Molecular Imaging and Biology

, Volume 21, Issue 2, pp 328–338 | Cite as

Near-Infrared Spatially Resolved Spectroscopy as an Indirect Technique to Assess Brown Adipose Tissue in Young Women

  • Francisco M. AcostaEmail author
  • Jörn Berchem
  • Borja Martinez-Tellez
  • Guillermo Sanchez-Delgado
  • Juan M. A. Alcantara
  • Lourdes Ortiz-Alvarez
  • Takafumi Hamaoka
  • Jonatan R. Ruiz
Research Article



Near-infrared spectroscopy (NIRS) has recently been proposed as an indirect technique to assess brown adipose tissue (BAT) in young men. NIRS arises as a novel technique to avoid the limitations of the “gold-standard” 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) positron emission tomography combined with X-ray computed tomography (PET/CT). The aim of this study was to examine the association between near-infrared spatially resolved spectroscopy (NIRSRS) parameters and BAT volume and activity estimated by [18F]DG-PET/CT in 18 young healthy women.


NIRSRS parameters [tissue saturation index and concentrations of total haemoglobin, oxy-haemoglobin, and deoxy-haemoglobin] were continuously measured in the supraclavicular and forearm regions, in both warm and cold (2 h of personalised cold exposure) conditions. Then, the NIRSRS data were analysed as an average of 5 min in 4 different periods: (i) warm period as the baseline record, (ii) cold period I, (iii) cold period II, and (iv) cold period III. The data were then correlated with BAT volume and activity (SUVmean and SUVpeak) estimated by [18F]DG-PET/CT.


There was no association between the NIRSRS parameters in the supraclavicular region in warm conditions (no previous cold exposure) and BAT volume and activity (P > 0.05). Similarly, the cold-induced changes of the NIRSRS parameters in the supraclavicular region were not associated with BAT volume and activity (P > 0.05).


NIRSRS does not seem to be a valid technique to indirectly assess BAT in young healthy women. Further research is needed to validate this technique against other methods such as PET/CT using different radiotracers or magnetic resonance imaging.

Key words

Acute cold exposure BAT perfusion Cold-induced thermogenesis Energy balance Molecular imaging Oxygen consumption Oxygen delivery 



We are grateful to Ms. Carmen Sainz-Quinn for the assistance with the English language and to Marco Dat (Artinis Medical Systems) for his excellent technical assistance.

Financial Support

The study was supported by the Spanish Ministry of Economy and Competitiveness (PTA 12264-I), Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), and Retos de la Sociedad (DEP2016-79512-R), Fondos Estructurales de la Unión Europea (FEDER), by the Spanish Ministry of Education (FPU 13/04365 and 15/04059), by the Fundación Iberoamericana de Nutrición (FINUT), by the Redes temáticas de investigación cooperativa RETIC (Red SAMID RD16/0022), by AstraZeneca HealthCare Foundation, and by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES). This study is part of a PhD thesis conducted in the Biomedicine Doctoral Studies, University of Granada, Spain.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11307_2018_1244_MOESM1_ESM.pdf (184 kb)
ESM 1 (PDF 183 kb)


