肿瘤组织自体荧光光谱测量与分析

首先介绍了对人工培养鼠肿瘤组织的激光诱导荧光光谱的实验测量结果，并与同一机体正常组织的自体荧光光谱进行了比较，然后对肿瘤组织自体荧光的来源，与正常组织光谱特征差异的本质进行了详细分析，从而得出结论，生物组织自体荧光光谱能够反映肿瘤组织的特异性，可以作为组织诊断的依据。     

肺癌的血清自体荧光检测

激光诱导荧光光谱是一种研究较为广泛的医用光谱技术,已经被用于组织、细胞学的检测.本文利用激光诱导荧光光谱技术,测定了肺癌患者和健康人的血清自体荧光光谱.并采用主成分分析法和判别分析法对荧光光谱数据进行了分析和处理,从大量的光谱数据中提出少量主成分值,并通过主成分值的差别对肺癌的诊断率进行分析.得到的结果为,对肺癌的诊断...     

荧光寿命成像在癌症诊断研究中的应用(特邀)

癌症是目前人类所面对的共同难题,降低癌症死亡率的关键是实现早期诊断。荧光寿命因对微环境的敏感性,不仅可以实现对早期癌症组织与正常组织的区分,还可以对药物治疗癌症进行监测,因此荧光寿命成像显微技术在癌症诊断方面具有巨大的应用潜力。本文介绍了荧光寿命成像显微技术的基本原理及检测方法,总结了内源性和外源性荧光团的特征及其与癌症诊断的关系,综述了近年来荧光寿命成像显微技术在神经系统、呼吸系统、消化系统、生殖系统、泌尿系统、内分泌系统以及皮肤系统等癌症诊断中的应用,讨论了荧光寿命成像显微技术在癌症诊断中的应用优势、局限性以及未来发展趋势。     

激光诱导荧光寿命及其测量

激光诱导荧光特性的研究可用于包括心血管病在内的多种疾病的诊断。荧光发射包括光谱（频域）和时间（时域）两方面的信息，后者表现为荧光寿命。在很多情况下，测量荧光寿命是比测量光谱更为有效的诊断方法。本文从理论上讨论了荧光寿命问题，并介绍两种测量方法，可用于测量人体正常组织和病变组织的激光诱导荧光寿命     

自体荧光在早期结肠癌诊断中的研究

本文以337nm氮分子激光器为激发光源，通过大量实验发现结肠组织自体荧光398nm次峰和461nm主峰能量之比可作为早期结肠癌识别判据之一，并对荧光的强度－时间特性进行研究，发现正常组织与癌变组织在该特性上存在差异，从而推动了激光诱导荧光在早期结肠癌诊断中的临床应用。     

提高结肠早癌诊断率的荧光光谱小波特征提取与神经网络分类方法研究

提出了一种新的荧光光谱特征提取与模式分类方法以提高激光诱导5-ALA-PpIX荧光光谱对早期结肠癌的诊断准确率。利用小波多尺度分析法提取荧光光谱特征量,对提取的特征量采用基于Rprop算法的BP神经网络进行模式分类。对20只DMH诱导的SD大鼠,12只诱导鼠的第二代鼠,8只正常SD大鼠,按25 mg·kg-1体重剂量尾静脉注射5-ALA溶液,150 min后利用波长为370 nm的钛宝石激光进行活体检测。对预处理后的504条荧光光谱,利用小波多尺度分析法提取12个特征量,BP神经网络将其分为正常组与非正常组(非典型增生、早癌和进展期癌),分类敏感性与特异性分别为98.91%和97.2%,非典型增生、早癌及进展期癌对正常组织的识别准确率分别为91.3%, 98.85%及98.79%。结果表明此方法不仅对早期结肠癌具有较高的诊断率,且更利于临床实时诊断。     

人体不同组织的拉曼光谱研究

测试了人体甲状腺、卵巢、输卵管、肺、子宫平滑肌、子宫颈等组织的拉曼光谱。结果显示,用氩离子激光514.5 nm激发,人体组织拉曼光谱的荧光背景强,在500～3 500 cm-1范围,肺和宫颈组织未显示特征带,甲状腺和子宫组织则显示了较多的带。在600～1800 cm-1范围,子宫、输卵管组织只显示了类胡萝卜素的拉曼带。正常甲状腺组织的光谱和甲状腺滤泡癌组织的光谱之间显示出明显差异,后者没有呈现1 585和1 634 cm-1特征带;正常肺组织与肺癌组织的拉曼光谱也有较大区别,肺癌组织的光谱强度比正常组织的低得多。拉曼光谱技术在临床医学诊断方面将会发挥重要的作用。     

