Bit-efficient, sub-millisecond wavefront measurement using a lock-in camera for time-reversal based optical focusing inside scattering media

Time-reversed ultrasonically encoded optical focusing measures the wavefront of ultrasonically tagged light, and then phase conjugates the tagged light back to the ultrasonic focus, thus focusing light deep inside the scattering media. In previous works, the speed of wavefront measurement was limited by the low frame rates of conventional cameras. In addition, these cameras used most of their bits to represent an informationless background when the signal-to-background ratio was low, resulting in extremely low efficiencies in the use of bits. Here, using a lock-in camera, we increase the bit efficiency and reduce the data transfer load by digitizing only the signal after rejecting the background. With this camera, we obtained the wavefront of ultrasonically tagged light after a single frame of measurement taken within 0.3 ms, and focused light in between two diffusers. The phase sensitivity has reached 0.51 rad even when the SBR is 6×10^(−4)

Focusing light through scattering media by full-polarization digital optical phase conjugation

Digital optical phase conjugation (DOPC) is an emerging technique for focusing light through or within scattering media such as biological tissue. Since DOPC systems are based on time reversal, they benefit from collecting as much information about the scattered light as possible. However, existing DOPC techniques record and subsequently phase-conjugate the scattered light in only a single-polarization state, limited by the operating principle of spatial light modulators. Here, we develop the first, to the best of our knowledge, full-polarization DOPC system that records and phase-conjugates scattered light along two orthogonal polarizations. When focusing light through thick scattering media, such as 2 mm and 4 mm-thick chicken breast tissue, our full-polarization DOPC system on average doubles the focal peak-to-background ratio achieved by single-polarization DOPC systems and improves the phase-conjugation fidelity

Suppressing excitation effects in microwave induced thermoacoustic tomography by multi-view Hilbert transformation

Microwave induced thermoacoustic tomography (TAT) images usually suffer from distortions arising from the microwave polarization effect and standing wave effect. The microwave polarization effect, resulting from linearly polarized microwave illumination, splits the image of the object along the polarization direction, while the standing wave effect, when the object size is larger than the microwave wavelength within the object, modulates the image of the object. Both effects cause non-uniform energy distribution in a uniformly absorbing object and create artifacts in the reconstructed images. To address these problems in TAT, we propose an image reconstruction method that combines multi-view Hilbert transformation with the back-projection algorithm. We experimentally validate this method by imaging breast and brain tumor phantoms, showing that the aforementioned distortions are significantly suppressed. We anticipate that this method will contribute to clinical tumor diagnosis

Sub-Nyquist sampling boosts targeted light transport through opaque scattering media

Optical time-reversal techniques are being actively developed to focus light through or inside opaque scattering media. When applied to biological tissue, these techniques promise to revolutionize biophotonics by enabling deep-tissue non-invasive optical imaging, optogenetics, optical tweezing, and phototherapy. In all previous optical time-reversal experiments, the scattered light field was well-sampled during wavefront measurement and wavefront reconstruction, following the Nyquist sampling criterion. Here, we overturn this conventional practice by demonstrating that even when the scattered field is under-sampled, light can still be focused through or inside scattering media. Even more surprisingly, we show both theoretically and experimentally that the focus achieved by under-sampling can be one order of magnitude brighter than that achieved under the well-sampling conditions used in previous works, where 3×3 to 5×5 pixels were used to sample one speckle grain on average. Moreover, sub-Nyquist sampling improves the signal-to-noise ratio and the collection efficiency of the scattered light. We anticipate that this newly explored under-sampling scheme will transform the understanding of optical time reversal and boost the performance of optical imaging, manipulation, and communication through opaque scattering media

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

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

Homogenizing microwave illumination in thermoacoustic tomography by a linear-to-circular polarizer based on frequency selective surfaces

A circularly polarized antenna, providing more homogeneous illumination compared to a linearly polarized antenna, is more suitable for microwave induced thermoacoustic tomography (TAT). The conventional realization of a circular polarization is by using a helical antenna, but it suffers from low efficiency, low power capacity, and limited aperture in TAT systems. Here, we report an implementation of a circularly polarized illumination method in TAT by inserting a single-layer linear-to-circular polarizer based on frequency selective surfaces between a pyramidal horn antenna and an imaging object. The performance of the proposed method was validated by both simulations and experimental imaging of a breast tumor phantom. The results showed that a circular polarization was achieved, and the resultant thermoacoustic signal-to-noise was twice greater than that in the helical antenna case. The proposed method is more desirable in a waveguide-based TAT system than the conventional method

Focusing light through scattering media by polarization modulation based generalized digital optical phase conjugation

