Photoacoustic Tomography of Biological Sample Using Phase-controlled Focus Algorithm

Photoacoustic (PA) imaging is a new imaging modality, which converts pressure signals received by a scanning detector to a local distribution of electromagnetic absorption density. In this paper an experiment result of a photoacoustic tomography to depths of ～7 mm for a real tissue is presented, using a 532-nm pulse YAG laser. The time-resolved stress detection technique was used for PA signal detection with a high temporal resolution. A phase-controlled focus algorithm was used for image reconstruction. Images of different depth profiles in tissue were obtained. The depth resolution was 30 μm and could be up to 10 μm using a wide-band tranducer.     

频谱编码深度成像实验研究

频谱编码显微镜是用衍射光栅和光谱分析装置来获得显微图像.样品上不同的位置被不同的波长照明,通过对反射光光谱进行解码来得到空间信息.搭建了一个基于超连续光源和自制光谱仪的频谱编码显微成像系统,其横向分辨率为1.72±0.13μm(编码线方向)和1.26±0.08μm(垂直于编码线方向),测得不同横向位置处的轴向分辨率有差异.对离体猪肝组织不同部位进行了成像(可见血管、肝窦内皮细胞和肝细胞);对鸡心组织以10μm深度间隔进行成像,测得不同深度处结构信息不一样.结果表明,采用该频谱编码成像的方法能够进行高分辨的深度成像.     

KBA显微镜成像系统的成像模拟及X光成像实验的研究

KBA显微镜是一种非轴对称、非共轴的掠入射成像系统。其结构复杂,调节精度要求很高,在实际成像实验操作中难以掌握其成像特性。利用光学设计软件模拟其成像,对系统的调节和成像分析提供有益的参考。利用光学设计软件ZEMAX模拟了KBA显微镜对点源的成像过程,给出了KBA显微镜成像系统的焦深约为1 mm,景深为50 mm左右。并且由模拟可知,掠入射角对成像的影响很大。对像素尺寸约10μm的探测设备,模拟得出KBA成像系统的空间分辨力上限为3μm左右。基于星光Ⅱ装置对周期为20μm的网格靶成像,获得了KBA显微镜较为清晰的X光图像。该项工作为进一步开展掠入射成像系统的研究奠定了基础。     

基于旋转扫描探头的OCT内窥成像系统设计

为了同时获取样品的表面和深度信息,研究光学相干层析的成像原理,建立了基于光学相干层析技术的内窥系统,实现了旋转扫描成像,系统的工作波长为1 310 nm,工作带宽为80 nm.理论推导及计算机仿真得到了系统信噪比与干涉仪的分光比、反射率之间的关系并分析了理论分辨率和探测深度.提出外径为5 mm的内窥镜扫描探头,聚焦距离为12 mm,数值孔径NA为0.47,折射率分布常量A=0.218 7.利用微型电机驱动直角棱镜实现扫描,旋转速度为25 rpm,旋转一周得到640个采样点.采用多层盖玻片和洋葱表皮作为样品进行实验分析,得到了盖玻片和洋葱的图像,横向分辨率和纵向分辨率分别为10 μm和15 μm.结果表明,设计的光学相干层析内窥系统能够用于旋转扫描成像,获取更多的组织信息.     

CO2 laser photoacoustic spectra and vibrational modes of heroin, morphine and narcotine

Heroin, morphine and narcotine are very large molecules having 50, 40 and 53 atoms respectively. Moderately high resolution photoacoustic (PA) spectra have been recorded in 9.6 μm and 10.6 μm regions of CO₂ laser. It is very difficult to assign the modes of vibrations for PA bands by comparison with conventional low resolution IR spectra. The ab initio quantum chemical calculations were used for determining the molecular geometries and normal mode frequencies of vibrations of these molecules for assignments of PA spectra.     

基于电动可调焦透镜的大范围快速光片显微成像

搭建了一种基于电动可调焦透镜(electrically tunable lens)的大范围快速光片荧光显微成像系统.通过引入电动可调焦透镜与一维振镜以实现成像物平面和光片位置的快速移动,再结合高速s CMOS完成快速光片荧光显微成像.另外实验中通过改善光路与提升动态成像质量,实现了大范围扫描并减少了伪像.最终对成像性能进行测试,本系统的纵向分辨率和横向分辨率分别达到约5.5μm和约0.7μm,单幅图像稳定成像的速度约为275 frames/s,成像深度可超过138μm,能满足对具有一定尺寸的生物样本进行实时清晰成像的需求.     

Development of phase-stabilized swept-source OCT for the ultrasensitive quantification of microbubbles

This paper describes the development of a novel-phase resolved system based on swept-source optical-coherence tomography (SSOCT) for the ultrasensitive imaging and monitoring of gas microbubbles in aqueous media. The developed phase-stabilized SSOCT (PhS-SSOCT) system has an axial resolution of 10 μm, a phase sensitivity of 0.03 rad, an imaging depth of up to 6 mm in air, and a scanning speed of 20 kHz for a single A line. The performance of the sensing system was evaluated in water-containing gas microbubbles with a different diameter. The obtained results demonstrate that bubbles with a diameter greater than 10 μm could be detected by both structural imaging and phase response, whereas bubbles with diameters of less than 10 μm could be detected by the phase response of the SSOCT with a high sensitivity. The accuracy for the measurement of the diameter of gas microbubbles is limited to 10 μm in structural imaging and 0.01 μm in phase-sensitive monitoring. The results from this study indicate that PhS-SSOCT could be used to detect fast-moving microbubbles in aqueous solutions and ultimately could be applied for rapid assessment in biofluids (e.g., blood) and tissues (e.g., skin) in vivo.     

镀膜型nMCP探测效率和位置分辨优化的蒙特卡罗模拟研究

中子敏感微通道板(Neutron sensitive microchannel plate,nMCP)因其具有高探测效率和位置分辨,配合先进的读出电子学可作为能量分辨中子成像探测器的优先选择。相比于基体掺杂型的nMCP,基于原子层沉积技术(Atomic Layer Deposition,ALD)的nMCP具有原材料消耗少、通道内壁具有高的二次电子发射系数等优势。首先,通过实验对掺杂natGd型nMCP的典型中子和伽马信号进行研究。然后,采用Geant4模拟和理论计算对镀膜10B₂O₃型nMCP的孔径、壁厚、倾角和镀膜厚度进行优化。计算结果表明,当nMCP的几何参数选择为镀膜厚度1 μm、孔径10 μm、壁厚1 μm以及倾角3°时,nMCP性能达到约56%的热中子探测效率和约22 μm的位置分辨。计算结果对CSNS能量选择中子成像探测器nMCP的几何参数设计具有重要意义。     

Holographic imaging with a nanometer resolution using compact table-top EUV laser

Holographic 2D/3D imaging with nanometer resolution using short wavelength extreme ultraviolet (EUV) light is presented in this paper. Gabor’s holograms were recorded with a highly coherent table top EUV laser with different numerical apertures demonstrating ultimately a spatial resolution of 46+/−2 nm, comparable with the illumination wavelength, in 2D holographic imaging. Three dimensional images were obtained from a single high numerical aperture hologram recorded in a high resolution photoresist and numerically reconstructed at different image planes, allowing numerical optical sectioning with a lateral resolution ∼170 nm and depth resolution of 2.4 μm. The holograms were recorded in a high resolution photoresist and digitized with an atomic force microscope. To assess the spatial resolution of the numerical reconstructions of the holograms a correlation method was used. The algorithm allows for simultaneous estimation of the resolution and the feature size of the image under analysis.     

Double-illumination photoacoustic microscopy

Recent developments of optical-resolution photoacoustic microscopy (OR-PAM) have improved its spatial resolution and imaging speed. However, the penetration depth of OR-PAM is still limited to ~1 mm in tissue, owing to the strong tissue scattering. Here, we have developed double-illumination PAM (DI-PAM), which illuminates the sample from both top and bottom sides simultaneously. Through phantom and in vivo experiments, we have demonstrated for thin targets that DI-PAM has a penetration depth of ~2 mm in tissue at 532 nm and a focal zone of 260 μm, both significant improvements over traditional reflection or transmission-mode OR-PAM.     

