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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 3  |  Page : 302-306

Demographic characteristics of cases with brown adipose tissue detected in 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging


Clinic of Nuclear Medicine, Istanbul Training and Research Hospital, University of Health Sciences Turkey, Istanbul, Turkey

Date of Submission21-Jun-2021
Date of Acceptance29-Jul-2021
Date of Web Publication7-Sep-2021

Correspondence Address:
Dr. Göksel Alçin
Istanbul Training and Research Hospital, Clinic of Nuclear Medicine, Org. Nafiz Gurman Street, Samatya, Kocamustafapasa, Fatih, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_124_21

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  Abstract 


Background: Brown adipose tissue (BAT) has an essential role in regulating energy, metabolism, and thermogenesis in mammals. BAT activation is often detected in winter, especially in the female gender and in individuals with normal body mass index (BMI) by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) modality. It has been reported to be associated with some factors such as age, plasma glucose, and outdoor temperature. Therefore, in this study, we aimed to investigate the characteristics of demographic, metabolic, and other variables of patients with FDG uptake in activated BAT on 18F-FDG PET/CT imaging in patients diagnosed with various types of cancer. Methods: 15752 patients diagnosed with various types of cancer who underwent whole-body 18F-FDG PET/CT imaging for routine diagnosis, staging, or follow-up between March 2017 and April 2019 were screened, and a total of 188 BAT-positive patients were included in this retrospective study. In addition to demographic patient characteristics such as age, height, and weight, data were collected such as BMI, date of birth, date and season of PET/CT imaging, laboratory findings, injection, and PET/CT imaging time, and the average outdoor temperature on the day of PET imaging and evaluated statistically. Results: A total of 188 BAT-positive patients (142 females [75.5%] and 46 males [24.5%]) were included in this study. The mean age of the patient group was 43.89 ± 13.67 years, and the mean BMI was 24.12 ± 3.56. About 103 patients (54.7%) with positive BAT were at normal weight (BMI 18.5–24.9), 49 patients (26.2%) were overweight (BMI 25–30), and 36 patients (19.1%) were obese (BMI >30). The injection time was 76.6% in the afternoon hours, whereas 77.1% of the imaging was performed in the afternoon hours. The mean fasting blood glucose (FBS) was 106.93 ± 14.28 mg/dl, and 61.7% (n = 116) of the patients were hyperglycemic. However, we found no significant relationship between BAT activation and the date of birth, place of birth, PET imaging season (relative to the northern hemisphere), and outdoor temperature. Conclusions: In our study, while BAT FDG uptake was not increased with cold exposure before PET scan and seasonally, female gender, younger age, and mean low BMI are the significant predictive value of BAT activation. Therefore, we aimed to emphasize that BAT activation should be considered to prevent the masking of the image and prevent false-positive involvement, especially in tumor tissue in risky groups.

Keywords: 18F-fluorodeoxyglucose positron emission tomography/computed tomography, brown adipose tissue, SUVmax


How to cite this article:
Alçin G, Arslan E. Demographic characteristics of cases with brown adipose tissue detected in 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Biomed Biotechnol Res J 2021;5:302-6

How to cite this URL:
Alçin G, Arslan E. Demographic characteristics of cases with brown adipose tissue detected in 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Biomed Biotechnol Res J [serial online] 2021 [cited 2021 Dec 6];5:302-6. Available from: https://www.bmbtrj.org/text.asp?2021/5/3/302/325607




  Introduction Top


In the human body, there are two types of adipose tissue: white and brown adipose tissue (BAT). Besides regulating energy and metabolism in mammals, BAT also has a protective role against hypothermia by increasing thermogenesis. BAT uncoupling protein-1 is a critical molecule in the release of energy in the form of heat by oxidative phosphorylation from ATP in mitochondria.[1] BAT activation can be detected in the cervical, supraclavicular, and thoracic-abdominal paravertebral regions by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) method, which is an imaging modality based on glucose hypermetabolism.[2] Moreover, PET/CT has become the gold standard method for active BAT detection.[3] Active BAT prevalence detected by the 18F-FDG PET/CT in adults ranges from 1% to 10%.[4] These metabolic activity foci cause false-positive evaluations by preventing tumor imaging.[5] BAT is often associated with low body mass index (BMI) and increased glucose levels. Furthermore, by demonstrating the protective effect of BAT activation-related thermogenesis against obesity and diabetes, today, it has begun to be defined as a potential target in the treatment of obesity and metabolic diseases.[6] However, in some studies, it has been reported that BAT activation is increased in the winter months, in young ages, in women, and patients with average weight compared to obese patients.[7],[8]

Furthermore, it has been shown that BAT activation is sensitive to β-adrenergic receptor agonists and cold exposure and can be suppressed by beta-blockers.[9] In the past, it has been tried to prevent BAT activation using body warming or beta-blockers.[2] Apart from these, it has been reported that the prevalence of active BAT varies with some factors such as age, plasma glucose level, ambient temperature, or drugs.[4]

Therefore, in our study, we aimed to investigate the demographic, metabolic, and environmental variable characteristics of patients with increased FDG uptake patterns due to BAT activation during 18F-FDG PET/CT imaging for diagnosis, staging, or follow-up in patients diagnosed with various cancer.


