Active Brown Fat During ¹⁸F-FDG PET/CT Imaging Defines a Patient Group with Characteristic Traits and an Increased Probability of Brown Fat Redetection

Abstract

Brown adipose tissue (BAT) provides a means of nonshivering thermogenesis. In humans, active BAT can be visualized by 18 F-FDG uptake as detected by PET combined with CT. The retrospective analysis of clinical scans is a valuable source to identify anthropometric parameters that influence BAT mass and activity and thus the potential efficacy of envisioned drugs targeting this tissue to treat metabolic disease. Methods: We analyzed 2,854 18 F-FDG PET/CT scans from 1,644 patients and identified 98 scans from 81 patients with active BAT. We quantified the volume of active BAT depots (mean values in mL 6 SD: total BAT, 162 6 183 [n 5 98]; cervical, 40 6 37 [n 5 53]; supraclavicular, 66 6 68 [n 5 71]; paravertebral, 51 6 53 [n 5 69]; mediastinal, 43 6 40 [n 5 51]; subphrenic, 21 6 21 [n 5 29]). Because only active BAT is detectable by 18 F-FDG uptake, these numbers underestimate the total amount of BAT. Considering only 32 scans of the highest activity as categorized by a visual scoring strategy, we determined a mean total BAT volume of 308 6 208 mL. In 30 BAT-positive patients with 3 or more repeated scans, we calculated a much higher mean probability to redetect active BAT (52% 6 25%) as compared with the overall prevalence of 4.9%. We calculated a BAT activity index (BFI) based on volume and intensity of individual BAT depots. Results: We detected higher total BFI in younger patients (P 5 0.009), whereas sex, body mass index, height, mass, outdoor temperature, and blood parameters did not affect total or depotspecific BAT activity. Surprisingly, renal creatinine clearance as estimated from mass, age, and plasma creatinine was a significant predictor of BFI on the total (P 5 0.005) as well as on the level of several individual depots. In summary, we detected a high amount of more than 300 mL of BAT tissue. Conclusion: BAT-positive patients represent a group with a higher than usual probability to activate BAT during a scan. Estimated renal creatinine clearance correlated with the extent of activated BAT in a given scan. These data imply an efficacy of drugs targeting BAT to treat metabolic disease that is at the same time higher and subject to a larger individual variation than previously assumed.

Mapping of human brown adipose tissue in lean and obese young men

“…BAT volumes have been reported to range from 14 mL to 665 mL (16), and thus BAT's functional relevance cannot be easily determined. Many of the previous studies quantifying BAT were retrospective and did not observe BAT under controlled, intentional stimulation (22,23). In addition to the methodological variability, several physiological factors impact BAT image acquisition and measurement.…”

Asymmetric perirenal brown adipose dormancy in adult humans is defined by local sympathetic activity

“…It is clear from studies performing PET/CT-scan based screenings of subjects with different age spans, that the amount of functionally competent BAT is less with increasing age 13,[59][60][61][62] . Our subjects were healthy kidney donors, mainly around 50-60 years of age which, according to previous reports 13,59 would be expected to have low, if any, prevalence of detectable active BAT.…”

Brown adipose tissue and glucose homeostasis – the link between climate change and the global rise in obesity and diabetes

“…23 It is now apparent that the total amount of brown and/or beige fat in adult humans could be up to ten-fold higher, even in obese adults. 19 This is based on studies that have been able to conduct repeated PET-CT scans of the same individual, 14 together with further refinements in image analysis. 19 Furthermore, a significant proportion of adipocytes present in brown or beige depots do not appear to be activated by acute cold exposure.…”

“…12 Consequently the extent to which environmentally induced changes in brown fat function can impact on glucose homeostasis remains a matter of debate. 13 It should be noted that with repeated PET-CT scans on the same subject then brown fat is identifiable in most, if not all, adults, 14 and comparable quantification of brown fat has been shown between PET-CT and thermal imaging. 15 Consequently, it is likely that brown fat is present in all adults, 16 and as shown in rodents its temperature fluctuates appreciably over a 24h period.…”