Background Art In recent years, endoscopic surgery has become the accepted standard for conducting many types of surgical procedures, both in the medical and dental arenas. The availability of imaging devices enabling a surgeon or dentist to view a particular surgical area through a small diameter endoscope which is introduced into small cavities or openings in the body results in much less patient trauma as well as many other advantages.

In many hospitals, the rod lens endoscope is still used in endoscopic surgery. The rod lens endoscope includes a very precise group of lenses in an elongate and rigid tube which are able to accurately transmit an image to a remote camera in line with the lens group. The rod lens endoscope, because of its cost of manufacture, failure rate, and requirement to be housed within a rigid and straight housing, is being increasingly replaced by solid state imaging technology which enables the image sensor to be placed at the distal tip of the investigating device. The three most common solid state image sensors include charged coupled devices (CCD), charge injection devices (CID) and photo diode arrays (PDA). In the mid-1980s, complementary metal oxide semiconductors (CMOS) were developed for industrial use. CMOS imaging devices offer improved functionality and simplified system interfacing. Furthermore, many CMOS imagers can be manufactured at a fraction of the cost of other solid state imaging technologies.

One particular advance in CMOS technology has been in the active pixel-type CMOS imagers which consist of randomly accessible pixels with an amplifier at each pixel site. One advantage of active pixel-type imagers is that the amplifier placement results in lower noise levels than CCDs or other solid state imagers. Another major advantage is that these CMOS imagers can be mass produced on standard semiconductor production lines. One particularly notable advance in the area of CMOS imagers including active pixel-type arrays is the CMOS imager described in U. S. Patent No. 5,471, 515 to Fossum, et al. This CMOS imager can incorporate a number of other different electronic controls that are usually found on multiple

circuit boards of much larger size. For example, timing circuits, and special functions such as zoom and anti-jitter controls can be placed on the same circuit board containing the CMOS pixel array without significantly increasing the overall size of the host circuit board.

Furthermore, this particular CMOS imager requires 100 times less power than a CCD-type imager. In short, the CMOS imager disclosed in Fossum, et al. has enabled the development of a"camera on a chip." Passive pixel-type CMOS imagers have also been improved so that they too can be <BR> <BR> used in an imaging device which qualifies as a"camera on a chip. "In short, the major difference between passive and active CMOS pixel arrays is that a passive pixel-type imager does not perform signal amplification at each pixel site. One example of a manufacturer which has developed a passive pixel array with performance nearly equal to known active pixel devices and being compatible with the read out circuitry disclosed in the U. S. Patent <BR> <BR> No. 5,471, 515 is VLSI Vision, Ltd. , 1190 Saratoga Avenue, Suite 180, San Jose, California 95129. A further description of this passive pixel device may be found in co-pending application, Serial No. 08/976,976, entitled"Reduced Area Imaging Devices Incorporated Within Surgical Instruments, "and is hereby incorporated by reference.

In addition to the active pixel-type CMOS imager which is disclosed in U. S. Patent No. 5,471, 515, there have been developments in the industry for other solid state imagers <BR> <BR> which have resulted in the ability to have a"camera on a chip. "For example, Suni Microsystems, Inc. of Mountain View, California, has developed a CCD/CMOS hybrid which combines the high quality image processing of CCDs with standard CMOS circuitry construction. In short, Suni Microsystems, Inc. has modified the standard CMOS and CCD manufacturing processes to create a hybrid process providing CCD components with their own substrate which is separate from the P well and N well substrates used by the CMOS components. Accordingly, the CCD and CMOS components of the hybrid may reside on different regions of the same chip or wafer. Additionally, this hybrid is able to run on a low power source (5 volts) which is normally not possible on standard CCD imagers which require 10 to 30 volt power supplies. A brief explanation of this CCD/CMOS hybrid can be found in the article entitled"Startup Suni Bets on Integrated Process"found in Electronic News, January 20,1997 issue. This reference is hereby incorporated by reference for purposes of explaining this particular type of imaging processor.

Another example of a recent development in solid state imaging is the development of CMOS imaging sensor which is able to achieve analog to digital conversion on each of the pixels within the pixel array. This type of improved CMOS imager includes transistors at every pixel to provide digital instead of analog output that enable the delivery of decoders and sense amplifiers much like standard memory chips. With this new technology, it may, therefore, be possible to manufacture a true digital"camera on a chip. "This CMOS imager has been developed by a Stanford University joint project and is headed by Professor Abbas el-Gamal.

A second approach to creating a CMOS-based digital imaging device includes the use of an over-sample converter at each pixel with a one bit comparator placed at the edge of the pixel array instead of performing all of the analog to digital functions on the pixel. This new design technology has been called MOSAD (multiplexed over sample analog to digital) conversion. The result of this new process is low power usage, along with the capability to achieve enhanced dynamic range, possibly up to 20 bits. This process has been developed by Amain Electronics of Simi Valley, California. A brief description of both of the processes developed by Stanford University and Amain Electronics can be found in an article entitled "A/D Conversion Revolution for CMOS Sensor ?," September 1998 issue of Advanced Imaging. This reference is also hereby incorporated by reference for purposes of explaining these particular types of imaging processors.

The above-mentioned developments in solid state imaging technology have shown that"camera on a chip"devices will continue to be enhanced not only in terms of the quality of imaging which may be achieved, but also in the specific construction of the devices which may be manufactured by new breakthrough processes.

Although the"camera on a chip"concept is one which has great merit for application in many industrial areas, a need still exists for a reduced area imaging device which can be used in even the smallest type of endoscopic instruments in order to view areas in the body that are particularly difficult to access, and to further minimize patient trauma by an even smaller diameter invasive instrument.

It is one object of this invention to provide reduced area imaging devices which take advantage of"camera on a chip"technology, but rearrange the circuitry in a stacked relationship so that there is a minimum profile presented when used within a surgical

instrument or other investigative device. It is another object of this invention to provide low <BR> <BR> cost imaging devices which may be"disposable. "It is yet another object of this invention to provide reduced area imaging devices which may be used in conjunction with standard endoscopes by placing the imaging device through channels which normally receive other surgical devices, or receive liquids or gases for flushing a surgical area. It is yet another object of this invention to provide a surgical device with imaging capability which may be battery powered and only requires one conductor for transmitting a pre-video signal to video processing circuitry within or outside the sterile field of the surgical area.

It is yet another object of the invention to provide a reduced area imaging device which utilizes selected charge integration periods in order to enhance the image in terms of a desired brightness or intensity. In the treatment of cancer, fluorescent markers have been used to help identify cancerous tissue within a patient. One example of a prior art reference which discloses a method of detection and treatment of malignant and non-malignant tumors is U. S. Patent No. 5,211, 938 to Kennedy et al. Specifically, this reference discloses a method of detection of malignant and non-malignant lesions by photo-chemotherapy of protoporphyrin IX precursors. 5-amino levulinic acid (5-ALA) is administered to the patient in an amount sufficient to induce synthesis of protoporphyrin IX in the lesions, followed by exposure of the treated lesion to a photo activating light in the range of 350-640 nanometers.

