F-FDG Uptake In Brown Adipose Tissue Research Articles

OR07-03 UCP1 Expression In Human Brown Adipose Tissue Is Inversely Associated With Cardiometabolic Risk Factors

Abstract Disclosure: T. Kwok: None. L.E. Ramage: None. K.J. Suchacki: None. C. Gray: None. K. Alexandra: None. L.D. Boyle: None. R.K. Semple: None. S.I. Semple: None. T. MacGillivray: None. E.J. van Beek: None. S. Wakelin: None. R.H. Stimson: None. Brown adipose tissue (BAT) is a promising therapeutic target for obesity. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET) is the most commonly used imaging modality to quantify human BAT activity. 18F-FDG uptake may be reduced in obesity but insulin resistance has been suggested as a potential confounding factor. Uncoupling protein 1 (UCP1) is the key thermogenic protein in BAT and thus serves as a surrogate measure of BAT thermogenic capacity. We quantified UCP1 expression in paired BAT and white adipose tissue (WAT) samples from 141 patients undergoing elective neck surgery. UCP1 mRNA was quantified in whole tissue (n=53) and differentiated pre-adipocytes (n=88). Data are presented as mean ± SEM. Individuals with high UCP1 expression in whole BAT (>2 arbitrary units) were younger (44.2 ± 3.5 vs 55.7 ± 2.0 years) with lower BMI (26.5 ± 1.2 vs 30.1 ± 1.0kg/m2), waist circumference (87.9 ± 2.9 vs 101.1 ± 2.6cm), waist-hip ratio (0.86 ± 0.01 vs 0.92 ± 0.01), fat percentage (29.1 ± 2.6 vs 35.3 ± 1.7%), insulin resistance (HOMA-IR 1.44 ± 0.18 vs 2.69 ± 0.35), systolic (131 ± 6 vs 143 ± 4mmHg) and diastolic blood pressure (79 ± 3 vs 86 ± 2mmHg) (all P<0.05). BAT UCP1 expression was lower in subjects on beta-blockers or with existing hypertension. BAT (but not WAT) UCP1 expression correlated negatively with age (r=−0.305), weight (r=−0.374), waist circumference (r=−0.296), fat mass (r=−0.388) and BMI (r=−0.282) (all P<0.05). However, UCP1 levels in differentiated brown adipocytes were not associated with any of the above measurements. In multiple regression, age was the only independent predictor of high BAT UCP1 expression. Interestingly, BAT UCP1 levels were not reduced in obese subjects aged <40 years. To determine whether BAT activity was preserved in young obese subjects in vivo, we performed 18F-FDG-PET/MR scanning during mild cold exposure (16-17°C) in 6 normal weight (BMI 22 ± 1kg/m2) and 6 obese (BMI 32 ± 1kg/m2) age-matched (22 ± 1 years) subjects. BAT 18F-FDG uptake (standard uptake value 5.1 ± 0.5 vs 4.2 ± 0.6 g/mL) and volume (69 ± 14 vs 72 ± 32 cm3) were similar between weight groups, despite greater insulin resistance in obese subjects (fasting glucose 5.5 ± 0.2 vs 4.3 ± 0.1mmol/L, insulin 11.9 ± 1.3 vs 5.8 ± 0.9mU/L, HOMA-IR 2.9 ± 0.3 vs 1.1 ± 0.2, free fatty acids 465 ± 78 vs 240 ± 34µM, all P<0.05), suggesting that 18F-FDG uptake by BAT is not significantly affected by insulin resistance. In conclusion, BAT UCP1 expression is reduced in individuals with adverse cardiometabolic risk factors, but these subjects retain brown pre-adipocytes with the capacity to form new thermogenic adipocytes after appropriate stimulation. UCP1 expression and cold-induced 18F-FDG uptake by BAT is preserved in young obese subjects. These data highlight the therapeutic potential of BAT mass expansion and activation as a therapeutic strategy to ameliorate the cardiometabolic consequences of obesity. Presentation: Thursday, June 15, 2023

Active Brown Adipose Tissue is Associated With a Healthier Metabolic Phenotype in Obesity.

