Thermal Imaging to Assess Age-Related Changes of Skin Temperature within the Supraclavicular Region Co-Locating with Brown Adipose Tissue in Healthy Children.
ABSTRACT To establish the feasibility of infrared thermal imaging as a reproducible, noninvasive method for assessing changes in skin temperature within the supraclavicular region in vivo.
Thermal imaging was used to assess the effect of a standard cool challenge (by placement of the participant's feet or hand in water at 20°C) on the temperature of the supraclavicular region in healthy volunteer participants of normal body mass index in 3 age groups, 3-8, 13-18, and 35-58 years of age.
We demonstrated a highly localized increase in temperature within the supraclavicular region together with a significant age-related decline under both baseline and stimulated conditions.
Thermogenesis within the supraclavicular region can be readily quantified by thermal imaging. This noninvasive imaging technique now has the potential to be used to assess brown adipose tissue function alone, or in combination with other techniques, in order to determine the roles of thermogenesis in energy balance and, therefore, obesity prevention.
- SourceAvailable from: Houchun Harry Hu[Show abstract] [Hide abstract]
ABSTRACT: As part of a current worldwide effort to understand the physiology of human BAT (hBAT) and whether its thermogenic activity can be manipulated to treat obesity, the workshop "Exploring the Roles of Brown Fat in Humans" was convened at the National Institutes of Health on February 25-26, 2014. Presentations and discussion indicated that hBAT and its physiological roles are highly complex, and research is needed to understand the health impact of hBAT beyond thermogenesis and body weight regulation, and to define its interactions with core physiological processes like glucose homeostasis, cachexia, physical activity, bone structure, sleep, and circadian rhythms.Cell metabolism. 09/2014; 20(3):408-415.
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ABSTRACT: The relevance of functional brown adipose tissue (BAT) depots in human adults was undisputedly proven approximately seven years ago. Here we give an overview of all dedicated studies that were published on cold-induced BAT activity in adult humans that appeared since then. Different cooling protocols and imaging techniques to determine BAT activity are reviewed. BAT activation can be achieved by means of air- or water-cooling protocols. The most promising approach is individualized cooling, during which subjects are studied at the lowest temperature for nonshivering condition, probably revealing maximal nonshivering thermogenesis. The highest BAT prevalence (i.e. close to 100%) is observed using the individualized cooling protocol. Currently, the most widely used technique to study the metabolic activity of BAT is [(18)F]FDG-PET/CT-imaging. Dynamic imaging provides quantitative information about glucose uptake rates, while static imaging reflects overall BAT glucose uptake, localization and distribution. In general, standardized uptake values (SUV) are used to quantify BAT activity. An accurate determination of total BAT volume is hampered by the limited spatial resolution of the PET-image, leading to spill over. Different research groups use different SUV threshold values, which make it difficult to directly compare BAT activity levels between studies. Another issue is the comparison of [(18)F]FDG uptake in BAT with respect to other tissues or upon with baseline values. This comparison can be performed by using the 'fixed volume' methodology. Finally, the potential use of other relatively noninvasive methods to quantify BAT, like MRI or thermography, is discussed.American journal of physiology. Regulatory, integrative and comparative physiology. 05/2014;
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ABSTRACT: PET-CT using 18F-FDG is employed for detecting brown adipose tissue (BAT) in humans. Alternative methods are needed because of the radiation and cost of PET-CT imaging. The aim was to evaluate the accuracy of infrared thermography (IRT) in detecting human BAT benchmarked to PET-CT imaging. Seventeen individuals underwent a total of 29 PET-CT scans, 12 of whom were studied twice, after 2 h of cold stimulation at 19°C, in parallel with measurement of skin temperatures overlying the supraclavicular (SCV) fossa and the lateral upper chest (control), before and after cold stimulation. Of the 29 scans, 20 were BAT positive after cold stimulation. The mean left SCV temperature tended to be higher in the BAT-positive group before and during cooling. It was significantly higher (P = 0.04) than the temperature of the control area, which fell significantly during cooling in the BAT-positive (−1.2 ± 0.3°C, P = 0.002) but not in the negative (−0.2 ± 0.4°C) group. The temperature difference (Δtemp) between left SCV and chest increased during cooling in the BAT-positive (1.2 ± 0.2 to 2.0 ± 0.3°C, P < 0.002) but not in the negative group (0.6 ± 0.1 to 0.7 ± 0.1°C). A Δtemp of 0.9°C conferred a positive predictive value of 85% for SCV BAT, superior to that of SCV temperature. The findings were similar on the right. In conclusion, the Δtemp is significantly and consistently greater in BAT-positive subjects. The Δtemp quantified by IRT after 2-h cooling shows promise as a noninvasive convenient technique for studying SCV BAT function.Physiological Reports. 11/2014; 2(11).