  1. 1.
    Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359CrossRefGoogle Scholar
  2. 2.
    Peirce V, Vidal-Puig A (2013) Regulation of glucose homoeostasis by brown adipose tissue. Lancet Diabetes Endocrinol 1:353–360CrossRefGoogle Scholar
  3. 3.
    Schilperoort M, Hoeke G, Kooijman S, Rensen PCN (2016) Relevance of lipid metabolism for brown fat visualization and quantification. Curr Opin Lipidol 27:242–248CrossRefGoogle Scholar
  4. 4.
    Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR (2009) Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360:1509–1517CrossRefGoogle Scholar
  5. 5.
    van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JMAFL, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJJ (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360:1500–1508CrossRefGoogle Scholar
  6. 6.
    Virtanen KAK, Lidell MME, Orava J et al (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360:1518–1525CrossRefGoogle Scholar
  7. 7.
    Leitner BP, Huang S, Brychta RJ, Duckworth CJ, Baskin AS, McGehee S, Tal I, Dieckmann W, Gupta G, Kolodny GM, Pacak K, Herscovitch P, Cypess AM, Chen KY (2017) Mapping of human brown adipose tissue in lean and obese young men. Proc Natl Acad Sci U S A 114:8649–8654CrossRefGoogle Scholar
  8. 8.
    Lee P, Smith S, Linderman J, Courville AB, Brychta RJ, Dieckmann W, Werner CD, Chen KY, Celi FS (2014) Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans. Diabetes 63:3686–3698CrossRefGoogle Scholar
  9. 9.
    Ouellet V, Labbé SM, Blondin DP, Phoenix S, Guérin B, Haman F, Turcotte EE, Richard D, Carpentier AC (2012) Brown adipose tissue oxidative metabolism contributes to energy expenditure during cold exposure in humans. J Clin Invest 122:545–552CrossRefGoogle Scholar
  10. 10.
    Blondin DP, Labbé SM, Phoenix S, Guérin B, Turcotte ÉE, Richard D, Carpentier AC, Haman F (2015) Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men. J Physiol 593:701–714CrossRefGoogle Scholar
  11. 11.
    Blondin DP, Frisch F, Phoenix S, Guérin B, Turcotte ÉE, Haman F, Richard D, Carpentier AC (2017) Inhibition of intracellular triglyceride lipolysis suppresses cold-induced brown adipose tissue metabolism and increases shivering in humans. Cell Metab 25:438–447CrossRefGoogle Scholar
  12. 12.
    Blondin DP, Tingelstad HC, Noll C, Frisch F, Phoenix S, Guérin B, Turcotte ÉE, Richard D, Haman F, Carpentier AC (2017) Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men. Nat Commun 8:14146CrossRefGoogle Scholar
  13. 13.
    Liu X, Cervantes C, Liu F (2017) Common and distinct regulation of human and mouse brown and beige adipose tissues: a promising therapeutic target for obesity. Protein Cell 8:446–454CrossRefGoogle Scholar
  14. 14.
    Cypess AM, Haft CR, Laughlin MR, Hu HH (2014) Brown fat in humans: consensus points and experimental guidelines. Cell Metab 20:408–415CrossRefGoogle Scholar
  15. 15.
    Jobsis FF (1977) Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198:1264–1267CrossRefGoogle Scholar
  16. 16.
    Hamaoka T, McCully KK, Quaresima V et al (2007) Near-infrared spectroscopy/imaging for monitoring muscle oxygenation and oxidative metabolism in healthy and diseased humans. J Biomed Opt 12:062105CrossRefGoogle Scholar
  17. 17.
    Boushel R, Langberg H, Olesen J, Gonzales-Alonzo J, Bulow J, Kjaer M (2001) Monitoring tissue oxygen availability with near infrared spectroscopy (NIRS) in health and disease. Scand J Med Sci Sports 11:213–222CrossRefGoogle Scholar
  18. 18.
    Ferrari M, Muthalib M, Quaresima V (2011) The use of near-infrared spectroscopy in understanding skeletal muscle physiology: recent developments. Philos Trans R Soc 369:4577–4590CrossRefGoogle Scholar
