An optimal condition for the evaluation of human brown adipose tissue by infrared thermography
An optimal condition for the evaluation of human brown adipose tissue by infrared thermography
Shinsuke NirengiID 0 1
Hitoshi Wakabayashi 1
Mami Matsushita 1
Masayuki Domichi 0 1
Shinichi Suzuki 1
Shin Sukino 0 1
Akiko Suganuma 0 1
Yaeko Kawaguchi 0 1
Takeshi Hashimoto 1
Masayuki Saito 1
Naoki Sakane 0 1
0 Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan, 2 Laboratory of Environmental Ergonomics, Faculty of Engineering, Hokkaido University , Sapporo , Japan , 3 Tenshi College, Department of Nutrition, Sapporo, Japan, 4 D-eyes Inc., Osaka, Japan, 5 Hokkaido University , Sapporo , Japan
1 Editor: Andrej A. Romanovsky, St. Joseph's Hospital and Medical Center , UNITED STATES
Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis and is an attractive therapeutic target for combating obesity and related diseases. Human BAT activity has been evaluated by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) under acute cold exposure, but the method has some serious limitations, including radiation exposure. Infrared thermography (IRT) may be a simple and less-invasive alternative to evaluate BAT activity. In the present study, to establish an optimal condition for IRT, using a thermal imaging camera, skin temperature was measured in the supraclavicular region close to BAT depots (Tscv) and the control chest region (Tc) in 24 young healthy volunteers. Their BAT activity was assessed as the maximal standardized uptake value (SUVmax) by 18FDG-PET/CT. Under a warm condition at 24-27?C, no significant correlation was found between the IRT parameters (Tscv, Tc,, and the difference between Tscv and Tc,, ?temp) and SUVmax, but 30-120 min after cold exposure at 19?C, Tscv and ?temp were significantly correlated with SUVmax (r = 0.40-0.48 and r = 0.68-0.76). ?temp after cold exposure was not affected by mean body temperature, body fatness, and skin blood flow. A lower correlation (r = 0.43) of ?temp with SUVmax was also obtained when the participant's hands were immersed in water at 18?C for 5 min. Receiver operating characteristic analysis revealed that ?temp after 30-60 min cold exposure can be used as an index for BAT evaluation with 74% sensitivity, 92% specificity, and 79% diagnostic accuracy. Thus, IRT may be useful as a simple and less-invasive method for evaluating BAT, particularly for large-scale screening and longitudinal repeat studies.
Data Availability Statement: All relevant data are
within the paper and its Supporting Information
Funding: This study was supported by Grant-in-Aid
for Scientific Research from the Ministry of
Education, Culture, Sports, Science, and
Technology of Japan (17J11622, 26291099,
18K11013) and Kao Research Council for the study
of Healthcare Science. D-eyes provided support in
the form of salaries for authors TH, but did not
have any additional role in the study design, data
Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis (NST) and is
therefore involved in the regulation of whole-body energy expenditure and body fatness [
curation and analysis, decision to publish, or
preparation of the manuscript. The specific roles of
these authors are articulated in the ?author
Competing interests: TH is the President at D-eyes
Inc. Although TH was involved in the data
collection, he did not contribute to any other aspect
of the study including that of funding support. This
does not alter our adherence to PLOS ONE policies
on sharing data and materials. There are no
patents, production in development, or marketed
products to declare.
humans, the current gold standard method to assess BAT is 18F-fluorodeoxyglucose (FDG)?
positron emission tomography (PET) in combination with computed tomography (CT) and
cold exposure, which uses cold-activated glucose uptake as an index of BAT activity [
However, this 18FDG-PET/CT method has some serious drawbacks such as radiation exposure, the
need for cold exposure, and the high cost of the device, which have limited its frequent use in
both experimental and clinical studies. Although several alternative methods to overcome
these limitations have been developed, including magnetic resonance imaging [
near-infrared time-resolved spectroscopy [
], and contrast-enhanced ultrasound [
], they are also
relatively expensive and not yet soundly confirmed for their validity and reliability [
There have been reports to assess the thermogenic activity of BAT by monitoring the
temperature of the skin (Tsk) overlying BAT depots. A few studies using a wire-less thermistor probe
revealed that cold-induced changes in Tsk of the supraclavicular region (Tscv) close to BAT
depots positively correlated with the activity and volume of BAT estimated by 18FDG-PET/CT
]. Infrared thermography (IRT) can also be used to evaluate Tsk with visualization by
measuring the infrared radiation emitted from the body surface. Jang et al. showed by IRT that
differences between Tsk in a control chest region and Tscv (?temp) were greater in subjects having
higher BAT activities after a 2-h cold exposure . Furthermore, a significant relationship
between the IRT method and 18FDG-PET/CT also has been confirmed [
]. However, during
the cold exposure experiments of these studies, Tsk was measured before and after a 2-h cold
exposure protocol, where the subjects with light-clothing were kept in a room at 19?C (cold
exposure) or on mattresses perfused with cooled water at ~17?C; these protocols may not induce
muscle shivering, but are apparently uncomfortable, stressful, and intolerable for most
individuals, particularly those with cardiovascular diseases. Therefore, less invasive and easier protocols
are needed for frequent assessment of BAT, in both experimental and clinical studies.
Symonds et al. [
] and Ang et al. [
] tested the feasibility of IRT as a non-invasive method
by monitoring the changes in Tscv 5 min after placing the hand and/or feet of the participant in
water at 20?C. This hand immersion protocol is apparently much less invasive and is easily
applicable in various experimental and clinical settings; however, they did not validate the
correlation of their data with the BAT activity assessed by 18FDG-PET/CT. In the present study,
to establish optimal conditions for IRT assessment of human BAT, we monitored the response
of Tsk to cold exposure for 10?120 min, in healthy subjects with a wide range of BAT activity.
We also examined Tsk response after 5-min hand immersion in the same subjects, and
compared the two protocols. Our results revealed that ?temp, only after 30-min exposure to cold
at 19?C, correlated well with the BAT activity assessed by 18FDG-PET/CT, indicating that this
protocol can be used for BAT evaluation with an accuracy of approximately 80%.
Twenty-four healthy male volunteers (age: 23.5 ? 3.6 years; body mass index [BMI]: 21.6 ? 2.5
kg/m2) participated in this study in winter from December 2017 to March 2018. This study
was carried out in accordance with the principles of the Declaration of Helsinki (Fortaleza
2013). The protocol was approved by the institutional review boards of Kyoto Medical Center
(no. 15?092) and was registered at the University Hospital Medical Information Network
(UMIN) center (UMIN000029206). Written informed consent was obtained from all
After overnight fasting for ~12 h, subjects were exposed to cold by being kept in an
air-conditioned room at 19?C with standardized light clothing (a patient gown), with intermittent
2 / 10
placement of their feet on an ice block wrapped in cloth for ~4 min at 5-min intervals to avoid
cooling-associated pain [
]. After 1 h under these cold conditions, each subject was
intravenously injected with 18F-FDG (1.66?5.18 mega  Becquerel (MBq)/kg body weight) and
kept under the same cold conditions. At 1 h after the 18F-FDG injection, 18FDG-PET/CT scans
were obtained with a PET/CT system (Aquiduo; Toshiba Medical Systems, Otawara, Japan).
BAT activity in both the right and left supraclavicular regions was quantified based on the
maximum standardized uptake value (SUVmax), defined as the radioactivity per ml within the
region of interest divided by the injected dose in mBq/g body weight. BAT was defined as
tissue with Hounsfield units ?300 to ?10 on CT with an SUV 1.5. PET and CT images were
co-registered and analyzed using VOXBASE workstation (J-MAC System, Sapporo, Japan).
IRT was carried out using a thermal imaging camera (DE-TC1000T; D-eyes Inc., Osaka,
Japan) fastened to a tripod. The thermal resolution was 160 ? 120. The Tscv of both the right
and left sides was measured from each image. The Tsk of the chest region (Tc) immediately
lateral to the sternum approximating the second intercostal space, which is apart from the
underlying BAT depots, was simultaneously measured as a control [
]. The subjects fasted for ~12
h, wore a light patient gown (about 0.2 clo), and underwent IRT successively for the following
two tests: 5-min hand immersion into 18?C water and 120-min cold exposure at 19?C, as
described below. IRT images were analyzed using a modified (D-eyes Inc.) version of
ThermalCam v.126.96.36.199 software (Laon People Inc., Seoul, Korea).
Cold exposure test
Cold exposure was performed using two adjacently located rooms controlled at 27?C and
19?C, respectively, with 40% relative humidity. The coefficient of variance (CV) was 2.5% in
the 27?C room and 1.1% in the 19?C room. Subjects were seated in an upright position looking
straight ahead for ~30 min in the 27?C room and underwent IRT and other measurements
including skin blood flow (SkBF), then moved to the 19?C room and underwent IRT at 10?30
min intervals for 120 min.
Hand immersion test
For the hand immersion test, the ambient room temperature and water temperature were
24?C and 18?C, respectively, with 40% relative humidity. The water temperature in a tank was
maintained using a thermostatic water circulator (LV-200; Toyo Roshi Kaisha, Tokyo, Japan),
and the CV of water temperature was 5.4%. After more than 30 min of rest, the subjects
immersed both hands into the water tank for 5 min [
Anthropometric parameters and others
BMI was calculated as body weight in kilograms divided by the square of the height in meters,
and body fat mass was estimated by the multifrequency bioelectric impedance method (Karada
Scan HBF-701; Omron, Kyoto, Japan). Visceral and subcutaneous fat areas at the abdominal
level of L4?L5 were estimated from the CT images. Total abdominal fat area was calculated as
the sum of visceral and subcutaneous fat areas.
Tympanic and sublingual temperature was measured using an earphone type infrared
tympanic thermometer (CET-101; Nipro, Osaka, Japan) and an electronic thermometer before
and after 2-h cold exposure (MC-172L; Omron Healthcare Co., Kyoto, Japan), respectively. A
small disc-type temperature data logger (Thermochron SL; KN Laboratories, Osaka, Japan)
3 / 10
was used to monitor Tsk on the forehead, left upper chest, non-dominant ventral forearm,
non-dominant ventral middle finger, left shin, and left instep as reported previously [
mean Tsk was calculated according to a modified Hardy and DuBois?s equation [
SkBF in the supraclavicular region and back (left scapula) was measured using a laser tissue
blood flowmeter (FLO-N1; Omegawave, Inc., Tokyo, Japan). Data were sampled using an A/D
converter and recorded at 1-s intervals using a personal computer. In the subsequent analysis,
artifacts observed in the raw data were eliminated using a 10-s median filter . Before and
after 2-h cold exposure, subjects were asked to rate shivering according to a modified version
of a previously used scale [
] consisting of four levels: 1 = no shivering, 2 = slight shivering,
3 = moderate shivering, and 4 = heavy shivering. Cold sensation [
] and discomfort  were
also assessed before and after 2-h cold exposure.
Data are expressed as mean ? standard deviation. Two-way analysis of variance with repeated
measures was used to test interactions (group ? time) and main effects (group, time). If there
was a significant interaction or main effect, time or group differences in variables between
baseline and after the test, were analyzed with the paired and unpaired t tests, respectively. The
relationship between the data of IRT and 18FDG-PET/CT was analyzed by Pearson?s
correlation analysis, where SUVmax was log-transformed because of the non-normal distribution
determined with the Shapiro-Wilk test. Values were considered statistically significant at
P < 0.05. Receiver operating characteristic (ROC) analysis was performed to evaluate the area
under the ROC curve (AUC), sensitivity, specificity, and the accuracy of IRT parameters. Then
the AUC of after cold exposure was compared to that of 27?C. The statistical analyses were
performed using SPSS v.19 (IBM, Armonk, NY, USA) and Easy R software (Saitama Medical
Center, Jichi Medical University, Saitama, Japan) [
18FDG-PET/CT revealed that 5 of 24 subjects showed undetectably low BAT activity (SUVmax
< 1.5), and thus, were defined as BAT-negative, whereas the remaining 19 subjects showed a
detectable activity (SUVmax = 1.8~26.8), and thus, were defined as BAT-positive. There was no
significant difference in the anthropometric parameters between the two subject groups
Fig 1 shows typical images of IRT and 18FDG-PET/CT at 27?C and 2 h after cold exposure.
Tsk was considerably different between the two subjects, both under warm (27?C) and cold
(19?C) conditions. Despite the individual differences, as summarized in Fig 2A and 2B, under
the warm condition at 27?C, Tscv was insignificantly higher than Tc in both BAT-negative and
positive groups. After cold exposure, Tscv and Tc seemed slightly higher and lower,
respectively, in the BAT-positive group. Although neither Tc nor Tscv was significantly different
between the two groups at any time point during the 2-h cold exposure, the cold-induced drop
in Tscv was significantly smaller (P < 0.05) in the BAT-positive group (0.7 ? 0.6?C) than in the
BAT-negative group (1.7 ? 1.1?C), while the drop in Tc was comparable in the two groups
(1.4 ? 0.7?C vs. 1.8 ? 1.0?C; P = 0.16).
To confirm the effect specific to the supraclavicular region, the difference between Tscv and
Tc was calculated and expressed as ?temp. As shown in Fig 2C, ?temp in the BAT-positive
group was 0.5 ? 0.3?C at 27?C, rose remarkably and significantly 10 min after cold exposure,
reached a steady level of 1.3 ? 0.5?C at 30 min, and was maintained at high levels of 1.2~1.3?C
thereafter. In contrast, ?temp in the BAT-negative group showed no significant change after
cold exposure, being 0.5~0.6?C, which was significantly lower (P < 0.05) than that of the
BAT4 / 10
Values represent mean ? standard deviation. BAT, brown adipose tissue; BMI, body mass index; SUVmax, maximal standardized uptake value.
23.8 ? 3.8
172.6 ? 5.0
65.4 ? 8.9
21.9 ? 2.6
17.4 ? 4.4
35.3 ? 1.8
45.0 ? 33.9
94.3 ? 56.4
139.3 ? 74.5
8.1 ? 6.1
positive group. Thus, cold-induced change in ?temp was observed only in the BAT-positive
group. As the supraclavicular region, but not the control chest region, is close to the
underlying BAT depots, ?temp after cold exposure is likely to reflect the thermogenic activity of BAT
and would serve as a BAT-specific index. Consistent with this idea, a fairly positive correlation
(r = 0.74) was observed between the ?temp at 2-h cold exposure and the BAT activity
expressed as log SUVmax (Fig 3). Significant correlations with SUVmax were also found in Tscv
itself and the cold-induced Tscv change (Tscv-time), but with lower correlation coefficients
(r = 0.48 and r = 0.59, Table 2). In contrast, neither Tscv nor ?temp at 27?C correlated with
SUVmax. Comparative positive correlations between IRT parameters and log SUVmax were also
observed even at 30 min after cold exposure, including those for Tscv (r = 0.40), ?temp
(r = 0.68) and Tscv-time (r = 0.57).
We also examined the effects of 2 h-cold exposure on tympanic and sublingual
temperatures and skin temperature in various regions including the forehead, forearm, hand, finger,
calf, and foot. Similar to the supraclavicular and chest regions, skin temperature in these
regions dropped, showing the mean Tsk from 33.1?C ? 0.4?C to 29.7?C ? 0.3?C (P < 0.01), but
no notable difference was found between the BAT-positive and -negative groups (data not
shown). The effects of cold-exposure on SkBF were also examined. After 2 h-cold exposure,
SkBF decreased by 15.6% (P < 0.05) in the back, whereas it did not change in the
supraclavicular region (P = 0.51), and no difference was found between the BAT-positive and -negative
Fig 1. Typical images of 18FDG-PET/CT and IRT. Typical images of 18FDG-PET/CT in BAT-negative (A) and
positive subjects (B). Typical images of IRT method in BAT-negative (C) and positive subjects (D) before (left) and
after 2-h cold exposure (right).
5 / 10
Fig 2. Skin temperature changes after cold exposure and hand immersion. Tscv, skin temperature of the
supraclavicular region; Tc, skin temperature of the chest region; ?temp, differences between Tscv and Tc. Tscv (A), Tc
(B), and ?temp (C) during cold exposure. Tscv (D), Tc (E), and ?temp (F) during hand immersion. vs 27?C or 0 m.
groups. We also investigated the relationship between possible confounding factors and Tsk
(Table 3). The % body fat was negatively correlated with Tscv and Tc at 27?C. The mean Tsk
was positively correlated with Tscv and Tc at 27?C and Tscv at 19?C. The SkBf was positively
correlated with Tc at 27?C and Tscv and Tc at 19?C. However, ?temp did not correlate with any
of the parameters or temperatures (Table 3). There was no perceived shivering either before
(0.3 ? 0.5) or after (-0.3 ? 0.5) cold exposure, while cold sensation was -2.1 ? 1.0 (-2 = cool)
and discomfort was ?1.0 ? 0.8 (?1 = uncomfortable) at the end of cold exposure.
