Abstract:
A system for macroscopic and confocal imaging of tissue having a macroscopic imager for capturing a macroscopic image of the tissue&#39;s surface, a confocal imager for capturing one or more optically formed sectional microscopic images on or within tissue, a computer for receiving images from such imagers, and a tissue attachment device in which the macroscopic imager and confocal imager are each individually presented to the tissue utilizing the tissue attachment device in a predefined alignment, such that imaging locations of the confocal imager with respect to the tissue surface spatially correlate with macroscopic image. A user interface is operable on the computer to enable display of the macroscopic image on a display coupled to the computer, and to indicate a region within the macroscopic image associated with the field of view of the tissue imagable by the confocal imager. The user interface enables graphical tracking and targeting of imaging locations of the confocal imager in macroscopic image, and marking on the macroscopic image of the locations of confocal images with respect to the tissue surface.

Description:
FIELD OF THE INVENTION 
     The present invention relates to a system (and method) for macroscopic and confocal imaging of tissue, and relates particularly to a system for macroscopic and confocal imaging of tissue having a macroscopic imager and a confocal imager each individually presentable to tissue, via a tissue attachment device, in a predefined alignment which spatially correlates images from the confocal imager within an image from the macroscopic image. Also, the present invention relates to a user interface operable on a computer coupled to such macroscopic and confocal imagers to enable display of the macroscopic image and confocal images from the macroscopic and confocal imagers, respectively, and graphical tracking and targeting of imaging locations of the confocal imager in the macroscopic image, and marking on the macroscopic image of the locations of selected confocal images with respect to the tissue surface. 
     BACKGROUND OF THE INVENTION 
     Confocal microscopes optically section tissue to produce sectional microscopic images of tissue, referred to herein as confocal images. An example of a confocal microscope is the VivaScope® manufactured by Lucid, Inc. of Rochester, N.Y. Other examples of confocal microscopes are described in U.S. Pat. Nos. 5,788,639, 5,880,880, and 5,995,867, and in articles by Milind Rajadhyaksha et al., “In vivo Confocal Scanning Laser Microscopy of Human Skin: Melanin provides strong contrast,” The Journal of Investigative Dermatology, Volume 104, No. 6, June 1995, and Milind Rajadhyaksha and James M. Zavislan, “Confocal laser microscope images tissue in vivo,” Laser Focus World, February 1997, pages 119-127. The confocal microscope may image naturally or surgically exposed in-vivo tissue, which is useful to evaluate a lesion in tissue without needing a biopsy and pathological evaluation on slides of histologically prepared, mechanically sectioned, tissue specimens from such biopsy. Also, confocal microscopes are useful for pathological examination of ex-vivo tissue, i.e., tissue removed from a patient, without requiring that such tissue be mechanically sectioned and histologically prepared for viewing on slides with a traditional microscope. 
     Systems have been developed for obtaining a macroscopic image of tissue for use in locating where sectional microscopic images were imaged in such tissue by a confocal microscope. U.S. Pat. Nos. 6,684,092 and 5,836,877 describe a telepathology system having a camera and confocal imager in a fixed spatial relationship, in which both are presented over the tissue, such that the camera captures a macroscopic image and the confocal imager captures one or more confocal images. Instead of the camera, the confocal imager described in these patents may utilize a different objective lens to obtain the macroscopic image. The locations for imaging by the confocal imager may be selected automatically, or manually by the user using the macroscopic image. The macroscopic image and confocal images taken are then viewable on the display of the computer, in which the location of confocal images may be referenced in the macroscopic image of the tissue. 
     U.S. Pat. No. 6,411,434 describes a system for imaging ex-vivo tissue in a cassette, where a camera views one side of the tissue to provide a macroscopic image, and on the other side of the tissue is imaged by a confocal microscope. A display can provide an image of both the macroscopic image and confocal images in which the relative location of the microscopic image is indicated by an outlined region in the displayed macroscopic image. 
     U.S. patent application Ser. No. 10/471,332, filed Feb. 23, 2004, which has priority to International Patent Application No. PCT/US02/07173, published on Sep. 19, 2002 under International Publication No. WO02/073246A2, describes a confocal microscope having a macroscope, and a turret having different objective lens to enable selection of an objective lens for macroscopic imaging or microscopic imaging, in which light from the tissue through the selected objective lens is provided to optics of the macroscope or confocal microscope, respectively. Sites may be marked, such as on a printout, of the macroscopic image, and then using the macroscopic image on a display, the tissue is moved to each site for obtaining sectional microscopic confocal image(s). 
