CA2483392A1 - Computerized analysis for abnormal cells in a cell block - Google Patents
Computerized analysis for abnormal cells in a cell block Download PDFInfo
- Publication number
- CA2483392A1 CA2483392A1 CA002483392A CA2483392A CA2483392A1 CA 2483392 A1 CA2483392 A1 CA 2483392A1 CA 002483392 A CA002483392 A CA 002483392A CA 2483392 A CA2483392 A CA 2483392A CA 2483392 A1 CA2483392 A1 CA 2483392A1
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- CA
- Canada
- Prior art keywords
- cells
- analysis
- tissue according
- cell block
- cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 238000004458 analytical method Methods 0.000 title claims abstract description 32
- 230000002159 abnormal effect Effects 0.000 title 1
- 239000008188 pellet Substances 0.000 claims abstract description 6
- 230000000877 morphologic effect Effects 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 6
- 238000001574 biopsy Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 101100114828 Drosophila melanogaster Orai gene Proteins 0.000 description 1
- 208000025814 Inflammatory myopathy with abundant macrophages Diseases 0.000 description 1
- 101100270435 Mus musculus Arhgef12 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000002380 cytological effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G06—COMPUTING; CALCULATING OR COUNTING
- G06V—IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING
- G06V20/00—Scenes; Scene-specific elements
- G06V20/60—Type of objects
- G06V20/69—Microscopic objects, e.g. biological cells or cellular parts
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/04—Devices for withdrawing samples in the solid state, e.g. by cutting
- G01N1/06—Devices for withdrawing samples in the solid state, e.g. by cutting providing a thin slice, e.g. microtome
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/36—Embedding or analogous mounting of samples
- G01N2001/368—Mounting multiple samples in one block, e.g. TMA [Tissue Microarrays]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N2015/1006—Investigating individual particles for cytology
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N2015/1477—Multiparameters
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
Landscapes
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Multimedia (AREA)
- Theoretical Computer Science (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
A system for analysis of cell blocks utilizing a computerized system to examine cell blocks cut from a pellet of cells, the cell block being mounted on the computerized system to examine a variety of characteristics including morphological color and boundary conditions between cells. The cell block may be cut in various ways to present different characteristics for examination by the computerized system.
Description
Ct~MPUTERI~Efl ANALYSIS FOR
BACKGROUND OF THE INVENTION
This invention relates to computer assisted cell!anaiysis, and mare particularly computer assisted cell analysis for cell blocks. Computer assisted cell analysis is widely employed, see references.
To the invenfiors' knowledge, all prior systems examine histologically or cytologically removed cells as they are normally found; in tissue. To the inventors' knowledge, there is no prior computerized system which employs computer assisfied cell analysis to examine cells in a cell block.
The following references are identified and ince~rporated by reference:
Computer Assisted Cytology and Histology: 6,5;53,15; Douglass , et al. April 22, 2003, Method and apparatus for automated imam analysis of biological specimens;~6,327,377 Rutenberg , et al. December 4,~~OO~t, Automated cytofogfcaf specimen classification s~~tem and method; 6,026,17 Palcic , et al. February 15, 2000, Sys_t~m and method for automatically detectinglmalianant cells and cells having rx~ali~ancy-associated chances; 5,939,278 Boon , et al. August 17, 1999, Automated histologiical specimen classification systeni and method; 5,287,272 Rutenberc,~. ,et al. February 15, 1994, Automated ~t~c~caf specimen classification sv sr tem andjmethod; 5,25T,782 Luck , et al. October 2~, 1993, Morphological classif~catioyystem and t~etf~fld; and, 4,9f5,?25 Rut~nfcerg flctflbet~ 23, 9990, Neural nefin~ork based automated cytological specimeh classification system and method.
Cell Block related: 5,318,795 Stokes , et al. June 7, 1994, Staining-methods for histoio ~'r and cYtoloayspecimens; and, 5,817,0321111i11iamson,111, et a1.
October 6, 1998, Mans arid method for ~hat~estma and bandaahg tisst~~ sat~n~les for biot~sy anal sis Brus~t Biopsy: 6,494,845 Rutenberg E?ecerr~ber' 17, 2002, Retractable brush for use with en~o_pe for brush biopsy; and, 6,297,044 Eisen , et al. October 2, ~f~fl'( , 1111inirjna~i invasive ai~paratus for tesfing lesions of she orai cavity and similar epithelium SUiVIPJi9~RY ~t~ID DESCRIPTIf3l~t OF 11t-IE IN~fENTfC~~t Applicants have developed and have recognized the significant benefit of employing computer assisted analysis with cells block.
