WO2016058052A1

WO2016058052A1 - System and method for generating digital pathology images

Info

Publication number: WO2016058052A1
Application number: PCT/AU2015/050635
Authority: WO
Inventors: Shane BATTYE
Original assignee: Pathobin Pty Ltd
Priority date: 2014-10-15
Filing date: 2015-10-15
Publication date: 2016-04-21

Abstract

A system for generating a digital pathology image from an optical. The system includes a first mount that is connectable to the eyepiece or photo tube, and is configured to support a digital image capture device so as to capture digital images of the specimen as viewed through the eyepiece or photo tube; a powered drive system that includes two or more electric actuators that, in use of the system, are each operable to cause the specimen slide to move in one of two orthogonal directions beneath the objective; and a controller in communication with the powered drive system, the controller being configured to receive an input representative of an instruction to move the specimen slide and, in response to that input, direct the powered drive system to move the specimen slide. Co-ordinated operation of the image capture device and provision of inputs to the controller enables capture of a series of overlapping digital images from which to generate the digital pathology image of the specimen.

Description

System And Method For Generating Digital Pathology Images

Field of the invention

The present invention relates to a system and method for generating digital pathology images.

Background

It is known to use photographic equipment in combination with optical microscopes to keep a permanent record of pathology images of specimens. Some basic optical microscopes have an observation tube that includes a photo tube in addition to the eyepiece. A photographic camera can be mounted to the photo tube for capturing the image of the portion of the specimen slide that is within the microscope field of view. Digital microscopes use a digital image sensor, such as CCD and CMOS, to generate a digital image of the portion of the specimen slide that is within the microscope field of view. Some digital microscopes have an electronic powered stage, in which movement of the microscope stage is performed by electric motors. The combination of a digital image sensors and an electronic powered stage provides the capacity to generate large, high-resolution pathology images by capturing a series of digital images and using software to "stitch" these images together.

Capturing a pathology image digitally has the advantage that the image can be readily transmitted to a separate location that is geographically spaced from the actual microscope and specimen via a computer network, enabling an operator - such as a pathologist - to review and analyze the image at the separate location. While there are advantages in digital pathology images, there are also significant equipment costs associated with digital microscopes. There is a need to address the above, and/or at least provide a useful alternative.

Summary

The present invention provides a system for generating a digital pathology image from an optical microscope having an objective beneath which a specimen slide is to be positioned, and an eyepiece or photo tube, the objective and eyepiece or photo tube being at opposing ends of a light path such that a specimen on the specimen slide is viewable through the eyepiece or photo tube, the system including:

a first mount that is connectable to the eyepiece or photo tube, and is configured to support a digital image capture device so as to capture digital images of the specimen as viewed through the eyepiece or photo tube;

a powered drive system that includes two or more electric actuators that, in use of the system, are each operable to cause the specimen slide to move in one of two orthogonal directions beneath the objective; and

a controller in communication with the powered drive system, the controller being configured to receive an input representative of an instruction to move the specimen slide and, in response to that input, direct the powered drive system to move the specimen slide;

whereby co-ordinated operation of the image capture device and provision of inputs to the controller enables capture of a series of overlapping digital images from which to generate the digital pathology image of the specimen.

In certain embodiments, the powered drive system includes:

a specimen slide holder onto which the specimen slide is mountable;

a platform to which the specimen slide holder is attached; and

a drive train that is coupled the platform, and driven by the electric actuators, whereby movement of each of the electric actuators is transferred through the drive train to cause the platform to move in a respective one of the orthogonal directions.

In some alternative embodiments, the powered drive system includes:

a platform with a support that is connectable to the specimen slide holder of the optical microscope; and

a drive train that is coupled to the electric actuators and the platform,

whereby movement of each of the electric actuators is transferred through the drive train to cause the platform to move in a respective one of the orthogonal directions.

The drive train preferably includes a first drive for moving the platform in the first of the two orthogonal directions, and a second drive for moving the platform in the second of the two orthogonal directions. In certain embodiments, the first drive includes:

at least one first support member that extends in the first direction; at least one carriage that is mounted on the first support member, and is displaceable along the at least one first support member by operation of a first of the electric actuators,

wherein the second drive is supported by the at least one carriage such that the second drive is displaceable in the first direction, and wherein the platform is supported by the second drive.

In at least some preferred embodiments, the first drive includes:

a pair of first support members that each extend in the first direction, and are spaced apart;

a pair of carriages, each carriage being mounted on a respective one of the first support member and being displaceable along the respective first support member by operation of one or more first electric actuators,

wherein the second drive is supported between the carriages such that the second drive is displaceable in the first direction, and wherein the platform is supported by the second drive.

Preferably, the second drive includes at least one second support member that extends in the second direction, wherein the platform is displaceable along the at least one second support member by operation of a second of the electric actuators.

In embodiments of the system that are used with an optical microscope that includes a stage disposed beneath the objective, the system is preferably configured such that the specimen slide when mounted in the specimen slide holder is supported vertically on the stage.

The system can further include a support structure for supporting the powered drive system above a surface on which the optical microscope rests. The present invention also provides a system for generating a digital pathology image from an optical microscope having a mechanical stage on which a specimen slide is to be mounted, the stage being movable in two orthogonal directions by manually- operated stage controllers, and an eyepiece or photo tube through which to view a specimen on the specimen slide, the system including: a first mount that is connectable to the eyepiece or photo tube, and is configured to support a digital image capture device so as to capture digital images of the specimen as viewed through the eyepiece;

a powered drive system that is connectable to each of the manually-operated stage controllers, such that operation of the drive system causes movement of the stage; a second mount for mounting the powered drive system to the microscope; and a controller in communication with the powered drive system, the controller being configured to receive an input representative of an instruction to move the stage and, in response to that input, direct the powered drive system to operate the stage controllers to move the stage;

whereby co-ordinated operation of the image capture device and provision of inputs to the controller enables capture of a series of overlapping digital images from which to generate the digital pathology image of the specimen. In at least some embodiments, the powered drive system includes, for each of the stage controllers, an electric actuator with an output drive member, and a drive train for transferring motion of the drive member to the respective stage controller.

