Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Simultaneous PET-MRI reveals brain function in activated and resting state on metabolic, hemodynamic and multiple temporal scales


Combined positron emission tomography (PET) and magnetic resonance imaging (MRI) is a new tool to study functional processes in the brain. Here we study brain function in response to a barrel-field stimulus simultaneously using PET, which traces changes in glucose metabolism on a slow time scale, and functional MRI (fMRI), which assesses fast vascular and oxygenation changes during activation. We found spatial and quantitative discrepancies between the PET and the fMRI activation data. The functional connectivity of the rat brain was assessed by both modalities: the fMRI approach determined a total of nine known neural networks, whereas the PET method identified seven glucose metabolism–related networks. These results demonstrate the feasibility of combined PET-MRI for the simultaneous study of the brain at activation and rest, revealing comprehensive and complementary information to further decode brain function and brain networks.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Figure 1: Comparison of PET and fMRI activation.
Figure 2: Quantification of PET-MRI stimulus response.
Figure 3: PET-MRI functional connectivity.
Figure 4: Networks in the whisker system.


  1. Ogawa, S., Lee, T.M., Kay, A.R. & Tank, D.W. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc. Natl. Acad. Sci. USA 87, 9868–9872 (1990).

    Article  CAS  Google Scholar 

  2. Phelps, M.E. & Mazziotta, J.C. Positron emission tomography: human brain function and biochemistry. Science 228, 799–809 (1985).

    Article  CAS  Google Scholar 

  3. Buxton, R.B. Interpreting oxygenation-based neuroimaging signals: the importance and the challenge of understanding brain oxygen metabolism. Front. Neuroenergetics 2, 8 (2010).

    PubMed  PubMed Central  Google Scholar 

  4. Logothetis, N.K. What we can do and what we cannot do with fMRI. Nature 453, 869–878 (2008).

    Article  CAS  Google Scholar 

  5. Biswal, B.B., Van Kylen, J. & Hyde, J.S. Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps. NMR Biomed. 10, 165–170 (1997).

    Article  CAS  Google Scholar 

  6. Zhang, D. & Raichle, M.E. Disease and the brain's dark energy. Nat. Rev. Neurol. 6, 15–28 (2010).

    Article  Google Scholar 

  7. Shih, Y.Y., Wey, H.Y., De La Garza, B.H. & Duong, T.Q. Striatal and cortical BOLD, blood flow, blood volume, oxygen consumption, and glucose consumption changes in noxious forepaw electrical stimulation. J. Cereb. Blood Flow Metab. 31, 832–841 (2011).

    Article  CAS  Google Scholar 

  8. Kinahan, P.E. & Noll, D.C. A direct comparison between whole-brain PET and BOLD fMRI measurements of single-subject activation response. Neuroimage 9, 430–438 (1999).

    Article  CAS  Google Scholar 

  9. Judenhofer, M.S. et al. Simultaneous PET-MRI: a new approach for functional and morphological imaging. Nat. Med. 14, 459–465 (2008).

    Article  CAS  Google Scholar 

  10. Schlemmer, H.P. et al. Simultaneous MR/PET imaging of the human brain: feasibility study. Radiology 248, 1028–1035 (2008).

    Article  Google Scholar 

  11. Hjornevik, T. et al. Metabolic plasticity in the supraspinal pain modulating circuitry after noxious stimulus-induced spinal cord LTP. Pain 140, 456–464 (2008).

    Article  Google Scholar 

  12. Magistretti, P.J. Neuron-glia metabolic coupling and plasticity. J. Exp. Biol. 209, 2304–2311 (2006).

    Article  CAS  Google Scholar 

  13. Wehrl, H.F. et al. Assessment of MR compatibility of a PET insert developed for simultaneous multiparametric PET/MR imaging on an animal system operating at 7 T. Magn. Reson. Med. 65, 269–279 (2011).

    Article  Google Scholar 

  14. Shimoji, K. et al. Measurement of cerebral glucose metabolic rates in the anesthetized rat by dynamic scanning with 18F-FDG, the ATLAS small animal PET scanner, and arterial blood sampling. J. Nucl. Med. 45, 665–672 (2004).

    CAS  PubMed  Google Scholar 

  15. Jonckers, E., Van Audekerke, J., De Visscher, G., Van der Linden, A. & Verhoye, M. Functional connectivity fMRI of the rodent brain: comparison of functional connectivity networks in rat and mouse. PLoS ONE 6, e18876 (2011).

    Article  CAS  Google Scholar 

  16. Paxinos, G. & Watson, C. The Rat Brain in Sterotaxic Coordinates (Academic Press, San Diego, 1998).

  17. Kennerley, A.J., Mayhew, J.E., Redgrave, P. & Berwick, J. Vascular origins of BOLD and CBV fMRI signals: statistical mapping and histological sections compared. Open Neuroimag. J. 4, 1–8 (2010).

    Article  Google Scholar 

  18. Sanganahalli, B.G., Herman, P. & Hyder, F. Frequency-dependent tactile responses in rat brain measured by functional MRI. NMR Biomed. 21, 410–416 (2008).

    Article  Google Scholar 

  19. Kornblum, H.I. et al. In vivo imaging of neuronal activation and plasticity in the rat brain by high resolution positron emission tomography (microPET). Nat. Biotechnol. 18, 655–660 (2000).

    Article  CAS  Google Scholar 

  20. Ravasi, L. et al. Use of [18F]fluorodeoxyglucose and the ATLAS small animal PET scanner to examine cerebral functional activation by whisker stimulation in unanesthetized rats. Nucl. Med. Commun. 32, 336–342 (2011).

    Article  Google Scholar 

  21. Koyama, Y., Koyama, T., Kroncke, A.P. & Coghill, R.C. Effects of stimulus duration on heat induced pain: the relationship between real-time and post-stimulus pain ratings. Pain 107, 256–266 (2004).

    Article  Google Scholar 

  22. Tran, T.D., Wang, H., Tandon, A., Hernandez-Garcia, L. & Casey, K.L. Temporal summation of heat pain in humans: evidence supporting thalamocortical modulation. Pain 150, 93–102 (2010).

    Article  Google Scholar 

  23. Yu, X. et al. Direct imaging of macrovascular and microvascular contributions to BOLD fMRI in layers IV–V of the rat whisker-barrel cortex. Neuroimage 59, 1451–1460 (2012).

    Article  Google Scholar 

  24. Backes, H. et al. Whiskers area as extracerebral reference tissue for quantification of rat brain metabolism using 18F-FDG PET: application to focal cerebral ischemia. J. Nucl. Med. 52, 1252–1260 (2011).

    Article  Google Scholar 

  25. Bosshard, S.C. et al. Assessment of brain responses to innocuous and noxious electrical forepaw stimulation in mice using BOLD fMRI. Pain 151, 655–663 (2010).

    Article  Google Scholar 

  26. Fox, P.T., Raichle, M.E., Mintun, M.A. & Dence, C. Nonoxidative glucose consumption during focal physiologic neural activity. Science 241, 462–464 (1988).

    Article  CAS  Google Scholar 

  27. Kim, S.G. & Ogawa, S. Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals. J. Cereb. Blood Flow Metab. 32, 1188–1206 (2012).

    Article  CAS  Google Scholar 

  28. Hutchison, R.M., Mirsattari, S.M., Jones, C.K., Gati, J.S. & Leung, L.S. Functional networks in the anesthetized rat brain revealed by independent component analysis of resting-state FMRI. J. Neurophysiol. 103, 3398–3406 (2010).

    Article  Google Scholar 

  29. Vaishnavi, S.N. et al. Regional aerobic glycolysis in the human brain. Proc. Natl. Acad. Sci. USA 107, 17757–17762 (2010).

    Article  CAS  Google Scholar 

  30. Fox, M.D. & Raichle, M.E. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat. Rev. Neurosci. 8, 700–711 (2007).

    Article  CAS  Google Scholar 

Download references


We thank F. Cay and M. Koenig for excellent technical support during this project. This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft PI 771/1-1, PI 771/5-1), the Wilhelm Schuler-Foundation and the Werner Siemens-Foundation.

Author information

Authors and Affiliations



H.F.W. and B.J.P. designed the study, evaluated and analyzed data and prepared the manuscript, H.F.W., M.H., K.L., C.-C.L., I.B. and B.J.P. developed the PET insert, G.R. produced the radiotracer, H.F.W. and M.H. made PET-MRI measurements, H.F.W., P.M. and F.S. developed the MRI sequence, and all authors read and edited the manuscript.

Corresponding author

Correspondence to Bernd J Pichler.

Ethics declarations

Competing interests

B.J.P. receives grant and research support from AstraZeneca, Bayer Healthcare, Boehringer-Ingelheim, Bruker, Oncodesign, Merck, Siemens and the Werner Siemens-Foundation. K.L. is an employee of Bruker.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–11, Supplementary Tables 1 and 2, Supplementary Results, Supplementary Discussion and Supplementary Methods (PDF 5899 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wehrl, H., Hossain, M., Lankes, K. et al. Simultaneous PET-MRI reveals brain function in activated and resting state on metabolic, hemodynamic and multiple temporal scales. Nat Med 19, 1184–1189 (2013).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing