice