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.     

太湖春季水体固有光学特性及其对遥感反射率变化的影响

吸收特性和后向散射特性是水体重要的光学特性,同时也是建立生物光学模型的基本参数。利用2009年4月太湖春季实测数据,结合生物光学模型推导了太湖春季水体颗粒物后向散射系数,在此基础上分析了太湖春季水体的吸收特性和后向散射特性,并利用经验正交分解方法对遥感反射率变化的影响因子进行了分析。结果表明：（1）非色素颗粒物是影响太湖春季水体吸收特性的主导因子,色素颗粒物和CDOM对总吸收（不包含纯水）的贡献相对较小,且色素颗粒物在梅梁湾湖区的包裹效应明显大于其他湖区。（2）颗粒物后向散射系数与总悬浮物和无机悬浮物具有很强的相关性（相关系数均在0.88以上）,与有机悬浮物的相关性相对较弱（相关系数均在0.73以下）,且水体中多次散射对水面总辐亮度有较大的贡献,平均贡献率高达93.46%。（3）利用经验正交分解方法将遥感反射率变化光谱分解成3个正交因子,3个正交因子总共解释了约99%的遥感反射率变化信息,其中,第一正交因子解释了93%的变化信息,第二和第三正交因子分别解释了5%和1%的变化信息。通过对各正交因子与水体不同组分的吸收和后向散射系数进行相关性分析得出,颗粒物的后向散射对水面反射光谱的形成具有非常重要的影响,太湖春季水体遥感反射率的变化主要取决于无机颗粒物的吸收和后向散射,有机颗粒物对遥感反射率的变化影响较小。     

激光与生物组织相互作用：光子迁移与生物传热理论

激光热疗中,激光与生物组织相互作用研究主要包含两方面：光子在生物组织中的迁移规律,以及光生扫热在生物组织在的传导。对前者的描述主要为,基于传输理论的解析法和Ｍｏｎｔｅ￣Ｃａｒｌｏ模拟,生物组织中光子迁移规律的研究能定量描述组织中的光分布,并进一步获得生物组织中的热分布;考虑到了生物组织特性,所建立了生物组织中温度场分布及变化规律。光子迁移与生物传热理论是研究激光热序不可分割的传热模型,全面描述了生     

国际生物光子及生物光子学会议将于2003年10月在北京召开

00 3年 10月 12～ 16日将在北京召开国际生物光子及生物光子学会议 (ＩＣＢＢ) ,议题包括 :生物光子的物理、化学和生物学性质 ;生物光子在医学、农业和环境中的应用 ;生物系统中光子传播、散射、反射的物理学 ;生物大分子荧光标记的新方法 ;肿瘤非损伤诊断、定位和治疗的光学新进展 ;光成像和内窥镜 ;亚细胞水平的光学成像 ;功能分子成像和分子化学成像 ;测量及可视化的新光学技术等等。感兴趣者 ,可与中国生物物理学会魏舜仪女士联系。Ｅ＿ｍａｉｌ:<ｓｂ @ｓｕｎ5 .ｉｂｐ .ａｃ .ｃｎ >.国际生物光子及生物光子学会议将于2003年10月在北…     

Kubelka—Munk模型下的兔血管对He—Cd激光的散射与吸收特性

测量了兔动脉和静脉夺He-Cd激光的反射和透射传输特性。实验采用两积分球系统及波长为441.6nm的He-Cd激光器,并根据测量数据及采用Kubelka-Munk模型分析和计算了兔动脉和静脉组织对该波长激光的吸收系统、散射系数及总的光强I（x）及前向散射通量i(x)和后向散射通量j(x）随厚度的变化情况。结果表明,兔动脉和静脉的温反射率和透射率有明显差别,而且,动脉对激光的吸收系数明显较静脉的要小,耐动脉对激光的散射系数却明显较静脉的要大,在动脉和静脉组织中总的光强I(x)及前向散射通量i(x)和后向散射通量j(x)随厚度的变化情况也有明显的区别。     

森林冠层辐射的数值模拟

一、引言太阳辐射是树木和各种作物生长过程中所需能量的直接或间接源泉。一定强度的太阳辐射达到林冠层表面时,由于叶、枝等器官的吸收、反射和透射作用,使得冠层内的辐射分布有其独具的特征。本文综合考虑天空散射和叶片的内部散射作用,从辐射通量的角度在计算机上模拟了各向同性叶角分布的冠层中辐射通量的分布特征,讨论了单叶反射系数和透射系     