Obesity is associated with increasing cardiometabolic morbidity and mortality worldwide. Not everyone with obesity, however, develops metabolic complications. Brown adipose tissue (BAT) has been suggested as a promoter of leanness and metabolic health. To date, little is known about the prevalence and metabolic function of BAT in subjects with severe obesity, a population at high cardiometabolic risk. In this cross-sectional study, we included 40 individuals with WHO class II-III obesity (BMI ≥ 35 kg/m2). Employing a 150-minute personalized cooling protocol and 18F-fluorodeoxyglucose positron emission tomography/computed tomography, cold-activated BAT was detectable in 14 (35%) of the participants. Cold-induced thermogenesis was significantly higher in participants with detectable BAT compared to those without. Notably, individuals with obesity and active BAT had 28.8% lower visceral fat mass despite slightly higher total fat mass compared to those without detectable BAT 18F-FDG uptake. This was accompanied by lower insulin resistance and systemic inflammation and improved NAFLD parameters, all adjusted for age, sex, and percent body fat. Contrary to previous assumptions, we show here that a significant fraction of individuals with severe obesity has active BAT. We found that decreased BAT 18F-FDG uptake was not associated with adiposity per se but with higher visceral fat mass. In summary, active BAT is linked to a healthier metabolic phenotype in obesity.

Diurnal variations of cold-induced thermogenesis in young, healthy adults: A randomized crossover trial

Harnessing cold-induced thermogenesis (CIT) and brown adipose tissue (BAT) activity has been proposed as a means of counteracting a positive energy balance, and thus of combating obesity and its related comorbidities. However, it has remained unclear whether CIT and BAT activity show diurnal variation in humans - knowledge that might allow treatments based on these factors to be time-optimized.A randomized crossover experiment was designed to examine whether CIT shows morning/evening variation in young, healthy adults (n = 14, 5 women). On the first experimental day, subjects' shivering thresholds were determined following a cooling protocol. After ≈96 h had elapsed, the subjects then returned on two further days (approx. 48 h apart) at 08:00 h or 18:00 in random order. On both the latter days, the resting energy expenditure (REE) was measured before the subjects underwent personalized cold exposure (i.e., according to their shivering threshold). CIT was then assessed for 60 min by indirect calorimetry. In an independent cross-sectional study (n = 133, 88 women), subjects came to the laboratory between 8:00 and 18:00 h and their BAT 18F-fluordeoxyglucose (18F-FDG) uptake was assessed after personalized cold stimulation.Both the REE and CIT were similar in the morning and evening (all P > 0.05). Indeed, 60 min of personalized-mild cold exposure in the morning or evening elicited a similar change in energy expenditure (16.8 ± 12.8 vs. 15.7 ± 15.1% increase above REE, P = 0.72). BAT 18F-FDG uptake was also similar in the morning, evening and afternoon (all P > 0.05).CIT does not appear to show morning/evening variation in young healthy adults, with the current study design and methodology. BAT 18F-FDG uptake appears not to change across the day either, although experiments with a within-subject study design are needed to confirm these findings. Registered under ClinicalTrials.gov Identifier no. NCT02365129.

Association between dietary factors and brown adipose tissue volume/18F-FDG uptake in young adults

To study the association between usual dietary factors (dietary energy density, nutrient intake, food group consumption, and dietary pattern) and brown adipose tissue (BAT) volume/18F-fluorodeoxyglucose (18F-FDG) uptake after personalized cold exposure in young healthy adults. A total of 122 young adults (n=82 women; 22.0±2.1 years old; 24.8±4.8kg/m2) took part in this cross-sectional study. Dietary factors were measured via a food frequency questionnaire and three non-consecutive 24h recalls. Dietary energy density (foods and caloric beverages included) and macronutrient intakes were subsequently estimated using EvalFINUT® software, food group consumption was estimated from the food frequency questionnaire, and different dietary patterns and quality indices were determined according to the reference methods. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18F-FDG uptake were assessed by static 18F-FDG positron-emission tomography and computed tomography (PET-CT) scans after a 2h personalized exposure to cold. A direct association was detected between dietary energy density and BAT Standardized Uptake Value (SUV)mean (β=0.215; R2=0.044; P=0.022), and between ethanol consumption and BAT volume (β=0.215; R2=0.044; P=0.022). The a priori Mediterranean dietary pattern was inversely associated with BAT SUVmean and SUVpeak (β=-0.273; R2=0.075; P=0.003 and β=-0.255; R2=0.066; P=0.005 respectively). In addition, the diet quality index for a Mediterranean diet and a pro-inflammatory dietary pattern (as determined via the dietary inflammatory index) were directly associated with BAT SUVmean and SUVpeak (SUVmean: β=0.238; R2=0.053; P=0.013 and β=0.256; R2=0.052; P=0.012 respectively; SUVpeak: β=0.278; R2=0.073; P=0.003 and β=0.248; R2=0.049; P=0.016 respectively). After controlling for multiplicity and possible confounders (sex, the evaluation wave and BMI), all the detected associations persisted. Dietary factors are slightly associated with BAT volume and/or 18F-FDG uptake after a personalized cold exposure in young adults. Our results provide an overall picture of the potential relationships between dietary factors and BAT-related variables in humans.

