Noninvasive photoacoustic angiography of animal brains in vivo with near-infrared light and an optical contrast agent

Optical contrast agents have been widely applied to enhance the sensitivity and specificity of optical imaging with near-infrared (NIR) light. However, because of the overwhelming scattering of light in biological tissues, the spatial resolution of traditional optical imaging degrades drastically as the imaging depth increases. Here, for the first time to our knowledge, we present noninvasive photoacoustic angiography of animal brains in vivo with NIR light and an optical contrast agent. When indocyanine green polyethylene glycol, a novel absorption dye with prolonged clearance, is injected into the circulatory system of a rat, it obviously enhances the absorption contrast between the blood vessels and the background tissues. Because NIR light can penetrate deep into the brain tissues through the skin and skull, we are able to successfully reconstruct the vascular distribution in the rat brain from the photoacoustic signals. On the basis of differential optical absorption with and without contrast enhancement, a photoacoustic angiograph of a rat brain is acquired that matches the anatomical photograph well and exhibits high spatial resolution and a much-reduced background. This new technology demonstrates the potential for dynamic and molecular biomedical imaging.     

High-resolution ultrasound-modulated optical tomography in biological tissues

We present a novel implementation of high-resolution ultrasound-modulated optical tomography that, based on optical contrast, can image several millimeters deep into soft biological tissues. A long-cavity confocal Fabry-Perot interferometer, which provides a large etendue and a short response time, was used to detect the ultrasound-modulated coherent light that traversed the scattering biological tissue. Using 15-MHz ultrasound, we imaged with high-contrast light-absorbing structures placed >3 mm below the surface of chicken breast tissue. The resolution along the axial and the lateral directions with respect to the ultrasound propagation direction was better than 70 and 120 microm, respectively. The resolution can be scaled down further by use of higher ultrasound frequencies. This technology is complementary to other imaging technologies, such as confocal microscopy and optical-coherence tomography, and has the potential for broad biomedical applications.     

Protein-based molecular contrast optical coherence tomography with phytochrome as the contrast agent

We report the use of phytochrome A (phyA), a plant protein that can reversibly switch between two states with different absorption maxima (at 660 and 730 nm), as a contrast agent for molecular contrast optical coherence tomography (MCOCT). Our MCOCT scheme builds up a difference image revealing the distribution of phyA within a target sample from pairs of consecutive OCT A-scans acquired at a probe wavelength of 750 nm, both with and without additional illumination of the target sample with 660-nm light. We demonstrate molecular imaging with this new MCOCT modality in a target sample containing a mixture of 0.2% Intralipid and 83 microM of phyA.     

Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent

We report a new molecular contrast optical coherence tomography (MCOCT) implementation that profiles the contrast agent distribution in a sample by measuring the agent's spectral differential absorption. The method, spectra triangulation MCOCT, can effectively suppress contributions from spectrally dependent scatterings from the sample without a priori knowledge of the scattering properties. We demonstrate molecular imaging with this new MCOCT modality by mapping the distribution of indocyanine green, a FDA-approved infrared red dye, within a stage 54 Xenopus laevis.     

Viscoelasticity imaging of biological tissues with phase-resolved photoacoustic measurement

A method for noninvasive viscoelasticity imaging of biological tissues using phase-resolved photoacoustic measurement is presented. We deduced the process of photoacoustic effect on the basis of thermal viscoelasticity theory, and established the relationship between the photoacoustic phase delay and the viscosity-elasticity ratio for soft solids. Agar phantoms with different densities and different absorption coefficients were used to verify the dependence of photoacoustic phase-resolved viscoelasticity measurements. Moreover, viscoelasticity imaging of tissues was obtained with a photoacoustic point scanning system. The photoacoustic phase-resolved method provides a basis for viscoelasticity imaging, which can potentially be used for detection of viscoelastic properties and lesions of biological tissues.     

