Spectral contrast imaging microscopy

We introduce a new technique, spectral contrast imaging microscopy (SCIM), for super-resolution microscopic imaging. Based on a novel contrast mechanism that encodes each local spatial frequency with a corresponding optical wavelength, SCIM provides a real-time high-resolution spectral contrast microscopic image with superior contrast. We show that two microscopic objects, separated by a distance smaller than the diffraction limit of the optical system, can be spatially resolved in the SCIM image as different colors. Results with numerical simulation and experiments using a high-resolution United States Air Force target are presented. The ability of SCIM for imaging biological cells is also demonstrated.     

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.     

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.     

Confocal enhanced optical coherence tomography for nondestructive evaluation of paints and coatings

We investigate confocal enhanced optical coherence tomography as a nondestructive evaluation tool for imaging with improved image contrast and depth resolution through a highly scattering paint layer. The depth responses provided by confocal microscopy, optical coherence tomography, and confocal enhanced optical coherence tomography for imaging through paint are investigated. We demonstrate that a new combination of confocal microscopy and optical coherence tomography provides significantly improved resolution and contrast for coherence gated imaging of substrate structures under the paint.     

Optical scatter imaging: subcellular morphometry in situ with Fourier filtering

We demonstrate a quantitative optical scatter imaging (OSI) technique, based on Fourier filtering, for detecting alterations in the size of particles with wavelength-scale dimensions. We generate our scatter image by taking the ratio of images collected at high and low numerical aperture in central dark-field microscopy. Such an image spatially encodes the ratio of wide to narrow angle scatter and hence provides a measure of local particle size. We validated OSI on sphere suspensions and live cells. In live cells, OSI revealed biochemically induced morphological changes that were not apparent in unprocessed differential interference contrast images. Unlike high-resolution imaging methods, OSI can provide size information for particles smaller than the camera's spatial resolution.     

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.     

超分辨重建技术及其研究进展

超高分辨成像技术一直是航天、遥感、目标识别等领域的研究热点。随着光学成像到光电数字成像的转变,如何提高CCD的几何分辨率,已成为研制高分辨光电成像系统亟待解决的问题。本文从理论和工程实现的角度介绍了超分辨成像的技术原理,分析了实现超分辨重建技术的几种方法,主要描述了微扫描和亚像元两种重建技术的实现方式,指出了目前超分辨技术存在的缺陷。最后,针对超分辨技术中无混淆重建带宽较窄的问题,提出了一种新的技术方案。该方案将光学编码技术与目前的亚像元技术相结合,可将重建带宽拓展3倍。研究结论指出：融合了光学,光电子学和信号处理的成像系统的综合设计,将是未来成像领域的一个重要研究方向。     

Object reconstruction in scattering medium using multiple elliptical polarized speckle contrast projections and optical clearing agents

In this paper, we present a hybrid method for improving the imaging quality of objects obscured within a scattering environment by combining multiple elliptical polarized speckle contrast projections with the use of optical clearing agents (OCAs). Elliptically polarized light enables the probing of subsurface volumes, where OCAs decrease light scattering while increasing photons׳ penetration depth through the medium. Experiments were conducted on object sample and prostate cancer cells embedded within ex vivo biological samples (chicken breasts) in reflection configuration. After immersion with OCAs, the medium was irradiated with an elliptically polarized laser beam and multiple polarized speckled images obtained from a lens array were first converted to speckled contrast images and then processed using a self-deconvolution shift-and-add algorithm. The conversion to contrast images and multiple perspectives acquisition was found to emphasize contrast. Analysis of image quality indicated improvement in object visualization by the combination of elliptical polarization and OCAs. This enhanced imaging strategy may advance the development of improved methods in biomedicine field, specifically biomedical tomography.     

Comparison of fast field-cycling magnetic resonance imaging methods and future perspectives

ABSTRACT

Fast field-cycling (FFC) nuclear magnetic resonance relaxometry is a well-established method to determine the relaxation rates as a function of magnetic field strength. This so-called nuclear magnetic relaxation dispersion gives insight into the underlying molecular dynamics of a wide range of complex systems and has gained interest especially in the characterisation of biological tissues and diseases. The combination of FFC techniques with magnetic resonance imaging (MRI) offers a high potential for new types of image contrast more specific to pathological molecular dynamics. This article reviews the progress in FFC-MRI over the last decade and gives an overview of the hardware systems currently in operation. We discuss limitations and error correction strategies specific to FFC-MRI such as field stability and homogeneity, signal-to-noise ratio, eddy currents and acquisition time. We also report potential applications with impact in biology and medicine. Finally, we discuss the challenges and future applications in transferring the underlying molecular dynamics into novel types of image contrast by exploiting the dispersive properties of biological tissue or MRI contrast agents.     

