Turbidity Suppression Research Articles

All-optical phase conjugation using diffractive wavefront processing

Optical phase conjugation (OPC) is a nonlinear technique used for counteracting wavefront distortions, with applications ranging from imaging to beam focusing. Here, we present a diffractive wavefront processor to approximate all-optical phase conjugation. Leveraging deep learning, a set of diffractive layers was optimized to all-optically process an arbitrary phase-aberrated input field, producing an output field with a phase distribution that is the conjugate of the input wave. We experimentally validated this wavefront processor by 3D-fabricating diffractive layers and performing OPC on phase distortions never seen during training. Employing terahertz radiation, our diffractive processor successfully performed OPC through a shallow volume that axially spans tens of wavelengths. We also created a diffractive phase-conjugate mirror by combining deep learning-optimized diffractive layers with a standard mirror. Given its compact, passive and multi-wavelength nature, this diffractive wavefront processor can be used for various applications, e.g., turbidity suppression and aberration correction across different spectral bands.

Molecularly Specific and Functional Live Cell Imaging by Label-Free Interference Microscopy

Optical interference microscopy is a powerful bioimaging technique by measuring the complex light fields associated with the specimen. Nowadays, the state-of-the-art interference microscopy makes it possible to directly visualize very small single biological nanoparticles and unlabeled macromolecules. The stable and indefinite linear scattering signal allows for continuous observation of the sample at a high speed, offering the opportunities to investigate single-molecule biophysics with the unprecedented details. Meanwhile, using interference microscopy to explore complex biological samples, such as a biological cell, emerges as an exciting research field. In this Perspective, we share our views on the impacts of optical interference microscopy on live cell imaging. Strategies for discriminating the scattering signals from different cell organelles and biological macromolecules are presented. In particular, the dynamic optical signal of live cells contains rich temporal information that is useful for enhancing the molecular specificity and functional information in label-free cell imaging. Finally, the challenges in three-dimensional imaging and turbidity suppression are discussed.

Detailed study on ill-conditioned transmission matrices when focusing light through scattering media based on wavefront shaping

Recent advances in wavefront shaping, i.e., wavefront modulated by a spatial light modulator, have opened hopeful venues to focus light through scattering media in particular and unparalleled ways, by means of codifying the values of pixels of the modulator. The transmission matrix approach is one of the most exciting recent advances to obtain optimal phase distributions, due to the consent of enabling turbidity suppression, in both transmitted and reflected waves, with high resolution and large efficiency. However, the transmission matrix is ill-conditioned, which seriously affects the precision of phase distributions. In this paper, we study the ill-condition of the transmission matrix in detail. An idea of optimizing the singular values of the transmission matrix is proposed, which improves the accuracy and stability of the phase distribution. Experiments verify this idea.

Implementation of an Off-Axis Digital Optical Phase Conjugation System for Turbidity Suppression on Scattering Medium

Due to the light scattering effect, it is difficult to directly achieve optical focusing and imaging in turbid media, such as milk and biological tissue. The turbidity suppression of a scattering medium and control of light through the scattering medium are important for imaging on biological tissue or biophotonics. Optical phase conjugation is a novel technology on turbidity suppression by directly creating phase conjugation light waves to form time-reversed light. In this work, we report a digital optical phase conjugation system based on off-axis holography. Compared with traditional digital optical phase conjugation methods, the off-axis holography acquires the conjugation phase using only one interference image, obviously saving photo acquisition time. Furthermore, we tested the optical phase conjugate reduction performance of this system and also achieved optical focusing through the diffuser. We also proved that the reversing of random scattering in turbid media is achievable by phase conjugation.

Axially shifted pattern illumination for macroscale turbidity suppression and virtual volumetric confocal imaging without axial scanning

Structured illumination has been widely used for optical sectioning and 3D surface recovery. In a typical implementation, multiple images under non-uniform pattern illumination are used to recover a single object section. Axial scanning of the sample or the objective lens is needed for acquiring the 3D volumetric data. Here we demonstrate the use of axially shifted pattern illumination for virtual volumetric confocal imaging without axial scanning. In the reported approach, we project illumination patterns at a tilted angle with respect to the detection optics. As such, the illumination patterns shift laterally at different z sections, and the 3D sample information can be recovered based on the captured 2D images. We demonstrate the reported approach for virtual confocal imaging through a diffusing layer and underwater 3D imaging through diluted milk. We show that we can acquire the entire confocal volume in ∼1 s with a throughput of 420 megapixels per second. Our approach may provide new insights for developing confocal light ranging and detection systems in degraded visual environments.

Relation between speckle decorrelation and optical phase conjugation (OPC)-based turbidity suppression through dynamic scattering media: a study on in vivo mouse skin.

Light scattering in biological tissue significantly limits the accessible depth for localized optical interrogation and deep-tissue optical imaging. This challenge can be overcome by exploiting the time-reversal property of optical phase conjugation (OPC) to reverse multiple scattering events or suppress turbidity. However, in living tissue, scatterers are highly movable and the movement can disrupt time-reversal symmetry when there is a latency in the OPC playback. In this paper, we show that the motion-induced degradation of the OPC turbidity-suppression effect through a dynamic scattering medium shares the same decorrelation time constant as that determined from speckle intensity autocorrelation - a popular conventional measure of scatterer movement. We investigated this decorrelation characteristic time through a 1.5-mm-thick dorsal skin flap of a living mouse and found that it ranges from 50 ms to 2.5 s depending on the level of immobilization. This study provides information on relevant time scales for applying OPC to living tissues.

