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1. 发明授权

US09983134B2 Systems and methods for imaging and processing tissue 有权
公开(公告)号：US09983134B2
公开(公告)日：2018-05-29
申请号：US14300425
申请日：2014-06-10
申请人： Timothy Ragan
发明人： Timothy Ragan
IPC分类号： G01N21/64 , G01N1/06 , G02B21/00 , G02B21/36 , A61B3/10 , G01B9/02 , C12Q1/68 , G01N1/30 , G01N33/53 , G01N21/65
CPC分类号： G01N21/6458 , A61B3/102 , C12Q1/686 , G01B9/02091 , G01N1/06 , G01N1/30 , G01N33/53 , G01N2001/068 , G01N2021/653 , G01N2223/40 , G01N2223/401 , G01N2223/419 , G02B21/008 , G02B21/367
摘要： In accordance with preferred embodiments of the present invention, a method for imaging tissue, for example, includes the steps of mounting the tissue on a computer controlled stage of a microscope, determining volumetric imaging parameters, directing at least two photons into a region of interest, scanning the region of interest across a portion of the tissue, imaging a plurality of layers of the tissue in a plurality of volumes of the tissue in the region of interest, sectioning the portion of the tissue, capturing the sectioned tissue, and imaging a second plurality of layers of the tissue in a second plurality of volumes of the tissue in the region of interest, and capturing each sectioned tissue, detecting a fluorescence image of the tissue due to said excitation light; and processing three-dimensional data that is collected to create a three-dimensional image of the region of interest. Further, captured tissue sections can be processed, re-imaged, and indexed to their original location in the three dimensional image.

2. 发明申请

US20140355862A1 SYSTEMS AND METHODS FOR VOLUMETRIC TISSUE SCANNING MICROSCOPY 有权
标题翻译：体积组织扫描显微镜的系统和方法
公开(公告)号：US20140355862A1
公开(公告)日：2014-12-04
申请号：US14270126
申请日：2014-05-05
申请人： Peter T.C. So , Bevin Engelward , Timothy Ragan , Karsten Bahlman , Ki-Hean Kim , Lily Hsu Laiho , Hayden Huang
发明人： Peter T.C. So , Bevin Engelward , Timothy Ragan , Karsten Bahlman , Ki-Hean Kim , Lily Hsu Laiho , Hayden Huang
IPC分类号： G06K9/00
CPC分类号： G06K9/00127 , G01N15/1456 , G01N2001/282 , G01N2015/1006
摘要： In accordance with preferred embodiments of the present invention, a method for imaging tissue, for example, includes the steps of mounting the tissue on a computer controlled stage of a microscope, determining volumetric imaging parameters, directing at least two photons into a region of interest, scanning the region of interest across a portion of the tissue, imaging a plurality of layers of the tissue in a plurality of volumes of the tissue in the region of interest, sectioning the portion of the tissue and imaging a second plurality of layers of the tissue in a second plurality of volumes of the tissue in the region of interest, detecting a fluorescence image of the tissue due to said excitation light; and processing three-dimensional data that is collected to create a three-dimensional image of the region of interest.
摘要翻译：根据本发明的优选实施例，例如，组织成像的方法包括以下步骤：将组织安装在显微镜的计算机控制的阶段上，确定体积成像参数，将至少两个光子引导到感兴趣的区域扫描组织的一部分上的感兴趣区域，在感兴趣区域的多个体积的组织中对组织的多个层进行成像，将组织的该部分切片并成像第二组在感兴趣区域中的组织的第二多个体积中的组织，由于所述激发光检测组织的荧光图像; 以及处理被收集以产生感兴趣区域的三维图像的三维数据。

3. 发明申请

US20070057211A1 Multifocal imaging systems and method 审中-公开
标题翻译：多焦点成像系统及方法
公开(公告)号：US20070057211A1
公开(公告)日：2007-03-15
申请号：US11442702
申请日：2006-05-25
申请人： Karsten Bahlman , Ki-Hean Kim , Timothy Ragan , Peter So
发明人： Karsten Bahlman , Ki-Hean Kim , Timothy Ragan , Peter So
IPC分类号： G03B42/08
CPC分类号： G01N21/6452 , G01N21/6458 , G01N21/6486 , G02B21/002 , G02B21/0032 , G02B21/0076 , G02B21/16
摘要： In the systems and methods of the present invention a multifocal multiphoton imaging system has a signal to noise ratio (SNR) that is reduced by over an order of magnitude at imaging depth equal to twice the mean free path scattering length of the specimen. An MMM system based on an area detector such as a multianode photomultiplier tube (MAPMT) that is optimized for high-speed tissue imaging. The specimen is raster-scanned with an array of excitation light beams. The emission photons from the array of excitation foci are collected simultaneously by a MAPMT and the signals from each anode are detected using high sensitivity, low noise single photon counting circuits. An image is formed by the temporal encoding of the integrated signal with a raster scanning pattern. A deconvolution procedure taking account of the spatial distribution and the raster temporal encoding of collected photons can be used to improve decay coefficient. We demonstrate MAPMT-based MMM can provide significantly better contrast than CCD-based existing systems.
摘要翻译：在本发明的系统和方法中，多焦点多光子成像系统具有在成像深度等于样本的平均自由路径散射长度的两倍的信噪比（SNR）下降一个数量级以上。基于区域检测器的MMM系统，例如针对高速组织成像而优化的多节点光电倍增管（MAPMT）。样品用激发光束阵列进行光栅扫描。来自激发焦点阵列的发射光子由MAPMT同时收集，并且使用高灵敏度，低噪声单光子计数电路检测来自每个阳极的信号。通过具有光栅扫描图案的积分信号的时间编码形成图像。考虑到收集的光子的空间分布和光栅时间编码的去卷积过程可以用来改善衰变系数。我们演示基于MAPMT的MMM可以提供比基于CCD的现有系统更好的对比度。

4. 发明申请

US20180045623A1 SYSTEMS AND METHODS FOR SERIAL STAINING AND IMAGING 审中-公开
公开(公告)号：US20180045623A1
公开(公告)日：2018-02-15
申请号：US15556862
申请日：2016-03-11
申请人： Timothy Ragan , Chiam Moshe Dimant
发明人： Timothy Ragan , Chiam Moshe Dimant
IPC分类号： G01N1/31 , G02B21/26 , G01N21/64 , G02B21/36 , G01N1/06 , G01N35/00
摘要： The present invention relates to systems and methods for sequential operation of staining, imaging and sectioning of tissue samples by a processing system. After each layer of the sample is removed by the sectioning system, the system automatically stains the exposed surface of a sample to a depth to enable imaging of the remaining tissue. The system then repeats the sectioning, staining and imaging steps in sequence to image the sample.

5. 发明授权

US08771978B2 Systems and methods for imaging and processing tissue 有权
标题翻译：用于成像和处理组织的系统和方法
公开(公告)号：US08771978B2
公开(公告)日：2014-07-08
申请号：US13297035
申请日：2011-11-15
申请人： Timothy Ragan
发明人： Timothy Ragan
IPC分类号： G01N1/30 , G01N33/48 , G06K9/00 , A61B6/00 , G01B9/021 , A61B3/10 , G01B9/02 , G01N21/65
CPC分类号： G01N21/6458 , A61B3/102 , C12Q1/686 , G01B9/02091 , G01N1/06 , G01N1/30 , G01N33/53 , G01N2001/068 , G01N2021/653 , G01N2223/40 , G01N2223/401 , G01N2223/419 , G02B21/008 , G02B21/367
摘要： In accordance with preferred embodiments of the present invention, a method for imaging tissue, for example, includes the steps of mounting the tissue on a computer controlled stage of a microscope, determining volumetric imaging parameters, directing at least two photons into a region of interest, scanning the region of interest across a portion of the tissue, imaging layers of the tissue, sectioning a portion of the tissue, capturing the sectioned tissue, and imaging additional layers of the tissue in a second volume of the tissue, and capturing each portion of sectioned tissue, and processing three-dimensional data that is collected to create a three-dimensional image of the region of interest. Further, captured tissue sections can be processed, re-imaged, and indexed to their original location in the three dimensional image.
摘要翻译：根据本发明的优选实施例，例如，组织成像的方法包括以下步骤：将组织安装在显微镜的计算机控制的阶段上，确定体积成像参数，将至少两个光子引导到感兴趣的区域扫描组织的一部分，组织的成像层，切片组织的一部分，捕获切片的组织，以及在组织的第二体积中成像组织的附加层，并捕获每个部分并且处理被收集以产生感兴趣区域的三维图像的三维数据。此外，捕获的组织部分可以在三维图像中被处理，重新成像和索引到其原始位置。