Two-dimensional photon counting imaging detector based on a Vernier position sensitive anode readout

A two-dimensional photon counting imaging detector based on a Vernier position sensitive anode is reported. The decode principle and design of a two-dimensionai Vernier anode axe introduced in detail. A photon counting imaging system was built based on a Vernier anode. The image of very weak optical radiation can be reconstructed by image processing in a period of integration time. The resolution is superior to 100 μm according to the resolution test. The detector may realize the imaging of very weak particle flow of high- energy photons, electrons and ions, so it can be used for high-energy physics, deep space exploration, spectral measurement and bio-luminescence detection.     

折/反混合式长波红外成像光谱仪光学系统设计

为了实现遥感目标的长波红外高光谱成像,满足目标探测对多信息量的需求,设计了高光谱分辨率长波红外(8~12 μm)成像光谱仪。前置望远系统采用离轴三反系统,以实现无遮拦、大口径及宽视场成像设计;光谱分光系统分别采用折射式和反射式结构进行优化设计。设计结果显示,采用折射式结构,可得到通光孔径为100 mm,F数为2,光谱分辨率16 nm,空间分辨率150 μrad,冷光阑效率100%,成像质量接近衍射极限的光学系统;采用反射式结构,为了保证光学系统无挡光,需采用多片离轴反射镜,增加了系统的非对称性,使得系统的像散、彗差和场曲难以校正到最佳状态。设计结果表明：折/反混合式成像光谱系统具有光谱分辨率高、成像质量好和结构合理等优点,点斑均方根直径与国内现有探测器像素尺寸匹配。     

基于辅助光学系统的KB显微镜瞄准方法

 研究了利用辅助可见光系统精确瞄准KB显微镜物点的方法。设计了工作能点8 keV的周期多层膜KB显微镜系统,通过光线追迹和X射线成像实验,得到5 μm空间分辨率所对应的视场和景深,进而计算出诊断实验对应的指向和景深要求。基于KB系统的物像关系和精度要求,设计了辅助的可见光成像系统,实现了可见光系统与X射线KB系统间的等效瞄准,利用耦合好的系统进行了瞄准和X射线成像实验。实验结果表明:辅助光路可以实现±20 μm的垂轴面和±300 μm的轴向定位精度,满足KB显微镜的瞄准要求。     

数字灰度光刻成像物镜设计

为了研究数字灰度光刻成像系统中栅格效应对像质的影响.在成像系统优化参量已有的研究基础上,综合考虑工作效率、光刻准确度、加工制造成本等因素,设计了一种能够有效消除数字灰度光刻成像栅格效应的光刻物镜.此光刻物镜技术指标为,数值孔径NA＝0.3,工作波长λ＝442 nm,倍率10×,分辨率R≤1.2 μm,焦深4 μm,且镜片数量少,光学加工、光学校装公差要求低.结果表明,该镜头完全满足数字灰度光刻高质量成像的需要.     

Lensless high-resolution photoacoustic imaging scanner for in vivo skin imaging

We previously launched a high-resolution photoacoustic (PA) imaging scanner based on a unique lensless design for in vivo skin imaging. The design, imaging algorithm and characteristics of the system are described in this paper. Neither an optical lens nor an acoustic lens is used in the system. In the imaging head, four sensor elements are arranged quadrilaterally, and by checking the phase differences for PA waves detected with these four sensors, a set of PA signals only originating from a chromophore located on the sensor center axis is extracted for constructing an image. A phantom study using a carbon fiber showed a depth-independent horizontal resolution of 84.0 ± 3.5 µm, and the scan direction-dependent variation of PA signals was about ± 20%. We then performed imaging of vasculature phantoms: patterns of red ink lines with widths of 100 or 200 μm formed in an acrylic block co-polymer. The patterns were visualized with high contrast, showing the capability for imaging arterioles and venues in the skin. Vasculatures in rat burn models and healthy human skin were also clearly visualized in vivo.     

用于大景深单分子定位显微的多功能全息相位片的设计及数值模拟

发展具有大轴向定位范围的单分子定位技术对于实现厚样品的超分辨成像具有重要的价值.基于波前编码技术,将变形多值纯相位光栅与双螺旋点扩散函数相位片相结合,提出一种可以通过空间光调制器实现的具有高衍射效率的新型全息相位片的设计方法.这种全息相位片可以将样品内多个层面的分子信息以双螺旋的形式成像在同一个探测面的不同位置,在无需扫描的情况下提高双螺旋点扩散函数工程的轴向定位范围和分辨率,解决活细胞内单分子定位和示踪技术中的大景深探测难题.数值模拟表明,设计的5×5全息相位片可以将样品内25个层面上的分子信息以双螺旋的形式成像在同一探测面上的不同位置,相邻两个层面的间隔为0.5μm,实现了轴向12μm的探测范围,证明了设计的可行性.     

Z箍缩装置的单色背光成像

 基于晶体布拉格衍射理论,搭建了X射线背光成像系统,核心色散元件为α-石英球面弯曲晶体。在中国工程物理研究院流体物体研究所“阳”加速器上进行了单色X射线背光成像实验,背光源为箍缩负载Al丝阵聚爆产生的激光等离子体X射线,成像物体为厚度100 μm的不锈钢网格阵列,接收装置得到Al丝阵聚爆的等离子体X射线2维分辨的空间单色成像,其空间分辨力为75 μm。目前实验中采用Al膜作为滤片,对Al的类He跃迁辐射线系都有吸收,得到的背光成像信噪比较小。     

新型显微成像光谱仪系统中线阵针孔离焦研究

显微成像光谱仪技术是最近新兴的一种生物组织检测方法,它可以广泛应用在生物医学检测,疑难病症分析、预防、诊断中,已经成为当今生物组织检测领域研究的热点。提出了一种新型的基于线阵针孔阵列的激光扫描共焦显微成像光谱仪系统LP-LSCMIS方案,介绍了其工作原理及优点,讨论了该装置中线阵针孔阵列离焦对系统性能的影响,分析了离焦对生物组织荧光图像的光谱分辨和自体荧光光谱的调制深度的影响。推导出了光谱分辨和调制深度与离焦量的关系式。结果表明,离焦对仪器的性能有较大的影响,因此在装置装调时要求有更高精度的调整机构。     

超宽带微波检测早期乳腺肿瘤三维仿真

超宽带微波成像技术可作为有效的方法用于乳房早期乳腺肿瘤的检测. 该方法基于乳房组织和肿瘤之间较大的电学特性差异的特点进行成像, 能提供足够的分辨率以及足够的穿透深度. 本文采用时域有限差分方法建立超宽带微波信号在三维乳房组织中传播的模型, 并采用单极德拜模型完成了生物组织色散特性的模拟. 利用8发9收的天线阵列实现微波肿瘤探测, 利用共焦成像算法对乳房组织进行图像重构并进行肿瘤定位. 仿真结果显示共焦成像算法能够实现最小直径3 mm的肿瘤的检测, 同时证实了超宽带微波成像技术应用于早期乳腺肿瘤检测的有效性. 关键词： 微波成像 肿瘤检测 时域有限差分 共焦成像算法     

基于旋转扫描探头的OCT内窥成像系统设计*

为了同时获取样品的表面和深度信息,研究光学相干层析的成像原理,建立了基于光学相干层析技术的内窥系统,实现了旋转扫描成像,系统的工作波长为1 310 nm,工作带宽为80 nm.理论推导及计算机仿真得到了系统信噪比与干涉仪的分光比、反射率之间的关系并分析了理论分辨率和探测深度.提出外径为5 mm的内窥镜扫描探头,聚焦距离为12 mm,数值孔径NA为0.47,折射率分布常量A=0.218 7.利用微型电机驱动直角棱镜实现扫描,旋转速度为25 rpm,旋转一周得到640个采样点.采用多层盖玻片和洋葱表皮作为样品进行实验分析,得到了盖玻片和洋葱的图像,横向分辨率和纵向分辨率分别为10 μm和15 μm.结果表明,设计的光学相干层析内窥系统能够用于旋转扫描成像,获取更多的组织信息.