In certain embodiments, each electric actuator is an electric motor with a rotary drive shaft, and each drive train includes an input pulley that is mounted on the drive shaft, and a belt that extends around the input pulley and transfers rotational motion of the input pulley to the respective stage controller.

Preferably, each drive train further includes an output pulley that is releasably mountable to the respective stage controller, and each belt extends around the respective input and output pulleys.

Each output pulley can have a central aperture to locate over the respective stage controller, and one or more locking screws that pass through a screw hole extending from a peripheral edge of the output pulley and open onto the central aperture.

Each electric motor can be a stepper motor. Preferably, each of the input and output pulleys has teeth, and each belt has a complementary tooth profile. The first mount can include a first clamping portion configured to locate around the eyepiece photo tube and releasably clamp the first mount to the eyepiece, and a second clamping portion configured to releasably clamp the image capture device. The second mount can include one or more retaining elements to releasably mount the second mount to a portion of the microscope such that the powered drive system is in a fixed position relative to the stage controllers. In some embodiments, the second mount includes an upper motor mount portion, and a lower motor mount portion, wherein each of the upper and lower motor mount portions includes one of the retaining elements to secure inner ends of the upper and lower motor mount portions to the microscope stage, wherein the electric motors are secured between outer ends of the upper and lower motor mount portions.

In certain embodiments, the controller is configured to receive the inputs by a wireless communication protocol.

In some instances, the image capture device can include a processing unit that is configured to generate an output signal that includes information representative of the magnitude of movement of the stage in each of the orthogonal directions to index the microscope stage to position corresponding with that of the next digital image to be captured in the series, whereby the output signal is provides the input to the controller.

The present invention provides a method of generating a digital pathology image from an optical microscope having an objective beneath which a specimen slide is to be positioned, and an eyepiece or photo tube, the objective and eyepiece or photo tube being at opposing ends of a light path such that a specimen on the specimen slide is viewable through the eyepiece or photo tube, the method involving:

mounting a digital image capture device at the eyepiece or photo tube in a position so as to capture digital images of the specimen as viewed through the eyepiece or photo tube;

providing a powered drive system and a slide holder being associated with the powered drive system, the powered drive system having two or more electric actuators, and being in communication with a controller that is configured to receive an input representative of an instruction to index the slide holder and, in response to that input, direct the powered drive to operate the electric actuators; positioning the powered drive system relative to the optical microscope such that operation of each of the electric actuators causes the slide holder to move in one of two orthogonal directions beneath the objective;

loading a specimen slide containing the specimen into the slide holder; and co-ordinating operation of the image capture device and provision of inputs to the controller so to capture of a series of overlapping digital images from which to generate the digital pathology image of the specimen.

The present invention provides a method of generating a digital pathology image from an optical microscope having a mechanical stage on which a specimen slide is to be mounted, the stage being movable in two orthogonal directions by manually-operated stage controllers, and an eyepiece or photo tube through which to view a specimen on the specimen slide, the method involving:

loading a specimen slide containing the specimen onto the stage;

connecting a powered drive system to each of the manually-operated stage controllers, such that operation of the powered drive system causes movement of the stage, the powered drive system being in communication with a controller that is configured to receive an input representative of an instruction to index the stage and, in response to that input, direct the powered drive to operate the stage controllers to move the stage; and

co-ordinating operation of the image capture device and provision of inputs to the controller so to capture of a series of overlapping digital images from which to generate the digital pathology image of the specimen.

In certain embodiments, the method may involve cropping each raw digital image captured by the image capture device to remove redundant information to form each of the overlapping digital images.

In at least some embodiments, the method further involves stitching at least some of the overlapping digital images to form the digital pathology image. The method may involve transmitting the series of overlapping digital images to another location that is remote from the microscope. In such embodiments, the stitching step may be performed at the other location. The co-ordinating step preferably involves alternately capturing one of the overlapping digital images in the series, and indexing the stage to a position corresponding with the position of subsequent overlapping digital image in the series.

The method can further involve:

determining one or more geometric properties of the specimen; and

determining a set of microscope stage indices required to produce the series based on the geometric properties.

The method can further involve identifying the objective power of the microscope to be used during capture of the series, wherein the step of determining the set of microscope stage indices is also based on the objective power, and the microscope field of view.

In certain embodiments, the method further involves:

identifying an initial position on the specimen slide that is to correspond with the position of the first overlapping digital image in the series, and

moving the microscope stage such that the microscope field of view is at the initial position.

Preferably, the step of determining the set of microscope stage indices is also based on the initial position. In some preferred embodiments, the digital image capture device includes a processor that is configured to generate an output signal that includes information representative of the magnitude of movement of the stage in each of the orthogonal directions to index the microscope stage to position corresponding with that of the next digital image to be captured in the series, whereby the output signal is provides the input to the controller, and whereby the method further involves instructing the image capture device to commence the co-ordinating step.