Thermal Imaging to Assess Age-Related Changes of Skin Temperature
within the Supraclavicular Region Co-Locating with
Brown Adipose Tissue in Healthy Children
Michael E. Symonds, BSc, PhD1,2, Katrina Henderson, BMedSci1, Lindsay Elvidge, BMedSci, MB ChB1,
Conrad Bosman, MBBS, MRCP1, Don Sharkey, BMedSci, BM BS, MRCPCH, PhD1,
Alan C. Perkins, BSc, MSc, PhD, CSci, FIPEM, ARCP, FRCR3,4, and Helen Budge, MA, BM BCh, MRCP, FRCPCH, PhD1,2
Objective To establish the feasibility of infrared thermal imaging as a reproducible, noninvasive method for as-
sessing changes in skin temperature within the supraclavicular region in vivo.
Study design Thermal imaging was used to assess the effect of a standard cool challenge (by placement of the
participant’s feet orhand in water at 20?C) on the temperature of the supraclavicular region inhealthy volunteer par-
ticipants of normal body mass index in 3 age groups, 3-8, 13-18, and 35-58 years of age.
Results We demonstrated a highly localized increase in temperature within the supraclavicular region together
with a significant age-related decline under both baseline and stimulated conditions.
Conclusion Thermogenesis within the supraclavicular region can be readily quantified by thermal imaging. This
noninvasive imaging technique now has the potential to be used to assess brown adipose tissue function alone, or
fore, obesity prevention. (J Pediatr 2012;161:892-8).
for it to be able to contribute 20% of daily energy expenditure,6,7an estimation that has now been confirmed.8A better un-
derstanding of BAT function and regulation in vivo is likely to be crucial to improving our understanding of the ongoing obe-
Currently, the main methods available to assess BAT activity are positron-emission tomography (PET) with18F-fluorodeox-
99mTc-tetrofosmin, and/or tissue biopsy.10-12These techniques have distinct disadvantages as they are expensive and require
either the administration of radiopharmaceuticals or tissue sampling. Their usefulness is, therefore, greatly limited as they
can only be conducted on a very small number of subjects and are unable to provide indices of BAT function in real-time.
In contrast, thermal imaging is a rapid, safe, and acceptable technique that has been suggested to be suitable for use in both an-
been demonstrated to be very closely related to the rise in depot temperature as measured by thermal imaging in mice.15The
ing the technique of thermal imaging for use on a population-wide basis. The aim of our study was, therefore, to undertake
thermal imaging in healthy volunteers of normal body mass index (BMI) to assess whether changes in temperature can be de-
time, we examined whether the change in temperature was greater in children compared with adolescents and adults.
t is established that brown adipose tissue (BAT) persists beyond the neonatal period and is primarily located within the
supraclavicular regions in adults of all ages.1-3Maximal heat production by BAT is of the order of 300 W/kg compared
All studies were undertaken in healthy volunteers who were at least 1 hour post-
prandial; had remained sedentary during this period; had not consumed any caf-
feine, drugs, or alcohol; and were maintained in a room of constant temperature
From the1The Early Life Nutrition Research Unit,
Academic Division of Child Health;2Respiratory and
3Digestive Diseases Biomedical Research Units; and
4Radiological and Imaging Sciences, School of Clinical
Sciences, University Hospital, Nottingham, United
Funded in part by the Nottingham University Hospital’s
Charity. The authors declare no conflicts of interest.