  Methods Top


Patients

In this study, 188 BAT-positive patients were included by retrospectively screening a total of 15,752 cases whose whole-body PET/CT imaging between March 2017 and April 2019. Our study has an 'Istanbul training and Research Hospital Local Ethics Committee' retrospective study approval (2018-1176). Verbal and written consent is obtained from all patients whose medical findings can be used for research purposes.

18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging

Patients with a blood glucose level of <150 mg/dl after at least 6 h of fasting before the administration were included in the study. Patients received a standard injection of 3.7–5.2 MBq/kg 18F-FDG intravenously. After 45–60 min, whole-body PET/CT imaging was performed in the supine position including the vertex-upper thigh. All of the images were performed with a Siemens mCT 20 ultra High Definition (HD) lutetium oxyorthosilicate (LSO) PET/CT device (Siemens molecular imaging, Hoffmann Estates, Illinois, USA).

For the calculation of SUVmax, “regions of interest” (ROI), which includes the highest involvement area in the primary tumor, was drawn over PET sections. SUVmax: The maximum activity in the ROI (MBq/ml)/injected dose of FDG (MBq/kg body weight) was calculated according to the formula.

Demographic analysis

In our study, the anthropometric measurements of the cases were obtained by retrospectively scanning the files (body weight, height, and BMI). BMI was obtained from the formula (weight/height2, kg/m2) by proportioning body weight to the square of height in meters. In conclusion, demographic features such as age, height, and weight of the patients included in the study, as well as laboratory findings such as BMI, date of birth, date of PET, fasting plasma glucose (FBG) level, injection time, the outdoor temperature during PET (the average outdoor temperatures for the PET/CT imaging day were obtained by scanning from the free website “tr.freemeteo.com”) and PET time were evaluated throughout the study.

Statistical analysis

All data were evaluated using the SPSS software for Windows (v21.0; IBM, Armonk, NY, USA) program. All data were evaluated by calculating the mean, standard deviation, median (min-max), distribution frequencies, and percentages. The Kolmogorov–Smirnov test evaluated the normalization of data distribution. Comparison of variables that do not conform to normal distribution Mann–Whitney U and Kruskal–Wallis H tests; correlation evaluation was evaluated using the Pearson test. The evaluation of categorizable variables was made using the Chi-square test. Results were considered statistically significant when a P < 0.05.


  Results Top


A total of 188 BAT-positive patients, 142 female (75.5%) and 46 male (24.5%), were included in our study. The most common diagnosis in patients was determined as breast (27.1%) and lung cancer (27.1%), followed by lymphomas (11.7%), head- and neck-cancers (4.3%), and other tumors. Our sample group with a mean age of 43.89 ± 13.67 years (range: 16–80 years); 63.3% (n = 119) were 50 years old and younger, whereas 36.7% were over 50 years old. The mean age of female patients was 44.50 ± 12.05, and the mean age of male patients was calculated as 42.02 ± 17.81 (P = 0.381).

The mean BMI of the patients was found to be 24.12 ± 3.56. In addition, the mean BMI of female patients was 24.13 ± 3.44, and the mean BMI of male patients was calculated as 24.10 ± 3.95 (P = 0.876). When the patients were classified according to their BMI values, 54.7% (n = 103) were average weight (BMI < 25), 26.2% (n = 49) were overweight (BMI 25–30), and 19.1% (n = 36) determined as obese (BMI >30). About 31.4% (n = 59) of the patients were born in the winter, 28.2% (n = 53) in the summer, 22.3% (n = 42) in the spring, and 18.1% (n = 34) in the autumn. PET imaging was performed in 34.0% (n = 64) of the patients in winter, 29.8% (n = 56) in spring, 18.6% (n = 35) in summer, and 17.6% (n = 33) in autumn. About 30.9% (n = 58) of the patients were born in the Black Sea region, followed by the Marmara region (27.7%), the Southeastern Anatolia region (15.4%), and the Eastern Anatolia region (13.3%).

