Multispectral Optoacoustic Tomography of Brown Adipose Tissue

  • Angelos Karlas
  • Josefine Reber
  • Evangelos Liapis
  • Korbinian Paul-Yuan
  • Vasilis NtziachristosEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 251)


MSOT has revolutionized biomedical imaging because it allows anatomical, functional, and molecular imaging of deep tissues in vivo in an entirely noninvasive, label-free, and real-time manner. This imaging modality works by pulsing light onto tissue, triggering the production of acoustic waves, which can be collected and reconstructed to provide high-resolution images of features as deep as several centimeters below the body surface. Advances in hardware and software continue to bring MSOT closer to clinical translation. Most recently, a clinical handheld MSOT system has been used to image brown fat tissue (BAT) and its metabolic activity by directly resolving the spectral signatures of hemoglobin and lipids. This opens up new possibilities for studying BAT physiology and its role in metabolic disease without the need to inject animals or humans with contrast agents. In this chapter, we overview how MSOT works and how it has been implemented in preclinical and clinical contexts. We focus on our recent work using MSOT to image BAT in resting and activated states both in mice and humans.


Brown adipose tissue Hemoglobin oxygenation Metabolic imaging MSOT Optoacoustics Photoacoustics Spectral unmixing 


  1. Buehler A, Diot G, Volz T, Kohlmeyer J, Ntziachristos V (2017) Imaging of fatty tumors: appearance of subcutaneous lipomas in optoacoustic images. J Biophotonics 10:983–989CrossRefGoogle Scholar
  2. Cai X, Li L, Krumholz A, Guo Z, Erpelding TN, Zhang C, Zhang Y, Xia Y, Wang LV (2012) Multi-scale molecular photoacoustic tomography of gene expression. PLoS One 7:e43999CrossRefGoogle Scholar
  3. Cedikova M, Kripnerova M, Dvorakova J, Pitule P, Grundmanova M, Babuska V, Mullerova D, Kuncova J (2016) Mitochondria in white, brown, and beige adipocytes. Stem Cells Int 2016:6067349CrossRefGoogle Scholar
  4. Cypess AM, Weiner LS, Roberts-Toler C, Elía EF, Kessler SH, Kahn PA, English J, Chatman K, Trauger SA, Doria A, Kolodny GM (2015) Activation of human brown adipose tissue by a β3-adrenergic receptor agonist. Cell Metab 21:33–38CrossRefGoogle Scholar
  5. Dean-Ben XL, Gottschalk S, Mc Larney B, Shoham S, Razansky D (2017) Advanced optoacoustic methods for multiscale imaging of in vivo dynamics. Chem Soc Rev 46:2158–2198CrossRefGoogle Scholar
  6. Dima A, Ntziachristos V (2016) In-vivo handheld optoacoustic tomography of the human thyroid. Photoacoustics 4:65–69CrossRefGoogle Scholar
  7. Diot G, Dima A, Ntziachristos V (2015) Multispectral opto-acoustic tomography of exercised muscle oxygenation. Opt Lett 40:1496–1499CrossRefGoogle Scholar
  8. Diot G, Metz S, Noske A, Liapis E, Schroeder B, Ovsepian SV, Meier R, Rummeny E, Ntziachristos V (2017) Multispectral optoacoustic tomography (MSOT) of human breast cancer. Clin Cancer Res 23:6912–6922CrossRefGoogle Scholar
  9. Enerback S (2009) The origins of brown adipose tissue. N Engl J Med 360:2021–2023CrossRefGoogle Scholar
  10. Ernande L, Stanford KI, Thoonen R, Zhang H, Clerte M, Hirshman MF, Goodyear LJ, Bloch KD, Buys ES, Scherrer-Crosbie M (2016) Relationship of brown adipose tissue perfusion and function: a study through β2-adrenoreceptor stimulation. J Appl Physiol (1985) 120:825–832CrossRefGoogle Scholar
  11. Filonov GS, Krumholz A, Xia J, Yao J, Wang LV, Verkhusha VV (2012) Deep-tissue photoacoustic tomography of a genetically encoded near-infrared fluorescent probe. Angew Chem Int Ed Engl 51:1448–1451CrossRefGoogle Scholar
  12. Giralt M, Villarroya F (2013) White, brown, beige/brite: different adipose cells for different functions? Endocrinology 154:2992–3000CrossRefGoogle Scholar
  13. Gottschalk S, Felix Fehm T, Luís Deán-Ben X, Razansky D (2015) Noninvasive real-time visualization of multiple cerebral hemodynamic parameters in whole mouse brains using five-dimensional optoacoustic tomography. J Cereb Blood Flow Metab 35:531–535CrossRefGoogle Scholar
  14. Gujrati V, Mishra A, Ntziachristos V (2017) Molecular imaging probes for multi-spectral optoacoustic tomography. Chem Commun (Camb) 53:4653–4672CrossRefGoogle Scholar
  15. Herzog E, Taruttis A, Beziere N, Lutich AA, Razansky D, Ntziachristos V (2012) Optical imaging of cancer heterogeneity with multispectral optoacoustic tomography. Radiology 263:461–468CrossRefGoogle Scholar