Leucine Potentiates Glucose-mediated 18F-FDG Uptake in Brown Adipose Tissue via β-Adrenergic Activation.

Significant depots of brown adipose tissue (BAT) have been identified in many adult humans through positron emission tomography (PET), with the amount of BAT being inversely correlated with obesity. As dietary activation of BAT has implications for whole body glucose metabolism, leucine was used in the present study to determine its ability to promote BAT activation resulting in increased glucose uptake. In order to assess this, 2-deoxy-2-(fluorine-18)fluoro-d-glucose (18F-FDG) uptake was measured in C57BL/6 mice using microPET after treatment with leucine, glucose, or both in interscapular BAT (IBAT). Pretreatment with propranolol (PRP) was used to determine the role of β-adrenergic activation in glucose and leucine-mediated 18F-FDG uptake. Analysis of maximum standardized uptake values (SUVMAX) determined that glucose administration increased 18F-FDG uptake in IBAT by 25.3%. While leucine did not promote 18F-FDG uptake alone, it did potentiate glucose-mediated 18F-FDG uptake, increasing 18F-FDG uptake in IBAT by 22.5%, compared to glucose alone. Pretreatment with PRP prevented the increase in IBAT 18F-FDG uptake following the combination of glucose and leucine administration. These data suggest that leucine is effective in promoting BAT 18F-FDG uptake through β-adrenergic activation in combination with glucose.

Brown adipose tissue volume and 18F-fluorodeoxyglucose uptake are not associated with energy intake in young human adults

ABSTRACTBackgroundSeveral studies have explored the role of human brown adipose tissue (BAT) in energy expenditure. However, the link between BAT and appetite regulation needs to be more rigorously examined.ObjectivesWe aimed to investigate the associations of BAT volume and 18F-fluordeoxyglucose (18F-FDG) uptake after a personalized cold exposure with energy intake and appetite-related sensations in young healthy humans.MethodsA total of 102 young adults (65 women; age: 22.08 ± 2.17 y; BMI: 25.05 ± 4.93 kg/m 2) took part in this cross-sectional study. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18F-FDG uptake were assessed by means of static 18F-FDG positron-emission tomography and computed tomography scans after a 2-h personalized exposure to cold. Energy intake was estimated via an objectively measured ad libitum meal and three nonconsecutive 24-h dietary recalls. Appetite-related sensations (i.e., hunger and fullness) were recorded by visual analog scales before and after a standardized breakfast (energy content = 50% of basal metabolic rate) and the ad libitum meal. Body composition was assessed by a whole-body DXA scan.ResultsBAT volume and 18F-FDG uptake were not associated with quantified ad libitum energy intake (all P > 0.088), nor with habitual energy intake estimated from the 24-h dietary recalls (all P > 0.683). Lean mass was positively associated with both the energy intake from the ad libitum meal (β: 17.612, R2 = 0.213; P < 0.001) and the habitual energy intake (β: 16.052, R2 = 0.123; P = 0.001). Neither the interaction BAT volume × time elapsed after meal consumption nor that of BAT 18F-FDG uptake × time elapsed after meal consumption had any significant influence on appetite-related sensations after breakfast or after meal consumption (all P > 0.3).ConclusionsNeither BAT volume, nor BAT 18F-FDG uptake after cold stimulation, are related to appetite regulation in young adults. These results suggest BAT plays no important role in the regulation of energy intake in humans.This trial was registered at clinicaltrials.gov as NCT02365129.

Relationship between the Daily Rhythm of Distal Skin Temperature and Brown Adipose Tissue 18F-FDG Uptake in Young Sedentary Adults.