Naturally occurring protoporphyrin IX is activatable by light in the incident red light range which more easily passes through human tissue as compared to light of other wave lengths.

An endoscopic procedure may then be used to locate the photo activated lesions.

Other methods relating to cancer screening using fluorescence detection systems require the use of interventional devices such as endoscopes which have the special capability of delivering specified light frequencies to a targeted area within a patient. These endoscopes illuminate the targeted part of the body in which cancer is suspected. The light illuminates the targeted area which has previously been subjected to some type of fluorescent marker, causing the malignant cells to illuminate or fluoresce under observation of light at the specified frequency.

One distinct disadvantage or problem associated with use of fluorescent markers to locate and treat cancerous tissue is that it is oftentimes difficult to locate the cancerous tissue at all locations, particularly when lesions are at their early stages in formation, or the

cancerous tissue has not yet grown to an extent which creates an observable amount of fluorescence. Furthermore, because an endoscopic procedure is undertaken to locate and treat many lesions, the surgeon does not have an infinite amount of time to locate or treat a particular lesion. Therefore, a need exists for enhancing observable fluorescence as well as being able to use an imager of such a small size that fluorescence endoscopy can be used in a wide array of surgical procedures.

In addition to the intended use of the foregoing invention with respect to medical purposes, it is also contemplated that the invention described herein has great utility with respect to oral surgery and general dental procedures wherein a very small imaging device can be used to provide an image of particularly difficult to access locations. Additionally, while the foregoing invention has application with respect to the medical and dental fields, it will also be appreciated by those skilled in the art that the small size of the imaging device set forth herein can be applied to other functional disciplines wherein the imaging device can be used to view difficult to access locations for industrial equipment and the like. Therefore, the imaging device of this invention could be used to replace many industrial boroscopes.

The"camera on a chip"technology can be furthered improved with respect to reducing its profile area and incorporating such a reduced area imaging device into very small investigative instruments which can be used in the medical, dental, or other industrial fields.

Disclosure of the Invention In accordance with the present invention, reduced area imaging devices are provided.

The term"imaging device"as used herein describes the imaging elements and processing circuitry which is used to produce a video signal which may be accepted by a standard video device such as a television or video monitor accompanying a personal computer. The term "image sensor"as used herein describes the components of a solid state imaging device which captures images and stores them within the structure of each of the pixels in the array of pixels found in the imaging device. As further discussed below, the timing and control circuits can be placed either on the same planar structure as the pixel array, in which case the image sensor can also be defined as an integrated circuit, or the timing and control circuitry can be placed remote from the pixel array. The terms"signal"or"image signal"as used herein, and unless otherwise more specifically defined, refer to an image which at some point

during its processing by the imaging device, is found in the form of electrons which have been placed in a specific format or domain. The term"processing circuitry"as used herein refers to the electronic components within the imaging device which receive the image signal from the image sensor and ultimately place the image signal in a usable format. The terms "timing and control circuits"or"circuitry"as used herein refer to the electronic components which control the release of the image signal from the pixel array.

In a first embodiment, the image sensor, with or without the timing and control circuitry, may be placed at the distal tip of the endoscopic instrument while the remaining processing circuitry may be found in a small remote control box which may communicate with the image sensor by a single cable.

In a second embodiment, the image sensor and the processing circuitry may all be placed in a stacked arrangement of circuit boards and positioned at the distal tip of the endoscopic instrument. In this embodiment, the pixel array of the image sensor may be placed by itself on its own circuit board while the timing and control circuitry and processing circuitry are placed on one or more other circuit boards. Alternatively, the circuitry for timing and control may be placed with the pixel array on one circuit board, while the remaining processing circuitry can be placed on one or more of the other circuit boards.

In another embodiment, the imaging device may be adapted for use with a standard rod lens endoscope wherein the imaging device is placed within a standard camera housing which is configured to connect to a standard"C"or"V"mount connector.

In yet another embodiment, the imaging device may be configured so that the processing circuitry is placed in the handle of the endoscope, which eliminates the necessity of having a remote box when the processing circuitry is remote from the pixel array. In this embodiment, the pixel array and the timing and control circuitry are placed at the distal tip of the endoscopic instrument, while the processing circuitry is placed within the handle of the endoscope.

For each of the embodiments, selected charge integration periods may be used to enhance the image to a desired brightness or intensity. Particularly in the field of medical fluorescence detection, the ability to adjust charge integration periods greatly enhances the ability to observe fluorescence from a group of cells which might otherwise be unobservable with normal or preset integration periods.

While the imager may be used within an endoscopic instrument, it is also contemplated that the image sensor may be incorporated within a microscope, or another imaging device which is used to view cell cultures and the like. Most commonly available fluorescence microscopes include CCD type imagers which are not capable of the variable charge integration. CCD imagers are charge storage and transfer devices wherein the detector signal produced is representative of the total light impinging or falling upon the pixel array during a preset exposure time. Because of the construction of CCD devices, these exposure times cannot be manipulated for charge integration because CCD imagers have destructive readout. In other words, each charge is read by transferring the collected charge in each pixel in a serial fashion to a readout amplifier. The same photon generated charge collected at the pixel site is transferred (coupled) pixel by pixel, one at a time, in a predesignated sequence that cannot be interrupted. When the pixel charge sequence is transferred to the readout amplifier, the pixel charge is destroyed. For CID (charge injection device) imagers, pixels accumulate charge which is injected into the substrate. Pixels in CID imagers can be individually accessed; however, in doing so, the charge is not destroyed by actual charge transfer, but is sensed and then replaced so that the integration process is not disturbed. Light continues to be collected for the preset integration period while the pixels continue to be monitored. This non-destructive readout capability of CID imagers makes it possible to carry out real time exposure monitoring and it also allows integration periods to be varied such that longer integration periods represent greater amounts of light being collected in the pixels.

By having the capability to adjust the integration periods, fluorescence detection can be enhanced by choosing an integration time which maximizes observable fluorescence.

CMOS imagers also have variable charge integration capability to enhance observed fluorescence. As with CID imagers, integration periods in CMOS imagers may be varied, and fluorescence detection can be enhanced by choosing an integration period which maximizes the same. These CMOS imagers, as well as commercially available CMOS-CID imagers such as those manufactured by CIDTEC of Liverpool, NY can be modified to include an imager integration time select switch which allows an operator to preselect a desired integration period which maximizes observable fluorescence. The imagers sold by CIDTEC are"camera on a chip"type CMOS devices. The imager integration time select

switch is coupled to video processing circuitry by clock select circuitry which varies the integration period as selected by the operator. Representative integration periods might include 250 milliseconds, 500 milliseconds, 2 seconds, 3 seconds and 5 seconds. The operator would adjust the integration periods to maximize the observed fluorescence. For example, an integration period selected at 5 seconds would result in charge being accumulated in the pixels of the imager for a 5-second period and thus, the observed fluorescence intensity would be greatly increased in comparison to standard readout cycles for CCD devices which may only be one-sixtieth of a second.

