光声成像及其在生物医学中的应用

光声成像是一种新近迅速发展起来、基于生物组织内部光学吸收差异、以超声作媒介的无损生物光子成像方法,它结合了纯光学成像的高对比度特性和纯超声成像的高穿透深度特性的优点,以超声探测器探测光声波代替光学成像中的光子检测,从原理上避开了光学散射的影响,可以提供高对比度和高分辨率的组织影像,为研究生物组织的结构形态、生理特征、代谢功能、病理特征等提供了重要手段,在生物医学临床诊断以及在体组织结构和功能成像领域具有广泛的应用前景.对光声成像技术的机理、光声成像技术和方法、光声图像重建算法以及光声成像在生物医学上的应用情况作一个简单介绍,希望有助于推动我国在该领域的科研和开发应用工作的迅速发展.     

Indocyanine green-enhanced multimodal photoacoustic microscopy and optical coherence tomography molecular imaging of choroidal neovascularization

Photoacoustic microscopy (PAM) has great potential for visualization of the microvasculature with high spatial resolution and contrast. Early detection and differentiation of newly developed blood vessels named choroidal neovascularization (CNV) from normal vasculature remains a challenge in ophthalmology. Exogenous contrast agents can assist with improving PAM sensitivity, leading to differentiation of CNV. Here, an FDA-approved indocyanine green (ICG) was utilized as a PAM contrast agent. ICG was conjugated with RGD peptides, allowing the ICG to bind to the integrin expressed in CNV. Molecular PAM imaging showed that ICG-RGD can target CNV for up to 5 days post intravenous administration in living rabbits with a model of CNV. The PAM image sensitivity and image contrast were significantly enhanced by 15-fold at 24 h post-injection. Overall, the presented approach demonstrates the possibility of targeted ICG to be employed in PAM molecular imaging, allowing more precise evaluation of neovascularization.     

热声成像技术及其在生物医学中的研究进展

摘要：成像技术在疾病的诊断、治疗和监测中起着重要的作用。热声成像作为一种非电离和非侵入性的新型生物医学成像技术,结合了微波成像高对比度和超声成像高分辨率的优点。因其具有利用内源性对比剂（如水和离子）或多种外源性对比剂（或两者兼有）提供结构、功能、和分子信息的能力,在预临床和临床应用中显示出了巨大的潜力。近几十年来,由于微波辐射源和超声硬件的不断发展,热声成像技术已被广泛用于生物医学成像领域。本文阐述了热声成像的基本原理及成像特点,介绍了近年来热声成像技术在生物医学上的应用、当前在解决相应临床问题应用中的优势及研究现状,最后针对热声成像技术在现有生物医学中面临的挑战对该技术进行了展望。     

High resolution,label‐free photoacoustic imaging of live chicken embryo developing in bioengineered eggshell

Chicken embryos have been proven to be an attractive vertebrate model for biomedical research. They have helped in making significant contributions for advancements in various fields like developmental biology, cancer research and cardiovascular studies. However, a non‐invasive, label‐free method of imaging live chicken embryo at high resolution still needs to be developed and optimized. In this work, we have shown the potential of photoacoustic tomography (PAT) for imaging live chicken embryos cultured in bioengineered eggshells. Laser pulses at wavelengths of 532 and 740 nm were used for attaining cross‐sectional images of chicken embryos at different developmental stages. Cross‐sections along different depths were imaged to gain knowledge of the relative depth of different vessels and organs. Due to high optical absorption of vasculature and embryonic eye, images with good optical contrast could be acquired using this method. We have thus reported a label‐free method of performing cross‐sectional imaging of chicken embryos at high resolution demonstrating the capacity of PAT as a promising tool for avian embryo imaging.     

超声分子成像的研究进展

超声成像无创、无放射性、低成本、实时成像的优点,使其成为目前世界上应用最广的成像手段之一。特别是超声造影剂引入之后,超声成像的图像分辨率和灵敏度得到了大大提高,使超声成像在临床上得到了进一步应用。近年来,随着分子生物学和超声成像技术的不断发展,人们提出了＂超声分子成像＂的概念。它是一项结合了分子靶向造影剂和超声影像技术的能在分子水平下观察病理变化的新兴技术,目前这一技术还处于研究初期阶段。但大量临床前的研究成果已表明超声分子成像在诊断血管生成、炎症和血栓三种疾病具有很大应用前景。本文主要综述了目前常用超声造影剂的种类以及超声分子成像技术的研究现状,并对该技术进行了讨论和展望。     