眼底视网膜色素上皮层细胞脂褐素及氧化黑色素自体荧光寿命成像研究

利用一种基于时间相关单光子计数器的双光子激发荧光寿命显微成像技术,对猪眼底视网膜色素上皮层细胞内的脂褐素和氧化黑色素颗粒的空间分布及其荧光寿命特性进行了研究,尤其对于这些色素颗粒在光致氧化环境中的荧光寿命差异进行了分析.结果表明,利用荧光寿命测量能有效区分视网膜色素上皮层细胞中的多组分荧光团,利用荧光寿命的衰减参数可分辨正常及异常的荧光现象.该方法有望发展成为一种用于眼科临床诊断及病理学研究的高灵敏度的工具,对眼底细胞随年龄增长的衰老机理的研究具有重要的意义. 关键词： 双光子激发荧光 荧光寿命成像 视网膜色素上皮层     

激光诱导荧光光谱探测系统用于癌症诊断

本文介绍了一种激光诱导荧光光谱探测系统。以３５５ｎｍ固体ＹＡＧ激光作为激光光源，ＯＭＡ光学多通道分析仪为荧光收集系统，通过在多个人体肺癌和食道癌样品上的应用，成功地测得了多种组织的荧光光谱。本文也初步探讨了一些与此相关的技术问题。     

基于i PLS的矿井突水激光诱导荧光光谱特征波段筛选

矿井突水一直威胁着煤矿井下施工人员的生命安全,准确且快速识别矿井突水水源类型对于矿井的安全生产起到关键性作用。激光诱导荧光(LIF)光谱技术识别矿井突水水源,有效避免了常规的水化学法需要测定多种化学参数,水源识别时间过长的缺点。提出一种间隔偏最小二乘法(iPLS)与粒子群联合支持向量分类算法(PSO-SVC)相结合的方法,iPLS算法常应用于光谱波段优选和模型的回归分析,PSO-SVC则在机器学习领域有着重要的应用,激光诱导荧光技术具有快速的时间响应、测量精度高等特点,iPLS和PSO-SVC算法运用于光谱图和光谱数据的分析,进而可以对突水水源类型识别分类。首先,用淮南矿区采集到的7种(每种水样30组)共210组荧光光谱数据进行实验,对老空水、灰岩水、灰岩水和老空水不同体积比混合水样的激光诱导荧光光谱图的差异性进行分析。比较了留出法和Kennard-Stone样本划分方法所得到的PSO-SVC模型分类准确率,采用留出法得到的训练集水样(140组)和测试集水样(70组)作为实验样本。其次,用iPLS算法将全光谱波段依次按10～25波段区间进行等分,选取划分区间的RMSECV(交叉验证均方根误差)值小于全光谱波段RMSECV值(阈值)的波段作为特征波段,结合光谱图对比分析了划分10和14个子区间的建模结果,发现通过直接观察得到的特征波段与iPLS算法筛选出的特征波段存在误差。最后,在不进行去噪、降维等预处理条件下,根据iPLS划分不同区间数的评价指标统计数据,选取划分11个区间所筛选出具有561个波长点的410.078～478.424和545.078～674.104 nm特征波段范围数据作为PSO-SVC模型的输入,以iPLS结合PSO-SVC算法筛选出的特征波段与全光谱波段、直接观察得到波段建模准确率相比,训练集与测试集的分类准确率高达100%,PSO寻优到的最佳惩罚系数c为1.367 0,核函数参数g为0.576 2。从实验结果可以看出,利用iPLS进行荧光光谱的特征波段筛选是切实可行的,提取出的特征波段能充分反映出全光谱波段的有效信息,为激光诱导荧光光谱技术用于矿井突水水源精准在线识别的研究提供了理论依据。     

具有图象处理功能的激光荧光内窥系统的研究

内窥镜荧光图象系统是体腔内早期肿瘤诊断和定位的有效手段.但是早期开发研究的LFE荧光成家系统由于存在假阳性和假阴性误诊而限制了它的广泛开展和应用.本文仔细探讨了该系统产生误诊的原因,并在此基础上提出了使用计算机图象处理技术的荧光图象系统,而且通过实验验证了这种新技术,它能有效地克服假阳性和假阴性误诊,为体腔内肿瘤的诊断提供可靠判据.     

