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A technique to rapidly scan an optical focus inside a turbid medium is attractive for various biomedical applications. Time-reversed ultrasonically encoded (TRUE) optical focusing has previously demonstrated light focusing into a turbid medium, using both analog and digital devices. Although the digital implementation can generate a focus with high energy, it has been time consuming to scan the TRUE focus inside a sample. Here, by sweeping the frequencies of both ultrasound and light, we demonstrate a multiplex recording of ultrasonically encoded wavefronts, accelerating the generation of multiple TRUE foci. Using this technique, we obtained a 2-D image of a fluorescent target centered inside a turbid sample having a thickness of 2.4 transport mean free paths. [ABSTRACT FROM AUTHOR]

Presents tomographic imaging of biological tissues by use of a microwave-induced acoustic signal. Microwave-induced acoustics toward biomedical applications; Imaging approach.

The focal point of a high-numerical-aperture (NA) ultrasonic transducer can be used as a virtual point detector. This virtual point detector detects omnidirectionally over a wide acceptance angle. It also combines a large active transducer surface and a small effective virtual detector size. Thus the sensitivity is high compared with that of a real point detector, and the aperture effect is small compared with that of a finite size transducer. We present two kinds of high-NA-based virtual point detectors and their successful application in photoacoustic tomography. They can also be applied in other ultrasound-related fields. [ABSTRACT FROM AUTHOR]

A time-resolved optical tomography, optical coherence computed tomography, is proposed to bridge the gap between diffuse optical tomography and optical coherence tomography. Both ballistic and multiple-scattered photons are measured at multiple source-detection positions by low-coherence interferometry providing a temporal resolution smaller than 100 fs. A light-tissue interaction model was established using the time-resolved Monte Carlo method. The optical properties were then reconstructed by solving the inverse transient radiative transport problem under the first Born approximation. Absorbing inclusions of 100 μm diameter were imaged through a 2.6-mm-thick (∼30 scattering mean-free-paths) scattering medium. [ABSTRACT FROM AUTHOR]

A novel spectral-domain optical coherence tomography (SD-OCT), in which the self-interferogram of the object wave and the standard SD-OCT interferogram are acquired asynchronously using an optical switch in the reference arm, is presented. After Fourier transformation, the autocorrelation of the object is removed simply by subtraction from the standard SD-OCT image. The measured sensitivity is 103.5 dB at z=0.115 mm, and it gradually reduces to 84.1 dB at z=3.275 mm. The axial resolution is 15 μm in the air. In vivo images of human skin are presented to demonstrate the performance of autocorrelation removal. [ABSTRACT FROM AUTHOR]

An optical imaging technique called ultrasound-modulated optical computed tomography is demonstrated for tomographic imaging of biological tissues. Ultrasound-modulated optical signals are extracted from scattered light to provide projection data for the image reconstruction. A filtered back-projection algorithm is implemented to reconstruct an image reflecting optical tissue properties from angular and linear scans of an ultrasonic beam across a sample. This reconstruction-based imaging technique provides a way to obtain images of cross sections containing the scanned ultrasonic axis in biological tissues, which enables three-dimensional ultrasound-modulated optical imaging. The technique combines the contrast advantage of optical waves and the resolution advantage of ultrasonic waves. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Noninvasive, high resolution imaging of mouse brain activity is poised to provide clinically translatable insights into human neurological disease progression. Toward noninvasive imaging of brain activity through the hemodynamic response, the dark-field photoacoustic microscopy (PAM) technique was enhanced to image the cortex vasculature of the mouse brain in vivo using endogenous hemoglobin contrast. Specifically, the PAM system was redesigned to efficiently collect photoacoustic waves originating from cortical vessels, providing high (70 ¿m lateral and 54 ¿m axial) resolution images of the mouse brain vasculature with a contrast-to-noise ratio of 25 dB. These findings confirm the efficacy of PAM to noninvasively image vascular structures in the mouse brain and the potential to image mouse brain function by tracking the hemodynamic response. [ABSTRACT FROM AUTHOR]

