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Towards the non-invasive imaging of brain networks and functions at high resolution

A new study describes a microscope combining three-photon excitation and adaptive optics capable of high-resolution in vivo imaging of fine neuronal structures in the mouse cortex through the intact skull. The authors demonstrate the use of this platform to guide precise laser-mediated microsurgery and for accurate and sensitive functional calcium imaging.

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Fig. 1: In vivo brain imaging with high resolution over large volumes through intact skull.


  1. Xu, H. T., Pan, F., Yang, G. & Gan, W. Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex. Nat. Neurosci. 10, 549–551 (2007). This paper shows that invasive imaging methods such as the use of an open skull window disrupt spine turnover and brain functions.

    CAS  Article  Google Scholar 

  2. Wang, T. et al. Three-photon imaging of mouse brain structure and function through the intact skull. Nat. Methods 15, 789–792 (2018). This paper demonstrates the great potential of three-photon microscopy for in vivo brain imaging, although image quality is limited by optical aberration and scattering caused by the opaque skull.

    Article  Google Scholar 

  3. Hampson, K. M. et al. Adaptive optics for high-resolution imaging. Nat. Rev. Methods Primers 1, 68 (2021). A recent Primer article that summarizes the application of AO for high-resolution optical microscopy.

    CAS  Article  Google Scholar 

  4. Liu, H. et al. In vivo deep-brain structural and hemodynamic multiphoton microscopy enabled by quantum dots. Nano Lett. 19, 5260–5265 (2019). This paper demonstrates that highly fluorescent quantum dots enable three-photon imaging of the mouse cerebral vasculature up to a depth of 2.1 mm.

    CAS  Article  Google Scholar 

  5. Papadopoulos, I. N., Jouhanneau, J.-S., Poulet, J. F. A. & Judkewitz, B. Scattering compensation by focus scanning holographic aberration probing (F-SHARP). Nat. Photonics 11, 116–123 (2017). This paper presents a method to measure and correct both optical aberration and scattering of biological tissues for multiphoton microscopy.

    CAS  Article  Google Scholar 

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This is a summary of: Qin, Z. et al. Deep tissue multi-photon imaging using adaptive optics with direct focus sensing and shaping. Nat. Biotechnol. (2022)

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Towards the non-invasive imaging of brain networks and functions at high resolution. Nat Biotechnol (2022).

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