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1.发明授权公开(公告)号：US06241662B1
公开(公告)日：2001-06-05
申请号：US09175232
申请日：1998-10-20
申请人： Rebecca Richards-Kortum , Anant Agrawal , Costas Pitris , Urs Utzinger , Carrie Brookner , Michele Follen Mitchell
发明人： Rebecca Richards-Kortum , Anant Agrawal , Costas Pitris , Urs Utzinger , Carrie Brookner , Michele Follen Mitchell
IPC分类号： A61B500
CPC分类号： G01N33/52 , A61B5/0071 , A61B5/4331 , G01N1/30 , G01N2015/1488
摘要： A method for using acetic acid as a signal enhancing contrast agent during fluorescence spectroscopy of normal and neoplastic tissue, particularly epithelium. In one aspect, the invention includes a method of detecting tissue abnormality in a diagnostic tissue sample in a patient, comprising the steps of obtaining a first fluorescence intensity spectrum from the diagnostic tissue sample; thereafter, applying acetic acid to the diagnostic tissue sample in sufficient concentration to alter the response of such diagnostic tissue sample to electromagnetic radiation for at least an effective period of time; during the effective period of time, obtaining a second fluorescence intensity spectrum from the diagnostic tissue sample; determining a parameter indicative of a change between the first and second fluorescence emission intensity spectra; and analyzing the determined parameter to determine a probability that the diagnostic tissue sample is normal or abnormal.
摘要翻译： 在正常和肿瘤组织，特别是上皮的荧光光谱学过程中使用乙酸作为信号增强造影剂的方法。 一方面，本发明包括检测患者的诊断性组织样本中的组织异常的方法，包括以下步骤：从所述诊断组织样品获得第一荧光强度光谱; 此后，以足够的浓度将乙酸施用于诊断组织样品，以将这种诊断性组织样品的响应改变为电磁辐射至少有效的一段时间; 在有效时间段内，从诊断组织样品获得第二荧光强度光谱; 确定指示所述第一和第二荧光发射强度光谱之间的变化的参数; 并分析确定的参数以确定诊断组织样本正常或异常的概率。
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2.发明授权Optical probe for the detection of cervical neoplasia using fluorescence spectroscopy and apparatus incorporating same 失效用于使用荧光光谱检测子宫颈瘤形成的光学探针和结合其的装置
公开(公告)号：US5699795A
公开(公告)日：1997-12-23
申请号：US415356
申请日：1995-03-31
CPC分类号： A61B5/0084 , A61B5/0071 , A61B5/4331 , A61B5/0075
摘要： A probe, and an apparatus incorporating the probe, for detecting tissue abnormality, particularly precancerous cervical tissue, through fluorescence spectroscopy are disclosed. In vivo fluorescence excitation and detection can be accomplished easily and accurately using a probe whose tip conforms to the surface of the cervix. In addition, a higher number of fiber pairs provides more information and, therefore, more accurate diagnosis.
摘要翻译： 公开了一种用于通过荧光光谱法检测组织异常，特别是癌前期宫颈组织的探针和结合有探针的装置。 可以使用尖端符合子宫颈表面的探针，容易且准确地实现体内荧光激发和检测。 此外，更多数量的光纤对提供更多信息，因此提供更准确的诊断。
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3.发明授权Diagnostic method and apparatus for cervical squamous intraepithelial lesions in vitro and in vivo using fluorescence spectroscopy 失效使用荧光光谱法在体外和体内宫颈鳞状上皮内病变的诊断方法和装置公开(公告)号：US06258576B1
公开(公告)日：2001-07-10
申请号：US08666021
申请日：1996-06-19
IPC分类号： G01N2164
CPC分类号： G01N21/6486 , A61B5/0059 , A61B5/7264 , G01N21/645 , G01N2021/6419 , G01N2021/6484
摘要： The present invention involves the use of fluorescence spectroscopy in the diagnosis of cervical cancer and precancer. Using multiple illumination wavelengths, it is possible to (i) differentiate normal or inflamed tissue from squamous intraepithelial lesions (SILs) and (ii) to differentiate high grade SILs from non-high grade SILs. The detection may be performed in vitro or in vivo. Multivariate statistical analysis was employed to reduce the number of fluorescence excitation-emission wavelength pairs needed to re-develop algorithms that demonstrate a minimum decrease in classification accuracy. Fluorescence at excitation-emission wavelength pairs was used to redevelop and test screening and diagnostic algorithms that have a similar classification accuracy to those that employ fluorescence emission spectra at three excitation wavelengths. Both the full-parameter and reduced-parameter screening algorithms discriminate between SILs and non-SILs with a similar specificity and a substantially improved sensitivity relative to Pap smear screening and differentiate high grade SILs from non-high grade SILs.
摘要翻译： 本发明涉及在宫颈癌和癌前期诊断中使用荧光光谱。 使用多个照明波长，可以（i）区分正常或发炎的组织与鳞状上皮内病变（SIL）和（ii）区分高等级SIL和非高等级SILs。 检测可以在体外或体内进行。 采用多元统计分析方法，减少重新开发算法所需的荧光激发 - 发射波长对数，证明其分类精度最小。 激发 - 发射波长对的荧光被用来重建和测试筛选和诊断算法，它们具有与在三个激发波长下采用荧光发射光谱相似的分类精度。 全参数和简化参数筛选算法都区分SILs和非SILs，具有相似的特异性，并且相对于Pap涂片筛选具有显着提高的敏感性，并区分高等级SIL和非高级SILs。
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公开(公告)号：US5842995A
公开(公告)日：1998-12-01
申请号：US672623
申请日：1996-06-28
CPC分类号： A61B5/444 , A61B5/0071 , A61B5/0075 , A61B5/0086 , A61B5/4331 , A61B5/445 , G01N21/65
摘要： An optical probe is disclosed which is suitable for rapidly measuring Raman spectra in vivo. The probe is designed to minimize interfering Raman and fluorescence signals generated within the probe itself. In addition, the probe design is compact, making it particularly suited for use in confined spaces such as body cavities. In one embodiment, the probe is employed to detect tissue abnormalities such as cervical cancers and precancers.
摘要翻译： 公开了适用于在体内快速测量拉曼光谱的光学探针。 探头设计用于最小化探针本身内产生的干扰拉曼和荧光信号。 此外，探头设计紧凑，使其特别适用于诸如体腔的密闭空间。 在一个实施方案中，探针用于检测组织异常，例如宫颈癌和胃癌。
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公开(公告)号：US06697666B1
公开(公告)日：2004-02-24
申请号：US09519153
申请日：2000-03-06
IPC分类号： A61B500
CPC分类号： A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4331
摘要： A method and apparatus for characterizing tissue of epithelial lined viscus in vivo including, for example, the endocervical canal. The method comprises illuminating an interior surface of the viscus with electromagnetic radiation wavelengths to produce a plurality of fluorescence intensity spectra, detecting a plurality of emission wavelengths from the fluorescence intensity spectra, and characterizing the epithelial viscus tissue as a function of the emission wavelengths. The apparatus includes a light source of emitting a plurality of electromagnetic radiation wavelengths, an optical probe connected to the light source, the probe being adapted to apply the plurality of electromagnetic radiation wavelengths to an interior surface of epithelial viscus tissue under test and to gather fluorescence emitted from the tissue, a detector connected to the probe for detecting at least one fluorescence spectrum emitted from the tissue under test and a programmed computer connected to the detector for processing the at least one fluorescence spectrum according to a predetermined algorithm to characterize the tissue under test.