Reversibly photoswitchable probes allow for a wide variety of optical imaging applications. In particular, photoswitchable fluorescent probes have significantly facilitated the development of super-resolution microscopy. Recently, stimulated Raman scattering (SRS) imaging, a sensitive and chemical-specific optical microscopy, has proven to be a powerful live-cell imaging strategy. Driven by the advances of newly developed Raman probes, in particular the pre-resonance enhanced narrow-band vibrational probes, electronic pre-resonance SRS (epr-SRS) has achieved super-multiplex imaging with sensitivity down to 250 nM and multiplexity up to 24 colors. However, despite the high demand, photoswitchable Raman probes have yet to be developed. Here, we propose a general strategy for devising photoswitchable epr-SRS probes. Toward this goal, we exploit the molecular electronic and vibrational coupling, in which we switch the electronic states of the molecules to four different states to turn their ground-state epr-SRS signals on and off. First, we showed that inducing transitions to both the electronic excited state and triplet state can effectively diminish the SRS peaks. Second, we revealed that the epr-SRS signals can be effectively switched off in red-absorbing organic molecules through light-facilitated transitions to a reduced state. Third, we identified that photoswitchable proteins with near-infrared photoswitchable absorbance, whose states are modulable with their electronic resonances detunable toward and away from the pump photon energy, can function as the photoswitchable epr-SRS probes with desirable sensitivity (<1 µM) and low photofatigue (>40 cycles). These photophysical characterizations and proof-of-concept demonstrations should advance the development of novel photoswitchable Raman probes and open up the unexplored Raman imaging capabilities. [ABSTRACT FROM AUTHOR]

Focusing light through or inside scattering media by the analog optical phase conjugation (AOPC) technique based on photorefractive crystals (PRCs) has been intensively investigated due to its high controlled degrees of freedom and short response time. However, the existing AOPC systems only phase-conjugate the scattered light in one polarization direction, while the polarization state of light scattered through a thick scattering medium is spatially random in general, which means that half of the scattering information is lost. Here, we propose dual-polarization AOPC for focusing light through scattering media to improve the efficiency and fidelity in the phase conjugation. The motivations of the dual-polarization AOPC are illustrated by theoretical analysis and numerical simulation, and then an experimental system is established to realize the dual-polarization AOPC. By separating and rotating the two orthogonal polarization components of the randomly polarized scattered light, light in all polarization states is recorded and phase-conjugated using the same PRC. Experimental results for focusing through a thick biological tissue show that the intensity of the time-reversed focus from the dual-polarization AOPC can be enhanced by a factor of approximate four compared with the existing single-polarization AOPC. [ABSTRACT FROM AUTHOR]

The authors propose and numerically demonstrate an ultra-high resolution (wavelength/50∼40 nm at wavelength λ=2.08 μm), high-throughput (∼66%), and non-destructive optical lens with a large contrast-to-noise ratio, based on the notion of correlated nano-torches formed in a subwavelength metallic grating. The correlations between the torches also allow the determination of the complex refractive index of the sample. [ABSTRACT FROM AUTHOR]

The multi-scale model is key to the evaluation of shear or compression mechanical properties of jujube branches at the microlevel. In this study, multi-scale models of the microstructure of jujube branches, namely, the natural model and the artificially simplified model, were built using computed tomography and Python. The equivalent compression and shear properties of the microstructure were predicted by the finite element method. The prediction results of the artificially simplified model were compared with those of the natural model, and the prediction deviation of the artificially simplified model was analyzed. The results showed that the transverse shear modulus obtained by the artificially simplified model was slightly higher than the predicted value of the natural model, with an average deviation of 1.84%. The transverse shear strain energy obtained by the artificially simplified model was lower than the predicted result of the natural model, with a maximum deviation of 5.59%. The cell distribution direction had an important effect on the accuracy of prediction for the transverse elastic modulus, and the deviation was 16.53%, indicating that the further optimization of the cell distribution direction could enhance the prediction accuracy and the effectiveness of the model. The results can be used to evaluate the unit compression or shear mechanical properties of plant stalks with hierarchical structuring and to analyze the quantitative relationship between the microstructure and equivalent mechanical properties. [ABSTRACT FROM AUTHOR]