Continuous optical coherence tomography monitoring of nanoparticles accumulation in biological tissues

In this study, dynamics of nanoparticles penetrating and accumulating in biotissue (healthy skin) was investigated in vivo by the noninvasive method of optical coherence tomography (OCT). Gold nanoshells and titanium dioxide nanoparticles were studied. The processes of the nanoparticles penetration and accumulation in biotissue are accompanied by the changes in optical properties of skin which affect the OCT images. The continuous OCT monitoring of the process of the nanoparticles penetration into skin showed that these changes appeared in 30 min after application of nanoparticles on the surface; the time of accumulation of maximal nanoparticles concentration in skin was observed in period of 1.5–3 h after application. Numerical processing of the OCT signal exhibited the increase in contrast between upper and lower parts of dermis and contrast decay of the hair follicle border during 60–150 min. The transmission electron microscopy technique confirmed accumulation of the both types of nanoparticles in biotissue. The novelty of this study is presentation of OCT ability to in vivo monitor dynamics of nanoparticles penetration and their re-distribution within living tissues.     

Backscattering spectroscopic contrast with angle-resolved optical coherence tomography

Backscattering spectroscopic contrast using angle-resolved optical coherence tomography is demonstrated as a powerful method for determining scatterer diameter with subwavelength resolution. By applying spectroscopic digital processing algorithms to interferograms acquired in the frequency domain with a wavelength-swept laser centered at 1295 nm, it was shown that differences in wavelength-dependent backscattering from 0.3 and 1 microm diameter microspheres can be clearly resolved. The observed backscattering spectra were found to be consistent with Mie theory. High levels of speckle noise reduction achieved by angular compounding increased the spatial resolution at which backscattering spectra could be accurately differentiated.     

Quadrature fringes wide-field optical coherence tomography and its applications to biological tissues

We propose and demonstrate quadrature fringes wide-field optical coherence tomography (QF WF OCT) to expand an optical Hilbert transformation to two-dimensions. This OCT simultaneously measures two quadrature interference images using a single InGaAs CCD camera to obtain en face OCT images. The axial and lateral resolutions are measured at 29 μm in air and 70 μm limited by a pixel size of camera using a superluminescent diode with a wavelength of 1.3 μm as the light source; the system sensitivity is determined to be −90 dB. The area of the en face OCT images is 4.0 mm × 4.0 mm (160 × 160  pixels). The OCT images are measured axially with steps of 10 μm. The en face OCT images of a in vivo human fingertip and a in situ rat brain are three-dimensionally measured up to the depth of about 3 mm with some degradations of a lateral resolution.     

生物光声层析成像中不均匀和不稳定照明解决方法

在生物组织光声层析成像(Photoacoustic?Tomography,?PAT)算法中,为了简化问题,通常假设在均匀和稳定照明的理想情况下,重建组织的初始声压分布图、光吸收能量分布图和光学特性参数分布图.但在实际应用中,当光在生物组织中传播时,会出现光衰减和光通量分布不均匀的情况,导致重建精度下降.本文对非理想条件...     

Differential phase contrast in optical coherence tomography

We report on a modification of optical coherence tomography (OCT) that allows one to measure small phase differences between beams traversing adjacent areas of a specimen. The sample beam of a polarization-sensitive low-coherence interferometer is split by a Wollaston prism into two components that traverse the object along closely spaced paths. After reflection at the various sample surfaces, the beams are recombined at the Wollaston prism. Any phase difference encountered between the two beams is converted into a change of polarization state of the recombined beam. This change is measured, and the resulting signals are converted to differential phase-contrast OCT images. The first images obtained from simple test objects allowed us to determine path-difference gradients with a resolution of the order of 5 x 10(-5) .     

Hemoglobin contrast in magnetomotive optical Doppler tomography

We introduce a novel contrast mechanism for imaging blood flow by use of magnetomotive optical Doppler tomography (MM-ODT), which combines an externally applied temporally oscillating high-strength magnetic field with ODT to detect erythrocytes moving according to the field gradient. Hemoglobin contrast was demonstrated in a capillary tube filled with moving blood by imaging the Doppler frequency shift, which was observed independently of blood flow rate and direction. Results suggest that MM-ODT may be a promising technique with which to image blood flow.     

Deeply penetrating waves in lossy media

The incidence of an inhomogeneous plane wave on the interface between two lossy media is analyzed. The analytical expressions of the incidence angle of the phase vector, for which the transmitted wave has the phase or the attenuation vector parallel to the interface, are obtained. The transmitted wave with the attenuation vector parallel to the interface is physically interpreted, finding a wave in a lossy medium without attenuation away from the interface. The same effect appears at the interface between a lossless medium and a lossy one.     