In a CMOS-CID device, photon charge collected by the photo-diodes are injected into the pixel substrate and stored. The photo-diodes continue to collect charge and transfers the charge into the substrate. The charge stored in the substrate continues to accumulate from <BR> <BR> the photo-diodes until the chosen integration period ends (i. e. , the integration period selected by the user). At that time, the pixels are read out and the integration process begins again.

Readout clock select circuitry creates a frequency which is fed into a series of CMOS divider circuits which divide the clock frequency down to a user selected clock rate. The user selected clock rate would correspond to the select switch positions enabling the operator to have a choice of a plurality of integration time periods. Because CMOS pixels can be accessed individually, the image can be updated as desired through various update cycles within the display monitor, while continuing to wait for the read out signal from the imager without disturbing the selected integration period. The user selectable integration time switch can be mounted as desired based upon the particular configuration of the imaging device. In the configuration of the imaging device which may utilize a control box, the integration time switch could be mounted on the front panel of the control box, and the additional circuitry required for charge integration would simply be incorporated within the control box. In the configuration of the imaging device in which all of the processing circuitry is housed within the particular endoscope or other instrument, the switch could simply be mounted on the handle of the instrument. Published papers which provide good background information on charge injection devices include"Charge Injection Devices for Use in Astronomy", by Z. Ninkov et al., SPIE Proceedings, 1994, Publication No. 2198, Vol.

868; and"Evaluation of a Charge Injection Device Array", by Z. Ninkov et al., SPIE

Proceedings, 1994, Publication No. 2172, Vol. 15. These two papers are hereby incorporated by reference.

For use of the imaging device in endoscopy, a generic endoscope may be used which includes a very small diameter tubular portion which is inserted within the patient. The tubular portion maybe made of a flexible material having a central lumen or opening therein for receiving the elements of the imaging device. The tubular portion may be modified to include an additional concentric tube placed within the central lumen and which enables a plurality of light fibers to be placed circumferentially around the periphery of the distal end of the tubular portion. Additionally, control wires may extend along the tubular portion in order to make the endoscope steerable. The material used to make the endoscope can be compatible with any desired sterilization protocol, or the entire endoscope can be made sterile and disposable after use.

For the configuration of the imaging device which calls for the array of pixels and the timing and control circuitry to be placed on the same circuit board, only one conductor is required in order to transmit the image signal to the processing circuitry. In the other configuration of the imaging device wherein the timing and control circuits are incorporated onto other circuit boards, a plurality of connections are required in order to connect the timing and control circuitry to the pixel array and the one conductor is also required to transmit the image signal.

In addition to use of the imaging device in endoscopy, it is also contemplated that the imaging device of the invention can be incorporated within a microscope which maybe used to analyze cell cultures and the like. Although size is not as much of a concern with use of the imaging device within a microscope, there are still great advantages to be obtained by providing the imaging device with selected charge integration periods to intensify the brightness of an image in fluorescence detection of cell culture media which has no observable fluorescence as observed under standard integration periods.

Brief Description of the Drawings Figure 1 a illustrates a first embodiment including a fragmentary cross-sectional view of a generic endoscopic instrument, and a fragmentary perspective view of a control box, the endoscope and control box each incorporating elements of a reduced area imaging device ;

Figure 1 b is an enlarged fragmentary partially exploded perspective view of the distal end of the endoscopic instrument specifically illustrating the arrangement of the image sensor with respect to the other elements of the tubular portion of the endoscope; Figure 2a is a fragmentary cross-sectional view of a second embodiment of this invention illustrating another generic endoscope wherein the imaging device is incorporated in its entirety at the distal tip of the endoscope ; Figure 2b is an enlarged fragmentary partially exploded perspective view of the distal end of the endoscope of Figure 2a illustrating the imaging device; Figure 3a is an elevational fragmentary cross-sectional view of the image sensor incorporated with a standard camera housing for connection to a rod lens endoscope; Figure 3b is a fragmentary cross-sectional view of the imaging device incorporated within the camera housing of Figure 3a; Figure 3c is a fragmentary cross-sectional view similar to that of Figure 3b illustrating a battery as an alternate source of power; Figure 4 is a schematic diagram of the functional electronic components which make up the imaging device; Figure 4a is an enlarged schematic diagram of a circuit board which may include the array of pixels and the timing and control circuitry ; Figure 4b is an enlarged schematic diagram of a video processing board having placed thereon the processing circuitry which processes the pre-video signal generated by the array of pixels and which converts the pre-video signal to a post-video signal which may be accepted by a standard video device; Figures 5a-5e are schematic diagrams that illustrate an example of specific circuitry which may be used to make the imaging device.

Figure 6 is a simplified schematic diagram of a passive pixel which may be placed in an array of passive pixels compatible with an imager of CMOS type construction ; Figure 7a illustrates another preferred embodiment including a fragmentary cross- sectional view of a generic endoscope wherein the handle of the endoscope houses processing circuitry of the imaging device ; Figure 7b is an enlarged fragmentary partially exploded perspective view of the distal end of the endoscope specifically illustrating the arrangement of the image sensor with respect to the other elements of the tubular portion of the endoscope ;

Figure 8a is another fragmentary cross-sectional view of the generic endoscope of Figure 7a, but showing only one processing circuitry element within the handle of the endoscope; Figure 8b is an enlarged fragmentary partially exploded perspective view of the distal end of the endoscope of Figure 8a specifically illustrating the array of pixels being placed on one planar structure, and the timing and control circuitry being placed on another planar structure adjacent to the pixel array; Figure 9 is a graphical representation of how variable charge integration periods can enhance the capability to observe light or fluorescence from a viewed area; and Figure 10 is a schematic diagram illustrating incorporation of variable charge integration capability with the imaging device of the invention.

Best Mode for Carrying Out the Invention In accordance with one embodiment of the invention as shown in Figure la, an endoscope 10 is provided which incorporates a reduced area imaging device 11, shown in Figure Ib. As further discussed below, the elements of the imaging device may all be found at one location or the elements may be separated from one another and interconnected by the appropriate cable (s). The array of pixels making up the image sensor captures images and stores them in the form of electrical energy by conversion of light photons to electrons. This conversion takes place by the photo diodes in each pixel which communicate with one or more capacitors which store the electrons. The structure of the endoscope 10 includes a flexible or rigid tubular portion 14 which is inserted into the body of the patient and is placed at the appropriate location for viewing a desired surgical area. The tubular portion 14 attaches at its proximal end to a handle portion 12 which may be grasped by a surgeon who is conducting the endoscopic procedure. The handle 12 may include a central lumen or channel 13 which receives therethrough one or more cables or other structures which extend to the distal end 16 of tubular portion 14. Handle portion 12 may further include a supplementary channel 15 which intersects with central channel 13 and which may provide another point of entry for other cables, fluids or operative instruments to be placed through the endoscope.

Figure lb illustrates the distal end of the endoscope 16. The distal end 16 may be characterized by an outer tube 18 which traverses the length of the tubular portion 14 and

connects to the handle portion 12. Placed concentrically within the outer tube 18 may be one or more inner tubes 20. In Figure lb, the gap between inner tube 20 and outer tube 18 forms a space in which one or more light fibers 22 or control wires 24 may be placed. As well understood by those skilled in the art, a plurality of circumferentially spaced light fibers as illustrated in Figure lb can be used to illuminate the surgical site. Additionally, the control wires 24 may communicate with a control mechanism (not shown) integrated on the handle portion 12 for manipulating the distal end 16 of the endoscope in a desired direction. The flexible tubular portion 14 coupled with a steerable feature enables the endoscope to be placed within winding bodily passages or other locations difficult to reach within the body.

An image sensor 40 may be placed within the central channel defined by inner tube 20. In the configuration shown in Figure lb, a cable 26 is used to house the conductors which communicate with the image sensor 40. An intermediate support tube 28 may be placed concentrically outside of cable 26 and concentrically within inner tube 20 to provide the necessary support for the cable 26 as it traverses through the inner channel defined by inner tube 20. In lieu of support tube 28, other well-known means may be provided to stabilize the cable 26 such as clips or other fastening means which may attach to the inner concentric surface of inner tube 20.

A control box 30 may be placed remote from the endoscope 10. The control box 30 contains some of the processing circuitry which is used to process the image signal produced by image sensor 40. Therefore, the imaging device 11 as previously defined would include the processing circuitry within control box 30 and the image sensor 40 located at the distal tip of the endoscope. Control box 30 communicates with image sensor 40 by means of cable 32 which may simply be an insulated and shielded cable which houses therein cable 26.

Cable 32 is stabilized with respect to the handle portion 12 by means of a fitting 34 which ensures that cable 32 cannot be inadvertently pushed or pulled within channel 13.

Additionally, an additional fitting 35 may be provided to stabilize the entry of a light cable 36 which houses the plurality of light fibers 22.

Image sensor 40 is illustrated as being a planar and square shaped member. However, the image sensor may be modified to be in a planar and circular shape to better fit within the channel defined by inner tube 20. Accordingly, Figure lb further shows an alternate shaped image sensor 40'which is round. A lens group or system 42 may be incorporated at the distal end of the endoscope in order to manipulate the image prior to it being impinged upon the

array of pixels on the image sensor 40. This lens system 42 may be sealed at the distal end 16 of the endoscope so that the tubular portion 14 is impervious to fluids entering through the distal end 16. In the configuration of the imaging device 11 in Figures la and lb, there are only three conductors which are necessary for providing power to the image sensor 40, and for transmitting an image from the image sensor 40 back to the processing circuitry found within control box 30. Namely, there is a power conductor 44, a grounding conductor 46, and an image signal conductor 48 each of which are hard wired to the image sensor.

Thus, cable 26 may simply be a three-conductor 50 ohm cable.

Image sensor 40 can be as small as 1 mm in its largest dimension. However, a more preferable size for most endoscopic procedures would dictate that the image sensor 40 be between 4 mm to 8 mm in its largest dimension. The image signal transmitted from the image sensor through conductor 48 is also herein referred to as a pre-video signal. Once the pre-video signal has been transmitted from image sensor 40 by means of conductor 48, it is received by video processing board 50. Video processing board 50 then carries out all the necessary conditioning of the pre-video signal and places it in a form so that it may be viewed directly on a standard video device, television or standard computer video monitor.

The signal produced by the video processing board 50 can be further defined as a post-video signal which can be accepted by a standard video device. As shown in Figure 1 a, a conductor 49 is provided which transmits the post-video signal to an output connector 58 on the exterior surface of control box 30. The cable (not shown) extending from the desired video device (not shown) may receive the post-video signal by means of connector 58. Power supply board 52 may convert incoming power received through power source 54 into the desired voltage. In the preferred imager incorporated in this invention, the power to the imaging device is simply a direct current which can be a 1.5 volt to a 12 volt source. Incoming power from, for example, a wall receptacle, communicates with power supply board 52 by connector 56. Power supply board 52 takes the incoming power source and regulates it to the desired level. Additionally, ground 46 is also shown as extending back to the source of power through connector 56.

Figure 2a illustrates a second embodiment of this invention wherein the imaging device is self-contained entirely within the distal end 16 of the endoscope, and a power source which drives the circuitry within the imaging device may come from a battery 66 housed within handle portion 12.

As shown in Figure 2b, the video processing board 50 may be placed directly behind image sensor 40. A plurality of pin connectors 62 serve to electrically couple image sensor 40 with video processing board 50 depending upon the specific configuration of image sensor 40, pin connectors 62 may be provided either for structural support only, or to provide a means by which image signals are transmitted between image sensor 40 and board 50. When necessary, one or more supplementary boards 60 may be provided which further contain processing circuitry to process the image signal and present it in a form which may be directly received by a desired video device. The area which is occupied by image sensor 40 may be defined as the profile area of the imaging device and which determines its critical dimensions. Any imaging elements that are found on boards 50 or 60 must be able to be placed on one or more circuit boards which are longitudinally aligned with image sensor 40 along longitudinal axis XX. If the profile area is not critical in terms of limiting the largest sized imaging element within the imaging device, then the additional circuit boards 50 and 60 which are normally placed in line with image sensor 40 can be aligned in an offset manner or may be larger than the profile area of image sensor 40. In the configuration of Figure 2b, it is desirable that elements 40,50 and 60 be approximately the same size so that they may fit uniformly within the central channel of the endoscope. Additionally, image sensor 40 may be bonded to lens system 42 in order to provide further structural support to the imaging device 11 when mounted within the distal end 16.

Referring back to the handle portion 12 in Figure 2a, an additional channel 64 may be provided in order that a power supply cable 68 may communicate with battery 66.

Conveniently, battery 66 may itself be mounted within a well 65 formed in handle portion 12. Cable 68 carries the conductor 44 and ground 46. Cable 68 may intersect with cable 33 within channel 13, cables 68 and 33 extending then to the distal end 16. Cable 33 can be a single conductor cable which transmits the post-video signal to a desired video device. In other words, cable 33 may simply be an insulated and shielded housing for conductor 49 which carries the post-video signal. Because a preferred image sensor of the imaging device 11 may only require a 5 volt power supply, a battery is an ideal power source in lieu of a conductor which would trail the endoscope. Accordingly, the endoscope is made more mobile and easier to handle by eliminating at least one of the trailing cables.

Figure 3a illustrates yet another preferred embodiment of this invention, wherein the imaging device can be used in conjunction with a standard rod lens endoscope 70. As shown,

rod lens endoscope 70 includes a lens train 72 which includes a plurality of highly precise lenses (not shown) which are able to transmit an image from the distal end of the endoscope, to a camera in line with the endoscope. The rod lens endoscope is equipped with a light guide coupling post 74. Light guide post 74 connects to a source of light in the form of a cable 77 having a plurality of fiber optic strands (not shown) which communicate with a source of light (not shown). The most common arrangement of the rod lens endoscope also includes a"C"or"V"mount connector 78 which attaches to the eyepiece 76. The"C"or "V"mount attaches at its other end to a camera group 80. The camera group 80 houses one or more of the elements of the imaging device. In this embodiment, the small size of the imaging device is not a critical concern since the imaging device is not being placed at the distal end of the endoscope. However, the incorporation of the imaging device in a housing which would normally hold a traditional camera still provides an advantageous arrangement.

