Intense acoustic bursts as a signal-enhancement mechanism in ultrasound-modulated optical tomography

Biophotonic imaging with ultrasound-modulated optical tomography (UOT) promises ultrasonically resolved imaging in biological tissues. A key challenge in this imaging technique is a low signal-to-noise ratio (SNR). We show significant UOT signal enhancement by using intense time-gated acoustic bursts. A CCD camera captured the speckle pattern from a laser-illuminated tissue phantom. Differences in speckle contrast were observed when ultrasonic bursts were applied, compared with when no ultrasound was applied. When CCD triggering was synchronized with burst initiation, acoustic-radiation-force-induced displacements were detected. To avoid mechanical contrast in UOT images, the CCD camera acquisition was delayed several milliseconds until transient effects of acoustic radiation force attenuated to a satisfactory level. The SNR of our system was sufficiently high to provide an image pixel per acoustic burst without signal averaging. Because of the substantially improved SNR, the use of intense acoustic bursts is a promising signal enhancement strategy for UOT.     

Imaging optically scattering objects with ultrasound-modulated optical tomography

We show the feasibility of imaging objects having different optical scattering coefficients relative to the surrounding scattering medium using ultrasound-modulated optical tomography (UOT). While the spatial resolution depends on ultrasound parameters, the image contrast depends on the difference in scattering coefficient between the object and the surrounding medium. Experimental measurements obtained with a CCD-based speckle contrast detection scheme are in agreement with Monte Carlo simulations and analytical calculations. This study complements previous UOT experiments that demonstrated optical absorption contrast.     

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.     

Multispectral optoacoustic tomography by means of normalized spectral ratio

Quantification of biomarkers using multispectral optoacoustic tomography can be challenging due to photon fluence variations with depth and spatially heterogeneous tissue optical properties. Herein we introduce a spectral ratio approach that accounts for photon fluence variations. The performance and imaging improvement achieved with the proposed method is showcased both numerically and experimentally in phantoms and mice.     

Effects of modulation phase of ultrasound-modulated light on the ultrasound-modulated optical image in turbid media

In this paper, our investigations suggest that the modulation phase of ultrasound-modulated light escaping from the different locations in the ultrasonic field is different. In turbid media, the modulation phase causes the ultrasound-modulated light intensity collected outside the media to fluctuate. However, the ultrasound-modulated optical technology uses the ultrasound-modulated light signals to image. Consequently, the modulation phase affects the quality of ultrasound-modulated optical imaging.     

Retrieval of chromophore concentration in a tissue phantom by diffuse reflectance spectroscopy

This study describes a method for analysis of back reflectance spectroscopic data to estimate the concentration of endogenous or exogenous chromophores of tissue, noninvasively and in real time. In the study, tissue phantoms were prepared using intralipid and two chromophores, indocyanine green and methylene blue. Reduced scattering and absorption coefficients ranges of tissue phantoms were kept in the range of biological tissues. Spectroscopic measurements on the tissue phantoms were carried out using a miniature spectrometer, an optical fiber probe, a halogen tungsten light source and a laptop. Monte Carlo simulations of the experiments were run, and an average optical path lengths of the detected photons were obtained for different absorption and scattering coefficients. The average optical path lengths of the photons were used to estimate concentrations of the chromophores in the tissue phantoms. Scattering and absorption coefficients were estimated with an average error of 4.7 and 5.4%, respectively. The developed method has the potential to be used in diagnosis of pathologic tissues based on the variation of biochemical composition of tissues and in photodynamic therapy to estimate the concentration of photosensitizers.     

Experimental study of ultrasound-modulated scattering light using different frequencies ultrasound probes

The focused ultrasound plays a role in localization and modulating the scattering light in ultrasound- modulated optical tomography （UOT）. Both the modulation efficiency of the scattering light and the spatial resolution of UOT are determined by ultrasound. The effects of repetition frequency and pulse energy of impulse ultrasound on the modulated scattering light are derived through experiment in this letter. Purthermore, we compare the imaging sensitivity with 1, 2.25, 5, and 10 MHz center frequencies of impulse ultrasound. Experimental results demonstrate that better signal-to-noise ratios and higher sensitivities can be gained by use of more intense ultrasound and lower ultrasound frequencies.     

Ar+激光和532 nm激光及其线偏振激光辐照光学模型下人正常小肠组织光学特性

采用双积分球系统和光辐射测量技术的基本原理以及运用生物组织的光学模型 ,研究了 4 76 5 ,4 88,4 96 5 ,5 14 5 ,5 32nm激光及其线偏振激光辐照人正常小肠组织的光学特性。结果表明 :组织对激光及线偏振激光的衰减系数和散射系数随着波长的减小而增大 ,而 5 14 5～ 5 32nm波长之间 ,线偏振光与非线偏振光入射则开始有明显差异。吸收系数是随着波长的减小而缓慢地增大 ,而 5 14 5～ 5 32nm波长之间吸收系数的改变则明显变小 ,与是否线偏振光入射无明显差异。平均散射余弦也是随着波长的减小而增大 ,光学穿透深度则是随着波长的增大而增大 ,折射率在这五个波长范围内的值在 (1 38～ 1 4 8)之间。Kubel ka Munk二流模型下组织对同一波长的激光及其线偏振激光的吸收系数、散射系数、总衰减系数、有效衰减系数没有显著性差异 (P >0 0 5 )。组织对不同波长的激光或其线偏振激光的吸收系数、散射系数、总衰减系数、有效衰减系数是有差异的。而在 5 14 5～ 5 32nm波长之间其光学特性参数有较为明显的差异。     