6. 发明申请

US20130142413A1 SYSTEMS AND METHODS FOR VOLUMETRIC TISSUE SCANNING MICROSCOPY 有权
标题翻译：体积组织扫描显微镜的系统和方法
公开(公告)号：US20130142413A1
公开(公告)日：2013-06-06
申请号：US13726931
申请日：2012-12-26
申请人： Peter T.c. So , Bevin Engelward , Timothy Ragan , Karsten Bahlman , Ki-Hean Kim , Lily Hsu Laiho , Hayden Huang
发明人： Peter T.c. So , Bevin Engelward , Timothy Ragan , Karsten Bahlman , Ki-Hean Kim , Lily Hsu Laiho , Hayden Huang
IPC分类号： G06K9/00
CPC分类号： G06K9/00127 , G01N15/1456 , G01N2001/282 , G01N2015/1006
摘要： In accordance with preferred embodiments of the present invention, a method for imaging tissue, for example, includes the steps of mounting the tissue on a computer controlled stage of a microscope, determining volumetric imaging parameters, directing at least two photons into a region of interest, scanning the region of interest across a portion of the tissue, imaging a plurality of layers of the tissue in a plurality of volumes of the tissue in the region of interest, sectioning the portion of the tissue and imaging a second plurality of layers of the tissue in a second plurality of volumes of the tissue in the region of interest, detecting a fluorescence image of the tissue due to said excitation light; and processing three-dimensional data that is collected to create a three-dimensional image of the region of interest.
摘要翻译：根据本发明的优选实施例，例如，组织成像的方法包括以下步骤：将组织安装在显微镜的计算机控制的阶段上，确定体积成像参数，将至少两个光子引导到感兴趣的区域扫描组织的一部分上的感兴趣区域，在感兴趣区域的多个体积的组织中对组织的多个层进行成像，将组织的该部分切片并成像第二组在感兴趣区域中的组织的第二多个体积中的组织，由于所述激发光检测组织的荧光图像; 以及处理被收集以产生感兴趣区域的三维图像的三维数据。

7. 发明授权

US08351675B2 Systems and methods for volumetric tissue scanning microscopy 有权
公开(公告)号：US08351675B2
公开(公告)日：2013-01-08
申请号：US12757139
申请日：2010-04-09
申请人： Peter So , Bevin Engelward , Timothy Ragan , Karsten Bahlmann , Ki Hean Kim , Lily Hsu-Laiho , Hayden Huang
发明人： Peter So , Bevin Engelward , Timothy Ragan , Karsten Bahlmann , Ki Hean Kim , Lily Hsu-Laiho , Hayden Huang
IPC分类号： G06K9/00
CPC分类号： G06K9/00127 , G01N15/1456 , G01N2001/282 , G01N2015/1006
摘要： In accordance with preferred embodiments of the present invention, a method for imaging tissue, for example, includes the steps of mounting the tissue on a computer controlled stage of a microscope, determining volumetric imaging parameters, directing at least two photons into a region of interest, scanning the region of interest across a portion of the tissue, imaging a plurality of layers of the tissue in a plurality of volumes of the tissue in the region of interest, sectioning the portion of the tissue and imaging a second plurality of layers of the tissue in a second plurality of volumes of the tissue in the region of interest, detecting a fluorescence image of the tissue due to said excitation light; and processing three-dimensional data that is collected to create a three-dimensional image of the region of interest.

8. 发明授权

US07724937B2 Systems and methods for volumetric tissue scanning microscopy 有权
标题翻译：体积组织扫描显微镜的系统和方法
公开(公告)号：US07724937B2
公开(公告)日：2010-05-25
申请号：US12152136
申请日：2008-05-12
申请人： Peter So , Bevin Engelward , Timothy Ragan , Karsten Bahlmann , Ki Hean Kim , Lily Hsu Laiho , Hayden Huang
发明人： Peter So , Bevin Engelward , Timothy Ragan , Karsten Bahlmann , Ki Hean Kim , Lily Hsu Laiho , Hayden Huang
IPC分类号： G06K9/00
CPC分类号： G06K9/00127 , G01N15/1456 , G01N2001/282 , G01N2015/1006
摘要： In accordance with preferred embodiments of the present invention, a method for imaging tissue, for example, includes the steps of mounting the tissue on a computer controlled stage of a microscope, determining volumetric imaging parameters, directing at least two photons into a region of interest, scanning the region of interest across a portion of the tissue, imaging a plurality of layers of the tissue in a plurality of volumes of the tissue in the region of interest, sectioning the portion of the tissue and imaging a second plurality of layers of the tissue in a second plurality of volumes of the tissue in the region of interest, detecting a fluorescence image of the tissue due to said excitation light; and processing three-dimensional data that is collected to create a three-dimensional image of the region of interest.
摘要翻译：根据本发明的优选实施例，例如，组织成像的方法包括以下步骤：将组织安装在显微镜的计算机控制的阶段上，确定体积成像参数，将至少两个光子引导到感兴趣的区域扫描组织的一部分上的感兴趣区域，在感兴趣区域的多个体积的组织中对组织的多个层进行成像，将组织的该部分切片并成像第二组在感兴趣区域中的组织的第二多个体积中的组织，由于所述激发光检测组织的荧光图像; 以及处理被收集以产生感兴趣区域的三维图像的三维数据。