The present study examines whether the daily rhythm of distal skin temperature (DST) is associated with brown adipose tissue (BAT) metabolism as determined by 18F-fluorodeoxyglucose (18F-FDG) uptake in young adults. Using a wireless thermometer (iButton) worn on the nondominant wrist, DST was measured in 77 subjects (26% male; age 22 ± 2 years; body mass index 25.2 ± 4.8 kg/m2) for 7 consecutive days. The temperatures to which they were habitually exposed over the day were also recorded. The interday stability of DST was calculated from the collected data, along with the intraday variability and relative amplitude; the mean temperature of the 5 and 10 consecutive hours with the maximum and minimum DST values, respectively; and when these hours occurred. Following exposure to cold, BAT volume and mean and peak standardized 18F-FDG uptake (SUVmean and SUVpeak) were determined for each subject via static 18F-FDG positron emission tomography/computed tomography scanning. Relative amplitude and the time at which the 10 consecutive hours of minimum DST values occurred were positively associated with BAT volume, SUVmean, and SUVpeak (p ≤ 0.02), whereas the mean DST of that period was inversely associated with the latter BAT variables (p ≤ 0.01). The interday stability and intraday variability of the DST were also associated (directly and inversely, respectively) with BAT SUVpeak (p ≤ 0.02 for both). All of these associations disappeared, however, when the analyses were adjusted for the ambient temperature to which the subjects were habitually exposed. Thus, the relationship between the daily rhythm of DST and BAT activity estimated by 18F-FDG uptake is masked by environmental and likely behavioral factors. Of note is that those participants exposed to the lowest ambient temperature showed 3 to 5 times more BAT volume and activity compared with subjects who were exposed to a warmer ambient temperature.

Dissociation Between Brown Adipose Tissue 18F-FDG Uptake and Thermogenesis in Uncoupling Protein 1-Deficient Mice.

18F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis, which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain, however, whether BAT 18F-FDG uptake is a reliable surrogate measure of UCP1-mediated heat production. Methods: UCP1 knockout (KO) and wild-type (WT) mice housed at thermoneutrality were treated with the selective β3 adrenergic receptor agonist CL 316, 243 and underwent metabolic cage, infrared thermal imaging and 18F-FDG PET/MRI experiments. Primary brown adipocytes were additionally examined for their bioenergetics by extracellular flux analysis as well as their uptake of 2-deoxy-3H-glucose. Results: In response to CL 316, 243 treatments, oxygen consumption, and BAT thermogenesis were diminished in UCP1 KO mice, but BAT 18F-FDG uptake was fully retained. Isolated UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy-3H-glucose uptake rates were largely unaffected. Conclusion: Adrenergic stimulation can increase BAT 18F-FDG uptake independently of UCP1 thermogenic function.

Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue.

Resistin has been originally identified as an adipokine that links obesity to insulin resistance in mice. In our previous studies in spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin (Retn) transgene specifically in adipose tissue (SHR-Retn), we have observed an increased lipolysis and serum free fatty acids, ectopic fat accumulation in muscles, and insulin resistance. Recently, brown adipose tissue (BAT) has been suggested to play an important role in the pathogenesis of metabolic disturbances. In the current study, we have analyzed autocrine effects of transgenic resistin on BAT glucose and lipid metabolism and mitochondrial function in the SHR-Retn vs. nontransgenic SHR controls. We observed that interscapular BAT isolated from SHR-Retn transgenic rats compared with SHR controls showed a lower relative weight (0.71 ± 0.05 vs. 0.91 ± 0.08 g/100 g body wt, P < 0.05), significantly reduced both basal and insulin stimulated incorporation of palmitate into BAT lipids (658 ± 50 vs. 856 ± 45 and 864 ± 47 vs. 1,086 ± 35 nmol/g/2 h, P ≤ 0.01, respectively), and significantly decreased palmitate oxidation (37.6 ± 4.5 vs. 57 ± 4.1 nmol/g/2 h, P = 0.007) and glucose oxidation (277 ± 34 vs. 458 ± 38 nmol/g/2 h, P = 0.001). In addition, in vivo microPET imaging revealed significantly reduced (18)F-FDG uptake in BAT induced by exposure to cold in SHR-Retn vs. control SHR (232 ± 19 vs. 334 ± 22 kBq/ml, P < 0.05). Gene expression profiles in BAT identified differentially expressed genes involved in skeletal muscle and connective tissue development, inflammation and MAPK and insulin signaling. These results provide evidence that autocrine effects of resistin attenuate differentiation and activity of BAT and thus may play a role in the pathogenesis of insulin resistance in the rat.