We also examined the effects of hand immersion in water for the same subjects
participating in the above-described cold exposure test. As shown in Fig 2D and 2E, during 5-min hand
immersion, Tc significantly decreased (P < 0.05), while Tscv did not change. The calculated
?temp was increased after the 5-min hand immersion only in the BAT-positive group
(P < 0.05). A significant positive correlation between ?temp and log SUVmax was found, but
the correlation coefficient (r = 0.43) was lower than that after cold exposure (Fig 3, Table 4).
The ROC analysis between ?temp and log SUVmax revealed that AUCs were 0.80 and 0.85
after 30-min and 120-min cold exposure, respectively, but 0.59 at 27?C and 0.77 after 5-min
hand immersion. As summarized in Table 5, the cut-off value of ?temp and accuracy seemed
to reach plateau levels 30 min after cold exposure. When the cut-off value for detecting
BATpositive subject was set as 1.01?C for ?temp after 30-min cold exposure, the sensitivity,
specificity, and diagnostic accuracy were 74.3%, 92.3%, and 79.2%, respectively, which were
comparable with those after 120-min cold exposure.
Fig 3. Relationship between log SUVmax and ?temp in the cold exposure test (A) and the hand immersion test
(B). ?temp, difference between skin temperature on the supraclavicular region (Tscv) and that on the chest region (Tc);
SUVmax, maximal standardized uptake value. The correlation coefficient in the cold exposure test (r = 0.74) was
significantly higher than that in the hand immersion test (r = 0.42) (P < 0.05). Data were obtained from both the right
and left sides in 24 subjects.
6 / 10
In this study, to investigate the optimal index for assessing BAT thermogenic activity using the
IRT method, healthy volunteer subjects were exposed to the cold for 2 h, and the skin
temperature of the supraclavicular region close to BAT depots (Tscv) was compared with the metabolic
activity (SUVmax) assessed by the standard 18FDG-PET/CT method. Our results showed that
the cold-induced response of ?temp, reflecting the difference between Tscv and a control chest
region apart from BAT depots (Tc), was the most relevant index of SUVmax.
Human BAT is mainly present in the supraclavicular region, which has been the focus of
most studies measuring the temperature response by the IRT method or using wire-less
thermistors. In a previous thermistor study, a correlation coefficient of r = 0.52 was found between
Tscv after cold exposure and SUVmax [
], which is similar to our result (r = 0.48). However, the
Tsk value itself may be affected by various factors such as the subcutaneous fat thickness
], SkBF, and possibly other thermogenic tissues. Therefore, to minimize the influence of
these factors, we calculated ?temp as the difference between Tscv and Tc, and found a higher
correlation coefficient (r = 0.74). In fact, Tscv and Tc correlated with body fatness (% body fat),
mean body temperature, and SkBf, while ?temp showed no significant correlation with these
7 / 10
Previous reports have shown that BAT activity could be evaluated by the IRT method using
thermoneutral conditioning [
] or the 5-min hand immersion test [
]. These methods
are simple and less invasive, and thus would be useful in clinical settings. However, these
methods have not been validated in relation to the BAT activity assessed by 18FDG-PET/CT.
In our study, under a thermoneutral condition without cold exposure, no correlation of Tscv
and ?temp with SUVmax was found. In the hand immersion test, however, ?temp correlated
with SUVmax, but with a lower correlation coefficient (0.43) than found in the cold exposure
test (r = 0.74). Thus, the hand immersion test may be feasible only for subjects with relatively
high BAT activity.