FDG injection 76.6% (n = 144) and PET/CT imaging 77.1% (n = 145) of the patients were performed most frequently in the afternoon (PM). During imaging, the average minimum outdoor temperature was measured as 8.42°C ± 5.46°C (range: ‒13°C–26°C), and the maximum average outdoor temperature was 14.80°C ± 6.33°C (Distribution range: 3°C–32°C). While the mean FBG in the patients was determined as 106.93 ± 14.28 mg/dl, 61.7% (n = 116) of the patients were found to be hyperglycemic. Furthermore, the mean FBG of female patients was calculated as 106.73 ± 14.45 and 107.54 ± 13.89 for male patients (P = 0.740). All demographic characteristics of the cases are shown in [Table 1].
Table 1: Clinical features of the cases

Click here to view



  Discussion Top


It is known that BAT activation with 18F-FDG PET/CT imaging is affected by various demographic and metabolic factors. The most common causes have been reported as female gender and young age.[7],[8] In a study of 742 patients with BAT in 18F-FDG PET/CT imaging, Bonacina et al. reported that adults showed a statistically higher rate of BAT detection in females (79% vs. 61%, P < 0.001).[2] Similarly, in the study of Cronin et al. including 12195 18F-FDG PET/CT imaging of 6867 patients, BAT activation was detected in 298 patients, and young female patients were reported to have a significantly higher rate of BAT activation (P < 0.001).[10] Furthermore, a significant increase in BAT activation with low BMI has been reported.[6] In Cypess et al., BAT activation was detected in 106 of 3640 patients, and the female/male ratio was 2:1 (P < 0.001). It was found that BAT activation was inversely proportional to age (P < 0.001) and BMI (P = 0.007).[11] Similarly, in Cronin et al., significantly higher FDG uptake was found in patients with low weight and BMI.[10] The study of Green et al., including 37 adult oncology patients with BAT activation and a control group of 74 patients without BAT activation, reported that BAT activation was increased in patients with lower severity of fatty liver disease and lower levels of central obesity. Besides, the researchers concluded that BAT activation might be protective against metabolic syndrome.[12] On the contrary, Truong et al. did not find a significant relationship between BAT and BMI. However, it should be noted that BAT activation was evaluated with only 15 patients in this study.[13] In addition, Bonacina et al. evaluated the results of 30,397 18F-FDG PET/CT over 13 years, and no significant difference was reported in overweight patients (BMI >25 kg/m2) (22% vs. 20%; P = 0.55). However, when only female patients were evaluated, the rate of active BAT in overweight patients (80% vs. 67%, P = 0.005) was statistically significantly higher. Although overweight has a negative predictive value for BAT activation, researchers have associated this situation with hormonal changes in women. As a result, the researchers concluded that gender and BMI values have a major predictive role in BAT activation.[2] Our study determined that the mean age of our patients was 43.89 ± 13.67 years, and 75.5% of them were female [Figure 1]. Besides, 63.3% of BAT-positive patients were 50 years old or younger [Figure 2]. The mean BMI of the patients was determined as 24.12 ± 3.56, and according to BMI values; 54.7% (n = 103) were average weight (BMI <25), 26.2% (n = 49) were overweight (BMI 25–30), and 19.1% (n = 36) were obese (BMI >30).
Figure 1: A 55-year-old female patient who was followed up for lymphoma, 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging revealed fluorodeoxyglucose uptake in the cervical, supraclavicular, mediastinal, and paravertebral areas without a lesion in equivalent computed tomography scans and was evaluated as Brown adipose tissue (shown with black and white arrows) PET: Positron emission tomography, CT: Computed tomography, F: Fusion, MIP: Maximum intensity projection

Click here to view
Figure 2: 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging was performed in a 33-year-old female patient followed up for breast cancer, relapse-metastasis research, and fluorodeoxyglucose uptake in the cervical, supraclavicular, and paravertebral areas without a lesion in equivalent computed tomography scans were evaluated as Brown adipose tissue (shown with black and white arrows) PET: Positron emission tomography, CT: Computed tomography, F: Fusion, MIP: Maximum intensity projection

Click here to view


Some studies have reported that BAT FDG uptake shows seasonal variation related to the season at the time of PET scan or the time patient was born and is sensitive to cold exposure. Accordingly, some authors reported high FDG uptake in BAT in FDG PET/CT imaging performed from January to March.[14] Similarly, Au-Yong et al. reported a significantly higher prevalence (P = 0.001) during the winter months in 167 BAT-positive patients.[15] In Ouellet et al., increased BAT activation associated with low outdoor temperature during injection and PET scan was reported.[16] In a study conducted by Saito et al. with 56 patients, participants aged between 23–35 and 38–65 were exposed to cold temperature (19°C) for 2 h. The authors reported a significant FDG uptake in BAT in the supraclavicular and paraspinal regions. Furthermore, the researchers reported a statistically significant increase in BAT activation in the winter months compared to the summer months (P < 0.001).[17] On the contrary, Kim et al. underlined that BAT activation occurs in acute weather changes (1–7 days) compared to seasonal changes. Long-term decreases in seasonal temperature do not affect.[18] Cypess et al. reported that outside temperature did not significantly affect 18F-FDG PET/CT imaging (P = 0.02).[11] Similarly, Bonacina et al. concluded that the birth season has no significant effect on determining BAT activation.[2] Similarly, in our study, it was found that the season in which the patients were born, the PET imaging season, the time of injection, or the outdoor temperature at the time of injection did not cause any statistically significant difference in FDG uptake for BAT.

