Focusing on moving targets through scattering samples

Focusing light through scattering media has been a longstanding goal of biomedical optics. While wavefront shaping and optical time-reversal techniques can in principle be used to focus light across scattering media, achieving this within a scattering medium with a noninvasive and efficient reference beacon, or guide star, remains an important challenge. Here, we show optical time-reversal focusing using a new technique termed Time Reversal by Analysis of Changing wavefronts from Kinetic targets (TRACK). By taking the difference between time-varying scattering fields caused by a moving object and applying optical time reversal, light can be focused back to the location previously occupied by the object. We demonstrate this approach with discretely moved objects as well as with particles in an aqueous flow, and obtain a focal peak-to-background strength of 204 in our demonstration experiments. We further demonstrate that the generated focus can be used to noninvasively count particles in a flow-cytometry configuration—even when the particles are hidden behind a strong diffuser. By achieving optical time reversal and focusing noninvasively without any external guide stars, using just the intrinsic characteristics of the sample, this work paves the way to a range of scattering media imaging applications, including underwater and atmospheric focusing as well as noninvasive in vivo flow cytometry

Focusing light through scattering media by transmission matrix inversion

Focusing light through scattering media has broad applications in optical imaging, manipulation and therapy. The contrast of the focus can be quantified by peak-to-background intensity ratio (PBR). Here, we theoretically and numerically show that by using a transmission matrix inversion method to achieve focusing, within a limited field of view and under a low noise condition in transmission matrix measurements, the PBR of the focus can be higher than that achieved by conventional methods such as optical phase conjugation or feedback-based wavefront shaping. Experimentally, using a phase-modulation spatial light modulator, we increase the PBR by 66% over that achieved by conventional methods based on phase conjugation. In addition, we demonstrate that, within a limited field of view and under a low noise condition in transmission matrix measurements, our matrix inversion method enables light focusing to multiple foci with greater fidelity than those of conventional methods

Method for auto-alignment of digital optical phase conjugation systems based on digital propagation

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~1.5 cm, rotation and tip/tilt of ~5∘, and in-plane displacement of ~5 mm (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

GATA binding protein 2 mediates leptin inhibition of PPARγ1 expression in hepatic stellate cells and contributes to hepatic stellate cell activation

AbstractHepatic stellate cell (HSC) activation is a crucial step in the development of liver fibrosis. Peroxisome-proliferator activated receptor γ (PPARγ) exerts a key role in the inhibition of HSC activation. Leptin reduces PPARγ expression in HSCs and plays a unique role in promoting liver fibrosis. The present studies aimed to investigate the mechanisms underlying leptin regulation of PPARγ1 (a major subtype of PPARγ) in HSCs in vivo and in vitro. Results revealed a leptin response region in mouse PPARγ1 promoter and indicated that the region included a GATA binding protein binding site around position −2323. GATA binding protein-2 (GATA-2) could bind to the site and inhibit PPARγ1 promoter activity in HSCs. Leptin induced GATA-2 expression in HSCs in vitro and in vivo. GATA-2 mediated leptin inhibition of PPARγ1 expression by its binding site in PPARγ1 promoter in HSCs and GATA-2 promoted HSC activation. Leptin upregulated GATA-2 expression through β-catenin and sonic hedgehog pathways in HSCs. Leptin-induced increase in GATA-2 was accompanied by the decrease in PPARγ expression in HSCs and by the increase in the activated HSC number and liver fibrosis in vivo. Our data might suggest a possible new explanation for the promotion effect of leptin on liver fibrogenesis

Glare suppression by coherence gated negation

Imaging of a weak target hidden behind a scattering medium can be significantly confounded by glare. We report a method, termed coherence gated negation (CGN), that uses destructive optical interference to suppress glare and allow improved imaging of a weak target. As a demonstration, we show that by permuting through a set range of amplitude and phase values for a reference beam interfering with the optical field from the glare and target reflection, we can suppress glare by an order of magnitude, even when the optical wavefront is highly disordered. This strategy significantly departs from conventional coherence gating methods in that CGN actively 'gates out' the unwanted optical contributions while conventional methods 'gate in' the target optical signal. We further show that the CGN method can outperform conventional coherence gating image quality in certain scenarios by more effectively rejecting unwanted optical contributions.Comment: main article (14 pages) and appendices (3 pages

Uplift Modeling based on Graph Neural Network Combined with Causal Knowledge

Uplift modeling is a fundamental component of marketing effect modeling, which is commonly employed to evaluate the effects of treatments on outcomes. Through uplift modeling, we can identify the treatment with the greatest benefit. On the other side, we can identify clients who are likely to make favorable decisions in response to a certain treatment. In the past, uplift modeling approaches relied heavily on the difference-in-difference (DID) architecture, paired with a machine learning model as the estimation learner, while neglecting the link and confidential information between features. We proposed a framework based on graph neural networks that combine causal knowledge with an estimate of uplift value. Firstly, we presented a causal representation technique based on CATE (conditional average treatment effect) estimation and adjacency matrix structure learning. Secondly, we suggested a more scalable uplift modeling framework based on graph convolution networks for combining causal knowledge. Our findings demonstrate that this method works effectively for predicting uplift values, with small errors in typical simulated data, and its effectiveness has been verified in actual industry marketing data.Comment: 6 pages, 6 figure

Focusing through dynamic tissue with millisecond digital optical phase conjugation

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 ∼200  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 ∼30  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

Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light

Noninvasive light focusing deep inside living biological tissue has long been a goal in biomedical optics. However, the optical scattering of biological tissue prevents conventional optical systems from tightly focusing visible light beyond several hundred micrometers. The recently developed wavefront shaping technique time-reversed ultrasonically encoded (TRUE) focusing enables noninvasive light delivery to targeted locations beyond the optical diffusion limit. However, until now, TRUE focusing has only been demonstrated inside nonliving tissue samples. We present the first example of TRUE focusing in 2-mm-thick living brain tissue and demonstrate its application for optogenetic modulation of neural activity in 800-μm-thick acute mouse brain slices at a wavelength of 532 nm. We found that TRUE focusing enabled precise control of neuron firing and increased the spatial resolution of neuronal excitation fourfold when compared to conventional lens focusing. This work is an important step in the application of TRUE focusing for practical biomedical uses