摘要翻译： 用于表征体内上皮内衬粘液的组织的方法和装置，包括例如子宫颈管。 该方法包括用电磁辐射波长照射粘液的内表面以产生多个荧光强度光谱，从荧光强度光谱检测多个发射波长，以及表征上皮粘液组织作为发射波长的函数。 该装置包括发射多个电磁辐射波长的光源，连接到光源的光学探针，该探针适于将多个电磁辐射波长施加到被测上皮粘液组织的内表面并收集荧光 从所述组织发射的检测器，连接到所述探针的检测器，用于检测从被检测组织发射的至少一个荧光光谱;以及编程计算机，连接到所述检测器，用于根据预定算法处理所述至少一个荧光光谱， 测试。
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6.发明授权Near-infrared raman spectroscopy for in vitro and in vivo detection of cervical precancers 失效近红外拉曼光谱法用于宫颈预处理的体外和体内检测
公开(公告)号：US5991653A
公开(公告)日：1999-11-23
申请号：US667993
申请日：1996-06-19
CPC分类号： G01N21/6486 , A61B5/0059 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4331 , G01N21/65 , A61B5/0086 , A61B5/7264 , G01N2021/656
摘要： Early diagnosis of cervical precancer is an important clinical goal. Optical spectroscopy has been suggested as a new technique to overcome limitations of current clinical practice. Herein, NIR Raman spectroscopy is applied to the diagnosis of cervical precancers. Using algorithms based on empirically selected peak intensities, ratios of peak intensities and a combination of Principal Component Analysis (PCA) for data reduction and Fisher Discriminant Analysis (FDA), normal tissues, inflammation and metaplasia were distinguishable from low grade and high grade precancers. The primary contributors to the tissue spectra appear to be collagen, nucleic acids, phospholipids and glucose 1-phosphate. These results suggest that near infrared Raman spectroscopy can be used effectively for cervical precancer diagnosis.
摘要翻译： 子宫颈癌的早期诊断是一个重要的临床目标。 光谱学被认为是克服当前临床实践的局限性的新技术。 在这里，NIR拉曼光谱法被应用于子宫颈预处理的诊断。 使用基于经验选择的峰值强度的算法，峰值强度的比率和用于数据降低的主成分分析（PCA）和Fisher判别分析（FDA），正常组织，炎症和化生的组合与低等级和高级别的预处理可以区分开。 组织光谱的主要贡献者似乎是胶原，核酸，磷脂和葡萄糖1-磷酸。 这些结果表明，近红外拉曼光谱可以有效地用于子宫颈癌前期诊断。
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7.发明授权Optical method and apparatus for the diagnosis of cervical precancers using raman and fluorescence spectroscopies 失效用于使用拉曼和荧光光谱诊断子宫颈预处理的光学方法和装置
公开(公告)号：US5697373A
公开(公告)日：1997-12-16
申请号：US403446
申请日：1995-03-14
CPC分类号： G01N21/6486 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4331 , A61B5/7264 , G01N21/65 , A61B5/0086 , G01N2021/656
摘要： A method and apparatus for detecting tissue abnormality, particularly precancerous cervical tissue, through fluorescence or Raman spectroscopy, or a combination of fluorescence and Raman spectroscopy. In vivo fluorescence measurements were followed by in vitro NIR Raman measurements on human cervical biopsies. Fluorescence spectra collected at 337, 380 and 460 nm excitation were used to develop a diagnostic method to differentiate between normal and dysplastic tissues. Using a fluorescence diagnostic method, a sensitivity and specificity of 80% and 67% were observed for differentiating squamous intraepithelial lesions (SILs) from all other tissues. In accordance with another aspect of the invention, using Raman scattering peaks observed at selected wavenumbers, SILs were separated from other tissues with a sensitivity and specificity of 88% and 100%. In addition, inflammation and metaplasia samples are correctly separated from the SILs.
摘要翻译： 一种用于通过荧光或拉曼光谱法或荧光和拉曼光谱的组合检测组织异常，特别是癌前期宫颈组织的方法和装置。 体内荧光测量之后是人体宫颈活检的体外NIR拉曼测量。 使用在337,380和460nm激发下收集的荧光光谱来开发用于区分正常组织和发育不良组织的诊断方法。 使用荧光诊断方法，从所有其他组织中鉴别出鳞状上皮内病变（SILs）的灵敏度和特异度为80％和67％。 根据本发明的另一方面，使用在选定波数处观察到的拉曼散射峰，将SIL与其他组织分离，灵敏度和特异性为88％和100％。 此外，炎症和化生样本正确地从SILs分离。
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8.发明授权Spectroscopic method and apparatus for optically detecting abnormal mammalian epithelial tissue 失效用于光学检测异常哺乳动物上皮组织的光谱法和装置
公开(公告)号：US6095982A
公开(公告)日：2000-08-01
申请号：US988840
申请日：1997-12-11
CPC分类号： G01N21/6486 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4331 , A61B5/7264 , G01N21/65 , A61B5/0086 , G01N2021/656
摘要： A method and apparatus for detecting tissue abnormality, particularly precancerous cervical tissue, through fluorescence or Raman spectroscopy, or a combination of fluorescence and Raman spectroscopy. In vivo fluorescence measurements were followed by in vitro NIR Raman measurements on human cervical biopsies. Fluorescence spectra collected at 337, 380 and 460 nm excitation were used to develop a diagnostic method to differentiate between normal and dysplastic tissues. Using a fluorescence diagnostic method, a sensitivity and specificity of 80% and 67% were observed for differentiating squamous intraepithelial lesions (SILs) from all other tissues. In accordance with another aspect of the invention, using Raman scattering peaks observed at selected wavenumbers, SILs were separated from other tissues with a sensitivity and specificity of 88% and 100%. In addition, inflammation and metaplasia samples are correctly separated from the SILs.