  19. 19.
    Muzik O, Mangner TJ, Leonard WR, Kumar A, Janisse J, Granneman JG (2013) 15O PET measurement of blood flow and oxygen consumption in cold-activated human brown fat. J Nucl Med 54:523–531CrossRefGoogle Scholar
  20. 20.
    u Din M, Raiko J, Saari T, Kudomi N, Tolvanen T, Oikonen V, Teuho J, Sipilä HT, Savisto N, Parkkola R, Nuutila P, Virtanen KA (2016) Human brown adipose tissue [15O]O2 PET imaging in the presence and absence of cold stimulus. Eur J Nucl Med Mol Imaging 43:1878–1886CrossRefGoogle Scholar
  21. 21.
    Cinti S (2009) Transdifferentiation properties of adipocytes in the adipose organ. Am J Physiol Endocrinol Metab 297:E977–E986CrossRefGoogle Scholar
  22. 22.
    Nirengi S, Yoneshiro T, Sugie H, Saito M, Hamaoka T (2015) Human brown adipose tissue assessed by simple, noninvasive near-infrared time-resolved spectroscopy. Obesity 23:973–980CrossRefGoogle Scholar
  23. 23.
    Orava J, Nuutila P, Lidell MEE et al (2011) Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab 14:272–279CrossRefGoogle Scholar
  24. 24.
    Khanna A, Branca RT (2012) Detecting brown adipose tissue activity with BOLD MRI in mice. Magn Reson Med 68:1285–1290CrossRefGoogle Scholar
  25. 25.
    Nirengi S, Yoneshiro T, Saiki T et al (2016) Evaluation of brown adipose tissue using near-infrared time-resolved spectroscopy. In: Elwell CE, Leung TS, Harrison DK (eds) Oxygen Transport to Tissue XXXVII. Springer, New York, pp 371–376CrossRefGoogle Scholar
  26. 26.
    Chen KY, Cypess AM, Laughlin MR, Haft CR, Hu HH, Bredella MA, Enerbäck S, Kinahan PE, Lichtenbelt WM, Lin FI, Sunderland JJ, Virtanen KA, Wahl RL (2016) Brown adipose reporting criteria in imaging STUDIES (BARCIST 1.0): recommendations for standardized FDG-PET/CT experiments in humans. Cell Metab 24:210–222CrossRefGoogle Scholar
  27. 27.
    Sanchez-Delgado G, Martinez-Tellez B, Olza J et al (2015) Activating brown adipose tissue through exercise (ACTIBATE) in young adults: rationale, design and methodology. Contemp Clin Trials 45:416–425CrossRefGoogle Scholar
  28. 28.
    Martinez-Tellez B, Sanchez-Delgado G, Garcia-Rivero Y et al (2017) A new personalized cooling protocol to activate brown adipose tissue in young adults. Front Physiol.
  29. 29.
    Chance B, Nioka S, Kent J et al (1989) Time-resolved spectroscopy of hemoglobin and myoglobin in resting and ischemic muscle. Anal Biochem 174:698–707CrossRefGoogle Scholar
  30. 30.
    Suzuki S, Takasaki S, Ozaki T, Kobayashi Y (1999) Tissue oxygenation monitor using NIR spatially resolved spectroscopy. Proc SPIE.
  31. 31.
    Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682CrossRefGoogle Scholar
  32. 32.
    Hasenclever D, Kurch L, Mauz-Körholz C, Elsner A, Georgi T, Wallace H, Landman-Parker J, Moryl-Bujakowska A, Cepelová M, Karlén J, Álvarez Fernández-Teijeiro A, Attarbaschi A, Fosså A, Pears J, Hraskova A, Bergsträsser E, Beishuizen A, Uyttebroeck A, Schomerus E, Sabri O, Körholz D, Kluge R (2014) qPET—a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma. Eur J Nucl Med Mol Imaging 41:1301–1308CrossRefGoogle Scholar
  33. 33.
    Blondin DP, Labbe SM, Tingelstad HC et al (2014) Increased brown adipose tissue oxidative capacity in cold-acclimated humans. J Clin Endocrinol Metab 99:1027–1036CrossRefGoogle Scholar
  34. 34.
    Davis SL (2006) Skin blood flow influences near-infrared spectroscopy-derived measurements of tissue oxygenation during heat stress. J Appl Physiol 100:221–224CrossRefGoogle Scholar
  35. 35.
