公开(公告)号：US08676283B2

公开(公告)日：2014-03-18

申请号：US11964665

申请日：2007-12-26

Applicant: Nathaniel Matter ,  Marwood Neal Ediger ,  John D Maynard

Inventor： Nathaniel Matter ,  Marwood Neal Ediger ,  John D Maynard

IPC: A61B5/1455

CPC classification number: A61B5/0059 ,  A61B5/0071 ,  A61B5/14532 ,  A61B5/443 ,  A61B5/4875

Abstract: A method of determining a measure of a tissue state (e.g., glycation end-product or disease state) in an individual is disclosed. A portion of the skin of the individual is illuminated with excitation light, then light emitted by the tissue due to fluorescence of a chemical with the tissue responsive to the excitation light is detected. The detected light can be combined with a model relating fluorescence with a measure of tissue state to determine a tissue state. The invention can illuminate the skin and detect responsive light over a time that spans a plurality of cardiac cycles of the individual, which can, as an example, help mitigate the effects of time-varying signals such as those due to hemoglobin. The invention can also determine the amount of light to be directed to the skin, for example by controlling the time that a light source is energized. The amount of illumination light can be determined from a skin reflectance characteristic such as pigmentation or melanin in the skin. Controlling the amount of light directed to the tissue can reduce the dynamic range required of a corresponding optical system, for example by allowing a single system to accurately measure individuals with very light skin and individuals with very dark skin.

Abstract translation: 公开了确定个体中组织状态（例如糖基化终产物或疾病状态）的测量方法。 用激发光照射个体皮肤的一部分，然后检测由组织响应于激发光的化学物质的荧光而由组织发出的光。 检测到的光可以与将荧光与组织状态的测量相关联的模型组合以确定组织状态。 本发明可以照亮皮肤并且在跨越个体的多个心脏周期的时间内检测响应光，其可以作为示例有助于减轻诸如由于血红蛋白引起的时变信号的影响。 本发明还可以例如通过控制光源被激励的时间来确定要引导到皮肤的光量。 照明光的量可以根据皮肤的皮肤反射特性如皮肤中的色素沉着或黑色素来确定。 控制指向组织的光量可以减少相应光学系统所需的动态范围，例如通过允许单个系统准确地测量具有非常浅的皮肤的个体和具有非常暗的皮肤的个体。

公开(公告)号：US08131332B2

公开(公告)日：2012-03-06

申请号：US11675524

申请日：2007-02-15

Applicant: John D Maynard ,  Marwood Neal Ediger ,  Robert D Johnson ,  Mark Ries Robinson

Inventor： John D Maynard ,  Marwood Neal Ediger ,  Robert D Johnson ,  Mark Ries Robinson

IPC: A61B5/1455

CPC classification number: A61B5/14532 ,  A61B5/0071 ,  A61B5/1455

Abstract: Embodiments of the present invention provide an apparatus suitable for determining properties of in vivo tissue from spectral information collected from various tissue sites. An illumination system provides light at a plurality of broadband ranges, which are communicated to an optical probe. The optical probe can be a flexible probe in some embodiments, allowing ease of application. Light homogenizers and mode scramblers can be employed to improve the performance in some embodiments. The optical probe in some embodiments physically contacts the tissue, and in some embodiments does not physically contact the tissue. The optical probe receives light from the illumination system and transmits it to tissue, and receives light diffusely reflected in response to the broadband light, emitted from the in vivo tissue by fluorescence thereof in response to the broadband light, or a combination thereof. The optical probe can communicate the light to a spectrograph which produces a signal representative of the spectral properties of the light. An analysis system determines a property of the in vivo tissue from the spectral properties.

Abstract translation: 本发明的实施方案提供一种适合于从各种组织部位收集的光谱信息确定体内组织的性质的装置。 照明系统提供多个宽带范围的光，其传送到光学探针。 在一些实施例中，光学探针可以是柔性探针，允许易于应用。 在一些实施例中，可使用光均质器和模式加扰器来提高性能。 在一些实施例中，光学探针物理接触组织，并且在一些实施例中，物理接触组织。 光学探针从照明系统接收光并将其传输到组织，并且响应于宽带光或其组合而接收从体内组织发出的响应于通过其荧光发射的宽带光而漫反射的光。 光学探针可以将光传送到产生表示光的光谱特性的信号的光谱仪。 分析系统根据光谱性质确定体内组织的性质。