Photorefractive detection of tissue optical and mechanical properties by ultrasound modulated optical tomography

Ultrasound-modulated optical tomography is a developing hybrid imaging modality that combines high optical contrast and good ultrasonic resolution for imaging soft biological tissue. We developed a photorefractive-crystal-based, time-resolved detection scheme with the use of a millisecond long ultrasound burst to image both the optical and the mechanical properties of biological tissues, with improved detection efficiency of ultrasound-tagged photons.     

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.     

“Molecular” MR imaging at high fields

Magnetic resonance imaging (MRI) and spectroscopy (MRS) have contributed considerably to clinical radiology, and a variety of MR techniques have been developed to evaluate pathological processes as well as normal tissue biology at the cellular and molecular level. However, in comparison to nuclear imaging, MRI has relatively poor sensitivity for detecting true molecular changes or for detecting the presence of targeted contrast agents, though these remain under active development. In recent years very high field (7 T and above) MRI systems have been developed for human studies and these provide new opportunities and technical challenges for molecular imaging. We identify 5 types of intrinsic contrast mechanisms that do not require the use of exogenous agents but which can provide molecular and cellular information. We can derive information on tissue composition by (i) imaging different nuclei, especially sodium (ii) exploiting chemical shift differences as in MRS (iii) exploiting specific relaxation mechanisms (iv) exploiting tissue differences in the exchange rates of molecular species such as amides or hydroxyls and (v) differences in susceptibility. The increased signal strength at higher fields enables higher resolution images to be acquired, along with increased sensitivity to detecting subtle effects caused by molecular changes in tissues.     

利用近红外光激发的光声血管造影成像

利用近红外光结合对应波长的光吸收增强对照剂来实现在体小鼠脑皮层血管的光声成像.近红外光在生物组织上有较深的穿透能力;而作为光吸收增强剂的外源染料吲哚菁绿注射到血液系统后则增加了血管对光的选择性吸收,从而增强了血管光声信号的强度.实验在不破坏脑头皮和头盖骨的前提下,通过静脉注射吲哚菁绿,获得小鼠脑皮层血管的光声造影成像.光声重建的血管网络与小鼠脑部解剖照片相当符合.实验结果证明近红外光结合光吸收增强剂的光声血管造影技术对于开展光声脑功能成像,光声分子成像提供了潜在的可行性. 关键词： 光声成像 光吸收增强剂 血管造影 光声信号     

Dynamic contrast-enhanced MRI of Implanted VX2 tumors in rabbit muscle: comparison of Gd-DTPA and NMS60

We studied the dynamics of injected contrast enhancement in implanted VX2 tumors in rabbit thigh muscle. We compared two contrast agents Gd-DTPA and NMS60, a novel gadolinium containing trimer of molecular weight 2.1 kd. T1-weighted spin echo images were acquired preinjection and at 5-60 min after i.v. injection of 0.1 mmol/kg of agent. Dynamic T1-weighted SPGR images (1.9 s/image) were acquired during the bolus injection. Male NZW rabbits (n = 13) were implanted with approximately 2 x 10(6) VX2 tumor cells and grew tumors of 28+/-27 mL over 12 to 21 days. NMS60 showed significantly greater peak enhancement in muscle, tumor rim, and core compared to DTPA in both T1-weighted and SPGR images. NMS60 also showed delayed peak enhancement in the dynamic scans (compared to Gd-DTPA) and significantly reduced leakage rate constant into the extravascular space for tumor rim (K21 = 5.1 min(-1) vs. 11.5 min(-1) based on a 2 compartment kinetic model). The intermediate weight contrast agent NMS60 offers greater tumor enhancement than Gd-DTPA and may offer improved regional differentiation on the basis of vascular permeability in tumors.     

Optical properties and biomedical applications of plasmonic nanoparticles

Nanoparticle plasmonics is a rapidly emerging research field that deals with the fabrication and optical characterization of noble metal nanoparticles of various size, shape, structure, and tunable plasmon resonances over VIS-NIR spectral band. The recent simultaneous advances in synthesis, characterization, electromagnetic simulation, and surface functionalization of plasmonic nanoparticles by biospecific molecular probes have led to a perfect publication storm in discoveries and potential biomedical applications of plasmon-resonant nanoparticle bioconjugates. Here, we present an overview of these topics. First, we discus basic wet-chemical routes to fabricate conjugates of gold, silver, or composite particles with controllable size, shape, structure and with surface functionalization by biospecific molecules. Second, we consider the single-particle dipole and multipole optics and coupled plasmonic nanoparticle arrays. Finally, we discus application of plasmonic bioconjugates to such fields as homogeneous and solid-phase assays, biomedical sensing and imaging, biodistribution and toxicity aspects, drug delivery and plasmonic photothermal therapy.     