0022-3476/$ - see front matter. Copyright ª 2012 Mosby Inc.
All rights reserved. 10.1016/j.jpeds.2012.04.056
Brown adipose tissue
Body mass index
Coefficient of variation
(19?-21?C). Informed written consent was obtained from all
participants and/or their parent/carer, in the case of children.
The study was performed with local institutional ethics com-
Each subject was in a relaxed “steady-state” within a famil-
iar environment. They were seated in an upright posture,
with arms adducted and with head, neck, and shoulders un-
clothed, in the center of the study room, away from all heat-
emitting objects and 1.0 m away from a thermal imaging
camera (FLIR b60 2.3 Megapixel Infrared Camera; FLIR Sys-
tems AB, Danderyd, Sweden) fixed on a tripod at a set dis-
tance, 1 m, from the floor. This positioning ensured
comfort as well as the optimum position for visualization
of the supraclavicular BAT depots.
Our initial studies were designed to produce a robust, ac-
ceptable procedure for use in subjects of all ages. These stud-
ies determined that to obtain consistent and comparable
measurements within each subject with time, relative head
position must remain constant. Consequently, a time course
was determined demonstrating that the change in tempera-
ture within the supraclavicular region reaches a maximum
within 5 minutes of exposure to cold water (Figure 1). As
this remains unchanged for the next 10-15 minutes and
subjects (especially children) were much less likely to remain
in the same position for prolonged periods, making further
detection of changes in temperature less reliable, we adopted
a standard recording period of 5 minutes following the cool
challenge. These initial studies also demonstrated that the
supraclavicular increase in temperature only occurs when
subjects are maintained in a cold environment at 19?-20?C
compared with a warm room of 25?-26?C, in keeping with
observations made in the clinical application of PET/CT.3,16
Furthermore, placement of an extremity in colder water did
not allow consistent thermal images to be recorded as subjects
either shivered (potentially producing heat by shivering
thermogenesis) or were unable to remain still for thermal
imaging as a consequence of discomfort relating to the water
at cooler temperatures. Therefore, a comfortable ambient
temperature and stimulus of cool water both at 19?-20?C were
adopted for all future studies.
Skin surface temperature determined from data continu-
ously obtained with iButtons (model DS1921H-F50; Maxim,
Figure 1. Anterior thermal images of the neck and upper thorax in a pre-pubertal 13 year old male. Representative example of
the increase in area and temperature of the thermally active supraclavicular region A, before and B, 1 minute, C, 2 minutes, and
D, 5 minutes after immersion of 1 hand into cold tap water at 20?C. Red pixels, 36.5?-37.0?C; orange pixels, 36.0?-36.5?C; yellow
pixels,35.5?-36.0?C.E,Meanchangeintemperatureofthethermallyactivesupraclavicular regionfollowing placementof1hand
into cold water at 20?C. Values are means with their standard errors. *P < .05 vs prechallenge temperature (n = 26).
Vol. 161, No. 5
Sunnyvale, California)17demonstrated that mean skin sur-
face temperature outside the area of interest does not change
significantly (D temperature [5 minutes before to 5 minutes
after hand immersion]: ?0.135?? 0.002?C; 39 ? 6 years old;
n = 6). A number of adjacent anatomic sites, including ster-
num and left and right deltoids, were used as negative con-
trols for changes in temperature as these regions did not
demonstrate thermal responses to cooling of the hand or
Therefore, 5 images were taken at 1-minute intervals be-
fore each thermal challenge and represented the control pe-
riod. Each subject (n = 8) then placed either both feet or 1
hand into cool tap water (19?-20?C). Imaging was repeated
at 1-minute intervals over the following 5-minute period.
To ensure any effects of the challenge had resolved, the stud-
ies were conducted in a random order on separate days with
a control period before each challenge. This comparison
demonstrated that all subjects showed a thermal response
to each challenge that was very similar regardless of whether
both feet or 1 hand was placed into cold water (D tempera-
ture: both feet, 0.47?? 0.11?C; 1 hand, 0.37?? 0.13?C).
We also established that the temperatures of the supraclavic-
ular regions for each subject at rest were consistent and re-
producible (within control period coefficient of variation
[CV]: 0.46%-0.67%; between control periods CV: 1.57%).
In addition, the overall mean temperatures and the mean
of the upper 10th percentile temperatures of the supraclavic-
ular regions were similar in the resting state before all chal-
lenges, regardless of whether the right or left side of the
neck was measured (CV: 0.42%). We went on to compare
the effect of hand cooling alone on a larger group of subjects
to determine the effect of age on BAT responsiveness.
The participants were grouped into 3 age groups: prepu-
bertal children aged 3-8 years (n = 7), postpubertal young
people aged 13-18 years (n = 12), and adults aged 35-58 years
(n = 7). All subjects were of normal BMI (3-8 years, 16.9 ?
0.95 kg/m2; 13-18 years, 22.6 ? 0.76 kg/m2; 35-58 years,
stant ambient temperature of 19?-20?C with participants
seated in an upright posture 1.0 m away from a thermal im-
aging camera, as detailed earlier. Thermal images were re-
peated at rest and following exposure to the thermal
challenge of placement of the participant’s hand in water at
19?-20?C. A standardized questionnaire for self-pubertal
staging was completed by participants aged 13-18 years.
In order to further establish that the area in which skin
surface temperature was raised is consistent with that of
BAT using PET/CT, we compared their locations using
PET/CT images from a comparable group of age- and sex-
matched subjects of normal BMI. The comparison was
undertaken by measuring the distance from the anatomic
midline to either the BAT depot (as determined using
PET/CT) or the area of raised temperature (as determined
using thermal imaging).
The thermal imaging camera saved the sequentially labeled
images in JPEG format, with encoded radiometric metadata.
The sequence of images was processed with FLIR Therma-
Cam QuickReport 1.2 proprietary software (FLIR Systems
AB). The software’s “area tool” was used to define an area
box encompassing the upper thorax and neck, using ana-
tomic landmarks of the shoulder tips laterally, the mandible
superiorly, and the nipple line inferiorly.
Radiometric temperature data from the defined area were
exported to Microsoft Excel 2007 (Microsoft Corporation,
Redmond, Washington) and analyzed using a macro, written
in Visual Basic. The algorithm calculated the change in mean
temperature between regions of thermal activity and is based
tification of tumors.18Data were divided into left and right
anatomic positions, overlying the known locations of BAT.
To define regions of thermal activity, temperature data
were ordered by
that is, in ascending order, where T is the temperature de-
tected by the thermal imaging camera sensor array (?C).
was calculated, where m is the size, and T
upper 10th percentile of temperatures in the region of inter-
est. The variance of repeated values and the difference be-
at the 5-minute post cool challenge endpoint and
the prechallenge T
(?C), were calculated.
Visual representations of the thermal data were displayed
as colored isotherms, and the area of the thermal activity in
the supraclavicular regions was determined, by defined
0.5?C isotherms, across the range of thermal activity detected
(35.5?-37.0?C) using Volocity Acquisition and Quantifica-
tion software (Version 4.2.1; Improvision Ltd, Coventry,
UK). Intraobserver and interobserver variabilities for mea-
surements of temperature and thermal area lay in the range
of 0.07%-1.17%. Data were confirmed as parametric by
Kolmorgov-Smirnov test and analyzed with ANOVA with
Bonferroni correction. A corrected P < .05 value was taken
to indicate statistical significance.
0is the mean of the
0, D T
The time course of the thermal response to placing 1 hand in
cold water was similar for all subjects and peaked within 5
minutes of the challenge (Figure 1, B). The anatomic site
in which the increase in temperature was recorded is shown
in Figures 2 and 3, indicating that the hottest site measured
established to be BAT on PET/CT.16Furthermore, Figure 3
demonstrates the position of this region in relation to the
visible surface anatomy. The anatomic position of the
increase in temperature within the supraclavicular region
measured by thermal imaging was very similar to that of
BAT measured using PET/CT in a comparable group of
age- and sex-matched subjects (PET/CT [n = 5], 8.00 ? 0.51
THE JOURNAL OF PEDIATRICS
Vol. 161, No. 5
Symonds et al
cm from the anatomic midline; thermal imaging [n = 5], 7.81
? 0.22 cm from the anatomic midline).
Having established a clear time course for the temperature
response, we compared the magnitude of the effect with age
gion both before and after the cold challenge was greatest in
children (Figure 4), declined into adolescence, and was
lowest in adults. The increase in temperature in the thermal
area in the supraclavicular region was, therefore, significantly
greater (P < .05) in children compared with adolescents
and adults (3-8 years, 0.62?? 0.14?C [n = 7]; 13-18 years,
0.25?? 0.08?C [n = 12]; 35-58 years, 0.20?? 0.08?C [n =
7]), as was the change in thermal area during the challenge
(3-8 years, 1107% ? 365% upper thorax [n = 7]; 13-18
We have demonstrated a consistent, and highly localized, in-
crease in local temperature within the supraclavicular region
that directly corresponds to the main site of BAT, previously
established from PET/CT scans and biopsy studies,1-3,14al-
though this remains to be correlated directly with tissue bi-
opsy and simultaneous PET/CT. The thermogenic response
in this region, indicative of nonshivering thermogenesis,
occurred rapidly (ie, within 5 minutes of any thermal
Figure 2. Examples of A, digital and B, C, thermal images of
with D, PET image,15and E, sequential PET/CT images of
comparable adult subjects showing BAT in the neck and
supraclavicular regions colocating tothermalareasmeasured
Figure 3. Examples of A, digital and B, C, thermal images of
the same individual (with colored isotherms) indicating the
position of the supraclavicular region in relation to the visible
surface anatomy and 11-cm scale. Illustrates the (i) sterno-
cleidomastoid, (ii) superior borders of the clavicles, (iii) exter-
nal jugular veins, and (iv) position of maximal carotid pulsation
Thermal Imaging to Assess Age-Related Changes of Skin Temperature within the Supraclavicular Region Co-Locating
with Brown Adipose Tissue in Healthy Children
challenge), which is in accord with the effect of acute cold ex-
posure on BAT metabolism in adults.19This is compatible
comitant unmasking of guanodine diphosphate binding sites
within uncoupling protein 1,20and the stimulatory effect of
catecholamines on heat production both in the newborn21,22
and in adults.23,24Furthermore, we have demonstrated that
only a modest cool challenge is required to cause a local tem-
perature increase within this supraclavicular region.
The consistency of baseline thermal activity within the
supraclavicular region where BAT is known to be located,
in conjunction with the magnitude and rapidity of response,
is indicative of a tissuethat canbe rapidly activated and deac-
clavicular region on exposure to a modest cool challenge and
would, therefore, be expected to contribute significantly to
heat production given the substantial capacity of BAT to rap-
vation that in some subjects a rise in temperature around the
ular vein and carotid artery (ie, the main blood vessels of the
neck) is expected as this is one site of BAT originally identi-
fied25and more recently confirmed26for infants.
Further detailed characterization of these effects needs to
be undertaken as it will be important to directly correlate
changes in skin surface temperature with direct measure-
ments of BAT activity and/or cutaneous blood flow. It is,
however, unlikely that these rapid highly localized thermal
changes in regions of BAT visualized using this technique
would simply be related to the immediate circulatory effects
of altered blood flow.18Moreover, the effect of an increase in
uptake rather than energy expenditure, at least in adults.27
Cooling of the hand would be expected to promote local
vasoconstriction and, therefore, a reduction in blood flow,
rather than vasodilatation, and this is supported by the
absence of any change in skin surface temperature outside
the region of interest.