     Other systems for locating confocal images captured by a confocal microscope have been developed without use of a camera or macroscopic image. For example, U.S. Pat. Nos. 6,424,852 and 6,745,067 each describe a pen or marker mechanically coupled to a translation stage of a confocal microscope to record movements of the stage on a paper pad or recording medium below the pen or marker. U.S. Pat. No. 6,745,067 also describes a system for marking on a physical recording medium located on the tissue, such as a label, after confocal imaging of the tissue is completed, in which the marks placed are in accordance with one or locations of selected confocal images during confocal imaging of the tissue. 
     Although the above-described systems are useful, it would be desirable if the macroscopic imaging means need not be physically integrated into the confocal microscope, such that the imaging head of the confocal microscope may be made less complex and smaller, and that the spatial relationship between a camera and confocal microscope were mechanically assured by their individual alignment to the same tissue attachment device, so as to facilitate the tracking, targeting, and marking of confocal images in a macroscopic image captured by such camera. 
     It would further be desirable to provide means for assisting a physician in future examinations of the same tissue to observe possible changes in the condition of the tissue when treatment of the lesion is deferred or is non-invasive. 
     SUMMARY OF THE INVENTION 
     Accordingly, it is one object of the present invention to provide a system for macroscopic and confocal imaging of tissue having a macroscopic imager and a confocal imaging head of a confocal microscope, where the macroscopic imager and confocal image head are each individually aligned to the same tissue attachment device for imaging tissue. 
     It is another object of the present invention to a system for macroscopic and confocal imaging of tissue having a computer system coupled to a macroscopic imager and confocal microscope for receiving macroscopic and confocal images, respectively, having a user interface facilitating the tracking, targeting, and marking of confocal images in a macroscopic image captured by such macroscopic imager. 
     It is a further would object of the present invention to a system for macroscopic and confocal imaging of tissue to having a computer system coupled to a macroscopic imager and confocal microscope for receiving macroscopic and confocal images, respectively, having a user interface which enables morphing of macroscopic images of the same tissue captured at different times to observe possible changes in the condition of the tissue. 
     Briefly described, the present invention embodies a system for imaging tissue having a macroscopic imager for capturing a macroscopic image, and a confocal imager for capturing one or more optically formed sectional microscopic (confocal) images on or within tissue, a tissue attachment device, such as a tissue ring, in which the macroscopic imager and confocal imager are each individually presented to the tissue utilizing the tissue attachment device in a predefined alignment with the device, thereby imaging locations of the confocal imager with respect to the tissue surface spatially correlate with the macroscopic image. A computer system is coupled to the macroscopic imager and microscopic imager, and has a display, and memory for storing at least one macroscopic image received from the macroscopic imager and confocal images when received from the confocal imager. 
     A user interface operable on the computer system enables display of the macroscopic image on a display coupled to the computer system, and then indicates a region within the macroscopic image associated with a field of view of the tissue imagable by the confocal imager. The user interface enables graphical tracking of the imaging location of the confocal imager in the macroscopic image, and targeting the confocal imager to capture confocal images at one or more imaging locations selected in the macroscopic image. The user interface also enables marking on the displayed macroscopic image of one or more locations of confocal images captured by the confocal imager that were selected by the user for storage in memory of the computer system. Such markings may be capable of indicating different types of confocal image capture. 
     The computer system may be capable of storing different macroscopic images of the same area of tissue captured at different times, and the user interface morphs (or overlays) two of the macroscopic images of the same area of tissue to produce a morphed (or overlaid) image, and user control of the contribution of the two macroscopic images in the morphed image so as to enable viewing of changes in the same area of tissue over the time period associated with the two macroscopic images. 
     The invention further embodies a method having the steps of displaying a macroscopic image of the surface of tissue captured by a macroscopic imager, indicating a region within the displayed macroscopic image associated with a field of view imagable by a confocal imager, tracking the two-dimensional position of the confocal imager with respect to the surface of the tissue in the displayed macroscopic image, targeting in the displayed macroscopic image the two-dimensional position of confocal images captured by the microscopic imager with respect to the tissue, and marking on the displayed macroscopic image the location of one or more user selected confocal images. 
     The user interface represents a graphical user interface operable on a computer system to provide a window displaying a macroscopic image, in which a region is indicated within the macroscopic image that is associated with the tissue imagable by a confocal imager. One or more first graphical elements are provided for enabling tracking and targeting in the region of a two-dimensional imaging location of the confocal imager with respect to the surface of the tissue, and one or more second graphical elements are provided for enabling marking in the region of the window the location of one or more of the confocal images after being captured by the confocal imager and stored in memory by the computer system. The macroscopic image in the window represents a current macroscopic image. The user interface may also have another window selectable by the user displaying one or more previously captured macroscopic images of the same area of tissue. When one of such previously captured macroscopic images is selected, a graphical slide is provided in which the window has an overlaid image of the selected previously captured macroscopic image on the current macroscopic image, in which the contribution of the current and previous macroscopic images in the first window is adjustable by the user utilizing the graphical slide such that the images morph (or blend) into each other. 