Real-time suppression of turbidity of biological tissues in motion by three-wave mixing phase-conjugation

We show that phase-conjugation by three-wave mixing allows turbidity suppression through biological tissues with thicknesses up to 5 mm, at a near-infrared wavelength included in the therapeutic window. Because of the ultrafast character of the imaging process, a motion of the tissue, which mimics in vivo imaging, can be exploited to significantly improve the signal-to-noise ratio and the resolution of the restored images.

Implementation of a digital optical phase conjugation system and its application to study the robustness of turbidity suppression by phase conjugation

In this work, we report a novel high capacity (number of degrees of freedom) open loop adaptive optics method, termed digital optical phase conjugation (DOPC), which provides a robust optoelectronic optical phase conjugation (OPC) solution. We showed that our prototype can phase conjugate light fields with ~3.9 x 10−3 degree accuracy over a range of ~3 degrees and can phase conjugate an input field through a relatively thick turbid medium (μsl ~13). Furthermore, we employed this system to show that the reversing of random scattering in turbid media by phase conjugation is surprisingly robust and accommodating of phase errors. An OPC wavefront with significant spatial phase errors (error uniformly distributed from – π/2 to π/2) can nevertheless allow OPC reconstruction through a scattering medium with ~40% of the efficiency achieved with phase error free OPC.

Turbidity suppression from the ballistic to the diffusive regime in biological tissues using optical phase conjugation

We describe the amplitude and resolution trends of the signals acquired by turbidity suppression through optical phase conjugation (TSOPC) with samples that span the ballistic and diffusive scattering regimes. In these experiments, the light field scattered through a turbid material is written into a hologram, and a time-reversed copy of the light field is played back through the sample. In this manner, the wavefront originally incident on the sample is reconstructed. We examine a range of scattering samples including chicken breast tissue sections of increasing thickness and polyacrylamide tissue-mimicking phantoms with increasing scattering coefficients. Our results indicate that only a small portion of the scattered wavefront (<0.02%) must be collected to reconstruct a TSOPC signal. Provided the sample is highly scattering, all essential angular information is contained within such small portions of the scattered wavefront due to randomization by scattering. A model is fitted to our results, describing the dependence of the TSOPC signal on other measurable values within the system and shedding light on the efficiency of the phase conjugation process. Our results describe the highest level of scattering that has been phase conjugated in biological tissues to date.

Raman Spectroscopy: An Emerging Tool for Clinical Diagnostics

B applications of lasers and laser spectroscopy are changing the face of medicine as it is currently practiced. Spectroscopy is a promising means of extracting biochemical and morphological information from tissue that is relevant to disease progression and diagnosis. In particular, Raman spectroscopy is a powerful tool for non-invasive and real time diagnosis due to its exquisite molecular specificity and lack of sample preparation requirements. Raman spectroscopy, which measures the molecular vibrations of a sample, is currently being used to study atherosclerosis, measure blood analytes, and detect dysplasia and cancer in various tissues including the breast, cervix, prostate, and skin. In this talk, we present our results on quantitative biological spectroscopy for non-invasive blood analyte detection. Our work in this area is primarily motivated by the necessity for accurate and frequent measurement of blood glucose levels, which is most commonly achieved by withdrawal of blood. Given the inconvenience and invasiveness of this procedure, a non-invasive method would greatly benefit the increasing number of diabetics. Our laboratory has successfully demonstrated the ability to measure glucose, urea and other blood analytes in serum, whole blood and individual human volunteers. In addition, we present our results for turbidity correction and suppression of tissue autofluorescence in biological Raman spectroscopy. We show that correction for these non-analyte specific variances provides a clinically accurate and robust calibration algorithm that can be used for prospective prediction in human population. Finally, we discuss our plans for miniaturization of the device for point of care and commercial applications. Raman Spectroscopy: An Emerging Tool for Clinical Diagnostics

An in vivo study of turbidity suppression by optical phase conjugation (TSOPC) on rabbit ear

We present a holography-based in vivo optical phase conjugation experiment performed on a living rabbit ear. The motion of live tissues caused the phase conjugate signal to decay with a consistent decay time of less than two seconds. We monitor the signal decay time variation after the ear is excised to postulate different mechanisms that cause the signal decay. The experimental findings address the minimum speed limit of a broad range of optical time reversal experiments for in vivo applications on tissues.

Observation of polarization-gate based reconstruction quality improvement during the process of turbidity suppression by optical phase conjugation

We present experiments that study the impact of polarization selection on the phenomenon of turbidity suppression by optical phase conjugation. Counter to intuition, we discovered that the preferential utilization of multiply scattered light field components over their sparsely scattered counterparts via appropriate polarization selection can lead to better image reconstruction quality. This effect was observed with tissue phantoms and biological tissue sections. The physical origin of this effect and its dependence on scatterer properties are discussed.

2-D PSTD Simulation of optical phase conjugation for turbidity suppression

Turbidity Suppression via Optical Phase Conjugation (TS-OPC) is an optical phenomenon that uses the back propagation nature of optical phase conjugate light field to undo the effect of tissue scattering. We use the computationally efficient and accurate pseudospectral time-domain (PSTD) simulation method to study this phenomenon; a key adaptation is the volumetric inversion of the optical wavefront E-field as a means for simulating a phase conjugate mirror. We simulate a number of scenarios and demonstrate that TS-OPC deteriorates with increased scattering in the medium, or increased mismatch between the random medium and the phase conjugate wave during reconstruction.