In most previous human studies, BAT was assessed after 2 h or longer cold exposure,
regardless of the 18FDG-PET/CT or IRT method [
]. In this study, we monitored Tsk
responses to cold exposure at 10~30-min intervals for 120 min, finding that the response in
?temp reached a steady level after 30 min and was maintained thereafter. In fact, comparative
positive correlations between the IRT parameters and SUVmax were observed even at 30 min
after cold exposure, including that for ?temp (r = 0.68). Accordingly, the ROC analysis for the
data after 30-min cold exposure revealed that the sensitivity, specificity, and diagnostic
accuracy were similar after a 120-min cold exposure. Thus, 120-min cold exposure, as applied in
the previous studies, is not necessary. Our easier protocol of 30-min cold exposure is sufficient
for BAT evaluation by the IRT method.
One of the limitations of this study is that all our participants were young and non-obese
males. To confirm the overall feasibility of our IRT method, it should also be tested in other
groups, particularly in female and/or obese individuals. They have more subcutaneous fat
which is insulating, and may influence ?temp depending on the mass/thickness of the fat.
Moreover, ?temp may not only be influenced by heat directly transmitted from underlying
BAT, but also from blood flow in the carotid and subclavian arteries. Further studies are
needed to examine the possible confounding effects of these factors.
In conclusion, ?temp calculated from IRT after 30-min cold exposure highly correlated
with SUVmax assessed by 18FDG-PET/CT. Thus, the IRT method may be useful as a simple
and less-invasive alternative for evaluating BAT, particularly for large-scale screening and
longitudinal repeat studies.
S1 File. Data sheet Fig 2.
S2 File. Data sheet of Fig 3.
The authors thank the volunteers who participated in this study.
Conceptualization: Shinsuke Nirengi, Masayuki Saito, Naoki Sakane.
Data curation: Shinsuke Nirengi.
Formal analysis: Shinsuke Nirengi, Akiko Suganuma.
Funding acquisition: Shinsuke Nirengi, Hitoshi Wakabayashi, Masayuki Saito, Naoki Sakane.
Investigation: Shinsuke Nirengi, Hitoshi Wakabayashi, Mami Matsushita, Masayuki Domichi,
Shinichi Suzuki, Shin Sukino, Yaeko Kawaguchi, Takeshi Hashimoto, Masayuki Saito,
Writing ? original draft: Shinsuke Nirengi.
Writing ? review & editing: Hitoshi Wakabayashi, Masayuki Saito, Naoki Sakane.
9 / 10
1. Kajimura S , Saito M. A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis . Annu Rev Physiol . 2014 ; 76 : 225 - 249 . https://doi.org/10.1146/annurevphysiol-021113 -170252 PMID: 24188710
2. Chen KY , Cypess AM , Laughlin MR , Haft CR , Hu HH , Bredella MA , et al. Brown adipose reporting criteria in imaging studies (BARCIST 1.0): Recommendations for standardized FDG-PET/CT experiments in humans . Cell Metab , 2016 ; 24 : 210 - 222 . https://doi.org/10.1016/j.cmet. 2016 . 07 .014 PMID: 27508870
3. Hu HH , Wu TW , Yin L , Kim MS , Chia JM , Perkins TG , et al. MRI detection of brown adipose tissue with low fat content in newborns with hypothermia . Magn Reson Imaging . 2014 ; 32 : 107 - 117 . https://doi. org/10.1016/j.mri. 2013 . 10 .003 PMID: 24239336
4. Nirengi S , Homma T , Inoue N , Sato H , Yoneshiro T , Matsushita M , et al. Assessment of human brown adipose tissue density during daily ingestion of thermogenic capsinoids using near-infrared timeresolved spectroscopy . J Biomed Opt . 2016 ; 21 : 91305 .
5. Flynn A , Li Q , Panagia M , Abdelbaky A , MacNabb M , Samir A , et al. Contrast-enhanced ultrasound: A novel noninvasive, nonionizing method for the detection of brown adipose tissue in humans . J Am Soc Echocardiogr . 2015 ; 28 : 1247 - 1254 . https://doi.org/10.1016/j.echo. 2015 . 06 .014 PMID: 26255029
6. Chondronikola M , Beeman SC , Wahl RL . Non-invasive methods for the assessment of brown adipose tissue in humans . J Physiol . 2018 ; 596 : 363 - 378 . https://doi.org/10.1113/JP274255 PMID: 29119565
7. Boon MR , Bakker LE , van der Linden RA , Pereira Arias-Bouda L , Smit F , Verberne HJ , et al. Supraclavicular skin temperature as a measure of 18F-FDG uptake by BAT in human subjects . PLoS One . 2014 ; 9:e98822 . https://doi.org/10.1371/journal.pone. 0098822 PMID: 24922545
8. Anouk AJJ , van der Lans AA , Vosselman MJ , Hanssen MJ , Brans B, van Marken Lichtenbelt WD . Supraclavicular skin temperature and BAT activity in lean healthy adults . J Physiol Sci . 2016 ; 66 : 77 - 83 . https://doi.org/10.1007/s12576-015-0398-z PMID: 26420686
9. Jang C , Jalapu S , Thuzar M , Law PW , Jeavons S , Barclay JL , et al. Infrared thermography in the detection of brown adipose tissue in humans . Physiol Rep . 2014 ; 2:e12167 . https://doi.org/10.14814/phy2. 12167 PMID: 25413316
10. Law J , Morris DE , Izzi-Engbeaya C , Salem V , Coello C , Robinson L , et al. Thermal imaging is a noninvasive alternative to PET/CT for measurement of brown adipose tissue activity in humans . J Nucl Med . 2018 ; 59 : 516 - 522 . https://doi.org/10.2967/jnumed.117.190546 PMID: 28912148
11. Symonds ME , Henderson K , Elvidge L , Bosman C , Sharkey D , Perkins AC , et al. Thermal imaging to assess age-related changes of skin temperature within the supraclavicular region co-locating with brown adipose tissue in healthy children . J Pediatr . 2012 ; 161 : 892 - 898 . https://doi.org/10.1016/j.jpeds. 2012 . 04 .056 PMID: 22677567
12. Ang QY , Goh HJ , Cao Y , Li Y , Chan SP , Swain JL , et al. A new method of infrared thermography for quantification of brown adipose tissue activation in healthy adults (TACTICAL): A randomized trial . J Physiol Sci . 2017 ; 67 : 395 - 406 . https://doi.org/10.1007/s12576-016 -0472-1 PMID: 27443171
13. 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 - 1531 . https://doi.org/10.2337/db09-0530 PMID: 19401428
14. Hardy JD , Dubois EF . The technique of measuring radiation and convection . J Nutr . 1938 ; 15 : 461 - 475 .
Wakabayashi H , Wijayanto T , Kuroki H , Lee JY , Tochihara Y. The effect of repeated mild cold water immersions on the adaptation of the vasomotor responses . Int J Biometeorol . 2012 ; 56 : 631 - 637 .
https://doi.org/10.1007/s00484-011 -0462-1 PMID: 21695574
16. Nielsen R , Endrusick TL . Sensations of temperature and humidity during alternative work/rest and the influence of underwear knit structure . Ergonomics . 1990 ; 33 : 221 - 234 . https://doi.org/10.1080/ 00140139008927112 PMID: 28080945
17. Gagge AP , Stolwijk JA , Hardy JD . Comfort and thermal sensations and associated physiological responses at various ambient temperatures . Environ Res . 1967 ; 1 : 1 - 20 . PMID: 5614624
Wu Z , Li N , Cui H , Peng J , Chen H , Liu P. Using upper extremity skin temperatures to assess thermal comfort in office buildings in Changsha, China . Int J Environ Res Public Health . 2017 ; 14 :E1092. https:// doi.org/10.3390/ijerph14101092 PMID: 28934173
19. Kanda K. Investigation of the freely available easy-to-use software 'EZR' for medical statistics . Bone Marrow Transplant . 2013 ; 48 : 452 - 458 . https://doi.org/10.1038/bmt. 2012 .244 PMID: 23208313
20. Sarasniemi JT , Koskensalo K , Raiko J , Nuutila P , Saunavaara J , Parkkola R , et al. Skin temperature may not yield human brown adipose tissue activity in diverse populations . Acta Physiol (Oxf) . 2018 : e13095.
21. Gatidis S , Schmidt H , Pfannenberg CA , Nikolaou K , Schick F , Schwenzer NF . Is it possible to detect activated brown adipose tissue in humans using single-time-point infrared thermography under thermoneutral conditions? impact of BMI and subcutaneous adipose tissue thickness . PLoS One . 2016 ; 11 : e0151152. https://doi.org/10.1371/journal.pone. 0151152 PMID: 26967519