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    System for the noninvasive estimation of relative age
    2.
    发明授权
    System for the noninvasive estimation of relative age 失效
    无创估计相对年龄系统

    公开(公告)号：US06501982B1

    公开(公告)日：2002-12-31

    申请号：US09487236

    申请日：2000-01-19

    申请人： Timothy L. Ruchti ,  Suresh Thennadil ,  Stephen F. Malin ,  Jessica Rennert

    发明人： Timothy L. Ruchti ,  Suresh Thennadil ,  Stephen F. Malin ,  Jessica Rennert

    IPC分类号： A61B600

    CPC分类号： A61B5/441 ,  A61B5/0059 ,  A61B5/0075 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/14546 ,  A61B5/1455 ,  A61B5/7264 ,  A61B5/7267 ,  A61B2560/0223 ,  G01N21/359 ,  G01N21/4785

    摘要： Noninvasive instrumentation and procedures have been developed for estimating the apparent age of human and animal subjects based on the irradiation of skin tissue with near-infrared light. The method of age estimation provides additional information about primary sources of systematic tissue variability due to chronological factors and environmental exposure. Therefore, categorization of subjects on the basis of the estimated apparent age is suitable for further spectral analysis and the measurement of biological and chemical compounds, such as blood analytes. Furthermore, age determination of subjects has particular benefit in assessment of therapies used to reduce the effects of ageing in tissue and measurement of tissue damage.

    摘要翻译： 已经开发了非侵入性仪器和程序，用于基于用近红外光照射皮肤组织来估计人和动物受试者的表观年龄。 年龄估计的方法提供了关于由于时间因素和环境暴露引起的系统组织变异性的主要来源的附加信息。 因此，根据估计的表观年龄对受试者的分类适用于进一步的光谱分析和生物和化学化合物如血液分析物的测量。 此外，受试者的年龄确定在评估用于减少组织中老化的影响和测量组织损伤的疗法方面特别有益。

    Non-invasive method of determining skin thickness and characterizing layers of skin tissue in vivo
    4.
    发明授权
    Non-invasive method of determining skin thickness and characterizing layers of skin tissue in vivo 失效
    确定皮肤厚度并在体内表征皮肤组织层的非侵入性方法

    公开(公告)号：US06456870B1

    公开(公告)日：2002-09-24

    申请号：US09514039

    申请日：2000-02-25

    申请人： Jessica Rennert ,  Glenn Aaron Kees ,  Timothy L. Ruchti

    发明人： Jessica Rennert ,  Glenn Aaron Kees ,  Timothy L. Ruchti

    IPC分类号： A61B500

    CPC分类号： G01N21/274 ,  A61B5/0059 ,  A61B5/0075 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/1495 ,  A61B5/7264 ,  A61B2560/0223 ,  A61B2560/0233 ,  G01N21/359 ,  G01N21/4785 ,  G01N21/49

    摘要： A novel approach to measuring the overall and layer-by-layer thickness of in vivo skin tissue based on near infrared absorbance spectra is described. The different biological and chemical compounds present in the various layers of a tissue sample have differing absorbance spectra and scattering properties that enable them to be discerned and quantified, thus allowing an estimate of the thickness of the tissue being sampled. The method of the invention also yields the chemical composition of the absorbing and/or scattering species of each layer. Additionally, a method of path length normalization for the purpose of noninvasive analyte prediction on the basis of skin thickness and layer constituents is provided.

    摘要翻译： 描述了基于近红外吸收光谱测量体内皮肤组织的整体和逐层厚度的新颖方法。 存在于组织样品各层中的不同的生物和化学化合物具有不同的吸收光谱和散射性质，使得它们能够被辨别和定量，从而允许估计被采样的组织的厚度。 本发明的方法还产生每层的吸收和/或散射物质的化学组成。 另外，提供了基于皮肤厚度和层成分的非侵入性分析物预测目的的路径长度归一化方法。

    Intra-serum and intra-gel for modeling human skin tissue
    5.
    发明授权
    Intra-serum and intra-gel for modeling human skin tissue 失效
    血清内和凝胶内用于建模人体皮肤组织

    公开(公告)号：US06475800B1

    公开(公告)日：2002-11-05

    申请号：US09502877

    申请日：2000-02-10

    申请人： Kevin H. Hazen ,  James Matthew Welch ,  Stephen F. Malin ,  Timothy L. Ruchti ,  Alexander D. Lorenz ,  Tamara L. Troy ,  Suresh Thennadil ,  Thomas B. Blank

    发明人： Kevin H. Hazen ,  James Matthew Welch ,  Stephen F. Malin ,  Timothy L. Ruchti ,  Alexander D. Lorenz ,  Tamara L. Troy ,  Suresh Thennadil ,  Thomas B. Blank

    IPC分类号： G01N3100

    CPC分类号： G01N21/274 ,  A61B5/0075 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/1495 ,  A61B5/7264 ,  A61B2560/0223 ,  A61B2560/0233 ,  G01N21/359 ,  G01N21/4785 ,  G01N21/49 ,  Y10T436/10

    摘要： The invention provides a class of samples that model the human body. This family of samples is based upon emulsions of oil in water with lecithin acting as the emulsifier. These solutions that have varying particle sizes may be spiked with basis set components (albumin, urea and glucose) to simulate skin tissues further. The family of samples is such that other organic compounds such as collagen, elastin, globulin and bilirubin may be added, as can salts such as Na+, K+ and Cl−. Layers of varying thickness with known index of refraction and particle size distributions may be generated using simple crosslinking reagents, such as collagen (gelatin). The resulting samples are flexible in each analyte's concentration and match the skin layers of the body in terms of the samples reduced scattering and absorption coefficients, &mgr;ms and &mgr;ma. This family of samples is provided for use in the medical field where lasers and spectroscopy based analyzers are used in treatment of the body. In particular, knowledge may be gained on net analyte signal, photon depth of penetration, photon radial diffusion, photon interaction between tissue layers, photon density (all as a function of frequency) and on instrument parameter specifications such as resolution and required dynamic range (A/D bits required). In particular, applications to delineate such parameters have been developed for the application of noninvasive glucose determination in the near-IR region from 700 to 2500 nm with an emphasis on the region 1000 to 2500 nm (10,000 to 4,000 cm−1).

    摘要翻译： 本发明提供了一类对人体进行建模的样品。 该样品系基于水中的油与卵磷脂作为乳化剂的乳液。 具有不同粒径的这些溶液可以加入基础组分（白蛋白，尿素和葡萄糖）以进一步模拟皮肤组织。 样品家族可以加入诸如胶原，弹性蛋白，球蛋白和胆红素的其它有机化合物，也可以加入诸如Na +，K +和Cl-的盐。 可以使用简单的交联试剂如胶原（明胶）产生具有已知折射率和粒度分布的不同厚度的层。 所得样品在每种分析物的浓度上是灵活的，并且根据样品减少的散射和吸收系数，妈妈和玛玛来匹配身体的皮肤层。 该样品系列用于医疗领域，其中使用激光和基于光谱的分析仪来治疗身体。 特别地，可以获得关于净分析物信号，光子穿透深度，光子径向扩散，组织层之间的光子相互作用，光子密度（全部作为频率的函数）以及仪器参数规格（例如分辨率和所需动态范围） 需要A / D位）。 特别地，已经开发了描绘这些参数的应用，用于在700至2500nm的近红外区域中应用非侵入性葡萄糖测定，重点在1000至2500nm（10,000至4000cm -1）的区域。

    Intra-serum and intra-gel for modeling human skin tissue
    6.
    发明授权
    Intra-serum and intra-gel for modeling human skin tissue 失效
    血清内和凝胶内用于建模人体皮肤组织

    公开(公告)号：US06777240B2

    公开(公告)日：2004-08-17

    申请号：US10241344

    申请日：2002-09-11

    申请人： Kevin H. Hazen ,  James Matthew Welch ,  Stephen F. Malin ,  Timothy L. Ruchti ,  Alexander D. Lorenz ,  Tamara L. Troy ,  Suresh Thennadil ,  Thomas B. Blank

    发明人： Kevin H. Hazen ,  James Matthew Welch ,  Stephen F. Malin ,  Timothy L. Ruchti ,  Alexander D. Lorenz ,  Tamara L. Troy ,  Suresh Thennadil ,  Thomas B. Blank

    IPC分类号： G01N3100

    CPC分类号： G01N21/274 ,  A61B5/0075 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/1495 ,  A61B5/7264 ,  A61B2560/0223 ,  A61B2560/0233 ,  G01N21/359 ,  G01N21/4785 ,  G01N21/49 ,  Y10T436/10