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。     

全光学光声/OCT双模态成像系统及其应用

本文提出了一种新型的全光学光声/OCT双模态成像系统。该系统利用同一个低相干迈克尔逊干涉仪即可实现非接触式光声成像和OCT于一体,系统装置结构简单,可同时获取生物组织的吸收与散射结构信息。通过模拟实验证明了该双模态成像系统的可行性及成像能力,并对活体小鼠耳朵同时进行光声/OCT成像测试,实验结果表明非接触式光声/OCT双模态成像系统可以实现生物组织内的微血管及散射结构的高分辨率成像。进一步地,我们将光声/OCT双模态成像系统应用于基底细胞癌的检测中,获得了初步的研究结果,表明了该系统在皮肤肿瘤诊断中的具有潜在的应用价值。     

采用OCT系统对组织光学通透的研究

组织通透方法采用高折射率化学试剂对生物组织进行渗透,改变组织的光学均匀性,可以有效地改善光学成像的穿透深度,受到生物医学光学研究领域的重视。利用光学相干层析成像技术,测量通透过程中不同测量深度下组织的散射特征的变化。通过采用系统信号对数的梯度值近似地表征光学散射系数,研究了通透过程中组织的散射特征随渗透时间和测量深度的动态关系。实验证明了组织通透可以有效地增加光子的穿透深度,并改善成像质量。研究发现:不同测量深度处组织的散射系数及其变化幅度、变化过程和变化趋势等均存在一定的差异性,并与组织的微观结构、其通透效果,化学试剂在组织中的渗透行为等有密切关系,有助于组织通透过程的理解,并为组织通透机制提供可能的实验依据。     

光学成像中兼具光学和力学性质的生物组织仿体

在生物医学光学成像方法的研发、评估和使用中,需要用到在较长时间内具有稳定的光学及力学属性的生物组织仿体,以使光学成像实验可以重复进行。这些仿体一般由混有散射、吸收粒子的基质制成。常用散射粒子包括脂质微粒、聚合物微球、金属氧化物粉末和金纳米粒子等,吸收粒子(及其溶液)包括血液、印度墨水(Indian Ink)和分子染料等。常用来模拟组织特性的基质包括硅胶、纤维蛋白和聚乙烯醇凝胶(Polyvinyl alcohol cryogel,PVA-C)等。讨论和分析常见仿体的光学性质(吸收系数、散射系数、折射率)和力学性质(弹性和粘弹性)。从生物相容性、制备难易程度及耗时情况、稳定性等方面比较了几种常见散射粒子、吸收粒子和基质的优缺点,并据此总结其适用范围。最后对仿体研究的发展进行了展望。     

Changes in the optical properties of cotyledons of Cucurbits pepo during the first seven days of their development

Abstract. We recently discussed a method for measuring optical properties of light scattering and absorbing plant tissue ( Seyfried, Fukshansky & Schafer, 1983 ). This method has been used to measure the changes in optical properties of cotyledons between 360 and 1000 run during the first 7d of development. The seedlings were either etiolated or grown under continuous white light, the latter either herbicide-treated (SAN 9789 = Norflurazon) or untreated. Some of the observed changes in seedlings grown under white light are due to chlorophyll accumulation. This accumulation leads to an increase in absorption coefficients at all wavelengths except in the 750 to 850 nm region. Reflectance, transmittance, and the scattering coefficient decreased markedly. Other changes seem to be independent of light conditions since they occur in much the same way under all treatments. These are a generally decreasing reflectance and scattering coefficient and an even stronger decrease of reflectance from the upper face of the cotyledon as compared to the reflectance from the lower face, in particular in the blue region of the spectrum. The observed changes are discussed in terms of light gradients and the resulting problems for in vivo spectroscopy.     

时间分辨反射确定生物组织光学性质的方法研究

通过考虑吸收系数对漫射常数的影响,改进了时间分辨反射中两点测量生物组织光学性质的方法,对约化散射系数与吸收系数之比较小的生物组织进行了模型测量,结果表明此种不仅减小了测量的系统误差,而且扩展了两点测量法的应用范围。同时也较为详细地讨论了有效时间的选择和光源与探测点间的距离对测量结果的影响。     

Monte Carlo simulation of NIR diffuse reflectance in the normal and diseased human breast tissues

