EP1497644A2 - Computerized analysis for abnormal cells in a cell block - Google Patents
Computerized analysis for abnormal cells in a cell blockInfo
- Publication number
- EP1497644A2 EP1497644A2 EP03728489A EP03728489A EP1497644A2 EP 1497644 A2 EP1497644 A2 EP 1497644A2 EP 03728489 A EP03728489 A EP 03728489A EP 03728489 A EP03728489 A EP 03728489A EP 1497644 A2 EP1497644 A2 EP 1497644A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- cells
- analysis
- tissue according
- cell
- cell block
- 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.)
- Withdrawn
Links
- 230000002159 abnormal effect Effects 0.000 title description 2
- 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 11
- 210000001519 tissue Anatomy 0.000 description 10
- 239000007788 liquid Substances 0.000 description 5
- 239000012634 fragment Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 238000001574 biopsy Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 238000012360 testing 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—Electro-optical investigation, e.g. flow cytometers
- 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
Definitions
- This invention relates to computer assisted cell! analysis, and more particularly computer assisted cell analysis for ceil blocks.
- Computer assisted cell analysis is widely emplpyed, see references.
- Automated cytolbgical specimen classification system andj method 5,257,182 Luck , et al. October 2J3, 1993. Morphological classification system and method: and, 4,965,725 Rutbnberg October 23, 1990, Neural network based automated cvtological specimeh classification system and method.
- Cell blocks are formed by putting the cells ⁇ o a liquid, floating them in the liquid, apd spinning the liquid down in a centrifuge! to obtain a pellet of the cells. This pellet embedded in something similar to paraffjn so that the density of the paraffin and; the cells is similar, and one may cut this resultant hardened mass with a microtome and not shatter it.
- the cell block preparation technique is employed in samples cohtaining numerous tissue fragments, for example fine needle aspiration samples (5,817,032 Williamson, IV, et al ) or brush bicpsy samples (6,297,044 Eisen, et al.,) which may be too small to be processe ih ⁇ stofogicalfy and too large to be viewed on a smear, cytospin or other liquid cytolog preparation
- the primary difference between examining celliblock material as compared to material fr ⁇ fn smears or other cytologicaJ preparation ⁇ s that single cells or clusters of cells in the $mear are intact cells, whereas in a cell block, the cells are artificially forced together into a pellet and instead of looking at a cell on a slide, one-sees a cross-secti ⁇ nal slice through the cell. For example, if fine were to consider the nucleus to fc>e a sphere, when it is in its lying down condition, it will always have a certain diameter. When one slices the nucleus located in the cell block, the resultant diameter depends on the unknown position of the siic&. In contrast to histological preparation, of a specimen, where the large-scale tissue architecture is intact and can be examined in the sliced specimen, the tissue architecture visible in a cell block is limited to th tissue fragments present in the liquid.
- One of the advantages of the present invention is [that computer assisted smear analysis provides a certain percentage accuracy in 'detecting suspect cells, whereas cell block analysis also has a certain percentage laccuracy as well. By combining both systems, the accuracy of detecting suspect celljs 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 mannier as previously encountered, the computer analysis will examine different morphological and color characteristics as related to cell block characteristics. Additionally, boundary characteristics! between cells will also be different in a cell block, and an examination of the boundaries between cells as indicating siiispect cells will also be examined.
- planar cuts, the direction of the planes and the thickness of the cuts may all be easily! varied and will produce different characteristics for computer assisted analysis.
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
COMPUTERIZED ANALYSl FOR ABNORMAL CELLS IN A CELL1 BLOCK
BACKGROUND OF THE INVENTION
This invention relates to computer assisted cell! analysis, and more particularly computer assisted cell analysis for ceil blocks. Computer assisted cell analysis is widely emplpyed, see references.
To the inventors' 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 whiph employs computer assisted cell analysis to examine cells in a cell block.
