Brown fat FDG Uptake - A Common Finding in FDG PET CT Scan and the Relation to Demographic, Environmental, and Clinical Factors

Introduction

Brown adipose tissue (BAT) is known for its capacity to generate heat through nonshivering thermogenesis, a process that is particularly active in colder environments. Current research was carried out in India, that is having a tropical climate, and our study has highlighted the metabolic significance of BAT in adults, linking its activity to overall energy expenditure and metabolic health. This study aims to investigate the demographic, clinical, and environmental factors affecting BAT uptake in a diverse cohort of adults.

Methods

We analyzed data from 139 participants, documenting demographic characteristics, body mass index (BMI), weight, and environmental temperatures. BAT uptake was assessed at various anatomical sites using imaging techniques. Statistical analyses were conducted to determine the associations between BAT uptake and the variables of interest, employing Chi-square tests, Fisher’s exact tests, and Mann–Whitney U-tests where appropriate.

Results

Temperature associations

Higher ambient room temperatures were significantly associated with increased BAT uptake at perivascular, periviscus, and solid organ sites (P < 0.01). Conversely, lower external maximum and minimum temperatures were linked to higher BAT uptake at similar sites, indicating that BAT activity increases in colder conditions to aid thermogenesis. The explanation for this remarkable observation was that during the winter season, the external temperature was significantly lower than the ambient room temperature [Figures 1,2 and Tables 5-7].

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Figure 1 Association between ambient room temperature and the number of sites of brown fat uptake. Higher ambient room temperature was associated with more number of sites of brown fat uptake. Fisher’s exact test was used to test the association. P<0.05 was considered statistically significant. Color bars 1–4 represent number of BAT uptake sites

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Table 5 Association of maximum temperature (outside) and brown fat uptake at different sites

Sites of brown fat uptake	Yes	No	P
Between the anterior neck muscles and supraclavicular fossa	29.83±6.37	-	-
Under the clavicles	28.80±6.40	31.81±5.81	<0.01
In the axilla	28.87±6.68	30.58±5.99	0.14
Anterior abdominal wall	21.50±6.36	29.94±6.29	0.08
Inguinal fossa	-	29.82±6.34	-
Perivascular	20.12±4.99	31.17±5.25	<0.01
Periviscus	22.56±3.13	30.32±6.21	<0.01
Around solid organs	20.37±4.94	31.32±5.15	<0.01

Table 6 Association of minimum temperature (outside) and brown fat uptake at different sites

Sites of brown fat uptake	Yes	No	P
Between the anterior neck muscles and supraclavicular fossa	16.35±5.74	-	-
Under the clavicles	16.05±6.02	16.83±5.13	0.29
In the axilla	16.27±6.34	16.35±5.23	0.66
Anterior abdominal wall	10.50±2.12	16.40±5.73	0.10
Inguinal fossa	-	16.31±5.73	-
Perivascular	10.92±3.41	17.07±5.59	<0.01
Periviscus	12.22±2.91	16.60±5.78	0.02
Around solid organs	11.04±3.16	17.15±5.61	<0.01

Table 7 Association of ambient room temperature and brown fat uptake at different sites

Sites of brown fat uptake	Yes	No	P
Between the anterior neck muscles and supraclavicular fossa	20.08±0.93	-	-
Under the clavicles	20.07±0.90	20.08±0.98	0.95
In the axilla	20.21±0.93	19.97±0.92	0.13
Anterior abdominal wall	21.35±1.48	20.06±0.91	0.08
Inguinal fossa	-	20.08±0.93	-
Perivascular	21.14±1.04	19.93±0.81	<0.01
Periviscus	21.34±1.01	19.99±0.86	<0.01
Around solid organs	21.19±1.06	19.90±0.77	<0.01

Discussion

This study underscores the complex interactions between demographic, environmental, and physiological factors in regulating BAT activity. There is a significant association between gender and BAT uptake under the clavicles. The correlation between environmental temperatures and BAT activity supports the thermogenic role of BAT, which becomes more active in colder environments to maintain body temperature. The distribution of fluorodeoxyglucose (FDG) avid brown fat uptake in our study was: Between anterior neck muscles and supraclavicular fossa, under the clavicles, in the axilla, perivascular, around solid organs, periviscus, and anterior abdominal wall-in descending order [Figure 2 and Table 8].