Relationship between wavelength combination and signal-to-noise ratio in measuring hemoglobin concentrations using visible or near-infrared light

The signal-to-noise ratio (SNR), when using visible or near-infrared light to measure the change in hemoglobin concentration length (the product of hemoglobin concentration and optical path length in this study), depends on the wavelength combination and the analysis method. Although the SNRs increase when detected or incident optical power increases, the optical power should be limited because of safety standards. Considering these safety standards, we assumed that the total optical power was constant by using the relationship between optical power and measurement error. We investigated the theoretical estimation errors of the changes in hemoglobin concentration length using two, three, and four different wavelengths. The SNRs of the changes in hemoglobin concentration length were high when fewer wavelengths were used. These SNRs decreased when the redox state change in cytochrome oxidase was included in the analysis.     

Diffuse reflectance spectroscopy with a self-calibrating fiber optic probe

Calibration of the diffuse reflectance spectrum for instrument response and time-dependent fluctuation as well as interdevice variations is complicated, time consuming, and potentially inaccurate. We describe a novel fiber optic probe with a real-time self-calibration capability that can be used for tissue optical spectroscopy. The probe was tested in a number of liquid phantoms over a relevant range of tissue optical properties. Absorption and scattering coefficients are extracted with an average absolute error and standard deviation of 6.9%+/-7.2% and 3.5%+/-1.5%, respectively.     

5个不同波长的激光及其线偏振激光辐照人正常膀胱组织光学特性

采用双积分球系统和光辐射测量技术的基本原理以及运用生物组织的光学模型,研究了476.5, 488, 496.5, 514.5和532 nm激光及其线偏振激光辐照人正常膀胱组织的光学特性。结果表明：组织对激光及线偏振激光的总衰减系数和散射系数均随着波长的增大而减小,而且线偏振激光与非线偏振激光入射是有明显的差异。吸收系数是随着波长的增大而缓慢地减小,但有一些起伏,而与是否线偏振光入射无明显差异。平均散射余弦也是随着波长的增大而减小,而且线偏振激光与非线偏振激光入射是有明显的差异。光学穿透深度则是随着波长的增大而增大,而有一些起伏。折射率在这5个波长范围内的值在(1.37～1.44)之间。Kubelka-Munk二流模型下组织对同一波长的激光及其线偏振激光的吸收系数、散射系数、总衰减系数和有效衰减系数没有显著性差异(P＞0.05)。组织对不同波长的激光或其线偏振激光的吸收系数、散射系数、总衰减系数和有效衰减系数则有些是有明显的差异。     

A comparison of laser ultrasound measurements and finite element simulations for evaluating the elastic properties of tissue mimicking phantoms

Advances in the field of laser ultrasonics have opened up new possibilities in medical applications. This paper presents a finite element modelling technique, which studies laser generated surface acoustic waves in different concentration of soft tissue mimicking agar-agar phantoms. In addition, we propose a novel approach that utilises a low coherence interferometer to detect the laser-induced surface acoustic waves from the tissue mimicking phantoms. A Nd:YAG focused laser line-source is applied to the agar-agar phantoms, which as the same with the FE simulation. The generated SAW signals are detected by a time domain low coherence interferometry system. SAW phase velocity dispersion curves from both of the FE simulation and experiment are calculated. By comparison, we show that the experimental results agree well with those of the FE simulation and theoretical expectations. This study is the first report that a laser-generated SAW phase velocity dispersion technique is applied to soft materials. This technique may open a way for laser ultrasonics to detect the mechanical properties of soft tissues, such as skin.     

In vivo integrated photoacoustic and confocal microscopy of hemoglobin oxygen saturation and oxygen partial pressure

We developed dual-modality microscope integrating photoacoustic microscopy (PAM) and fluorescence confocal microscopy (FCM) to noninvasively image hemoglobin oxygen saturation (sO?) and oxygen partial pressure (pO?) in vivo in single blood vessels with high spatial resolution. While PAM measures sO? by imaging hemoglobin optical absorption at two wavelengths, FCM quantifies pO? using phosphorescence quenching. The variations of sO? and pO? values in multiple orders of vessel branches under hyperoxic (100% oxygen) and normoxic (21% oxygen) conditions correlate well with the oxygen-hemoglobin dissociation curve. In addition, the total concentration of hemoglobin is imaged by PAM at an isosbestic wavelength.     