     The user interface of the present invention may be a combined user interface for displaying image from the macroscopic imager and confocal microscope on a single screen, or different screens may be used to provide macroscopic image and confocal images. 
     Although the application describes confocal imagers for imaging optical formed microscopic sections utilizing confocal microscopy, other imager may be used to provide optical formed microscopic sections operating in accordance with two-photon microscopy or optical coherence tomography. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The foregoing objects, features and advantages of the invention will become more apparent from a reading of the following description in connection with the accompanying drawings, in which: 
         FIG. 1  is a block diagram of the system of the present invention having a confocal microscope with a confocal imager (or imaging head), and a computer system, and a macroscopic imager coupled to the same computer system; 
         FIG. 1A  is a perspective view of tissue attachment device, or tissue ring, attachable to the macroscopic imager and the confocal imager of  FIG. 1 ; 
         FIG. 2A  is a perspective view of the macroscopic imager of  FIG. 1  and the tissue attachment device of  FIG. 1A ; 
         FIG. 2B  is an exploded view of the macroscopic imager of  FIG. 1 ; 
         FIG. 2C  is an exploded view of the tissue mount ring of the macroscopic imager of  FIG. 2B ; 
         FIG. 3  is a partial view of the front of the macroscopic imager of  FIG. 1  when connected and aligned to the tissue attachment device of  FIG. 1A  which is adhesively coupled to the surface of tissue via a window; 
         FIG. 4  is a partial view of the front of the confocal imager of  FIG. 1  when connected and aligned to the tissue attachment device of  FIG. 1A  which is adhesively coupled to the surface of tissue via a window; 
         FIGS. 5 ,  6 , and  7  are examples of the user interface operable on the computer system of  FIG. 1  showing example of a macroscopic image captured by the macroscopic imager in which a central square region in such window represents the imagable area of the tissue by the confocal imager; 
         FIG. 8  is an example of another window of the user interface of  FIGS. 5-7  operable on the computer system of  FIG. 1  for viewing one or more previously captured macroscopic images stored in memory of the computer system; 
         FIG. 9  is an example of a dialog screen of the user interface of  FIGS. 5-7  for display and storing information about one of the images of  FIG. 8 ; and 
         FIG. 10  is an example of another user interface operable on the computer system of  FIG. 1  for viewing on the same screen of the display of the computer system images from the macroscopic imager and confocal imager. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring to  FIG. 1 , the system  10  has a confocal microscope  12  as described in U.S. patent Ser. No. 10/557,461, filed Nov. 18, 2005, having priority to International Patent Application No. PCT/US04/16255, and published Dec. 2, 2004 under International Publication No. WO 2004/104645A2. Such confocal microscope may be a VivaScope®1500 manufactured by Lucid Inc. of Rochester, N.Y. Confocal microscope  12  has a computer system  14 , such as a personal computer (PC), coupled to a display  16 . The computer system  14  receives confocal images representing optically formed microscopic sectional images, such as cells or other tissue structures, from a confocal imager (imaging head)  18  that is gimble mounted on a multi-axis arm mechanism  20  having front and rear arms  21  and  22 . The confocal imager  18  has a nose tube  24 , preferably made of clear plastic, which is attached to a conical hub  26  on the front of the confocal imager  18 . Handles  28  are manually grasped and moved to permit multi-axis movement of the confocal imager. Cables extend along arms  21  and  22  to supply power and enable communication between confocal imager  18  and computer system  14 . There are three stepper motor drivers provided in confocal imager  18  which drive an X direction stage drive motor, a Y direction stage drive motor, and a motor which moves the objective lens of the confocal optics in the confocal imager in the Z direction, respectively, where X, Y, Z are orthogonal dimensions. In imaging tissue, X and Y dimensional are substantially parallel to the surface of tissue being imaged on or through, and Z is substantially perpendicular to such surface to control depth of confocal imaging. The motors are driven either by the user changing the imaging position via the computer system sending signals such motor(s), or via buttons on a control panel  29 . As confocal microscope  12  is described in U.S. patent Ser. No. 10/557,461 and International Patent Application No. PCT/US04/16255, which are herein incorporated by reference, a detailed discussion of the confocal microscope  12  and its confocal imager  18  are not provided herein. 
     System  10  further has a macroscopic imager (or camera)  32  which is connected for data communication via a cable  31  to a port, such as a USB port, of computer system  14 , such that the computer system can receive macroscopic images from imager  32 . Conventional hardware and software at the imager  32  and computer system  14  may be provided for interfacing and communicating digital images. 
     Referring to  FIGS. 2A and 2B , macroscopic imager  32  is shown in more detail. Imager  32  has a housing  34  which is formed by the mating rear housing member  34   a  and front housing member  34   b . Housing members  34   a  and  34   b  may be of molded plastic. A pair of printed circuit boards  36  supports the imaging electronics, and includes a CCD array  38 . Such CCD array  38  may be a color CCD array similar to that used in a conventional digital camera. The imaging electronics may have a microcontroller or microprocessor programmed to operate the camera for providing live images from the CCD array  38 , via cable  31 , to computer system  14 , and sending a high resolution still image when a switch  41  is pressed, via a cable  31 , to computer system  14 . Internal electronic components for enabling operation of the imager  32  may be manufactured by Lumenera Corp. of Canada, under model no. Lu100. Communication between the macroscopic imager  32  and computer system  14  for transmitting signals and data between them may be specified by camera electronics&#39; manufacturer. However, conventional electronics of a digital camera may also be used. 
     A nose tube  38  is attached to housing  34  over an opening  37  in front housing member  34   b . Within the nose tube  38  is an assembly of components including a mounting  40  and an IR filter  39  (also available from Lumenera Corp.) received in the backside of mounting  40 . Mounting  40  has a threaded hole  42  for receiving a threaded optics barrel  44 . Optics  44  may represent one or more lenses for focusing an image onto CCD array  38 . For example, two lens doublets may be used. An LED board  46  has a ring of spaced LEDs  45  around an opening  46   a . LEDs  45  provide white light illumination and receive power by a cable from circuit boards  36 . 
     Optionally, either in addition to or instead of the ring of white light LEDs, one or more rings of different color LEDs may be provided on board  45  to allow selection of illumination of tissue with different wavelengths or wavelength ranges, in which macroscopic imager&#39;s CCD array  38  is sensitive to light is such wavelength or wavelength ranges. When different color LED light is available, housing  34  has button(s) or switch(es) connected to board  36  to enable the user to select which LEDs to activate. Optionally, different color LEDs may be selected by the user via the user interface of the computer system, such that the computer system  14  can instruct the macroscopic camera electronics, via cable  31 , to enable the desired LEDs. 
     A tissue ring mount  48  is attached to the front of nose tube  38 . As best shown in  FIG. 2C , tissue ring mount  48  is substantially conical in shape and has circular front surface  48   a  from which extends four prongs  48   b  having curved inner surface shaped to receive tissue ring  30 , as shown in  FIG. 2B . In the tissue ring mount  48  is a movable plastic collar  51  having four holes  51   a  into which four cylindrical shaped magnets  49  are received and fixed therein, such that they partial extend from the collar  51  can be received into four openings  48   c  extending through front surface  48   a . The magnets  49  may be fixed in their respective holes  51   a  by adhesive (e.g., epoxy). Thus, when the collar  51  is in its forward position the magnets  49  extend through openings  48   c , such that they can contact and magnetically capture tissue ring  30  when positioned by a user between prongs  48   b . The magnets  49  and openings  48   c  may be sized such that the top  30   b  of the tissue ring  30  will abut both front surface  48   a  and magnets  49  when the tissue ring  30  is magnetically captured, as shown in  FIG. 2B . 
     To assist in detaching the tissue ring  39  from mount  48 , two levers  50  are attached in holes  51   b  via slots  48   d  in the tissue ring mount  48 , such that a user can pull levers  50  backwards in slots  48   d  in a direction away from tissue ring  30  so as to pull the collar  51  back from its front position, thereby pulling magnets  49  away from tissue ring  30  to reduce the magnet attraction between the magnets  49  and the tissue ring  30 . The levers  50  may be screwed into threaded holes  51   b , and/or fixed by an adhesive in holes which then need not be threaded. Although magnetic coupling of the tissue ring  30  to mount  48  is preferred, other releasable coupling means may be used, such as use of mechanical latches. Also keys may be provided such that the tissue ring  30  is only locatable is a certain registration with respect to mount  48 . 
     As best shown in  FIGS. 1A and 2A , tissue ring  30  represents a tissue attachment device having a central opening  30   a . Tissue ring  30  is of metal material magnetically attractive to magnets so as to be releasably engagable by magnetic force to tissue ring mount  48 . In use, a circular thin transparent material window  52 , such as of plastic or glass, is attached by a ring of adhesive (e.g., double-sided adhesive tape) to the lower face of tissue ring  30 , where such ring of adhesive is outside the field of view of opening  30   a . A tab  52   b  extends from the window  52  for use in later detachment of window  52  from tissue ring  30 , and for alignment as will be described later below. Another ring of adhesive (e.g., double-sided adhesive tape) is similarly outside the field of view of opening  30   a  along front surface  52   b  for attachment to tissue. The tissue ring  30  is shown attached to tissue in the example of  FIGS. 3 and 4 , whereby tissue is viewable through tissue ring opening  30   a  and extends beyond the attached tissue ring  30 . 
     To assembly the components together, two screws are received through holes  35  from the interior of front housing member  34   b  into threaded holes of mount  40 . Three screws then extend through holes  46   b , via three spacers  43 , into threaded holes  40   b  of mount  40 . When assembled, barrel  42  extends through central opening  46   a  of LED board  46 . The back of tube  38  is mounted, such as with adhesive (e.g., epoxy) along annular ledge  40   a  of mount  40 , and tissue ring mount  48  is mounted to the front end of tube  38 , such as shown in  FIG. 2A . Prior to mounting of tube  38 , the optics  44  may be adjusted in the lens barrel  42  to fix the focus of such optics onto CCD array  38  at the plane at or just below the front surface  52   a  of window  52  when such window is disposed on tissue ring  30 . The assembled microscopic imager  32  may be of size and weight to be handheld by a user. 
     As shown in  FIG. 1 , an identical tissue ring mount  48  to that described above is mounted on the front of nose tube  24 , such that confocal imager  18  may be coupled to tissue ring  30  so as to enable imaging through openings  30   a  and window  52 . 
     Preferably, the macroscopic imager  32  is calibrated by the user with the attached tissue ring and window assembly to assure that imaging is proper. This can be performed by placing the tissue ring  30  over a white sheet of paper, and providing a window to set image properties. Such image properties may includes fields for adjusting CCD exposure time (e.g. max 65 ms), gain, and white point balance (red, green, and blue gain). If available, the user can enable exposure time, gain, and white point balance to be set automatically by the computer system  14 . The computer system  14  may send signals to the macroscopic imager  32  to communicate to macroscopic imager electronics such imaging parameters, and thereby control macroscopic imager  32  operation. Color and white point balance correction may be performed by the computer system on each macroscopic image received. 
     In operation, the tissue ring  30  with attached window  52  is located on the tissue  53  to be imaged by the macroscopic imager and then the confocal imager  18 . Surface  52   b  of window  52  has a ring of adhesive material to facilitate retaining the tissue ring and its attached window  52  on the tissue surface. Alternatively, the window  52  may be adhesively coupled to tissue and then the tissue ring  30  located over and adhesively coupled to window  52 . Either way, the area of the tissue of interest is viewable through opening  30   a  and thus is centered in opening  30   a  by the user. Optionally, cross-hair indicia may be printed, or otherwise provided, on one of the flat surfaces of window  52  outside of view of opening  30   a  and inside the rings of adhesive on such each of said flat surfaces, to assist the user in centering the area of tissue interest. 
     The macroscopic imager  32  is then presented to the tissue ring  30  which are magnetically attached to mount  48  of imager  32  as described earlier. An arrow  48   a  on the mount  48  is aligned with the center or window tab  52   b  by the user rotating the macroscopic imager housing  34  to couple such rotation to tissue mount  48 , as shown for example in  FIG. 3 . Switch  41  is operated by a user to capture a macroscopic image of the tissue surface  53  below and pressed against window  52  through window  52  and tissue ring opening  30   a . The macroscopic imager  32  is then removed from the tissue ring  30  with the assistance of moving levers  50  backward, without removal of tissue ring  30  from tissue  53 , and replaced with the confocal imager  18  having mount  48  which is then similarly aligned with its arrow  48   a  centered on window tab  52   a , as shown for example in  FIG. 4 . An immersion fluid may be placed inside the tissue ring  30  before connecting the confocal imager  18 . The confocal imager  18  remains so located on the tissue ring  30  throughout the confocal imaging session. Other indicia than arrow  48   a  may be used to align the tab  52   a , such as centered cross hair, or an arrow on such tab, to assist the user in alignment. Optionally, automatic rather than manual alignment may be provided, where the ring  30  has features which key into features of ring mount  48 . 
     The macroscopic image provides a 10×10 mm macroscopic image to computer system  14 , which may be, for example, 1000×1000 pixels. This is in contrast with the 4×4 mm imagable area of the confocal imager. Power to the board  36  in imager  32  may be supplied via the USB cable  31  or by a battery in housing  43 . The housing members  34   a  and  34   b , mount  40 , tube  38 , barrel  44 , and tissue ring mount  48  may be of molded plastic material, and preferably tissue ring mount  48  is of clear molded plastic. The macroscopic imager of the present invention also may represent a conventional digital camera adapted to have mount  48 , which can be interfaced to computer system  12  so as to received digital images from the camera. 
     The macroscopic imager  32  may optionally be used to assist the user in the selection of the tissue to be confocally imaged while the tissue ring  30 , and window  52  attached thereto, is attached to imager  32 , but before the tissue ring and window assembly is adhesively attached to tissue. Thus, the macroscopic imager  32  sends to macroscopic image to computer system  14  for display as live macroscopic images on the user interface  33  while the user moves the imager  32  along and slightly above the tissue surface to scan for an area of interest, such as a lesion in the tissue. When such area is viewed it is centered in the field of view of the macroscopic image, the user than applies sufficient pressure on the macroscopic imager in the direction of the tissue such that adhesive on the lower surface of the window  52  facing the tissue adheres and retains the tissue ring and window assembly on the tissue. When the tissue ring is so applied, alignment of the macroscopic imager  32  is verified and a macroscopic image is then captured. The macroscopic imager is then detached from the tissue ring  30 , and confocal imager  18  attached and aligned to the tissue ring for capture of confocal images as described earlier. 
     Referring to  FIGS. 5-9 , the user interface  33  for the macroscopic imager  32  will now be described. The user interface represents a program or application operating in memory of the computer system  14 , and preferably is running when the macroscopic imager is connected to the computer system. The user interface  33  is a graphical user interface in that a typical pointing mechanism such as a mouse  17  ( FIG. 1 ) is coupled to computer system  14  to enable the user to move, select (click) and/or drag a displayed cursor or graphical element, as typical of mouse functionality. Other pointing mechanisms may also be used, such as a touch screen, track ball, or the like, coupled to the computer system  14 . The user interface has various tabs  54  along the side of a window  56 . Selection of the macro camera tab  54   a  provides the macroscopic imager user interface  33  shown. The macroscopic imager  32  when placed and aligned in the tissue ring  30 , as describe above, provides live images in window  56 . When switch  41  is pressed a high resolution macroscopic image  57  is displayed in window  56 . A center region  58  within the window  56  represents a two-dimensional representation of 4×4 mm field of view of the tissue imagable by the confocal imager  18  of confocal microscope  12 . The part of the window  56  outside of this region  58  may be darkened by reducing brightness of pixels in this region, and/or effecting contrast or color. Cross hairs  59  may added or removed by selecting button  60   a.    
     In  FIG. 6 , a small square box  62  illustrates the present location of a 0.5×0.5 mm image capture frame of the confocal imager  18  from the current X and Y imaging position (e.g., of X and Y motors) of the confocal imager. The imaging frame position (with respect to the tissue surface) of the confocal imager  18  spatially correlates with the macroscopic image by the alignment of the macroscopic imager and confocal imager with the same tissue ring  30 . The box  62  follows, or is, the mouse cursor and represents the X and Y positions that the operator can navigate the confocal imager to, and as the box is so moved the X and Y motors are controlled such that the optics of the confocal imager is directed in X and Y at the user desired imaging positions with respect to the actual tissue surface, as well as to the earlier captured picture of the tissue surface of the macroscopic image  57  in window  56 . The Z motor controls the depth of the confocal image in tissue, which is not controllable from the macroscopic imaging user interface. 
     Selection of VivaScope® 1500 tab  54   b  provides live confocal images on the display  16  from confocal microscope  12 . During operation of the VivaScope® 1500, confocal image(s) may be selected for storage in memory of the computer system in one or more formats described latter. The position of selected image(s) stored is recorded in a two-dimensional map in memory of the computer system, which is the same size as region  58 . Such map  64  is shown as an overlay on region  58  in which graphical icons  66  are used to represent the position of stored confocal images, as shown in  FIG. 7 . Each of the graphical icons  66  represents a different type of image captured. For example, each of icons  66   a  represents the position with respect to the tissue surface of a video of multiple frames of confocal images. Icon  66   b  represents the capture of still confocal image. Icon  66   c  represents the position of a VivaStack® which are multiple confocal images at successive depths in the tissue at a common X,Y frame location. The darken path  67  shows the track of the confocal imager  18  taken, in which the box  62  shows the current imaging position of the confocal imager. Other types of images may also be captured, stored, and marked. For example, a VivaBlock® image represents tissue sections arranged to map a region of tissue at a common depth in the tissue. The map  64  may be cleared or hidden from view by selection of buttons  60   b  and  60   c , respectively. 
     Other tabs selectable by the user, are patient records tab  54   c  for editing or viewing patient information, archive tab  54   d  for viewing images of previous sessions stored with the same or a different patient, system settings tab  54   c  to view or change parameters of imaging, such as dimensions and/or depth of VivaBlock® or VivaStack® map, coarse or fine X, Y, and Z motor step settings, freeze and hold time for a static image capture, and typical print preferences. For example, button  61   a  may be click by the user to capture a confocal image by the confocal microscope at a location in the tissue selected by box  62 . Other buttons on the screen may be provided to adjust color  61   b , or reset  61   c  the user interface to clear the displayed macroscopic image  57  and its overlaid map  64  thereby enabling capture of a new macroscopic image, if desired. Adjust color  61   b  allows the user to open a window to adjust imaging properties described earlier, which may be desirable for different skin types. 
     Each time the Add Lesion button  60   d  is selected, a new record is generated in which images stored in the session from thereon after are annotated (or tagged, or revised file name) with the new lesion name. 