    摘要： The invention provides a class of samples that model the human body. This family of samples is based upon emulsions of oil in water with lecithin acting as the emulsifier. These solutions that have varying particle sizes may be spiked with basis set components (albumin, urea and glucose) to simulate skin tissues further. The family of samples is such that other organic compounds such as collagen, elastin, globulin and bilirubin may be added, as can salts such as Na+, K+and Cl−. Layers of varying thickness with known index of refraction and particle size distributions may be generated using simple crosslinking reagents, such as collagen (gelatin). The resulting samples are flexible in each analyte's concentration and match the skin layers of the body in terms of the samples reduced scattering and absorption coefficients, &mgr;'s and &mgr;a. This family of samples is provided for use in the medical field where lasers and spectroscopy based analyzers are used in treatment of the body. In particular, knowledge may be gained on net analyte signal, photon depth of penetration, photon radial diffusion, photon interaction between tissue layers, photon density (all as a function of frequency) and on instrument parameter specifications such as resolution and required dynamic range (A/D bits required). In particular, applications to delineate such parameters have been developed for the application of noninvasive glucose determination in the near-IR region from 700 to 2500 nm with an emphasis on the region 1000 to 2500 nm (10,000 to 4,000 cm−1).

    摘要翻译： 本发明提供了一类对人体进行建模的样品。 该样品系基于水中的油与卵磷脂作为乳化剂的乳液。 具有不同粒径的这些溶液可以加入基础组分（白蛋白，尿素和葡萄糖）以进一步模拟皮肤组织。 样品家族可以加入其它有机化合物如胶原蛋白，弹性蛋白，球蛋白和胆红素，也可以加入诸如Na +，K +和Cl - 的盐。 可以使用简单的交联试剂如胶原（明胶）产生具有已知折射率和粒度分布的不同厚度的层。 所得样品在每种分析物的浓度上是柔性的，并且根据样品减少的散射和吸收系数mu和μa来匹配身体的皮肤层。 该样品系列用于医疗领域，其中使用激光和基于光谱的分析仪来治疗身体。 特别地，可以获得关于净分析物信号，光子穿透深度，光子径向扩散，组织层之间的光子相互作用，光子密度（全部作为频率的函数）以及仪器参数规格（例如分辨率和所需动态范围） 需要A / D位）。 特别地，已经开发出描绘这些参数的应用，用于在700至2500nm的近红外区域中应用非侵入性葡萄糖测定，重点在1000至2500nm（10,000至4000cm -1）的区域。

    Non-invasive in vivo tissue classification using near-infrared measurements
    7.
    发明授权
    Non-invasive in vivo tissue classification using near-infrared measurements 失效
    使用近红外测量的非侵入性体内组织分类

    公开(公告)号：US06405065B1

    公开(公告)日：2002-06-11

    申请号：US09487547

    申请日：2000-01-19

    申请人： Stephen F. Malin ,  Timothy L. Ruchti ,  Jessica Rennert

    发明人： Stephen F. Malin ,  Timothy L. Ruchti ,  Jessica Rennert

    IPC分类号： A61B500

    CPC分类号： G01N21/4785 ,  A61B5/0075 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/14546 ,  A61B5/1455 ,  A61B5/7264 ,  A61B5/7267 ,  A61B2560/0223 ,  G01N21/359 ,  Y10S128/923

    摘要： An in vivo, non-invasive method of tissue classification using near-IR (NIR) spectral measurements. A classification model is based on NIR spectral absorbance measurements from an exemplary population. Spectral features representing variation between tissue types are identified. Analytic techniques enhance the features of interest and correct spectral interference to improve the predictive ability of the classification model. A classification routine defines classes based on variation between tissue types, such that variation within a class is small compared to variation between classes. A decision rule assigns individual samples from the exemplary population to classes. An in-vivo, non-invasive procedure applies the classification model to individual tissue samples. A preferred embodiment of the invention distinguishes transgenic mice from non-transgenic individuals based on variation in fat composition within muscle tissue.

    摘要翻译： 使用近红外（NIR）光谱测量的体内非侵入性组织分类方法。 分类模型基于来自示例性群体的近红外光谱吸收测量。 识别表示组织类型之间变化的光谱特征。 分析技术增强了感兴趣的特征和正确的光谱干扰，从而提高了分类模型的预测能力。 分类程序基于组织类型之间的变化来定义类，使得类之间的变化与类之间的变化相比较小。 决策规则将个体样本从示例性群体分配到类别。 体内非侵入性手术将分类模型应用于个体组织样本。 本发明的优选实施方案基于肌肉组织内脂肪组成的变化来区分转基因小鼠与非转基因个体。

    Fiber optic illumination and detection patterns, shapes, and locations for use in spectroscopic analysis
    8.
    发明授权
    Fiber optic illumination and detection patterns, shapes, and locations for use in spectroscopic analysis 失效
    用于光谱分析的光纤照明和检测图案，形状和位置

    公开(公告)号：US06411373B1

    公开(公告)日：2002-06-25

    申请号：US09415389

    申请日：1999-10-08

    申请人： Jeffrey J. Garside ,  Stephen Monfre ,  Barry C. Elliott ,  Timothy L. Ruchti ,  Glenn Aaron Kees ,  Frank S. Grochocki

    发明人： Jeffrey J. Garside ,  Stephen Monfre ,  Barry C. Elliott ,  Timothy L. Ruchti ,  Glenn Aaron Kees ,  Frank S. Grochocki

    IPC分类号： G01N3348

    CPC分类号： G01N21/474

    摘要： The invention provides a design process that is used in the determination of the pattern of detector and illumination optical fibers at the sampling area of a subject. Information about the system, specifically a monochromator (e.g. to determine the optimal number of fibers at an output slit) and the bundle termination at a detector optics stack (e.g. to determine the optimal number of fibers at the bundle termination), is of critical importance to this design. It is those numbers that determine the ratio and number of illumination to detection fibers, significantly limiting and constraining the solution space. Additional information about the estimated signal and noise in the skin is necessary to maximize the signal-to-noise ratio in the wavelength range of interest. Constraining the fibers to a hexagonal perimeter and prescribing a hex-packed pattern, such that alternating columns contain illumination and detection fibers, yields optimal results. In the preferred embodiment of the invention, two detectors share the totality of the detection fibers at the sampling interface. A third group of detection fibers is used for classification purposes.

    摘要翻译： 本发明提供了一种设计过程，其用于确定被检体的取样区域处的检测器和照明光纤的图案。 关于系统的信息，特别是单色仪（例如，确定输出狭缝处的光纤的最佳数量）和检测器光学堆叠处的束终止（例如，以确定束终止时的最佳光纤数量）是至关重要的 到这个设计。 这些数字决定了对检测光纤的照射比例和数量，显着限制和限制了解决方案的空间。 关于皮肤估计的信号和噪声的附加信息对于使感兴趣的波长范围内的信噪比最大化是必要的。 将纤维限制在六边形周边，并规定六方填充图案，使得交替的列包含照明和检测纤维，产生最佳结果。 在本发明的优选实施例中，两个检测器在采样接口处共享检测光纤的总体。 第三组检测纤维用于分类目的。

    Combinative multivariate calibration that enhances prediction ability through removal of over-modeled regions
    9.
    发明授权
    Combinative multivariate calibration that enhances prediction ability through removal of over-modeled regions 失效
    组合多变量校准，通过去除过度模拟区域增强预测能力

    公开(公告)号：US06871169B1

    公开(公告)日：2005-03-22

    申请号：US09630201

    申请日：2000-08-01

    申请人： Kevin H. Hazen ,  Suresh Thennadil ,  Timothy L. Ruchti

    发明人： Kevin H. Hazen ,  Suresh Thennadil ,  Timothy L. Ruchti

    IPC分类号： G01N21/27 ,  G01N21/35 ,  G06F7/60 ,  G06F17/10 ,  G06F101/00

    CPC分类号： G01N21/359 ,  G01N21/274 ,  G01N21/3577

    摘要： A novel multivariate model for analysis of absorbance spectra allows for each wavelength or spectral region to be modeled with just enough factors to fully model the analytical signal without the incorporation of noise by using excess factors. Each wavelength or spectral region is modeled utilizing its own number of factors independently of other wavelengths or spectral regions. An iterative combinative PCR algorithm allows a different number of factors to be applied to different wavelengths. In an exemplary embodiment, a three-factor model is applied over a given spectral region. The residual of the three-factor model is calculated and used as the input for an additional five-factor model. Prior to the additional five factors being applied, some of the wavelengths are removed. This leads to a three-factor model over the first region and an eight-factor model over the second region. This analysis of residuals can be repeated such that a one to n factor model could be applied to any given wavelength, or rather any number of factors may be employed to model any given frequency or spectral region. A method of predicting concentration of a target analyte from sample spectra applies a calibration developed using the inventive PCR algorithm to a matrix of sample spectral to generate a vector of predicted concentrations for the target analyte.