超声分子成像的研究进展

超声成像无创、无放射性、低成本、实时成像的优点,使其成为目前世界上应用最广的成像手段之一。特别是超声造影剂引入之后,超声成像的图像分辨率和灵敏度得到了大大提高,使超声成像在临床上得到了进一步应用。近年来,随着分子生物学和超声成像技术的不断发展,人们提出了"超声分子成像"的概念。它是一项结合了分子靶向造影剂和超声影像技术的能在分子水平下观察病理变化的新兴技术,目前这一技术还处于研究初期阶段。但大量临床前的研究成果已表明超声分子成像在诊断血管生成、炎症和血栓三种疾病具有很大应用前景。本文主要综述了目前常用超声造影剂的种类以及超声分子成像技术的研究现状,并对该技术进行了讨论和展望。     

多功能磁共振造影剂研究进展

磁共振成像技术因对人体无创、任意方向断层扫描三维图像且分辨率较高、提供形态与功能两方面诊断评价等突出优点,成为了临床上用于疾病诊断的重要手段之一。临床上使用磁共振造影剂可以提高成像的分辨率和灵敏度,提高图像质量,增强对比度和可读性。但是,各种成像技术由于实现原理不同,具有各自的优势和缺陷,靠传统单一的诊断模式无法提供疾病的全面信息,因而在对各种复杂疾病进行诊断时会受到一定的限制。因此,将磁共振成像与其他成像技术如CT成像、超声成像等联合起来使用,则可以达到优势互补的效果,能为疾病的临床诊断提供更快捷精确的信息,同时可将磁共振成像与各种治疗方式结合在一起,即开发基于磁共振成像的诊断治疗一体化试剂,以实现对疾病的即时治疗和实时监控。本文主要介绍了磁共振成像造影剂的原理和种类,并且综述了目前国内外在基于磁共振成像的多功能造影剂/诊疗制剂这一领域的研究进展,最后就未来可能的研究方向进行了展望。     

高时空分辨的脑功能光学成像研究进展

脑功能成像技术对深入分析脑的信息加工过程,揭示脑的高级功能至关重要,是目前国际研究热点,已经在神经科学研究和神经系统疾病的临床诊断方面取得了很大的进展.已有脑功能成像技术如:功能磁共振成像(fMRI)、正电子断层成像(PET)、脑电图(EEG)、脑磁图(MEG)等等,虽然已被成功用于脑功能研究,但是目前这些方法也存在着时间或空间分辨率不够的局限.比较而言,光学成像方法表现出其独特魅力.激光散斑衬比成像和内源信号光学成像由于能提供空间取样、时间分辨率及空间分辨率三者的最佳组合和不需加入外源性标记物等特点,与其他脑功能成像技术相比其优势可能更为突出.具有较高的时间和空间分辨率的这两种脑功能光学成像技术及其应用都取得了重大发展,成为研究脑皮层功能构筑和脑病理生理的有力工具.但是目前这两种成像方法也面临着一些挑战.     

光学相干层析分子成像方法初探

介绍了分子对比剂在光学相干层析成像(optical coherence tom ography,OCT)技术中的研究现状,概述了迄今出现的几种不同的光学相干层析分子成像方法(m olecu lar contrast OCT,简称为MCOCT),讨论了MCOCT的几个重要的实际问题:对比剂的选择范围、激发光强的限制、各种方法灵敏度比较以及MCOCT应用于临床与生物学领域需要考虑的因素。     

Perspectives,potentials and trends of ex vivo and in vivo optical molecular pathology

It is pivotal for medical applications, such as noninvasive histopathologic characterization of tissue, to realize label‐free and molecule‐specific representation of morphologic and biochemical composition in real‐time with subcellular spatial resolution. This unmet clinical need requires new approaches for rapid and reliable real‐time assessment of pathologies to complement established diagnostic tools. Photonic imaging combined with digitalization offers the potential to provide the clinician the requested information both under in vivo and ex vivo conditions. This report summarizes photonic approaches and their use in combination with image processing, machine learning and augmented virtual reality that might solve current challenges in modern medicine. Details are given for pathology, intraoperative diagnosis in head and neck cancer and endoscopic diagnosis in gastroenterology.      