The following references are identified and incorporated by reference:
Com uter Assisted Cytology and Histology: 6,553,135; Douglass , et al. April 22, 2003, Method and apparatus for automated imag analysis of biological specimens:'6.327,377 Rutenberg , et al. December 4, ^001, Automated cvtofoαical specimen classification system and method: 6,026,17^ Palcic , etal. February 15, 2000, Svstelm and method for automatically detecting [malignant cells and cells having maltønancv-associated changes: 5,939,278 Boon , etal. August 17, 1999, Automated histological specimen classification svstenj and method: 5,287,272 Rutenberg ,| et al. February 15, 1994. Automated cytolbgical specimen classification system andj method: 5,257,182 Luck , et al. October 2J3, 1993. Morphological classification system and method: and, 4,965,725 Rutbnberg October 23, 1990, Neural network based automated cvtological specimeh classification system and method.
Cell Block related: 5,318,795 Stokes , et al. Jurie 7, 1994. Staining methods for histology and cytology specimens: and, 5,817,032 iWHIiamson, IV , et al. October
6, 1998, Means and method for harvesting and handtih tissue samples for biopsy analysis
Brush Biopsy: 6,494,845 Rutenberg December 17, 2002. Retractable brush for use withjendoscope for brush biopsv: and, 6,297,044 Eisen , et al. October 2, 2001, MiniTJnatly invasive apparatus for testing lesionsl of the oral cavity and similar epithelium
SUMMARY AND DESCRIPTION OF THE INVENTION
Applicants have developed and have recognized the significant benefit of employing computer assisted analysis with cells blocks.
Computerized analysis 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 tissue fragments or micro- biopsies. Cell blocks are formed by putting the cells μ\o a liquid, floating them in the liquid, apd spinning the liquid down in a centrifuge! to obtain a pellet of the cells. This pellet embedded in something similar to paraffjn so that the density of the paraffin and; the cells is similar, and one may cut this resultant hardened mass with a microtome and not shatter it. The cell block preparation technique is employed in samples cohtaining numerous tissue fragments, for example fine needle aspiration samples (5,817,032 Williamson, IV, et al ) or brush bicpsy samples (6,297,044 Eisen, et al.,) which may be too small to be processe ihϊstofogicalfy and too large to be viewed on a smear, cytospin or other liquid cytolog preparation
The primary difference between examining celliblock material as compared to material frøfn smears or other cytologicaJ preparation \s that single cells or clusters of cells in the $mear are intact cells, whereas in a cell block, the cells are artificially
forced together into a pellet and instead of looking at a cell on a slide, one-sees a cross-sectiønal slice through the cell. For example, if fine were to consider the nucleus to fc>e a sphere, when it is in its lying down condition, it will always have a certain diameter. When one slices the nucleus located in the cell block, the resultant diameter depends on the unknown position of the siic&. In contrast to histological preparation, of a specimen, where the large-scale tissue architecture is intact and can be examined in the sliced specimen, the tissue architecture visible in a cell block is limited to th tissue fragments present in the liquid.
Prior art computer assisted analysis of cytology! and histology has not addressed Examination cf tissue fragments .or micro-bliopsies, too large to be examined cytologically, where tissue architecture is preserved intact on a small scale, but c s- large scale tissue structures used i hjistological diagnosis. Computer sisted analysis has materially advanced the detection of suspect cells. This is because computer assisted analysis has the capability of examining, huge numbers of ^individual specimens by analyzing a largejnumber of parameters very rapidly. Clearly, computers can work 24 hours a day, and the ability to process enormous ajmounts of data makes the computer assisted analysis an effective tool for the pathølogist examining cellular material to find sjuspect cells which may be indicative of or a precursor to cancer. One of the advantages of the present invention is [that computer assisted smear analysis provides a certain percentage accuracy in 'detecting suspect cells, whereas cell block analysis also has a certain percentage laccuracy as well. By combining both systems, the accuracy of detecting suspect celljs 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 mannier as previously encountered, the computer analysis will examine different morphological and color characteristics as related to cell block characteristics. Additionally, boundary characteristics! between cells will also be different in a cell block, and an examination of the boundaries between cells as indicating siiispect cells will also be examined.
It is anticipated that the computer assisted cell block 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 will then examine the most suspect or representative cells to determine the likelihood of precancerous conditions.
The planar cuts, the direction of the planes and 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 invention and its practical application to thereby enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. All such modifications and variatiohs are within the scope of the invention as; determined by the appended claims wheiji interpreted in accordance with the breadth to which they are fairly legally and equitably entitled.
Claims
1. A system for analysis of cells of tissue comprising: a computerized system to examine a lar^e number of cell parameters to detect suøpect cells; apparatus to form a pellet of cells and sli ing means to slice said pellet to form a cejl 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 accc-rding 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 cellβ 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 charadteristics between cells.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37515002P | 2002-04-22 | 2002-04-22 | |
| US375150P | 2002-04-22 | ||
| PCT/US2003/012534 WO2003089905A2 (en) | 2002-04-22 | 2003-04-22 | Computerized analysis for abnormal cells in a cell block |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EP1497644A2 true EP1497644A2 (en) | 2005-01-19 |
| EP1497644A4 EP1497644A4 (en) | 2007-12-05 |
Family
ID=29251235
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP03728489A Withdrawn EP1497644A4 (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) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0408225A2 (en) * | 1989-07-10 | 1991-01-16 | Life Sciences International (Europe) Limited | Cell block preparation |
| US5939278A (en) * | 1988-04-08 | 1999-08-17 | Neuromedical Systems, Inc. | Automated histological specimen classification system and method |
| WO2000019897A1 (en) * | 1998-10-05 | 2000-04-13 | Williamson Warren N | Apparatus and method for harvesting and handling tissue samples for biopsy analysis |
| US6327377B1 (en) * | 1988-04-08 | 2001-12-04 | Autocyte North Carolina, L.L.C. | Automated cytological specimen classification system and method |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5478722A (en) * | 1991-02-17 | 1995-12-26 | The Curators Of The University Of Missouri | Preserved cell preparations for flow cytometry and immunology |
| 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 AU AU2003234180A patent/AU2003234180A1/en not_active Abandoned
- 2003-04-22 WO PCT/US2003/012534 patent/WO2003089905A2/en not_active Application Discontinuation
- 2003-04-22 EP EP03728489A patent/EP1497644A4/en not_active Withdrawn
- 2003-04-22 CA CA002483392A patent/CA2483392A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5939278A (en) * | 1988-04-08 | 1999-08-17 | Neuromedical Systems, Inc. | Automated histological specimen classification system and method |
| US6327377B1 (en) * | 1988-04-08 | 2001-12-04 | Autocyte North Carolina, L.L.C. | Automated cytological specimen classification system and method |
| EP0408225A2 (en) * | 1989-07-10 | 1991-01-16 | Life Sciences International (Europe) Limited | Cell block preparation |
| WO2000019897A1 (en) * | 1998-10-05 | 2000-04-13 | Williamson Warren N | Apparatus and method for harvesting and handling tissue samples for biopsy analysis |
Non-Patent Citations (2)
| Title |
|---|
| MINIMO CORRADO ET AL: "Grading of upper urinary tract transitional cell carcinoma by computed DNA content and p53 expression" UROLOGY, vol. 50, no. 6, December 1997 (1997-12), pages 869-874, XP002455892 ISSN: 0090-4295 * |
| See also references of WO03089905A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003234180A8 (en) | 2003-11-03 |
| WO2003089905A2 (en) | 2003-10-30 |
| EP1497644A4 (en) | 2007-12-05 |
| AU2003234180A1 (en) | 2003-11-03 |
| WO2003089905A3 (en) | 2004-02-12 |
| CA2483392A1 (en) | 2003-10-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 20041025 |
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| AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT RO SE SI SK TR |
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| AX | Request for extension of the european patent |
Extension state: AL LT LV MK |
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| A4 | Supplementary search report drawn up and despatched |
Effective date: 20071105 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
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| 18D | Application deemed to be withdrawn |
Effective date: 20080205 |