摘要翻译： 一种用于通过荧光或拉曼光谱法或荧光和拉曼光谱的组合检测组织异常，特别是癌前期宫颈组织的方法和装置。 体内荧光测量之后是人体宫颈活检的体外NIR拉曼测量。 使用在337,380和460nm激发下收集的荧光光谱来开发用于区分正常组织和发育不良组织的诊断方法。 使用荧光诊断方法，从所有其他组织中鉴别出鳞状上皮内病变（SILs）的灵敏度和特异度为80％和67％。 根据本发明的另一方面，使用在选定波数处观察到的拉曼散射峰，将SIL与其他组织分离，灵敏度和特异性为88％和100％。 此外，炎症和化生样本正确地从SILs分离。
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公开(公告)号：US20090068108A1
公开(公告)日：2009-03-12
申请号：US11877476
申请日：2007-10-23
IPC分类号： A61K49/00 , G01N33/543 , A61P35/00
CPC分类号： A61B5/0059 , A61B5/411 , A61B5/415 , A61B5/416 , A61B5/418 , A61K49/00 , A61K49/0017 , A61K49/0058 , A61K49/0067 , B82Y15/00 , B82Y30/00 , G01N33/587 , G01N33/588
摘要： Methods and apparatuses for detecting a condition of a sample (including cervical cancers and pre-cancers) through reflectance and/or fluorescence imaging. A sample is obtained. One or more metallic nanoparticles and/or one or more quantum dots are obtained. The one or more metallic nanoparticles and/or one or more quantum dots are coupled to one or more biomarkers of the sample that are associated with the condition. A reflectance and/or fluorescence image of the sample is then taken. The image(s) exhibit characteristic optical scattering from the one or more metallic nanoparticles and/or characteristic fluorescence excitation from the one or more quantum dots to signal the presence of the one or more biomarkers. In this way, the condition can be readily screened or diagnosed.
摘要翻译： 通过反射和/或荧光成像检测样品（包括宫颈癌和癌前病症）的方法和装置。 获得样品。 获得一种或多种金属纳米颗粒和/或一个或多个量子点。 将一种或多种金属纳米颗粒和/或一个或多个量子点偶联到与该条件相关联的样品的一个或多个生物标志物上。 然后取样品的反射率和/或荧光图像。 该图像表现出来自一种或多种金属纳米颗粒的特征光学散射和/或来自一个或多个量子点的特征荧光激发以发出一个或多个生物标志物的存在。 以这种方式，可以容易地筛选或诊断病症。
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公开(公告)号：US20070038120A1
公开(公告)日：2007-02-15
申请号：US11428806
申请日：2006-07-05
IPC分类号： A61B6/00
CPC分类号： G01N21/49 , A61B5/0071 , A61B5/0075 , A61B5/0088 , A61B5/443 , A61B5/444 , A61B2562/0242
摘要： Methods and apparatus for depth-resolved spectroscopy. A ball lens may be used to redirect light from a fiber-optic probe so that the light intersects the detection region of a collection probe in a specific depth layer of the specimen. A fiber-optic probe may comprise a collection fiber proximal to a central axis of a ball lens and a pair of illumination fibers distal to the central axis.
摘要翻译： 深度分辨光谱法的方法和装置。 可以使用球透镜来重定向光纤探针的光，使得光与样本的特定深度层中的收集探针的检测区域相交。 光纤探针可以包括靠近球透镜的中心轴线的收集光纤和远离中心轴线的一对照明光纤。
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