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    Method and apparatus for dynamically monitoring multiple in vivo tissue chromophores
    1.
    发明授权
    Method and apparatus for dynamically monitoring multiple in vivo tissue chromophores 有权
    用于动态监测多个体内组织发色团的方法和装置

    公开(公告)号：US07248909B2

    公开(公告)日：2007-07-24

    申请号：US11103963

    申请日：2005-04-12

    申请人： Jangwoen Lee ,  Bruce J. Tromberg ,  Albert E. Cerussi ,  Matthew Brenner

    发明人： Jangwoen Lee ,  Bruce J. Tromberg ,  Albert E. Cerussi ,  Matthew Brenner

    IPC分类号： A61B5/00

    CPC分类号： A61B5/14551 ,  A61B5/14552 ,  A61B5/412 ,  G01N21/31 ,  G01N21/359 ,  G01N21/49 ,  G01N2201/08

    摘要： A device and method utilizes a broadband diffuse optical spectroscopy (DOS) system to dynamically calculate the concentrations of multiple chromophores in vivo using a non-invasive probe. The device and method permit dynamic monitoring of multiple in vivo tissue chromophores non-invasively with sensitivities necessary for effective therapeutic monitoring. The device includes a probe containing first and second source optical fibers as well as first and second detector optical fibers. The probe is placed adjacent to a sample of interest and detects reflected light which is passed to a proximally located detector and spectrometer. The concentrations of multiple chromophores are determined in real time. In a preferred embodiment, the multiple tissue chromophores include at least two of methemoglobin (MetHb), deoxyhemoglobin (Hb-R), oxyhemoglobin (Hb-O2), water (H2O), and methylene blue (MB). The device and method can be used quantify and monitor methemoglobin formation in subjects suffering from methemoglobinemia.

    摘要翻译： 一种使用宽带漫射光谱（DOS）系统的装置和方法使用非侵入性探针来动态地计算体内多个发色团的浓度。 该装置和方法允许非侵入性地动态监测多个体内组织发色团，具有有效治疗监测所需的灵敏度。 该装置包括包含第一和第二源光纤以及第一和第二检测器光纤的探针。 将探针放置在感兴趣的样本附近，并检测反射光，其被传递到位于近端的检测器和光谱仪。 多个发色团的浓度实时测定。 在优选实施方案中，多组织发色团包括高铁血红蛋白（MetHb），脱氧血红蛋白（Hb-R），氧合血红蛋白（Hb-O 2 H），水（H 2 O 2） SUB）和亚甲基蓝（MB）。 该装置和方法可用于定量和监测患有高铁血红蛋白血症的受试者中的高铁血红蛋白形成。

    Quantitative broadband absorption and scattering spectroscopy in turbid media by combined frequency-domain and steady state methodologies
    2.
    发明授权
    Quantitative broadband absorption and scattering spectroscopy in turbid media by combined frequency-domain and steady state methodologies 有权
    通过组合的频域和稳态方法在浑浊介质中定量宽带吸收和散射光谱

    公开(公告)号：US07428434B2

    公开(公告)日：2008-09-23

    申请号：US10191693

    申请日：2002-07-09

    申请人： Bruce J. Tromberg ,  Andrew J. Berger ,  Albert E. Cerussi ,  Frederic Bevilacqua ,  Dorota Jakubowski

    发明人： Bruce J. Tromberg ,  Andrew J. Berger ,  Albert E. Cerussi ,  Frederic Bevilacqua ,  Dorota Jakubowski

    IPC分类号： A61B6/00

    CPC分类号： A61B5/0091 ,  A61B5/4312

    摘要： A technique for measuring broadband near-infrared absorption spectra of turbid media that uses a combination of frequency-domain and steady-state reflectance methods. Most of the wavelength coverage is provided by a white-light steady-state measurement, whereas the frequency-domain data are acquired at a few selected wavelengths. Coefficients of absorption and reduced scattering derived from the frequency-domain data are used to calibrate the intensity of the steady-state measurements and to determine the reduced scattering coefficient at all wavelengths in the spectral window of interest. The absorption coefficient spectrum is determined by comparing the steady-state reflectance values with the predictions of diffusion theory, wavelength by wavelength. Absorption spectra of a turbid phantom and of human breast tissue in vivo, derived with the combined frequency-domain and steady-state technique, agree well with expected reference values.

