US 9,435,738 B2Granted

System and device for characterizing cells

AssigneesThe Johns Hopkins University, University of Florida

InventorsDenis Wirtz, Pei-Hsun Wu, Shyam B. Khatau, Wei-Chang Chen, Jude M. Phillip, Jr., Zev A. Binder, Yiider Tseng

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Abstract

A diagnostic device includes a microscope configured to obtain image data on a plurality of cells and a computing device. The computing device is configured to receive the image data, identify at least a portion of each of the plurality of cells based on the received image data, determine at least one of a value of a morphological parameter for each identified at least a portion of the plurality of cells or a relative organization among the identified at least a portion of the plurality of cells, and calculate statistics for the plurality of cells based on the at least one of the determined values of the morphological parameter or the determined relative organization, the statistics including information suitable for distinguishing metastatic cells from non-metastatic cells. The diagnostic device further includes an output device configured to output the statistics for diagnosis.

Claims9

Dependent claims

A microscopy device comprising:

a microscope configured to obtain image data on a plurality of cells in different cell cycle phases on a substrate;
a computing device configured to:
receive the image data;
normalize the received image data;
identify at least a portion of each of the plurality of cells based on the normalized image data;
determine a value of a morphological parameter for each identified at least a portion of each of the plurality of cells;
and
determine values of the morphological parameter for corresponding cell cycle phases and fractions of the plurality of cells in the corresponding cell cycle phases based on the determined value of the morphological parameter for each identified at least a portion of each of the plurality of cells;
and
an output device configured to output the values of the morphological parameter for corresponding cell cycle phases and fractions of the plurality of cells in the corresponding cell cycle phases,
wherein identifying at least a portion of each of the plurality of cells based on the normalized image data comprises segmenting at least a portion of each of the plurality of cells based on the normalized image data comprises segmenting nuclei of the plurality of cells in the normalized image data,
wherein segmenting the at least a portion of each of the plurality of cells comprises:
obtaining Gaussian intensity image data of the normalized image data;
obtaining averaged intensity image data of the normalized image data;
obtaining nuclear intensity image data based on the difference between the Gaussian intensity image data and the averaged intensity image data;
and
segmenting nuclei based on the nuclear intensity image data.

14 more elements

A microscopy device comprising:

a microscope configured to obtain image data on a plurality of cells in different cell cycle phases on a substrate;
a computing device configured to:
receive the image data;
normalize the received image data;
identify at least a portion of each of the plurality of cells based on the normalized image data;
determine a value of a morphological parameter for each identified at least a portion of each of the plurality of cells;
and
determine values of the morphological parameter for corresponding cell cycle phases and fractions of the plurality of cells in the corresponding cell cycle phases based on the determined value of the morphological parameter for each identified at least a portion of each of the plurality of cells;
and
an output device configured to output the values of the morphological parameter for corresponding cell cycle phases and fractions of the plurality of cells in the corresponding cell cycle phases,
wherein identifying at least a portion of each of the plurality of cells based on the normalized image data comprises segmenting at least a portion of each of the plurality of cells based on the normalized image data comprises segmenting nuclei of the plurality of cells in the normalized image data,
wherein segmenting at least a portion of each of the plurality of cells based on the normalized image data further comprises segmenting cell boundaries of the plurality of cells in the normalized image data,
wherein said segmenting cell boundaries comprises:
obtaining averaged image data of the normalized image data;
obtaining an average background intensity of the averaged image data;
obtaining a noise in background intensity magnitude;
filtering the normalized image data based on the average background intensity and the noise in background intensity magnitude;
and
segmenting cell boundaries based on the filtered normalized image data.

16 more elements

A microscopy device comprising:

a microscope configured to obtain image data on a plurality of cells in different cell cycle phases on a substrate;
a computing device configured to:
receive the image data;
normalize the received image data;
identify at least a portion of each of the plurality of cells based on the normalized image data;
determine a value of a morphological parameter for each identified at least a portion of each of the plurality of cells;
and
determine values of the morphological parameter for corresponding cell cycle phases and fractions of the plurality of cells in the corresponding cell cycle phases based on the determined value of the morphological parameter for each identified at least a portion of each of the plurality of cells;
and
an output device configured to output the values of the morphological parameter for corresponding cell cycle phases and fractions of the plurality of cells in the corresponding cell cycle phases,
wherein identifying at least a portion of each of the plurality of cells based on the normalized image data comprises segmenting at least a portion of each of the plurality of cells based on the normalized image data comprises segmenting nuclei of the plurality of cells in the normalized image data,
wherein segmenting at least a portion of each of the plurality of cells based on the normalized image data further comprises segmenting cell boundaries of the plurality of cells in the normalized image data,
wherein the image data of the plurality of cells comprises first fluorescence channel data and second fluorescence channel data,
wherein said segmenting nuclei of the cells in the normalized image data is based on the first fluorescence channel data,
wherein said segmenting cell boundaries in the normalized image data is based on the second fluorescence channel data,
wherein segmenting at least a portion of each of the plurality of cells based on the normalized image data comprises segmenting nuclei of the plurality of cells in the normalized image data,
wherein segmenting the at least a portion of each of the plurality of cells further comprises:
obtaining Gaussian intensity image data of the normalized image data;
obtaining averaged intensity image data of the normalized image data;
obtaining nuclear intensity image data based on the difference between the Gaussian intensity image data and the averaged intensity image data;
and
segmenting nuclei based on the nuclear intensity image data.

19 more elements

A microscopy device comprising:

a microscope configured to obtain image data on a plurality of cells in different cell cycle phases on a substrate;
a computing device configured to:
receive the image data;
normalize the received image data;
identify at least a portion of each of the plurality of cells based on the normalized image data;
determine a value of a morphological parameter for each identified at least a portion of each of the plurality of cells;
and
determine values of the morphological parameter for corresponding cell cycle phases and fractions of the plurality of cells in the corresponding cell cycle phases based on the determined value of the morphological parameter for each identified at least a portion of each of the plurality of cells;
and
an output device configured to output the values of the morphological parameter for corresponding cell cycle phases and fractions of the plurality of cells in the corresponding cell cycle phases,
wherein identifying at least a portion of each of the plurality of cells based on the normalized image data comprises segmenting at least a portion of each of the plurality of cells based on the normalized image data comprises segmenting nuclei of the plurality of cells in the normalized image data,
wherein segmenting at least a portion of each of the plurality of cells based on the normalized image data further comprises segmenting cell boundaries of the plurality of cells in the normalized image data,
wherein the image data of the plurality of cells comprises first fluorescence channel data and second fluorescence channel data,
wherein said segmenting nuclei of the cells in the normalized image data is based on the first fluorescence channel data,
wherein said segmenting cell boundaries in the normalized image data is based on the second fluorescence channel data,
wherein segmenting at least a portion of each of the plurality of cells based on the normalized image data comprises segmenting nuclei of the plurality of cells in the normalized image data
wherein segmenting at least a portion of each of the plurality of cells based on the normalized image data further comprises segmenting cell boundaries of the plurality of cells in the normalized image data,
wherein said segmenting cell boundaries comprises:
obtaining averaged image data of the normalized image data;
obtaining an average background intensity of the averaged image data;
obtaining a noise in background intensity magnitude;
filtering the normalized image data based on the average background intensity and the noise in background intensity magnitude;
and
segmenting cell boundaries based on the filtered normalized image data.

21 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/560,759Filed 4 Dec 2014 · division
Priority: 22 Jun 2011
Published: US 2015/0093779 A12 Apr 2015
Granted: 6 Sep 2016
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

G06T 7/0012
Inspection of images, e.g. flaw detection: biomedical image inspection
G01N 15/14
Investigating individual particles: optical investigation techniques, e.g. flow cytometry
G01N 21/6458
Spatial resolved fluorescence measurements; Imaging: fluorescence microscopy
G01N 21/6486
Fluorescence; Phosphorescence: measuring fluorescence of biological material, e.g. DNA, RNA, cells

Family

Application61/499,955Us provisional application · filed 22 Jun 2011
Application61/500,234Us provisional application · filed 23 Jun 2011
Application61/500,244Us provisional application · filed 23 Jun 2011
Application61/533,446Us provisional application · filed 12 Sep 2011
Application61/645,930Us provisional application · filed 11 May 2012
Application13/530,772Parent of this division · filed 22 Jun 2012
US 2015/0093779 A1Pre-grant publication · published 2 Apr 2015
US 8,934,698 B2Parent of this division
US 2013/0071003 A1Published application
US 9,435,738 B2This patent

From the US filing history. Foreign family members aren’t listed.

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