Laser-Induced Fluorescence Bronchoscopy for Detection and Localization of Early Lung Cancer

Experimenatal results on the development of a Laser-Induced Fluorescence Bronchoscopy(LIFB) for the detection and localization of early lung cancer are reported in this paper. The system utilizes fluorescence of photosensitizer drug to provide real time video imaging for the examined lung tissue. Color filters are used to differentiate signal from background and a computer image processing technique is also applied to subtract the background. Moreover, a pseudocolor contrast enhancement method was developed to enhance the fluorescence image displayed on the vidio monitor. Suspicious areas are identified by pseudocolor image to guide biopsy, and several clinical trials show that sensitivity and contrast capability of the system should permit the detection and localization of early lung cancer.     

Laser-Induced Fluorescence Bronchoscopy for Detection and Localization of Early Lung Cancer

Experimenatal results on the development of a Laser-Induced Fluorescence Bronchoscopy(LIFB) for the detection and localization of early lung cancer are reported in this paper. The system utilizes fluorescence of photosensitizer drug to provide real time video imaging for the examined lung tissue. Color filters are used to differentiate signal from background and a computer image processing technique is also applied to subtract the background. Moreover, a pseudocolor contrast enhancement method was developed to enhance the fluorescence image displayed on the vidio monitor. Suspicious areas are identified by pseudocolor image to guide biopsy, and several clinical trials show that sensitivity and contrast capability of the system should permit the detection and localization of early lung cancer.     

肺癌荧光图象的伪彩色增强处理

近年来,作者开发了肿瘤荧光成象法用于诊断和定位早期支气管癌.由于所获得的荧光图象使用了象增强器进行增益放大,因此还消除了肺癌荧光图象的彩色信息.本文给出了一种荧光图象伪彩色增强处理的方法,并证实了伪彩色增强技术用于早期肺癌荧光诊断的可行性.经增强处理后,内镜医生只要根据彩色视频图象中与黑白荧光图象强度相对应的颜色就可以鉴别肺癌存在与否.同增强处理前的黑白图象相比,医生从伪彩色图象中获得了病灶内部结构、边缘效果和立体感方面的更多信息.临床结果表明可疑组织与正常组织之间获得了足够高的颜色衬比,有助于诊断早期肺癌病灶.     

一种带可调光照部分的专用彩色图像处理系统

介绍了肺癌介入治疗模拟实验的专用彩色图像处理系统 ,硬件由可调光照部分、CCD摄像头、视频采集卡和微机四大部分构成。软件不仅可以进行一般的数字图像处理 ,而且针对肺癌介入治疗模拟实验中的特殊要求 ,设计了比例测量、导管口跟踪等专用功能。该系统除了用于肺癌介入治疗模拟实验 ,还可用做指导临床介入治疗 ,具有乐观的应用前景。     

Metamaterials-based terahertz sensor for quick diagnosis of early lung cancer

We experimentally demonstrate a metamaterials(MMs)-based terahertz(THz) sensor to quickly distinguish the cancer tissues from normal tissues.The MMs-based THz sensor has two strong resonance absorption peaks at about 0.706 and 1.14 THz,respectively.When the sensor is covered with cancer tissues,the redshifts at about 0.706 and 1.14 THz are 31 and 19 GHz,respectively.However,if normal tissue is attached to the surface of the sensor,the corresponding redshifts are only 15 and 12 GHz,respectively.This study proposes a new method for quick diagnosis of early lung cancer and other cancers.     