An ultrasonic virtual point detector is constructed using the center of a ring transducer. The virtual point detector provides ideal omnidirectional detection free of any aperture effect. Compared with a real point detector, the virtual one has lower thermal noise and can be scanned with its center inside a physically inaccessible medium. When applied to photoacoustic tomography, the virtual point detector provides both high spatial resolution and high signal-to-noise ratio. It can also be potentially applied to other ultrasound-related technologies. [ABSTRACT FROM AUTHOR]

An ultra-long light needle is highly desired in optical microscopy for its ability to improve the lateral resolution over a large depth of field (DOF). However, its use in image acquisition usually relies on mechanical raster scanning, which compromises between imaging speed and stability and thereby restricts imaging performance. Here, we propose a synthetic Bessel light needle (SBLN) that can be generated and scanned digitally by complex field modulation using a digital micromirror device. In particular, the SBLN achieves a 45-fold improvement in DOF over its counterpart Gaussian focus. Further, we apply the SBLN to perform motionless two-dimensional and three-dimensional microscopic imaging, achieving both improved resolution and extended DOF. Our work is expected to open up opportunities for potential biomedical applications. [ABSTRACT FROM AUTHOR]

Conventional helical and horn antennas based on frequency selective surfaces have been used to provide microwave illumination in microwave-induced thermoacoustic tomography (TAT). However, the electromagnetic waves radiated from the conventional antennas are not circularly polarized and thus impair image quality. In addition, conventional antennas can provide uniform radiations only within a relatively small area and thus limit their clinical applications (e.g., breast imaging). To address these problems, we propose a quasi-conical log-spiral antenna for homogenous illumination over a large field. We theoretically and experimentally validated this approach. Tissue-mimicking phantoms were imaged. The antenna produced not only an electric field with a circular polarization but also a homogeneous illumination area with a 10 cm diameter. Accordingly, our method has advanced TAT by improving microwave illumination. [ABSTRACT FROM AUTHOR]

In biological applications, optical focusing is limited by the diffusion of light, which prevents focusing at depths greater than ~1mm 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. [ABSTRACT FROM AUTHOR]

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 4K displays, these SLMs are inexpensive and valuable devices for wavefront shaping. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ultrasound-modulated optical tomography (UOT) images optical contrast deep inside scattering media. Heterodyne holography based UOT is a promising technique that uses a camera for parallel speckle detection. In previous works, the speed of data acquisition was limited by the low frame rates of conventional cameras. In addition, when the signal-to-background ratio was low, these cameras wasted most of their bits representing an informationless background, 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. Moreover, compared with the conventional four-frame based amplitude measurement method, our single-frame method is more immune to speckle decorrelation. Using lock-in camera based UOT with an integration time of 286 μs, we imaged an absorptive object buried inside a dynamic scattering medium exhibiting a speckle correlation time (τc) as short as 26 μs. Since our method can tolerate speckle decorrelation faster than that found in living biological tissue (τc ℓ100-1000 μs), it is promising for in vivo deep tissue non-invasive imaging. [ABSTRACT FROM AUTHOR]

As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography. [ABSTRACT FROM AUTHOR]

We present a generic wide-field optical sectioning scheme, photobleaching imprinting microscopy (PIM), for depth-resolved cross-sectional fluorescence imaging. Wide-field PIM works by extracting a nonlinear component that depends on the excitation fluence as a result of photobleaching-induced fluorescence decay. Since no specific fluorescent dyes or illumination modules are required, wide-field PIM is easy to implement on a standard microscope. Moreover, wide-field PIM is superior to deconvolution microscopy in removing background fluorescence, yielding a six-fold improvement in image contrast. [ABSTRACT FROM AUTHOR]

Measuring intracellular temperature is critical to understanding many cellular functions but still remains challenging. Here, we present a technique-fluorescence-assisted photoacoustic thermometry (FAPT)-for intracellular temperature mapping applications. To demonstrate FAPT, we monitored the intracellular temperature distribution of HeLa cells with sub-degree (0.7 °C) temperature resolution and sub-micron (0.23 μm) spatial resolution at a sampling rate of 1 kHz. Compared to traditional fluorescence-based methods, FAPT features the unique capability of transforming a regular fluorescence probe into a concentration- and excitation-independent temperature sensor, bringing a large collection of commercially available generic fluorescent probes into the realm of intracellular temperature sensing. [ABSTRACT FROM AUTHOR]

A correction to the article “Photoacoustic Doppler flow measurement in optically scattering media” is presented.