Characterization of brown adipose tissue 18F-FDG uptake in PET/CT imaging and its influencing factors in the Chinese population

18F-FDG PET/CT has been widely applied for tumor imaging. However, it is reported that many normal tissues, e.g., brown adipose tissue, can also uptake 18F-FDG. The purpose of this study was to determine the imaging characteristics of 18F-FDG uptake in brown adipose tissue (BAT) in PET/CT. A total of 2,944 patients who underwent PET/CT from September 2011 to March 2013 were analyzed retrospectively. Imaging features of 18F-FDG uptake in BAT were analyzed. Univariate analysis and logistic regression analysis were performed to evaluate the effect of age, gender, cancer status, body mass index (BMI), average daily maximum temperature of imaging month and fasting plasma glucose (Glu) on the positive rate of 18F-FDG uptake in BAT. The results showed that 1.9% (57/2944) patients had 18F-FDG uptake in BAT. 18F-FDG, manifested as flaky, nodular and beaded shape, was symmetrically distributed in the adipose tissues of cervical and supraclavicular, mediastinal, paravertebral, and perirenal areas. Uptake of 18F-FDG within cervical/supraclavicular area was most common (89.5%, 51/57) with an SUVmax ranging from 2.8 to 31.4. Univariate analysis showed that gender and cancer status were not significantly correlated with the BAT 18F-FDG uptake rate. In contrast, age, BMI, Glu and average daily maximum temperature in the imaging month were significantly correlated with the BAT 18F-FDG uptake rate (P<0.05). Further logistic regression analysis showed that only age, BMI and average daily maximum temperature were significant (OR<1, P<0.05). Based on the value of OR, the most significant factor that affects BAT 18F-FDG uptake rate was age, followed by the average daily maximum temperature and BMI. We concluded that Chinese adult has low positive rate of 18F-FDG uptake in BAT. Cervical/Supraclavicular is the most common area with BAT 18F-FDG uptake. Age, average daily maximum temperature and BMI are independent factors affecting 18F-FDG uptake.

Brown Adipose Tissue Activity in Relation to Weight Gain During Chemotherapy in Breast Cancer Patients: A Pilot Study

Weight gain has been reported in early stage breast cancer patients during chemotherapy, but the involved mechanisms remain unclear. A chemotherapy-induced decrease of brown adipose tissue (BAT) activity may partly contribute to weight gain in these patients. A positron emission tomography/computed tomography scan was performed at baseline and after 1 course of docetaxel + trastuzumab treatment in 26 breast cancer women. Variation of the maximal standardized uptake value of BAT in the cervical and supraclavicular regions between the 2 measures was assessed according to weight changes. Overall, 18F-FDG uptakes in BAT decreased by 11.3% after 1 course of chemotherapy (p = 0.03). No correlation was found between the baseline values of 18F-FDG uptake and body mass index or age of patients, but as expected 18F-FDG uptake was dependent on season period. Among the patients, 35% gained weight, 25% lost weight, and 40% remained stable. Women who gained weight during chemotherapy experienced a significant decrease of 18F-FDG uptake in BAT (p = 0.005). Decreased activity of BAT was associated with body weight gain during chemotherapy. These original data suggest for the first time that BAT modulation by chemotherapy would be a potential contributor to body weight gain through blunted thermogenesis in breast cancer patients.

Combining 123I-Metaiodobenzylguanidine SPECT/CT and 18F-FDG PET/CT for the Assessment of Brown Adipose Tissue Activity in Humans During Cold Exposure