  16. Jathoul AP, Laufer J, Ogunlade O, Treeby B, Cox B, Zhang E, Johnson P, Pizzey AR, Philip B, Marafioti T, Lythgoe MF, Pedley RB, Pule MA, Beard P (2015) Deep in vivo photoacoustic imaging of mammalian tissues using a tyrosinase-based genetic reporter. Nat Photonics 9:239–246CrossRefGoogle Scholar
  17. Jiang Y, Sigmund F, Reber J, Dean-Ben XL, Glasl S, Kneipp M, Estrada H, Razansky D, Ntziachristos V, Westmeyer GG (2015) Violacein as a genetically-controlled, enzymatically amplified and photobleaching-resistant chromophore for optoacoustic bacterial imaging. Sci Rep 5:11048CrossRefGoogle Scholar
  18. Karlas A, Reber J, Diot G, Bozhko D, Anastasopoulou M, Ibrahim T, Schwaiger M, Hyafil F, Ntziachristos V (2017) Flow-mediated dilatation test using optoacoustic imaging: a proof-of-concept. Biomed Opt Express 8:3395–3403CrossRefGoogle Scholar
  19. Laufer J, Johnson P, Zhang E, Treeby B, Cox B, Pedley B, Beard P (2012) In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy. J Biomed Opt 17:056016CrossRefGoogle Scholar
  20. Ntziachristos V (2010) Going deeper than microscopy: the optical imaging frontier in biology. Nat Methods 7:603–614CrossRefGoogle Scholar
  21. Ntziachristos V, Razansky D (2010) Molecular imaging by means of multispectral optoacoustic tomography (MSOT). Chem Rev 110:2783–2794CrossRefGoogle Scholar
  22. Omar M, Schwarz M, Soliman D, Symvoulidis P, Ntziachristos V (2015) Pushing the optical imaging limits of cancer with multi-frequency-band raster-scan optoacoustic mesoscopy (RSOM). Neoplasia 17:208–214CrossRefGoogle Scholar
  23. Philip R, Penzkofer A, Bäumler W, Szeimies RM, Abels C (1996) Absorption and fluorescence spectroscopic investigation of indocyanine green. J Photochem Photobiol A Chem 96:137–148CrossRefGoogle Scholar
  24. Razansky D, Vinegoni C, Ntziachristos V (2007) Multispectral photoacoustic imaging of fluorochromes in small animals. Opt Lett 32:2891–2893CrossRefGoogle Scholar
  25. Razansky D, Distel M, Vinegoni C, Ma R, Perrimon N, Köster RW, Ntziachristos V (2009) Multispectral opto-acoustic tomography of deep-seated fluorescent proteins in vivo. Nat Photonics 3:412–417CrossRefGoogle Scholar
  26. Reber J, Willershäuser M, Karlas A, Paul-Yuan K, Diot G, Franz D, Fromme T, Ovsepian SV, Bézière N, Dubikovskaya E, Karampinos DC, Holzapfel C, Hauner H, Klingenspor M, Ntziachristos V (2018) Non-invasive measurement of brown fat metabolism based on optoacoustic imaging of hemoglobin gradients. Cell Metab 27:689–701.e684CrossRefGoogle Scholar
  27. Shu X, Royant A, Lin MZ, Aguilera TA, Lev-Ram V, Steinbach PA, Tsien RY (2009) Mammalian expression of infrared fluorescent proteins engineered from a bacterial phytochrome. Science (New York, NY) 324:804–807CrossRefGoogle Scholar
  28. Taruttis A, Claussen J, Razansky D, Ntziachristos V (2012) Motion clustering for deblurring multispectral optoacoustic tomography images of the mouse heart. J Biomed Opt 17:016009CrossRefGoogle Scholar
  29. Taruttis A, Timmermans AC, Wouters PC, Kacprowicz M, van Dam GM, Ntziachristos V (2016) Optoacoustic imaging of human vasculature: feasibility by using a handheld probe. Radiology 281:256–263CrossRefGoogle Scholar
  30. Tzoumas S, Ntziachristos V (2017) Spectral unmixing techniques for optoacoustic imaging of tissue pathophysiology. Philos Transact A Math Phys Eng Sci 375Google Scholar
  31. Tzoumas S, Zaremba A, Klemm U, Nunes A, Schaefer K, Ntziachristos V (2014) Immune cell imaging using multi-spectral optoacoustic tomography. Opt Lett 39:3523–3526CrossRefGoogle Scholar
  32. Tzoumas S, Nunes A, Olefir I, Stangl S, Symvoulidis P, Glasl S, Bayer C, Multhoff G, Ntziachristos V (2016) Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues. Nat Commun 7:12121CrossRefGoogle Scholar
  33. Weber J, Beard PC, Bohndiek SE (2016) Contrast agents for molecular photoacoustic imaging. Nat Methods 13:639–650CrossRefGoogle Scholar
  34. Weissleder R (2001) A clearer vision for in vivo imaging. Nat Biotechnol 19:316–317CrossRefGoogle Scholar
  35. Weissleder R, Pittet MJ (2008) Imaging in the era of molecular oncology. Nature 452:580–589CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Angelos Karlas
    • 1
    • 2
  • Josefine Reber
    • 1
    • 2
  • Evangelos Liapis
    • 1
    • 2
  • Korbinian Paul-Yuan
    • 1
    • 2
  • Vasilis Ntziachristos
    • 1
    • 2
    Email author
  1. 1.Chair of Biological ImagingTechnical University MunichMunichGermany
  2. 2.Institute of Biological and Medical Imaging (IBMI), Helmholtz Zentrum MünchenNeuherbergGermany

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