Photoacoustic guided wavefront shaping using digital micromirror devices

Research on photoacoustic microscopy imaging based on photoacoustic transmission matrix with a digital micromirror device

When light propagates through complex medium, such as biological tissue and multimode fiber, refractive index inhomogeneity causes multiple scattering and distortion. This phenomenon is usually seen as obstacles for biomedical imaging, telecommunications, photodynamic therapy and so on. Thus, manipulation of the incident wavefront to compensate for the wavefront distortion due to multiple scattering has been an interdisciplinary subject of interest. Fortunately, wavefront shaping technologies have emerged to provide versatile solutions to minimize the influence of light scattering. By modulating the incident light into a special wavefront with a spatial light modulator, focusing through scattering medium is obtained. To date, several wavefront shaping techniques have been proposed, mainly including transmission matrix inversion, feedback based iterative optimization, and digital optical phase conjugation. Unlike a planar wavefront, the modulated light with special wavefront is transformed into a bright optical focus spot or a desired focus pattern after the scattering medium. Among the proposed approaches, the transmission matrix is considered as a significant tool to characterize a multiple scattering medium with the purpose of manipulating light propagation through it, which contains all the information related to the input field and the scattered output field. In this work, we experimentally measure the transmission matrix of scattering media based on self-reference interference method with a digital micromirror device. Unlike the conventional setup, which divides the incident wavefront into a signal part and reference part, in the self-reference interference method, the reference light is superimposed directly on the signal light to form a new set of input light fields. This self-reference interference method effectively improves the degree of freedom of optical field modulation. Moreover, the intensity ratio between the signal light and the reference light can be adjusted conveniently. In our experiment, this superimposed field is generated by a digital micromirror device with superpixel method. We measure the Hadamard basis and the OAM-basis transmission matrices of scattering medium, respectively. With the measured transmission matrices, single-spot, multi-spot and vortex focusing are achieved after scattering medium, verifying the accuracy of the measured transmission matrices. The strong diagonal presented in the norm of focusing operator also proves the accuracy of the measured transmission matrices. The proposed method may have potential applications in optical imaging and optical communication under scattering environment.

A major limiting factor of optical imaging in biological applications is the diffusion of light by tissue, preventing focusing at depths greater than ~1 mm in the body. To overcome this issue, phase-based wavefront shaping alters the phase of sections of the incident wavefront to counteract aberrations in phase caused by scattering. This enables focusing through scattering media beyond the optical diffusion limit and increases signal compared to amplitude-based compensation. However, in previous studies, speed of optimization has typically been limited by the use of a liquid crystal spatial light modulator (SLM) for measurement and display. SLMs usually have refresh rates of less than 100 Hz and require much longer than the speckle correlation time of tissue in vivo, usually on the order of milliseconds, to determine the optimal wavefront. Here, we present a phase-based iterative wavefront shaping method based on an onaxis digital micromirror device (DMD) in conjunction with an electro-optic modulator (EOM) for measurement and a fast SLM for display. By combining phase modulation from an EOM with the modal selection of the DMD, we take advantage of DMDs higher refresh rate, approximately 23 kHz, for iterative phase measurement. The slower SLM requires one update for display following the rapid determination of the optimal wavefront via the DMD, allowing for high-speed wavefront shaping. Using this system, we are able to focus through scattering media using 64 modes in under 8 milliseconds, on the order of the speckle correlation time for tissue in vivo.

Optical imaging through highly scattering media such as biological tissue is limited by light scat tering. Recently, it has been shown that wavefront shaping is a powerful tool to overcome this problem. In this work, wavefront shaping using spatial light modulators is used to compensate static scattering media (piece of translucent tape) to allow focu sing of different intensity distributions. Light propagation is engineered into a specific region of interest. For this purpose, a sequential phase shape algorithm was implemented experimentally. This algorithm is used to encode a phase distribution on an incident beam to pre -compensate phase distortions acquired by the beam after propagating through the tape. The sequential algorithm combined with a spatial light modulator is used to synthesize a phase distribution required for re -directing light using wav efront shaping. The scattered light was re -directed at the detector plane, in order to be: i) focused at a single pixel, ii) at squared regions of 3x3 and 5x5 pixeles and iii ) a line pattern of 41 pixels of the camera. Furthermore, the region of interest was placed outside the central area of the camera opening the possibility of image formation. Keywords: Focusing light, controlling light propagation, scattering media, wavefront shaping, SLM