Com~~terized ana-lysis provides increased accuracy and speed, and with specially prepared cell blocks for use with a computerized examination system major benefits are realized, especially in the examination of ~ESSUe fragments or micro-biopsies. dell blocks are formed by putting the cells i~to a liquid, floating them in the Iiqt~id, a~td spinwing the ~I-iyid down in a centnft~g~! to obta-i-n a pellet of thecells.
This pellet i',s embedded in something similar to paraffin so that the density of the paraffin any the cells is simitar, and one may cut this resultant hardened mass with a microtome end not shatter it. The cell block preparation technique is employed in samples co~faining numerous tissue fragments, for e~tample fine needle aspiration samples (5"817.,02 Williamson., IV., et al ) or brush biopsy samples (5.,297,044 Eisen, et al.,) which may be too small to be processed ihistolog'ically and too large to be viewed on a sm.ea.rr cytospin or other Lictu.id cytolog.~ preparation.
The primary difference between examining celliblock material as compared to .materia.l fra~n .s.mears .ar .other .cytologicaa prepa.rati.on .~s that ~i.ng.l.e .cel.ls .o.r .clusters .of cells in the smear are intact cells, whereas in a cell block, the cells are artificially -forced toge~h~r -into -a -pellet arid -instead -ef -looking at a -cell en a slide, -one-sees a cross-sectional slice through the cell. For example, if one were to consider the =nucleus to kav a sphere, when it is in its lying etorrrn ccrrt-d-ition-, it will a~lway~ ha a a-certain diameter. Vllhen one slices the nucleus located in the cell block, the resultant diameter depends on the -unknown ~p~sition ofithe slid. -In cantrast-to histo~log~ical _prc~paration,of a specimen, where the large-scale tissue architecture is intact and can be examined in the sliced- specimen, the tissue archifpcfure visible in a calf block is limited to thrr tissue fragments present in the liquid.
Prior art computer assisted analysis of cytology and histology has not .ad.dressed .~:xaminati.on .~f .tiss.ue .frag.ments _or .micro-..t~i-opsies., .too .Larg.e to -be examined cytoiogically, where tissue architecture is preserved intact on a small scale, but I~cks=large scale.tiss~e structures- used io. h~~stological~
diagnosis.
Computer assisted analysis has materially advanced the detection of suspect cells.
This is because computer assisted analysis has the capability of examining.
huge numbers ofiindividual specimens by analyzing a large!number of parameters very rapidly. Clearly, computers can work 24 hours a day, and the ability to process enormous amounts of data makes the computer assisted analysis an effective tool for the pathologist examining cellular material to find s~,uspect cells which may be w indicative o~ or a precursor to cancer. One of the advantages of the present invention is !that computer assisted smear analysis prdvides a cerfain percentage accuracy in!detecting suspect cells, whereas cell block analysis also has a certain percentage~accuracy as well. By combining both systems, the accuracy of detecting suspect cells material increases. Of course, the preparation of the cell block for proper analysis enhances the effectiveness of the system.
BACKGROUND OF THE INVENTION
This invention relates to computer assisted cell!anaiysis, and mare particularly computer assisted cell analysis for cell blocks. Computer assisted cell analysis is widely employed, see references.
To the invenfiors' knowledge, all prior systems examine histologically or cytologically removed cells as they are normally found; in tissue. To the inventors' knowledge, there is no prior computerized system which employs computer assisfied cell analysis to examine cells in a cell block.
The following references are identified and ince~rporated by reference:
Computer Assisted Cytology and Histology: 6,5;53,15; Douglass , et al. April 22, 2003, Method and apparatus for automated imam analysis of biological specimens;~6,327,377 Rutenberg , et al. December 4,~~OO~t, Automated cytofogfcaf specimen classification s~~tem and method; 6,026,17 Palcic , et al. February 15, 2000, Sys_t~m and method for automatically detectinglmalianant cells and cells having rx~ali~ancy-associated chances; 5,939,278 Boon , et al. August 17, 1999, Automated histologiical specimen classification systeni and method; 5,287,272 Rutenberc,~. ,et al. February 15, 1994, Automated ~t~c~caf specimen classification sv sr tem andjmethod; 5,25T,782 Luck , et al. October 2~, 1993, Morphological classif~catioyystem and t~etf~fld; and, 4,9f5,?25 Rut~nfcerg flctflbet~ 23, 9990, Neural nefin~ork based automated cytological specimeh classification system and method.
Cell Block related: 5,318,795 Stokes , et al. June 7, 1994, Staining-methods for histoio ~'r and cYtoloayspecimens; and, 5,817,0321111i11iamson,111, et a1.
October 6, 1998, Mans arid method for ~hat~estma and bandaahg tisst~~ sat~n~les for biot~sy anal sis Brus~t Biopsy: 6,494,845 Rutenberg E?ecerr~ber' 17, 2002, Retractable brush for use with en~o_pe for brush biopsy; and, 6,297,044 Eisen , et al. October 2, ~f~fl'( , 1111inirjna~i invasive ai~paratus for tesfing lesions of she orai cavity and similar epithelium SUiVIPJi9~RY ~t~ID DESCRIPTIf3l~t OF 11t-IE IN~fENTfC~~t Applicants have developed and have recognized the significant benefit of employing computer assisted analysis with cells block.
Com~~terized ana-lysis provides increased accuracy and speed, and with specially prepared cell blocks for use with a computerized examination system major benefits are realized, especially in the examination of ~ESSUe fragments or micro-biopsies. dell blocks are formed by putting the cells i~to a liquid, floating them in the Iiqt~id, a~td spinwing the ~I-iyid down in a centnft~g~! to obta-i-n a pellet of thecells.
This pellet i',s embedded in something similar to paraffin so that the density of the paraffin any the cells is simitar, and one may cut this resultant hardened mass with a microtome end not shatter it. The cell block preparation technique is employed in samples co~faining numerous tissue fragments, for e~tample fine needle aspiration samples (5"817.,02 Williamson., IV., et al ) or brush biopsy samples (5.,297,044 Eisen, et al.,) which may be too small to be processed ihistolog'ically and too large to be viewed on a sm.ea.rr cytospin or other Lictu.id cytolog.~ preparation.
The primary difference between examining celliblock material as compared to .materia.l fra~n .s.mears .ar .other .cytologicaa prepa.rati.on .~s that ~i.ng.l.e .cel.ls .o.r .clusters .of cells in the smear are intact cells, whereas in a cell block, the cells are artificially -forced toge~h~r -into -a -pellet arid -instead -ef -looking at a -cell en a slide, -one-sees a cross-sectional slice through the cell. For example, if one were to consider the =nucleus to kav a sphere, when it is in its lying etorrrn ccrrt-d-ition-, it will a~lway~ ha a a-certain diameter. Vllhen one slices the nucleus located in the cell block, the resultant diameter depends on the -unknown ~p~sition ofithe slid. -In cantrast-to histo~log~ical _prc~paration,of a specimen, where the large-scale tissue architecture is intact and can be examined in the sliced- specimen, the tissue archifpcfure visible in a calf block is limited to thrr tissue fragments present in the liquid.
Prior art computer assisted analysis of cytology and histology has not .ad.dressed .~:xaminati.on .~f .tiss.ue .frag.ments _or .micro-..t~i-opsies., .too .Larg.e to -be examined cytoiogically, where tissue architecture is preserved intact on a small scale, but I~cks=large scale.tiss~e structures- used io. h~~stological~
diagnosis.
Computer assisted analysis has materially advanced the detection of suspect cells.
This is because computer assisted analysis has the capability of examining.
huge numbers ofiindividual specimens by analyzing a large!number of parameters very rapidly. Clearly, computers can work 24 hours a day, and the ability to process enormous amounts of data makes the computer assisted analysis an effective tool for the pathologist examining cellular material to find s~,uspect cells which may be w indicative o~ or a precursor to cancer. One of the advantages of the present invention is !that computer assisted smear analysis prdvides a cerfain percentage accuracy in!detecting suspect cells, whereas cell block analysis also has a certain percentage~accuracy as well. By combining both systems, the accuracy of detecting suspect cells material increases. Of course, the preparation of the cell block for proper analysis enhances the effectiveness of the system.
Although some of the computer analysis will bei looking at layered cells in the same manner as previously encountered, the computer analysis will examine different morphological and color characteristics as rebated to cell block characteristics. Additionally, boundary characteristics;between cells will also be difFerent in ~ cell block, and an examination of the bo~indaries between cells as indicating suspect cells will also be examined.
It is anticipated that the computer assisted cell Mock analysis will select perhaps only 100 or 200 cells out of hundreds of thousands to find the most suspect cells. Ultimately, at the conclusion of the computer assisted analysis, a trained pathologist inrill then examine the most suspect or representative cells to determine the likelihood of precancerous conditions.
The planar cuts, the direction of the planes andl the thickness of the cuts may all be easily. varied and will produce different characteristics for computer assisted analysis.
It should be understood that the preferred embodiment was described to provide the;best illustration of the principles of the inv~ntian and its practical application fio thereby enable one of ordinary skill in th;~e art to utilize the invention in various embodiments and with various modifications ~s are suited to the particular use contemplated. Ali such modifications and variations are within the scope of the invention a~ detenrined,by the appended claims when interpreted in accordance with the breadth to which they are fairly legally and eqhitably entitled.
It is anticipated that the computer assisted cell Mock analysis will select perhaps only 100 or 200 cells out of hundreds of thousands to find the most suspect cells. Ultimately, at the conclusion of the computer assisted analysis, a trained pathologist inrill then examine the most suspect or representative cells to determine the likelihood of precancerous conditions.
The planar cuts, the direction of the planes andl the thickness of the cuts may all be easily. varied and will produce different characteristics for computer assisted analysis.
It should be understood that the preferred embodiment was described to provide the;best illustration of the principles of the inv~ntian and its practical application fio thereby enable one of ordinary skill in th;~e art to utilize the invention in various embodiments and with various modifications ~s are suited to the particular use contemplated. Ali such modifications and variations are within the scope of the invention a~ detenrined,by the appended claims when interpreted in accordance with the breadth to which they are fairly legally and eqhitably entitled.
Claims (10)
1.~A system for analysis of cells of tissue comprising:
a computerized system to examine a large number of cell parameters to detect suspect cells;
apparatus to form a pellet of cells and slicing means to slice said pellet to form a cell block for analysis; and mounting means for mounting said cell blocks to be examined by said computerized system.
a computerized system to examine a large number of cell parameters to detect suspect cells;
apparatus to form a pellet of cells and slicing means to slice said pellet to form a cell block for analysis; and mounting means for mounting said cell blocks to be examined by said computerized system.
2. ~A system for analysis of cells of tissue according to claim 1, wherein said slicing means is controllable to form prescribed cell blocks with preset parameters.
3. ~A system for analysis of cells of tissue according to claim 2, wherein said preset parameters are geometrical.
4. ~A system for analysis of cells of tissue according to claim 3, wherein said geometrical parameters include cell block thickness.
5. ~A system for analysis of cells of tissue according to claim 1, wherein said suspect cells are precancerous.
6. ~A system for analysis of cells of tissue according to claim 5, wherein said suspect cells are cancerous.
7. ~A system for analysis of cells of tissue according to claim 1, wherein said computerized system examines morphological characteristics.
8. ~A system for analysis of cells of tissue according to claim 1, wherein said computerized system examines color characteristics.
9. A system for analysis of cells of tissue according to claim 1, wherein said computerized system examines geometric characteristics of said cell block.
10. A system for analysis of cells of tissue according to claim 1, wherein said computerized system examines boundary characteristics between cells.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37515002P | 2002-04-22 | 2002-04-22 | |
| US60/375,150 | 2002-04-22 | ||
| PCT/US2003/012534 WO2003089905A2 (en) | 2002-04-22 | 2003-04-22 | Computerized analysis for abnormal cells in a cell block |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2483392A1 true CA2483392A1 (en) | 2003-10-30 |
Family
ID=29251235
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002483392A Abandoned CA2483392A1 (en) | 2002-04-22 | 2003-04-22 | Computerized analysis for abnormal cells in a cell block |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP1497644A4 (en) |
| AU (1) | AU2003234180A1 (en) |
| CA (1) | CA2483392A1 (en) |
| WO (1) | WO2003089905A2 (en) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5740270A (en) * | 1988-04-08 | 1998-04-14 | Neuromedical Systems, Inc. | Automated cytological specimen classification system and method |
| US5544650A (en) * | 1988-04-08 | 1996-08-13 | Neuromedical Systems, Inc. | Automated specimen classification system and method |
| GB8915759D0 (en) * | 1989-07-10 | 1989-08-31 | Shandon Scient Ltd | Cell block preparation |
| US5478722A (en) * | 1991-02-17 | 1995-12-26 | The Curators Of The University Of Missouri | Preserved cell preparations for flow cytometry and immunology |
| WO2000019897A1 (en) * | 1998-10-05 | 2000-04-13 | Williamson Warren N | Apparatus and method for harvesting and handling tissue samples for biopsy analysis |
| US6300124B1 (en) * | 1999-11-02 | 2001-10-09 | Regents Of The University Of Minnesota | Device and method to directly control the temperature of microscope slides |
-
2003
- 2003-04-22 CA CA002483392A patent/CA2483392A1/en not_active Abandoned
- 2003-04-22 AU AU2003234180A patent/AU2003234180A1/en not_active Abandoned
- 2003-04-22 EP EP03728489A patent/EP1497644A4/en not_active Withdrawn
- 2003-04-22 WO PCT/US2003/012534 patent/WO2003089905A2/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003234180A1 (en) | 2003-11-03 |
| EP1497644A4 (en) | 2007-12-05 |
| WO2003089905A3 (en) | 2004-02-12 |
| EP1497644A2 (en) | 2005-01-19 |
| AU2003234180A8 (en) | 2003-11-03 |
| WO2003089905A2 (en) | 2003-10-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |