WO2001033196A2

WO2001033196A2 - Controlled review of medical sample

Info

Publication number: WO2001033196A2
Application number: PCT/CA2000/001278
Authority: WO
Inventors: Dragan Skugor; Iouri Lappa; Ryan S. Raz
Original assignee: Veracel Inc.
Priority date: 1999-10-29
Filing date: 2000-10-27
Publication date: 2001-05-10
Also published as: WO2001033196A3; AU1122901A

Abstract

A method and apparatus for reviewing specimens of cells. The system includes a review station (10) including a microscope (40) for reviewing fields of view on a specimen. The microscope (40) has a movable stage (46) for bringing fields of view into position so that they are visible through the microscope (40). Characterizations are manually assigned to the fields of view by actuating one of a plurality of input devices (30) representing a characterization. The characterization assigned to a field of view is added to data associated with the location of the field of view on the specimen.

Description

CONTROLLED REVIEW OF MEDICAL SAMPLE TECHNICAL FIELD

The present invention relates to methods and apparatus for analyzing specimens of cells and developing a diagnosis, involving physicians, pathologists , technicians, and other medical professionals. BACKGROUND ART

A specimen of cells, such as a specimen of cervical cells for a Pap smear test, is typically prepared by a physician or personnel working with the physician. The specimen is applied to a carrier which normally comprises a slide for a microscope. The slide is viewed through a microscope and analyzed by a cytotechnologist who then reaches a diagnosis. If the slide shows irregular cells, a pathologist is called upon to review the technician's work and reach a final diagnosis.

Attempts have been made to automate this process. For example, as disclosed in U.S. Patent No. 5,428,690, a slide is prepared and a technician utilizes an automated system to select points of interest for action by the system. The actions performed by the system include adjusting the microscope to display a specified point on the specimen. However, automatic analysis of specimens is not disclosed.

An apparatus and system for analyzing specimens is disclosed in U.S. Patent No. 5,627,908. Portions of the specimen are classified and the specimen is classified as a whole. Objects within the specimen are analyzed objects of interest are identified and a mask is created which identifies the size, shape, and location of the objects of interest. The data concerning the objects is analyzed to classify the specimen. The number of normal objects, the number of abnormal objects, and the number of artifacts identified in the specimen are combined to create an overall rating for the specimen. However, this method fails to assist the cytotechnologist or pathologist during human-reviewed slides of specimens and relies upon the proportion of abnormal objects to classify slides. DISCLOSURE OF THE INVENTION

One aspect of the present invention is directed to methods and apparatus for reviewing specimens of cells, including automatically retrieving a first location from a list of locations of fields of view on the specimen. The first location corresponds to a first field of view. The first field of view is reviewed and a characterization is manually assigned to the first field of view by actuating one of a plurality of input devices which are in communication with a computer so that a characterization is added to data associated with the location. It is also preferred that the fields of view in the list are those fields of view which have been determined to have the greatest likelihood of abnormality so that the locations on the slide having the greatest likelihood of abnormality are reviewed. However, the present invention also encompasses review of locations on a slide from a randomly generated list of locations, or any list of locations which has been previously mapped out on a slide.

Aspects of the present invention include methods and apparatus for reviewing fields of view of a specimen which were previously mapped out on the specimen. Either a technician or a pathologist may review fields of view from the previously generated list and characterize the fields of view by actuating one of a plurality of input devices, each representing a characterization. The fields of view are manually reviewed by a person looking through a microscope. The assignment of characterizations to the fields of view is also manual, involving a person actuating one of the input devices. The term "manual", as used in this application means carried out by a person, as opposed to a machine.

Preferably, the method includes automatically retrieving a next location from the list, corresponding to the next field of view in the list. The next location is retrieved in response to actuation of any of the plurality of input devices representing characterizations of fields of view. Successive fields of view from the list are reviewed. Characterizations are preferably assigned to fields of view by actuating one of the plurality of input devices for each characterization assigned.

Desirably, the steps of reviewing the successive fields of view include a person looking at the specimen through a microscope. The microscope includes a stage for supporting the specimen on a carrier. The steps of reviewing successive fields of view desirably include moving the stage so that the fields of view of the specimen are visible through the microscope seriatim.

Preferably, the method includes adding the characterizations assigned fields of view to data associated with the fields of view. The reviewing step may include selecting a desired field of view from the list and reviewing the field of view.

Each of the plurality of input devices represents a characterization for a field of view or a specimen. In certain preferred embodiments, the characterizations include the following: abnormal, benign cellular changes, questionable, transitional zone material and within normal limits.

In certain preferred embodiments, the fields of view have an associated likelihood of abnormality and the list is sorted according to the likelihood of abnormality. Preferably, the fields of view with a greater likelihood of abnormality are reviewed first.

In certain preferred embodiments, the reviewing steps include reviewing fields of view of specimens by a first person and then reviewing the fields of view of specimens by a second person. The steps of assigning characterizations to fields of view desirably include characterizing the fields of view by the first person and the second person. In certain preferred embodiments, the second person may amend the characterizations assigned by the first person. For example, specimens may be viewed by a cytotechnologist and then specimens which were characterized as abnormal are then reviewed by a pathologist. In another aspect of the present invention, a method of reviewing specimens of cells includes reviewing a series of fields of view of one or more specimens and the step of reviewing the fields of view includes a person looking at the specimen through the microscope. The review is automatically controlled so that only a predetermined number of fields of view are reviewed per unit time. A cytotechnologist or pathologist may be prevented from reviewing fields of view too quickly without adequate consideration. In certain preferred embodiments, the review is controlled by allowing review of a field of view only after a prescribed unit of time has passed since the time a previous field of view was reviewed. A next field of view in the series of fields of view is preferably presented in response to a manual input.

The series of specimens may include specimens of more than one patient. The manual assignment of characterizations may include entering characterizations into data for a computer system. In another aspect of the present invention, a method of reviewing specimens of cells comprises manually reviewing a series of specimens, manually assigning characterizations to fields of view of each specimen, and automatically determining at least one statistic regarding the characterizations assigned during review of the series of specimens. The operators of a clinical laboratory, for example, may review the statistics to assist in reaching conclusions concerning the characterizations assigned fields of view or specimens by cytotechnologist or pathologists. In addition, statistics concerning the classifications assigned by automated classifiers may be compiled.

In certain preferred embodiments, the computer automatically compiles said at least one statistic based upon the characterization entered into the computer. The step of automatically determining at least one statistic may include automatically compiling at least one statistic regarding fields of view assigned a particular characteristic. The step of automatically determining at least one statistic may include automatically compiling at least one statistic regarding a comparison of characterizations entered by a first person and characterizations entered by a second person. For example, the number of abnormal characterizations assigned by cytotechnologists , per slides reviewed is also compiled. These figures may be expressed as a ratio or percentage of abnormal characterizations entered by cytotechnologists per abnormal characterizations entered by pathologists. Statistics may be compiled for particular persons utilizing the equipment in performing a review of specimens.

The step of automatically determining at least one statistic may include automatically compiling at least one statistic regarding specimens assigned a particular characteristic. At least one statistic regarding a comparison of the characterizations of specimens entered by a first person and the characterizations of specimens entered by a second person may be automatically compiled. At least one statistic regarding a comparison of the characterizations of fields of view entered by a first person and the characterizations of fields of view which are automatically assigned may also be automatically compiled.

Preferably, a characterization is manually assigned to each specimen as a whole. The method desirably includes the step of automatically assigning characterizations to fields of view of each specimen.