     Selecting the lesion/image tab  54   e  provides a display of one or more previously stored images in memory of computer system  14 . The particular type of image displayed from memory is selected by one of radio buttons  68  to be one of a still image captures, VivaBlock® images, VivaStack® images, movie (video) image, or macro (macroscopic) images. When multiple images of different lesions (or different parts of the same lesion) are stored for the same patient record, each may be entered in field  70   e  or selected from a drop down menu by clicking on the down arrow adjacent this field. 
     By clicking on one of images displayed, the user may make a selection (e.g., graphically shown on the screen by a color outline of the boundaries of the image). (For purposes of illustration, one macroscopic image is shown by selection of the radio button  68  labeled macro) The user then by clicking with the mouse on one of the Lesion  70   a  or Image  70   d  buttons provides another screen/window having detailed information about the lesion or image, respectively, associated with the selected image. For example,  FIG. 9  shows an example of such a screen/window when lesion information is presented by clinking Lesion button  70   a  for a macroscopic image, such as to display imaging parameters, date and time captured, or other information. Text may be entered in notes field  71  by the user, via a keyboard coupled to the computer system  13 , and stored in associated with the image. Other buttons  72   a  on screen of  FIG. 9  provide saving such comments in field  71  for associated with the image, deleting the stored image from memory of the computer system  13 , or canceling edit or entered comments in field  71 . Clicking cancel, save, or delete buttons  72   a  returns the user interface to screen of  FIG. 8 . A similar type of screen is provided by use of the Image button  70   a  to provide imaging detail, such as in the case of stored VivaBlock® (e.g., the depth of the image map), VivaStack® (e.g., the depths of each of the images from the tissue surface), or other images stored. Other buttons on  FIG. 8  may be provided for printing  70   b  a selected image on a printer that may be coupled to computer system  14 , or macros  70   c  to return to the main user interface  33  screen. 
     One feature of the user interface  33  is that two macroscopic images captured at different times of the same tissue surface may be compared. The current macroscopic image in window  56  represent a first one of such images, the second macroscopic image is selected by clicking on the Open as Comparison Button  72 . For instance, the second macroscopic image may be an image of the same tissue captured several months ago. When such second macroscopic image is selected, the slide graphic  73  is activated having a slider  73   a . The first and second macroscopic images morph (or blend) into each other by controlling their respective amount of contribution (or opacity of each image) controlled by clicking and dragging the slide graphic  73  right or left, where rightmost slide position is the most recent macroscopic image and leftmost slide position is the previous macroscopic image. Such comparison image is referred to as a morphed image, and the processing of changing the contribution of each of the images is referred to as morphing. Such morphing may be in accordance with typical alpha blending for processing two images into a single image. Where each macroscopic image is of the same area of tissue captured at different times, a user can view changes in the tissue over time. 
     Optionally a single screen may be provided with a common user interface to the macroscopic imager and confocal imager, such that the user can view confocal images, target and track on a macroscopic image without having to switch between screens as in the case of user interface  33 . An example of such single screen user interface  74  is shown in  FIG. 10 . User interface  74  has a window  76  for display of the 4×4 mm region  58  with box  62 , and a window  83  for display of a confocal image  79  from the confocal microscope  12  associated at the box  62  position. The images in the two windows  76  and  83  can switch (or flip) with each other by user selecting the magnifying glass graphic  77 . When the image in window  76  is region  58  of the macroscopic image, box  62  is movable using the mouse to set the X and Y position of the confocal imager  18 . To display live confocal images  79  in box  83  from the confocal microscope  12 , the user clicks on Scan button  90 . The capture button  88  stores in memory of the computer system  13  a still video image of the confocal image  79  shown in window  83 . To capture a movie, three controls  95 , record, pause, and stop buttons are selectable by the user to capture multiple frames which when played back will appear as a movie. 
     A window  78  is provided to obtain or review different images. For example, when graphic icon  81   a  is selected, a VivaBlock® map is captured by confocal imager  18  automatically scanning at a user desired depth a two-dimensional array of multiple images shown at locations corresponding to the entire 4×4 mm of region  58  (or user defined Xmm×Ymm rectangle or square) in window  76 , and when graphic icon  81   b  is selected a VivaStack® is captured by the confocal imager at multiple depths at a frame associated with the X and Y position of box  62 . A box  80  is provided which can be navigated by the user through the thumbnail (low-resolution) images in window  78  of either the VivaBlock® or VivaStack® captured. By clicking on graphical icon  81   c , box  80  can click and move any edge of the box and make it a larger or smaller box. Such box  80  icon can be freely panned across images, such that it includes one image, multiple images, even parts of multiple images across image boundaries. As soon as the user starts to click and drag on box  80  with the mouse, the image selected in box  80  automatically replaces the image in window  83  to allow the user to view in high-resolution such image based on image content in box  80 . Multiple graphic icons to zoom in and zoom out the image in window  78  by making the box larger or smaller in window  78  may replace icon  81   c . Also, an icon may be provided to enable a drop down menu to provide field and button similar to field  70   e  and buttons  68 , to enable window  78  to display thumbnail images of previously stored images. Again, icon  81   c  (or other icons enabling zoom in and out) with box  80  allows high-resolution images in window  83  of desired stored images. To resume scan of live confocal images, the Scan button  90  is selected by the user. Thus, the user may provide in window  78  any collection of stored images for review. 
     One feature of user interface  74  is that the user can move the X, Y, and Z motors of the confocal imager  18  using panel  82 , rather than panel  26  ( FIG. 1 ). For example, Y position is controlled by up and down arrows select two different step sizes in which arrows  84   a  and  84   b  can select a large or small step each time the arrow is clicked upon, or held down, by the user. X position is controlled by up and down arrows select two different step sizes in which arrows  85   a  and  85   b  can select a large or small step each time the arrow is clicked upon, or held down, by the user. The center circular button shown between arrows  84   a ,  84   b ,  85   a  and  85   b  when selected returns the X and Y motors each to their middle position. Z position is controlled by up and down arrows select two different step sizes in which arrows  86   a  and  86   b  can select a large or small step each time the arrow is clicked upon, or held down, by the user. To reset the current depth of imaging in the tissue as the zero depth position, the user can click on the Flag button  87 . The center circular button shown between arrows  86   a  and  86   b  returns the Z motor to its top position, or to such Flagged position if set by button  87 . Panel  82  thus includes at least a software version of panel  26  ( FIG. 1 ) of the confocal imager  18 . 
     The illumination power of the confocal imager  18  is shown by the ramp graphic  92 . Text shown on this graphic represents the current illumination power setting. The power may be adjusted to a desired level by the user clicking on one on part of the graphic  92 . If the mouse has a wheel, rotating the wheel may be used to change illumination power. A bottom bar  94  of interface  74  provide patient information, lesion information, and current confocal imaging position in X, Y, and Z. 
     Other graphical icons  96  are displayed on the user interface  74  as an overlay when the user directs the cursor the right portion of window  83 . These icons  96  provide user tools as follows: add/remove cross-hairs in window  78  (e.g., cross graphic), add/remove series of centered circles of different diameters (circle graphic, annotating/drawing in an overlay on the image in window  83  (e.g., pencil graphic), measuring tool (e.g., ruler graphic), or desired operations, e.g., save (disk graphic) or print (printer graphic). 
     One or more measuring tool icons may be provided. For purposes of illustration, a straight measuring tool is shown, in which clicking on the tool provides a line which has two movable end points, in which the measurement between such points in terms of dimension of the tissue is displayed. Other measuring tool icons may be provided to enable a measuring square (or rectangle) and circle (or oval) by overlaying the image in window  83  in which their major vertices of such shape are connected by lines and such vertices are movable by the user, in which the measurements of dimensions in terms of tissue distances is displayed. Other measurement shaped tools may also be provided, such as polygon. The question mark graphic, if provided, allow user access to a help topics or user manual stored in memory of the computer system. When the capture button  88  is selected, any overlaid information added is stored in association with the image, such that when the image is selected by the user for later display in window  78 , such overlaid information will be displayed. Also, map  64  ( FIG. 7 ) with icons  66  is shown in window  76  as an overlay on a macroscopic region  58 , as described earlier. The settings and archive buttons  89   a  operate similar to tabs  54   c  and  54   d  described earlier. The Quit button  89   b  exits the user interface  74 . Icons  96  may also be active when any image is presented in window  83 , such that both confocal and macroscopic images may be annotated by the user. 
     Other VivaScope® confocal microscope available from Lucid, Inc., such as the VivaScope® 2100 or VivaScope® 2500 may also be used in system  10  by adapting their imaging heads with tissue mount  48  so that they can be positioned to engage a tissue ring when mounted to in-vivo patient or ex-vivo tissue sample. Also other optical microscopes may be also adapted with such tissue mount  48 . Such as, for example, microscopes operating in accordance with optical coherence tomography or interferometry, such as described in Schmitt et al., “Optical characterization of disease tissues using low-coherence interferometry,” Proc. Of SPIE, Volume 1889 (1993), or two-photon microscopy, such as described in U.S. Pat. No. 5,034,613 to Denk et al., issued Jul. 23, 1991. 
     From the foregoing description, it will be apparent that a system, method, and user interface for macroscopic and confocal imaging of tissue has been provided. Variations and modifications in the herein described system, method, and user interface in accordance with the invention will undoubtedly suggest themselves to those skilled in the art. Accordingly, the foregoing description should be taken as illustrative and not in a limiting sense.