    摘要翻译： 用于测量使用频域和稳态反射方法组合的混浊介质的宽带近红外吸收光谱的技术。 大多数波长覆盖由白光稳态测量提供，而频域数据是以几个选定的波长获得的。 来自频域数据的吸收系数和减少的散射用于校准稳态测量的强度，并确定感兴趣的光谱窗口中所有波长处的降低的散射系数。 通过将稳态反射率值与扩散理论的预测值，波长的波长进行比较来确定吸收系数谱。 通过组合的频域和稳态技术衍生的体内浑浊体模和人体乳腺组织的吸收光谱与预期的参考值吻合良好。

    METHOD AND APPARATUS FOR ASSESSING THE MOLECULAR WATER BINDING OF DEEP TISSUE IN VIVO USING NONIONIZING RADIATION
    3.
    发明申请
    METHOD AND APPARATUS FOR ASSESSING THE MOLECULAR WATER BINDING OF DEEP TISSUE IN VIVO USING NONIONIZING RADIATION 审中-公开
    使用非放射性辐射评估体内深层组织分子水结合的方法和装置

    公开(公告)号：US20070282179A1

    公开(公告)日：2007-12-06

    申请号：US11757673

    申请日：2007-06-04

    申请人： Sean Merritt ,  Bruce J. Tromberg ,  Albert E. Cerussi ,  Anthony J. Durkin ,  So Hyun Chung

    发明人： Sean Merritt ,  Bruce J. Tromberg ,  Albert E. Cerussi ,  Anthony J. Durkin ,  So Hyun Chung

    IPC分类号： A61B5/00

    CPC分类号： A61B5/0059 ,  A61B5/0064 ,  A61B5/0075 ,  A61B5/0091 ,  A61B5/441 ,  A61B5/4875

    摘要： A method of optically analyzing tissue in vivo in an individual to obtain a unique spectrum for the tissue of the individual includes the steps of optically measuring the tissue of the individual using broadband diffuse optical spectroscopy (DOS) to measure a normalized tissue water spectrum of the individual or noninvasively optically line scanning a tissue site on the individual at a plurality of points, then determining spectral differences between the normalized tissue water spectrum and a pure water spectrum at each point of a line scan, generating a bound water index (BWI) corresponding to the spectral differences, and identifying a tissue state corresponding to the scanned tissue based on the BWI.

    摘要翻译： 在个体中光学分析体内组织以获得个体组织的唯一光谱的方法包括以下步骤：使用宽带漫射光谱（DOS）光学测量个体的组织，以测量标准化组织水谱 个体或非侵入式光线在多个点上扫描个体上的组织部位，然后确定标准化组织水谱与在线扫描的每个点处的纯水谱之间的光谱差异，生成对应的结合水指数（BWI） 并且基于BWI识别与扫描的组织相对应的组织状态。

    Method and apparatus for detecting enzymatic activity using molecules that change electrophoretic mobility
    4.
    发明授权
    Method and apparatus for detecting enzymatic activity using molecules that change electrophoretic mobility 失效
    使用改变电泳迁移率的分子检测酶活性的方法和装置

    公开(公告)号：US07157223B2

    公开(公告)日：2007-01-02

    申请号：US09945396

    申请日：2001-08-30

    申请人： Nancy Allbritton ,  Christopher Sims ,  Michael W. Berns ,  Gavin D. Meredith ,  Tatiana B. Krasieva ,  Bruce J. Tromberg ,  Chao L. Lee

    发明人： Nancy Allbritton ,  Christopher Sims ,  Michael W. Berns ,  Gavin D. Meredith ,  Tatiana B. Krasieva ,  Bruce J. Tromberg ,  Chao L. Lee

    IPC分类号： C12Q1/00

    CPC分类号： C12M41/46 ,  C12M35/02 ,  C12M47/06 ,  C12Q1/00 ,  C12Q1/485 ,  G01N27/44721 ,  G01N27/44743 ,  G01N33/50 ,  G01N33/5017

    摘要： The activity of intracellular chemical reactions of molecules is measured by the use of fluorescently labeled substrate molecules that undergo a change in electrophoretic mobility upon chemical reaction such as that catalyzed by an enzyme. Specificity is achieved by using labeled substrate molecules that can be acted upon only by specific enzymes. Thus the activity of a specific enzyme or class of enzymes can be determined. Measurements are made with the intracellular presence of such substrate molecules, at some time of interest, typically after exposure of the cell to a stimulus that activates a particular enzymatic pathway. To ensure accuracy, measurements must be made in a timely manner so as to minimize chemical reactions occurring subsequent to the time of interest. Fast controllable laser lysis is used to obtain the contents of a single cell into which reporter substrate molecules have been introduced. The cell contents are then subjected to capillary electrophoresis and enzymatic activity is determined by comparing amounts of substrate molecules to amounts of enzymatically altered substrate molecules which are separated by the electrophoresis and identified by the presence of a fluorescent label.

    摘要翻译： 通过使用荧光标记的底物分子来测量分子的细胞内化学反应的活性，所述底物分子在诸如由酶催化的化学反应时经历电泳迁移率的变化。 通过使用只能被特定酶作用的标记底物分子来实现特异性。 因此，可以确定特异性酶或酶类的活性。 通常在感兴趣的某个时间通常在将细胞暴露于激活特定酶促途径的刺激之后，通过细胞内存在这样的底物分子进行测量。 为了确保准确性，必须及时进行测量，以最大限度地减少感兴趣的时间后发生的化学反应。 使用快速可控的激光裂解来获得引入了报告基质分子的单细胞的含量。 然后对细胞内容物进行毛细管电泳，并通过将底物分子的量与通过电泳分离并通过荧光标记的存在鉴定的酶促改变的底物分子的量进行比较来确定酶活性。

    Intrauterine device for laser light diffusion and method of using the same
    5.
    发明授权
    Intrauterine device for laser light diffusion and method of using the same 失效
    用于激光扩散的子宫内装置及其使用方法

    公开(公告)号：US5478339A

    公开(公告)日：1995-12-26

    申请号：US297752

    申请日：1994-08-30

    申请人： Yona Tadir ,  Michael W. Berns ,  Lars O. Svaasand ,  Bruce J. Tromberg

    发明人： Yona Tadir ,  Michael W. Berns ,  Lars O. Svaasand ,  Bruce J. Tromberg

    IPC分类号： A61B18/20 ,  A61B18/22 ,  A61N5/06 ,  A61B17/36

    CPC分类号： A61N5/062 ,  A61N5/0601 ,  A61B2018/2261 ,  A61N2005/0611

    摘要： An improved device for delivery of photoenergy from a light source, such as a laser, into a uterine cavity for photodynamic therapy is comprised of a plurality of optic fibers, which are bundled together and inserted into the uterine cavity by means of a uterine cannula. The cannula is positioned within the uterine cavity at a preferred location and then withdrawn thereby allowing the plurality of optic fibers to splay or diverge one from the other within the cavity. Different portions of the distal tip of the optic fiber is provided with a light diffusing tip, the remainder being provided with a nondiffusing tip portion. The fiber optic shape, as well as the segment which is permitted to actively diffuse light through the tip, is selected in order to provide a more uniform exposure intensity of the photo energy or at least sufficient radiation directed to each segment of the uterine walls.

    摘要翻译： 用于将光能从诸如激光器的光源递送到用于光动力疗法的子宫腔中的改进的装置由多个光纤组成，多个光纤通过子宫套管捆绑在一起并插入到子宫腔中。 套管位于子宫腔内的优选位置处，然后被抽出，从而允许多个光纤在空腔内使另一个光纤展开或发散。 光纤的远端的不同部分设置有光扩散尖端，其余部分设置有非扩散尖端部分。 选择纤维光学形状以及被允许主动地通过尖端漫射光束的片段，以便提供光能的更均匀的曝光强度或至少足够的辐射指向子宫壁的每个部分。

    Vaginal speculum for photodynamic therapy and method of using the same
    6.
    发明授权
    Vaginal speculum for photodynamic therapy and method of using the same 失效
    阴道窥器用于光动力疗法及其使用方法

    公开(公告)号：US5458595A

    公开(公告)日：1995-10-17

    申请号：US168553

    申请日：1993-12-16

    申请人： Yona Tadir ,  Michael W. Berns ,  Brad J. Monk ,  Glen Profeta ,  Bruce J. Tromberg