Hyaluronan functionalizing QDs as turn-on fluorescent probe for targeted recognition CD44 receptor

The recognition of tumor markers in living cancer cells has attracted increasing interest. In the present study, the turn-on fluorescence probe was designed based on the fluorescence of thiolated chitosan-coated CdTe QDs (CdTe/TCS QDs) quenched by hyaluronan, which could provide the low background signal for sensitive cellular imaging. This system is expected to offer specific recognition of CD44 receptor over other substances owing to the specific affinity of hyaluronan and CD44 receptor (~8–9 kcal/mol). The probe is stable in aqueous and has little toxicity to living cells; thus, it can be utilized for targeted cancer cell imaging. The living lung cancer cell imaging experiments further demonstrate its value in recognizing cell-surface CD44 receptor with turn-on mode. In addition, the probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. And, the western blot test further confirmed that the expression level of the CD44 receptor in lung cancer cells is different. Therefore, this probe may be potentially applied in recognizing lung cancer cells with higher contrast and sensitivity and provide new tools for cancer prognosis and therapy.

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Graphical abstract ? Hyaluronan functionalizing sulfhydryl chitosan-coated CdTe QDs were designed as a “turn-on” fluorescence probe for recognizing cancer cells. ? The fabricating probe is based on the high affinity of hyaluronan and CD44 receptor for specific recognition of CD44 receptor in lung cancer cell. ? The probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. ? The probe showed the lower background signal than that of always-on nanoprobes avoiding the non-specific adsorption on the surface of the normal cells.

     

基于生物阻抗谱成像的生物组织检测方法

基于电阻抗成像技术和生物阻抗谱技术,提出一种面向生物组织检测的生物阻抗谱成像方法.该方法将目标区域可视化并精准识别目标种类,可用于肺癌早期检测,协助临床医生对早期肺癌进行精准检测,提高早期肺癌的治愈率.本文通过数值仿真的方法验证生物阻抗谱成像方法在肺癌早期检测中的可行性和有效性,仿真结果表明:1)生物阻抗谱成像方法可以实现早期肺癌区域的可视化,并精确判别出早期肺癌种类; 2)生物阻抗谱成像方法中阻抗谱的最佳采集模式是4次循环采集,最佳分类器是Linear-SVM, 5折交叉验证的平均分类准确率可以达到99.9%.为了验证仿真结果,本文选取3种具有不同电学特性的生物组织模拟癌变区域进行了检测.实验结果表明该方法可以对生物组织区域可视化,并判别出生物组织的种类.该方法可以兼顾电阻抗成像和生物阻抗谱方法的优点,有望用于肺癌早期检测.     

Frequency-domain fluorescence lifetime imaging for endoscopic clinical cancer photodetection: Apparatus design and preliminary results

We describe a new fluorescence imaging device for clinical cancer photodetection in hollow organs in which the tumor/normal tissue contrast is derived from the fluorescence lifetime of endogenous or exogenous fluorochromes. This fluorescence lifetime contrast gives information about the physicochemical properties of the environment which are different between normal and certain diseased tissues. The excitation light from a CW laser is modulated in amplitude at a radio frequency by an electrooptical modulator and delivered by an optical fiber through an endoscope to the hollow organ. The image of the tissue collected by the endoscope is separated in two spectral windows, one being the backscattered excitation light and the other the fluorescence of the fluorochrome. Each image is then focused on the photocathode of image intensifiers (II) whose optical gain is modulated at the same frequency as the excitation intensity, resulting in homodyne phase-sensitive images. By acquiring stationary phase-sensitive frames at different phases between the excitation and the detection, it is possible to calculate in quasi-real time the apparent fluorescence lifetime of the corresponding tissue region for each pixel. A result obtained by investigating the endogenous fluorochromes present in the mucous membrane of an excised human bladder is presented to illustrate this method and most of the optical parameters which are of major importance for this photodetection modality have been evaluated.     

用于胃癌早期检测的可见光显微光谱研究

反射光谱技术在早期癌症检测中具有非常好的应用前景。对比常见的漫反射可见光谱技术,可见光显微光谱技术能够获取细胞大小范围内的信息,而且不受探头结构差异导致的传输光程长短,以及测量时探头施加压力导致的血红蛋白浓度异常变化的影响。基于光纤共聚焦显微系统,建立了可见光显微光谱实验装置,测量了离体正常和癌变胃组织的显微光谱,给出了样品在600-700nm波长范围内的显微光谱分布情况,实验结果表明可见光显微光谱技术简单、有效,可用于胃癌的早期检测。