In a further aspect of the present invention, a method of reviewing specimens of cells comprises reviewing fields of view of the specimen by looking at the specimen through a microscope, manually adding characterizations for the fields of view to data associated with the specimen, manually inputting a characterization for the specimen as a whole into the data, and automatically preventing the addition to the data of any characterization for the specimen as a whole as normal if any field of view in the list is assigned the characterization of abnormal. The characterization of the specimen as a whole as normal may, in certain embodiments, be inconsistent with any of the fields of view for the specimen having an abnormal characterization. Preventing the addition of a normal characterization may be used as an indication to the cytotechnologist or pathologist that an error was made.

The step of reviewing a series of fields of view desirably includes automatically presenting fields of view to be reviewed so that the area of view of the microscope is centered on the particular location for the field of view being reviewed. The area of view is the area which is visible through the objective of the microscope.

In a further aspect of the present invention, a series of fields of view of a specimen are reviewed according to a list of fields of view and their locations on the specimen with respect to a reference position. The step of reviewing the fields of view includes manually looking at the specimen through a microscope, the microscope having an area of view for viewing one field of view at a time. During viewing of a particular field of view in the series, the area of view of the microscope is manually adjusted to a new location on the specimen which is different from the location for such particular field view.

Preferably, the method includes assigning a characterization to fields of view on the list. In certain preferred embodiments, the method includes automatically amending the location for the particular field of view. The location is amended in response to the assignment of a characterization after the area of view has been adjusted to a new location. The location for the previously viewed field of view is automatically replaced with the new location.

The new location for the particular field of view may be the position of a center of the area of view of the microscope at the new location with respect to the reference position. The new location preferably comprises the position of a center of the area of view respect to the reference position. In another aspect of the present invention, a method of reviewing specimens of cells comprises reviewing a series of fields of view and their locations on the specimen with respect to a reference position. The step of reviewing the fields of view includes manually looking at the specimen through the microscope, the microscope having an area of view for viewing one field of view at a time. During viewing of a particular field of view in the series, the area of view is manually adjusted to a new location on the specimen which is different from the location for such particular field view. A new field of view is automatically defined in response to assignment of a characterization after the area of view has been adjusted to a new location. The new field of view is automatically added to data associated with the list. Desirably, the characterization for the field of view at the new location is added to data associated with the list.

In a further aspect of the present invention, a method of reviewing specimens of cells comprises reviewing fields of view of the specimen by manually sweeping the area of view of a microscope across the specimen. The step of reviewing the fields of view includes manually looking at the specimen through the microscope. A prescribed pattern of movement of the area of view across the specimen is provided, and the manual movement of the area of view across the specimen is controlled so that the area of view follows the pattern until a manual input to deviate from the pattern is entered.

Performing a sweep across a specimen may assist the cytotechnologist or pathologist in reaching a characterization for the specimen. The pattern of movement may be used by a cytotechnologist or pathologist to ensure that the entire specimen is reviewed when sweeping across a specimen.

In certain preferred embodiments, the manual input comprises movement of an input device greater than a predetermined amount. The manual input may comprise actuation of a first input device. A second input device may be utilized to manually sweep the area of view of the microscope across the specimen. The pattern of movement preferably includes fields of view previously defined for the specimen.

During review of a particular field of view, the area of view of the microscope may be manually adjusted from a particular field of view to a new location on the specimen which is different from the particular field of view. In certain preferred embodiments, the control of the manual review is arrested in response to the manual adjustment of the area of view to a new location. Upon actuating an input device, the area of view may return to the pattern.

In a further aspect of the invention, apparatus for controlled review of specimens of cells comprises at least one computer for storing data associated with the specimen, including a list of locations of fields of view on a specimen having a first location corresponding to a first field of view. The apparatus includes a device for reviewing the first field of view, and a plurality of input devices in communication with the at least one computer. The plurality of input devices each represent characterizations and are actuatable for assigning a characterization to the first field of view.

The at least one computer is preferably arranged to retrieve a next location from said list, corresponding to a next field of view in response to actuation of any of said plurality of input devices. The at least one computer is also preferably arranged to retrieve successive locations from the list for review through the device for reviewing.

Desirably, a likelihood of abnormality is associated with each field of view and the at least one computer is arranged to sort said list so that said fields of view are retrieved and reviewed according to the fields of view having the greatest likelihood of abnormality on the list.

The apparatus preferably includes a microscope including a stage for supporting the specimen on a carrier. The at least one computer is in communication with the microscope for effecting movement on the stage so that one of the fields of view of the specimen is visible through the microscope. The at least one computer is preferably arranged to store characterizations assigned by a first person and characterizations assigned by a second person in the data associated with the specimen. In certain preferred embodiments, each of the plurality of input devices represents a characterization. The characterization may comprise any of the following: abnormal, benign cellular changes, questionable, transitional zone material and within normal limits. In another aspect of the present invention, an apparatus for controlled review of specimens of cells comprises at least one computer for storing data associated with the specimen, including a list of locations of fields of view on a specimen, a microscope for reviewing said fields of view by looking at the specimen through the microscope. The at least one computer is in communication with said microscope and arranged so as to control retrieval of the data so that only a predetermined number of said fields of view are reviewed per unit time. In another aspect of the present invention, an apparatus for controlled review of specimen of cells comprises a device for manually reviewing a series of fields of view of the specimen, a plurality of input devices, each representing characterizations and being manually actuatable for assigning a characterization to said fields of view, at least one computer in communication with said plurality of input devices, said at least one computer being arranged to control and manipulate data associated with the specimen. The at least one computer is arranged to determine at least one statistic regarding characterizations manually assigned to fields of view of the specimen during review of a series of specimens.

In a further aspect of the present invention, an apparatus for controlled review of specimens of cells comprises a plurality of input devices, each representing characterizations and being manually actuatable for assigning a characterization to fields of view of the specimen and to the specimen as a whole, and at least one computer in communication with the plurality of input devices. The at least one computer is arranged to input the characterizations into data associated with the specimen. The at least one computer is arranged to prevent addition to the data of any characterization for the specimen as a whole as normal if any field of view in the list is assigned the characterization of abnormal.

In another aspect of the present invention, an apparatus for controlled review of specimens of cells comprises a device for manually reviewing the series of fields of view of the specimen including an area of view for viewing one of the fields of view at a time. The device is manually adjustable so that during review of a particular field of viewing the series, the area of view is moveable to a new location on the specimen which is different from the location for such particular field of view. The apparatus also includes a plurality of input devices for assigning a characterization to the fields of view and at least one computer in communication with said plurality of input devices. The at least one computer is arranged to store and manipulate data in at least one data storage medium for storing data associated with the specimen including a series of fields of view and their locations on the specimen with respect to a reference position. The at least one computer is also arranged to change the location for the field of view in the data. Changing the location for the particular field of view with the new location.

In a further aspect of the present invention, an apparatus for controlled review of specimens of cells comprises a device for manually reviewing a series of fields of view of the specimen including an area of view for viewing one of the fields of view at a time. The device is manually adjustable so that during review of a particular field of view in the series, the area of views moveable to a new location on the specimen which is different from the location for such particular field of view on the specimen with respect to a reference position. The apparatus includes a plurality of input devices for assigning a characterization to the fields of view and at least one computer in communication with the plurality of input devices . The at least one computer is arranged to store and manipulate data associated with the specimen including the series of fields of view and their locations on the specimen with respect to the reference position. The at least one computer is also arranged to add a new field of view to said data, including automatically adding the new field of view and the location of the new field of view on the specimen with respect to said reference position.

Another aspect of the present invention includes an apparatus for controlled review of specimens of cells comprising a device for manually reviewing fields of view of the specimen. The device includes an area of view for viewing one of the fields of view at a time, the device being manually moveable so as to sweep the area of view across the specimen. The apparatus includes a manually actuatable input device and at least one computer in communication with the input device and the device for reviewing. The at least one computer is arranged to control the manual movement of the area of view so that the movement of the area of view so that the movement follows a prescribed pattern sweeping the area of view across the specimen until the input device is actuated.