Over the last two decades, spatial light modulators (SLMs) have revolutionized our ability to shape optical fields. They grant independent dynamic control over thousands of degrees-of-freedom within a single light beam. In this work we test a new type of SLM, known as a phase-only light modulator (PLM), that blends the high efficiency of liquid crystal SLMs with the fast switching rates of binary digital micro-mirror devices (DMDs). A PLM has a 2D mega-pixel array of micro-mirrors. The vertical height of each micro-mirror can be independently adjusted with 4-bit precision. Here we provide a concise tutorial on the operation and calibration of a PLM. We demonstrate arbitrary pattern projection, aberration correction, and control of light transport through complex media. We show high-speed wavefront shaping through a multimode optical fiber – scanning over 2000 points at 1.44 kHz. We make available our custom high-speed PLM control software library developed in C++. As PLMs are based upon micro-electromechanical system (MEMS) technology, they are polarization agnostic, and possess fundamental switching rate limitations equivalent to that of DMDs – with operation at up to 10 kHz anticipated in the near future. We expect PLMs will find high-speed light shaping applications across a range of fields including adaptive optics, microscopy, optogenetics and quantum optics.

Wavefront shaping based on optoacoustic (photoacoustic) feedback has recently emerged as a promising tool to control the light distribution in optically-scattering media. In this approach, the phase of a short-pulsed light beam is spatially-modulated to create constructive light interference (focusing) at specific locations in the speckle pattern of the scattered wavefield. The optoacoustic signals generated by light absorption provide a convenient feedback mechanism to optimize the phase mask of the spatial light modulator in order to achieve the desired light intensity distribution. The optimization procedure can be done by directly considering the acquired signals or the reconstructed images of the light absorption distribution. Recently, our group has introduced a volumetric (three-dimensional) optoacoustic wavefront shaping platform that enables monitoring the distribution of light absorption in an entire volume with frame rates of tens of Hz. With this approach, it is possible to simultaneously control the volumetric light distribution through turbid media. Experiments performed with absorbing microparticles distributed in a three-dimensional region showcase the feasibility of enhancing the light intensity at specific points, where the size of particles is also essential to maximize the signal enhancement. The advantages provided by optoacoustic imaging in terms of spatial and temporal resolution anticipate new capabilities of wavefront shaping techniques in biomedical optics.

We present a 3D electromagnetic simulation of a digital micromirror device (DMD) from 0.4 µm to 5 µm, which accurately models DMD reflectance and contrast ratio, including the effects of diffraction. A DMD is a spatial light modulator with a wide range of applications, including projection displays, 3D printing, and imaging spectroscopy. The physical structure of the DMD induces strong wavelength-dependent diffraction effects that impact the stray light, optical throughput, and pupil illumination distribution of a system. To quantify this, we perform a 3-dimensional electromagnetic finite-difference time-domain simulation, illuminating the DMD with a focused, incoherent beam, explicitly calculating the near-field electric fields, and calculating the far-field distribution of light. The far-field data determines diffraction efficiency and the distribution of light across the pupil. With these models, we are able to study the DMD’s optical efficiency in three key regimes: the specular regime, where the DMD behaves like a segmented mirror with a diffractive component (λ < 1 µm); the diffraction-dominated regime, which is also described by analytic diffraction grating theory (3 µm < λ < 5 µm); and, uniquely, the transition region, where the specular reflection and diffraction contributions are comparable (1 µm < λ < 3 µm). Our results inform system performance parameters, provide optical design constraints, and create a framework of use cases for DMDs.