The present invention also provides an image capture device, including:

a digital camera;

a communications interface; and

a processing unit configured to: capture a plurality of images of an object using the camera; generate movement data for indexing a mechanically actuated stage on which the object is mounted, the stage being movable relative to the field of view of the camera; and

provide said movement data to the communications interface, whereby the communications interface sends one or more output signals for an external controller to control a system for electronically driving the stage;

whereby the plurality of images form a series of overlapping digital images of the object.

The present invention also provides a computer program product for storage on a memory device, and comprising code for:

generating movement data for indexing a mechanically actuated stage on which an object is mounted, the stage being movable relative to the field of view of a camera; provide said movement data to a communications interface, whereby the communications interface sends one or more output signals for a controller to control a system for driving the stage; and

capturing a plurality of images of the object using the camera, wherein the plurality of images form a series of overlapping digital images of the object.

The memory device may be part of an image capture device including the camera, the communications interface and a processor.

In certain embodiments, the generated movement data is representative of an instruction to move the stage in two orthogonal directions that are in a plane perpendicular to the line of sight of the camera.

Preferably, the generated movement data is representative of an instruction to move the electronically driven stage in at least one of the two orthogonal directions by an amount that is less than the field of view of the object as viewed by the camera.

The image capture device can be configured to alternately capture of one of the plurality of images, and generate movement data and send an output signal.

The image capture device can receive inputs that include any one or more of: one or more geometric properties of the object of which the plurality of images are to be captured;

the magnification power of an optical magnification device that is between the camera and the object; and

the position of the camera field of view relative to the object when the first of the plurality of images is captured,

wherein the movement data is generated based on the inputs.

In certain embodiments, the image capture device is configured to crop each raw digital image captured by the camera to remove redundant information to form each of the plurality of images.

In one example, the optical magnification device is an optical microscope.

In one preferred embodiment, the image capture device is a smart phone.

The image capture device can be used in the capture of a series of overlapping digital images of a specimen that is loaded onto a stage of the optical microscope as viewed.

Brief description of the drawings

In order that the invention may be more easily understood, embodiments will now be described, by way of example only, with reference to the accompanying drawings, in which:

Figure 1 : is a front view of an optical microscope, and a system for use in generating digital pathology images, the system being in accordance with a first embodiment of the present invention;

Figure 2 is a first elevation view of region A in Figure 1 ;

Figure 3 is a second elevation view of region A in Figure 1 ;

Figure 4 is an isometric view of the image capture device mount of the system of Figure 1 ;

Figure 5: is an isometric view of an upper motor mount portion of the system of

Figure 1 ; Figure 6: is an isometric view of a lower motor mount portion of the system of Figure 1 ;

Figure 7: is a schematic view of the drive train of the system of Figure 1 ;

Figure 8: is a schematic view of the operation of the system of Figure 1 ;

Figure 9: is a flow chart showing steps in a method of generating a digital pathology image according to a second embodiment of the present invention;

Figure 10: is an elevation view of an image capture device showing a user interface for use in connection with the system of Figure 1 ;

Figure 1 1 : is a schematic representation of a first series of overlapping digital images from which to generate the digital pathology image of a specimen;

Figure 12: is a schematic representation of a second series of overlapping digital images from which to generate the digital pathology image of a specimen;

Figure 13: is a front view of an optical microscope, and a system for use in generating digital pathology images, the system being in accordance with a third embodiment of the present invention;

Figure 14: is a schematic view of a powered drive and support of the system of

Figure 13; and

Figure 15: is a partial front view of an optical microscope, and a system for use in generating digital pathology images, the system being in accordance with a fourth embodiment of the present invention.

Detailed description

Figures 1 to 8 show a system 10 according to a first embodiment of the present invention. The system 10 is capable of generating a digital pathology image from an optical microscope 60 that has a mechanical stage 62 on which a specimen slide (not shown) is to be mounted. As shown most clearly in Figure 8, the stage 60 can be moved in two orthogonal directions by two manually-operated stage controllers 64, 66. An eyepiece 68 allows an operator to view a specimen mounted on the specimen slide at various magnifications depending on the selected objective 70. In use, stage controller 64 provides movement in the X-direction to the stage 62, and stage controller 66 provides movement in the Y-direction to the stage 62.

The system 10 includes a first mount 12 that is connectable to the eyepiece 68. The first mount 12 is configured to support a digital image capture device P so as to capture digital images of the specimen as viewed through the eyepiece 68. A powered drive system 14 is connectable to each of the manually-operated stage controllers 64, 66. As discussed in further detail below, operation of the drive system 14 causes movement of the stage 62. A second mount 16 mounts the drive system 14 to the microscope stage 62. A controller 18 is provided, which is in communication with the drive system 16. The controller 18 is configured to receive an input representative of an instruction to move the stage 62. In response to that input, the controller 18 directs the drive system 16 to operate the stage controllers 64, 66 to move the stage 62. In use of the system 10, co-ordinated operation of the image capture device P and provision of inputs to the controller 18 enables capture of a series of overlapping digital images from which to generate the digital pathology image of the specimen. Further, image stitching processes can be applied to the series of overlapping digital images to form a high resolution, digital pathology image. If desired, the series of overlapping digital images, and/or the digital pathology image can be transmitted electronically to a separate location that is remote to the microscope 60.

Figure 4 shows the first mount 12 in further detail. A first clamping portion is configured to locate around the eyepiece 68 and releasably clamp the first mount 12 to the eyepiece 68. To this end, the first clamping portion 20 has a pair of opposable saddles 20, 22 that can be placed on opposite sides of the eyepiece 68. Two pairs of screws and wingnuts 24 (not shown in Figure 4) secure the saddles 20, 22 on the eyepiece 68. A second clamping portion extends from one of the saddles 22 and is configured to releasably clamp the image capture device. In preferred use of the system 10, the image capture device P is a smart phone with a rearward facing camera. In order to clamp the device P, the second clamping portion includes three tracks 26a, 26b, 26c that are arranged in general crucifix shape. Thus, tracks 26a, 26b are co-linear, and track 26c is orthogonal to both tracks 26a, 26b. Inner ends of the tracks 26a, 26b, 26c meet at a centre of the second clamping portion. A clasp 28 is provided to each of the tracks 26; each clasp 28 can slide along its respective track, and can be fastened in place with a screw and wingnut. The device P can be mounted in the first mount 12, and aligned such th at its rearward facing camera is aligned at the eyepiece 68 to view the image of the specimen slide as viewed through the eyepiece 68.

In the illustrated example, the microscope 60 is an Olympus System Microscope Model BHT BH-2. In this particular microscope, the stage controllers 64, 66 are mounted to move with the stage 62. Accordingly, in this embodiment, the second mount 16 is configured to mount the drive system 14 in a position that is fixed relative to the stage 62. To this end, the second mount 16 includes an upper motor mount portion 30, and a lower motor mount portion 32, which are shown in Figures 5 and 6, respectively. Inner ends of the upper and lower motor mount portions 30, 32 are releasably secured to the microscope stage 62 by retaining elements. It is preferred that the retaining elements do not interfere with operation of the microscope 60. In this example, the inner end of the upper motor mount portion 30 is secured to the top surface of the microscope stage 62 with a double-sided adhesive tape. The inner end of the lower motor mount portion 32 has a through hole through which to pass a screw fastener for secure the lower motor mount portion 32 to the under surface of the microscope stage 62. It will be appreciated that in alternative embodiments, different retaining means may be used, including complementary magnets, hook and loop fasteners, and the like. The outer end of the lower motor mount portion 32 provides a platform on which to secure the powered drive system 14. As is described below, the powered drive system 14 is secured between outer ends of the upper and lower motor mount portions 30, 32.

The powered drive system 14 includes, for each of the stage controllers 64, 66, an electric actuator with an output drive member, and a drive train for transferring motion of the drive member to the respective stage controller. In this particular embodiment, each electric actuator is an electronic stepper motor 34, 36 with a rotary drive shaft. The drive trains for the stage controllers are shown in Figure 7. An input pulley 38 is mounted on the drive shaft of stepper motor 34, and an output pulley 42 that is releasably mountable to the X-direction stage controller 64. A belt 46 extends around the input and output pulleys 38, 42 to transfer rotational motion of the stepper motor 34 to the X-direction stage controller 64. Similarly, an input pulley 40 is mounted on the drive shaft of stepper motor 36, and an output pulley 44 that is releasably mountable to the Y-direction stage controller 66. A belt 48 extends around the input and output pulleys 40, 44 to transfer rotational motion of the stepper motor 36 to the Y-direction stage controller 66. As is most evident from Figures 3 and 7, the pulleys 38, 40, 42, 44 have teeth, and the belts 46, 48 have a complementary tooth profile. In this way, rotation of the stage controllers 64, 66 can be precisely controlled by the stepper motors 34, 36. In Figure 7, the belts 46, 48 are shown schematically. Each output pulley 42, 44 has a central aperture 50, 52 that is shaped to locate over the respective stage controller 64, 66. Screw holes 54 extend from peripheral edge of each output pulley 42, 44 and open onto the central aperture 50, 52. Locking screws 56 pass through the screw holes 54 to secure the output pulleys 42, 44 on the stage controllers 64, 66. Each of the stepper motors 34, 36 has a housing with a pair of through holes.

Screw fasteners extend through the through holes to secure the stepper motors 34, 36 between the outer ends of the upper and lower motor mount portions 30, 32.

When the controller 18 receives an input as previously described, the controller 18 directs the drive system 14 to move the stage 62 to a position that corresponds with the field of view from the eyepiece 68 located at a position for capturing the next image in the series of overlapping digital images. In this particular embodiment, the controller 18 is connected by electrical wires to the stepper motors 34, 36, and provides drive signals through those wires causing the stepper motors 34, 36 to rotate the respective rotary drive shaft. The mechanism that these inputs are provided to the controller 18 is dependent on the particular embodiment. In the illustrated embodiment in which the image capture device P is a smart phone, the input can be an electrical signal that is transmitted, either by a wired connection or wirelessly, to the controller 18. As indicated in Figure 8, the device P can generate an output signal that is transmitted by a wireless communication protocol to the controller 18; the output signal forms the input to the controller 18. The wireless communication protocol can be in any suitable protocol, including (but not limited to) Bluetooth, ANT+, ZigBee, WiFi, NFC, or even a custom communication protocol. In some alternative embodiments, a wireless output signal can be generated by a separate device that is directly connected to the image capture device P.

In some instances, the output signal may consist of an instruction to the controller 18 to operate the powered drive system 14 to index the stage 62 to the next position in a pre-determined series of positions. Alternatively, the output signal can include information representative of the magnitude of movement of the stage 62 in each of the orthogonal directions to index the microscope stage 62 to position corresponding with that of the next digital image to be captured in the series of overlapping digital images.

In some embodiments, the image capture device P can co-ordinate the capturing of images and provision of inputs to the controller 18 (by generation of appropriate output signals) such that an image is captured at a predetermined time interval after the output signal has been sent from that device P. In one alternative, the controller 18 can be configured to generate and transmit a confirmation signal when the powered drive system 14 has arrived at the indexed position. The device P receives that confirmation signal, and captures a digital image of the specimen at the indexed position, before issuing a further output signal as appropriate. In one further alternative, the image capture device P can be configured to analyze the image at the eyepiece 68 after generating the output signal and, when that image has become static for a predetermined period, the device P captures a digital image of the specimen at the indexed position as appropriate.