    摘要翻译： 用于分析吸收光谱的新型多变量模型允许将每个波长或光谱区域用足够的因子进行建模，以完全建模分析信号，而不会通过使用过量因子来引入噪声。 每个波长或光谱区域都利用独立于其他波长或光谱区域的其自身数量的因子进行建模。 迭代组合PCR算法允许将不同数量的因子应用于不同波长。 在示例性实施例中，三因素模型被应用于给定的光谱区域。 计算三因素模型的残差，并将其用作额外的五因素模型的输入。 在应用额外的五个因素之前，一些波长被去除。 这导致了第一个区域的三因素模型和第二个区域的八因素模型。 可以重复残差的这种分析，使得可以对任何给定波长应用一到一因子模型，或者可以采用任何数量的因素来建模任何给定的频率或光谱区域。 从样品光谱预测目标分析物的浓度的方法将使用本发明的PCR算法开发的校准应用于样品光谱的矩阵，以产生靶分析物的预测浓度的载体。

    Multi-tier method of classifying sample spectra for non-invasive blood analyte prediction
    10.
    发明授权
    Multi-tier method of classifying sample spectra for non-invasive blood analyte prediction 失效
    对非侵入性血液分析物预测的样本光谱进行分类的多层方法

    公开(公告)号：US06512936B1

    公开(公告)日：2003-01-28

    申请号：US09665201

    申请日：2000-09-18

    申请人： Stephen L. Monfre ,  Thomas B. Blank ,  Timothy L. Ruchti ,  Suresh Thennadil

    发明人： Stephen L. Monfre ,  Thomas B. Blank ,  Timothy L. Ruchti ,  Suresh Thennadil

    IPC分类号： A61B500

    CPC分类号： G06K9/6217 ,  A61B5/1075 ,  A61B5/14532 ,  A61B5/1455 ,  A61B5/1495 ,  A61B5/7264 ,  A61B2560/0223 ,  A61B2560/0233 ,  G01N21/274 ,  G01N21/359 ,  G01N21/4785 ,  G01N21/49 ,  Y10S128/92

    摘要： A method of multi-tier classification and calibration in noninvasive blood analyte prediction minimizes prediction error by limiting co-varying spectral interferents. Tissue samples are categorized based on subject demographic and instrumental skin measurements, including in vivo near-IR spectral measurements. A multi-tier intelligent pattern classification sequence organizes spectral data into clusters having a high degree of internal consistency in tissue properties. In each tier, categories are successively refined using subject demographics, spectral measurement information and other device measurements suitable for developing tissue classifications. The multi-tier classification approach to calibration utilizes multivariate statistical arguments and multi-tiered classification using spectral features. Variables used in the multi-tiered classification can be skin surface hydration, skin surface temperature, tissue volume hydration, and an assessment of relative optical thickness of the dermis by the near-IR fat band. All tissue parameters are evaluated using the NIR spectrum signal along key wavelength segments.

    摘要翻译： 非侵入性血液分析物预测中的多层分类和校准方法通过限制共同变化的光谱干扰来最小化预测误差。 组织样品根据受试者的人口统计学和仪器皮肤测量进行分类，包括体内近红外光谱测量。 多层智能图案分类序列将光谱数据组织成具有组织性质内部高度一致性的簇。 在每个层次中，使用主题人口统计学，光谱测量信息和适合于开发组织分类的其它装置测量法来连续地改进类别。 校准的多层分类方法利用多变量统计学参数和使用光谱特征的多层次分类。 用于多层分类的变量可以是皮肤表面水合，皮肤表面温度，组织体积水合，以及近红外脂肪带对真皮的相对光学厚度的评估。 使用沿关键波长段的NIR光谱信号评估所有组织参数。