聚吡咯修饰的金纳米棒对肿瘤的光学相干层析成像的影响

聚吡咯(PPy)制备简单、生物相容性好,且在近红外(NIR)光谱范围内有很强的吸收,可作为一种良好的光热治疗试剂;同时,其NIR光吸收性质也可用于增强光学相干层析成像(OCT)的对比效果。因此,采用PPy对传统的OCT对比试剂——金纳米棒(GNR)进行表面修饰,有望获得对比效果更好且生物毒性较小的新型OCT对比试剂。选用吡咯为起始原料,在GNR表面进行一步简单的氧化聚合反应即可制备得到PPy修饰的金纳米棒(GNR-PPy)。利用紫外-可见吸收光谱,拉曼光谱和透射电子显微镜对制备的样品进行了分析和表征。构建小鼠荷瘤模型,以研究GNR-PPy对肿瘤OCT图像对比度的增强效果。采用中心波长为840 nm的OCT系统对注射了纳米粒子的肿瘤区域进行OCT成像。结果表明,肿瘤组织注射了GNR-PPy后,OCT信号衰减非常明显;与注射了GNR的OCT图像相比,840 nm光在GNR-PPy的OCT图像中的穿透深度明显更低。从OCT图像中抽提出一维的衰减曲线对OCT图像进行定量分析,发现注射有GNR-PPy肿瘤组织的OCT信号衰减系数明显高于注射了GNR的组织。表明,相对于GNR,GNR-PPy具有更好的OCT信号对比效果,这在增强肿瘤成像效果方面具有潜在应用价值。     

Imaging magnetically labeled cells with magnetomotive optical coherence tomography

We introduce a novel contrast mechanism for optical coherence tomography (OCT) whereby the optical scattering of magnetically labeled cells is modified by means of an externally applied magnetic field. This modification is made through the addition of a small electromagnet to the imaging arm of a conventional OCT interferometer. We measure the magnetomotive OCT signal by differencing pairs of axial scans (A-scans) acquired with the magnetic field on and off. Magnetomotive contrast is demonstrated in bulk three-dimensional cell scaffolds containing macrophages labeled with microparticles of iron oxide, demonstrating magnetic-specific contrast over a dynamic range of 30 dB.     

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.     

Spectroscopic optical coherence tomography

Spectroscopic optical coherence tomography (OCT), an extension of conventional OCT, is demonstrated for performing cross-sectional tomographic and spectroscopic imaging. Information on the spectral content of backscattered light is obtained by detection and processing of the interferometric OCT signal. This method allows the spectrum of backscattered light to be measured over the entire available optical bandwidth simultaneously in a single measurement. Specific spectral features can be extracted by use of digital signal processing without changing the measurement apparatus. An ultrabroadband femtosecond Ti:Al(2)O(3) laser was used to achieve spectroscopic imaging over the wavelength range from 650 to 1000 nm in a simple model as well as in vivo in the Xenopus laevis (African frog) tadpole. Multidimensional spectroscopic data are displayed by use of a novel hue-saturation false-color mapping.     

Compact,low-cost Ti:Al2O3 laser for in vivo ultrahigh-resolution optical coherence tomography

A compact, low-cost, prismless Ti:Al2O3 laser with 176-nm bandwidth (FWHM) and 20-mW output power was developed. Ultrahigh-resolution ophthalmic optical coherence tomography (OCT) ex vivo imaging in an animal model with approximately 1.2-microm axial resolution and in vivo imaging in patients with macular pathologies with approximately 3-microm axial resolution were demonstrated. Owing to the pump laser, this light source significantly reduces the cost of broadband OCT systems. Furthermore, the source has great potential for clinical application of spectroscopic and ultrahigh-resolution OCT because of its small footprint (500 mm x 180 mm including the pump laser), user friendliness, stability, and reproducibility.     

Spectroscopic spectral-domain optical coherence microscopy

The spectroscopic content within optical coherence tomography (OCT) data can provide a wealth of information. Spectroscopic OCT methods are frequently limited by time-frequency trade-offs that limit high spectral and spatial resolution simultaneously. We present spectroscopic spectral-domain optical coherence microscopy performed with a multimodality microscope. Restricting the spatial extent of the signal by using high-numerical-aperture optics makes high-resolution spectroscopic information accessible, facilitated with spectral-domain detection. Simultaneous acquisition of multiphoton microscopy images is used to validate tissue structure and localization of nuclei within individual cells.     

Gold Nanocages as Effective Photothermal Transducers in Killing Highly Tumorigenic Cancer Cells

Numerous gold nanostructures have the potential for photothermal therapy in cancers. Here, gold nanocages and gold nanoshells are synthesized, the sizes of which are fine‐tuned for a response at 750 nm wavelength. Their photothermal therapeutic efficiency is compared at gold concentration of 100 lg mL^?1 using a near‐infrared laser (750 nm). The biocompatibility for varying concentrations of gold (1 to 100 lg mL^?1) is performed in a normal cell line and laser‐mediated cell cytotoxicity for varying time intervals (7.5 and 10 min) is carried out in breast cancer cells. This study shows that when analyzed under similar conditions, the gold nanocages show better biocompatibility and are more efficient in near‐infrared absorption and photothermal conversion in comparison with conventional gold nanoshells. When subjected to photothermal laser ablation of breast cancer cell line for 7.5 min and 10 min, the nanocages are able to induce 62.92 ± 3.25% and 96.41 ± 3.04% reduction in cell viability, respectively, in comparison to nanoshells, in which a 43.35 ± 1.91% and 79.89 ± 4.74% reduction in cell viability is observed. The current study shows that the gold nanocages can outperform gold nanoshells and effectively kill cancer cells without any significant cytotoxic effect on normal cells.     