As will be appreciated, digital image capture devices are typically configured capture rectangular images, whereas the field of view through a microscope eyepiece 68 is typically a circular image of the specimen, and the circular image is surrounded by a vignette. Accordingly, the device P may perform some basic image processing on raw images as captured by the device, such as to crop each raw image to a rectangular image that constitutes one of the overlapping digital images. For instance, the cropping action may remove redundant information to form each of the raw images, such as an image vignette, and/or circular segments surrounding a usable portion of the raw image. The image processing can be implemented either prior to storage of the image, or after that image has been stored.

As is also indicated in Figure 8, the device P can transmit images via one or more wireless or wired networks, such as the internet W, to a remote location. The images transmitted can be any of a collection of raw images of the specimen as captured by the device P, processed images that form the series of overlapping images of the specimen, and/or a digital pathology image that has been processed, including stitched, by the device P.

Figure 9 illustrates show steps in a method 100 of generating a digital pathology image according to a second embodiment of the present invention. The method 100 involves: • loading a specimen slide containing a specimen onto the stage of a microscope - step 102.

• mounting a digital image capture device at the eyepiece of the microscope - step 104;

· connecting a powered drive system to each of the manually-operated stage controllers of the microscope - step 106; and

• co-ordinating operation of the image capture device and provision of inputs to the controller - step 108. The microscope used in connection with the method is to be an optical microscope having a mechanical stage on which a specimen slide containing the specimen is to be mounted, the stage being movable in two orthogonal directions by manually-operated stage controllers, and an eyepiece through which to view a specimen on the specimen slide. The microscope 60 illustrated in Figures 1 to 3, and 8 is an example of such a microscope. Further, in one example, the method 100 can be implemented using the system 10 described and illustrated in reference to Figures 1 to 8, in conjunction with an image capture device P as previously described.

In step 106, the powered drive system is to be connected to the stage controllers such that operation of the powered drive system causes movement of the stage. The powered drive system is in communication with a controller that is configured to receive an input representative of an instruction to index the stage. In response to that input, the controller directs the powered drive to operate the stage controllers to move the stage. In step 108, the operation of the image capture device and provision of inputs to the controller is co-ordinated so to capture of a series of overlapping digital images from which to generate the digital pathology image of the specimen.

The method 100 can further involve stitching at least some of the overlapping digital images to form the digital pathology image - step 1 10.

In some embodiments, step 108 includes alternately capturing one of the overlapping digital images in the series (step 1 12), and indexing the stage (step 1 14) to a position corresponding with the position of subsequent overlapping digital image in the series. Once the final image in the series has been captured, the series of overlapping digital images can then be stitched 1 10 to form the digital pathology image by the image capture device P, or transmitted to another location or processing device for image processing and stitching.

In one illustrative embodiment, the method can further involve determining one or more geometric properties of the specimen. For instance, prior to step 102, an operator may manually take measurements of the specimen on the specimen slide. The measurements may include at least one of specimen diameter, specimen width, and specimen height. As will be appreciated, the term "specimen width" used here may correspond with a dimension of the specimen as measured in one of the X-direction or Y- direction in the reference frame established by the position in which the specimen slide is loaded onto the stage, and X-direction/Y-direction movement of the stage. Further, the term "specimen height" used here may correspond with a dimension of the specimen as measured orthogonally to the specimen width. The measured geometric properties can be used in determining the sequence of movements of the stage in order to capture a series of overlapping digital images of the specimen. In other words, the method can further involve determining a set of microscope stage indices required to produce the series based on the geometric properties.

The method can additionally or alternatively involve identifying an initial position on the specimen slide that is to correspond with the position of the first overlapping digital image in the series, and moving the microscope stage such that the microscope field of view is at the initial position. By way of examples only, the initial position on the specimen slide may be any of: Top, Left corner; Top, Right corner; Bottom, Left corner; Bottom, Right corner; Geometric Centre.

The method may involve prompting the operator to select an initial position, or alternatively a predefined initial position may be utilized. In embodiments in which the initial position is selected by the operator, the step of determining the set of microscope stage indices is also based on the selected initial position.

It will be understood that the objective power of the microscope will influence the upper limit of movement of the stage that enables overlapping images to be captured. It has been determined that at an objective power of 20 ^χ , the upper limit of stage movement in one of the X-direction and Y-direction is approximately 0.8 mm in order to capture images with sufficient overlap that image stitching can be reliably performed. Similarly, it has been determined that at an objective power of 40 ^χ , the upper limit of stage movement in one of the X-direction and Y-direction is approximately 0.4 mm in order to capture images with sufficient overlap that image stitching can be reliably performed. In some embodiments, the method can be performed with a predefined objective power. Alternatively, the method can further involve prompting the operator to select the objective power of the microscope to be used during capture of the series. In embodiments in which the objective power is selected by the operator, the step of determining the set of microscope stage indices is also based on the selected objective power.

It will be appreciated that the method 100 is one example only. In other applications of the method, steps 102 to 108 do not need to be performed in this sequence. For instance, steps 104 and 106 may be performed once during an initial setup of the microscope. Steps 102 and 108 can be performed for a number of different samples, whether on the same specimen slide, or on separate specimen slides.

