Hossein Jadvar, MD, PhD, MPH, MBAAssociate Professor of Radiology and Biomedical Engineering

Director of Radiology ResearchUniversity of Southern California

Los Angeles, California

BAT: Structure and FunctionOne of two types of adipose tissue (white and brown)Contains smaller fat vacuoles, higher number of

mitochondria, more capillaries than white fatRichly innervated by sympathetic nerves (1, 2, 3)Uncoupling protein-1 (UCP-1, thermogenin) in inner

mitochondrial membrane uncouples oxidative phosphorylation producing heat energy (non-shivering thermogenesis) with ATP provided by glycolysis

Present in newborns (5% body mass) and hibernating animals; most disappear in adulthood (not in mice)

Contribution to evolutionary success of mammalsCannon B et al. Physiol Rev 2004 (Sweden)

BAT: Structure and Function

Brown Fat White Fat

BAT: Structure and Function

Hematoxylin-Eosin Hematoxylin & anti-UCP-1 AbTatsumi M et al. J Nucl Med 45:1189-93, 2004.

BAT: Distribution in Humans Human depots differently located from than those in rodentsMain depots:

Supraclavicular Fossa (USA-Fat), Axillae, and NeckMediastinalParavertebral, Para-aortic, Parahepatic, ParacolicSuprarenal/Perinephric

Acutely cold-induced, stimulated by sympathetic nervous systemAlmost all mediastinal/suprarenal BAT FDG uptake associated with

concurrent supraclavicular/paravertebral uptakeNeck (2.3%) > Paravertebral (1.4%) > Mediastinum (0.9%) >

Perinephric (0.8%), overall (up to 4%)females > males; children > adults (15% vs. 2%) (p<0.01)

Hany TF et al. Eur J Nucl Med Mol Imaging 2002 (Switzerland); Yeung HW et al. J Nucl Med 2003 (MSKCC, NY); Cohade C et al J Nucl Med 2003 (Johns Hopkins); Kim S et al. Clin Nucl Med 2006 (Mount Sinai, NY); Nedergaard J et al. Am J Physiol 2007.

Brown Adipose Tissue

Brown Adipose Tissue

BAT: Effect of Cold and Pharmacologic Interventions on FDG Uptake

Female Lewis rats injected with FDG under conditions of:Control (no pre-medication and exposure to cold)Exposure to cold (4 C for 4 h)Propranolol, or Reserpine, or Dizepam

Cold Exposure: 5x increase in uptake (vs. control)Propranolol or Reserpine: 70% decline in uptake (vs. control)Diazepam: no significant change

Tatsumi M et al. J Nucl Med 2004 (Johns Hopkins)

BAT: Effect of Fentanyl and Diazepam on FDG Uptake Gelfand MJ et al. Pediatr Radiol 2005

69 pediatric patients received iv Fentanyl, or low (0.06 mg/kg) or moderate dose (0.1 mg/kg) diazepam prior to PET

Visual grading BAT FDG uptakeFentanyl reduced BAT FDG uptake significantly (p=0.004)Low dose diazepam no effect (p=0.98)Medium dose diazepam indeterminateLower FDG uptake in age<10 y compared to age>10 y (p=0.02)

baseline after fentanyl

BAT: Effect of -adrenergic agonistson FDG UptakeFemale Lewis rats injected with caffeine, ephedrine, or

nicotine 30 min before iv FDGIncrease in BAT FDG uptake compared to control rats:

Ephedrine 3.7xNicotine 7.9xNicotine + Ephedrine 12.0xCaffeine slight (p=ns)

Effects blocked by prior -adrenergic antagonist“Patients should avoid nicotine, ephedrine before FDG PET”

Baba S et al. J Nucl Med 2007 (Johns Hopkins)

BAT: Effect of -adrenergic antagonistson FDG Uptake

26 patients with FDG PET scans before and after propranolol (20 mg po 60 min prior to iv FDG)

No adverse effects in patients or on tumor FDG uptakeBAT SUVmax (p<0.0001)

Pre-propranolol 5.52+/-2.30Post-propranolol 1.39+/-0.42

Post-propranolol scan improved image interpretation most notably in the mediastinum

Similar findings with 80 mg propranolol po 2 hrs prior to FDGParysow O et al. Clin Nucl Med 2007 (Argentina)

Soderlund V et al. Eur J Nucl Med Mol Imaging 2007 (Sweden)

BAT: Reduction of FDG Uptake with Warm TemperatureUptake incidence of 13.7% during January through March

and 4.1%, during the rest of the year.Warm clothing, avoidance of exposure to cold air during

transit to PET facility, temperature-controlled room (75 F) reduces BAT FDG uptake significantly

Warm temperature reduces FDG uptake in BAT despite no effect by benzodiazepine

Cohade C et al. J Nucl Med 2003 (Johns Hopkins) Garcia CA et al. Mol Imaging Biol 2006 (Washington DC)Garcia CA et al. Mol Imaging Biol 2004 (Washington DC)

BAT: Reduction of FDG Uptake with Warm Temperature Garcia CA et al. Mol Imaging Biol 2006

BAT and FDG Uptake: SummaryNon-shivering thermogenesisFunction of age, sex, ambient temperature, sympathetic

nervous systemSupraclavicular, Axillae, Neck, Mediastinum, Paravertebral, Para-

aortic, Parahepatic, Paracolic, Suprarenal, PerinephricAvoid nicotine and sympathetic NS stimulatory agentsCan be reduced with warm temperature and pharmacologicallyWarm clothing, avoidance of exposure to cold, temperature-

controlled room (75 F)Propranolol (20 mg orally one hour prior to FDG)