Time-gated Fourier-domain optical coherence tomography

A novel optical coherence tomography (OCT) system is presented that combines Fourier-domain OCT with incoherent nonlinear time gating. By processing backscattered light in the optical domain, the user can select a restricted depth field of view for improved contrast and acquisition speed. This technique has the additional advantage that imaging is done in the infrared (approximately 1280 nm) but is detected in the visible(approximately 504 nm).     

Wavelength-dependent nonlinear absorption of gold nanocages

The dipole resonances of gold nanocages were investigated theoretically using finite difference time domain method.The results show that field enhancement is obtained at the walls of the gold nanocages.It is believed that the effect can cause a strong optical nonlinear property.To test the hypothesis,nonlinear absorption was investigated using a broadband 5 ns Z scan.It was found that at low intensities the sample shows saturable absorption(SA),while at higher intensities a switch from SA to reverse SA occurs.Moreover,the nonlinear absorption of the sample is sensitively wavelength-dependent,and,in the resonant region,saturation intensity is the largest.     

Dual-modality photothermal optical coherence tomography and magnetic-resonance imaging of carbon nanotubes

We demonstrate polyethylene-glycol-coated single-walled carbon nanotubes (CNTs) as contrast agents for both photothermal optical coherence tomography (OCT) and magnetic-resonance imaging (MRI). Photothermal OCT was accomplished with a spectral domain OCT system with an amplitude-modulated 750 nm pump beam using 10 mW of power, and T(2) MRI was achieved with a 4.7 T animal system. Photothermal OCT and T(2) MRI achieved sensitivities of nanomolar concentrations to CNTs dispersed in amine-terminated polyethylene glycol, thus establishing the potential for dual-modality molecular imaging with CNTs.     

Linear optical coherence tomography system with extended measurement range

Optical coherence tomography (OCT) sensors traditionally use scanning optical delay lines with moving parts and a single detector. OCT systems with a linear detector array (linear OCT or L-OCT) are simple and robust, but a detector with approximately 10,000 pixels is needed for an imaging depth of 2mm, which is necessary for most biomedical applications. We present a new optical setup for L-OCT with an increased measurement range. An additional grating performs a reduction of the spatial frequencies of the fringe pattern on the detector without loss in the signal-to-noise ratio, so the signal can be sampled with a minimal number of pixels. The theory for this approach is addressed and the first measurements are presented.     

Near-infrared dyes as contrast-enhancing agents for spectroscopic optical coherence tomography

Optical coherence tomography (OCT) images of biological tissues often have low contrast. Spectroscopic optical coherence tomography (SOCT) methods have been developed to enhance contrast but remain limited because most tissues are not spectrally active in the frequency bands of laser sources commonly used in OCT. Near-infrared (NIR) dyes with absorption spectra features within the OCT source spectrum can be used for enhancing contrast in this situation. We introduce and demonstrate the use of NIR dyes as contrast agents for SOCT. Contrast-enhanced images are compared with fluorescence microscopy, demonstrating a link between SOCT and fluorescence imaging.     

Simulation of polarization-sensitive optical coherence tomography images by a Monte Carlo method

We introduce a new Monte Carlo (MC) method for simulating optical coherence tomography (OCT) images of complex multilayered turbid scattering media. We demonstrate, for the first time of our knowledge, the use of a MC technique to imitate two-dimensional polarization-sensitive OCT images with nonplanar boundaries of layers in the medium like a human skin. The simulation of polarized low-coherent optical radiation is based on the vector approach generalized from the iterative procedure of the solution of Bethe-Saltpeter equation. The performances of the developed method are demonstrated both for conventional and polarization-sensitive OCT modalities.     

In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography

We describe a novel optical system for bidirectional color Doppler imaging of flow in biological tissues with micrometer-scale resolution and demonstrate its use for in vivo imaging of blood flow in an animal model. Our technique, color Doppler optical coherence tomography (CDOCT), performs spatially localized optical Doppler velocimetry by use of scanning low-coherence interferometry. CDOCT is an extension of optical coherence tomography (OCT), employing coherent signal-acquisition electronics and joint time-frequency analysis algorithms to perform flow imaging simultaneous with conventional OCT imaging. Cross-sectional maps of blood flow velocity with <50-microm spatial resolution and <0.6-mm/s velocity precision were obtained through intact skin in living hamster subdermal tissue. This technology has several potential medical applications.     