Microthermomechanical infrared sensors

We present a state-of-the-art overview of microthermomechanical infrared sensor technology. The working principle of this sensor is based on a bi-material actuated micromechanical deflection, generated by an induced temperature rise due to incident infrared radiation absorption. In order to generate a thermal image the thermomechanical deflections of the freestanding microstructures are read by either capacitive, piezoresistive or optical means. Research and development activities in this field began in the early 1990s. The development of this technology within the last 20 years has resulted in innovations such as uncooled multiband infrared detection, high-speed infrared sensing and uncooled THz imaging. This paper outlines representative milestones of this technology and analyses important results of notable groups. Significant activities on capacitive and optical readout techniques of thermomechanical infrared arrays are presented. Furthermore the advantages of microthermomechanical infrared sensors over current well-established uncooled infrared technologies are summarized. In conclusion the latest developments of this technology offer a highly potential solution for a variety of important energy-saving, safety and security applications.     

新型Gd基T2造影剂的制备和应用

设计并合成了结构为TPP-Lys（Acp-DOTA-Gd）-COOH（简称Gd-DOTA-TPP）的小分子磁共振探针,通过电转染的方式用探针标记人源脐带间充质干细胞（hMSCs）.11.7 T磁共振成像（MRI）扫描结果表明,Gd-DOTA-TPP标记的hMSCs在细胞内Gd含量为9×10⁹ Gd/cell时,T₂加权信号强度即可低至背景信号强度,呈现较强暗信号.将Gd-DOTA-TPP标记的hMSCs移植入小鼠脑室,可明显提高移植干细胞在MRI设备上的检测灵敏度,检测限可低至10³个细胞.     

Optimal design of gold nanoshells for optical imaging and photothermal therapy

Gold nanoshells are of great interest in optical imaging based on their light scattering properties and photothermal therapy due to their light absorption properties. Strong light scattering is essential for optical imaging, while effective photothermal therapy requires high light absorption. In this article, the optimal core radii and shell thicknesses of silica–gold and hollow gold nanoshells, possessing maximal light scattering and absorption at wavelengths between 700 and 1100 nm, are obtained using the Mie theory of a coated sphere. The results show that large-sized gold nanoshells of high aspect ratios (the aspect ratio is defined as the ratio of core radius to shell thickness) are the efficient contrast agents for optical imaging, while smaller gold nanoshells of high aspect ratios are the ideal therapeutic agents for photothermal therapy. From the comparison of the numerical results for silica–gold and hollow gold nanoshells, the latter are seen to offer a little superior light scattering and absorption at smaller particle size. Fitting expressions for the optimal core radii and shell thicknesses are also obtained, which can provide design guidelines for experimentalists to optimize the synthetic process of gold nanoshells.     

Photoacoustic microscopy

Photoacoustic microscopy (PAM) is a hybrid in vivo imaging technique that acoustically detects optical contrast via the photoacoustic effect. Unlike pure optical microscopic techniques, PAM takes advantage of the weak acoustic scattering in tissue and thus breaks through the optical diffusion limit (∼1 mm in soft tissue). With its excellent scalability, PAM can provide high‐resolution images at desired maximum imaging depths up to a few millimeters. Compared with backscattering‐based confocal microscopy and optical coherence tomography, PAM provides absorption contrast instead of scattering contrast. Furthermore, PAM can image more molecules, endogenous or exogenous, at their absorbing wavelengths than fluorescence‐based methods, such as wide‐field, confocal, and multi‐photon microscopy. Most importantly, PAM can simultaneously image anatomical, functional, molecular, flow dynamic and metabolic contrasts in vivo. Focusing on state‐of‐the‐art developments in PAM, this Review discusses the key features of PAM implementations and their applications in biomedical studies.     

Second-harmonic optical coherence tomography

Second-harmonic optical coherence tomography, which uses coherence gating of second-order nonlinear optical responses of biological tissues for imaging, is described and demonstrated. Femtosecond laser pulses were used to excite second-harmonic waves from collagen harvested from rat tail tendon and a reference non-linear crystal. Second-harmonic interference fringe signals were detected and used for image construction. Because of the strong dependence of second-harmonic generation on molecular and tissue structures, this technique imparts contrast and resolution enhancement to conventional optical coherence tomography.