Figure 10 is a schematic view of a device P that is configured to be used with the system 10, and also to facilitate implementing the method 100. The device P has a user interface 200 that has the capacity for an operator to enter the following parameters of the specimen and microscope:

• Objective power: Field 202 - being the magnifying power of the objective

70 that has been selected on the microscope for use during the capture of the series of images;

• Starting point: Field 204 - being the position on the specimen slide that is to correspond with the position of the first overlapping digital image in the series;

• X-dimension: Field 206 - being the specimen width; and

• Y-dimension: Field 208 - being the specimen height.

The user interface 200 that has the capacity for an operator to drive the microscope stage 62 from the device P. To this end, the microscope stage 62 can be driven in four directions: Left (Field 210); Right (Field 212); Forward (Field 214); and Back (Field 216). As will be appreciated, Left and Right are opposing directions on the X-direction. An operator pressing the Left or Right fields 210, 212 causes the device P to generate an output signal that is representative of the desired movement. That output signal is received by the controller 18 as an input, and the controller 18 directs the powered drive system 14 to cause the X-direction stage controller 64 to rotate in an appropriate direction. Similarly, an operator pressing the Forward or Back fields 214, 216 causes the device P to generate an output signal that is representative of the desired movement. That output signal is received by the controller 18 as an input, and the controller 18 directs the powered drive system 14 to cause the Y-direction stage controller 66 to rotate in an appropriate direction.

The user interface further has a "Start Scan" field 218 that an operator is to press to initiate the capture of the series of overlapping digital images by the device P, in the manner previously described. As will be appreciated, an operator using an optical microscope 60 will typically narrow in on a target location on the specimen slide by alternately moving the stage 62 to position the specimen slide with the target location centred within the field of view at the eyepiece 68, and then increasing the objective power. This process is repeated until the desired objective power is reached. It will be apparent that the microscope has two eyepieces 68. One eyepiece 68 is not utilized by the system 10, and this eyepiece 68 remains available for the operator to use in this initialization procedure.

Figures 1 1 and 12 show a specimen S and, schematically, examples of series of overlapping digital images that are captured and from which to generate the digital pathology image of the specimen. In Figure 1 1 , the microscope field of view is located on the approximate geometric centre of the specimen, and this is the position of first image in the series. Squares 1 to 25 represent the series of overlapping digital images that are captured by the device P using the system 10 and the microscope 60. As is evident from Figure 1 1 , the 25 images in this series are generated by a generally spiroidal movement of the stage 62.

In Figure 12, the microscope field of view is located at the top, left corner of the specimen, and this is the position of first image in the series. Squares 1 to 25 represent the series of overlapping digital images that are captured by the device P using the system 10 and the microscope 60. As is evident from Figure 12, the 25 images in this series are generated by a generally serpentine movement of the stage 62 along the X-and Y-directions.

Figures 13 and 14 show a system 310 according to a third embodiment of the present invention. The system 310 is capable of generating a digital pathology image from an optical microscope 60 that has an eyepiece 68, and an objective 70 beneath which a specimen slide is to be positioned. The optical microscope 60 has a light path that extends between the eyepiece 68 and the objective 70. A specimen on the specimen slide that is placed beneath the objective 70 is viewable through the eyepiece 68. The system 310 is substantially similar to the system 10 of Figures 1 to 8. In

Figures 13 and 14, the features of the system 310 that are substantially similar to those of the system 10 in form and function have the same reference numeral with the prefix "3".

In Figure 13, the first mount 312 is connected to the eyepiece 68. Further, the first mount 312 is rotated approximately 90^e anti-clockwise from a position in which it supports an digital image capture device so as to capture digital images of the specimen as viewed through the eyepiece 68. In the illustrated position, the first mount 312 remains attached to the eyepiece 68, but does not interfere with an operator viewing the specimen on the specimen slide; for instance, to identify an initial position on the specimen slide that is to correspond with the position of the first overlapping digital image in the series.

In the system 310, the powered drive 314 includes electric actuators that, in use of the system, are each operable to cause the specimen slide to move in one of two orthogonal directions beneath the objective 70. In this particular embodiment, there are three electric actuators, in the form of electronic stepper motors 334a, 334b, 336. The stepper motors are discussed in further detail below.

The powered drive 314 further includes a specimen slide holder that is to hold specimen slide. In this embodiment, the specimen slide holder is in the form of a pair of pincers 380 that co-operate to hold the specimen slide. In one form, the pincers 380 may be spring-biased to press against opposing side edges of the specimen slide.

The pincers 380 extend from a platform 382 of the powered drive 314. A drive train coupled to the platform 382 is driven by the stepper motors 334a, 334b, 336. Thus, movement of each of the stepper motors 334a, 334b, 336 is transferred through the drive train to cause the platform 382 to move in a respective one of the orthogonal directions.

The drive train includes a first drive for moving the platform 382 in the first of the two orthogonal directions, and a second drive for moving the platform 382 in the second of the two orthogonal directions. In use, the first drive moves the platform 382 in the X-direction relative to the stage 62 of the microscope, and second drive moves the platform 382 in the Y-direction relative to the stage 62.

In this particular embodiment, the first drive has two X-direction guide rods 384a, 384b that extend in the X-direction. The X-direction guide rods 384a, 384b are spaced apart by a sufficient distance such that in use of the system 310 the stage 62 of the microscope 60 is disposed between the guide rods 384a, 384b. Each rod 384a, 384b is supported at opposing ends by mounting brackets 398 that are part of a support 399 of the system 314. In addition, the first drive includes two X-direction carriages 386a, 386b that are each slidably mounted on one of the X-direction guide rods 384a, 384b.

Stepper motors 334a, 334b operate synchronously to move the X-direction carriages 386a, 386b along their respective guide rods 384a, 384b. To this end, the first drive has two threaded rods 388a, 388b that are each connected to one of the two X- stepper motors 334a, 334b. Each threaded rod 388a, 388b extends parallel to one of the guide rods 384a, 384b, and passes through an internally threaded hole in the respective X-direction carriage 386a, 386b. Accordingly, rotation of the threaded rods 388a, 388b by the X-stepper motors 334a, 334b causes the X-direction carriages 386a, 386b to be displaced along their respective guide rods 384a, 384b.

In this particular embodiment, the second drive has two Y-direction guide rods 390a, 390b that extend in the Y-direction. The ends of the Y-direction guide rods 390a, 390b are mounted in the X-direction carriages 386a, 386b. The platform 382 is slidably mounted on the Y-direction guide rods 390a, 390b. The Y-direction stepper motor 336 is mounted on X-direction carriage 386a. The second drive also has a toothed belt 392 that extends around a toothed drive wheel that is fixedly mounted on an output shaft of the Y- direction stepper motor 336. The toothed belt 392 also extends around a pulley that is rotatably mounted on a shaft in X-direction carriage 386b. The drive wheel and pulley are contained internally within the respective X-direction carriage 386a, 386b, and hence are not shown in the Figures. The platform 382 is fixedly attached to the belt 392 at one location on the belt. Thus, rotational motion of the Y-direction stepper motor 336 is transferred to the belt 392, which displaces the platform 382 along the Y-direction guide rods 390a, 390b. The system 310 is configured such that the specimen slide when mounted in the pincers 380 is supported vertically on the stage 62. To this end, the support 399 is configured, or is configurable, such that the powered drive 314 is supported above a surface (such as a workbench) on which the optical microscope 60 rests. Further, the pincers 380 can hold the specimen slide at a suitable height about the surface that the specimen slide can be vertically supported on the stage 62.

As will be understood, the system 310 requires that the original slide holder of the optical microscope 60 is removed from the stage 62 so as to not interfere with operation of the system 310. Figure 15 shows a portion of a system 410 according to a fourth embodiment of the present invention. Figure 15 also shows a stage 62 and objective 70 of an optical microscope. The system 410 is substantially similar to the system 310, and in Figure 15 the features of the system 410 that are substantially similar to those of the system 310 in form and function have the same reference numeral with the prefix "4" replacing the prefix "3".

The system 410 differs from the system 310 in that the platform 480 includes a support 481 that is connectable to the original slide holder H of the optical microscope 60. To this end, the optical microscope 60 has screws that fasten the original slide holder H to the of the stage 62. These screws are removed to release the slide holder H. In this particular case, the slide holder H is rotated 180° such that the threaded holes in the slide holder H are oriented towards the platform 482. Fasteners 494 then secure the support 481 to the slide holder H. Thus, the slide holder H is moved with the platform 480 by the stepper motors (not shown in Figure 15), as previously described.

Claims

CLAIMS:

1 . A system for generating a digital pathology image from an optical microscope having an objective beneath which a specimen slide is to be positioned, and an eyepiece or photo tube, the objective and eyepiece or photo tube being at opposing ends of a light path such that a specimen on the specimen slide is viewable through the eyepiece or photo tube, the system including:

2. A system according to claim 1 , wherein the powered drive system includes:

a specimen slide holder onto which the specimen slide is mountable;

a platform to which the specimen slide holder is attached; and

3. A system according to claim 1 , wherein the optical microscope includes a specimen slide holder onto which the specimen slide is mountable, and wherein the powered drive system includes:

a platform with a support that is connectable to the specimen slide holder; and a drive train that is coupled to the electric actuators and the platform,

4. A system according to either claim 2 or 3, wherein the drive train includes a first drive for moving the platform in the first of the two orthogonal directions, and a second drive for moving the platform in the second of the two orthogonal directions.

5. A system according to claim 4, wherein the first drive includes:

6. A system according to either claim 4 or 5, wherein the second drive includes: at least one second support member that extends in the second direction;

wherein the platform is displaceable along the at least one second support member by operation of a second of the electric actuators.

7. A system according to any one of claims 2 to 6, wherein the optical microscope includes a stage disposed beneath the objective, and wherein the system is configured such that the specimen slide when mounted in the specimen slide holder is supported vertically on the stage.

8. A system according to any one of claims 1 to 9, further including a support structure for supporting the powered drive system above a surface on which the optical microscope rests.

9. A system for generating a digital pathology image from an optical microscope having a mechanical stage on which a specimen slide is to be mounted, the stage being movable in two orthogonal directions by manually-operated stage controllers, and an eyepiece or photo tube through which to view a specimen on the specimen slide, the system including:

a first mount that is connectable to the eyepiece or photo tube, and is configured to support a digital image capture device so as to capture digital images of the specimen as viewed through the eyepiece or photo tube; a powered drive system that is connectable to each of the manually-operated stage controllers, such that operation of the drive system causes movement of the stage; a second mount for mounting the powered drive system to the microscope; and a controller in communication with the powered drive system, the controller being configured to receive an input representative of an instruction to move the stage and, in response to that input, direct the powered drive system to operate the stage controllers to move the stage;

10. A system according to claim 9, wherein the powered drive system includes, for each of the stage controllers, an electric actuator with an output drive member, and a drive train for transferring motion of the drive member to the respective stage controller.

1 1 . A system according to claim 10, wherein each electric actuator is an electric motor with a rotary drive shaft, and each drive train includes an input pulley that is mounted on the drive shaft, and a belt that extends around the input pulley and transfers rotational motion of the input pulley to the respective stage controller.