Preferably, movement of the input device greater than a predetermined amount effects a deviation from the prescribed pattern. For example, a rotatable ring may be used to move the area of view with respect to the area of view of the microscope. Movement of the ring greater than a predetermined amount may allow free movement without the prescribed pattern. Alternatively, the input device may comprise a button on a keypad. The input device is preferably actuatable so that the area of view returns to the prescribed pattern.

In another aspect of the present invention, an apparatus for entering characterizations during controlled review of specimens of cells comprises an input device for communicating with at least one computer. The input device for communicating with at least one computer. The input device includes a plurality of keys, each representing a characterization of cells within the specimen.

In certain preferred embodiments, each of the plurality of keys represents a characterization. The characterization may comprise any of the following: abnormal, benign cellular changes, questionable, transitional zone material, and within normal limits. BRIEF DESCRIPTION OF THE DRAWINGS These and other features, aspects and advantages of the present invention will become better understood with regard to the following description, appended claims, and accompanying drawings where :

Fig. 1 is a schematic, elevational view of a computer station for reviewing specimens of cells in accordance with one embodiment of the invention;

Fig. 1A is a schematic, top plan view of a slide in accordance with the embodiment of Fig. 1;

Fig. 2 is a schematic front right perspective view of an apparatus for automated analysis of specimens in accordance with the embodiments of FIGS. 1 and 1A;

Fig. 3 is a schematic top plan view of specimen on a turntable of FIGS. 1-2;

Fig. 4 is a schematic view of a display on a screen in a method in accordance with the embodiment of FIGS. 1-3;

Fig. 4A is a schematic elevational view of a microscope in a method in accordance with the embodiment of FIGS. 1-4;

Fig. 5 is a schematic flow diagram of steps in a method in accordance with the embodiment of FIGS. 1-4A;

Fig. 6 is a schematic flow diagram of steps in a method in accordance with the embodiment of FIGS. 1-5;

Fig. 7 is a schematic flow diagram of steps in a method in accordance with the embodiment of FIGS. 1-6; Fig. 8 is a schematic, top plan view of a slide in a method in accordance with the embodiment of FIGS. 1-7;

Fig. 9 is a schematic, top plan view of a slide in a method in accordance with the embodiment of FIGS. 1-8; Fig. 10 is a schematic, top plan view of a slide in a method in accordance with the embodiment of FIGS. 1-9; and

Fig. 11 is a schematic, top plan view of an apparatus in accordance with the another embodiment of the invention. MODES FOR CARRYING OUT THE INVENTION An apparatus for controlled review of the specimens of cells in accordance with one embodiment of the invention is shown in Fig. 1. The apparatus 10 may be located in a clinical laboratory. The apparatus 10 comprises a review station including a personal computer 20 having a monitor 21 with a screen 22, a housing 25 and input devices. The housing 25 includes a memory storage device 28 and a processor 26. The memory storage device 28 has a database stored thereon. Alternatively, the personal computer is connected to another memory storage device separate from the personal computer and having the database stored thereon. The input devices include buttons 30 on a keyboard 27, a mouse 32, or another device for entering information into a computer. Preferably, predetermined buttons 30 correspond to characterizations which may be selected by the cytotechnologist or pathologist. The processor 26 of the personal computer 20 is operatively connected to an encoder 62 for controlling a motorized microscope 40. The microscope 40 has an eyepiece 42, an objective 44, a stage 46 on which a slide 50 for a specimen is supported, a motor 64 for moving the stage 46, and a stand 48 for supporting the microscope 40 thereon. The motor 64 may comprise a separate device for moving the stage 46 in the X-axis and a separate device for moving the stage 46 in the Y-axis. The encoder 62 is supported on a shaft 63 connected to the stand 48. An X-axis control ring 66 and Y-axis control ring 68 are rotatably mounted on the shaft 63. The control rings 66 and 68 are used to vary the position of the stage 46 with respect to the objective 44 of the microscope 40, so that the user views a different portion of the slide 50 through the eyepiece 42. By rotating the X-axis control ring 66 on the shaft 63, the user moves the stage 46 along the X-axis. By rotating the Y-axis control ring 68, the user moves the stage 46 along the Y-axis. In this manner, the slide 50 may be moved from an initial position 50A to a second position 50B with respect to the objective 44 so that different cells are viewed through the field of view 51 of the microscope 40. For example, as shown in Fig. 1A, cells in a bottom right-side of the slide are seen in the field of view 51 when the slide is in the initial position 50A. When the slide is in the second position 50B, cells in the upper left-side of the slide are seen in the field of view 51. The encoder 62 is operatively connected to the motor

64 for tracking the movements of the stage 46 in response to the user's manipulation of the control rings 66 and 68, and in response to commands from the processor 26 of the personal computer 20. The personal computer includes components for interfacing with the encoder 62 and motor 64. The components may comprise a control card insertable in a drive on the personal computer.

Cellular specimens are typically collected by a physician, or personnel working for the physician and the specimen and a document requesting clinical analysis of the specimen is transmitted to a clinical laboratory. The specimen is received by a clinical laboratory having the apparatus 10 discussed above. Preferably, an identification number is applied to each of the request, the vial having the specimen therein, and a microscope slide. For example, a barcode label may be applied to the request form, vial and slide. The request document preferably includes the patient's name, the physician's name, and other personal information which may be of assistance in developing a diagnosis based upon the specimen. Information from the request document is entered into the database. In entering the patient's personal information into the database, a record is created in the database. Preferably, the request document includes predetermined information. Preferably, the personal information is entered into the database via a window presented on the screen 22 of the personal computer. The window preferably has specified fields identifying the predetermined information to be entered. The information includes the identification number from the vial, slide and request document. The information may include the name of the patient, date of birth, age, date the specimen was taken, the type of specimen, whether the patient is pregnant, is post menopausal, has had a hysterectomy, is postpartum and the name and telephone number of the physician.

The slide may be prepared following any protocol and a multi-layer or monolayer slide may be used. For example, one slide preparation procedure involves providing a medical specimen in a solution, shaking the solution, and passing the solution through a filter so that the specimen remains on the filter. The specimen is then transferred to a slide so that a single layer of cells is formed on the slide.

For example, a uniform layer of cells may be created on the slide utilizing a method in accordance with certain preferred embodiments of commonly assigned WO 98/53297, the disclosure of which is hereby incorporated by reference herein. A technician may manually prepare a slide with the specimen, or utilize an apparatus for automatically creating a slide utilizing the specimen. Preferably, the slide is a monolayer slide having a single layer of cells distributed on the surface of a slide. A monolayer slide is preferred for certain embodiments where automatic analysis of the slide is utilized.

In certain preferred embodiments, the specimen is stained. For example, the specimen may be stained using conventional papinicolou stains for a pap smear exam on cervical cells. Either a manual or automated technique may be used in staining the slide. A cover slip is then applied to the slide to cover the specimen. In preferred embodiments, automatic analysis is performed on the slide. The slide is mounted in an apparatus 70 comprising an automated cell classifier for performing the analysis, as shown in Fig. 2. The apparatus 70 has a turntable 72 for manipulating slides, a slide dotter 74 for placing marks on the slide, hardware including a processor and memory storage device 76, a camera 78, and a light source 80. A robotic arm (not shown) places the slide in a predetermined position on the scanning turntable 72, which is motorized for manipulating the position of the slide. The barcode of the slide is read by an optical scanner (not shown) in the apparatus 70 and a file corresponding to the slide identification number on the barcode is created in the memory storage device 76. The slide dotter 74 places a physical reference mark on the slide at a predetermined reference position.

