The present invention relates to imaging systems in general and more particularly to molecular imaging systems for use in bioluminescent and biofluorescent imaging applications.
Molecular imaging systems are known in the art and are commonly used to capture various types or modes of images from an object or specimen being analyzed. The object or specimen that may be imaged may comprise any of a wide range of compositions, tissues, and animal specimens, as is well-known. Primarily, such imaging systems are configured to detect extremely low levels of light emitted by the object under study. The light emitted by the object may be generated by a bioluminescence process, a biofluorescence process, or by a combination of both. The resulting emitted light image may be used for any of a wide variety of purposes, including, for example, research studies relating to gene function and disease progression in living organisms.
Such imaging systems may also be capable of capturing reflected light images, in which light reflected by the object is captured by the imaging system camera. The reflected light image may then be used to correlate or compare certain features and attributes of the emitted light image with the external, physical configuration of the object shown in the reflected light image. Typically, the two types of images, i.e., the emitted and reflected light images, are combined with one another to form a combined or composite image. Such a composite image allows a user to more easily correlate features and attributes of the emitted light image(s) with physical locations on the object or other characteristics shown in the reflected light image. Generally speaking, such composite images are particularly useful when studying living organisms in-vivo, although they may be used when studying any type of object, either in-vivo or in-vitro.
An imaging system includes a main enclosure having at least one access door, the main enclosure defining a substantially light-tight imaging compartment when the access door is in a closed position. An object platform defining an image region therein is provided within the imaging compartment of the main enclosure. A primary camera positioned on a first side of the object platform is operable to capture a primary image of the image region on the object platform. An auxiliary camera positioned on the first side of the object platform is operable to produce an auxiliary image of the image region on the object platform.
A method for capturing an image of an object according to one embodiment of the invention may include: Positioning the object on an object platform; capturing an auxiliary image of the object with an auxiliary camera; displaying the auxiliary image of the object on a display device; observing the auxiliary image of the object on the display device; and capturing a primary image of the object with a primary camera.
Illustrative and presently preferred exemplary embodiments of the invention are shown in the drawings in which:
An imaging system 10 according to one embodiment of the present invention is illustrated in
The auxiliary camera 16 may be used to capture reflected light images of the object 12. Such reflected light images may be used to correlate or compare certain features and attributes of the emitted light images with the external, physical configuration of object 12. The reflected light images may also be used to advantage in other situations and circumstances, many of which are described herein and others of which will become apparent to persons having ordinary skill in the art after having become familiar with the teachings provided herein.
Referring now primarily to
The main enclosure 18 of imaging system 10 may be provided with an access door 30 that can be moved vertically between a closed position (shown in
Referring now primarily to
The camera support structure 42 may be configured to receive or mount the primary camera 14 as well as the auxiliary camera 16, as best seen in
The primary and auxiliary cameras 14 and 16 are mounted adjacent one another on a first side 64 (
The primary camera 14 of image system 10 may comprise a high-performance, high-sensitivity camera suitable for capturing the extremely low light intensities typically emitted by biofluorescent and bioluminescent objects 12. During operation, the light sensitive element (not shown) of the primary camera 14 may be cooled to very low temperatures to improve the sensitivity, dynamic range, and signal-to-noise ratio of the camera.
In contrast to the primary camera 14, the auxiliary camera 16 may comprise a general purpose electronic (e.g., CCD) camera of the type commonly used in cellular telephones and so-called “consumer grade” cameras. The auxiliary camera 16 may be used to capture an auxiliary image of the object 12 provided in the imaging compartment 32. In most embodiments, the auxiliary image produced by the auxiliary camera 16 will comprise a reflected light image of the object 12. The auxiliary camera 16 may be operated in a still picture mode and in a video image mode. When operated in the still picture mode, the auxiliary image captured by auxiliary camera 16 will comprise a still or non-moving image of the object 12. When operated in the video image mode, the auxiliary image captured by auxiliary camera 16 will comprise a video or moving picture image of the object 12.