    发明人： Yona Tadir ,  Michael W. Berns ,  Brad J. Monk ,  Glen Profeta ,  Bruce J. Tromberg

    IPC分类号： A61B1/32 ,  A61B17/22 ,  A61B17/42 ,  A61B18/22 ,  A61B19/00 ,  A61N5/06 ,  A61B17/32

    CPC分类号： A61B1/32 ,  A61B1/07 ,  A61B17/42 ,  A61B18/22 ,  A61N5/0601 ,  A61N5/062 ,  A61B2017/22087 ,  A61B2090/062

    摘要： An improved vaginal speculum for photodynamic therapy of intraepithelial tissue and in particular vaginal, cervical and vulvar neoplasia utilizes a precisely and accurately positionable optic fiber through which a predetermined dose of light in the range of 620 to 700 nanometers is delivered over a controlled area which has been previously treated with photodynamic therapeutic substances. In particular, the neoplastic area has been treated with hematoporphyrin derivatives and other photosensitizers which are selectively taken into the cancerous tissue. Exposure to the appropriate wavelength laser light photoactivates the absorbed hematoporphyrins causing the release of singlet oxygen which internally oxidizes and ultimately causes cell death. The fiber optic tip from which the laser light is transmitted is precisely positioned within the body cavity at a predetermined distance from the intraepithelial neoplasia in order to obtain the appropriate spot size and location to minimize damage to healthy tissue and maximize damage to the selectively impregnated cancerous tissue.

    摘要翻译： 用于上皮内组织，特别是阴道，宫颈和外阴肿瘤的光动力治疗的改进的阴道窥器利用精确和准确的可定位的光纤，通过该光纤将620-700纳米范围内的预定剂量的光量传送到具有 以前用光动力治疗物质治疗。 特别地，肿瘤区域已被血卟啉衍生物和其它选择性摄入癌组织的光敏剂中治疗。 暴露于合适的波长激光光激活吸收的血卟啉，导致释放内在氧化并最终导致细胞死亡的单线态氧。 将激光从其传播的光纤尖端精确地定位在距离上皮内瘤变形预定距离的体腔内，以便获得适当的斑点大小和位置，以最小化对健康组织的损伤并最大限度地损害选择性浸润的癌性 组织。

    High resolution biosensor for in-situ microthermometry
    8.
    发明授权
    High resolution biosensor for in-situ microthermometry 失效
    高分辨率生物传感器用于原位微量测定

    公开(公告)号：US5631141A

    公开(公告)日：1997-05-20

    申请号：US435354

    申请日：1995-05-05

    申请人： Gregory J. Sonek ,  Yagang Liu ,  Bruce J. Tromberg ,  Michael W. Berns

    发明人： Gregory J. Sonek ,  Yagang Liu ,  Bruce J. Tromberg ,  Michael W. Berns

    IPC分类号： G01N31/22 ,  C12Q1/02

    CPC分类号： G01N31/229 ,  Y10S435/968

    摘要： The present invention comprises a method for use of a biosensor for in-situ microthermometry. This biosensor is a substantially spherical vesicle impregnated with a dopant which varies its optical emission spectrum as a function of the local environmental temperature of the biosensor in the temperature range to be observed. In the preferred embodiment of the present invention, this dopant is the fluorescent dye 6-dodecanoyl-2-dimethylamino-naphthalene (Laurdan.TM.). This method for in-situ measurement of temperature in a biological system uses such a vesicle by introduction of the vesicle into the biological system to be measured and manipulation of the vesicle to the location where temperature is to be measured. The temperature is then calculated from the optically measured generalized polarization at that location and the known relationship between temperature and generalized polarization for the membrane of the vesicle.

    摘要翻译： 本发明包括使用生物传感器进行原位微量测定的方法。 该生物传感器是浸渍有掺杂剂的基本上球形的囊泡，其在要观察的温度范围内改变其作为生物传感器的局部环境温度的函数的光发射光谱。 在本发明的优选实施方案中，该掺杂剂是荧光染料6-十二酰基-2-二甲基氨基 - 萘（Laurdan TM）。 用于生物系统中温度原位测量的方法通过将囊泡引入要测量的生物系统中并将囊泡操作到要测量温度的位置来使用这种囊泡。 然后从该位置处的光学测量的广义极化计算温度，以及温度和囊泡膜的广义极化之间的已知关系。