Although a recent pediatric study using PET assessment of
BAT indicatesthat BMIis a primary factor related to BAT ac-
tivity,28all subjects studied here were of normal BMI with
minimal subcutaneous tissue overlying the supraclavicular
region such that thermal responses in the supraclavicular re-
dividuals studied regardless of overlying tissues.
We have also shown that thermal activity of the supracla-
vicular region is greater in children than in adults in accord
with a recent publication using PET in children and adoles-
cents with cancer.28The latter study, although not exposing
the patients to an external challenge or examining normal
imal studies have shown cancer per se can promote BAT
function,29suggesting these are a subgroup of patients in
which BAT function is preferentially enhanced.
Although BAT is detected in only 10% of adult subjects
undergoing PET/CT scans for clinical indications, its inci-
dence appears to be increased in the small number of studies
of healthy adult volunteers where, in some cases, all subjects
small number of cancer patients studied, uncoupling protein
1 can be detected within supraclavicular adipose tissue irre-
spective of whether the subject is BAT “positive” or “nega-
tive” on PET/CT scan.31Therefore, not only does BAT
detection in patients undergoing PET/CT scanning for clini-
cal indications possibly not reflect functioning BAT deposits
in healthy subjects, as a minority may be BAT “positive” on
PET/CT scanning,30also, substantial numbers of patients
would be required to undergo both PET/CT and thermal
showing representative examples of the increase in area and temperature of the thermally active supraclavicular region A, C, E,
before and B, D, F, 5 minutes after immersion of 1 hand into cold tap water at 20?C. Red pixels, 36.5?-37.0?C; orange pixels,
36.0?-36.49?C; yellow pixels, 35.5?-35.99?C.
THE JOURNAL OF PEDIATRICS
Vol. 161, No. 5
Symonds et al
imaging to provide the quantitative validation previously il-
lustrated in animal studies.15In addition, while previous
studies in human subjects have used PET/CT, the relatively
large amounts of radiation exposure (?8 mSv) that accom-
panies its use (eg, exposing a child of 35 kg to the equivalent
ionizing radiation of ?160 chest radiographs), it is very dif-
ficult to justify its use in healthy volunteer subjects. Adjuvant
thermal imaging has, therefore, the potential to add addi-
tional functional information in real-time to information
gained from static PET/CT images.
One explanation for the reduction of thermal activity in
the supraclavicular area overlying BAT with increasing age
is that the endocrine stimulatory factors that are responsible
for switching on BAT thermogenesis at birth32persist at
higher levels in childhood compared with adulthood. This
is supported by studies in sheep that indicate that these re-
main above adult values well into later life.33The mecha-
nisms by which BAT activity is enhanced are likely be
important in the prevention of excess adiposity because of
its unique capacity to use cellular energy for heat produc-
tion.4Enhanced BAT thermogenesis in prepubertal children
may beof particular importance inthecontext of theincreas-
ing prevalence of childhood obesity. Therefore, we hypothe-
size that those children who become obese in early life are
characterized not only as having more white fat cells34but
also as having reduced BAT.
In conclusion, given the comparative ease and reproduc-
ibility of our assessments, this widely available, noninvasive
imaging technique has great potential in exploring thermo-
genesis through the life cycle, which, although well defined
in animal studies,35has previously been elusive in human
health and disease. Thermal imaging could also be combined
with other techniques for assessing both BAT and white ad-
ipose tissue distribution across the body to provide new
insights into the relationship between white adipose tissue
and BAT in the metabolic syndrome. n
to data analysis.
Submitted for publication Jun 7, 2011; last revision received Mar 15, 2012;
accepted Apr 20, 2012.
School of Clinical Sciences, University Hospital, Nottingham, NG7 2UH, UK.
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