    Koga S, Poole DC, Kondo N et al (2014) Effects of increased skin blood flow on muscle oxygenation/deoxygenation: comparison of time-resolved and continuous-wave near-infrared spectroscopy signals. Eur J Appl Physiol 115:335–343CrossRefGoogle Scholar
  36. 36.
    Ferreira LF, Hueber DM, Barstow TJ (2007) Effects of assuming constant optical scattering on measurements of muscle oxygenation by near-infrared spectroscopy during exercise. J Appl Physiol 102:358–367CrossRefGoogle Scholar
  37. 37.
    Sato C, Yamaguchi T, Seida M, Ota Y, Yu I, Iguchi Y, Nemoto M, Hoshi Y (2007) Intraoperative monitoring of depth-dependent hemoglobin concentration changes during carotid endarterectomy by time-resolved spectroscopy. Appl Opt 46:2785–2792CrossRefGoogle Scholar
  38. 38.
    Charkoudian N (2003) Skin blood flow in adult human thermoregulation: how it works, when it does not, and why. Mayo Clin Proc 78:603–612CrossRefGoogle Scholar
  39. 39.
    Sacks H, Symonds ME (2013) Anatomical locations of human brown adipose tissue: functional relevance and implications in obesity and type 2 diabetes. Diabetes 62:1783–1790CrossRefGoogle Scholar
  40. 40.
    Boushel R, Saltin B (2013) Ex vivo measures of muscle mitochondrial capacity reveal quantitative limits of oxygen delivery by the circulation during exercise. Int J Biochem Cell Biol 45:68–75CrossRefGoogle Scholar
  41. 41.
    van der Lans AAJJ, Wierts R, Vosselman MJ, Schrauwen P, Brans B, van Marken Lichtenbelt WD (2014) Cold-activated brown adipose tissue in human adults: methodological issues. Am J Physiol Regul Integr Comp Physiol 307:R103–R113CrossRefGoogle Scholar
  42. 42.
    Fadel PJ, Keller DM, Watanabe H, Raven PB, Thomas GD (2004) Noninvasive assessment of sympathetic vasoconstriction in human and rodent skeletal muscle using near-infrared spectroscopy and Doppler ultrasound. J Appl Physiol 96:1323–1330CrossRefGoogle Scholar
  43. 43.
    Engel PAK, Severinghaus JW, Munson E (1965) The influence of temperature and pH on the dissociation curve of oxyhemoglobin of human blood. Scand J Clin Lab Invest 17:515–523CrossRefGoogle Scholar
  44. 44.
    Tew GA, Ruddock AD, Saxton JM (2010) Skin blood flow differentially affects near-infrared spectroscopy-derived measures of muscle oxygen saturation and blood volume at rest and during dynamic leg exercise. Eur J Appl Physiol 110:1083–1089CrossRefGoogle Scholar
  45. 45.
    Paulus A, van Marken Lichtenbelt W, Bauwens M (2017) Brown adipose tissue and lipid metabolism imaging. Methods 130:105–113CrossRefGoogle Scholar
  46. 46.
    Sun L, Yan J, Sun L, Velan SS, Leow MKS (2017) A synopsis of brown adipose tissue imaging modalities for clinical research. Diabetes Metab 43:401–410CrossRefGoogle Scholar

Copyright information

© World Molecular Imaging Society 2018

Authors and Affiliations

  • Francisco M. Acosta
    • 1
    Email author
  • Jörn Berchem
    • 1
    • 2
  • Borja Martinez-Tellez
    • 1
    • 3
  • Guillermo Sanchez-Delgado
    • 1
  • Juan M. A. Alcantara
    • 1
  • Lourdes Ortiz-Alvarez
    • 1
  • Takafumi Hamaoka
    • 4
  • Jonatan R. Ruiz
    • 1
  1. 1.PROFITH “PROmoting FITness and Health through physical activity” Research Group, Department of Physical and Sports Education, Faculty of Sports ScienceUniversity of GranadaGranadaSpain
  2. 2.Department of Sports Medicine, Institute of Sports SciencesJustus-Liebig-University GiessenGiessenGermany
  3. 3.Department of Medicine, Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular MedicineLeiden University Medical CenterLeidenThe Netherlands
  4. 4.Department of Sports Medicine for Health PromotionTokyo Medical UniversityTokyoJapan

Personalised recommendations