High-speed single-exposure time-reversed ultrasonically encoded optical focusing against dynamic scattering

Abstract

Focusing light deep inside live scattering tissue promises to revolutionize biophotonics by enabling deep tissue noninvasive optical imaging, manipulation, and therapy. By combining with guide stars, wavefront shaping is emerging as a powerful tool to make scattering media optically transparent. However, for in vivo biomedical applications, the speeds of existing techniques are still too slow to accommodate the fast speckle decorrelation of live tissue. To address this key bottleneck, we develop a quaternary phase encoding scheme to enable single-exposure time-reversed ultrasonically encode optical focusing with full-phase modulations. Specifically, we focus light inside dynamic scattering media with an average mode time down to 29 ns, which indicates that more than 10⁴ effective spatial modes can be controlled within 1 millisecond. With this technique, we demonstrate in vivo light focusing in between a highly opaque adult zebrafish of 5.1 millimeters in thickness and a ground glass diffuser. Our work presents an important step toward in vivo deep tissue applications of wavefront shaping.

Fig. 1.. A scatter plot comparing the performance (the number of independent wavefront modulation elements and the average mode time) of different high-speed wavefront shaping systems in the literature.

Fig. 2.. Principle of the single-exposure TRUE optical focusing.

(A) Schematic illustration of the method for determining the wavefront of the ultrasonically tagged light. BS, beam splitter; GPU, graphics processing unit; L, lens; R, reference beam; S, signal beam; SM, scattering medium; UT, ultrasonic transducer. (B) Speckle pattern is formed by both ultrasonically tagged light and untagged light. (C) QPEM. (D) Retrieved phase map of the ultrasonically tagged light.

Fig. 3.. Experimental setup of the single-exposure TRUE optical focusing.

(A) Recording step. (B) Playback step. AOM, acousto-optical modulator; BB, beam block; HWP, half-wave plate; M, mirror; PBS, polarizing BS; S, sample beam; US focus, ultrasonic focus.

Fig. 4.. Quantification of the system latency through DOPC.

(A to D) Camera captured optical foci through the dynamic scattering media with correlation times of 10, 8, 5, and 2 ms, respectively. Scale bar, 100 μm. (E) Normalized PBR as a function of the speckle correlation time. Error bars show the SD of three measurements. Fitting curve: exp{−2[5.5 (ms)/τ_c]²}.

Fig. 5.. Experimental demonstration of TRUE optical focusing in between a live adult zebrafish and a ground glass diffuser.

(A) Illustrative scheme of TRUE optical focusing, where we focus light inside a composite scattering medium composed of a ground glass diffuser (GD) and a live adult zebrafish. A camera is placed aside to capture the TRUE focus. Inset: A photo of the zebrafish captured during the experiments. The position of the illumination spot is labeled with a black circle. (B) Typical speckle correlation curve measured for the live adult zebrafish. Speckle correlation time is estimated to be around 46 ms. (C) Camera-captured image of the TRUE optical focus. PBR is estimated to be ~9.1. Scale bar, 300 μm. (D) Demonstration of the continuous mode of operation, which has a repetition rate of 10 Hz (100-ms cycle time). Four representative points that correspond to the measured peak intensity are recorded for each cycle and plotted for a 1-s duration.

Fig. 6.. Workflow of the single-exposure TRUE optical focusing.