As shown, the camera group 80 may include a housing 82 which connects to a power/video cable 86. Fitting 87 is provided to couple cable 86 to the interior elements of the camera group 80 found within housing 82. Figure 3a illustrates an arrangement of the imaging device 11 wherein the image sensor 40 is placed by itself within the housing 82 and the processing circuitry of the imaging device can be positioned in a remote control box as shown in Figure la. Accordingly, only three conductors 44,46 and 48 are necessary for providing power to the image sensor 40 and for transmitting the pre-video signal to the control box. Alternatively, as shown in Figure 3b, the entire imaging device 11 may be incorporated within camera group 80, each of the elements of the imaging device being placed in the stacked arrangement similar to Figure 2b. As discussed above, size is not as much of a concern in the embodiment of Figure 3a and 3b since the camera group housing 82 is much larger than the distal tip of the endoscope of Figures 1 a and 2a.

Figure 3c also illustrates the use of a battery 66 which provides source of power to the imaging device in either Figure 3a or 3b. In this arrangement, housing 82 is altered to include a battery housing 69 which houses the battery 66 therein. Battery housing 69 may include a very small diameter channel which may allow conductor 48 or 49 to communicate directly with the processing circuitry or video device, respectively. It will also be understood that the embodiment in Figure la may incorporate the use of a battery 66 as the source of power. Thus, handle 12 in Figure 1 a may be altered in the same way as housing 82 to allow a battery to be attached to the handle portion 12.

Figure 4 is a schematic diagram illustrating one way in which the imaging device 11 may be constructed. As illustrated, the image sensor 40 may include the timing and control circuits on the same planar structure. Power is supplied to image sensor 40 by power supply board 52. The connection between image sensor 40 and board 52 may simply be a cable having two conductors therein, one for ground and another for transmitting the desired voltage. These are illustrated as conductors 44 and 46. The output from image sensor 40 in the form of the pre-video signal is input to video processor board 50 by means of the conductor 48. In the configuration of Figure 4, conductor 48 may simply be a 50 ohm conductor. Power and ground also are supplied to video processing board 50 by conductors 44 and 46 from power supply board 52. The output signal from the video processor board 50 is in the form of the post-video signal and which may be carried by conductor 49 which can also be a 50 ohm conductor.

In the first embodiment illustrated in Figure la, cable 32 can be used to house conductors 44,46 and 48. In the embodiment shown in Figure 2a, cable 33 can be used to house conductor 49 by itself when a battery power source is used, or alternatively, cable 33 may house conductors 44,46 and 49 if the embodiment of Figure 2a utilizes a power source from board 52.

Optionally, a supplementary processing board 60 may be provided to further enhance the pre-video signal. As shown in Figure 4, the supplementary board 60 may be placed such that the pre-video signal from image sensor 40 is first sent to the supplementary board and then output to the video processor board 50. In this case, the output from board 50 can be carried along conductor 51. This output can be defined as an enhanced pre-video signal.

Furthermore, the post-video signal from video processor board 50 may return to the supplementary board 60 for further processing, as further discussed below. The conductor used to transmit the post-video signal back to the supplementary board is shown as conductor 59. The power supply board 52 may also provide power to the supplementary board in the same manner as to image sensor 40 and board 50. That is, a simple hard-wired connection is made onto the supplementary board for the ground and voltage carrying conductors. As discussed above, image sensor 40 may be placed remotely from boards 50 and 60.

Alternatively, image sensor 40, and boards 50 and 60 each may be placed within the distal end of the endoscope.

Although Figure 4 illustrates the image sensor and the timing and control circuits being placed on the same planar structure, it is possible to separate the timing and control circuits from the pixel array and place the timing and control circuits onto video processing board 50. The advantage in placing the timing and control circuits on the same planar structure as the image sensor is that only three connections are required between image sensor 40 and the rest of the imaging device, namely, conductors 44,46 and 48.

Additionally, placing the timing and control circuits on the same planar structure with the pixel array results in the pre-video signal having less noise. Furthermore, the addition of the timing and control circuits to the same planar structure carrying the image sensor only adds a negligible amount of size to one dimension of the planar structure. If the pixel array is to be the only element on the planar structure, then additional connections must be made between the planar structure and the video processing board 50 in order to transmit the clock signals and other control signals to the pixel array. For example, a ribbon-type cable (not shown) or a plurality of 50 ohm coaxial cables (not shown) must be used in order to control the downloading of information from the pixel array. Each of these additional connections would be hard wired between the boards.

Figure 4a is a more detailed schematic diagram of image sensor 40 which contains an array of pixels 90 and the timing and control circuits 92. One example of a pixel array 90 which can be used within the invention is similar to that which is disclosed in U. S. Patent <BR> <BR> No. 5,471, 515 to Fossum, et al. , said patent being incorporated by reference herein. More specifically, Figure 3 of Fossum, et al. illustrates the circuitry which makes up each pixel in the array of pixels 90. The array of pixels 90 as described in Fossum, et al. is an active pixel group with intra-pixel charged transfer. The image sensor made by the array of pixels is formed as a monolithic complementary metal oxide semiconductor integrated circuit which may be manufactured in an industry standard complementary metal oxide semiconductor process. The integrated circuit includes a focal plane array of pixel cells, each one of the cells including a photo gate overlying the substrate for accumulating the photo generated charges. In broader terms, as well understood by those skilled in the art, an image impinges upon the array of pixels, the image being in the form of photons which strike the photo diodes in the array of pixels. The photo diodes or photo detectors convert the photons into electrical energy or electrons which are stored in capacitors found in each pixel circuit. Each pixel circuit has its own amplifier which is controlled by the timing and control circuitry

discussed below. The information or electrons stored in the capacitors is unloaded in the desired sequence and at a desired frequency, and then sent to the video processing board 50 for further processing.

Although the active pixel array disclosed in U. S. Patent No. 5,471, 515 is mentioned herein, it will be understood that the hybrid CCD/CMOS described above, or any other solid state imaging device may be used wherein timing and control circuits can be placed either on the same planar structure with the pixel array, or may be separated and placed remotely.

Furthermore, it will be clearly understood that the invention claimed herein is not specifically limited to an image sensor as disclosed in the U. S. Patent No. 5,471, 515, but encompasses any image sensor which may be configured for use in conjunction with the other processing circuitry which makes up the imaging device of this invention.

The timing and control circuits 92 are used to control the release of the image information or image signal stored in the pixel array. In the image sensor of Fossum, et al., the pixels are arranged in a plurality of rows and columns. The image information from each of the pixels is first consolidated in a row by row fashion, and is then downloaded from one or more columns which contain the consolidated information from the rows. As shown in Figure 4a, the control of information consolidated from the rows is achieved by latches 94, counter 96, and decoder 98. The operation of the latches, counter and decoder is similar to the operation of similar control circuitry found in other imaging devices. That is, a latch is a means of controlling the flow of electrons from each individual addressed pixel in the array of pixels. When a latch 94 is enabled, it will allow the transfer of electrons to the decoder 98. The counter 96 is programmed to count a discrete amount of information based upon a clock input from the timing and control circuits 92. When the counter 96 has reached its set point or overflows, the image information is allowed to pass through the latches 94 and be sent to the decoder 98 which places the consolidated information in a serial format. Once the decoder 98 has decoded the information and placed it in the serial format, then the row driver 100 accounts for the serial information from each row and enables each row to be downloaded by the column or columns. In short, the latches 94 will initially allow the information stored in each pixel to be accessed. The counter 96 then controls the amount of information flow based upon a desired time sequence. Once the counter has reached its set point, the decoder 98 then knows to take the information and place it in the serial format.

The whole process is repeated, based upon the timing sequence that is programmed. When

the row driver 100 has accounted for each of the rows, the row driver reads out each of the rows at the desired video rate.

The information released from the column or columns is also controlled by a series of latches 102, a counter 104 and a decoder 106. As with the information from the rows, the column information is also placed in a serial format which may then be sent to the video processing board 50. This serial format of column information is the pre-video signal carried by conductor 48. The column signal conditioner 108 places the column serial information in a manageable format in the form of desired voltage levels. In other words, the column signal conditioner 108 only accepts desired voltages from the downloaded column (s).

The clock input to the timing and control circuits 92 may simply be a quartz crystal timer. This clock input is divided into many other frequencies for use by the various counters. The run input to the timing and control circuit 92 may simply be an on/off control.

The default input can allow one to input the pre-video signal to a video processor board which may run at a frequency of other than 30 hertz. The data input controls functions such as zoom. At least for a CMOS type active pixel array which can be accessed in a random manner, features such as zoom are easily manipulated by addressing only those pixels which locate a desired area of interest by the surgeon.

A further discussion of the timing and control circuitry which may be used in conjunction with an active pixel array is disclosed in U. S. Patent No. 5,471, 515 and is also described in an article entitled"Active Pixel Image Sensor Integrated With Readout Circuits" appearing in NASA Tech Briefs, October 1996, pp. 38 and 39. This particular article is also incorporated by reference.

Once image sensor 40 has created the pre-video signal, it is sent to the video processing board 50 for further processing. At board 50, as shown in Figure 4b, the pre- video signal is passed through a series of filters. One common filter arrangement may include two low pass filters 114 and 116, and a band pass filter 112. The band pass filter only passes low frequency components of the signal. Once these low frequency components pass, they are then sent to detector 120 and white balance circuit 124, the white balance circuit distinguishing between the colors of red and blue. The white balance circuit helps the imaging device set its normal, which is white. The portion of the signal passing through low pass filter 114 then travels through gain control 118 which reduces the magnitude or amplitude of this portion to a manageable level. The output from gain control 118 is then fed

back to the white balance circuit 124. The portion of the signal traveling through filter 116 is placed through the processor 122. In the processor 122, the portion of the signal carrying the luminance or non-chroma is separated and sent to the Y chroma mixer 132. Any chroma portion of the signal is held in processor 122.

Referring to the output of the white balance circuit 124, this chroma portion of the signal is sent to a delay line 126 where the signal is then further reduced by switch 128. The output of switch 128 is sent through a balanced modulator 130 and also to the Y chroma mixer 132 where the processed chroma portion of the signal is mixed with the processed non- chroma portion. Finally, the output from the Y chroma mixer 132 is sent to the NTSC/PAL encoder 134, commonly known in the art as a"composite"encoder. The composite frequencies are added to the signal leaving the Y chroma mixer 132 in encoder 134 to produce the post-video signal which may be accepted by a television.

Referring back to Figure 4, it further illustrates supplementary board 60 which may be used to digitally enhance or otherwise further condition the pre-video signal produced from image sensor 40. For example, digital enhancement can brighten or otherwise clarify the edges of an image viewed on a video screen. Additionally, the background images may be removed thus leaving only the foreground images or vice versa. The connection between image sensor 40 and board 60 may simply be the conductor 48 which may also transfer the pre-video signal to board 50. Once the pre-video signal has been digitally enhanced on supplementary board 60, it is then sent to the video processor board 50 by means of another conductor 51. The pre-video signal is an analog signal. The digitally enhanced pre-video signal may either be a digital signal or it may be converted back to the analog domain prior to being sent to board 50.

In addition to digital enhancement, supplementary board 60 may further include other circuitry which may further condition the post-video signal so that it may be viewed in a desired format other than NTSC/PAL. As shown in Figures 4, intermediate conductor 59 may transmit the signal output from Y chroma mixer 132 back to the supplementary board 60 where the signal is further encoded for viewing in a particular format. One common encoder which can be used includes an RGB encoder 154. The RGB encoder separates the signal into three separate colors (red, green and blue) so that the surgeon may selectively choose to view only those images containing one or more of the colors. Particularly in tissue

analysis where dyes are used to color the tissue, the RGB encoder may help the surgeon to identify targeted tissue.

The next encoder illustrated in Figure 4 is a SVHS encoder 156 (super video home system). This encoder splits or separates the luminance portion of the signal and the chroma portion of the signal prior to entering the video device. Some observers believe that a cleaner signal is input to the video device by such a separation which in turn results in a more clear video image viewed on the video device. The last encoder illustrated in Figure 4 is a VGA encoder 158 which enables the signal to be viewed on a standard VGA monitor which is common to many computer monitors.

One difference between the arrangement of image sensor 40 and the outputs found in Figure 3 of the Fossum, et al. patent is that in lieu of providing two analog outputs <BR> <BR> [namely, VS out (signal) and VR out (reset) ], the reset function takes place in the timing and control circuitry 92. Accordingly, the pre-video signal only requires one conductor 48.

Figures 5a-5e illustrate in more detail one example of circuitry which may be used in the video processing board 50 in order to produce a post-video signal which may be directly accepted by a video device such as a television. The circuitry disclosed in Figures 5a-5e is very similar to circuitry which is found in a miniature quarter-inch Panasonic camera, Model KS-162. It will be understood by those skilled in the art that the particular arrangement of elements found in Figures 5a-5e are only exemplary of the type of video processing circuitry which may be incorporated in order to take the pre-video signal and condition it to be received by a desired video device.

As shown in Figure 5a, 5 volt power is provided along with a ground by conductors 44 and 46 to board 50. The pre-video signal carried by conductor 48 is buffered at buffer 137 and then is transferred to amplifying group 138. Amplifying group 138 amplifies the signal to a usable level as well as achieving impedance matching for the remaining circuitry.

The next major element is the automatic gain control 140 shown in Figure 5b.

Automatic gain control 140 automatically controls the signal from amplifying group 138 to an acceptable level and also adds other characteristics to the signal as discussed below. More specifically, automatic gain control 140 conditions the signal based upon inputs from a 12 channel digital to analog converter 141. Converter 141 retrieves stored information from EEPROM (electrically erasable programmable read only memory) 143. EEPROM 143 is a non-volatile memory element which may store user information, for example, settings for

color, tint, balance and the like. Thus, automatic gain control 140 changes the texture or visual characteristics based upon user inputs. The signal leaving the automatic gain control 140 is an analog signal until being converted by analog to digital converter 142.