窄等离子体吸收谱线宽度的纳米金锥用于光声成像

无损光声成像技术结合了纯光学成像高选择特性和纯超声成像中深穿透特性的优点,克服了光散射限制,实现了对活体深层组织的高分辨、高对比度成像。该成像技术对内源物质例如脱氧血红蛋白、含氧血红蛋白、黑色素、脂质等进行成像,提供了活体生物组织结构和功能信息,已经在生物医学领域表现出巨大的应用前景。然而,很多与病理过程相关的特征分子的光吸收能力较弱,在活体环境中难以被光声成像系统所识别,从而限制了光声成像技术的应用范围。基于功能纳米探针的光声成像-光声分子成像极大拓展光声成像的应用范围,可以在活体层面对病理过程进行分子水平的定性和定量研究,将为实现目标疾病的早期诊断提供强大的技术支持。本文发展在近红外具有窄吸收线宽(半高宽仅为60 nm)的纳米金锥作为新型的光声探针。通过选择不同径长比的纳米金锥,可以任意调节纳米金锥的吸收峰。通过调谐激光器的波长,可实现对不同吸收峰纳米金锥的选择性激发。纳米金锥将有可能用于多光谱光声成像,实现对不同靶标的目标分子探测。     

激光散斑成像技术在脑科学研究中的应用

激光散斑衬比成像(laser speckle contrast imaging,LSCI)是一种非扫描式实时血流动力学成像技术,具有高分辨率、快速实时成像、非接触、仪器结构较简单等优势.尽管由于深度分辨率的限制,LSCI主要用于浅表组织测量,但其在神经疾病、皮肤病等领域的基础研究及临床应用中展现出良好的应用潜力.本文简要介绍了激光散斑衬比成像技术的基本原理与技术进展,综述其在脑卒中、吸毒成瘾、阿尔茨海默病等脑疾病及其他脑科学应用中的研究进展,并展望其发展前景.     

Real‐time functional optical‐resolution photoacoustic microscopy using high‐speed alternating illumination at 532 and 1064 nm

Optical‐resolution photoacoustic microscopy (OR‐PAM), which has been widely used and studied as a noninvasive and in vivo imaging technique, can yield high‐resolution and absorption contrast images. Recently, metallic nanoparticles and dyes, such as gold nanoparticles, methylene blue, and indocyanine green, have been used as contrast agents of OR‐PAM. This study demonstrates real‐time functional OR‐PAM images with high‐speed alternating illumination at 2 wavelengths. To generate 2 wavelengths, second harmonic generation at 532 nm with an LBO crystal and a pump wavelength of 1064 nm is applied at a pulse repetition rate of 300 kHz. For alternating illumination, an electro‐optical modulator is used as an optical switch. Therefore, the A‐line rate for the functional image is 150 kHz, which is half of the laser repetition rate. To enable fast signal processing and real‐time displays, parallel signal processing using a graphics processing unit (GPU) is performed. OR‐PAM images of the distribution of blood vessels and gold nanorods in a BALB/c‐nude mouse's ear can be simultaneously obtained with 500 × 500 pixels and real‐time display at 0.49 fps.      

A deep‐learning‐based approach for noise reduction in high‐speed optical coherence Doppler tomography

Optical coherence Doppler tomography (ODT) increasingly attracts attention because of its unprecedented advantages with respect to high contrast, capillary‐level resolution and flow speed quantification. However, the trade‐off between the signal‐to‐noise ratio of ODT images and A‐scan sampling density significantly slows down the imaging speed, constraining its clinical applications. To accelerate ODT imaging, a deep‐learning‐based approach is proposed to suppress the overwhelming phase noise from low‐sampling density. To handle the issue of limited paired training datasets, a generative adversarial network is performed to implicitly learn the distribution underlying Doppler phase noise and to generate the synthetic data. Then a 3D based convolutional neural network is trained and applied for the image denoising. We demonstrate this approach outperforms traditional denoise methods in noise reduction and image details preservation, enabling high speed ODT imaging with low A‐scan sampling density.     

应用基于内源信号的光学成像技术的视觉脑研究现状

基于脑内源信号的光学成像技术是近来国际上出现的一种脑功能成像方法。该技术既无毒,又具有较高的空间分辨率,因而被迅速应用于动物的视觉、听觉、体感皮层功能构筑的研究中。本文综述了这种光学脑功能成像在视觉脑研究方面所取得的重要进展,并分析了该方法与其他脑成像技术、微电极单细胞技术的关系。报道了国内自行研制第、套脑功能光学成像系统的研究工作,该系统已在猫初级视觉皮层不同深度获得了清晰的方位功能图,并已经和     

Gadolinium-containing carbon nanomaterials for magnetic resonance imaging: Trends and challenges