Brown adipose tissue (BAT) has become a focus of research in the hope of finding a new target to fight obesity. Metabolic BAT activity can be visualized with (18)F-FDG PET/CT. Furthermore, the sympathetic innervation of BAT can be visualized with the radiolabeled norepinephrine analog (123)I-metaiodobenzylguanidine ((123)I-MIBG). We aimed to determine whether (123)I-MIBG SPECT/CT and (18)F-FDG PET/CT identify the same anatomic regions as active BAT in adult humans. Furthermore, we investigated whether the magnitude of BAT activity measured by these techniques correlated. Finally, we tried to establish the optimal time interval between (123)I-MIBG administration and subsequent SPECT/CT acquisition to visualize sympathetic stimulation of BAT. Ten lean (body mass index, 19-25 kg/m(2)), healthy Caucasian men (age, 18-32 y) underwent one (18)F-FDG PET/CT and two (123)I-MIBG-SPECT/CT scans within a 2-wk interval. On 2 separate occasions, the subjects were exposed to mild cold (17°C) for 2 h after an overnight fast. After 1 h of cold exposure, (18)F-FDG (one occasion) or (123)I-MIBG (other occasion) was administered. (18)F-FDG PET/CT was performed at 1 h after (18)F-FDG administration, and (123)I-MIBG-SPECT/CT was performed at 4 and 24 h after (123)I-MIBG injection. (18)F-FDG uptake in BAT was observed in 8 of 10 subjects, whereas (123)I-MIBG uptake was observed in 7 of 10 subjects in both the SPECT/CT scans acquired at 4 h after (123)I-MIBG administration and the SPECT/CT scans acquired at 24 h after (123)I-MIBG administration. All subjects who showed (123)I-MIBG uptake in BAT also showed (18)F-FDG uptake in BAT. There was no statistically significant correlation between maximal standardized uptake value of (18)F-FDG and semiquantitative uptake of (123)I-MIBG at 4 h after administration. However, a positive correlation was found between the maximal standardized uptake value of (18)F-FDG and semiquantitative uptake of (123)I-MIBG at 24 h after administration (r = 0.64, P = 0.04). (123)I-MIBG SPECT/CT, as a marker of sympathetic activity, and (18)F-FDG PET/CT, as a marker of metabolic activity, identified the same anatomic regions as active BAT. Moreover, when (123)I-MIBG SPECT/CT was performed at 24 h after (123)I-MIBG administration, the magnitude of BAT activity measured with these techniques correlated strongly. This finding not only supports that BAT activity in humans is sympathetically influenced but also identifies (123)I-MIBG SPECT/CT, when performed 24 h after (123)I-MIBG injection, as a method to visualize and quantify sympathetic stimulation of BAT.

Fasting and Postprandial Activity of Brown Adipose Tissue in Healthy Men

The role of brown adipose tissue (BAT) in adult metabolism is poorly understood. This study aimed to examine the differential effects of an overnight fast and the postprandial state on BAT activity. We included 10 healthy, lean male volunteers. BAT uptake of glucose was visualized using (18)F-FDG PET/CT during mild cold exposure. Each subject underwent PET/CT twice. The first scan was obtained after an overnight fast; the second after a standardized meal. (18)F-FDG uptake in BAT was observed in 6 of 10 volunteers. These subjects were found to have a higher maximal standardized uptake value when fasting (median, 13.1 g/mL; range, 6.1-27.6 g/mL) than when in the postprandial state (median, 6.8 g/mL; range, 2.1-13.4 g/mL) (P = 0.03). Cold-stimulated (18)F-FDG uptake by BAT in humans is more pronounced during fasting. The lower maximal standardized uptake value in the postprandial state may be explained by increased insulin-stimulated glucose uptake in muscle.

Intervention to Lower Anxiety of 18F-FDG PET/CT Patients by Use of Audiovisual Imagery During the Uptake Phase Before Imaging

Many patients referred for PET suffer from anxiety, possibly affecting the workflow and patient experience. In addition, patient anxiety may affect image quality through uptake of (18)F-FDG in muscles or brown adipose tissue (BAT).This study investigated the effects of a nonpharmacologic intervention-the use of audiovisual imagery in the PET uptake room-on patient anxiety and false-positive uptake of (18)F-FDG (in muscles and BAT). A 2-stage study was conducted on 101 patients. The cohort undergoing the intervention included 51 patients. The first stage (n = 35) included physiologic measurements (cardiovascular activity, muscular activity, skin conductance, and cortisol), a state anxiety questionnaire, and visual evaluation of (18)F-FDG uptake in muscles and BAT; the second stage (n = 66) included only the state anxiety questionnaire and the (18)F-FDG uptake evaluation. Throughout the stay in the uptake room, a significant decrease in overall anxiety was found, together with several other significant changes in patient physiology. In the cohort with audiovisual intervention, however, the decrease in patient anxiety was significantly larger. The cohort with intervention also showed significantly lower (18)F-FDG uptake in BAT but not in muscles. The investigated audiovisual intervention helps to lower patient anxiety in the PET uptake room and can lower false-positive (18)F-FDG uptake in BAT.