公开(公告)号：US08078243B2

公开(公告)日：2011-12-13

申请号：US11561380

申请日：2006-11-17

Applicant: Marwood Neal Ediger ,  John D Maynard ,  Robert D Johnson ,  Edward L Hull ,  Christopher D Brown

Inventor： Marwood Neal Ediger ,  John D Maynard ,  Robert D Johnson ,  Edward L Hull ,  Christopher D Brown

IPC: A61B5/1455

CPC classification number: A61B5/1455 ,  A61B5/0059 ,  A61B5/0064 ,  A61B5/0066 ,  A61B5/0068 ,  A61B5/0071 ,  A61B5/0075 ,  A61B5/14532 ,  A61B5/412 ,  A61B5/441

Abstract: A method of determining a measure of a tissue state (e.g., glycation end-product or disease state) in an individual. A portion of the tissue of the individual is illuminated with excitation light, then light emitted by the tissue due to fluorescence of a chemical with the tissue responsive to the excitation light is detected. The detected light can be combined with a model relating fluorescence with a measure of tissue state to determine a tissue state. The invention can comprise single wavelength excitation light, scanning of excitation light (illuminating the tissue at a plurality of wavelengths), detection at a single wavelength, scanning of detection wavelengths (detecting emitted light at a plurality of wavelengths), and combinations thereof. The invention also can comprise correction techniques that reduce determination errors due to detection of light other than that from fluorescence of a chemical in the tissue. For example, the reflectance of the tissue can lead to errors if appropriate correction is not employed. The invention can also comprise a variety of models relating fluorescence to a measure of tissue state, including a variety of methods for generating such models. Other biologic information can be used in combination with the fluorescence properties to aid in the determination of a measure of tissue state. The invention also comprises apparatuses suitable for carrying out the method, including appropriate light sources, detectors, and models (for example, implemented on computers) used to relate detected fluorescence and a measure of tissue state.

Abstract translation: 确定个体中组织状态（例如，糖基化终产物或疾病状态）的量度的方法。 用激发光照射个体组织的一部分，然后检测由组织响应于激发光的化学物质的荧光而由组织发出的光。 检测到的光可以与将荧光与组织状态的测量相关联的模型组合以确定组织状态。 本发明可以包括单波长激发光，激发光的扫描（以多个波长照射组织），单个波长的检测，检测波长的扫描（检测多个波长的发射光）及其组合。 本发明还可以包括校正技术，其减少由于检测到除了组织中的化学物质的荧光以外的光的测定误差。 例如，如果不采用适当的校正，组织的反射率可能导致错误。 本发明还可以包括将荧光与组织状态的测量相关联的各种模型，包括用于产生这种模型的各种方法。 其他生物信息可与荧光性质结合使用，有助于测定组织状态。 本发明还包括适于执行该方法的装置，包括用于检测荧光和组织状态测量的适当的光源，检测器和模型（例如，在计算机上实现）。

公开(公告)号：US08238993B2

公开(公告)日：2012-08-07

申请号：US11960260

申请日：2007-12-19

Applicant: John D Maynard ,  Marwood Neal Ediger

Inventor： John D Maynard ,  Marwood Neal Ediger

IPC: A61B5/1455

CPC classification number: A61B5/0059 ,  A61B5/0071 ,  A61B5/412 ,  G01N21/6408 ,  G01N2021/6417

Abstract: A method of determining a measure of a tissue state (e.g., glycation end-product or disease state) in an individual. A portion of the tissue of the individual is illuminated with excitation light, then light emitted by the tissue due to fluorescence of a chemical with the tissue responsive to the excitation light is detected. The detected light can be combined with a model relating fluorescence with a measure of tissue state to determine a tissue state. The invention can comprise measuring the fluorescence lifetime in either time-domain or frequency domain modes. The invention can also comprise a variety of models relating fluorescence to a measure of tissue state, including a variety of methods for generating such models. For example, multivariate models can be developed that relate lifetime trends of one or more constituents to increasing propensity to diabetes and pre-diabetes. Other biologic information can be used in combination with the fluorescence properties to aid in the determination of a measure of tissue state. The invention also comprises apparatuses suitable for carrying out the method, including appropriate light sources, detectors, and models (for example, implemented on computers) used to relate detected fluorescence and a measure of tissue state.

Abstract translation: 确定个体中组织状态（例如，糖基化终产物或疾病状态）的量度的方法。 用激发光照射个体组织的一部分，然后检测由组织响应于激发光的化学物质的荧光而由组织发出的光。 检测到的光可以与将荧光与组织状态的测量相关联的模型组合以确定组织状态。 本发明可以包括以时域或频域模式测量荧光寿命。 本发明还可以包括将荧光与组织状态的测量相关联的各种模型，包括用于产生这种模型的各种方法。 例如，可以开发多变量模型，其将一种或多种成分的寿命趋势与增加糖尿病和前期糖尿病的倾向相关联。 其他生物信息可与荧光性质结合使用，有助于测定组织状态。 本发明还包括适于执行该方法的装置，包括用于检测荧光和组织状态测量的适当的光源，检测器和模型（例如，在计算机上实现）。

公开(公告)号：US08140147B2

公开(公告)日：2012-03-20

申请号：US11677498

申请日：2007-02-21

Applicant: John D Maynard ,  Marwood Neal Ediger ,  Robert D Johnson ,  Mark Ries Robinson

Inventor： John D Maynard ,  Marwood Neal Ediger ,  Robert D Johnson ,  Mark Ries Robinson

IPC: A61B5/00 ,  A61B5/1455

CPC classification number: A61B5/1455 ,  A61B5/0071 ,  A61B5/0075 ,  A61B5/14532 ,  A61B5/14546 ,  G01N21/255 ,  G01N21/49 ,  G01N21/645 ,  G01N21/6486

Abstract: Embodiments of the present invention provide an apparatus with a flexible probe suitable for determining properties of in vivo tissue from spectral information collected from various tissue sites. An illumination system provides light at a plurality of broadband ranges, which are communicated to a flexible optical probe. Light homogenizers and mode scramblers can be employed to improve the performance in some embodiments. The optical probe in some embodiments physically contacts the tissue, and in some embodiments does not physically contact the tissue. The optical probe receives light from the illumination system and transmits it to tissue, and receives light diffusely reflected in response to the broadband light, emitted from the in vivo tissue by fluorescence thereof in response to the broadband light, or a combination thereof. The optical probe can communicate the light to a spectrograph which produces a signal representative of the spectral properties of the light. An analysis system determines a property of the in vivo tissue from the spectral properties.

Abstract translation: 本发明的实施方案提供一种具有柔性探针的装置，其适合于从各种组织部位收集的光谱信息来确定体内组织的性质。 照明系统在多个宽带范围内提供光，其传送到柔性光学探针。 在一些实施例中，可使用光均质器和模式加扰器来提高性能。 在一些实施例中，光学探针物理接触组织，并且在一些实施例中，物理接触组织。 光学探针从照明系统接收光并将其传输到组织，并且响应于宽带光或其组合而接收从体内组织发出的响应于通过其荧光发射的宽带光而漫反射的光。 光学探针可以将光传送到产生表示光的光谱特性的信号的光谱仪。 分析系统根据光谱性质确定体内组织的性质。

公开(公告)号：US08581697B2

公开(公告)日：2013-11-12

申请号：US12107764

申请日：2008-04-23

Applicant: Trent D Ridder ,  Rob Johnson ,  Russell Abbink ,  John D Maynard

Inventor： Trent D Ridder ,  Rob Johnson ,  Russell Abbink ,  John D Maynard

IPC: G05B23/00

CPC classification number: A61B5/0059 ,  A61B5/0075 ,  A61B5/14546 ,  A61B5/1455

Abstract: Methods and apparatuses for the determination of an attribute of the tissue of an individual use non-invasive Raman spectroscopy. For example, the alcohol concentration in the blood or tissue of an individual can be determined non-invasively. A portion of the tissue is illuminated with light, the light propagates into the tissue where it is Raman scattered within the tissue. The Raman scattered light is then detected and can be combined with a model relating Raman spectra to alcohol concentration in order to determine the alcohol concentration in the blood or tissue of the individual. Correction techniques can be used to reduce determination errors due to detection of light other than that from Raman scattering from the alcohol in the tissue. Other biologic information can be used in combination with the Raman spectral properties to aid in the determination of alcohol concentration, for example age of the individual, height of the individual, weight of the individual, medical history of the individual and his/her family, ethnicity, skin melanin content, or a combination thereof. The method and apparatus can be highly optimized to provide reproducible and, preferably, uniform radiance of the tissue, low tissue sampling error, depth targeting of the tissue layers or sample locations that contain the attribute of interest, efficient collection of Raman spectra from the tissue, high optical throughput, high photometric accuracy, large dynamic range, excellent thermal stability, effective calibration maintenance, effective calibration transfer, built-in quality control, and ease-of-use.

Abstract translation: 用于确定个体使用非侵入性拉曼光谱的组织属性的方法和装置。 例如，可以非侵入性地确定个体的血液或组织中的酒精浓度。 组织的一部分用光照射，光传播到组织中，其中拉曼散布在组织内。 然后检测拉曼散射光，并且可以将与拉曼光谱相关的模型与酒精浓度组合以确定个体的血液或组织中的酒精浓度。 校正技术可用于减少除了来自组织中的醇的拉曼散射以外的光的检测的测定误差。 其他生物信息可以与拉曼光谱性质结合使用，以帮助确定酒精浓度，例如个体的年龄，个体的身高，个体的体重，个体及其家人的病史， 种族，皮肤黑色素含量或其组合。 该方法和装置可以被高度优化以提供组织的可再现的，优选地均匀的辐射，低组织取样误差，组织层的深度瞄准或包含感兴趣属性的样本位置，从组织中有效收集拉曼光谱 ，光学吞吐量高，光度精度高，动态范围大，热稳定性好，有效的校准维护，有效的校准传输，内置的质量控制和易于使用。

公开(公告)号：US08515506B2

公开(公告)日：2013-08-20

申请号：US12107765

申请日：2008-04-23

Applicant: Trent D Ridder ,  Rob Johnson ,  Russell Abbink ,  John D Maynard

Inventor： Trent D Ridder ,  Rob Johnson ,  Russell Abbink ,  John D Maynard

IPC: A61B5/1455 ,  G06F7/04 ,  G05B19/00

CPC classification number: A61B5/0075 ,  A61B5/0059 ,  A61B5/14546 ,  A61B5/1455

Abstract: Methods and apparatuses for the determination of an attribute of the tissue of an individual use non-invasive Raman spectroscopy. For example, the alcohol concentration in the blood or tissue of an individual can be determined non-invasively. A portion of the tissue is illuminated with light, the light propagates into the tissue where it is Raman scattered within the tissue. The Raman scattered light is then detected and can be combined with a model relating Raman spectra to alcohol concentration in order to determine the alcohol concentration in the blood or tissue of the individual. Correction techniques can be used to reduce determination errors due to detection of light other than that from Raman scattering from the alcohol in the tissue. Other biologic information can be used in combination with the Raman spectral properties to aid in the determination of alcohol concentration, for example age of the individual, height of the individual, weight of the individual, medical history of the individual and his/her family, ethnicity, skin melanin content, or a combination thereof. The method and apparatus can be highly optimized to provide reproducible and, preferably, uniform radiance of the tissue, low tissue sampling error, depth targeting of the tissue layers or sample locations that contain the attribute of interest, efficient collection of Raman spectra from the tissue, high optical throughput, high photometric accuracy, large dynamic range, excellent thermal stability, effective calibration maintenance, effective calibration transfer, built-in quality control, and ease-of-use.

Abstract translation: 用于确定个体使用非侵入性拉曼光谱的组织属性的方法和装置。 例如，可以非侵入性地确定个体的血液或组织中的酒精浓度。 组织的一部分用光照射，光传播到组织中，其中拉曼散布在组织内。 然后检测拉曼散射光，并且可以将与拉曼光谱相关的模型与酒精浓度组合以确定个体的血液或组织中的酒精浓度。 校正技术可用于减少除了来自组织中的醇的拉曼散射以外的光的检测的测定误差。 其他生物信息可以与拉曼光谱性质结合使用，以帮助确定酒精浓度，例如个体的年龄，个体的身高，个体的体重，个体及其家人的病史， 种族，皮肤黑色素含量或其组合。 该方法和装置可以被高度优化以提供组织的可再现的，优选地均匀的辐射，低组织取样误差，组织层的深度瞄准或包含感兴趣属性的样本位置，从组织中有效收集拉曼光谱 ，光学吞吐量高，光度精度高，动态范围大，热稳定性好，有效的校准维护，有效的校准传输，内置的质量控制和易于使用。