Gadolinium-containing carbon nanomaterials are a new class of contrast agent for magnetic resonance imaging. They are characterized by a superior proton relaxivity to any current commercial gadolinium contrast agent and offer the possibility to design multifunctional contrasts. Intense efforts have been made to develop these nanomaterials because of their potential for better results than the available gadolinium contrast agents. The aim of the present work is to provide a review of the advances in research on gadolinium-containing carbon nanomaterials and their advantages over conventional gadolinium contrast agents. Due to their enhanced proton relaxivity, they can provide a reliable imaging contrast for cells, tissues or organs with much smaller doses than currently used in clinical practice, thus leading to reduced toxicity (as shown by cytotoxicity and biodistribution studies). Their active targeting capability allows for improved MRI of molecular or cellular targets, overcoming the limited labelling capability of available contrast agents (restricted to physiological irregularities during pathological conditions). Their potential of multifunctionality encompasses multimodal imaging and the combination of imaging and therapy.     

SPECT neuroimaging in translational research of CNS disorders

High resolution SPECT imaging is an emerging field and there are only limited studies as yet available in this direction. Still there is continuous effort to achieve better spatial and temporal resolution in order to obtain detailed structural and functional information of different brain regions in small experimental animals. Recently, SPECT imaging system has been used to perform in vivo imaging using specific radioligands to further elucidate the role of dopaminergic, serotonergic, and cholinergic neurotransmission in relation to regional cerebral blood flow in various human CNS disorders and in gene-manipulated mouse models of neurodegeneration. Although in vivo and non-invasive translational research can be performed by high-resolution microPET imaging system, its limited spatial resolution restricts detailed anatomical and functional information of different brain regions involved in disease process. Recently developed NanoSPECT/CT imaging system has a better spatial resolution hence can be used to correlate and confirm microPET imaging data and determine the precise structural and functional anatomy of CNS disorders and their remission. Moreover SPECT imaging system reduces the cost and number of animals and provides detailed information of CNS disorders at the cellular, molecular and genetic level. Furthermore, SPECT system is economical, provides less radiation burden, and can be used to study bio-distribution of newly synthesized radioligands with increased target to non-target ratios, quality control, and clinical applications. It is envisaged that high-resolution SPECT imaging system will further improve in vivo non-invasive translational research on CNS disorders of unknown etiopathogenesis and their treatment in future.     

‘Go with the flow ’: A review of methods and advancements in blood flow imaging

Physics has delivered extraordinary developments in almost every facet of modern life. From the humble thermometer and stethoscope to X‐Ray, CT, MRI, ultrasound, PET and radiotherapy, our health has been transformed by these advances yielding both morphological and functional metrics. Recently high resolution label‐free imaging of the microcirculation at clinically relevant depths has become available in the research domain. In this paper, we present a comprehensive review on current imaging techniques, state‐of‐the‐art advancements and applications, and general perspectives on the prospects for these modalities in the clinical realm. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

原子力显微技术在观测微生物表面形态中的应用

原子力显微技术作为一门新发展起来的显微成像技术,不仅具有在近生理条件下对样本实时、高分辨率三维成像等特点,而且能通过力矩测量探知样本物理性状。即给人们认识微生物的表面结构提供又一平台,也为揭示微生物表面结构与功能之间的关系提供一种新方法。介绍了对微生物表面形态观测中常用测量模式和某些样品固定方法:多孔膜技术、凹陷技术,概括近年来原子力显微技术在微生物学中的应用情况。     

Raman ChemLighter: Fiber optic Raman probe imaging in combination with augmented chemical reality

Raman spectroscopy using fiber optic probe combines non‐contacted and label‐free molecular fingerprinting with high mechanical flexibility for biomedical, clinical and industrial applications. Inherently, fiber optic Raman probes provide information from a single point only, and the acquisition of images is not straightforward. For many applications, it is highly crucial to determine the molecular distribution and provide imaging information of the sample. Here, we propose an approach for Raman imaging using a handheld fiber optic probe, which is built around computer vision–based assessment of positional information and simultaneous acquisition of spectroscopic information. By combining this implementation with real‐time data processing and analysis, it is possible to create not only fiber‐based Raman imaging but also an augmented chemical reality image of the molecular distribution of the sample surface in real‐time. We experimentally demonstrated that using our approach, it is possible to determine and to distinguish borders of different bimolecular compounds in a short time. Because the method can be transferred to other optical probes and other spectroscopic techniques, it is expected that the implementation will have a large impact for clinical, biomedical and industrial applications.