title: In vivo optical imaging of interscapular brown adipose tissue with (18)F-FDG via Cerenkov luminescence imaging.
abstract: OBJECTIVE
  Brown adipose tissue (BAT), a specialized tissue for thermogenesis, plays important roles for metabolism and energy expenditure. Recent studies validated BAT's presence in human adults, making it an important re-emerging target for various pathologies. During this validation, PET images with (18)F-FDG showed significant uptake of (18)F-FDG by BAT under certain conditions. Here, we demonstrated that Cerenkov luminescence imaging (CLI) using (18)F-FDG could be utilized for in vivo optical imaging of BAT in mice.
  
  
  METHODS
  Mice were injected with (18)F-FDG and imaged 60 minutes later with open filter and 2 minute acquisition. In vivo activation of BAT was performed by norepinephrine and cold treatment under isoflurane or ketamine anesthesia. Spectral unmixing and 3D imaging reconstruction were conducted with multiple-filter CLI images.
  
  
  RESULTS
  1) It was feasible to use CLI with (18)F-FDG to image interscapular BAT in mice, with the majority of the signal (>85%) at the interscapular site originating from BAT; 2) The method was reliable because excellent correlations between in vivo CLI, ex vivo CLI, and ex vivo radioactivity were observed; 3) CLI could be used for monitoring BAT activation under different conditions; 4) CLI signals from the group under short-term isoflurane anesthesia were significantly higher than that from the group under long-term anesthesia; 5) The CLI spectrum of (18)F-FDG with a peak at 640 nm in BAT after spectral unmixing reflected the actual context of BAT; 6) Finally 3D reconstruction images showed excellent correlation between the source of the light signal and the location and physical shape of BAT.
  
  
  CONCLUSIONS
  CLI with (18)F-FDG is a feasible and reliable method for imaging BAT in mice. Compared to PET imaging, CLI is significantly cheaper, faster for 2D planar imaging and easier to use. We believe that this method could be used as an important tool for researchers investigating BAT.
authors: Molecular Imaging Laboratory, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Charlestown, Massachusetts, United States of America.
authors: Xueli
authors: X
authors: Zhang
authors: Chaincy
authors: C
authors: Kuo
authors: Anna
authors: A
authors: Moore
authors: Chongzhao
authors: C
authors: Ran
mesh_terms: D002001:Adipose Tissue, Brown / Q000000981:diagnostic imaging*; D000818:Animals; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D061848:Optical Imaging / Q000379:methods*; D011877:Radionuclide Imaging; D015203:Reproducibility of Results; D012540:Scapula / Q000000981:diagnostic imaging*
chemical_list: D019788:Fluorodeoxyglucose F18
references: Diabetes. 2012 Mar;61(3):674-82
references: 22315305
references: Am J Physiol Regul Integr Comp Physiol. 2011 May;300(5):R1115-25
references: 21368268
references: Opt Lett. 2010 Apr 1;35(7):1109-11
references: 20364233
references: Opt Lett. 2010 Dec 1;35(23):3889-91
references: 21124555
references: Physiol Rev. 2004 Jan;84(1):277-359
references: 14715917
references: Nat Rev Endocrinol. 2010 Apr;6(4):195-213
references: 20195269
references: Nucl Med Commun. 2008 Nov;29(11):931-3
references: 18836369
references: Phys Med Biol. 2010 Jan 21;55(2):483-95
references: 20023328
references: Q J Nucl Med Mol Imaging. 2012 Jun;56(3):280-90
references: 22695338
references: N Engl J Med. 2009 Apr 9;360(15):1509-17
references: 19357406
references: Opt Express. 2011 Jun 20;19(13):12605-18
references: 21716501
references: Mol Imaging Biol. 2012 Apr;14(2):156-62
references: 21538154
references: J Nucl Med. 2006 Jun;47(6):999-1006
references: 16741310
references: Genes Dev. 2003 Mar 1;17(5):545-80
references: 12629038
references: Front Biosci (Landmark Ed). 2011 Jan 01;16:1233-60
references: 21196229
references: Nature. 2012 Jan 11;481(7382):463-8
references: 22237023
references: PLoS One. 2010 Mar 01;5(3):e9470
references: 20208993
references: Philos Trans A Math Phys Eng Sci. 2011 Nov 28;369(1955):4605-19
references: 22006909
references: J Biomed Opt. 2007 Mar-Apr;12(2):024007
references: 17477722
references: Eur J Nucl Med Mol Imaging. 2011 Mar;38(3):592-5
references: 21174087
references: FASEB J. 2009 Sep;23(9):3113-20
references: 19417078
references: Annu Int Conf IEEE Eng Med Biol Soc. 2011;2011:6158-61
references: 22255745
references: Mol Imaging. 2011 Jun;10(3):177-86, 1-3
references: 21496448
references: PLoS One. 2012;7(5):e37623
references: 22629431
references: Phys Med Biol. 2009 Aug 21;54(16):N355-65
references: 19636082
references: J Infect Dis. 2012 Mar 1;205(5):830-40
references: 22293433
references: Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1086-93
references: 17609311
references: J Biomed Opt. 2013 Feb;18(2):20502
references: 23334715
references: Clin Endocrinol (Oxf). 2011 Jun;74(6):661-70
references: 21521287
references: Nature. 2008 Aug 21;454(7207):1000-4
references: 18719589
references: J Nucl Med. 2012 Oct;53(10):1579-84
references: 22904353
references: J Biomed Biotechnol. 2011;2011:159834
references: 21541240
references: J Nucl Med. 2012 Sep;53(9):1438-45
references: 22872741
references: J Nucl Med. 2010 Jul;51(7):1123-30
references: 20554722
references: Obesity (Silver Spring). 2012 Jul;20(7):1519-26
references: 22343821
references: Mol Imaging Biol. 2012 Jun;14(3):286-92
references: 21786071
references: J Biomed Opt. 2011 Dec;16(12):126011
references: 22191928
references: J Nucl Med. 2011 Dec;52(12):2009-18
references: 22080446
references: N Engl J Med. 2009 Apr 9;360(15):1500-8
references: 19357405
references: FEBS Lett. 2010 Aug 4;584(15):3250-9
references: 20600006
references: Annu Rev Med. 1997;48:307-16
references: 9046964
references: J Nucl Med. 2012 Feb;53(2):312-317
references: 22241909
references: Obesity (Silver Spring). 2011 Sep;19(9):1755-60
references: 21566561
references: Small. 2010 May 21;6(10):1087-91
references: 20473988
references: J Nucl Med. 2004 Jul;45(7):1189-93
references: 15235065
references: Biochem Pharmacol. 2004 Aug 1;68(3):463-77
references: 15242813
references: J Clin Invest. 2012 Feb;122(2):545-52
references: 22269323
references: Ageing Res Rev. 2010 Jan;9(1):69-76
references: 19969105
references: Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E444-52
references: 17473055
references: J Biomed Opt. 2012 Apr;17(4):040506
references: 22559672
references: Mol Cell Biol. 2010 Sep;30(17):4224-33
references: 20584981
references: PLoS One. 2010 Oct 11;5(10):e13300
references: 20949021
references: Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):240-5
references: 20007767
references: Phys Med Biol. 2012 Feb 7;57(3):771-83
references: 22252144