Digital signal processor 144 of Figure 5c further processes the converted signal into a serial type digital signal. One function of the microprocessor 146 is to control the manner in which digital signal processor 144 sorts the digital signals emanating from converter 142.

Microprocessor 146 also controls analog to digital converter 142 in terms of when it is activated, when it accepts data, when to release data, and the rate at which data should be released. Microprocessor 146 may also control other functions of the imaging device such as white balance. The microprocessor 146 may selectively receive the information stored in the EEPROM 143 and carry out its various commands to further control the other elements within the circuitry.

After the signal is processed by digital signal processor 144, the signal is sent to digital encoder 148 illustrated in Figure 5d. Some of the more important functions of digital encoder 148 are to encode the digital signal with synchronization, modulated chroma, blanking, horizontal drive, and the other components necessary so that the signal may be placed in a condition for reception by a video device such as a television monitor. As also illustrated in Figure 5d, once the signal has passed through digital encoder 148, the signal is reconverted into an analog signal through digital to analog converter 150.

This reconverted analog signal is then buffered at buffers 151 and then sent to amplifier group 152 of Figure 5e which amplifies the signal so that it is readily accepted by a desired video device. Specifically, as shown in Figure 5e, one SVHS outlet is provided at 160, and two composite or NTSC outlets are provided at 162 and 164, respectively.

In addition to the active pixel-type CMOS imager discussed above, certain advances in passive pixel-type CMOS imagers have been made such that the traditional noise associated with such passive arrangements can be overcome by improved manufacturing technologies which therefore does not require each signal to be amplified at each pixel site.

Accordingly, Figure 6 illustrates a simplified schematic diagram of a passive pixel which may be incorporated directly into the read out circuitry of Fossum, et al. (see Figure 3, U. S.

Patent No. 5,471, 515; read out circuit or correlated double sampling circuit 70). As shown in Figure 6, each passive pixel 160 in a passive pixel array comprises a photo diode 162 with a transistor 164 that passes the photoelectrically generated signal from photo diode 162 to a

charge integration amplifier (not shown) outside the pixel array. After photo charge integration, the timing and control circuitry activates the access transistor 164. The photoelectrically generated signal from photo diode 162 then transfers to the capacitance of the column bus 166 where the charge integration amplifier (not shown) at the end of the column bus 166 senses the resulting voltage. The column bus voltage resets the photo diode 162, and the timing and control circuitry then places the access transistor 164 in an off condition. The pixel 160 is then ready for another integration cycle. The signal output from either the active or passive pixel arrays are processed identically. Accordingly, Figure 6 illustrates that the readout circuit 70 of Fossum, et al. is compatible with either the active or passive pixel arrays disclosed herein. One example of a manufacturer who has developed a passive pixel array with performance nearly equal to that of known active pixel devices and compatible with the read out circuitry of Fossum, et al. is VLSI Vision Ltd. , 1190 Saratoga Avenue, Suite 180, San Jose, California 95129.

Figures 7a and 7b illustrate yet another preferred embodiment of this invention. This embodiment also incorporates a generic endoscope, such as shown in Figures 1 a and 2a.

Specifically, the generic endoscope 170 includes a handle 172 which may be grasped by the surgeon. The handle 172 has an interior opening 173 which allows wiring to pass through to the distal tip 177 of the endoscope. This interior opening 173, as further discussed below, also houses the processing circuitry of the imaging device. The generic endoscope further includes a tubular portion 174 which is placed within the patient's body and which is defined by a flexible outer tube 178. A battery channel 175 may also be incorporated within the handle 172 to receive a battery 176. Figure 7b shows the distal tip 177 of the endoscope in an enlarged fashion. A lens system 180 may be used to manipulate an image. Images are received upon a planar structure in the form of an image sensor 182 which includes an array of pixels and corresponding timing and control circuitry. This planar structure is the same as that illustrated in Figure 4a. Image sensor 182 incorporating the pixel array and timing and control circuitry produces a pre-video signal (either analog or digital) which is transmitted by pre-video out conductor 188. A 5-volt power source and a ground are provided to image sensor 182 by conductors 184 and 186, respectively. A protective cable or sheathing 190 houses conductors 184,186 and 188 as they extend proximally back toward the handle 172 of the endoscope 170. Additionally, a support tube 192 may fit over the protective cable 190 to provide further protection for the conductors. Referring back to

Figure 7a, desired processing circuitry can be placed directly within the handle of the endoscope since the processing circuitry is such a small size. In Figure 7a, the processing circuitry incorporated within the handle 172 includes two planar structures, namely, a supplementary board 194 and a video processor board 196. In terms of the construction of these boards, the boards 194 and 196 are the same as video processor board 50 and supplementary board 60, respectively, of the first embodiment. Boards 194 and 196 may also be spaced apart from one another and placed in an aligned position as by pin connectors 195.

Pin connectors 195 are also of the same type as pin connectors 62 shown in Figure 2b. The pre-video signal transmitted by conductor 188 is processed by the processing circuitrywithin the handle, and a post-video out signal is produced and transmitted by post-video out conductor 198. Conductor 198 then connects directly to the desired video device (not shown) such as a video screen or personal computer. As shown in Figure 7a, 5-volt power conductor 184, ground conductor 186, and post-video out conductor 198 may be housed within cable 199 which connects to the video device and a source of power (not shown). A fitting 200 may be used to stabilize cable 199 in its attachment to the handle 172. As also shown in Figure 7a, a light fiber bundle 202 may extend through the endoscope to provide light to the distal tip 177. Accordingly, a cable 203 would extend back to a source of light (not shown), and fitting 204 would be used to stabilize the connection of cable 203 to the handle 172.

Figure 7a further illustrates a power and ground conductor 206 which extends from the battery compartment/channel 175 in order to provide an alternate source of power to the endoscope. Figure 7a has been simplified to better illustrate the differences between it and the previous embodiments. Accordingly, the light fibers and control wires which may extend to the distal end 177 are not illustrated (corresponding to light fibers 22 and control wires 24 of the first embodiment).

Figures 8a and 8b illustrate another endoscope which differs from Figures 7a and 7b by modifications made to the arrangement of the imaging device. Figure 8a also does not illustrate the use of an alternate power source; however, it shall be understood, of course, that this Figure could also utilize a battery source of power as shown in Figure 7a. More specifically, Figures 8a and 8b illustrate an imaging device wherein the array of pixels 208 and the timing and control circuitry 210 are on two separate planar structures placed back to back to one another in an aligned fashion. A multistrand conductor 212 transmits image signals produced by the pixel array 208, and also carries the timing and control signals to the

pixel array allowing the image signals to be read or unloaded at the desired speed, frequency, and sequence. Also Figure 8a illustrates the use of video processor board 196, and no supplementary board 194. It shall be understood that, for both Figures 7a and 8a, the specific processing circuitry found within the interior opening 173 of the handle can include whatever type of processing circuitry as needed to create a post-video out signal which is readily acceptable by a video device without any further processing. Thus, Figure 7a could be used without supplementary board 194, and Figure 8a could incorporate the use of supplementary board 194. It shall also be understood that boards 194 and 196 have been greatly enlarged to better show their spatial arrangement and detail within interior opening 173. Although it is possible that these boards may be of such illustrated size, as mentioned above with respect to the previous embodiment and boards 50 and 60, these boards can be made small enough that the opening 173 within the endoscope has ample room to house the processing circuitry therein. In terms of the actual structure which is used to support the processing circuitry within the handle, the handle may be equipped with any suitable non-conductive support flanges or other extensions within the interior opening 173 which would allow the processing circuitry to be mounted thereon. Because of the extremely small size and insignificant weight of the processing circuitry, such supporting structure within interior opening 173 would be minimal.

