Digital optical phase conjugation (DOPC) is a new technique employed in wavefront shaping and phase conjugation for focusing light through or within scattering media such as biological tissues. DOPC is particularly attractive as it intrinsically achieves a high fluence reflectivity in comparison to nonlinear optical approaches. However, the slow refresh rate of liquid crystal spatial light modulators and limitations imposed by computer data transfer speeds have thus far made it difficult for DOPC to achieve a playback latency of shorter than $\sim 200\mathrm{ms}$ and, therefore, prevented DOPC from being practically applied to thick living samples. In this paper, we report a novel DOPC system that is capable of 5.3 ms playback latency. This speed improvement of almost 2 orders of magnitude is achieved by using a digital micromirror device, field programmable gate array (FPGA) processing, and a single-shot binary phase retrieval technique. With this system, we are able to focus through 2.3 mm living mouse skin with blood flowing through it (decorrelation time $\sim 30\mathrm{ms}$) and demonstrate that the focus can be maintained indefinitely—an important technological milestone that has not been previously reported, to the best of our knowledge.

Light scattering in biological tissue significantly limits the accessible depth for localized optical interrogation and deep-tissue optical imaging. This challenge can be overcome by exploiting the time-reversal property of optical phase conjugation (OPC) to reverse multiple scattering events or suppress turbidity. However, in living tissue, scatterers are highly movable and the movement can disrupt time-reversal symmetry when there is a latency in the OPC playback. In this paper, we show that the motion-induced degradation of the OPC turbidity-suppression effect through a dynamic scattering medium shares the same decorrelation time constant as that determined from speckle intensity autocorrelation – a popular conventional measure of scatterer movement. We investigated this decorrelation characteristic time through a 1.5-mm-thick dorsal skin flap of a living mouse and found that it ranges from 50 ms to 2.5 s depending on the level of immobilization. This study provides information on relevant time scales for applying OPC to living tissues.

Using ultrasound-guided optical wavefront shaping, the authors show enhanced optogenetic control in thick acute brain slices.

Optical phase conjugation (OPC) has enabled many optical applications such as aberration correction and image transmission through fiber. In recent years, implementation of digital optical phase conjugation (DOPC) has opened up the possibility of its use in biomedical optics (e.g. deep-tissue optical focusing) due to its ability to provide greater-than-unity OPC reflectivity (the power ratio of the phase conjugated beam and input beam to the OPC system) and its flexibility to accommodate additional wavefront manipulations. However, the requirement for precise (pixel-to-pixel matching) alignment of the wavefront sensor and the spatial light modulator (SLM) limits the practical usability of DOPC systems. Here, we report a method for auto-alignment of a DOPC system by which the misalignment between the sensor and the SLM is auto-corrected through digital light propagation. With this method, we were able to accomplish OPC playback with a DOPC system with gross sensor-SLM misalignment by an axial displacement of up to$~1.5cm$, rotation and tip/tilt of $~5^{\circ }$, and in-plane displacement of $~5mm$ (dependent on the physical size of the sensor and the SLM). Our auto-alignment method robustly achieved a DOPC playback peak-to-background ratio (PBR) corresponding to more than $~30\%$ of the theoretical maximum. As an additional advantage, the auto-alignment procedure can be easily performed at will and, as such, allows us to correct for small mechanical drifts within the DOPC systems, thus overcoming a previously major DOPC system vulnerability. We believe that this reported method for implementing robust DOPC systems will broaden the practical utility of DOPC systems.

Focusing light inside scattering media in a freely addressable fashion is challenging, as the wavefront of the scattered light is highly disordered. Recently developed ultrasound-guided wavefront shaping methods are addressing this challenge, albeit with relatively low modulation efficiency and resolution limitations. In this paper, we present a new technique, time-reversed ultrasound microbubble encoded (TRUME) optical focusing, which can focus light with improved efficiency and sub-ultrasound wavelength resolution. This method ultrasonically destroys microbubbles, and measures the wavefront change to compute and render a suitable time-reversed wavefront solution for focusing. We demonstrate that the TRUME technique can create an optical focus at the site of bubble destruction with a size of ∼2 μm. We further demonstrate a twofold enhancement in addressable focus resolution in a microbubble aggregate target by exploiting the nonlinear pressure-to-destruction response of the microbubbles. The reported technique provides a deep tissue-focusing solution with high efficiency, resolution, and specificity.