The imaging system 10 may be operated as follows to capture various kinds of images of the object 12. A first step in the process may involve positioning the object 12 on the object platform or stage 40 (
At this point, the user may observe the auxiliary image on the display system(s) 24 and/or 34 to confirm that the object 12 is positioned at a desired location and orientation on the object platform 40. For example, the user can ensure that the object 12 is positioned within a preferred image region 66 (
In one embodiment, the imaging system 10 is configured to display (i.e., on display systems 24 and/or 34) an image area outline 66′ along with the auxiliary image, as best seen in
Once the user has properly positioned, and, if necessary, re-positioned, the object 12 on the object platform 40, the access door 30 may be moved to the closed position. When the access door 30 is closed, the imaging compartment 32 will be substantially light-tight, thereby allowing the primary camera 14 to capture the extremely low-light (i.e., emitted light image) produced by the bioluminescent and/or biofluorescent object 12. If the object is bioluminescent, then the primary camera 14 may directly capture an emitted light image of the object 12 by opening a shutter (not shown) on the primary camera 14 for a time sufficient to capture the desired low-light bioluminescent image. Alternatively, if a biofluorescent image of the object 12 is to be captured, then the fluorescent material(s) in the object 12 will first need to be activated or excited. In one embodiment, the excitation of the biofluorescent material in the object 12 may be activated or excited by illuminating the object 12 with excitation light of the appropriate wavelength, which may be provided by one or more of the light sources 62 provided in light source assembly 56. After an appropriate period of time, the excitation light source(s) 62 may be extinguished. An emitted light image of the now biofluorescing object 12 then may be captured by the primary camera 14.
The primary (i.e., emitted light) image(s) captured by the primary camera 14 may be displayed on display system 24. Such images may also be displayed on the auxiliary display system 34, if desired. At some point during the imaging process, e.g., either before or after the capture of the emitted light image by the primary camera 14, the imaging system 10 may activate the auxiliary camera 16 to capture an auxiliary image of the object 12. In many cases, the auxiliary image captured by the auxiliary camera 16 will comprise a reflected light “still” image of the object 12, as opposed to a video image. Moreover, such an auxiliary image usually will be captured with the access door 30 still in the closed position. Light sufficient for illuminating the object 12 may be provided by activating one or more of the light sources 62 comprising light source assembly 56. The auxiliary image from the auxiliary camera 16 can then be combined with the primary image from the primary camera 14 to produce a composite image 68, i.e., an image comprising both the emitted and reflected light images of the object 12, as best seen in
In some embodiments (e.g., wherein the auxiliary camera 16 is displaced from the primary camera 14, as described below), it may be necessary or desirable to transform the auxiliary image so that it is in substantial registration with the primary image. If so, image processing system 70 may use one or more image transformation techniques to transform the auxiliary image data so that features thereof are in substantial registration with corresponding features in the primary image data.
Significant advantages and beneficial features of the imaging system 10 according to the present invention are associated with the provision of the primary and auxiliary cameras 14 and 16. For example, the provision of the auxiliary camera 16 allows a user to readily confirm (i.e., by viewing displays 24 and/or 34) that the object 12 has been properly positioned and oriented on the image platform 40 without the need to activate the primary camera 14. Moreover, in an embodiment wherein the auxiliary camera 16 may be operated in a video image mode, the user may position and orient the object 12 on the object platform 40 with reference to a real-time video image provided on the display device(s) 24 and/or 34. Generally speaking, the presentation of such a real-time video image on the auxiliary display device 34 provided on the access door 30 will allow the user to rapidly position (or re-position) the object 12 on the object platform 40 by simply viewing the video image presented on auxiliary display system 34. That is, the auxiliary display system 34 will be in a convenient position for the user during the object positioning step. Still further, in an embodiment wherein the system 10 is configured to display an image area outline 66′ (
The provision of the imaging system 10 with both the primary and auxiliary cameras 14 and 16 provides yet other significant advantages not recognized in the art. For example, conventional imaging systems use the primary camera to capture or take both emitted light and reflected light images of the object. However, the primary camera is ill-suited to capture reflected light images, primarily because of the high light levels typically involved. Even if care is taken to ensure that the ambient light levels are sufficiently low, the light levels involved may still impair the ability of the primary camera to subsequently capture high quality emitted light images of the object.
More specifically, the high-performance, high-sensitivity cameras used by such conventional imaging systems are highly sensitive to a so-called residual or latent image phenomenon when exposed to high light levels, either within a localized region of the light sensor or over its entire area. The residual or latent image phenomenon not only degrades the current image, but also results in the formation of a residual image that appears in subsequent images captured by the camera. In extreme cases, it may be necessary to deactivate the camera cooling system and allow the image sensor to warm in order to dissipate the latent image. Obviously, such a remedy is less than desirable in day-to-day operations of such devices.
Because the residual or latent image problem is currently viewed as inherent in such systems, manufacturers typically select primary cameras that have the most favorable performance specifications relating to the latent image phenomenon, commonly referred to as a latent image specification. Significantly, however, not all light sensors manufactured by a given fabrication process have the same latent image specification. Thus, in conventional systems it is necessary to select only those image sensors having the best latent image specifications. A significant advantage of the present invention is that the imaging system 10 does not require a primary camera 14 having such a favorable latent image specification, thereby allowing a wider range of primary cameras to be used. Stated another way, because the primary camera 14 of the present invention need not be used to capture a reflected light image of the object 12, the latent image specification of the primary camera 14 may be considerably relaxed compared to those required for conventional imaging systems.
Still further, and as discussed above, the provision of an auxiliary camera 16 that can be operated in both a video image mode and a still picture mode provides additional advantages. For example, operating the auxiliary camera 16 in the video image mode allows the user to observe the position and orientation of the object 12 in real-time simply by observing the video image presented on the display 24 and/or the auxiliary display 34. The ability to display such video images provides significant advantages over conventional systems because the primary cameras thereof cannot be operated in a video image mode. Even if they could, there is still a concern about operating the primary camera in circumstances involving high light levels, such as when the door 30 is open.
Yet other advantages of the present invention are associated with the display of the image area outline 66′ along with the video image provided by the auxiliary camera 16. As mentioned, the displayed image area outline 66′ allows the user to readily confirm that the object 12 is positioned at the desired location on the object platform 40. Therefore, the object platform 40 itself need not be provided with an indication of the boundaries of the preferred image region 66. Still further, because most such indications are typically provided by paints or dyes (for easy recognition by the user), there is no need to avoid the use of paints or dyes that may be luminescent or fluorescent. With the present invention, there is no need to provide such an indication on the object platform 40.
Still yet other advantages are associated with the movable mounting arrangement for the auxiliary camera 16. For example, the ability to move the auxiliary camera 16 to the second position (i.e., wherein the image axis 52 of auxiliary camera 16 is substantially aligned with the image axis 54 of primary camera 14) simplifies subsequent image processing steps. Moreover, the ability to move the auxiliary camera 16 in the longitudinal direction 48 allows the auxiliary camera 16 to be conveniently moved out of the field of view 50 of primary camera 14 when primary camera 14 is to be used.
Having briefly described one exemplary embodiment of an illumination system 10 according to the present invention, as well as some of its more significant features and advantages, various embodiments of the illumination system 10 will now be described in detail.
Referring back now to
Computer system 20 may comprise a conventional “PC” type of computer system and may be provided with a display system 24, along with one or more input devices, such as a keyboard 26 and a mouse 28. The computer system 20 may be provided with one or more software packages or computer programs that allow the computer system 20 to interface with the imaging system 10. The computer program(s) may be configured to allow the computer 20 to control various functions and operations of the imaging system 10. In addition, the computer programs may be configured to perform various image processing functions to allow the various primary and auxiliary images to be displayed on display system(s) 24, 34 in the manner described herein. Alternatively, some or all of the image processing may be performed by the image processing system 70 contained within main enclosure 18.
Software suitable for providing the functionality described herein may be readily provided by persons having ordinary skill in the art after having become familiar with the teachings provided herein. Consequently, the particular computer programs or software packages that may be provided to computer system 20 will not be described in further detail herein, other than to note those functions and processes that may be implemented thereby.
As briefly described above, the main enclosure 18 of imaging system 10 may be provided with an access door 30 that can be moved vertically between a closed position (shown in
In one embodiment, the access door 30 may be provided with an auxiliary display system 34, as best seen in
In the particular embodiment shown and described herein, the imaging system 10 may include an imaging system sub-assembly 38 comprising an object platform or stage 40 as well as a mounting or camera support structure 42, as best seen in
The camera support structure 42 may also mount a light source assembly 56. In the particular embodiment shown and described herein, light source assembly 56 may comprise a generally round or circular structure defining a central opening 58 therein that is sized to receive a lens assembly 60 of primary camera 14, in the manner best seen in
Light source assembly 56 may comprise a plurality of light sources 62 suitable for illuminating the object 12 with light in various wavelength regions or bands. More specifically, the light sources 62 may be used to produce excitation light of a wavelength range suitable for exciting the particular fluorescent material in the object 12 to be imaged. Because the imaging system 10 is designed or configured to image a wide variety of fluorescent materials, each of which may require excitation light of a different wavelength or wavelengths, each of the light sources 62 of light source assembly 56 produces light in a different wavelength range. Accordingly, a wide range of fluorescent materials may be excited or made to fluoresce by simply activating the particular light source or sources 62 that produce light in a wavelength range suitable for exciting the particular fluorescent material to be imaged. In the embodiment shown and described herein, at least one of the light sources 62 may comprise a broad-band (e.g., white light) source suitable for illuminating the object 12. So illuminating the object 12 with a broad-band or white light source will allow the auxiliary camera 16 to capture a true color reflected light image of the illuminated object 12, if desired.