Wavefront shaping holds great potential for high-resolution imaging or light delivery either through or deep inside living tissue. However, one of the biggest barriers that must be overcome to unleash the full potential of wavefront shaping for practical biomedical applications is the fact that wavefront shaping, especially based on iterative feedback, requires lengthy measurements to obtain useful correction of the output wavefront. As biological tissues are inherently dynamic, the short decorrelation time sets a limit on the achievable wavefront shaping enhancement. Here we show that for wavefront shaping in thin anisotropic scattering media such as biological tissues, we can optimize the wavefront shaping quality by simply limiting the numerical aperture (NA) of the incident wavefront. Using the same number of controlled modes, and therefore the same wavefront measurement time, we demonstrate that the wavefront shaped focus peak to background ratio can be increased by a factor of 2.1 while the energy delivery throughput can be increased by a factor of 8.9 through 710 µm thick brain tissue by just limiting the incident NA.

The digital micromirror device DMD is widely used in visible light projection, special-purpose spatial light modulation, and infrared scene simulation, due to its high resolution, uniformity and energy concentration. In some applications that require high frame rate scene image display, it is necessary to ensure that the DMD displays high gray level images at a high frame rate. However, the display frame rate of the pulse width modulation (PWM) method is limited by the minimum time required for DMD loading data, unable to achieve high frame rate display. Although the DMD binary display mode can meet the requirements of high frame rate display, it cannot meet the requirements of high gray level. The paper proposes an image display method that uses light source and DMD to synchronize modulation. Decompose the high-order gray image into bit planes according to the gray threshold, and the DMD displays each bit plane in binary mode under the trigger of an sync pulse. The intensity of the illumination laser source is modulated by an acousto-optic modulator to match the bit plane and the radiated laser power. This method makes use of the function of high frame rate display in DMD binary mode cooperate with light intensity modulation of illumination laser source, and realizes high frame rate and high dynamic range image display. With this method, the maximum frame rate of 8-bit gray level image with 1920 ×1080 resolution can reach 2KHz. The experimental system has realized 200Hz frame rate display of 8-bit gray level image with 1920 ×1080 resolution.

Wavefront shaping is becoming increasingly attractive as it promises to enable various biomedical applications by breaking through the optical diffusion limit that prevents light focusing at depths larger than in biological tissue. However, despite recent advancements in wavefront shaping technology, such as those exploiting non-invasive photoacoustic-guidance, in vivo demonstrations remain challenging mainly due to rapid tissue speckle decorrelation. In this work, we report a high-speed photoacoustic-guided wavefront shaping method with a relatively simple experimental setup, based on the characterization of a scattering medium with a real-valued intensity transmission matrix. We demonstrated light focusing through an optical diffuser by optimizing 4096 binary amplitude modulation modes of a digital micromirror device within , leading to a system runtime of 75 µs per input mode, which is 3 orders of magnitude smaller than the smallest runtime reported in literature so far using photoacoustic-guided wavefront shaping. Thus, our method is a solid step forward toward in vivo applications of wavefront shaping.

Controllable light delivery to the region of interest is essential to biomedical optical imaging methods like photoacoustic microscopy. It is, however, challenging beyond superficial depths in biological tissue (~1 mm beneath human skin) due to the strong scattering of light that scrambles the photon propagation paths. Recently, optical wavefront shaping has been proposed to modulate the incident light wavefront to compensate for the scattering-induced phase distortions, and consequentially, convey light optimally to a desired location behind or inside turbid media. To reach an optimum wavefront, a searching algorithm is usually required to optimize a feedback signal. In this work, we present our latest explorations, which use photoacoustic signals as the feedback to remotely and non-invasively guide the wavefront shaping process. Our method does not require direct optical access to the target region or the invasive embedding of fluorescence probes inside turbid media. Experimentally, we have demonstrated that diffuse light can be converged to the ultrasound focus by maximizing the amplitude of photoacoustic emissions from the intended absorbing site. Moreover, we show that wavefront-shaped light focusing can enhance existing optical imaging modalities like photoacoustic microscopy, in regard to signal-to-noise ratio, imaging depth, and potentially, resolution.

In biological applications, optical focusing is limited by the diffusion of light, which prevents focusing at depths greater than ∼1 mm in soft tissue. Wavefront shaping extends the depth by compensating for phase distortions induced by scattering and thus allows for focusing light through biological tissue beyond the optical diffusion limit by using constructive interference. However, due to physiological motion, light scattering in tissue is deterministic only within a brief speckle correlation time. In in vivo tissue, this speckle correlation time is on the order of milliseconds, and so the wavefront must be optimized within this brief period. The speed of digital wavefront shaping has typically been limited by the relatively long time required to measure and display the optimal phase pattern. This limitation stems from the low speeds of cameras, data transfer and processing, and spatial light modulators. While binary-phase modulation requiring only two images for the phase measurement has recently been reported, most techniques require at least three frames for the full-phase measurement. Here, we present a full-phase digital optical phase conjugation method based on off-axis holography for single-shot optical focusing through scattering media. By using off-axis holography in conjunction with graphics processing unit based processing, we take advantage of the single-shot full-phase measurement while using parallel computation to quickly reconstruct the phase map. With this system, we can focus light through scattering media with a system latency of approximately 9 ms, on the order of the in vivo speckle correlation time.

The optical imaging depth in biological materials is limited by the scattering of light in tissue. New methods which control light propagation through scattering media have been introduced with the potential to overcome the scattering of light in biological materials. These techniques shape the incident wavefront to pre-compensate for the scattering effects of light propagation in the material and beyond. However, living biological materials have speckle decorrelation times on the millisecond timescale. This fast rate of change makes liquid crystal spatial light modulation (LC-SLM) devices too slow for this task. To achieve the required wavefront control with high modulation speeds we present binary-amplitude off-axis computer-generated holography implemented on a digital micro-mirror device (DMD). Binary amplitude off-axis holography is a method for the generation of arbitrary wavefronts, and in particular uniform-amplitude phase-modulated images. As a result, we are able to simultaneously encode phase modulated wavefronts at the high frame rate of binary amplitude DMDs. This wavefront encoding technique allows for focusing through temporally dynamic turbid materials at a rate which approaches the decorrelation time of living biological tissue. We demonstrate this technique by high speed wavefront optimization for focusing through turbid media as well as through a dynamic, strongly scattering sample with short speckle decorrelation times. With this approach we attain an order of magnitude improvement in measurement speed over the previous fastest wavefront determination method and three orders of magnitude improvement over LC-SLM methods.

A digital micromirror device (DMD) is a kind of widely used spatial light modulator. We apply DMD as wavelength selector in tunable fiber lasers. Based on the two-dimensional diffraction theory, the diffraction of DMD and its effect on properties of fiber laser parameters are analyzed in detail. The theoretical results show that the diffraction efficiency is strongly dependent upon the angle of incident light and the pixel spacing of DMD. Compared with the other models of DMDs, the 0.55 in. DMD grating is an approximate blazed state in our configuration, which makes most of the diffracted radiation concentrated into one order. It is therefore a better choice to improve the stability and reliability of tunable fiber laser systems.

Photoacoustic imaging (PAI) has gradually developed into a new and important imaging technology, which combines the high contrast of optical imaging and the high resolution of ultrasonic imaging to achieve a deeper imaging of biological tissue, and has been widely used in biological imaging. The basic principle of photoacoustic imaging is that a short pulse of laser is used to illuminate biological tissue. As photons pass through biological tissue, some of them are absorbed by biological molecules such as hemoglobin, DNA-RNA, fat, water, melanin and cytochrome. In PAI, the light absorption mechanisms generally include electron absorption, vibration absorption, stimulated Raman absorption and surface plasmon resonance absorption. The absorbed light energy is usually completely converted to heat energy by the non-radiative relaxation of the excited molecules, and the pressure wave caused by the heat energy is transmitted in the tissue to form ultrasonic wave, namely the photoacoustic signal. The photoacoustic signal reconstruction generated by the detection of ultrasonic transducer can be obtained from biological tissue. The absorption of blood in visible band is much higher than that of other tissues (except melanin) to achieve high resolution imaging of blood vessels without exogenous markers. Due to the characteristics of biological tissue, it has different degrees of absorption to different wavelengths of light, resulting in different heat and pressure waves generated, the final received ultrasonic wave is different, which will affect the final image results. Based on the finite element analysis method, this paper establishes four complete coupling modules in COMSOL software: coefficient form partial differential equation module, biological heat transfer module, solid mechanics module and transient pressure acoustic module. By setting different optical parameters to explore the degree of absorption of different light waves by biological tissues, so as to find the best wavelength of light for the experiment.