Engineered microsphere contrast agents for optical coherence tomography

Contrast agents are utilized in virtually every imaging modality to enhance diagnostic capabilities. We introduce a novel class of optical contrast agent, namely, encapsulating microspheres, that are based not on fluorescence but on scattering nanoparticles within the shell or core. The agents are suitable for reflection- or scattering-based techniques such as optical coherence tomography, light microscopy, and reflectance confocal microscopy. We characterize the optical properties of gold-, melanin-, and carbon-shelled contrast agents and demonstrate enhancement of optical coherence tomography imaging after intravenous injection of such an agent into a mouse.     

Cross-polarized backscatter in optical coherence tomography of biological tissue

We have observed that cross-polarized backscatter measured by optical coherence tomography of human skin in vivo is surprisingly strong. We identify and give evidence of its main origins: single scattering from nonspherical particles and multiple scattering by particles with sizes much larger than a wavelength. Our findings show that depolarized light scattered by dense large-diameter particles maintains a high degree of temporal coherence and that differential-polarization imaging improves contrast between particles of different sizes.     

Adaptive multi-sample-based photoacoustic tomography with imaging quality optimization

The energy of light exposed on human skin is compulsively limited for safety reasons which affects the power of photoacoustic(PA) signal and its signal-to-noise ratio(SNR) level. Thus, the final reconstructed PA image quality is degraded. This Letter proposes an adaptive multi-sample-based approach to enhance the SNR of PA signals and in addition, detailed information in rebuilt PA images that used to be buried in the noise can be distinguished. Both ex vivo and in vivo experiments are conducted to validate the effectiveness of our proposed method which provides its potential value in clinical trials.     

Quantum optical coherence tomography of a biological sample

Quantum optical coherence tomography (QOCT) makes use of an entangled-photon light source to carry out dispersion-immune axial optical sectioning. We present the first experimental QOCT images of a biological sample: an onion-skin tissue coated with gold nanoparticles. 3D images are presented in the form of 2D sections of different orientations. In the context of quantum information, this represents the first experiment in which a quantum-entangled entity interacts with a biological specimen, generating a collection of quantum interferograms, from which an image is constructed.     

Performance improvement of magneto-acousto-electrical tomography for biological tissues with sinusoid-Barker coded excitation

By combining magnetics, acoustics and electrics, the magneto-acoustic-electrical tomography(MAET) proves to possess the capability of differentiating electrical impedance variation and thus improving the spatial resolution. However,the signal-to-noise ratio(SNR) of the collected MAET signal is still unsatisfactory for biological tissues with low-level electrical conductivity. In this study, the formula of MAET measurement with sinusoid-Barker coded excitation is derived and simplified for a planar piston transducer. Numerical simulations are conducted for a four-layered gel phantom with the 13-bit sinusoid-Barker coded excitation, and the performances of wave packet recovery with side-lobe suppression are improved by using the mismatched compression filter, which is also demonstrated by experimentally measuring a three-layered gel phantom. It is demonstrated that comparing with the single-cycle sinusoidal excitation, the amplitude of the driving signal can be reduced greatly with an SNR enhancement of 10 dB using the 13-bit sinusoid-Barker coded excitation. The amplitude and polarity of the wave packet filtered from the collected MAET signal can be used to achieve the conductivity derivative at the tissue boundary. In this study, we apply the sinusoid-Barker coded modulation method and the mismatched suppression scheme to MAET measurement to ensure the safety for biological tissues with improved SNR and spatial resolution, and suggest the potential applications in biomedical imaging.     

Ultrasound tomography of soft biological tissues containing strong inhomogeneities

Applied aspects concerning experimental data processing have been discussed. The data are obtained on a prototype of ultrasound medical acoustic tomograph, designed for early diagnostics of benign and malignant tumors in soft biological tissues. The result of the study is the reconstructed distribution patterns of speed of sound and absorption in an organ under test.     

Gold nanocages as contrast agents for spectroscopic optical coherence tomography

We describe gold nanocages as a new class of potential contrast agent for spectroscopic optical coherence tomography (OCT). Monodispersed gold nanocages of an approximately 35 nm edge length exhibit strong optical resonance, with the peak wavelength tunable in the near-infrared range. We characterized the optical properties of the nanocage by using OCT experiments along with numerical calculations, revealing an absorption cross section approximately 5 orders of magnitude larger than conventional dyes. Experiments with tissue phantoms demonstrated that the nanocages provide enhanced contrast for spectroscopic as well as conventional intensity-based OCT imaging.