title: Contrast-Enhanced Ultrasound: A Novel Noninvasive, Nonionizing Method for the Detection of Brown Adipose Tissue in Humans.
abstract: BACKGROUND
  Brown adipose tissue (BAT) consumes glucose when it is activated by cold exposure, allowing its detection in humans by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT). The investigators recently described a novel noninvasive and nonionizing imaging method to assess BAT in mice using contrast-enhanced ultrasound (CEUS). Here, they report the application of this method in healthy humans.
  
  
  METHODS
  Thirteen healthy volunteers were recruited. CEUS was performed before and after cold exposure in all subjects using a continuous intravenous infusion of perflutren gas-filled lipid microbubbles and triggered imaging of the supraclavicular space. The first five subjects received microbubbles at a lower infusion rate than the subsequent eight subjects and were analyzed as a separate group. Blood flow was estimated as the product of the plateau (A) and the slope (β) of microbubble replenishment curves. All underwent (18)F-FDG PET/CT after cold exposure.
  
  
  RESULTS
  An increase in the acoustic signal was noted in the supraclavicular adipose tissue area with increasing triggering intervals in all subjects, demonstrating the presence of blood flow. The area imaged by CEUS colocalized with BAT, as detected by ¹⁸F-FDG PET/CT. In a cohort of eight subjects with an optimized CEUS protocol, CEUS-derived BAT blood flow increased with cold exposure compared with basal BAT blood flow in warm conditions (median Aβ = 3.3 AU/s [interquartile range, 0.5-5.7 AU/s] vs 1.25 AU/s [interquartile range, 0.5-2.6 AU/s]; P = .02). Of these eight subjects, five had greater than twofold increases in blood flow after cold exposure; these responders had higher BAT activity measured by (18)F-FDG PET/CT (median maximal standardized uptake value, 2.25 [interquartile range, 1.53-4.57] vs 0.51 [interquartile range, 0.47-0.73]; P = .02).
  
  
  CONCLUSIONS
  The present study demonstrates the feasibility of using CEUS as a noninvasive, nonionizing imaging modality in estimating BAT blood flow in young, healthy humans. CEUS may be a useful and scalable tool in the assessment of BAT and BAT-targeted therapies.
authors.affiliation: Cardiac Ultrasound Laboratory, Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Aidan
authors.initials: A
authors.lastname: Flynn
authors.affiliation: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Cardiac Ultrasound Laboratory, Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Marcello
authors.initials: M
authors.lastname: Panagia
authors.affiliation: Department of Nuclear Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Amr
authors.initials: A
authors.lastname: Abdelbaky
authors.affiliation: Department of Nuclear Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Megan
authors.initials: M
authors.lastname: MacNabb
authors.affiliation: Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Anthony
authors.initials: A
authors.lastname: Samir
authors.affiliation: Section of Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts; Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Cypess
authors.affiliation: Cardiac Ultrasound Laboratory, Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Weyman
authors.affiliation: Department of Nuclear Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
authors.affiliation: Cardiac Ultrasound Laboratory, Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: marielle@crosbie.com.
authors.forename: Marielle
authors.initials: M
authors.lastname: Scherrer-Crosbie
mesh_terms: D002001:Adipose Tissue, Brown / Q000000981:diagnostic imaging*; D000328:Adult; D001783:Blood Flow Velocity; D015331:Cohort Studies; D003080:Cold Temperature; D003287:Contrast Media; D019788:Fluorodeoxyglucose F18; D064368:Healthy Volunteers; D006439:Hemodynamics; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D012680:Sensitivity and Specificity; D018608:Ultrasonography, Doppler / Q000379:methods*; D055815:Young Adult
chemical_list: D003287:Contrast Media; D019788:Fluorodeoxyglucose F18
keywords: Activation; Brown adipose tissue; Contrast-enhanced ultrasound; Imaging; Positron emission tomography