The spectral reflectance measurements in tissue reveal physiological meaning. Normally, functional changes like, increase in total hemoglobin concentration, decrease in oxygen saturation, etc., are observed when there is an abnormality creeping in the normal tissue. These functional changes can act together to reveal disease by non-invasive near-infrared (NIR) spectroscopy, as it influence its optical properties. In the present study, a simple two dimensional, four layer model of breast is proposed. The four layers are (i) skin (ii) adipose layer (iii) glandular tissue and (iv) muscle. Each layer is modeled with appropriate biological chromophores like hemoglobin, water, lipid and melanin. From the literature, the concentrations and molar extinction coefficients of the chromophores in various layers of the model are obtained. These values are used to calculate the wavelength dependent absorption characteristics of a particular layer. Monte Carlo simulation of diffuse reflectance (percentage of back reflected photons after multiple scattering with the broad variety of angles) are simulated for the modeled breast tissue with and without diseased condition. Near-infrared wavelengths are chosen, as the depth of penetration in tissue is more compared to UV and visible region. Simulations are carried out on the modeled breast tissue for different races (skin colors) at different NIR wavelengths. Results show significant changes in diffuse reflectance and relative absorbance for normal and diseased breast tissues for differently pigmented model. This model can be used to study the photo dynamical therapy, drug delivery and prognosis of cancer.     

Wide‐field color imaging of scatter‐based tissue contrast using both high spatial frequency illumination and cross‐polarization gating

This study characterizes the scatter‐specific tissue contrast that can be obtained by high spatial frequency (HSF) domain imaging and cross‐polarization (CP) imaging, using a standard color imaging system, and how combining them may be beneficial. Both HSF and CP approaches are known to modulate the sensitivity of epi‐illumination reflectance images between diffuse multiply scattered and superficially backscattered photons, providing enhanced contrast from microstructure and composition than what is achieved by standard wide‐field imaging. Measurements in tissue‐simulating optical phantoms show that CP imaging returns localized assessments of both scattering and absorption effects, while HSF has uniquely specific sensitivity to scatter‐only contrast, with a strong suppression of visible contrast from blood. The combination of CP and HSF imaging provided an expanded sensitivity to scatter compared with CP imaging, while rejecting specular reflections detected by HSF imaging. ex vivo imaging of an atlas of dissected rodent organs/tissues demonstrated the scatter‐based contrast achieved with HSF, CP and HSF‐CP imaging, with the white light spectral signal returned by each approach translated to a color image for intuitive encoding of scatter‐based contrast within images of tissue. The results suggest that visible CP‐HSF imaging could have the potential to aid diagnostic imaging of lesions in skin or mucosal tissues and organs, where just CP is currently the standard practice imaging modality.      

Temporo-Spectral Imaging of Intrinsic Optical Signals during Hypoxia-Induced Spreading Depression-Like Depolarization

Spreading depression (SD) is characterized by a sustained near-complete depolarization of neurons, a massive depolarization of glia, and a negative deflection of the extracellular DC potential. These electrophysiological signs are accompanied by an intrinsic optical signal (IOS) which arises from changes in light scattering and absorption. Even though the underlying mechanisms are unclear, the IOS serves as non-invasive tool to define the spatiotemporal dynamics of SD in brain slices. Usually the tissue is illuminated by white light, and light reflectance or transmittance is monitored. Using a polychromatic, fast-switchable light source we now performed temporo-spectral recordings of the IOS associated with hypoxia-induced SD-like depolarization (HSD) in rat hippocampal slices kept in an interface recording chamber. Recording full illumination spectra (320-680 nm) yielded distinct reflectance profiles for the different phases of HSD. Early during hypoxia tissue reflectance decreased within almost the entire spectrum due to cell swelling. HSD was accompanied by a reversible reflectance increase being most pronounced at 400 nm and 460 nm. At 440 nm massive porphyrin absorption (Soret band) was detected. Hypotonic solutions, Ca(2+)-withdrawal and glial poisoning intensified the reflectance increase during HSD, whereas hypertonic solutions dampened it. Replacement of Cl(-) inverted the reflectance increase. Inducing HSD by cyanide distorted the IOS and reflectance at 340-400 nm increased irreversibly. The pronounced changes at short wavelengths (380 nm, 460 nm) and their cyanide sensitivity suggest that block of mitochondrial metabolism contributes to the IOS during HSD. For stable and reliable IOS recordings during HSD wavelengths of 460-560 nm are recommended.     