18F-Fluorobenzyl Triphenyl Phosphonium: A Noninvasive Sensor of Brown Adipose Tissue Thermogenesis

Recent studies have proposed activation of brown adipose tissue (BAT) thermogenesis as a new strategy to combat obesity. Currently, there is no effective noninvasive imaging agent to directly detect unstimulated BAT and quantify the core mechanism of mitochondrial thermogenesis. We investigated an approach to detect BAT depots and monitor thermogenesis using the mitochondria-targeting voltage sensor radiolabeled fluorobenzyltriphenyl phosphonium (FBnTP). (18)F-FBnTP, (14)C-FBnTP, (18)F-FDG, and (99m)Tc-sestamibi uptake in BAT at room temperature (n = 8) and cold-treated (n = 8) Lewis rats was assayed. The effect of the cold condition on (18)F-FBnTP retention in BAT was assessed in 8 treated and 16 control rats. The effect of the noradrenergic inhibitor propranolol on (14)C-FBnTP response to cold stimulation was investigated in an additional 8 treated and 8 control mice. At room temperature, (18)F-FBnTP accumulated in BAT to an extent similar to that in the heart, second only to the kidney and twice as much as (99m)Tc-sestamibi. Prior exposure to cold (4°C) for 4 h resulted in an 82% decrease of (14)C-FBnTP uptake and an 813% increase of (18)F-FDG uptake in BAT. (99m)Tc-sestamibi uptake was not affected by cold. Administration of (18)F-FBnTP at room temperature 60 min before 120 and 240 min of exposure to cold resulted in marked washout of the tracer from BAT. Propranolol significantly diminished the effect of cold on (14)C-FBnTP and (18)F-FDG uptake into BAT. The intense uptake of (18)F-FBnTP into BAT at room temperature and the response to cold stimulation suggest the unique potential advantage of (18)F-FBnTP not only in detecting unstimulated BAT at high contrast but also in quantifying the mitochondrial thermogenic activity. (18)F-FBnTP PET may serve as a useful technique to assess BAT volume and function.

Brown Adipose Tissue Can Be Activated or Inhibited within an Hour before 18F‐FDG Injection: A Preliminary Study with MicroPET

Brown adipose tissue (BAT) is emerging as a potential target for treating human obesity. It has been indicated that BAT is rich in innervations of sympathetic nerve control. Using 18F-FDG microPET imaging, this study aims at evaluating how factors related to sympathetic activation/inhibition changed BAT metabolism of mice. BAT 18F-FDG uptake were semiquantitatively evaluated in different groups of mice under temperature (cold or warm stimulus) or pharmacological interventions (norepinephrine, epinephrine, isoprenaline, or propranolol) and were compared with the corresponding controls. It was found that BAT activation can be stimulated by cold exposure (P = 1.96 × 10−4), norepinephrine (P = .002), or both (P = 2.19 × 10−6) within an hour before 18F-FDG injection and can also be alleviated by warming up (P = .001) or propranolol lavage (P = .027). This preliminary study indicated that BAT function could be evaluated by 18F-FDG PET imaging through short-term interventions, which paved the way for further investigation of the relationship between human obesity and BAT dysfunction.

Brown adipose tissue 18F-FDG uptake in pediatric PET/CT imaging

Positron emission tomography (PET) using [F-18]2-fluoro-2-deoxyglucose (FDG) fused with CT ((18)F-FDG PET/CT) has been widely adopted in oncological imaging. However, it is known that benign lesions and other metabolically active tissues, such as brown adipose tissue (BAT), can accumulate (18)F-FDG, potentially resulting in false-positive interpretation. Previous studies have reported that (18)F-FDG uptake in BAT is more common in children than in adults. We illustrate BAT FDG uptake in various anatomical locations in children and adolescents. We also review what is known about the effects of patient-related physical attributes and environmental temperatures on BAT FDG uptake, and discuss methods used to reduce BAT FDG uptake on (18)F-FDG PET.