As seen in Figure 9, the intensity or brightness of an image may be enhanced by a CMOS-CID imager which has a variable charge integration capability. The example at Figure 9 shows a situation in which a viewed area may only reflect or emit an amount of light which is not normally capable of being seen by the human eye through a fluorescence microscope, endoscope, or may otherwise be very difficult to find. By adjusting the integration period, the image produced by the CMOS-CID imaging device intensifies the brightness or intensity of the image over the integration period to a much more readily observable amount of light. In the example of Figure 9, the brightness of a particular image is measured on the vertical axis, while the time in which the image is viewed or observed is measured on the horizontal axis. A threshold level of observable light or fluorescence is shown at horizontal line 304, and which represents an average amount of light or fluorescence which can be observed by a currently available fluorescence microscope or endoscope without the aid of any special equipment. Any level of light or fluorescence falling below this threshold level 304 would be considered very difficult to observe. Dashed

line 306 represents the level of light or fluorescence which may be observed in viewing a particular area without the aid of an imager having variable charge integration capability. In accordance with the methods of this invention, an imager having charge integration capability could be used to enhance or brighten the observable light or fluorescence. The observed light or fluorescence using such an imager is depicted as line 308. As shown, a three-second integration period has been chosen. During the first second of observation, there is no observable difference between viewing the area by use of a CCD type imager versus viewing the image with the aid of an imager having charge integration capability. However, between one and two seconds, the observed light or fluorescence 308 is now above the threshold level 304 which makes the area under investigation much more easy to locate and view. Between two and three seconds, the image is further brightened or enhanced due to the continuing charge integration period wherein charge continues to accumulate in the pixels of the imager.

The stepped pattern of observed light or fluorescence 308 is due to the monitor update cycle or period. Thus, between one and two seconds, a first update of the monitor period occurs which reflects the increased charge accumulating in the pixels of the imager. Charge accumulates in the pixels in a linear fashion. Therefore, the monitor update period could be reduced to show a more linear increase of brightness of observed fluorescence. In some cases, it may be desirable to have more of a stepped visual image, as shown in Figure 9.

When the charge integration period ends, the accumulated charge is then released or dumped from the pixels, and a new charge integration period begins. Thus, the example of Figure 9 shows the brightness of an image being repeated in a similar pattern between three and six seconds. It can be seen that the capability to view observed light or fluorescence is greatly enhanced by use of an imager having variable charge integration capability which may overcome low light conditions or low fluorescence of a particular bodily tissue.

Figure 10 is a schematic diagram of an imager and its processing circuitry which incorporate variable charge integration capability. Imager 40 is coupled to its video processing circuitry 50. Power supply 52 supplies power to the imaging device and the additional circuitry to achieve charge integration. In order to incorporate variable charge integration capability, imager readout clock select circuitry 318 is added which communicates with one or more of the video processor boards 50. An imager integration time select switch 320 is provided enabling an operator to manually select the desired integration period. As shown, the integration periods may be periods of less than one second,

or more than one second. Figure 10 illustrates a situation in which an operator has chosen a three-second integration period. As the area is observed by the imager 40, the imager will accumulate charge based upon the selected integration period. The image is viewed on the display monitor 316. As also discussed above, the monitor update period can also be adjusted to provide more or less of a stepped brightness image. The operator would then adjust the charge integration period to obtain the most desirable image of the area being viewed.

It should be understood that the imager 40 may be used in conjunction with the optics of a fluorescence microscope. Many fluorescence microscopes today also have miniature cameras which are used to record images observed by the fluorescence microscope. Thus, the imager 40 could replace the miniature camera or imager used on commercially available fluorescence microscopes. Also, it shall be understood that an endoscope which maybe used in fluorescence guided endoscopy may also incorporate variable charge integration capability in order to enhance the ability to find and evaluate fluorescing cells. Thus, the use of variable charge integration capability has multiple benefits not only in viewing cells which have been removed from a body, but also to view cells in the body which may undergo some treatment or surgical procedure, and are to be located by fluorescence guided endoscopy.

Fluorescence-assisted surgery and fluorescence-assisted endoscopy can also be enhanced by providing an endoscope utilizing a CMOS-CID imager which has variable charge integration capability. The ability of a surgeon to view a cancerous growth inside the patient can be enhanced by choosing an integration period which greatly expands the imaging sensitivity of the endoscope. The faint or slight amount of fluorescence which might not be observable through a CCD imager can be enhanced by using a CMOS-CID imager modified with variable charge integration capability, resulting in readily observable fluorescence.

Thus, in every conceivable aspect of endoscopy and cancer screening, use of an endoscope having a variable charge integration capability is advantageous for finding a cancerous growth.

One example of fluorescence guided endoscopy might be fluorescence endoscopy to find colon cancer. Once the patient has been administered 5-ALA or another similar compound, the surgeon would conduct the endoscopic procedure looking for fluorescing colon tissue. As the surgeon conducts the endoscopic procedure, the charge integration periods could be adjusted to maximize observable fluorescence. In some cases, it may be

very difficult for the surgeon to find all fluorescing tissues within the colon. By using the variable charge integration capability incorporated within the endoscope, the surgeon is more capable of finding each and every fluorescing groups of tissue within the colon to make a proper diagnosis. Also, light delivery to the surgical site can be chosen from a desired frequency of light corresponding to the excitation frequency of the compound administered to the patient.

From the foregoing, it is apparent that an entire imaging device may be incorporated within the distal tip of an endoscope, or may have some elements of the imaging device being placed in a small remote box adjacent to the endoscope. Based upon the type of image sensor used, the profile area of the imaging device may be made small enough to be placed into an endoscope which has a very small diameter tube. Additionally, the imaging device may be placed into the channels of existing endoscopes to provide additional imaging capability without increasing the size of the endoscope. The imaging device may be powered by a standard power input connection in the form of a power cord, or a small lithium battery may be used.

The imaging device of the invention can be further enhanced by incorporating a charge integration feature which enhances the ability of a user to selectively adjust the brightness of an image. As discussed above, fluorescence detection in patient screening and treatment for a wide array of photo-dynamic treatments can be greatly improved by utilizing the imaging device of the invention having charge integration capability.

This invention has been described in detail with reference to particular embodiments thereof, but it will be understood that various other modifications can be effected within the spirit and scope of this invention.