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Figure 2 Association between ambient room temperature and the number of sites of brown fat uptake. Higher ambient room temperature was associated with more number of sites of brown fat uptake. Fisher’s exact test was used to test the association. p<0.05 was considered statistically significant

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BAT is contributing to nonshivering thermogenesis. It is active under cold stress via sympathetic nervous system activation. There is evidence that BAT may also be active at thermo-neutrality and in a postprandial state. BAT has superior energy dissipation capacity compared to white adipose tissue and muscles.[1]

Specific regions of functionally active BAT are present in humans and are seen more frequently in women than men. [¹⁸F]fluorodeoxyglucose positron Emission Tomography and Computed Tomography. can noninvasively quantify this specific distribution. BAT is inversely correlated with body mass index, especially in older people, suggesting a potential role in adult human metabolism through regulating the energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1.[2]

BAT activity is related to the anthropometric factors, metabolic syndrome, and the beta-receptors’ activity.[3] Neoplastic status is determinant for BAT activity in patients living in the tropics.[4]

A study observed that higher total Brown fat FDG uptake is seen in younger patients, whereas sex, BMI, height, mass, outdoor temperature, and blood parameters are not significantly affecting total or depot of specific BAT activity.[5]

Hypermetabolic brown fat is also seen in the mediastinum, and knowledge of this potential pitfall, as well as other important places of distribution, is important in preventing misinterpretation as malignancy.[6]

A study of 6867 patients demonstrated FDG uptake in the brown fat in 298 (4.33%) patients. And prevalence of brown fat was significantly higher in females, the most common location was the neck and above the clavicle, and the least common area was the axilla.[7]

The presence of brown fat on FDG PET can lead to misinterpretation and unnecessary usage of various invasive tests. This can be avoided during performing FDG PET CT scan by using measures such as ensuring warm ambient temperature to the patient, thus reducing FDG uptake in brown fat before the procedure, and correlating it at a specific anatomic location with PET/CT fusion imaging.[8]

On examination and interpretation of FDG PET/CT scan, it is mandatory that the PET images are correlated with CT images and Hounsfield Units of specific locations/areas, thus minimizing the false-positive findings.[9]

Analyzing all the confounding factors influencing BAT and retrospective confirmation of previously identified factors with a larger data set can be used to more accurately identify patients at risk for BAT activation to develop prevention strategies before performing FDG PET CT scan.[10]

Our findings highlight key factors influencing BAT uptake, contributing to the understanding of its role in human metabolism.

There was no association between BMI levels and the site of subcutaneous fat uptake, except for brown fat uptake around solid organs. Individuals within the normal BMI category (18.5–24.9 kg/m²) had the highest percentage of brown fat uptake around solid organs as compared to higher and lower BMI categories. The Chi-square test of independence (Fisher’s exact test in case of expected cell frequency <5) was used to test the association.

A statistically significant association was observed between gender and brown fat uptake under the clavicles. A higher percentage of females (60, 65.22%) had brown fat uptake under the clavicles as compared to males (32, 34.78%). The Chi-square test of independence (Fisher’s exact test in case of expected cell frequency <5) was used to test the association.

Statistically significant lower maximum temperature of the outside environment was associated with brown fat uptake under the clavicles, perivascular, periviscus, and around solid organs. Mann–Whitney U-test was used to compare the distribution of temperature between individuals with or without brown fat uptake at different sites.

Statistically significant lower minimum temperature of the outside environment was associated with brown fat uptake at perivascular, periviscus, and around solid organs. Mann–Whitney U-test was used to compare the distribution of temperature between individuals with or without brown fat uptake at different sites.

Statistically significantly higher ambient room temperature was associated with brown fat uptake at perivascular, periviscus, and around solid organs. Mann–Whitney U-test was used to compare the distribution of temperature between individuals with or without brown fat uptake at different sites.

Significantly higher BMI was associated with higher brown fat uptake at the perivascular site and around solid organs. Mann–Whitney U-test was used to compare the distribution of BMI between individuals with or without brown fat uptake at different sites.

Conclusion

Our findings highlight key factors and confounding factors influencing BAT uptake, contributing to the understanding of its role in human metabolism. Our study data set can help to accurately identify patients at risk for BAT activation and thus use preventive strategies before performing FDG PET CT scan. Future research should explore the underlying mechanisms driving these associations and their implications for metabolic health interventions.