Quantification of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging

Akira Nakayama, Antonio C. Bianco, Chen Yu Zhang, Bradford B. Lowell, John V. Frangioni

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Brown adipose tissue (BAT; brown fat) is the principal site of adaptive thermogenesis in the human newborn and other small mammals. Of paramount importance for thermogenesis is vascular perfusion, which controls the flow of cool blood in, and warmed blood out, of BAT. We have developed an optical method for the quantitative imaging of BAT perfusion in the living, intact animal using the heptamethine indocyanine IR-786 and near-infrared (NIR) fluorescent light. We present a detailed analysis of the physical, chemical, and cellular properties of IR-786, its biodistribution and pharmacokinetics, and its uptake into BAT. Using transgenic animals with homozygous deletion of Type II iodothyronine deiodinase, or homozygous deletion of uncoupling proteins (UCPs) 1 and 2, we demonstrate that BAT perfusion can be measured non-invasively, accurately, and reproducibly. Using these techniques, we show that UCP -1/-2 knockout animals, when compared to wild-type animals, have a higher baseline perfusion of BAT but a similar maximal response to β3-receptor agonist. These results suggest that compensation for UCP deletion is mediated, in part, by the control of BAT perfusion. Taken together, BAT perfusion can now be measured non-invasively using NIR fluorescent light, and pharmacological modulators of thermogenesis can be screened at relatively high throughput in living animals.

Original languageEnglish
Pages (from-to)37-49
Number of pages13
JournalMolecular Imaging
Volume2
Issue number1
DOIs
StatePublished - Jan 1 2003

Fingerprint

Brown Adipose Tissue
Optical Imaging
Transgenic Mice
Animals
Perfusion
Fluorescence
Tissue
Thermogenesis
Infrared radiation
Imaging techniques
Proteins
Blood
Light
Genetically Modified Animals
Wild Animals
Mammals
Perfusion Imaging
Pharmacokinetics
Oils and fats
Modulators

Keywords

  • Adaptive thermogenesis
  • Brown adipose tissue
  • Brown fat
  • IR-786
  • Near-infrared fluorescence imaging
  • Perfusion

ASJC Scopus subject areas

  • Engineering(all)

Cite this

Quantification of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging. / Nakayama, Akira; Bianco, Antonio C.; Zhang, Chen Yu; Lowell, Bradford B.; Frangioni, John V.

In: Molecular Imaging, Vol. 2, No. 1, 01.01.2003, p. 37-49.

Research output: Contribution to journalArticle

Nakayama, Akira ; Bianco, Antonio C. ; Zhang, Chen Yu ; Lowell, Bradford B. ; Frangioni, John V. / Quantification of brown adipose tissue perfusion in transgenic mice using near-infrared fluorescence imaging. In: Molecular Imaging. 2003 ; Vol. 2, No. 1. pp. 37-49.
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