Tissue-simulating Phantoms for Assessing Potential Near-infrared Fluorescence Imaging Applications in Breast Cancer Surgery

Inaccuracies in intraoperative tumor localization and evaluation of surgical margin status result in suboptimal outcome of breast-conserving surgery (BCS). Optical imaging, in particular near-infrared fluorescence (NIRF) imaging, might reduce the frequency of positive surgical margins following BCS by providing the surgeon with a tool for pre- and intraoperative tumor localization in real-time. In the current study, the potential of NIRF-guided BCS is evaluated using tissue-simulating breast phantoms for reasons of standardization and training purposes.Breast phantoms with optical characteristics comparable to those of normal breast tissue were used to simulate breast conserving surgery. Tumor-simulating inclusions containing the fluorescent dye indocyanine green (ICG) were incorporated in the phantoms at predefined locations and imaged for pre- and intraoperative tumor localization, real-time NIRF-guided tumor resection, NIRF-guided evaluation on the extent of surgery, and postoperative assessment of surgical margins. A customized NIRF camera was used as a clinical prototype for imaging purposes.Breast phantoms containing tumor-simulating inclusions offer a simple, inexpensive, and versatile tool to simulate and evaluate intraoperative tumor imaging. The gelatinous phantoms have elastic properties similar to human tissue and can be cut using conventional surgical instruments. Moreover, the phantoms contain hemoglobin and intralipid for mimicking absorption and scattering of photons, respectively, creating uniform optical properties similar to human breast tissue. The main drawback of NIRF imaging is the limited penetration depth of photons when propagating through tissue, which hinders (noninvasive) imaging of deep-seated tumors with epi-illumination strategies.     

Investigation of the source‐detector separation in near infrared spectroscopy for healthy and clinical applications

Understanding near infrared light propagation in tissue is vital for designing next generation optical brain imaging devices. Monte Carlo (MC) simulations provide a controlled mechanism to characterize and evaluate contributions of diverse near infrared spectroscopy (NIRS) sensor configurations and parameters. In this study, we developed a multilayer adult digital head model under both healthy and clinical settings and assessed light‐tissue interaction through MC simulations in terms of partial differential pathlength, mean total optical pathlength, diffuse reflectance, detector light intensity and spatial sensitivity profile of optical measurements. The model incorporated four layers: scalp, skull, cerebrospinal‐fluid and cerebral cortex with and without a customizable lesion for modeling hematoma of different sizes and depths. The effect of source‐detector separation (SDS) on optical measurements' sensitivity to brain tissue was investigated. Results from 1330 separate simulations [(4 lesion volumes × 4 lesion depths for clinical +3 healthy settings) × 7 SDS × 10 simulation = 1330)] each with 100 million photons indicated that selection of SDS is critical to acquire optimal measurements from the brain and recommended SDS to be 25 to 35 mm depending on the wavelengths to obtain optical monitoring of the adult brain function. The findings here can guide the design of future NIRS probes for functional neuroimaging and clinical diagnostic systems.      

Quantitative subsurface spatial frequency‐domain fluorescence imaging for enhanced glioma resection

The rate of complete resection of glioma has improved with the introduction of 5‐aminolevulinic acid‐induced protoporphyrin IX (PpIX) fluorescence image guidance. Surgical outcomes are further enhanced when the fluorescence signal is decoupled from the intrinsic tissue optical absorption and scattering obtained from diffuse reflectance measurements, yielding the absolute PpIX concentration, [PpIX]. Spatial frequency domain imaging was used previously to measure [PpIX] in near‐surface tumors under blue fluorescence excitation. Here, we extend this to subsurface [PpIX] fluorescence under red‐light excitation. The decay rate of the modulation amplitude of the fluorescence signal was used to calculate the PpIX depth, which was then applied in a forward diffusion model to estimate [PpIX] at depth. For brain‐like optical properties in phantoms with PpIX fluorescent inclusions, the depth can be recovered up to depths of 9.5 mm ± 0.4 mm, with [PpIX] ranging from 5 to 15 μg/mL within an average deviation of 15% from the true [PpIX] value.      

Heat generation in laser irradiated tissue

Many medical applications involving lasers rely upon the generation of heat within the tissue for the desired therapeutic effect. Determination of the absorbed light energy in tissue is difficult in many cases. Although UV wavelengths of the excimer laser and 10.6 microns wavelength of the CO2 laser are absorbed within the first 20 microns of soft tissue, visible and near infrared wavelengths are scattered as well as absorbed. Typically, multiple scattering is a significant factor in the distribution of light in tissue and the resulting heat source term. An improved model is presented for estimating heat generation due to the absorption of a collimated (axisymmetric) laser beam and scattered light at each point r and z in tissue. Heat generated within tissue is a function of the laser power, the shape and size of the incident beam and the optical properties of the tissue at the irradiation wavelength. Key to the calculation of heat source strength is accurate estimation of the light distribution. Methods for experimentally determining the optical parameters of tissue are discussed in the context of the improved model.