Breaking the spatial resolution barrier via iterative sound-light interaction in deep tissue microscopy

TL;DR

This paper introduces an iterative light focusing method using phase conjugation to surpass traditional resolution limits in deep tissue fluorescence microscopy, enabling high-resolution imaging beyond the ballistic regime.

Contribution

It presents a novel iterative focusing technique that overcomes the spatial resolution barrier in deep tissue imaging by combining light and sound interactions.

Findings

Achieved threefold resolution improvement in deep tissue fluorescence microscopy.

Realized fivefold increase in image contrast.

Demonstrated practical deep tissue high-resolution imaging.

Abstract

Optical microscopy has so far been restricted to superficial layers, leaving many important biological questions unanswered. Random scattering causes the ballistic focus, which is conventionally used for image formation, to decay exponentially with depth. Optical imaging beyond the ballistic regime has been demonstrated by hybrid techniques that combine light with the deeper penetration capability of sound waves. Deep inside highly scattering media, the sound focus dimensions restrict the imaging resolutions. Here we show that by iteratively focusing light into an ultrasound focus via phase conjugation, we can fundamentally overcome this resolution barrier in deep tissues and at the same time increase the focus to background ratio. We demonstrate fluorescence microscopy beyond the ballistic regime of light with a threefold improved resolution and a fivefold increase in contrast. This development opens up practical high resolution fluorescence imaging in deep tissues.