Focusing light through biological tissue and tissue-mimicking phantoms up to 9.6 cm in thickness with digital optical phase conjugation

Abstract

Optical phase conjugation (OPC)-based wavefront shaping techniques focus light through or within scattering media, which is critically important for deep-tissue optical imaging, manipulation, and therapy. However, to date, the sample thickness in OPC experiments has been limited to only a few millimeters. Here, by using a laser with a long coherence length and an optimized digital OPC system that can safely deliver more light power, we focused 532-nm light through tissue-mimicking phantoms up to 9.6 cm thick, as well as through ex vivo chicken breast tissue up to 2.5 cm thick. Our results demonstrate that OPC can be achieved even when photons have experienced on average 1000 scattering events. The demonstrated penetration of nearly 10 cm (∼100 transport mean free paths) has never been achieved before by any optical focusing technique, and it shows the promise of OPC for deep-tissue noninvasive optical imaging, manipulation, and therapy.

Fig. 1

Illustration of OPC. (a) A narrow beam illuminates a scattering medium and is scattered inside the medium. The distorted wave coming out of the medium is intercepted by a PCM. (b) The PCM generates phase conjugated light, which retraces the original path back through the scattering medium and recovers the narrow incident beam.

Fig. 2

Schematic of the digital OPC system. AOM, acousto-optic modulator; BB, beam block; BS, beamsplitter; CL, camera lens; HWP, half-wave plate; L, lens; M, mirror; MLS, motorized linear stage; P, polarizer; PBS, polarizing beamsplitter; R, reference beam; S, sample beam; sCMOS, scientific CMOS camera; SLM, spatial light modulator.

Fig. 3

(a) Side view of two chicken breast tissue samples with 2.5 and 2.0 cm thicknesses. A cubic beamsplitter with a side length of 2.0 cm is also shown for comparison. (b) Images of the OPC foci after light has passed through chicken breast tissue of various thicknesses. (c) PBR as a function of sample thickness. The error bar shows the standard deviation obtained from three samples of the same thickness.

Fig. 4

(a) Side view of the intralipid-galetin phantoms with 9.6 cm and 8.5 cm thicknesses. A forearm of a 28-year-old male adult is also shown for comparison. (b) Images of the OPC foci after light has passed through phantoms of various thicknesses. (c) PBR as a function of sample thickness. The error bar shows the standard deviation obtained from three samples of the same thickness.

Fig. 5

(a) Schematic of photon paths to reach the location denoted by the red dot in a scattering medium. (b) Normalized photon fluence rate as a function of time delay $t$ at a given position $r$.

Fig. 6

PDF of the phase errors calculated from ${10}^6$ data points in one simulated phase map. The simulation parameters were chosen based on the experimental conditions with the 2.5-cm-thick chicken tissue sample.

Fig. 7

Experimentally measured average transmitted sample light power detected on each camera pixel (expressed in number of photoelectrons) as a function of sample thickness. Based on curve fitting, the decay constant is $2.7{\mathrm{cm}}^{-1}$.

Fig. 8

PDFs of phase errors in the simulated phase maps for chicken tissue samples with thicknesses ranging from 3.0 cm to 6.0 cm.

Fig. 9

PBR reduction coefficient $\eta$ and the SNR as a function of chicken tissue sample thickness.