In addition, it is well known that BAT activation is directly affected by diabetic state, insulin resistance, and glucose metabolism.[19] Zhang et al. found a statistically significantly lower fasting insulin and insulin resistance in the BAT-positive group.[20] In the study of Jacene et al., patients without FDG uptake in BAT had a higher risk of glucose ≥100 mg/dL (odds ratio: 3.4, 95% confidence interval = 1.6–7.3; P = 0.0007).[21] Bonacina et al. found a statistically high rate of BAT activation in hyperglycemic (>100 mg/dL) patients (24% vs. 16%, P = 0.02) and concluded that blood glucose levels have a major predictive role in BAT activation.[2] In our study, 61.7% of the patients were found to be hyperglycemic.


  Conclusion Top


While there was no increase in BAT FDG uptake due to cold exposure and seasonal changes in our study, female gender, young age, and low mean BMI significantly predictive value in BAT activation. Therefore, considering BAT activation in risky groups, especially in preventing the masking of the image in tumor tissue and false-positive uptake, we will contribute to the evaluation of 18F-FDG PET/CT imaging.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Cannon B, Nedergaard J. Brown adipose tissue: Function and physiological significance. Physiol Rev 2004;84:277-359.  Back to cited text no. 1
    
2.
Bonacina M, Albano D, Gazzilli M, Durmo R, Cerudelli E, Bosio G, et al. 18F-FDG PET/CT brown fat detection: Differences between adult and pediatric population in a 12 year experience. Rev Esp Med Nucl Imagen Mol (Engl Ed) 2019;38:224-8.  Back to cited text no. 2
    
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Crandall JP, Gajwani P, O JH, Mawhinney DD, Sterzer F, Wahl RL. Repeatability of brown adipose tissue measurements on FDG PET/CT following a simple cooling procedure for BAT activation. PLoS One 2019;14:e0214765.  Back to cited text no. 3
    
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Chondronikola M, Volpi E, Børsheim E, Chao T, Porter C, Annamalai P, et al. Brown adipose tissue ıs linked to a distinct thermoregulatory response to mild cold in people. Front Physiol 2016;7:129.  Back to cited text no. 7
    
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Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, et al. Functional brown adipose tissue in healthy adults. N Engl J Med 2009;360:1518-25.  Back to cited text no. 8
    
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Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009;360:1509-17.  Back to cited text no. 11
    
12.
Green AL, Bagci U, Hussein S, Kelly PV, Muzaffar R, Neuschwander-Tetri BA, et al. Brown adipose tissue detected by PET/CT imaging is associated with less central obesity. Nucl Med Commun 2017;38:629-35.  Back to cited text no. 12
    
13.
Truong MT, Erasmus JJ, Munden RF, Marom EM, Sabloff BS, Gladish GW, et al. Focal FDG uptake in mediastinal brown fat mimicking malignancy: A potential pitfall resolved on PET/CT. AJR Am J Roentgenol 2004;183:1127-32.  Back to cited text no. 13
    
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Cohade C, Osman M, Pannu HK, Wahl RL. Uptake in supraclavicular area fat (”USA-Fat”): Description on 18F-FDG PET/CT. J Nucl Med 2003;44:170-6.  Back to cited text no. 14
    
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Ouellet V, Labbé SM, Blondin DP, Phoenix S, Guérin B, Haman F, et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest 2012;122:545-52.  Back to cited text no. 16
    
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Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: Effects of cold exposure and adiposity. Diabetes 2009;58:1526-31.  Back to cited text no. 17
    
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Kim S, Krynyckyi BR, Machac J, Kim CK. Temporal relation between temperature change and FDG uptake in brown adipose tissue. Eur J Nucl Med Mol Imaging 2008;35:984-9.  Back to cited text no. 18
    
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Matsushita M, Yoneshiro T, Aita S, Kameya T, Sugie H, Saito M. Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans. Int J Obes (Lond) 2014;38:812-7.  Back to cited text no. 19
    
20.
Zhang Q, Ye H, Miao Q, Zhang Z, Wang Y, Zhu X, et al. Differences in the metabolic status of healthy adults with and without active brown adipose tissue. Wien Klin Wochenschr 2013;125:687-95.  Back to cited text no. 20
    
21.
Jacene HA, Cohade CC, Zhang Z, Wahl RL. The relationship between patients' serum glucose levels and metabolically active brown adipose tissue detected by PET/CT. Mol Imaging Biol 2011;13:1278-83.  Back to cited text no. 21
    


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