9. 发明申请

US20090072171A1 Systems and methods for volumetric tissue scanning microscopy 有权
标题翻译：体积组织扫描显微镜的系统和方法
公开(公告)号：US20090072171A1
公开(公告)日：2009-03-19
申请号：US12152136
申请日：2008-05-12
申请人： Peter So , Bevin Engelward , Timothy Ragan , Karsten Bahlmann , Ki Hean Kim , Lily Hsu Laiho , Hayden Huang
发明人： Peter So , Bevin Engelward , Timothy Ragan , Karsten Bahlmann , Ki Hean Kim , Lily Hsu Laiho , Hayden Huang
IPC分类号： G01N23/04 , H04N7/18
CPC分类号： G06K9/00127 , G01N15/1456 , G01N2001/282 , G01N2015/1006
摘要： In accordance with preferred embodiments of the present invention, a method for imaging tissue, for example, includes the steps of mounting the tissue on a computer controlled stage of a microscope, determining volumetric imaging parameters, directing at least two photons into a region of interest, scanning the region of interest across a portion of the tissue, imaging a plurality of layers of the tissue in a plurality of volumes of the tissue in the region of interest, sectioning the portion of the tissue and imaging a second plurality of layers of the tissue in a second plurality of volumes of the tissue in the region of interest, detecting a fluorescence image of the tissue due to said excitation light; and processing three-dimensional data that is collected to create a three-dimensional image of the region of interest.
摘要翻译：根据本发明的优选实施例，例如，组织成像的方法包括以下步骤：将组织安装在显微镜的计算机控制的阶段上，确定体积成像参数，将至少两个光子引导到感兴趣的区域扫描组织的一部分上的感兴趣区域，在感兴趣区域的多个体积的组织中对组织的多个层进行成像，将组织的该部分切片并成像第二组在感兴趣区域中的组织的第二多个体积中的组织，由于所述激发光检测组织的荧光图像; 以及处理被收集以产生感兴趣区域的三维图像的三维数据。

10. 发明申请

US20140356876A1 SYSTEMS AND METHODS FOR IMAGING AND PROCESSING TISSUE 有权
标题翻译：用于成像和处理组织的系统和方法
公开(公告)号：US20140356876A1
公开(公告)日：2014-12-04
申请号：US14300425
申请日：2014-06-10
申请人： Timothy Ragan
发明人： Timothy Ragan
IPC分类号： G01N21/64 , G01N1/30 , G01N33/53 , C12Q1/68 , G01B9/02 , G01N1/06
CPC分类号： G01N21/6458 , A61B3/102 , C12Q1/686 , G01B9/02091 , G01N1/06 , G01N1/30 , G01N33/53 , G01N2001/068 , G01N2021/653 , G01N2223/40 , G01N2223/401 , G01N2223/419 , G02B21/008 , G02B21/367
摘要： In accordance with preferred embodiments of the present invention, a method for imaging tissue, for example, includes the steps of mounting the tissue on a computer controlled stage of a microscope, determining volumetric imaging parameters, directing at least two photons into a region of interest, scanning the region of interest across a portion of the tissue, imaging a plurality of layers of the tissue in a plurality of volumes of the tissue in the region of interest, sectioning the portion of the tissue, capturing the sectioned tissue, and imaging a second plurality of layers of the tissue in a second plurality of volumes of the tissue in the region of interest, and capturing each sectioned tissue, detecting a fluorescence image of the tissue due to said excitation light; and processing three-dimensional data that is collected to create a three-dimensional image of the region of interest. Further, captured tissue sections can be processed, re-imaged, and indexed to their original location in the three dimensional image.
摘要翻译：根据本发明的优选实施例，例如，组织成像的方法包括以下步骤：将组织安装在显微镜的计算机控制的阶段上，确定体积成像参数，将至少两个光子引导到感兴趣的区域扫描组织的一部分上的感兴趣区域，在感兴趣区域的多个体积的组织中成像组织的多个层，切片组织的部分，捕获切片的组织，以及成像在感兴趣区域的第二组多个体积的组织中的第二多层组织，并捕获每个切片的组织，检测由于所述激发光引起的组织的荧光图像; 以及处理被收集以产生感兴趣区域的三维图像的三维数据。此外，捕获的组织部分可以在三维图像中被处理，重新成像和索引到其原始位置。

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