An adaptive optics module for deep tissue multiphoton imaging in vivo

Rodríguez, Cristina; Chen, Anderson; Rivera, José A.; Mohr, Manuel; Liang, Yajie; Natan, Ryan G.; Sun, Wenzhi; Milkie, Daniel E.; Bifano, Thomas G.; Chen, Xiaoke; Ji, Na

doi:10.1038/s41592-021-01279-0

Cited by 73 publications

(71 citation statements)

References 40 publications

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“…Indirect wavefront sensing methods use serial evaluations of image metrics (e.g. brightness, spatial resolution, contrast, point spread function) while manipulating the excitation light to deduce the wavefront profile [32][33][34][35][36]. When implemented properly, both types of methods are capable of forming a diffraction-limited focus deep in tissue to excite fluorescence at diffraction-limited spatial resolution.…”

Section: Statusmentioning

confidence: 99%

Roadmap on wavefront shaping and deep imaging in complex media

et al. 2022

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The last decade has seen the development of a wide set of tools, such as wavefront shaping, computational or fundamental methods, that allow to understand and control light propagation in a complex medium, such as biological tissues or multimode fibers. A vibrant and diverse community is now working on this field, that has revolutionized the prospect of diffraction-limited imaging at depth in tissues. This roadmap highlights several key aspects of this fast developing field, and some of the challenges and opportunities ahead.

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Section: Statusmentioning

confidence: 99%

Roadmap on wavefront shaping and deep imaging in complex media

et al. 2022

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“…As powerful tools, optical imaging techniques have been widely used because of their high spatiotemporal resolutions. Examples such as optical coherence tomography (OCT), [ 6 , 7 ] photoacoustic imaging, [ 8 ] and multiphoton laser scanning microscopy imaging [ 9 , 10 ] facilitate studies on the structural and functional dynamics of cells and vasculature. However, the imaging depth and resolution are limited due to the high scattering of skull.…”

Section: Introductionmentioning

confidence: 99%

A Long‐Term Clearing Cranial Window for Longitudinal Imaging of Cortical and Calvarial Ischemic Injury through the Intact Skull

2022

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Skull is a reservoir for supplying immune cells that mediate brain immune surveillance. However, during intravital optical imaging of brain, conventional cranial windows requiring skull thinning or removal disrupt brain immunity integrity. Here, a novel long‐term clearing cranial window (LCCW) based on the intact skull, dedicated to chronic skull transparency maintenance, is proposed. It significantly improves optical imaging resolution and depth, by which the cortical and calvarial vascular injury and regeneration processes after ischemic injury are longitudinally monitored in awake mice. Results show that calvarial blood vessels recover earlier than the cortex. And the transcriptome analysis reveals that gene expression patterns and immune cells abundances exist substantial differences between brain and skull after ischemic injury, which may be one of the causes for the time lag between their vascular recovery. These findings bring great enlightenment to vascular regeneration and reconstruction. Moreover, LCCW provides a minimally invasive approach for imaging the brain and skull bone marrow.

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“…In the former, a wavefront sensor is installed in the pupil plane to measure the aberration, and a wavefront shaping device is used to compensate for the measured aberration (7)(8)(9). Alternatively, the wavefront shaping device is controlled to optimize the image quality metrics, such as the image brightness and sharpness, without wavefront sensing (10)(11)(12)(13)(14). They have been used to visualize synaptic structures in deep cortical and subcortical areas of the mouse brain and somatosensory-evoked calcium responses in the mouse spinal cord (14).…”

Section: Introductionmentioning

confidence: 99%

“…Alternatively, the wavefront shaping device is controlled to optimize the image quality metrics, such as the image brightness and sharpness, without wavefront sensing (10)(11)(12)(13)(14). They have been used to visualize synaptic structures in deep cortical and subcortical areas of the mouse brain and somatosensory-evoked calcium responses in the mouse spinal cord (14).…”

Section: Introductionmentioning

confidence: 99%

Through-skull brain imaging in vivo at visible wavelengths via dimensionality reduction adaptive-optical microscopy

Lee

Hong

et al. 2022

Sci. Adv.

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Compensation of sample-induced optical aberrations is crucial for visualizing microscopic structures deep within biological tissues. However, strong multiple scattering poses a fundamental limitation for identifying and correcting the tissue-induced aberrations. Here, we introduce a label-free deep-tissue imaging technique termed dimensionality reduction adaptive-optical microscopy (DReAM) to selectively attenuate multiple scattering. We established a theoretical framework in which dimensionality reduction of a time-gated reflection matrix can attenuate uncorrelated multiple scattering while retaining a single-scattering signal with a strong wave correlation, irrespective of sample-induced aberrations. We performed mouse brain imaging in vivo through the intact skull with the probe beam at visible wavelengths. Despite the strong scattering and aberrations, DReAM offered a 17-fold enhancement of single scattering–to–multiple scattering ratio and provided high-contrast images of neural fibers in the brain cortex with the diffraction-limited spatial resolution of 412 nanometers and a 33-fold enhanced Strehl ratio.

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An adaptive optics module for deep tissue multiphoton imaging in vivo

Cited by 73 publications

References 40 publications

Roadmap on wavefront shaping and deep imaging in complex media

Roadmap on wavefront shaping and deep imaging in complex media

A Long‐Term Clearing Cranial Window for Longitudinal Imaging of Cortical and Calvarial Ischemic Injury through the Intact Skull

Through-skull brain imaging in vivo at visible wavelengths via dimensionality reduction adaptive-optical microscopy

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