Image enhancement in near-field scanning optical microscopy with laser-trapped metallic particles

A trapped-particle near-field scanning optical microscope is constructed by use of submicrometer- or micrometer-sized metallic particles (gold and silver) to increase scattering efficiency. The image contrast of the evanescent-wave interference pattern on the surface of a prism upon total internal reflection, obtained with trapped gold particles of diameter 0.1 and 2microm , is improved by a factor of approximately 2 and 1.5, respectively, compared with that obtained with trapped polystyrene particles of similar size. The use of a 2-microm gold particle leads to image contrast that is approximately three times as great as that obtained with a 0.1-microm gold particle, and interference patterns of a subwavelength period are obtained in both cases.     

基于受激辐射信号的谱域光学相干层析分子成像方法

鉴于不同生理病理状态下组织复折射率实部的变化不大,传统光学相干层析(OCT)成像技术在分子特异性识别上存在先天不足.为此,本文提出了基于受激辐射信号的OCT成像方法,可在实现传统散射成像的同时,实现基于受激辐射信号的分子成像.在超高分辨率谱域OCT系统的基础上,通过增设光谱分光与调制抽运光支路,建立了基于单宽谱光源的抽运探测谱域OCT系统,详细推导了调制抽运下受激辐射信号的获取与成像公式.利用搭建的抽运探测谱域OCT系统,实现了瞬态受激辐射信号的相干探测.基于同时获取的受激辐射OCT信号和传统OCT信号,成功重构了氮化物粉末构建样品的基于受激辐射信号的分子对比OCT图像.     

Rotational dynamics of gold nanoparticle chains in water solution

In this study, the optical properties of two nano-sized polymer colloids in optical coherence tomography (OCT) were compared in vitro with respect to their potential use as contrast agents. We used two types of particles: compact hydrophobic spherical polystyrene (PS) particles and soft water-swollen nanogel (NG) particles both with grafted hydrophilic shell, both prepared at two different sizes (PS at 300 and 150?nm, NG at 300 and 200?nm). The OCT backscattering signals of the particles in a vessel-mimicking highly scattering agar/TiO₂ phantom were compared on either number of particles or weight percent. Larger particles and higher concentrations produced higher OCT contrast. At each concentration tested, a markedly higher contrast was achieved by PS particles than NG particles. PS particles generated a markedly higher OCT contrast than the phantom at concentrations of at least 1?×?10¹⁰ or 0.1?% for PS 300?nm and at least 3?×?10¹¹ particles/mL or 0.4?% for PS 150?nm. The contrast generated by NG 300?nm was above the phantom contrast at concentrations of at least 3?×?10¹¹ particles/mL or 1?%, whereas NG 200?nm only at 4?%. At any given weight percent, the differences in OCT contrast between differently sized particles were much less evident than in the comparison based on particle number. PS 300?nm generated also a good contrast ex vivo on chicken muscle tissue. These results strongly suggest that PS spheres have strong potential as intravascular OCT contrast agent, while NG particles need further contrast enhancer for being used as OCT contrast agent.     

Rapid-scanning forward-imaging miniature endoscope for real-time optical coherence tomography

We developed a miniature endoscope that is capable of rapid lateral scanning and is suitable for real-time forward-imaging optical coherence tomography (OCT). The endoscope has an outer diameter of 2.4 mm, consisting of a miniature tubular lead zirconate titanate (PZT) actuator, a single-mode fiber-optic cantilever, and a graded-index lens. Rapid lateral scanning at 2.8 kHz is achieved when the fiber-optic cantilever is resonated with the PZT actuator. This allows OCT imaging to be performed by fast lateral beam scanning followed by slow depth scanning, which is different from the conventional OCT imaging sequence. Real-time OCT imaging with the endoscope operated in the new image acquisition sequence at 6 frames/s is demonstrated.     

Molecular contrast in optical coherence tomography by use of a pump-probe technique

We describe a novel technique for contrast enhancement in optical coherence tomography (OCT) that makes possible molecular-specific imaging for what is believed to be the first time. A pump-probe technique is employed in which a pulsed pump laser is tuned to ground-state absorption in a molecule of interest. The location of the target molecule population is derived from the resulting transient absorption of OCT sample-arm light acting as probe light. A signal processing technique for three-dimensional localization of the transient absorption signal is described, and preliminary results exhibiting OCT contrast from methylene blue dye in multilayer and scattering phantoms are presented.     

Optical Coherence Tomography Implemented by Photonic Crystal Fiber

We report a photonic crystal fiber (PCF)-based optical coherence tomography (OCT) system, in which conventional single-mode fiber for the transmission line and the fiber coupler for the beam splitter/combiner are replaced with PCF and PCF coupler. The PCF coupler fabricated using the fused biconical tapered (FBT) method showed a nearly flat coupling ratio over a broad spectral bandwidth of 400 nm, which provided an axial resolution of 3-μm for OCT imaging. With a white-light source, the 8-μm thick air gap between two stacked cover glasses was measured, and with a conventional superluminecent diode (SLD) source, the in vitro images of rat eye and Misgurnus mizolepis skin were successfully obtained. The PCF and PCF coupler might enable a white-light as the source for the cost effective and high-resolution OCT system.