The automated cell classifier maps out fields of view on the slide and the location of each field of view with respect to the reference position. The slide is scanned to define the fields of view 82. The motorized turntable 72 is manipulated so that different regions on the slide are viewed through the camera 78. The apparatus 70 monitors the position of the slide as the images are captured. The slide may be manipulated in a spiral path to cover the circular area on the slide on which the specimen is located, as shown in Fig. 3. Preferably, the turntable 72 comprises a stage and motor similar to the stage and motor of the microscope and the slide is manipulated along an X-axis and Y-axis to map out fields of view. Preferably, the fields of view are mapped out so that little or no translation between coordinate systems of the automated cell classifier and the microscope stage are required. At each position of the slide, the apparatus determines the location of the field of view 82 with respect to the reference mark. For example, a system for automatically scanning a series of slides as disclosed in commonly assigned International Publication No. WO 97/04347, the disclosure of which is hereby incorporated by reference herein. At each position on the slide, the apparatus preferably determines the optimum focus for imaging the field of view 82 at that position on the side through the lens of the camera. The apparatus 70 stores X, Y coordinate locations and focus for each field of view in the file in the memory storage device 76.

After the entire specimen has been covered by at least one field of view, the apparatus 70 moves the slide to the position corresponding to the first field of view identified in the file so that the first field of view is viewed through the lens of the camera 78. Light source 80 illuminates the specimen as the turntable 72 is manipulated to move the slide to the position for each field of view. Preferably, stroboscopic illumination is utilized to flash the specimen with light at a rate of 30 flashes per second. For each flash, at least one digital image of the cells within a field of view is captured.

In certain preferred embodiments, the light from the illuminated specimen is separated into different predetermined spectral bands by a prism assembly associated with the light source. Camera 78 comprises 3 cameras and each camera captures images in one of the predetermined spectral band. A controller controls the light source and cameras and a processor converts the images into data suitable for processing. The system for capturing images of the slide may comprise a system according to certain embodiments disclosed in commonly assigned WO 98/52016 and WO 98/35262, the disclosures of which are hereby incorporated by reference herein.

Next, the images are analyzed by an automated cell classifier of the apparatus. The automated cell classifier performs an analytical scan of the slide and identifies cells which may be irregular. For example, preferred automated cell classifiers are described in commonly assigned International Patent Publications WO 98/30317; WO 98/22909; WO 97/11350; WO 97/04419; WO 97/04418; WO 97/04348; and WO 97/50003, the disclosures of which are hereby incorporated by reference herein. Preferred devices are also disclosed in commonly assigned United States Patent Nos . 5,532,874 and 5,708,830, the disclosures of which are hereby incorporated by reference herein. Other preferred devices are disclosed in commonly assigned United States Patent Application of Ryan S. Raz entitled "Automatic Focus System", Serial No. 09/019,714, filed February 6, 1998 and the commonly assigned United States Patent application of Ryan S. Raz and Iouri Lappo, entitled "Database Element Retrieval by Example", Serial No. 09/115,608, filed July 15, 1998, the disclosures of which are all hereby incorporated by reference herein. The automated cell classifier 70 digitizes the images captured by the camera 78 and the images are manipulated using known techniques. Preferably, the techniques used are techniques disclosed in certain embodiments of the publications incorporated by reference above, such as, for example, International Publication Nos. WO 98/22909 and WO 97/11350, the disclosures of which are hereby incorporated by reference herein. The images captured by the camera 78 comprise data concerning cells and background material in each of the fields of view 82, Furthermore, each cell comprises nuclear and cytoplasm material. The data is analyzed to determine which portions of the images represent background material, cytoplasm material, or nuclear material. Segmentation is performed by the automated cell classifier to distinguish the background, nucleus and cytoplasm within each image. Segmentation analysis is known to persons of ordinary skill in the art. Preferred methods of performing segmentation are disclosed in certain embodiments of International Publication Nos. WO 98/22909, WO 97/11350, and WO 97/04418, the disclosures of which are incorporated by reference herein. The automated cell classifier 70 performs feature extraction, in which each nucleus identified during segmentation is analyzed separately. The automated cell classifier uses neural networks and algorithms to reach a classification for the nuclei identified during segmentation. The classification may be performed utilizing a neural network or elliptical basis function, as known by those of ordinary skill in the skill in the art. The classifications preferably comprise a score, such as, for example, a score on a scale of 0 to 1. On such a scale, for example, 0 may identify nuclei of benign cells and 1 may identify nuclei of abnormal cells. Thus, in preferred embodiments, the classifications developed by the automated cell classifier comprise a score representing the likelihood that the nucleus is abnormal or benign.

The output of the automated cell classifier 70 is a classifier list listing the X,Y coordinates of the fields of view on the specimen, an associated field of view number or other tag used to denote each particular field of view. Preferably, the list includes the physical reference mark as the first location and the X,Y coordinates of 0,0 for the physical reference mark. Preferably, the data includes the "score" associated with each field of view as well as the location of such field. Alternatively, the scores may be stored in a different data file from the locations for each field of view on one or more memory storage devices (a list of the nuclei and their associated scores) .

Preferably, the automated cell classifier utilizes a threshold value to classify nuclei over the threshold value as abnormal. For example, if the threshold value was 0.8, all nuclei having a score of 0.8 and above would be classified as abnormal. Many cells may be located in each field of view. Preferably, any field of view having at least one cell classified as abnormal after applying the threshold is included in the classifier list. Preferably, the list is sorted according to fields of view having the highest score being listed before fields of view having lower scores. The data is added to the data stored on the memory storage device 76 of apparatus 70.

The data from the memory storage device 76 of the automated cell classifier 70 is transmitted to memory storage device 28 of the personal computer 20 discussed above. Alternatively, the data may be transmitted to a database on another memory device connected to the review station. The data is incorporated with the database on the memory storage device 28 and the patient information stored in the database. The output of the automated cell classifier 70 is associated with the patient's personal information via the identification number on the bar code on the slide, which is the same identification number utilized to create the record in the database upon entry of the patient's personal information. When the cytotechnologist is prepared to review a slide, the cytotechnologist logs into the personal computer 20 utilizing the keyboard 27 and mouse 32, preferably entering the cytotechnologist ' s name, and commands the processor 26 to retrieve a patient's information from the database. A display 90 is displayed on the screen 22. For example, the screen may include a window having the patient's information 92, a window including the classifier list 94 from the automated cell classifier, a window for the cytotechnologist list 96 and other windows. Preferably, the display 90 includes an area for entry of notes from the cytotechnologist and an indication of the adequacy of the specimen or other factors. The display 90 also includes buttons 98 for indicating completion of the review by the cytotechnologist. (See Fig. 4) .

The cytotechnologist may indicate the particular patient's specimen for review either by entry of the bar code from the slide or by selection of the identification number utilizing the keyboard 27 and/or mouse 32. Preferably, the microscope 40 includes an optical scanner for reading the barcode when the slide 50 is mounted on the stage 46. Preferably, the barcode is read and an error message is presented to the cytotechnologist if the scanner fails to read the barcode. Failure to read the barcode may be utilized as a check to ensure that the slide is mounted on the stage 46 in the proper position.

Preferably, the encoder is calibrated by driving the stage 46 to the maximum positions on the X and Y axes and determining the location of a predetermined position on the slide with respect to the maximum Y and Y positions. It may also be necessary to calibrate the encoder utilizing a calibration slide having marks at predetermined, known positions on the slide.

The review process is illustrated in Fig. 5. The cytotechnologist mounts the slide 50 on the stage 36 of the microscope 40. The identification number is read from the bar code on the slide to determine which record in the database to retrieve. The processor 26 retrieves the record corresponding to the identification number from the database on memory storage device 28. The processor 26 commands the encoder 62 to move the stage 46 into the first position in the classifier list so that the first field of view is viewed through the objective 44 of the microscope 40. Preferably, the microscope 40 is controlled so that the optimum focus for the field of view is obtained. For example, a system for automatically focusing a microscope lens is disclosed in commonly assigned International Publication No. WO 97/04348, the disclosure of which is hereby incorporated by reference herein.