12. A system according to either claim 10 or 1 1 , wherein each drive train further includes an output pulley that is releasably mountable to the respective stage controller, and each belt extends around the respective input and output pulleys.

13. A system according to claim 9, wherein each output pulley has a central aperture to locate over the respective stage controller, and one or more locking screws that pass through a screw hole extending from a peripheral edge of the output pulley and open onto the central aperture.

14. A system according to either claim 12 or 13, wherein each of the input and output pulleys has teeth, and each belt has a complementary tooth profile.

15. A system according to any one of claims 9 to 14, wherein the second mount includes one or more retaining elements to releasably mount the second mount to a portion of the microscope such that the powered drive system is in a fixed position relative to the stage controllers.

16. A system according to any one of claims 1 to 15, wherein the first mount includes a first clamping portion configured to locate around the eyepiece or photo tube and releasably clamp the first mount to the eyepiece or photo tube, and a second clamping portion configured to releasably clamp the image capture device.

17. A system according to any one of claims 1 to 16, wherein the controller is configured to receive the inputs by a wireless communication protocol.

18. A method of generating a digital pathology image from an optical microscope having an objective beneath which a specimen slide is to be positioned, and an eyepiece or photo tube, the objective and eyepiece or photo tube being at opposing ends of a light path such that a specimen on the specimen slide is viewable through the eyepiece or photo tube, the method involving:

providing a powered drive system and a slide holder being associated with the powered drive system, the powered drive system having two or more electric actuators, and being in communication with a controller that is configured to receive an input representative of an instruction to index the slide holder and, in response to that input, direct the powered drive to operate the electric actuators;

positioning the powered drive system relative to the optical microscope such that operation of each of the electric actuators causes the slide holder to move in one of two orthogonal directions beneath the objective;

19. A method of generating a digital pathology image from an optical microscope having a mechanical stage with a slide holder on which a specimen slide is to be mounted, the stage being movable in two orthogonal directions by manually-operated stage controllers, and an eyepiece or photo tube through which to view a specimen on the specimen slide, the method involving:

loading a specimen slide containing the specimen onto the stage; mounting a digital image capture device at the eyepiece in a position so as to capture digital images of the specimen as viewed through the eyepiece or photo tube; connecting a powered drive system to each of the manually-operated stage controllers, such that operation of the powered drive system causes movement of the stage, the powered drive system being in communication with a controller that is configured to receive an input representative of an instruction to index the stage and, in response to that input, direct the powered drive to operate the stage controllers to move the stage; and

20. A method according to either claim 18 or 19, further involving cropping each raw digital image captured by the image capture device to remove redundant information to form each of the overlapping digital images.

21 . A method according to any one of claims 18 to 20, further involving stitching at least some of the overlapping digital images to form the digital pathology image.

22. A method according to either claim 18 or 19, further involving transmitting the series of overlapping digital images to another location that is remote from the microscope.

23. A method according to any one of claim 18 to 22, wherein the co-ordinating step involves alternately capturing one of the overlapping digital images in the series, and indexing the slide holder to a position corresponding with the position of subsequent overlapping digital image in the series.

24. A method according to any one of claims 18 to 23, further involving:

determining one or more geometric properties of the specimen; and

determining a set of slide holder indices required to produce the series based on the geometric properties.

25. A method according to claim 24, further involving identifying the objective power of the microscope to be used during capture of the series, wherein the step of determining the set of slide holder indices is also based on the objective power, and the microscope field of view.

26. A method according to any one of claims 18 to 25, further involving:

moving the specimen slide such that the microscope field of view is at the initial position.

27. A method according to claim 26, wherein the step of determining the set of slide holder indices is also based on the initial position.

28. A method according to any one of claims 18 to 27, wherein the digital image capture device includes a processor that is configured to generate an output signal that includes information representative of the magnitude of movement of the slide holder in each of the orthogonal directions to index the slide holder to position corresponding with that of the next digital image to be captured in the series, whereby the output signal is provides the input to the controller, and whereby the method further involves instructing the image capture device to commence the co-ordinating step.

28. An image capture device, including:

a digital camera;

a communications interface; and

a processing unit configured to:

capture a plurality of images of an object using the camera; generate movement data for indexing a movable slide holder on which the object is mounted, the slide holder being movable relative to the field of view of the camera; and

provide said movement data to the communications interface, whereby the communications interface sends one or more output signals for an external controller to control a system for electronically driving the slide holder;

29. An image capture device according to claim 28, wherein the generated movement data is representative of an instruction to move the stage in two orthogonal directions that are in a plane perpendicular to the line of sight of the camera.

30. An image capture device according to either claim 28 or 29, further configured to alternately capture of one of the plurality of images, and generate movement data and send an output signal.

31 . An image capture device according to any one of claims 28 to 30, wherein the image capture device can receive inputs that include any one or more of:

one or more geometric properties of the object of which the plurality of images are to be captured;

wherein the movement data is generated based on the inputs.

32. An image capture device according to any one of claims 28 to 31 , wherein the image capture device is further configured to crop each raw digital image captured by the camera to remove redundant information to form each of the plurality of images.

33. A computer program product for storage on a memory device, and comprising code for:

generating movement data for indexing a movable slide holder on which an object is mounted, the slide holder being movable relative to the field of view of a camera;

provide said movement data to a communications interface, whereby the communications interface sends one or more output signals for a controller to control a system for driving the slide holder; and

34. A computer program product according to claim 33, wherein the generated movement data is representative of an instruction to move the slide holder in two orthogonal directions that are in a plane perpendicular to the line of sight of the camera.