Optical focusing inside scattering media with iterative time-reversed ultrasonically encoded near-infrared light.

Focusing light inside scattering media is a long-sought goal in optics. Time-reversed ultrasonically encoded (TRUE) focusing, which combines the advantages of biological transparency of the ultrasound and the high efficiency of digital optical phase conjugation (DOPC) based wavefront shaping, has been proposed to tackle this problem. By invoking repeated acousto-optic interactions, iterative TRUE (iTRUE) focusing can further break the resolution barrier imposed by the acoustic diffraction limit, showing great potential for deep-tissue biomedical applications. However, stringent requirements on system alignment prohibit the practical use of iTRUE focusing, especially for biomedical applications at the near-infrared spectral window. In this work, we fill this blank by developing an alignment protocol that is suitable for iTRUE focusing with a near-infrared light source. This protocol mainly contains three steps, including rough alignment with manual adjustment, fine-tuning with a high-precision motorized stage, and digital compensation through Zernike polynomials. Using this protocol, an optical focus with a peak-to-background ratio (PBR) of up to 70% of the theoretical value can be achieved. By using a 5-MHz ultrasonic transducer, we demonstrated the first iTRUE focusing using near-infrared light at 1053 nm, enabling the formation of an optical focus inside a scattering medium composed of stacked scattering films and a mirror. Quantitatively, the size of the focus decreased from roughly 1 mm to 160 µm within a few consecutive iterations and a PBR up to 70 was finally achieved. We anticipate that the capability of focusing near-infrared light inside scattering media, along with the reported alignment protocol, can be beneficial to a variety of applications in biomedical optics.

Coaxial interferometry for camera-based ultrasound-modulated optical tomography with paired illumination.

Ultrasound-modulated optical tomography (UOT), which combines the advantages of both light and ultrasound, is a promising imaging modality for deep-tissue high-resolution imaging. Among existing implementations, camera-based UOT gains huge advances in modulation depth through parallel detection. However, limited by the long exposure time and the slow framerate of modern cameras, the measurement of UOT signals always requires holographic methods with additional reference beams. This requirement increases system complexity and is susceptible to environmental disturbances. To overcome this challenge, we develop coaxial interferometry for camera-based UOT in this work. Such a coaxial scheme is enabled by employing paired illumination with slightly different optical frequencies. To measure the UOT signal, the conventional phase-stepping method in holography can be directly transplanted into coaxial interferometry. Specifically, we performed both numerical investigations and experimental validations for camera-based UOT under the proposed coaxial scheme. One-dimensional imaging for an absorptive target buried inside a scattering medium was demonstrated. With coaxial interferometry, this work presents an effective way to reduce system complexity and cope with environmental disturbances for camera-based UOT.

Modeling of iterative time-reversed ultrasonically encoded optical focusing in a reflection mode.

Time-reversed ultrasonically-encoded (TRUE) optical focusing is a promising technique to realize deep-tissue optical focusing by employing ultrasonic guide stars. However, the sizes of the ultrasound-induced optical focus are determined by the wavelengths of the ultrasound, which are typically tens of microns. To satisfy the need for high-resolution imaging and manipulation, iterative TRUE (iTRUE) was proposed to break this limit by triggering repeated interactions between light and ultrasound and compressing the optical focus. However, even for the best result reported to date, the resolutions along the ultrasound axial and lateral direction were merely improved by only 2-fold to 3-fold. This observation leads to doubt whether iTRUE can be effective in reducing the size of the optical focus. In this work, we address this issue by developing a physical model to investigate iTRUE in a reflection mode numerically. Our numerical results show that, under the influence of shot noises, iTRUE can reduce the optical focus to a single speckle within a finite number of iterations. This model also allows numerical investigations of iTRUE in detail. Quantitatively, based on the parameters set, we show that the optical focus can be reduced to a size of 1.6 µm and a peak-to-background ratio over 104 can be realized. It is also shown that iTRUE cannot significantly advance the focusing depth. We anticipate that this work can serve as useful guidance for optimizing iTRUE system for future biomedical applications, including deep-tissue optical imaging, laser surgery, and optogenetics.