Camera support structure 42 may also be configured to receive various other components and systems (e.g., motor and camera control systems as well as a cooling system for the primary camera 14) required to capture various kinds of images (e.g., emitted and reflected light images) of the object 12. However, because a detailed description of such other components and systems is not required to understand and practice the current invention, the particular components and systems that may also be provided to the imaging system 10 will not be described in further detail herein.
Referring now to FIGS. 3 and 5-7, the auxiliary camera 16 may be moveably mounted to camera support structure 42 by means of gantry assembly 46. Gantry assembly 46 allows the auxiliary camera 16 to be translated or moved along longitudinal direction 48, as best seen in
Referring now primarily to
In one embodiment, the actuator system 80 comprises a lead screw 84 mounted for rotation on guide rail 76. A lead screw follower or nut assembly 86 mounted to the transverse support member 74 (to which is mounted auxiliary camera 16) and engaged with lead screw 84 moves the auxiliary camera 16 along the guide rails 76, 78 (i.e., in longitudinal direction 48) in response to rotation of the lead screw 84. A drive motor 88 operatively connected to lead screw 84 rotates lead screw 84, thereby causing the auxiliary camera 16 to move along the guide rails 76, 78 in the longitudinal direction 48 in the manner already described.
The position sensor 82 may comprise a rotary encoder (not shown) operatively connected to the lead screw 84 that produces an output signal relating to the rotation of the lead screw 84. Alternatively, a linear encoder or sensor may be used to sense linear movement or translation of the auxiliary camera 16 along the guide rails 76, 78.
When it is desired to capture an image with auxiliary camera 16, the actuator system 80 may be operated to move auxiliary camera 16 along gantry assembly 46 until auxiliary camera 16 is substantially aligned with primary camera 14, i.e., so that the image axis 52 of auxiliary camera 16 is substantially aligned with image axis 54 of primary camera 14. Auxiliary camera 16 may then be used to capture auxiliary images. When the auxiliary camera 16 is no longer needed, the actuator system 80 may again be operated to move the auxiliary camera 16 along the gantry assembly 46 until it is at a position that will not substantially obstruct the field of view 50 (
Other mounting arrangements for the auxiliary camera 16 are possible. For example, another embodiment may mount an auxiliary camera 16′ to the light source assembly 56, as best seen in
The primary camera 14 of image system 10 may comprise any of a wide range of high-sensitivity cameras that are now known in the art or that may be developed in the future that are or would be suitable for capturing the extremely low light intensities associated with bioluminescent and/or biofluorescent objects 12. Consequently, the present invention should not be regarded as limited to any particular primary camera 14. Moreover, and as discussed above, a significant advantage of the present invention is that it will allow primary cameras 14 having lowered or relaxed latent image specifications to be used, in that the primary camera 14 need not be used to capture reflected light images of the object. Cameras suitable for use as the primary camera 14 may be obtained from Spectral Instruments, Inc., of Tucson, Ariz.
Auxiliary camera 16 (and/or auxiliary camera 16′) may comprise any of a wide range of cameras suitable for providing the desired image functionality. For example, it is generally preferred, but not required, that the auxiliary camera 16 be operable in both a still picture mode and in a video image mode. Operation of the auxiliary camera 16 in the video image mode will allow a video image to be displayed on the display system(s) 24 and/or 34 while the user is placing the object 12 on the object platform 40. The user will then be able to view the placement of the object 12 in real time. The auxiliary camera 16 may later be operated in the still picture mode to capture a reflected image of the object 12 suitable for combination with the emitted light image captured by the primary camera 14.
In accordance with the foregoing considerations, then, the auxiliary camera 16 may comprise any of a wide range of cameras that are now known in the art or that may be developed in the future that are, or would be, suitable for providing the desired functionality and for the particular application. Consequently, the present invention should not be regarded as limited to any particular type of camera. By way of example, in one embodiment, the auxiliary camera 16 comprises a CCD camera of the type commonly used in cellular telephones.
The imaging system 10 may be operated as follows to capture various kinds of images, particularly low-light or emitted light images of the object 12. In a first step, the user may position the object 12 on the object platform 40 (
At this point, the user may observe the auxiliary image on the display system 24 and/or auxiliary display system 34 to confirm that the object 12 is positioned at a desired location and in a desired orientation on the object platform 40. For example, the user can ensure that the object 12 is positioned within the preferred image region 66 (
In one embodiment, the imaging system 10 is configured to display an image area outline 66′ on the display system 24 and/or auxiliary display system 34 along with the auxiliary image, as best seen in
Once the user has properly positioned, and, if necessary, re-positioned, the object 12 on the object platform 40, the access door 30 may be moved to the closed position. When the access door 30 is closed, the imaging compartment 32 will be substantially light-tight, thereby allowing for the capture of the extremely low-light (i.e., emitted light image) produced by the bioluminescent and/or biofluorescent object 12. If the object 12 is bioluminescent, then the primary camera 14 may immediately capture an emitted light image of the object 12 by opening a shutter (not shown) on the primary camera 14 for a time sufficient to capture the desired low-light bioluminescent image. Alternatively, if the object 12 is biofluorescent, then the fluorescent material(s) in the object 12 may first be activated or excited by illuminating the object 12 with excitation light of the appropriate wavelength. In the particular embodiment shown and described herein, the excitation light may be provided by one or more of the light sources 62 of light source assembly 56, as best seen in
The primary (i.e., emitted light) images captured by the primary camera 14 may be displayed on display system 24 and/or auxiliary display system 34. At some point during this process, e.g., either before or after the capture of the emitted light image, the imaging system 10 may capture an auxiliary image of the object 12. Generally speaking, the auxiliary image will comprise a reflected light “still” image of the object 12. The auxiliary image may be captured with the access door 30 still in the closed position. Light sufficient for illuminating the object 12 may be provided by activating one or more of the light sources 62 of light source assembly 56.
The auxiliary image from the auxiliary camera 16 may comprise a color image and may be displayed on display system(s) 24, 34 as a color image. Alternatively, the image from the auxiliary camera 16 may be converted into a grayscale image before it is displayed on the display system(s) 24, 34. Generally speaking, it will be desirable to convert the auxiliary image to a grayscale image so that color renditions thereof do not interfere with the emitted light image, which typically comprises a “false color” image to more readily depict the variations in intensity levels of the emitted light image.
As mentioned above, the auxiliary image from the auxiliary camera 16 may also be combined with the primary image from the primary camera 14 (e.g., by an image processing system 70 and/or as may be implemented in software running on computer system 20) to produce a composite image 68, i.e., an image comprising both the emitted and reflected light images of the object 12. See
In an embodiment wherein the auxiliary camera 16 is displaced from the primary camera 14, the image processing system 70 may be configured to first transform the auxiliary image so that it is in substantial registration with the primary image. Techniques and processes for conducting such image transformations are well-known in the art and could be readily provided by persons having ordinary skill in the art after having become familiar with the teachings provided herein. For example, in one embodiment, a suitable transfer function may be arrived at or developed by placing a calibration grid on the object platform 40. Images of the calibration grid may then be captured by both the primary camera 14 and the auxiliary camera 16. The image processing system may then transform or “warp” the auxiliary image to the corresponding primary image by correlating the corresponding grid locations and features from the two images. The developed transfer functions may then be used by the image processing system to transform subsequent auxiliary images so that they are in substantial registration with the primary images captured by primary camera 14.
Having herein set forth preferred embodiments of the present invention, it is anticipated that suitable modifications can be made thereto which will nonetheless remain within the scope of the invention. The invention shall therefore only be construed in accordance with the following claims:
This application claims the benefit of U.S. Provisional Patent Application No. 61/450,463, filed on Mar. 8, 2011, and U.S. Provisional Patent Application No. 61/529,727, filed on Aug. 31, 2011, both of which are hereby incorporated herein by reference for all that they disclose.
Number | Date | Country | |
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61450463 | Mar 2011 | US | |
61529727 | Aug 2011 | US |