High-resolution adaptive optical imaging within thick scattering media using closed-loop accumulation of single scattering

Abstract

Thick biological tissues give rise to not only the multiple scattering of incoming light waves, but also the aberrations of remaining signal waves. The challenge for existing optical microscopy methods to overcome both problems simultaneously has limited sub-micron spatial resolution imaging to shallow depths. Here we present an optical coherence imaging method that can identify aberrations of waves incident to and reflected from the samples separately, and eliminate such aberrations even in the presence of multiple light scattering. The proposed method records the time-gated complex-field maps of backscattered waves over various illumination channels, and performs a closed-loop optimization of signal waves for both forward and phase-conjugation processes. We demonstrated the enhancement of the Strehl ratio by more than 500 times, an order of magnitude or more improvement over conventional adaptive optics, and achieved a spatial resolution of 600 nm up to an imaging depth of seven scattering mean free paths.

Deep optical imaging within complex scattering media

“…6f), a signal in an aberration-corrected CLASS image (Fig. 6g) was increased more than 20-fold 126 . The finest structures in the resolution target are also clearly visible, confirming the recovery of near-diffraction-limited spatial resolution.…”

“…In this section, we first introduce methods that simultaneously suppress multiple scattering and sample-induced aberrations without using guide stars and then describe approaches based on the coherent superposition of MS waves. Subsequently, a method termed closed-loop accumulation of single scattering (CLASS) 126 was developed that separately identifies the aberrations in SS waves incident on and reflected from an object, even in the presence of multiple light scattering. Using an experimental set-up similar to that used in CASS microscopy, complex-field images of backscattered waves, E(r o ,k i ;τ 0 ), were measured at a conjugate image plane for a set of wavevectors {k i } that cover all of the orthogonal input free modes, where r o is the position vector in image coordinates.…”

“…Optical-scale imaging using acousto-optic interactions and the selective detection of single optical speckles is advancing towards realistic conditions in which the speckle grain size reaches half of the wavelength 121,124 . High-resolution imaging based on a time-gated reflection matrix is also starting to gain control of MS waves in reconstructing the object image 126,127,139 . Additionally, improvements in the sensitivity and speed of cameras and the increase in the number of pixels and control speed of the SLM will help to resolve some of the practical issues.…”

Light scattering control in transmission and reflection with neural networks

“…Alternatively, back-scattered excitation light can provide feedback about the beam [53][54][55]. These signals need to be additionally filtered to remove out-of-focus light and using various combinations of temporal, frequency, or spatial gating [53][54][55][56][57][58][59] one aims for extracting photons that are scattered little and therefore retain image information. Since such weakly scattered photons disappear exponentially with depth, they in turn limit imaging depth.…”

Deep tissue space-gated microscopy via acousto-optic interaction

“…Similarly, spatial correlation within a time-gated transmission or reflection matrix has recently been used to selectively extract image information 12,13 . Furthermore, various adaptive optics approaches have been proposed to maintain the effectiveness of gating operations in spite of sampleinduced aberration [14][15][16][17] .…”