公开(公告)号：US07157223B2

公开(公告)日：2007-01-02

申请号：US09945396

申请日：2001-08-30

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

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

IPC: C12Q1/00

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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US5478339A

公开(公告)日：1995-12-26

申请号：US297752

申请日：1994-08-30

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

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

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

CPC classification number: A61N5/062 ,  A61N5/0601 ,  A61B2018/2261 ,  A61N2005/0611

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US5458595A

公开(公告)日：1995-10-17

申请号：US168553

申请日：1993-12-16

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

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

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

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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US07428434B2

公开(公告)日：2008-09-23

申请号：US10191693

申请日：2002-07-09

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

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

IPC: A61B6/00

CPC classification number: A61B5/0091 ,  A61B5/4312

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20070282179A1

公开(公告)日：2007-12-06

申请号：US11757673

申请日：2007-06-04

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

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

IPC: A61B5/00

CPC classification number: A61B5/0059 ,  A61B5/0064 ,  A61B5/0075 ,  A61B5/0091 ,  A61B5/441 ,  A61B5/4875

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US08509879B2

公开(公告)日：2013-08-13

申请号：US12016918

申请日：2008-01-18

Applicant: Anthony J. Durkin ,  David Cuccia ,  Bruce J. Tromberg ,  Amaan Mazhar ,  Bernard Choi

Inventor： Anthony J. Durkin ,  David Cuccia ,  Bruce J. Tromberg ,  Amaan Mazhar ,  Bernard Choi

IPC: A61B6/00

CPC classification number: A61B5/0073 ,  A61B5/4094 ,  G01N21/4795 ,  G01N21/6456

Abstract: An apparatus for wide-field functional imaging (WiFI) of tissue includes a spatially modulated reflectance/fluorescence imaging (SI) device capable of quantitative subsurface imaging across spatial scales, and a laser speckle imaging (LSI) device capable of quantitative subsurface imaging across spatial scales using integrated with the (SI) device. The SI device and LSI device are capable of independently providing quantitative measurement of tissue functional status.

Abstract translation: 用于组织的广域功能成像（WiFI）的装置包括能够跨越空间尺度进行定量地下成像的空间调制反射/荧光成像（SI）装置，以及能够在空间上进行定量地下成像的激光散斑成像（LSI）装置 使用与（SI）设备集成的刻度。 SI装置和LSI装置能够独立地提供组织功能状态的定量测量。

公开(公告)号：US20090118622A1

公开(公告)日：2009-05-07

申请号：US12016918

申请日：2008-01-18

Applicant: Anthony J. Durkin ,  David Cuccia ,  Bruce J. Tromberg ,  Amaan Mazhar ,  Bernard Choi

Inventor： Anthony J. Durkin ,  David Cuccia ,  Bruce J. Tromberg ,  Amaan Mazhar ,  Bernard Choi

IPC: A61B6/00

CPC classification number: A61B5/0073 ,  A61B5/4094 ,  G01N21/4795 ,  G01N21/6456

Abstract: An apparatus for wide-field functional imaging (WIFI) of tissue includes a spatially modulated reflectance/fluorescence imaging (SI) device capable of quantitative subsurface imaging across spatial scales, and a laser speckle imaging (LSI) device capable of quantitative subsurface imaging across spatial scales using integrated with the (SI) device. The SI device and LSI device are capable of independently providing quantitative measurement of tissue functional status.

Abstract translation: 用于组织的广域功能成像（WIFI）的装置包括能够跨越空间尺度进行定量地下成像的空间调制反射/荧光成像（SI）装置，以及能够在空间上进行定量地下成像的激光散斑成像（LSI）装置 使用与（SI）设备集成的刻度。 SI装置和LSI装置能够独立地提供组织功能状态的定量测量。

公开(公告)号：US06958815B2

公开(公告)日：2005-10-25

申请号：US10391166

申请日：2003-03-18

Applicant: Frederic Bevilacqua ,  David Cuccia ,  Anthony J. Durkin ,  Bruce J. Tromberg

Inventor： Frederic Bevilacqua ,  David Cuccia ,  Anthony J. Durkin ,  Bruce J. Tromberg

IPC: G01N21/49 ,  G01N21/55

CPC classification number: G01N21/49

Abstract: Illumination with a pattern of light allows for subsurface imaging of a turbid medium or tissue, and for the determination of the optical properties over a large area. Both the average and the spatial variation of the optical properties can be noninvasively determined. Contact with the sample or scanning is not required but may be desired. Subsurface imaging is performed by filtering the spectrum of the illumination in the Fourier domain but other filtering approaches, such as wavelet transform, principle component filter, etc may be viable as well. The depth sensitivity is optimized by changing the spatial frequency of illumination. A quantitative analysis of the average optical properties and the spatial variation of the optical properties is obtained. The optical properties, i.e. reduced scattering and absorption coefficients are determined from the modulated transfer function, MTF.