The cytotechnologist examines the first field of view through the eyepiece 42 and objective 44 of the microscope 40. The cytotechnologist selects a characterization for the cells within the field of view by manually assigning a characterization to the field of view using a user interface of the personal computer 20. The cytotechnologist assigns a characterization through use of the keyboard 27 or mouse 32, by selecting an input device comprising a button 30 of the keyboard 27 or mouse 32, corresponding to the desired characterization. For example, each of several buttons 30 may represent a characterization of normal, abnormal, a specific condition, or some other characterization relating to the diagnosis of the patient, such as cellular transitional zone material, and within normal limits. Upon selection of a characterization for a field of view, the characterization is added to the data in the database. In certain preferred embodiments, the characterizations include abnormal, normal and questionable. Preferably, upon entry of the characterization, the processor 26 controls the encoder 62 to move the stage 46 to the next field of view in the classifier list 94. The cytotechnologist reviews successive fields of view in the classifier list 94 and assigns characterizations to the fields of view by actuating one of the input devices 30 of the keyboard 27 or mouse 32. Upon assignment of each characterization, the characterization is added to the cytotechnologist list, in the data corresponding to the field of view being reviewed by the cytotechnologist. After assignment of each characterization, the processor 26 commands the encoder 62 to move the stage 46 so that the next field of view in the list is visible through the microscope 40.

In certain preferred embodiments, the review of successive fields of view is controlled so that only a predetermined number of fields of view are reviewed per unit time. Preferably, a next field of view can be reviewed only after a prescribed unit of time has passed since the time a previous field of view was reviewed. The processor 26 of the personal computer 20 is connected to a timer for determining the relative times commands are entered by the cytotechnologist. When the cytotechnologist enters a characterization for a first field of view, the processor 26 determines the time the cytotechnologist manipulated the input device 30 on the keyboard 27 or mouse 32. The processor 26 determines the time the characterization was entered by referring to the timer. The processor 26 controls the encoder 62 to bring a second field of view in the classifier list 94 into position with respect to the objective 34 of the microscope 40. After the cytotechnologist reviews the second field of view, the cytotechnologist selects a characterization for that field of view. The processor 26 refers to the timer and obtains a time for the use of the input device 30 representing the characterization selected by the cytotechnologist. The difference between the time values provided by the timer roughly indicate the amount of time the cytotechnologist took in reviewing the second field of view. As a quality control measure, to ensure that the cytotechnologist does not rush through each of the fields of view, the database may be designed to prevent retrieval of the next field of view after assignment of a characterization until a predetermined amount of time has passed since the entry of the last characterization by the cytotechnologist. In certain preferred embodiments, the cytotechnologist may not complete review of a specimen until a predetermined unit of time has passed since completion of the review of the last specimen. In this embodiment, the processor utilizes the timer to obtain the time the cytotechnologist selects a button 98 on the screen 90 in completing review of two specimens, to determine the amount of time the cytotechnologist took in reviewing a specimen. Review of the next specimen may be prevented by the database, or an error message may be presented to the screen 22 to inform the cytotechnologist that the time took to review the specimen was shorter than the predetermined unit of time.

In preferred embodiments, the cytotechnologist may alter the location of a field of view in the database. Upon viewing a particular field of view, the cytotechnologist may find cells of interest within that field of view. The cytotechnologist manipulates the X-axis control ring 66 and Y-axis control ring 68 to position the stage 46 so that the cells of interest are centered when viewed through the eyepiece 42 and objective 44. Upon altering the position of the stage 46, the cytotechnologist selects a "mark" command utilizing the input devices of the keyboard 27 and the mouse 32. The new position for the field of view with respect to the reference position on the slide is determined by the encoder 62 and entered into the database for the field of view. In preferred embodiments, a predetermined input device on the keyboard or mouse corresponds to the mark command.

In preferred embodiments, the cytotechnologist may create a new field of view having a new location with respect to the reference position on the slide. After adjusting the position of the slide to center cells of interest as viewed through the microscope, the cytotechnologist enters a characterization for the cells of interest by selecting the input device 30 corresponding to the characterization. The database responds to actuation of the input device 30 by entering a new field of view having the new location into the data corresponding to the new field of view. The new location corresponds to the location of center of the area of view seen through the microscope. Thus, either new fields of view may be created or the location of a field of view may be revised by a cytotechnologist. In adding a new field of view, an additional listing is added to the classifier list 94 and cytotechnologist list 96. In revising a location for a field of view, the data in the classifier list 94 concerning the location of the field of view being reviewed is revised. After creating a new field of view or revising a location of a field of view, the cytotechnologist enters a "next" command to review another field of view on the list in window 94. Preferably, a predetermined input device 30 on the keyboard or mouse corresponds to the next command .

Preferably, an input device 30 on the keyboard or mouse corresponds to a "previous" command which may be selected at any time to view the previous field of view in the classifier list 94.

In certain preferred embodiments, the cytotechnologist may also place physical marks on the cover slip of the slide to denote cells of interest. The microscope 40 includes a slide dotter 110 which is movable toward the slide 50. (See Fig. 4A) After the cytotechnologist marks cells of interest utilizing the mark command discussed above, the encoder 62 and database control the stage so that the marked position is located beneath the slide dotter. The slide dotter is also connected to the processor 26 and is commanded to move downwardly to place a mark on the slide 50. The physical marks preferably include several colors or shapes which may be selected by the cytotechnologist according to the characterization of the cells at the physical mark. For example, the slide dotter may include several pens 112 which may be changed by the cytotechnologist (see Fig. 4A) . The database determines whether all the fields of view listed in the list 94 have been reviewed. The fields of view in the list 94 are reviewed until the database determines that all the fields of view have been reviewed and the cytotechnologist has entered a classification for each. Preferably, the cytotechnologist may review each of the fields of view in the list 94 and revise any of the classifications entered. The database then determines whether any abnormal characterizations have been entered by the cytotechnologist. If the cytotechnologist list 96 includes an abnormal characterization, the cytotechnologist is free to view the slide 50 from any position by manipulating the X-axis control ring 66 and Y-axis control ring 68. This is called free motion review. After free motion review, the cytotechnologist may enter a diagnosis indicating the specimen to be abnormal, if the cytotechnologist ' s opinion is that the specimen as a whole is abnormal. If no abnormal characterization was entered in the cytotechnologist characterization list 96, the cytotechnologist typically enters a diagnosis indicating that the specimen as a whole is normal. If the characterizations in the cytotechnologist list 96 include any questionable characterizations, the cytotechnologist is preferably allowed to perform a free motion review. Typically, the cytotechnologist will manipulate the X-axis control ring 66 and Y-axis control ring 68 so as to sweep across the specimen during free motion review. After free motion review, the cytotechnologist may classify the specimen as either abnormal or normal, depending upon the cytotechnologist ' s opinion. In certain embodiments, the questionable characterizations entered by the cytotechnologist may be changed to normal or abnormal in the list 96 after free motion review.

Free motion review enables the cytotechnologist to manipulate the X-axis control ring 66 any Y-axis control ring 68 without interference from the controller 62 or motor 64. In certain preferred embodiments, the cytotechnologist may review the slide by manipulating the X-axis control ring 66 and Y-axis control ring 68 so that the objective 44 of the microscope 40 sweeps across the specimen on the slide 50. In certain preferred embodiments, manual movement of the stage 46 moves the area of view of the microscope across the specimen in a controlled manner, according to a predetermined pattern. This is referred to as controlled sweep mode. The predetermined pattern may comprises a pattern as shown in Fig. 8. The encoder 62 substantially disables the Y-axis control ring 68 and permits the cytotechnologist to move along the X-axis utilizing the X-axis control ring 66 to move the stage 46 so that the objective 44 moves across the slide 50 as shown in Fig. 8. The objective 44 moves in a lane 110 along the X-axis. At an end 112 of the lane, the cytotechnologist may manipulate the Y-axis control ring 68 to move to a next lane 114. A predetermined number of lanes are anticipated so that the spacing between the lanes is also predetermined. If the cytotechnologist manipulates the X-axis control ring 66 or Y-axis control ring 68 greater than a predetermined amount, the controlled sweep mode is overridden and the cytotechnologist may return to a free motion review without interference by the controller 62 or motor

64. For example, if the control ring 66 or 68 is moved greater than the amount corresponding to the distance between the lanes, controlled sweep mode is overridden.

In other preferred embodiments, the predetermined pattern comprises the pattern shown in Fig. 9. Preferably, the lanes are designed so as to slightly overlap and to include all of the specimen on the slide. As shown in Fig. 10, each lane defines an area on the specimen. For example, lane 110 in Fig. 11, defines an elongated area of view 118 comprising the area covered by the objective 44 when the slide is moved in a direction along the X-axis with respect to the objective 44. Similarly, lane 114 has an area 120. Preferably, each area has an overlap region extending substantially the length of the area. For example, area 118 and area 120 have an overlap region 116 as shown in Fig. 11. The lanes are also preferably defined so that the areas cover the entire specimen. In certain preferred embodiments, actuation of an input device 30 ends the controlled sweeping according to a predetermined pattern. For example, during sweeping according to the pattern shown in Fig. 8, the cytotechnologist may actuate an input device 30 on the keyboard 27 or mouse 32 so as to permit free motion review without interference from the encoder 62 or motor 64. In other preferred embodiments, actuating an input device 30 on the keyboard 27 or mouse 32 reinitiates the controlled sweeping according to a predetermined pattern. Preferably, the cytotechnologist may not enter a characterization for the specimen as a whole of abnormal, if any of the characterizations in the cytotechnologist characterization list 96 are abnormal. The database is programmed to refuse the characterization of abnormal for the specimen as a whole. Preferably, the display 90 includes a field 100 through which the cytotechnologist may enter the characterization of the specimen as a whole. The field 100 may have predetermined characterizations associated with the field, such as normal, abnormal, specific conditions, cellular changes, transitional zone material and within normal limits. Preferably, after the cytotechnologist enters the characterization into field 100, the database determines whether any characterization in the cytotechnologist list 96 is an abnormal characterization. If any abnormal characterization is included in the list 96, the database does not store the cytotechnologist ' s characterization along with the data for the particular slide. Preferably, an error message in another window is presented to the screen 22 of the personal computer 20. In preferred embodiments, the cytotechnologist reviews a series of specimens in the manner discussed above. To complete review of a specimen, the cytotechnologist selects a button 98 representing "close" and the window 90 having the patient information is no longer displayed. After entry of the barcode number for the next specimen, a new display having the patient information and classifier list 94 for the next specimen is displayed on the screen 22 of the personal computer 20.

Preferably, and as depicted in Fig. 6, a pathologist reviews the slides 50 that the cytotechnologist classifies the specimen as abnormal utilizing the review station apparatus 10. The pathologist examines each of the fields of view in the cytotechnologist list 96 and may enter a different characterization for each field of view. In certain preferred embodiments, a pathologist list is generated in the database for any characterizations entered by the pathologist. In other preferred embodiments, the pathologist ' s characterizations are added to the cytotechnologist list 96 so as to amend the characterizations entered by the cytotechnologist. The pathologist may also change the location for fields of view using the mark command, or create new fields of view, as discussed above. During review by the pathologist, the processor 26 commands the controller 62 to move the stage 46 so that each field of view can be viewed through the eyepiece 42 by the pathologist. After each field of view in the cytotechnologist list 96 has been reviewed by the pathologist, the pathologist may again review each field of view in the list. After review, the pathologist enters a diagnosis for the specimen as a whole. In certain preferred embodiments, the pathologist may engage in free motion review. The method of reviewing specimens of cells discussed above may be implemented on a number of computer systems . The computer system may include a personal computer, as discussed above, which is operatively connected to the apparatus 70 for performing an automatic review of slides. In other embodiments, the apparatus 70 includes a disk drive for storing the data generated by the automated cell classifier on a floppy disk, and the data is transferred from the floppy disk to the personal computer through a disk drive on the personal computer. In another embodiment, both the personal computer and automated cell classifier 70 are connected to a central computer which stores the patient's information, the data generated by the automated cell classifier 70, and the data generated during the review of the specimen utilizing the microscope 40. Hardware for accomplishing a system for implementing the method of reviewing specimens is known in the art. An example of a microscope which may be used is the Olympus BX40. General purpose personal computers, network servers, or any other computer devices now known are to be developed may be used to construct a system for implementing a method of reviewing specimens of cells. The software for implementing the method of reviewing specimens of cells may include custom-designed software or a preexisting software tools customized to create the method of reviewing specimens of cells. For example, the database discussed above may comprise a customized or preexisting database software programmed to control the review of specimens on a slide as discussed above. The patient information may be entered into a preexisting database associated with, or separate from, the information generated by the automated cell classifier. For example, a preexisting laboratory information system may be used to create a record for a patient. The record may be imported into the database of information stored on the memory storage device of the review station. Alternatively, the patient information is maintained separately from the database having the classifier list and cytotechnologist list. Patient information need not be entered in the database. If a database for the patient information is not used, the request document, or other documentation, may be maintained in paper form.

In another embodiment of the invention, a memory storage device for storing the cytotechnologist list and classifier list is provided on a central computer remote from the review station. The review station includes the microscope, motorized stage and associated control devices for moving the stage so that fields of view are visible through the microscope. A plurality of review stations arranged in communication with the central computer may be provided. For example, the review stations and central computer may be networked. In preferred embodiments, the monitor 21 and screen 22 are omitted and a small LCD screen or small VGA screen is provided at the review station to reduce the special requirements of the review station. In this embodiment, only the classifier list and cytotechnologist characterization list, or portions thereof, are visible on the screen. In another preferred embodiment, no monitor or screen is provided.

In certain preferred embodiments, the computerized system includes software for automatically determining statistics regarding the characterizations assigned during review of a series of specimens. The cytotechnologist typically reviews a series of specimens on slides, from more than one patient. The cytotechnologist reviews each field of view from the classifier list and enters characterizations utilizing the input devices 30 of the keyboard 27 and mouse 32 as discussed above. After the cytotechnologist has completed a session, either based upon the predetermined amount of time, such as a day or a week, or based on a predetermined a number of slides, software stored on a computer automatically compiles at least one statistic based upon the characterizations entered by the cytotechnologist. The software for compiling the statistics may be stored on the memory storage device 28 of the personal computer 20 shown in Fig. 1. Alternatively, the software for determining the statistics may be stored on a central computer in communication with the review station. The statistics may include statistics regarding characterizations entered by a number of different cytotechnologists working at one or more personal computers. For example, the number of abnormal characteristics entered by each cytotechnologist may be determined and a sorted list according to the cytotechnologists who enter the most abnormal characterizations may be compiled. In addition, the number of abnormal characterizations per fields of view reviewed for a particular cytotechnologist, or an average for a number of cytotechnologists, may be determined. Statistics concerning the characterizations entered by cytotechnologists, as compared to the characterizations entered by the pathologist may also be compiled automatically. For example, the number of characterizations amended by a pathologist for a particular cytotechnologist may be determined. In addition, the number of characterizations amended by a particular pathologist may be determined. The number of characterizations of abnormal amended to characterizations of normal per fields of view reviewed, may be determined. The number of characterizations of normal amended to characterizations of abnormal, per fields of view reviewed, may also be determined.

In certain preferred embodiments, statistics concerning the characterizations of the specimens as a whole may be automatically compiled. The number of specimens assigned a particular characteristic per specimens reviewed by the clinical laboratory may be determined automatically. The statistics may include a comparison of the characterizations entered by a first person, such as a cytotechnologist, and the characterizations of specimens entered by a second person, such as a pathologist. For example, the number of characterizations entered by pathologist for specimens which differ from the number of characterizations entered by cytotechnologist, per number of specimens reviewed, may be determined.

In other preferred embodiments, the characterizations entered by the cytotechnologists or pathologists, or both, may be compared to the results of the automated cell classifier. As discussed above, the automated cell classifier assigns a classification of abnormal to fields of view having a score over a predetermined threshold. Statistics concerning the number of classifications by the automated cell classifier which differ from the characterizations of the cytotechnologists, per number of fields of view reviewed may be automatically determined. Thus, statistics may be automatically compiled by the computer system and periodically reviewed by administrators or other personnel in the clinical laboratory to draw conclusions as to the efficiency and accuracy of the lab and/or the automated cell classifier . In certain preferred embodiments, a separate specialized device, such as keypad 132 in Fig. 11 may be used to characterize the fields of view. The keypad 132 is connected to the personal computer 20 so that the cytotechnologist or pathologist may enter commands to the database. The keypad 132 is connected to a port on the personal computer 20 through a wire 137. The keypad 132 includes input devices comprising buttons 133 for entering commands. Preferably, the keypad 132 includes a specific button for a normal classification, a specific button for an abnormal classification, a specific button for the next command, and a specific button for the mark command, and a specific button for completing review of a specimen.

In other preferred embodiments, the input devices comprise a plurality of predetermined voice-activated commands and the personal computer 20 includes a microphone for receiving the voice of the user. The personal computer also includes software stored on the memory storage device 28 for recognizing the predetermined commands spoken by the user. As used herein "input device" means any user- interface for receiving predetermined computer commands . In other preferred embodiments, the input device comprises buttons on the screen 22 which are activated by using mouse 32 in the known manner.

In another embodiment, selection of the mark command is utilized to both add a new field of view to the classifier list 94 and revise the location for a field of view in the list. After selection of the mark command, the database determines the position marked by the cytotechnologist. The position marked is the center of the area of view of the microscope when the cytotechnologist selects the mark command. The database compares the marked position to the position of the last field of view reviewed by the cytotechnologist. If the marked position and position for the field of view are within a predetermined distance from one another, the location for the field of view is revised in the classifier list 94. If the marked position and position for the field of view are further apart than the predetermined distance, a new field of view having the location for the marked position is added to list 94.

As will be readily appreciated, numerous other variations and combinations of the features discussed above will be employed without departing from the present invention. Accordingly, the foregoing description of certain preferred embodiments should be taken by way of illustration, rather than by way of limitation, of the features discussed above. INDUSTRIAL APPLICABILITY The present invention can be applied in the review of slides of cellular specimens in a laboratory.

Claims

CLAIMS :

1. A method of reviewing specimens of cells, comprising: a. automatically retrieving a first location from a list of locations of fields of view on a specimen, the first location corresponding to a first field of view; b. reviewing the first field of view; c. manually assigning a characterization to the first field of view by actuating one of a plurality of input devices representing characterizations, the input devices being in communication with a computer so that a characterization is added to data associated with such location.

2. The method of claim 1, further comprising automatically retrieving a next location from the list, corresponding to the next field of view, responsive to actuation of any of the plurality of input devices representing characterizations of fields of view.

3. The method of claim 1, further comprising reviewing successive fields of view from the list and assigning characterizations to fields of view by actuating one of the plurality of input devices for each characterization assigned.

4. The method of claim 3, wherein the fields of view have an associated likelihood of abnormality and the list is sorted according to the likelihood of abnormality so that fields of view with a greater likelihood of abnormality are reviewed first.

5. The method of claim 3, wherein the steps of reviewing the successive fields of view include a person looking at the specimen through a microscope, the microscope including a stage for supporting the specimen on a carrier.

6. The method of claim 5, wherein the steps of reviewing the successive fields of view include moving the stage so that the fields of view of the specimen are visible through the microscope seriatim.

7. The method of claim 3 , wherein the reviewing steps include reviewing fields of view of specimens by a first person and then reviewing fields of view of specimens by a second person.

8. The method of claim 7, wherein the steps of assigning characterizations to fields of view include characterizing the fields of view by the first person and characterizing fields of view by the second person.

9. The method of claim 8, further comprising the second person amending the characterizations assigned by the first person.

10. The method of claim 3, wherein the reviewing step includes selecting a desired field of view from the list and reviewing that field of view.

11. The method of claim 3, further comprising adding the characterizations assigned fields of view to data associated with the fields of view.

12. The method of claim 1, wherein each of the plurality of input devices represents a characterization selected from the group consisting of abnormal, benign cellular changes, questionable, transitional zone material and within normal limits.

13. A method of reviewing specimens of cells, comprising : a. reviewing a series of fields of view of one or more specimens, the step of reviewing the fields of view including a person looking at the specimen through the microscope; and b. automatically controlling the review so that only a predetermined number of fields of view are reviewed per unit time .

14. The method of claim 13, wherein a field of view can be reviewed only after a prescribed unit of time has passed since the time a previous field of view was reviewed.

15. The method of claim 14, wherein a next field of view in the series is presented in response to a manual input .

16. A method of reviewing specimens of cells, comprising: a. manually reviewing a series of specimens; b. manually assigning characterizations to fields of view of each specimen; and c. automatically determining at least one statistic regarding the characterizations assigned during review of the series of specimens.

17. The method of claim 15, wherein the series of specimens includes specimens of more than one patient.

18. The method of claim 15, wherein the manual assignment of characterizations includes entering characterizations into data for a computer system.

19. The method of claim 18, wherein the computer automatically compiles said at least one statistic based upon the characterization entered into the computer.

20. The method of claim 15, wherein the step of automatically determining at least one statistic includes automatically compiling at least one statistic regarding fields of view assigned a particular characterization.

21. The method of claim 15, wherein the step of automatically determining at least one statistic includes automatically compiling at least one statistic regarding a comparison of the characterizations entered by a first person and the characterizations entered by a second person.

22. The method of claim 15, further comprising manually assigning a characterization to each specimen as a whole.

23. The method of claim 21 wherein the step of automatically determining at least one statistic includes automatically compiling at least one statistic regarding specimens assigned a particular characteristic.

24. The method of claim 22, wherein the step of automatically determining at least one statistic includes automatically compiling at least one statistic regarding a comparison of the characterizations of specimens entered by a first person and the characterizations of specimens entered by the second person.

25. The method of claim 15, further comprising the step of automatically assigning classifications to fields of view of each specimen.

26. The method of claim 24, wherein the step of automatically determining at least one statistic includes automatically compiling at least one statistic regarding a comparison of the characterizations of fields of view entered by a first person and classifications of fields of view automatically assigned.

27. A method of reviewing specimens of cells, comprising: a. reviewing fields of view of the specimen, the step of reviewing the fields of view including a person looking at the specimen through a microscope; b. manually adding characterizations for the fields of view to data associated with the specimen; c. manually inputting a characterization for the specimen as a whole into the data; and d. automatically preventing addition to the data any characterization for the specimen as a whole as normal if any field of view in the list is assigned the characterization of abnormal .

28. The method of claim 27, wherein the step of reviewing a series of fields of view includes automatically presenting fields of view to be reviewed so that the area of view of the microscope is centered on the particular location for the field of view being reviewed.

29. A method of reviewing specimens of cells, comprising: a. reviewing a series of fields of view of the specimen, according to a list of fields of view and their locations on the specimen with respect to a reference position, the step of reviewing the fields of view including manually looking at the specimen through the microscope, the microscope having an area of view for viewing one field of view at a time; and b. during viewing of a particular field of view in the series, manually adjusting the area of view to a new location on the specimen which is different from the location for such particular field view.

30. The method of claim 29, further comprising assigning a characterization to fields of view on the list.

31. The method of claim 30, further comprising automatically amending the location for said particular field of view responsive to assignment of a characterization after the area of view has been adjusted to a new location, including automatically replacing the location for the previously viewed field of view with the new location.

32. The method of claim 31, wherein the new location for said particular field of view is the position of a center of the area of view with respect to the reference position after the manual adjusting step.

33. The method of claim 31, wherein the new location comprises the position of a center of the area of view with respect to the reference position.

34. A method of reviewing specimens of cells, comprising: a. reviewing a series of fields of view of the specimen, according to a list of fields of view and their locations on the specimen with respect to a reference position, the step of reviewing the fields of view including manually looking at the specimen through the microscope, the microscope having an area of view for viewing one field of view at a time; b. during viewing of a particular field of view in the series, manually adjusting the area of view to a new location on the specimen which is different from the location for such particular field view; and c. automatically defining a new field of view responsive to assignment of a characterization after the area of view has been adjusted to a new location, including automatically adding the new field of view and associated new location to data associated with the list.

35. The method of claim 31, further comprising adding the characterization for the field of view at the new location to data associated with the list.

36. A method of reviewing specimens of cells, comprising: a. reviewing fields of view of the specimen, by manually sweeping the area of view of a microscope across the specimen, the step of reviewing the fields of view including manually looking at the specimen through the microscope; b. providing a prescribed pattern of movement of the area of view across the specimen; and c. controlling the manual movement of the area of view across the specimen so that the area of view follows the pattern until a manual input to deviate from the pattern is entered.

37. The method of claim 36, wherein the manual input comprises movement of an input device greater than a predetermined amount .

38. The method of claim 36, wherein the manual input comprises actuation of a first input device.

39. The method of claim 38, wherein a second input device is utilized to manually sweep the area of view across the specimen.

40. The method of claim 36, wherein the pattern includes fields of view previously defined for the specimen.

41. The method of claim 40, further comprising, during review of a particular field of view, manually adjusting the area of view to a new location on the specimen which is different from such particular field of view, arresting such control of manual review in response to the manual adjustment of the area of view to a new location.

42. The method of claim 41, further comprising actuating an input device so that the area of view returns to such pattern.

43. Apparatus for controlled review of specimens of cells, comprising: a . at least one computer for storing data associated with the specimen, including a list of locations of fields of view on a specimen, including a first location corresponding to a first field of view; b. a device for reviewing said first field of view; c. a plurality of input devices in communication with said at least one computer, said plurality of input devices each representing characterizations and being actuatable for assigning a characterization to said first field of view.

44. The apparatus of claim 43, wherein said at least one computer is arranged to retrieve a next location from said list, corresponding to a next field of view in response to actuation of any of said plurality of input devices.

45. The apparatus of claim 43, wherein said at least one computer is arranged to retrieve successive locations from said list for review through said device for reviewing.

46. The apparatus of claim 45, wherein said data includes a likelihood of abnormality associated with each said field of view and said at least one computer is arranged to sort said list so that said fields of view are retrieved and reviewed according to the fields of view having the greatest likelihood of abnormality on the list.

47. The apparatus of claim 45, further comprising a microscope including a stage for supporting the specimen on a carrier .

48. The apparatus of claim 47, wherein said at least one computer is in communication with said microscope for effecting movement of the stage so that one of said fields of view of the specimen is visible through said microscope.

49. The apparatus of claim 45, wherein said at least one computer is arranged to store said characterizations assigned by a first person and said characterizations assigned by a second person into said data.

50. The apparatus of claim 43, wherein each of the plurality of input devices represents a characterization selected from the group consisting of abnormal, benign cellular changes, questionable, transitional zone material and within normal limits.

51. An apparatus for controlled review of specimens of cells, comprising: a. at least one computer for storing data associated with the specimen, including a list of locations of fields of view on a specimen; b. a microscope for reviewing said fields of view by looking at the specimen through the microscope; and c . said at least one computer being in communication with said microscope and controlling retrieval of said data so that only a predetermined number of said fields of view are reviewed per unit time.

52. An apparatus for controlled review of specimens of cells, comprising: a. a device for manually reviewing a series of fields of view of the specimen; b. a plurality of input devices, each representing characterizations and being manually actuatable for assigning a characterization to said fields of view; and c . at least one computer in communication with said plurality of input devices, said at least one computer being arranged to control and manipulate data associated with the specimen, d. said at least one computer being arranged to determine at least one statistic regarding characterizations manually assigned to fields of view of the specimen during review of a series of specimens.

53. An apparatus for controlled review of specimens of cells, comprising: a. a plurality of input devices, each representing characterizations and being manually actuatable for assigning a characterization to fields of view of the specimen and to the specimen as a whole; and b. at least one computer in communication with said plurality of input devices, said at least one computer being arranged to input said characterizations into data associated with the specimen, c. said at least one computer being arranged to preventing addition to said data any characterization for the specimen as a whole as normal if any field of view in the list is assigned the characterization of abnormal.

54. An apparatus for controlled review of specimens of cells, comprising: a. a device for manually reviewing said series of fields of view of the specimen including an area of view for viewing one of said fields of view at a time, said device being manually adjustable so that during review of a particular field of view in said series, said area of view is moveable to a new location on the specimen which is different from the location for such particular field of view; b. a plurality of input devices for assigning a characterization to said fields of view; and c. at least one computer in communication with said plurality of input devices, said at least one computer being arranged to store and manipulate data in at least one data storage medium for storing data associated with the specimen, including a series of fields of view and their locations on the specimen with respect to a reference position; and d. said at least one computer being arranged to change the location for the field of view in said data, including replacing the location for said particular field of view with said new location.

55. An apparatus for controlled review of specimens of cells, comprising: a. a device for manually reviewing a series of fields of view of the specimen including an area of view for viewing one of said fields of view at a time, said device being manually adjustable so that during review of a particular field of view in said series, said area of view is moveable to a new location on the specimen which is different from the location for such particular field of view on the specimen with respect to a reference position; b. a plurality of input devices for assigning a characterization to said fields of view; and c . at least one computer in communication with said plurality of input devices, said at least one computer being arranged to store and manipulate data associated with the specimen including said series of fields of view and their locations on the specimen with respect to the reference position; and d. said at least one computer being arranged to add a new field of view to said data, including automatically adding said new field of view and the location of said new field of view on said specimen with respect to said reference position.

56. An apparatus for controlled review of specimens of cells, comprising: a. a device for manually reviewing fields of view of the specimen, said device including an area of view for viewing one of said fields of view at a time, said device being manually moveable so as to sweep said area of view across the specimen; b. a manually actuatable input device; and c. at least one computer in communication with said input device and said device for reviewing, said at least one computer being arranged to control the manual movement of said area of view so that said movement follows a prescribed pattern sweeping said area of view across the specimen until said input device is actuated.

57. The apparatus of claim 56, wherein said input device comprises a ring for moving a stage supporting the specimen, movement of said ring greater than a predetermined amount effecting a deviation from said pattern.

58. The apparatus of claim 56, wherein said input device comprises a button on a keypad.

59. The apparatus of claim 56, said input device being actuatable so that said area of view returns to said pattern.

60. An apparatus for entering characterizations during controlled review of specimens of cells, comprising: a. an input device for communicating with at least one computer, said input device including a plurality of keys, each representing a characterization of cells within the specimen.

61. The apparatus of claim 60, wherein each of said plurality of keys represent a characterization selected from the group consisting of abnormal, benign cellular changes, questionable, transitional zone material, and within normal limits .