Slow light has been extensively studied for applications ranging from optical delay lines to single photon quantum storage. Here, we show that the time delay of slow-light significantly improves the performance of the narrowband spectral filters needed to optically detect ultrasound from deep inside highly scattering tissue. We demonstrate this capability with a 9 cm thick tissue phantom, having 10 cm-1 reduced scattering coefficient, and achieve an unprecedented background-free signal. Based on the data, we project real time imaging at video rates in even thicker phantoms and possibly deep enough into real tissue for clinical applications like early cancer detection. [ABSTRACT FROM AUTHOR]

Picosecond absorption relaxation-central to many disciplines-is typically measured by ultrafast (femtosecond or picosecond) pump-probe techniques, which however are restricted to optically thin and weakly scattering materials or require artificial sample preparation. Here, we developed a reflection-mode relaxation photoacoustic microscope based on a nanosecond laser and measured picosecond absorption relaxation times. The relaxation times of oxygenated and deoxygenated hemoglobin molecules, both possessing extremely low fluorescence quantum yields, were measured at 576 nm. The added advantages in dispersion susceptibility, laser-wavelength availability, reflection sensing, and expense foster the study of natural-including strongly scattering and nonfluorescent-materials. [ABSTRACT FROM AUTHOR]

We applied a submegahertz nonlinear optical filter afforded by a cryogenically cooled spectral-hole burning crystal to ultrasound-modulated optical tomography. Our experimental results show that this technique, having the largest etendue among all available ultrasound-modulated optical tomography techniques and being immune to speckle decorrelation, offers potential for imaging in vivo and forming high resolution optical tomograms in real time. It opens an opportunity for the development of a clinically applicable high resolution optical imaging modality. [ABSTRACT FROM AUTHOR]

Photoacoustic microscopy was used to noninvasively image variations in hemoglobin oxygen saturation (SO2) in the subcutaneous microvasculature of rats in vivo. In phantom tests, the calculated concentration fractions of red ink in double-ink mixtures matched the actual values with a 1% error. In ex vivo studies, the calculated SO2 in bovine blood agreed with the standard spectrophotometric measurements within a 4% systematic difference. In in vivo studies, arteries and veins were separated based on the measured SO2 values and variations in SO2 between different physiological states (hyperoxia, normoxia, and hypoxia) were imaged in single blood vessels. [ABSTRACT FROM AUTHOR]

We propose a method for photoacoustic flow measurement based on the Doppler effect from a flowing homogeneous medium. Excited by spatially modulated laser pulses, the flowing medium induces a Doppler frequency shift in the received photoacoustic signals. The frequency shift is proportional to the component of the flow speed projected onto the acoustic beam axis, and the sign of the shift reflects the flow direction. Unlike conventional flowmetry, this method does not rely on particle heterogeneity in the medium; thus, it can tolerate extremely high particle density. A red-ink phantom flowing in a tube immersed in water was used to validate the method in both the frequency and time domains. The phantom flow immersed in an intralipid solution was also measured. [ABSTRACT FROM AUTHOR]

We propose to enhance the axial resolution of photoacoustic microscopy (PAM) by reducing the speed of sound within the imaging region of interest. With silicone oil immersion, we have achieved a finest axial resolution of 5.8 μm for PAM, as validated by phantom experiments. The axial resolution was also enhanced in vivo when mouse ears injected with silicone oil were imaged. When tissue-compatible low-speed liquid becomes available, this approach may find broad applications in PAM as well as in other imaging modalities, such as photoacoustic computed tomography and ultrasound imaging. [ABSTRACT FROM AUTHOR]