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Through-skull fluorescence imaging of the brain in a new near-infrared window

Nature Photonics volume 8, pages 723–730 (2014)Cite this article

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Abstract

To date, brain imaging has largely relied on X-ray computed tomography and magnetic resonance angiography, with their limited spatial resolution and long scanning times. Fluorescence-based brain imaging in the visible and traditional near-infrared regions (400–900 nm) is an alternative, but at present it requires craniotomy, cranial windows and skull-thinning techniques, and the penetration depth is limited to 1–2 mm due to light scattering. Here, we report through-scalp and through-skull fluorescence imaging of mouse cerebral vasculature without craniotomy, utilizing the intrinsic photoluminescence of single-walled carbon nanotubes in the 1.3–1.4 μm near-infrared window (NIR-IIa window). Reduced photon scattering in this spectral region allows fluorescence imaging to a depth of >2 mm in mouse brain with sub-10-μm resolution. An imaging rate of ∼5.3 frames per second allows for dynamic recording of blood perfusion in the cerebral vessels with sufficient temporal resolution, providing real-time assessment of a blood flow anomaly in a mouse middle cerebral artery occlusion stroke model.

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Figure 1: Imaging in various NIR subregions.
Figure 2: In vivo mouse brain imaging with SWNT–IRDye800 in different NIR subregions.
Figure 3: Non-invasive, high-resolution NIR-IIa fluorescence imaging of mouse brain vasculature.
Figure 4: Dynamic NIR-IIa fluorescence imaging of mouse cerebral vasculature.

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Acknowledgements

This study was supported by the National Cancer Institute of the US National Institutes of Health (NIH, grant 5R01CA135109-02, to H.D.), the American Heart Association (Innovative Science Award to C.J.K.), the NIH (grant 1R01NS064517, to C.J.K.) and a William S. Johnson Fellowship (to G.H.). The authors thank J. M. Pauly, D. Wong and T. Zhang for discussions.

Author information

Author notes

  1. Guosong Hong, Shuo Diao and Junlei Chang: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Chemistry, Stanford University, Stanford, 94305, California, USA

    Guosong Hong, Shuo Diao, Alexander L. Antaris, Changxin Chen, Bo Zhang, Su Zhao & Hongjie Dai

  2. Division of Hematology, School of Medicine, Stanford University, Stanford, 94305, California, USA

    Junlei Chang & Calvin J. Kuo

  3. Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Charlestown, 02129, Massachusetts, USA

    Dmitriy N. Atochin & Paul L. Huang

  4. Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, 94305, California, USA

    Katrin I. Andreasson

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  1. Guosong Hong
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Contributions

H.D., C.J.K., G.H., S.D. and J.C. conceived and designed the experiments. G.H., S.D., J.C., A.L.A., C.C., B.Z., S.Z. and D.N.A. performed the experiments. G.H., S.D., J.C., A.L.A., C.C., B.Z., S.Z., D.N.A., P.L.H., K.I.A., C.J.K. and H.D. analysed the data and wrote the manuscript. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Calvin J. Kuo or Hongjie Dai.

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Hong, G., Diao, S., Chang, J. et al. Through-skull fluorescence imaging of the brain in a new near-infrared window. Nature Photon 8, 723–730 (2014). https://doi.org/10.1038/nphoton.2014.166

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