Determinants of Physiologic 18F-FDG Uptake in Brown Adipose Tissue in Sequential PET/CT Examinations

The aim of this study was to assess independent predictors of 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) uptake in brown adipose tissue (BAT) in patients undergoing repeated positron emission tomography (PET)/computed tomography (CT) scans. Eight hundred forty-eight (mean age 50.9 ± 16 years) patients in whom PET/CT scan was repeated (mean interval 5 ± 1.5 months) constituted the study group. (18)F-FDG uptake in characteristic areas of BAT, with CT density of adipose tissue, greater than background soft-tissue activity was considered as evidence of BAT uptake. Both distribution and maximum standardized uptake values (SUVmax) were registered. Clinical and anamnestic data were collected for each patient. (18)F-FDG uptake in BAT was present in 8.6% patients at first scan. Independent predictors of presence of uptake were age (younger), gender (female), body mass index (lower), and maximum outdoor temperature (lower). Age was the only independent predictor of BAT (18)F-FDG uptake distribution, while SUVmax was related to both age and outdoor temperature. Independent determinants of persistence of BAT (18)F-FDG uptake at second PET/CT were outdoor temperature at time of second scan and extension of metabolically active BAT at first scan. Age, body mass index, and outdoor temperature are significant determinants of BAT evidence at (18)F-FDG PET/CT. Moreover, extension of BAT and outdoor temperature are the strongest determinants of persistence of BAT evidence on (18)F-FDG PET/CT in repeated scan.

FDG uptake in brown adipose tissue—A brief report on brown fat with FDG uptake mechanisms and quantitative analysis using dual-time-point FDG PET/CT

Aims Brown adipose tissue (BAT) is a potential source of false-positive findings on [ 18F] FDG PET. In this report, we have discussed the 18F-FDG uptake mechanisms in BAT and have aimed to determine if dual time point PET imaging helps to differentiate BAT from malignant lesions. Methods Patients with dual-time-point PET/CT scans were reviewed retrospectively and 31 cases (11 males, 20 females, age: 28.6±9.7) having hypermetabolic BAT were included for this study. 18F-FDG uptake in BAT was quantitatively analyzed by maximum standardized uptake values (SUVmax), and average percent change in SUVmax of BAT between early and delayed images was calculated. Results Compared to the initial scans, 18F-FDG uptakes in BAT in delayed images were higher in 26 of the patients, and lower in one patient. In terms of body regions, 18F-FDG uptake increased in 80.6%, remained unchanged in 5.5% and decreased in 13.9% of the body regions. Mean percent change in SUVmax, including all BAT regions, was 19.8±19.1% while the mean percent increase was calculated as 69±25% in regions where progressive accumulation was observed. The increase in SUVmax correlated with the time interval between the two scans. Conclusion Physiologic 18F-FDG uptake in BAT increases over time and may mimic the behavior of malignant lesions on dual time point PET imaging. Without the exact anatomic definition of the CT scan, false positive interpretation of PET data may be possible in cases with atypical BAT.

Prevention of Brown Adipose Tissue Activation in 18F-FDG PET/CT of Breast Cancer Patients Receiving Neoadjuvant Systemic Therapy

(18)F-FDG uptake in brown adipose tissue (BAT) can complicate interpretation and quantification of PET images, especially in regions of possible lymph node metastases such as the axilla and the mediastinum. The aim of this study was to prospectively evaluate the effect of patient preparation using a single oral dose of diazepam and controlled indoor temperature to prevent (18)F-FDG uptake in BAT in breast cancer patients referred for monitoring of therapy response with (18)F-FDG PET. During the fall and winter months, 53 patients referred for (18)F-FDG PET/CT of breast cancer were included. A cohort of 25 patients was imaged without an intervention, and a second cohort of 28 patients was prepared according to a new protocol that included 10 mg of diazepam and adequate indoor temperature. The generated images were visually assessed for the presence of (18)F-FDG at the location of fat-density tissue on CT images using a 4-point scale. In the cohort without intervention, relevant (18)F-FDG uptake in BAT was identified in 4 patients (16%); in the cohort prepared according to the proposed protocol, in only 1 patient (4%). The mean score of BAT (18)F-FDG uptake evaluated with the 4-point system was 0.04 in the group treated according to the new protocol and 0.16 in the group treated according to the previous protocol. In the clinically relevant group of breast cancer patients, (18)F-FDG uptake in BAT can be reduced by a single oral administration of diazepam combined with controlled room temperature in resting rooms.