Abstract translation: 具有光图案的照明允许混浊的介质或组织的地下成像，并且用于确定大面积上的光学性质。 光学性质的平均和空间变化都可以非侵入性地确定。 不需要与样品接触或扫描，但可能需要。 通过对傅立叶域中的照明光谱进行滤波来进行地下成像，但也可以采用小波变换，主成分滤波等其他滤波方法。 通过改变照明的空间频率来优化深度灵敏度。 获得光学特性的平均光学性质和空间变化的定量分析。 从调制传递函数MTF确定光学性质，即减小的散射和吸收系数。

公开(公告)号：US06661574B2

公开(公告)日：2003-12-09

申请号：US10126141

申请日：2002-04-19

Applicant: Tatiana B. Krasieva ,  Alexander S. Dvornikov ,  Bruce J. Tromberg ,  Michael W. Berns

Inventor： Tatiana B. Krasieva ,  Alexander S. Dvornikov ,  Bruce J. Tromberg ,  Michael W. Berns

IPC: G02B2106

CPC classification number: G02B21/125

Abstract: An illuminator and a reflectance microscope or system utilizing the illuminator for eliminating the need of a special light source, a reflected light vertical illuminator, and condenser lenses. The system may utilize an ordinary light source. The illuminator includes embedded chromophoric and diffusion properties. The illuminator further has a size and a shape to enable proximate positioning relative to the specimen to be observed. The illuminator further has an opening or aperture through which the specimen may be viewed. As such, the opening of the illuminator permits placement of the illuminator between the objective lens and the specimen. This positioning enables reflectance type or dark field microscopy with a simple and durable illuminator without complex optics. A method of using the reflectance microscope includes illuminating a specimen by the illuminator on a same side of the specimen as is the objective lens relative to a plane of the specimen normal to the optical path.

Abstract translation: 使用照明器的照明器和反射显微镜或系统，用于消除对特殊光源，反射光垂直照明器和聚光透镜的需要。 该系统可以利用普通的光源。 照明器包括嵌入式发色和扩散特性。 照明器还具有尺寸和形状，以使得能够相对于要观察的样本的邻近定位。 照明器还具有可以观察样本的开口或孔。 因此，照明器的开口允许照明器在物镜和样本之间放置。 这种定位使得反射型或暗视野显微镜具有简单耐用的照明器，无需复杂的光学元件。 使用反射型显微镜的方法包括：在与所述物镜相同的样本的与所述光路的垂直方向的平面相同的侧面照射所述样本。

公开(公告)号：US20210022623A1

公开(公告)日：2021-01-28

申请号：US17068463

申请日：2020-10-12

Applicant: Tyler Bywaters Rice ,  Michael Ghijsen ,  Bruce J. Tromberg ,  Bruce Yee Yang ,  Sean Michael White

Inventor： Tyler Bywaters Rice ,  Michael Ghijsen ,  Bruce J. Tromberg ,  Bruce Yee Yang ,  Sean Michael White

IPC: A61B5/021 ,  A61B5/02 ,  A61B5/026 ,  A61B5/029 ,  A61B5/00

Abstract: Systems and methods are disclosed for determining physiological information in a subject. The system includes; a light source positionable along a first location outside of the subject; a photo-sensitive detector positionable along a second location outside of the subject and configured to detect scattered light and generate a signal; a processor having a program and a memory, wherein the processor is operably coupled to the detector and configured to receive and store the signals generated over a period of time; wherein the processor is programmed to derive contrast metrics from the stored signals, calculate a waveform from the contrast metrics, decompose the waveform into basis functions and respective amplitudes, and compare the basis function amplitudes to determine the physiological information.