Optical scattering prevents light from being focused through thick biological tissue at depths greater than ∼1 mm. To break this optical diffusion limit, digital optical phase conjugation (DOPC) based wavefront shaping techniques are being actively developed. Previous DOPC systems employed spatial light modulators that modulated either the phase or the amplitude of the conjugate light field. Here, we achieve optical focusing through scattering media by using polarization modulation based generalized DOPC. First, we describe an algorithm to extract the polarization map from the measured scattered field. Then, we validate the algorithm through numerical simulations and find that the focusing contrast achieved by polarization modulation is similar to that achieved by phase modulation. Finally, we build a system using an inexpensive twisted nematic liquid crystal based spatial light modulator (SLM) and experimentally demonstrate light focusing through 3-mm thick chicken breast tissue. Since the polarization modulation based SLMs are widely used in displays and are having more and more pixel counts with the prevalence of 4 K displays, these SLMs are inexpensive and valuable devices for wavefront shaping

PO-272 Cancer immunotherapy impedes skeletal muscle repair

Objective To observe the difference of the capacity of skeletal muscle repair and the corresponding immune response in melanoma mice treated with cancer immunotherapy after acute skeletal muscle contusion. Methods  96 males C57BL/6 mice were used in this experiment. They were divided into control group and injury group. The control group included normal control group (C group, n = 8), tumor control group (T group, n = 8) and tumor immunotherapy group (A group, n = 8).The skeletal muscle injury group was divided into normal injury group (D group, n = 24), tumor mice injury group (DT group, n = 24) and cancer immunotherapy injury group (DA group, n = 24). B16 cells were injected subcutaneously into the dorsum of C57/BL mice to prepare melanoma mice model. Immunotherapy is the injection of anti CTLA-4 and anti PD-1 antibodies. The model of gastrocnemius muscle contusion was established. At different time points after damage, mice were sacrificed. The gastrocnemius muscle of mice was made into cryosections. After HE staining and Mason staining, the regeneration of skeletal muscle and the healing of fibrotic scar were observed. The expression of CD8 T Cells and Regulatory T Cells (Treg) were detected by immunofluorescence. Results 1.H&E staining of muscle slices at 7 days after injury showed that myofibers in the non-injured muscles are polygonal in shape with peripheral nuclei. Quantitative evaluation of the skeletal muscle in the cancer immunotherapy injury group (DA group) showed that the number of centrally nucleated fibers was significantly lower than that in the other injury groups（D group，DT group）and there was an enlarged interstitial space. Immunotherapy leads to greater muscle degeneration: vacuolated myofibers could be seen. Collagen deposition was detected by Masson trichrome staining, and collagen deposits were found in the injury group. However, the regenerated muscles of the cancer immunotherapy injury group (DA group) showed more collagen deposits than those of the other injury groups（D group，DT group）, no collagen deposits were found in the control group. On 14 day after injury, the density of muscle fibers in the other injury groups（D group，DT group） was higher than that in immunotherapy group (DA group), which was about 1.5 times of that in immunotherapy group (DA group). The other injury groups（D group，DT group） showed a larger proportion of regenerated muscle fibers with different diameters, whereas the cancer immunotherapy injury group (DA group) had fewer regenerated muscle fibers. Compared with the control group, the mice in the other injury groups（D group，DT group）still had a small amount of collagen deposits, the mice in the cancer immunotherapy injury group (DA group) had more collagen deposits. 3.On 21 day after injury, the average diameter on 21 day higher than that on day 7 in the three injury groups. The mean muscle fiber diameter in the other injury groups（D group，DT group） was significantly larger than that in the immunotherapy injury group. In addition, the regenerated muscle fibers in the other injury groups（D group，DT group） showed better organization and basically returned to normal compared with the immunotherapy group (DA group). There were still some collagen deposits in the immunotherapy group (DA group) mice, but no collagen deposits were found in the other injury groups（D group，DT group）mice. 4.Immunofluorescence staining showed that CD8 T cells were continuously expressed and no Treg cells were found in the immunotherapy group (DA group) mice at 7, 14 and 21 days after contusion. In the other injury groups（D group，DT group）, Treg and CD8 T cells were expressed in skeletal muscle tissue adjacent to the regenerated muscle fibers on 7 days. On day 14, a small number of CD8 T cells and a large number of Treg cells infiltrated the damaged muscles. On day 21, almost no CD8 T cells were detected, and Treg cells continued to express. There was no expression of Treg cells and CD8 T cells in the control group. Conclusions Cancer immunotherapy will delay the repair of damaged skeletal muscle and reduce the capacity of skeletal muscle repair and regeneration. &nbsp