Frequency-swept ultrasound-modulated optical tomography in biological tissue by use of parallel detection

A frequency-swept ultrasonic beam was focused into a biological tissue sample to modulate the laser light passing through the ultrasonic beam inside the tissue. Parallel detection of the speckle field formed by the transmitted laser light was implemented with the source-synchronous-illumination lock-in technique to improve the signal-to-noise ratio. The ultrasound-modulated laser light reflects the local optical and mechanical properties in the ultrasonic beam and can be used for tomographic imaging of the tissue. Sweeping the ultrasonic frequency provides spatial resolution along the ultrasonic axis, which is scalable with the frequency span of the sweep. Two-dimensional images of biological tissue with buried objects were successfully obtained experimentally.     

Optical coherence tomography with plasmon resonant nanorods of gold

We explored plasmon resonant nanorods of gold as a contrast agent for optical coherence tomography (OCT). Nanorod suspensions were generated through wet chemical synthesis and characterized with spectrophotometry, transmission electron microscopy, and OCT. Polyacrylamide-based phantoms were generated with appropriate scattering and anisotropy coefficients (30 cm(-1) and 0.89, respectively) to image distribution of the contrast agent in an environment similar to that of tissue. The observed signal was dependent on whether the plasmon resonance peak overlapped the source bandwidth of the OCT, confirming the resonant character of enhancement. Gold nanorods with plasmon resonance wavelengths overlapping the OCT source yielded a signal-to-background ratio of 4.5 dB, relative to the tissue phantom. Strategies for OCT imaging with nanorods are discussed.     

人膀胱癌组织对不同波长的激光及其线偏振激光的衰减特性比较研究

采用双积分球系统和光辐射测量技术的基本原理以及运用生物组织的光学模型,研究了4765,488,4965,5145,532nm激光及其线偏振激光辐照人膀胱癌组织的光衰减特性。结果表明在5个不同的激光波长范围内,KubelkaMunktwoflux模型下的人膀胱癌组织对不同波长的激光及线偏振激光的衰减特性是不同的,人膀胱癌组织对4765,4965,532nm激光及其线偏振激光的总衰减系数或有效衰减系数均具有显著性差异(P<005),而对488,5145nm波长的激光及其线偏振激光的总衰减系数或有效衰减系数则均没有显著性差异(P>005),人膀胱癌组织对532nm激光及其线偏振激光的总衰减系数或有效衰减系数均明显大于其他4个波长的Ar 激光及其线偏振激光的总衰减系数或有效衰减系数。在传输理论下人膀胱癌组织对5个不同波长的激光及其线偏振激光的总衰减系数均随着波长的增大而减小,人膀胱癌组织对4765,4965,5145nm波长的激光及其线偏振激光的总衰减系数均有显著性差异(P<005),其对488,532nm波长的激光及其线偏振激光的总衰减系数均没有显著性差异(P>005)。     

Shot-noise detection of ultrasound-tagged photons in ultrasound-modulated optical imaging

We propose a new detection method for ultrasound-modulated optical tomography that allows us to perform parallel speckle detection with optimum shot-noise sensitivity, using a CCD camera. Moreover, we show that making use of a spatial filter system allows us to fully filter out speckle decorrelation noise. This method is confirmed by a test experiment.     

Simultaneous correction of the influence of skin color and fat on tissue spectroscopy by use of a two-distance fiber-optic probe and orthogonalization technique

We have demonstrated simultaneous correction for the optical interference of skin and fat in tissue spectra by using a two-distance fiber-optic probe. We obtained the correction by orthogonalizing the spectra collected at a long source-detector distance (SD) to the spectra collected at a short SD and mapped to the long SD space. The method was validated in tissuelike three-layer phantoms as well as preliminarily in human tissue. After the correction, a partial-least-squares model of the phantoms showed enhanced prediction performance.     

超声调制介质中漫散射光自相关性质研究

研究了超声调制随机介质中漫散射光自相关性质,推导出均匀无限介质中有超声场调制时漫散射光时间自相关函数的表达式,讨论了调制参数、调制幅度及其衰减与超声参数、光散射参数等的关系.用Monte Carlo方法研究了随机介质中隐含异物成像的可行性.结果表明,正常生物组织和病变生物组织的超声调制自相关函数有明显的差别,该方法为光学医学诊断提供了一种新参考 关键词： 自相关 漫散射光 超声调制 光学成像     

Correlation transfer and diffusion of ultrasound-modulated multiply scattered light

We develop a temporal correlation transfer equation (CTE) and a temporal correlation diffusion equation (CDE) for ultrasound-modulated multiply scattered light. These equations can be applied to an optically scattering medium with embedded optically scattering and absorbing objects to calculate the power spectrum of light modulated by a nonuniform ultrasound field. We present an analytical solution based on the CDE and Monte Carlo simulation results for light modulated by a cylinder of ultrasound in an optically scattering slab. We further validate with experimental measurements the numerical calculations for an actual ultrasound field. The CTE and CDE are valid for moderate ultrasound pressures and on a length scale comparable with the optical transport mean-free path. These equations should be applicable to a wide spectrum of conditions for ultrasound-modulated optical tomography of soft biological tissues.