Systems and methods related to endoscopic imaging

Abstract

Devices, kits, and methods for in vivo imaging, such as fluorescent imaging, are provided. Specifically, fluorescent endoscopy accessory devices may be utilized with any prior endoscopy equipment to allow fluorescent imaging of tissue properties (e.g. tissue autofluorescence) or applied fluorescent molecular probes or tracers. Various kits incorporating one or more fluorescent endoscopy accessory devices as well as other endoscopy-related tools, products, or materials is further detailed. Also disclosed are methods of using the fluorescent endoscopy accessory devices and kits.

Description

[0001]

[0002] Systems and Methods Related to Endoscopic Imaging

[0003] Field of the invention

[0004] The invention relates to improved devices, or tools, kits and methods for in vivo imaging, such as fluorescent imaging of endoscopy-accessible tissues, and more specifically for imaging native tissue properties (e.g. tissue autofluorescence) or applied fluorescent molecular probes and / or tracers.

[0005] Background of the invention

[0006] Current endoscopy procedures rely on clinical examination of tissue to detect suspicious or diseased areas warranting biopsy or resection. Unfortunately, the ability to visibly distinguish suspected diseased tissue from normal tissue is very difficult clinically and requires significant expertise. As a result, if suspicious tissue is expected in an esophagus, for example in a patient with chronic gastric reflux, the current clinical protocol for detecting Barrett’s esophagus or dysplasia is called the Seattle protocol, which involves taking quadrant biopsies of the esophagus every l-2cm. In many patients, this protocol can result in 10-40 biopsies which results in unnecessary pain for the patient, medical cost and complexity, and potential complications.

[0007] Molecular imaging of tissue properties (e.g. tissue autofluorescence) or molecular probes and / or tracers may provide a better method of disease detection and diagnosis. Some devices have been commercialized for tissue autofluorescence or narrow-band imaging (e.g. Saneso, Karl Storz, etc.). However, these devices are very costly and take up significant space in the operating room. Additionally, most of these machines take the place of a facility’s (e.g., clinic or hospital) existing endoscope equipment resulting in expensive redundant equipment and retraining of staff to the new units. Therefore, purchasing these expensive pieces of equipment are a significant financial burden to medical institutions and health care costs. Also, typically fluorescent molecular probes and / or tracers are applied systemically in vivo via an injection or topically in vivo via a swab, spray, or sponge, which may complicate clinical usability.

[0008] Accordingly, improved systems and methods to enable more efficient autofluorescence imaging are desired.

[0009] Summary of the Invention

[0010] The present invention provides systems and methods to enable more efficient autofluorescence imaging than known prior devices.

[0011] According to an aspect of an embodiment of an endoscope accessory device according to the present invention, an illumination ring is provided to be secured to an endoscope for use in an imaging procedure. The illumination ring generally includes a distal surface oppositely disposed from a proximal surface, and a thickness extending therebetween.

[0012] According to an aspect of an embodiment of a device according to the present invention, the device includes a ring extending about an opening, a portion of the ring being at least one of radially and circumferentially extensible, a light source (e.g., light emitting diode) supported by the ring (e.g., on a first axial side thereof), the light source configured to emit a first light substantially in a first direction away from a first surface of the ring, and an imaging device supported by the ring (e.g., on the first axial side), the imaging device configured to receive a second light substantially from a second direction, the second direction being opposite the first direction. The light source(s) are preferably capable of emitting 50mW to 150mW of optical power, and at least one light source is capable of exciting an endogenous or exogenous fluorophore.

[0013] According to another aspect of an embodiment of a device according to the present invention, the imaging device comprising an image sensor (e.g., CMOS or CCD) and optics (lens and / or light filter) through which the second light passes prior to reaching the image sensor.

[0014] According to still another aspect of an embodiment of a device according to the present invention, the image sensor (e.g., RGB-IR sensor) is reactive to second light having wavelengths in the range of 365 nanometers to 3000 nanometers, such as infrared light having a wavelength between 825-875nm. An RGB-IR sensor comprises a plurality of pixels, wherein preferably at least 15% of the pixels are sensitive to infrared electromagnetic waves, and the sensor is operable on preferably less than 300mW of electrical power. A preferred RGB-IR sensor has a quantum efficiency of at least 20% and a sensitivity of at least 1500 mV / lux*sec. The RGB-IR sensor may be cooled using a thermoelectric cooler.

[0015] According to yet another aspect of an embodiment of a device according to the present invention, the ring comprises a disk, a majority of which is formed from an elastomeric material. At least one heat transfer agent may be embedded in the elastomeric material.

[0016] According to a further aspect of an embodiment of a device according to the present invention, the ring is formed about a first axis. The opening is formed about a second axis, the second axis being spaced from and at least substantially parallel to the first axis.

[0017] According to still a further aspect of an embodiment of a device according to the present invention, the second light comprises at least one of first light reflected from in vivo animal tissue, fluorescence of in vivo animal tissue, and fluorescence of molecular probes.

[0018] According to yet a further aspect of an embodiment of a device according to the present invention, wherein the imaging device comprises a camera module having a field of view of at least 70 degrees and a depth of field of 3mm - 25mm.

[0019] According to a farther aspect of an embodiment of a device according to the present invention, the ring has a thickness extending between and including a first axial side and a second axial side, the thickness being a maximum of 4mm.

[0020] According to a farther aspect of an embodiment of a device according to the present invention, the light source is capable of transmitting at least two wavelengths light, wherein at least one wavelength is capable of, in vivo, causing autofluorescence of animal bodily tissue and at least one other wavelength is capable of causing fluorescence of a molecular probe. Additionally or alternatively, at least one wavelength of light is in the human visible spectrum and at least one wavelength is capable of causing at least one of in vivo tissue autofluorescence and fluorescence of a molecular probe.

[0021] According to an aspect of an embodiment of a system according to the present invention, the system includes a ring extending about an opening, a portion of the ring being at least one of radially and circumferentially extensible, a light source (e.g., light emitting diode) supported by the ring (e.g., on a first axial side thereof), the light source configured to emit a first light substantially in a first direction away from a first surface of the ring, and an imaging device supported by the ring (e.g., on the first axial side), the imaging device configured to receive a second light substantially from a second direction, the second direction being opposite the first direction. The light source(s) are preferably capable of emitting 50mW to 150mW of optical power, and at least one light source is capable of exciting an endogenous or exogenous fluorophore. In addition to the ring, the system further includes a controller operatively coupled (by wires or wirelessly) to the ring and configured to receive image data from the imaging device. The controller is configured to at least one of activate the imaging device, deactivate the imaging device, set one or more parameters of the imaging device, and vary one or more parameters of the imaging device. Additionally or alternatively, the controller is configured to at least one of activate the light source, deactivate the light source, and vary an intensity of the light source. The controller is configured to receive image data from the imaging device and enables a visualization of a white light (e.g., human visible spectrum) images or video, fluorescent images or video, and / or an overlay thereof.

[0022] According to another aspect of an embodiment of a system according to the present invention, the system further includes a second light source supported by the ring, the second light source configured to emit a third light substantially in the first direction. The imaging device being configured to receive a fourth light substantially from the second direction, the second direction being opposite the first direction.

[0023] According to an aspect of an embodiment of a method according to the present invention, the method includes the step of attaching a fluorescent endoscopic accessory device to an endoscope. The accessory device includes an illumination ring supporting a camera module containing an RGB-IR sensor, at least one light emitting diode (LED) capable of exciting an endogenous or exogenous fluorophore, and an optical filter. The camera module includes a field of view of at least 70 degrees and a depth of field of 3mm - 25mm, and the at least one LED is capable of emitting at least 50mW of optical power. The accessory device is introduced into an opening (natural or incised) in an animal (e.g., human, canine, feline, bovine, porcine, etc.) body. Using the RGB-IR sensor, fluorescence of a fluorophore is sensed. The fluorophore may be selected from the group consisting of an endogenous fluorophore and previously applied exogenous fluorophore.

[0024] According to an aspect of an embodiment of a kit according to the present invention, the kit includes an endoscopic accessory device and a controller capable of operatively coupling to the accessory device to provide power and / or control. The accessory device includes an illumination ring supporting a camera module containing an RGB-IR sensor, at least one light emitting diode (LED) capable of exciting an endogenous or exogenous fluorophore, and an optical filter. The camera module includes a field of view of at least 70 degrees and a depth of field of 3mm - 25mm, and the at least one LED is capable of emitting at least 50mW (e.g., 50-150m W) of optical power.

[0025] According to another aspect of an embodiment of a kit according to the present invention, the kit may further include at least one syringe, wherein each syringe contains a substance selected from the group consisting of: a buffer rinse solution (e.g., isotonic saline), a pretreatment solution (e.g., n- acetylcysteine), and an aqueous solution comprising a fluorescent molecule (e.g., near-infrared dye). Additionally or alternatively, the kit may include at least one spray catheter.

[0026] Accordingly, endoscope accessory devices according to the present invention easily integrates with all existing endoscopy equipment and provides fluorescence imaging capabilities of tissue (e.g. autofluorescence or narrow-band imaging) and / or molecular probes and / or tracers. Therefore, medical institutions do not need to purchase more expensive and bulky equipment that takes up limited space in the operating room.

[0027] The present invention provides improved devices, or tools, for imaging of tissue properties (including autofluorescence and narrow band imaging) and / or molecular imaging of fluorescent molecular probes and / or tracers in vivo. The disclosed invention(s) is(are) intended to be useful in vivo for fluorescence imaging of the following mucosal / epithelial sites where various endoscopic equipment (or similar visualization equipment) is utilized: oral cavity, oropharynx, pharynx, larynx, esophagus, nasal cavity, cervix, vulvar, uterus, anus, small intestines, bile duct, colon, rectum, and bladder. In some preferred embodiments, the fluorescence endoscopy accessory device is administered through the working channel of existing endoscopes. In other preferred embodiments, the fluorescence endoscopy accessory device is placed on the exterior of the endoscope and then administered in vivo. In the latter embodiment, the fluorescence endoscopy accessory device might be clinically advantageous as it does not inhibit the use of existing working channel(s) (also called instrument port(s)) within the endoscope. In other words, this type of device would provide clinical usability advantages and benefits.

[0028] A further embodiment of the invention is a method of utilizing the inventive device(s) in vivo in combination with various fluorescent molecules, dyes, or agents for the detection of disease in real-time. Additionally, a pre-treatment may be used to selectively condition target bodily tissue prior to fluorescence visualization utilizing the disclosed equipment. As an example, n-acetylcysteine might be applied as a mucolytic agent prior to the topical application of fluorescent dyes, molecules, and / or tracers. Alternative pretreatment solutions may comprise ethanol, one or more alcohols, water, and / or various surfactants to help clean the epithelial surface prior to further analysis.

[0029] Specifically, a method according to the present invention includes steps of attaching a fluorescent endoscopy accessory device to an exterior distal end of an endoscope (motherscope) and inserting the joined fluorescent endoscopy accessory device and endoscope into an animal (e.g., human) patient’s esophagus. Optionally, a tissue pretreatment solution may be applied to bodily tissue in vivo using a spray catheter, the tissue may be rinste with water or saline, and tissue autofluorescence may be visualized. A fluorescent solution, molecule, dye, or tracer may be topically applied in vivo to the tissue using a spray catheter. The fluorescent solution, molecule, dye, or tracer may be visualized in vivo utilizing the fluorescent endoscopy accessory device, wherein a visible deviation (i.e. increase or decrease) in fluorescence, from the fluorescent solution, molecule, dye, or tracer in vivo, is indicative of disease, such visible deviations being identified automatically or manually noted. Instead of visualizing the fluorescent solution, molecule, dye, or tracer in vivo utilizing the fluorescent endoscopy accessory device, the method may alternatively include simultaneously visualizing the fluorescent solution, molecule, dye, or tracer and normal white light tissue imaging in vivo utilizing the fluorescent endoscopy accessory device. Additionally or alternatively, a method according to the present invention may include performing a biopsy on one or more areas of visible aberrant fluorescence (i.e. increased or decreased relative to normal). In other embodiments, any area of aberrant fluorescence compared to visibly normal tissue may be considered suspicious and then biopsied if desired. In alternative embodiments of the invention, the described method can be used in the oral cavity, oropharynx, pharynx, larynx, nasal cavity, cervix, vulva, uterus, anus, small intestines, bile duct, colon, rectum, and bladder.

[0030] The above summary of the present invention is not intended to describe each disclosed embodiment or every implementation of the present invention. The description that follows more particularly exemplifies illustrative embodiments. In several places throughout the description, guidance is provided through lists of examples, which examples can be used in various combinations. In each instance, the list serves only as a representative group and should not be interpreted as an exclusive list.

[0031] Brief Description of the Drawings

[0032] Figure l is a perspective view of an embodiment of an illumination ring according the present invention.

[0033] Figure 3 is a front elevation of a second embodiment of an illumination ring according to the present invention.

[0034] Figure 4A is a schematic block diagram of a system including the illumination ring of Figure 3.

[0035] Figure 3B is a front elevation view taken along lines 3B-3B of Figure 3 A.

[0036] Figure 4 is a front elevation view of an embodiment of an accessory endoscope according to the present invention in a deployed position.

[0037] Figure 5 is a perspective view of the embodiment of Figure 4 extending from a working channel of a motherscope.

[0038] Figure 6 is diagrammatic view of an accessory endoscope according to the present invention disposed within a working channel of a motherscope.

[0039] Figure 7A is a graph of spectral sensitivity for red, green, and blue pixels in a complementary metal-oxide-semiconductor (CMOS) sensor.

[0040] Figure 7B is a perspective view of a typical RGGB pattern of a CMOS sensor.

[0041] Detailed Description

[0042] Although the disclosure hereof is detailed and exact to enable those skilled in the art to practice the invention, the physical embodiments herein disclosed merely exemplify the invention which may be embodied in other specific structures. While the preferred embodiment has been described, the details may be changed without departing from the invention.

[0043] The present invention provides an endoscopic accessory system designed to enable real-time fluorescence imaging of tissue during standard endoscopy procedures. In contrast to existing fluorescence-enabled endoscopes that require replacement of legacy equipment, retraining of personnel, or significant capital investment, the disclosed device is modular, lightweight, and universally compatible with current endoscopic systems. This accessory system can be deployed without substantial disruption of existing clinical workflows or requiring new scopes, which represents a significant advantage over the limited adaptability of commercial narrow-band or fluorescence imaging systems.

[0044] The modular design of the system and related kits (e.g., packages) may be provided in a variety of configurations:

[0045] • a first configuration including an illumination ring to be supported by an endoscope, wherein the illumination ring is utilized with a fluorescence capable imaging endoscope, which may or may not be according to the present invention;

[0046] • a second configuration including an illumination ring to be supported by an endoscope and a control box operatively coupled to the illumination ring to activate, deactivate, and / or control intensities of light sources on the illumination ring, wherein the illumination ring is utilized with a fluorescence capable imaging endoscope, which may or may not be according to the present invention;

[0047] • a third configuration including a first accessory endoscope according to the present invention, and a control box operatively coupled to the accessory endoscope to activate, deactivate, and / or control intensities of light sources supported by the accessory endoscope and to control or receive data from an imaging device also supported by the accessory endoscope;

[0048] • a fourth configuration including an illumination ring to be supported by an endoscope, an imaging device supported by the illumination ring, and a control box operatively coupled to the illumination ring to activate, deactivate, and / or control intensities of light sources supported by the ring and to control or receive data from the imaging device.

[0049] This flexibility in configuration allows clinicians to select the best option for the anatomy and procedure of interest while preserving full access to the working channel of the endoscope — a constraint not addressed in many existing designs. The accessory is optimized for imaging both intrinsic tissue autofluorescence and extrinsic fluorescent molecular tracers, and provides visual overlay functionality to support diagnostic decisions in real time.

[0050] By preferably retrofitting existing endoscopic platforms rather than replacing them, this invention provides a cost-effective, minimally disruptive path to advanced fluorescence diagnostics across multiple clinical indications, including gastrointestinal, urologic, and gynecologic procedures.

[0051] A first embodiment of an endoscope accessory according to the present invention is an illumination ring 100, as shown in Figure 1. The illumination ring 100 is preferably at least partially radially or circumferentially extensible (e.g., flexible and / or stretchable in one or both of those directions), a majority of which may be formed from a biocompatible elastomer such as silicone, which preferably attaches (e.g., compressionally) externally to an external circumference of a distal end of a standard, preexisting endoscope (as a “motherscope”). The ring 100 is formed substantially in the shape of a disk about a central ring axis 102 and includes a central opening 104 (preferably cylindrical in shape in free state) formed about an opening axis 106, the opening axis 106 positioned preferably spaced radially from but parallel to the ring axis 102. The disk generally includes a distal surface 101 and an axially opposite proximate surface 103. The opening 104 is bounded by a substantially cylindrical or partially cylindrical mounting surface 105. The ring 100 is preferably placed and supported externally on a distal portion of the motherscope (extending through the opening 104) and (if it is not battery operated) may include wires (not shown) that run parallel with the motherscope for power and / or control (similar to those shown in Figure 6A). The ring 100 has a preferred maximum thickness 107 (extending between and including the distal surface 101 and the proximal surface 103) of less than 10 millimeters, but more preferably about 4 millimeters, and the thickness 107 may vary across its diameter or about its circumference.

[0052] The ring 100 supports one or more light sources 110 (e.g., light-emitting diodes (LEDs), which may be high-intensity). The light sources 110 may be all the same, but preferably comprise at least two different sources, and may be used for white light imaging, tissue autofluorescence in a subject animal (e.g., human) body, and / or narrow band imaging, which is then visualized (e.g., by an imaging system, such as a digital camera). Additionally or alternatively, these light sources 110 may be used to visualize fluorescence or luminescence of applied molecular probes and / or tracers. Therefore, more than one wavelength of light may be incorporated into the illumination ring by including different color LEDs 110. For example, one or more ultraviolet LEDs 112, and / or one or more blue LEDs 114 can be used to excite autofluorescent tissue components (e.g., NADH, collagen), while red or near-infrared (NIR) LEDs 116 can excite exogenous fluorophores such as methylene blue or IR800CW. In a preferred embodiment, the LEDs 110 are configured or controlled to enable both singlewavelength and multi -wavelength excitation, including serial (e.g., in order of increasing or decreasing wavelength, or other predetermined order) or simultaneous (more than one color at a time, such as with broadband white light and / or a plurality of different color LEDs) illumination modes. In a preferred embodiment of the invention, the light sources 110 are modular and manually (e.g., with a human hand or with a simple hand tool) exchangeable or replaceable within the ring 100 to allow a user to easily change between different illumination wavelengths.

[0053] To enable white light imaging, the illumination ring 100 may include at least one white light LED 118. By alternating or pulsing activation of white light and fluorescence excitation sources, or by continuously emitting both, at least substantially simultaneous realtime overlay of anatomical and biochemical imagery on the same video feed, depending on the imaging system used with the ring 100. This feature is not currently available in most commercially available fluorescence-capable endoscopy systems, which often require switching modes or scopes.

[0054] The light sources 110 may be separately packaged LEDs (i.e. each their own discrete part) or in multi-die packaged LEDs, wherein a single LED package can emit at least two different wavelength peaks or at least three different wavelength peaks. Optical filters may or may not be located in front of the light source / LEDs. Due to the size constraints of the silicone illumination ring, only certain miniature LEDs can fit and preferred LEDs occupy less than 25 square millimeters (mm2), more preferred LEDs occupy less than 10 mm2, and most preferred LEDs occupy less than 5 mm2. For fluorescence, the LED(s) may provide between about 20 to about 50 milliwatts (mW) of optical power (radiant flux or radiant power). More preferred, the LED(s) for fluorescence will provide between 50mW - 250mW of optical power, and most preferred, the LED(s) for fluorescence will provide between 250 - 500mW of optical power. These optical power values may correlate to power from one single LED or may be summed from at least two LEDs of the same type and / or color / wavelength. Depending on the optical filters used for imaging (described further below), pulsing of the separate white light LED and other wavelength LED may not be necessary to obtain distinct images. All light sources 110 may emit the same wavelength(s), but varied sources 110 are advantageous, wavelengths of light may be used by including at least one LED of each different wavelength / color in the illumination ring. This may be useful to provide 1) white light illumination, 2) autofluorescence illumination (typically UV or blue LEDs are used), and 3) illumination to cause fluorescence of molecular probes and / or tracers (e.g. far-red or nearinfrared light). No known existing endoscopy device can visualize white light, autofluorescence, and fluorescence from molecular probes and / or tracers in vivo and provide independent images and / or video and overlay images and / or video, which is possible using the inventive system.

[0055] The illumination ring 100 is preferably made of biocompatible materials and can be sterilizable and reprocessable (e.g., intended for reuse after autoclave, for example) or disposable (e.g., intended for single-use or repeat use with same patient during same procedure). While silicone is a preferred material for the illumination ring 100, in certain embodiments the ring 100 may comprise non-silicone materials such as polyurethane, polydimethylsiloxane, or other elastomeric materials. Optionally, additives may be incorporated into the ring material. For example, heat transfer agents may be incorporated into the ring material to assist in heat-conductive (or dispersive) dampening of potential hotspots that may be caused by the light sources 110, or by other electrical components supported by the ring 100, or by other devices in vivo, or by the body itself. Exemplary and non-limiting examples of heat transfer agents include: graphite fibers, graphene flakes, ceramic particles (e.g. metal nitrides, boron nitride, silicon carbide, and silicon nitride), metal oxides (e.g. aluminum oxides), metal particles, and carbon nanotubes. In a preferred embodiment, at least one heat transfer agent is added to the ring material at a concentration of about 0.01%-20%.

[0056] The illumination ring 100 requires a power source to power the light sources 110. The power may be provided from outside of the ring 100, such as through a wired connection previously mentioned. An alternative design of the illumination ring can be powered by a battery housed within the ring 100. In another design of the silicone illumination ring, the electrical power is provided via induction from the supporting endoscope (motherscope) and / or an accessory endoscope and / or another supply.

[0057] The illumination ring 100 preferably includes electronic circuitry that is configured to control or at least bias the light sources 110. Control of the light sources 110 may be provided onboard the ring 100 or may originate outside the ring 100, such as from a control box (further described below) through wired or wireless communications. Onboard control of light sources 110 may include a predetermined or random or pseudorandom program of control (on / off, intensity, and / or color / wavelength selection) for each light source 110 or a combination of light sources 110. For example, prior to introducing a motherscope supporting the ring 100 into an animal body, the ring 100 may be powered to an on state. In the on state, each light source 110 may be powered on to emit a particular wavelength of light at a continuous brightness for an entire duration of a procedure. Alternatively, parameters of each light source 110 or a plurality of each light source 110 may be automatically varied, such as through a repetitive predetermined cycle of on / off, varying intensity, and / or varying color(s), at one or more predetermined times or time intervals. Alternatively, parameters of each light source 110 or a plurality of each light source 110 may be automatically varied, such as through a random or pseudorandom control of on / off, varying intensity, and / or varying color(s).

[0058] To make the ring 100, a preferred material is selected and formed into a desired shape. For instance, a preferably elastomeric material (e.g., silicone or polyurethane, preferably medical grade) is selected and preferably molded into the desired shape. The material may be molded, and electrical components and connections (if any) may be mounted thereafter. However, a more preferred construction methodology includes assembly of electrical components and circuitry (preferably on a printed circuit board or flex circuit board) and then overmolding that assembly with the selected ring material into the desired shape. Material can be removed from, or prevented from being deposited over, the light sources 110.

[0059] In use, a ring 100 is secured to a motherscope (e.g., motherscope 10 in Figures

[0060] 6A-6B) in a preferred manner such that it does not interfere with a motherscope working channel 12, thereby preserving clinician ability to use instruments therethrough, such as spray catheters or biopsy forceps. The motherscope 10 is inserted into a subject animal body (preferably live and at least partially sedated), either through a natural opening in the body (e.g., mouth, nostril, anus, vagina, cervix) or through an incision made in the body. The ring 100 is operated as described herein to emit light from the light source(s) 110 onto biological or and / or fluorescent material(s) within the body. Light reflected or fluoresced is then sensed by an imaging system, such as a digital camera mounted on an endoscope (such as the accessory endoscope 200, described below) inserted through a working channel 12 of the motherscope 10 or mounted on the motherscope 10 itself. Image data captured by the imaging system may be stored locally in the imaging system in vivo, but is preferably transmitted (substantially live or in real-time) for display, storage, and / or analysis ex vivo.

[0061] A second embodiment of an endoscope accessory according to the present invention is an accessory endoscope 200, as shown in Figures 2-4, where like numbering refers to at least similar functional components to the first accessory 100. Generally, the accessory endoscope 200 includes a distal surface 201 supporting an imaging device 222, such as a CMOS camera (with optics). The distal surface 201 may also support a light source 210 such as a white light LED 218. The accessory endoscope 200 may be used in conjunction with the illumination ring 100, or by itself. The accessory endoscope 200 has a diameter of about 2.3 millimeters (mm) (+0.15 mm / -0.5 mm; more preferred +0.15 mm / -0.25 mm), which allows it to be introduced down a working channel 12 of standard endoscopes, gastroscopes, colonoscopes, cystoscope (each a “motherscope”) during these types of in vivo procedures. The working channel 12 of such motherscopes 10 typically ranges from about 2.7 mm to about 3.2 mm in diameter 12a (though larger diameters may be available). The accessory endoscope, while it may be larger for introduction through different modalities, preferably has a maximum working diameter of less than 3.2 mm, more preferably less than 2.75 mm. The accessory endoscope described herein has a most preferred working diameter of approximately 2.3 mm (+0.15 mm / -0.25 mm), allowing it to be used with nearly all existing endoscopic systems without modification.

[0062] The imaging system has a field of view of preferably at least 70 degrees, and more preferably at least 120 degrees. The camera 222 on the accessory endoscope 200 has a depth of field of 3 mm - 25 mm, and more preferably a depth of field of 3 mm - 50 mm. Ideally the CMOS sensor located within the camera has wafer-level optics, although glass optics are acceptable. Preferably, the CMOS sensor includes an array of at least 150k pixels. More preferably, the CMOS sensor includes an array of at least 250,000 pixels. Most preferably, the CMOS sensor includes an array of at least 1,000,000 pixels. Preferably, the CMOS sensor has a sensitivity (responsivity) of at least 500 mV / lux*sec. More preferred, the CMOS sensor has a sensitivity of at least 1500 mV / lux*sec. Most preferred, the CMOS sensor has a sensitivity of at least 2500 mV / lux*sec. The CMOS sensor is preferably relatively low power and consume preferably less than 500 mW, more preferably less than 300 mW, and most preferably less than 150 mW. Preferred CMOS sensors include, but are not limited to, OV6946, OV2744, OV2736, OV2778, OV4686, OV9756, OX05B, and OX02C (all such sensors available from Omnivision, Santa Clara, CA). In certain embodiments, the CMOS sensor has a quantum efficiency of preferably at least 10%, more preferably at least 20% and most preferably at least 35%. Although specific embodiments are provided which illustrate the invented fluorescent endoscope accessory device having one CMOS sensor camera, it should be noted that an imaging system to be employed in connection with embodiments according to the present invention may use multiple distinctly separate CMOS sensors or cameras included in one endoscope accessory device.

[0063] Light sources 210 may be provided in addition to the imaging system 222. An embodiment of light source mounting includes flexible circuit connections coupled to one or more wing structures 20 la, 20 lb, which are preferably moveable from a collapsed position, as shown in Figure 3, to a deployed position, as shown in Figure 2. At least substantially similar to the configuration of the light sources 110 in the first embodiment 100, the light sources 210 (LEDs or alternative light sources) may be able to emit different (from another light source 210 or selectively) wavelengths for different purposes (e.g. white light imaging, autofluorescence imaging, and / or fluorescent imaging of molecular probes / tracers). The wing structures 20 la, 20 lb are coupled to a distal end of the accessory endoscope 200 by way of, and my comprise, flex PCBs. In their free state, or collapsed position, the wing(s) 201a(,b) extend longitudinally from the distal surface 201, which facilitates the introduction of the accessory endoscope 200 through a working channel of a motherscope 10. Once the accessory endoscope 200 is inserted through a motherscope 10 working channel 12 past a distal end of the motherscope 10 (preferably by a distance at least as long as a wing length 201c), guidewires 18 (or alternative mechanical, such as gears, or electrical means, such as piezoelectric actuators) can be used to bend the flex PCBs such that the wings 201a, b pivot in substantially opposite directions 14,16 to extend radially from the distal surface 201 (approximately perpendicular to a longitudinal length of the accessory endoscope) so the light sources 210 can provide illumination to the target tissue in vivo. This accessory endoscope 200 (with light sources 210) is preferred to be used during cystoscopy procedures (i.e. screening of the bladder) as the cystoscope cannot significantly increase in diameter (i.e. with a silicone ring) as it has to be introduced through a urethra. Preferably the length 201c of each wing 201a,b is approximately 4 mm, more preferably the length of each wing 201a,b is about 2 mm to about 4 mm. Due to limited space to heat sink the light sources 210, it is preferred to power them at a current less than 100mA and more preferably about or less than 50mA. Testing using a flex PCB has confirmed that an LED powered at 2.7V and 50mA did not lose any optical power after 1 hour of continuous run time. If necessary, cooling of light sources 210 may be accomplished using a miniature Peltier cooler, thermoelectric cooler, Peltier heat pump, or equivalent.

[0064] To manage thermal load at the sensor 222, active or passive cooling techniques may be employed. This includes miniature thermoelectric (Peltier) coolers, heat sinks, or airflow mechanisms to stabilize the sensor’s performance over extended procedures. The distal portion of the accessory endoscope, which houses the sensor and optics, is less than 15 mm in length, and preferably under 10 mm, with most preferred embodiments having a length below 7 mm. This compactness enables the device to pass through sharply angled or deflected motherscope channels 12, as shown in Figure 4, without obstruction, which is an advantage over bulkier rigid-tip systems.

[0065] The accessory endoscope 200 is made of biocompatible materials and can be sterilizable and reprocessable or disposable. A hardware portion of the accessory endoscope 200, containing at least the camera hardware and being substantially rigid, is located proximate the distal surface 201a. The hardware portion is preferably less than 15mm in length, more preferably less than 10mm in length and most preferably less than 7mm in length to facilitate navigation through the working channel of a bent endoscope / motherscope (see Fig. 4). In another embodiment, the hardware portion is preferably less than 12 mm in length to be able to navigate through the working channel of a bent endoscope / motherscope.

[0066] To further distinguish embodiments according to the present invention from other devices, it is noted that most prior endoscopic fluorescence systems integrate the imaging optics directly into the primary scope body, which limits flexibility and forces complete hardware replacement. In contrast, the disclosed accessory endoscope can be interchanged or removed independently and can be sterilized, reprocessed, or used in single-use formats as needed for specific clinical or regulatory requirements.

[0067] A third embodiment of an endoscope accessory according to the present invention is another embodiment of an illumination ring 300, which further includes an imaging device 322, such as a CMOS camera. The ring 300 is at least substantially similar to the first embodiment 100, where like numbering indicates at least substantially similar structure and / or functionality. Rather than requiring use with a separate imaging device, such as a device provided on an accessory endoscope or a motherscope, the ring 300 includes an on-board imaging device 322 (similar or identical to the imaging device 222), which provides ex vivo visualization / analysis of data acquired in an in vivo environment. Integration of an imaging device 322 into the ring 300 which is then coupled to a motherscope 10 eliminates the need for another endoscope for viewing as both illumination and visualization are accomplished using the ring 300, which would be advantageous to simplify the use of the accessory device and for keeping the motherscope working channel open for other endoscopy tools (e.g. spray catheter, biopsy forceps, etc). Preferred CMOS sensors for incorporation into the ring 300 include: OV6946, OV6930, OV9732, OV7676, OV9732, OV01A1S, OV7695, OV2744, OV2736, OV2778, OV4686, OV9756, OX05B, and OX02C which are all available from Omnivision. In particular, OV9738, OV01A1S, OV2744, OV2736, OV2778, OV4686, OV9756, OX05B, and OX02C are further preferred as they are RGB-IR sensors.

[0068] Optional cooling of the CMOS sensor may be accomplished using a miniature Peltier cooler, thermoelectric cooler, Peltier heat pump, or equivalent. Alternatively, other cooling methods may be utilized including at least one heat sink or utilizing forced air within the camera system to cool the CMOS sensor. In certain embodiments, the heat sink may facilitate heat transfer to the housing of the illumination ring. Similar cooling strategies may be utilized for the LEDs on the illumination ring. Preferably, the CMOS sensor or camera module occupies an area on the silicone ring less than 50 mm2, more preferably less than 30 mm2, even more preferably less than 20 mm2, and most preferably less than 12 mm2. As an alternative embodiment, the device may incorporate at least one CMOS sensor-based camera and at least one CCD sensor-based camera.

[0069] While the preferred embodiment utilizes a flexible silicone or polyurethane or elastomeric illumination ring for integration with and / or mounting to a motherscope, the invention also supports a variety of alternative mounting structures, offering expanded options for different clinical workflows, device form factors, and anatomical access requirements.

[0070] In place of the standard ring-shaped structure, the illumination and imaging module may be incorporated into other securement mechanisms, including but not limited to:

[0071] • Snap-on clips that attach to the distal end of the endoscope;

[0072] • Strap-based or sleeve-based wraps for larger-diameter scopes;

[0073] • Adhesive-backed pads or double-sided biocompatible adhesives for temporary attachment;

[0074] • Set screws or clamp fixtures for semi-permanent (removable with tools) integration;

[0075] • Magnet-based mounts, especially in applications involving metallic endoscope tips or ferromagnetic docking stations.

[0076] These options enable clinicians to rapidly attach or detach the accessory based on procedural needs, sterilization protocols, or device reuse policies. Furthermore, they allow for customization of the imaging geometry (e.g., top-down, side-facing) and the flexibility to use the system in non-traditional endoscopic applications, such as rigid scopes or specialty catheters.

[0077] In one embodiment, the modular components — including the camera and LEDs — may be embedded in interchangeable cartridges that lock into a base housing affixed to the motherscope. This configuration provides the added benefit of hot-swapping imaging modules without removing the entire mount.

[0078] Where an imaging device is used, a filter may be located between the CMOS sensor and lens assembly within the imaging device. In a preferred embodiment, an optical filter is located between the CMOS sensor and lens assembly within the camera unit which improves filtering of visualized light because the filtering occurs after focusing and collimating of the light. Fig. 3 also details that a CMOS sensor / camera can be included in the design of this part. Fig. 4 shows another embodiment with white light LEDs, far-red LEDs, and a CMOS camera module. Specifically, the silicone illumination ring 1 consists of a silicone body 2 defined by two circular shapes 7 and 8 that result in a ring shape with an empty center 3. Incorporated on at least one printed circuit board (PBC), preferably at least one metal clad PCB (mcPCB), housed within the silicone body 2, is at least one white light LED 4, at least one far- red LED 22, and at least one camera module 23. In certain embodiments, other wavelength LEDs may be utilized. Preferably the camera module incorporates a CMOS sensor, however, a CCD sensor could be utilized. The camera module comprises a sensor (CMOS or CCD), connectors, lenses and spacers, mounts or housings, and optional optical filters, amongst other industry-known components. Fig. 5 shows the entire fluorescent endoscopy accessory device (silicone illumination ring from Fig. 4, control box, and connection means) mating with a traditional endoscope. Specifically, the silicone illumination ring 1 (incorporating a CMOS camera module; identical to Fig. 4) is mounted distally on the endoscope 9. The silicone illumination ring is connected to the control box 12 via a ribbon cable 11. The control box 12 is connected to a monitor 13 via standard video connection wires (e.g. HDMI, VGA, etc.) 14. The inset image 10 shows a front view of the silicone illumination ring 1 (from Fig. 4) mating to the distal portion of the endoscope / motherscope 9. The endoscope / motherscope 9 contains an instrument port / working channel 15, a spray nozzle 16, and a camera module 17.

[0079] Figure 6A depicts a system 1300 according to the present invention, including an illumination ring 300 supported by a motherscope 10 at or near its distal end. The ring 300 (while it may be used by itself, such as for gathering photographic or visual images and storing them in onboard, preferably nonvolatile, memory) is preferably used with a controller 1310. The ring 300 may be coupled to the controller 1310, such as by electrical conductors (wires) 1312, or such coupling may be wireless. Through the coupling, the ring 300 preferably receives electrical power and / or control signals from the controller 1310. The controller 1310 serves as an interface for the operation and configuration of the imaging accessory system, and visualization or generation or passthrough of image data. Designed for use in clinical environments, the controller 1310 provides control over illumination, camera parameters, and video output, streamlining integration into standard endoscopy workflows while delivering advanced functionality. The controller 1310 has input connection means (not shown) for electrical power, electrical and / or communication coupling means for one or more devices, such as the illumination ring 100, the accessory endoscope 200, and the illumination ring 300. The controller 1310 also has an integrated display or output video connection means, such as HDMI or VGA outputs. Alternatively, if the silicone ring includes the CMOS sensor / camera, the controller 1310 preferably includes only coupling means to manage both illumination and camera control. The controller 1310 provides a user interface to allow a user to control the illumination and camera operation. For example, the user can alter various camera settings such as exposure time, frame rate, gain, contrast, etc. The camera’s frame rate is set to provide adequate fluorescence imaging, which can be as slow as 1 frame per second (fps), although more preferably the frame rate is between 5-15 fps, even more preferably the frame rate is between 15-30 fps, and most preferably the frame rate is between 30- 90fps. The controller 1310 may be programmed to automatically define camera settings to obtain the best fluorescent video / image to the user. Using the controller 1310, the user can alter delivered illumination, which may include changing illumination strengths (e.g. optical powers), patterns, and timing. Depending on the number and types of LEDs utilized, the controller 1310 can offer various modes that offer significant clinical advantages. For example, white light images and fluorescent images may be overlayed to visualize tissue anatomy and fluorescence simultaneously. The fluorescent images could be from tissue autofluorescence and / or narrow band imaging and / or fluorescence from molecular probes / tracers. This is but one advantage over many current systems, which often require physical mode-switching or do not support concurrent white light and fluorescence visualization. The disclosed controller preferably allows seamless, non-disruptive switching between modes during a live procedure, minimizing cognitive and procedural delays.

[0080] The control box preferably is capable of intelligent image processing and diagnostic assistance software. These software features transform the system from a passive imaging system into an active diagnostic aid, capable of enhancing contrast, guiding clinical decisions, and even flagging pathological findings in at least substantially real time. In a particular example, fluorescent measurements from normal tissue (either autofluorescence measurements or fluorescent measurements from an exogenous molecule) are first obtained using the disclosed imaging system. The fluorescent measurements from normal tissue may be obtained automatically by the device or via user selection of visibly normal tissue. The disclosed imaging system will then automatically normalize subsequent fluorescent measurements to the “normal” tissue measurement to facilitate easier visualization and interpretation of fluorescent differences compared to the “normal” tissue measurement result. In another embodiment, the user can select areas of visual suspicion, from which fluorescent measurements can be obtained. In this situation, using the recorded fluorescent results from the visibly “normal” and “suspicious” tissue, the imaging system may automatically modify the displayed video stream to enhance the contrast and / or visualization between “normal” and “suspicious” tissue. In some cases, depending on the measured fluorescent results, the software may highlight / indicate areas of suspicion for the clinician and could provide a hypothetical diagnosis (for example in the esophagus the diagnosis could read “normal tissue”, “Barrett’s

[0081] Esophagus”, “dysplasia”, or “cancer”. Such an approach would facilitate disease detection through better displaying suspicious areas compared to normal tissue areas in vivo.

[0082] One or more of the inventive devices may be provided in a kit for ease of integration, which may include instructions for assembly and use. An endoscope-compatible fluorescence imaging kit may include one or more of an illumination ring 100, accessory endoscope 200 (with or without wings 201a, 201b), an illumination ring 300, a controller 1310. In a first configuration of a kit (i.e., preferably in an air- and water-impervious package) an illumination ring 100 is provided. In a second configuration of a kit (i.e., preferably in an air- and water-impervious package) an illumination ring 100 and a controller 1310 are provided. In a third configuration of a kit (i.e., preferably in an air- and water-impervious package) an illumination ring 100 and an accessory endoscope 200 (with or without wings 20 la, 20 lb) are provided. In a fourth configuration of a kit (i.e., preferably in an air- and water-impervious package) an illumination ring 100, an accessory endoscope 200 (with or without wings 201a, 201b) and a controller 1310 are provided. In a fifth configuration of a kit (i.e., preferably in an air- and water-impervious package) an illumination ring is provided. In a sixth configuration of a kit (i.e., preferably in an air- and water-impervious package) an illumination ring 300 and a controller 1310 are provided.

[0083] Any of the above kit configurations may further include one or more of the following items: at least one syringe containing a mucolytic solution, at least one syringe containing sterile water or isotonic solution (e.g. 0.9% sodium chloride) or a buffer rinse solution, at least one syringe containing a solution containing at least one fluorescent molecular probe, and / or at least one spray catheter for applying the solutions contained in the kit. Any kit configuration may further include one or more of the following items: biopsy forceps, biopsy specimen vials, gauze, and / or tissue fixative solutions.

[0084] While the light sources 110,210,310 may be selected for in vivo (animal) imaging at any detectable wavelength, typical wavelength ranges are summarized in Table 1, below. Additionally, the disclosed invention may detect fluorescence properties of other organisms within a subject animal (e.g., human) body such as bacteria, yeast, fungi, viruses, prions, amongst others. This technique is useful to detect infections, or other types of diseases.

[0085] Table 1: Generated, sensed or detected wavelength ranges typically used for in vivo fluorescence imaging. The disclosed invention can be utilized for any wavelength within the electromagnetic spectrum, however, these wavelength ranges are preferred.

[0086] The following definitions are provided for ease of reference.

[0087] Endogenous - found naturally inside a subject animal body. For example, endogenous fluorophores are naturally occurring and present within cells or tissues of a subject animal (e.g., human) body.

[0088] Exogenous - not naturally found in a subject animal body; external. For example, exogenous fluorophores are fluorescent molecules that are not naturally found within a subject animal (e.g., human) body but are instead introduced for fluorescence visualization purposes.

[0089] Emission Wavelength - wavelength emitted from a fluorophore after the fluor ophore has been excited via its excitation wavelength.

[0090] Excitation Wavelength - wavelength of electromagnetic radiation that most efficiently excites a fluorophore and typically yields the highest amount of fluorescence emission from the fluorophore.

[0091] Fluorescence - visible or invisible radiation emitted by certain substances / molecules as a result of incident radiation of a shorter wavelength.

[0092] Fluorophore (or fluorochrome, similarly to a chromophore) - a fluorescent chemical compound, substance, or molecule that can emit light in response to light excitation.

[0093] Motherscope - a primary endoscope utilized during endoscopy procedures, which typically contains at least one working channel, and other accessories (e.g. spray nozzle, etc).

[0094] Tissue autofluorescence - natural emission of light by biological structures within tissue when they have absorbed light of a lower wavelength. Typically, tissue autofluorescence is accomplished by illuminating the tissue with blue light and observing a resulting green light emitted by biological structures within tissue. Usually a loss of autofluorescence is indicative of non-normal tissue due to inflammation, or diseases such as cancer. Tissue autofluorescence is different than fluorescent light originating from artificially added fluorescent markers (fluorophores). “Tissue autofluorescence” also refers to any native tissue fluorescent property that is commonly known to provide diagnostic benefit, for example, narrow band imaging.

[0095] Molecular probe - molecule that has a high affinity for a target molecule. Throughout the disclosure, it is to be understood that a molecular probe is conjugated to a reporter molecule, which allows for the detection of the molecular probe’s binding. In a preferred embodiment, the reporter molecule is a fluorophore (unless stated otherwise), which allows for the fluorescent visualization of the molecular probe binding patterns using a camera or the human eye. Additionally, in another embodiment of the invention, the molecular probe may be itself fluorescent, such as a nuclear fluorescent stain (e.g. DAPI) which has an affinity for nucleic acids and acidic molecules and is also fluorescent.

[0096] Molecular imaging - molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although data is gathered in vivo, it is normally received or accessed ex vivo for visualization, characterization, and measurement, though some preprocessing and / or temporary or nonvolatile storage may occur in vivo. Molecular imaging typically consists of 2- or 3-dimensional imaging as well as quantification over time. The techniques used include radiotracer imaging / nuclear medicine, magnetic resonance (MR) imaging, MR spectroscopy, optical imaging, fluorescence-based imaging, ultrasound, and others. One important variable during molecular imaging is ensuring a molecular probe and / or reporter molecule signal is obtained that exceeds the noise floor or background signal. Typically researchers discuss this as the “signal to noise” or “signal to background” ratio.

[0097] Reporter molecule - molecule that is chemically bonded to a molecular probe to provide a means of measuring or quantifying the molecular probe’s binding to a target. Reporter molecules may comprise quantum dots, fluorophores, colored microspheres, computed tomography (CT) contrast agents, MRI contrast agents, or radiolabels.

[0098] Tracer - synonymous with molecular probe; see molecular probe.

[0099] As used herein, “molecular probe”, “tracers”, “fluorescent dyes”, “reporter molecules”, and “fluorophores” are used interchangeably.

[0100] As used herein, “camera”, “CMOS sensor camera”, and “endoscope camera” are used interchangeably. Furthermore, as used herein “camera” is preferably specific to a CMOS sensor-based camera, but may also be a CCD sensor-based camera. Systems and methods according to the present invention preferably utilize and / or include an imaging system, such as a digital camera including a CMOS sensor, and operative optics (e.g., lens(es)) and biasing and / or control electronics (not shown). Figures 7A and IB provide a relative pixel response for pixels arranged in a pixel array on a CMOS sensor 1000 as shown. CMOS sensors are bayer filters that contain pixels sensitive to different wavelengths of light. For instance, pixels 1012 that are more sensitive to red light red light may be arranged in perpendicular rows and columns in alternating fashion with pixels 1014 that are more sensitive to green light. Additionally, pixels 1016 that are more sensitive to blue light may be arranged in perpendicular rows and columns in alternating fashion with pixels 1014 that are more sensitive to green light, and the rows / columns including red pixels 1012 may be alternated with those including blue pixels 1016. Typical CMOS sensors are RGGB, which means that alternating rows of the sensor are composed of red & green “RG” pixels and green & blue “GB” pixels. Fig. 7A shows the typical wavelength sensitivity of the RGB pixels and the typical RGGB pattern. In particular embodiments of the invention, specific CMOS sensors are utilized that contain only one pixel type (i.e. only red, green, or blue pixels) or contain only two pixel types (i.e. only two color pixels: red and green, green and blue, or red and blue). In other embodiments of the invention,

[0101] RGB-IR sensors are utilized which consist of 75% RGB pixels and 25% infrared (IR) pixels. RGB-IR sensors are preferred for applications involving near-infrared fluorophores, as they allow simultaneous visible and NIR signal capture. In this format, the sensor is created by alternating rows of pixels consist of “RGGB” pixels and “G-IR” pixels. Thus, the final sensor yields approximately 12.5% red pixels, 12.5% blue pixels, 50% green pixels, and 25% IR pixels. Additionally, in a preferred embodiment of the invention, the CMOS sensor is composed of at least two of the following pixel types: red, green, blue and infrared. Preferably, the IR pixels are most sensitive to light having a wavelength between 750-2500 nanometers (nm), more preferably to light having a wavelength between 800-1500 nm, even more preferably to light having a wavelength between 800-1000 nm, and most preferably to light wavelengths of about 825 nm to about 875 nm. In such an embodiment, preferably the IR pixels comprise at least 5% of all sensor pixels, more preferably comprise at least 15% of all sensor pixels and most preferably comprise at least 30% of all sensor pixels.

[0102] Integrated, interchangeable, and / or replaceable optical filters may be included, optionally positioned to filter light passed to the CMOS sensor (e.g., positioned between a lens assembly and the CMOS sensor). These filters selectively block light having specific wavelengths and allow transmission of light having different wavelengths to optimize, contrast and suppress background signals. Typically, as shown in Figure 1, a 690 nm short-pass filter may be used to block unwanted near-infrared light from reaching the CMOS sensor. This is because the RGB pixels have similar sensitivities above 690 nm, which would distort normal color interpretation from CMOS sensors. For example, near infrared light of 850 nm is not visible to the human eye but would be captured by a CMOS sensor’s RGB pixels which are equally as sensitive to 850 nm; thus, 850 nm light would look like white light on the CMOS sensor. Depending on the wavelength of light utilized for fluorescence, this near-infrared filter can be removed, for example, if one wanted to view the fluorescence of a near-infrared dye. The dye can be conjugated to a protein (e.g. protein-indocyanine green or protein-IR800CW) or used by itself (e.g. indocyanine green). Therefore, the miniature endoscope may include one or more optical filters depending on what wavelength of light is desired to view. In a preferred embodiment these filters are interchangeable or replaceable to allow the user to change fluorescence visualization based upon the utilized filter. In a preferred embodiment, the filter is located between the CMOS sensor and lens assembly within the camera unit. Preferably, the fluorescence visualized using the disclosed endoscope accessory matches the peak response intensities for at least one pixel type (i.e. either R, G, B, or IR). Most preferably, the visualized fluorescence is green light because CMOS sensors contain more green pixels than any other pixel color or type. FITC fluorescence provides green light that matches the green pixel wavelength sensitivity. Alternatively, near-infrared fluorescence, for example from the fluorophore IR800CW, is preferred to be utilized with the endoscope accessory as all CMOS pixels have equal and similar intensity at near-infrared wavelengths. A near-infrared fluorophore would also be advantageous in situations when the disclosed invention utilizes an RGB-IR sensor.

[0103] In a further embodiment of the invention the collective or individual sensitivity(ies) of CMOS sensor pixels and fluorophore emission wavelength spectrum correlate to a significant degree to allow for optimized fluorescence visualization of the fluorophore using the CMOS sensor. To illustrate this aspect of the invention, let “Al” represent the integral of collective or individual normalized sensitivity(ies) of the CMOS sensor pixels over a certain wavelength range, “ A2” represent the integral of the normalized fluorophore emission wavelength spectrum over a certain wavelength range, and “A3” represent the overlap area between “Al” and “A2”. In specific aspects of the invention, “A3” is at least 5%, preferably at least 10%, more preferably at least 20%, even more preferably at least 30%, and most preferably at least 50%, which allows for adequate fluorescence visualization of the fluorophore utilizing the CMOS sensor.

[0104] The foregoing is considered as illustrative only of the principles of the invention. Furthermore, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation shown and described. While the preferred embodiment has been described, the details may be changed without departing from the invention.

Claims

What is claimed is:

1. A device comprising: a ring extending about an opening, a portion of the ring being at least one of radially and circumferentially extensible; a light source supported by the ring, the light source configured to emit a first light substantially in a first direction away from a first surface of the ring; an imaging device supported by the ring configured to receive a second light substantially from a second direction, the second direction being opposite the first direction.

2. The device of claim 1, wherein the light source is a light emitting diode (LED).

3. The device of claim 1, the imaging device comprising an image sensor and optics through which the second light passes prior to reaching the image sensor.

4. The device of claim 3, wherein the optics comprises at least one of a lens and a filter.

5. The device of claim 3, the image sensor selected from the group consisting of complimentary metal-oxide-semiconductor (CMOS) sensor and a charge-coupled device (CCD).

6. The device of claim 3, the image sensor being reactive to second light having wavelengths in the range of 365 nanometers to 3000 nanometers.

7. The device of claim 3, the image sensor being an RGB-IR sensor.

8. The device of claim 8, wherein the RGB-IR sensor is reactive to infrared light having a wavelength between 825-875nm.

9. The device of claim 7, wherein the RGB-IR sensor comprises a plurality of pixels, wherein at least 15% of the pixels are sensitive to infrared electromagnetic waves.

10. The device of claim 7, wherein the RGB-IR sensor is operable on less than 300mW of electrical power.

11. The device of claim 7, wherein the RGB-IR sensor has a quantum efficiency of at least 20%.

12. The device of claim 1, wherein the RGB-IR sensor has a sensitivity of at least 1500 mV / lux*sec.

13. The device of claim 7, wherein the RBG-IR sensor is cooled using a thermoelectric cooler.

14. The device of claim 1, wherein the ring comprises a disk, a majority of which is formed from an elastomeric material.

15. The device of claim 14, further comprising at least one heat transfer agent embedded in the elastomeric material.

16. The device of claim 1, wherein the light source and imaging device are supported on a first axial side of the ring.

17. The device of claim 1, wherein the ring is formed about a first axis.

18. The device of claim 17, wherein the opening is formed about a second axis, the second axis being spaced from and at least substantially parallel to the first axis.

19. The device of claim 1, wherein the second light comprises at least one of first light reflected from in vivo animal tissue, fluorescence of in vivo animal tissue, and fluorescence of molecular probes.

20. The device of claim 1, wherein the imaging device comprises a camera module having a field of view of at least 70 degrees and a depth of field of 3mm - 25mm;21. The device of claim 1, wherein the at least one light source is capable of emitting 50mW to 150mW of optical power;22. The device of claim 1, wherein the ring has a thickness extending between and including a first axial side and a second axial side, the thickness being a maximum of 4mm.

23. The device of claim 1, wherein the light source is capable of exciting an endogenous or exogenous fluorophore.

24. The device of claim 1, wherein the light source is capable of transmitting at least two wavelengths light.

25. The device of claim 24, wherein at least one wavelength is capable of, in vivo, causing autofluorescence of animal bodily tissue and at least one other wavelength is capable of causing fluorescence of a molecular probe.

26. The device of claim 24, wherein at least one wavelength of light is in the human visible spectrum and at least one wavelength is capable of causing at least one of invivo tissue autofluorescence and fluorescence of a molecular probe.

27. A system comprising: a device according to claim 1; and, a controller operatively coupled to the device and configured to receive image data from the imaging device.

28. The system of claim 27, the controller being configured to at least one of activate the imaging device, deactivate the imaging device, set one or more parameters of the imaging device, and vary one or more parameters of the imaging device.

29. The system of claim 27, the controller being configured to at least one of activate the light source, deactivate the light source, and vary an intensity of the light source.

30. The system of claim 27, the device comprising: a second light source supported by the ring, the second light source configured to emit a third light substantially in the first direction; the imaging device configured to receive a fourth light substantially from the second direction, the second direction being opposite the first direction.

31. The system of claim 27, wherein the operative coupling is at least one of electrical wires and wireless communications.

32. The system of claim 27, wherein the controller receives data from the imaging device and enables a visualization of a white light and fluorescent overlay video.

33. A method of in vivo fluorescence imaging comprising: attaching a fluorescent endoscopic accessory device to an endoscope, the accessory device comprising an illumination ring supporting a camera module containing an RGB-IR sensor, at least one light emitting diode (LED) capable of exciting an endogenous or exogenous fluorophore, and an optical filter, wherein, the camera module includes a field of view of at least 70 degrees and a depth of field of 3mm - 25mm, and, wherein the at least one LED is capable of emitting at least 50mW of optical power; introducing the fluorescent endoscopic accessory device and endoscope into an opening in an animal body; andusing the RGB-IR sensor, sensing fluorescence of a fluorophore.

34. The method of claim 33, wherein the opening is a naturally formed opening in the animal body.

35. The method of claim 33, further comprising the step of incising the body to create the opening.

36. The method of claim 33, wherein the fluorophore is selected from the group consisting of an endogenous fluorophore and previously applied exogenous fluorophore.

37. A kit for in vivo fluorescence imaging comprising: an endoscopic accessory device comprising an illumination ring supporting a camera module containing an RGB-IR sensor, at least one light emitting diode (LED) capable of exciting an endogenous or exogenous fluorophore, and an optical filter, wherein, the camera module includes a field of view of at least 70 degrees and a depth of field of 3mm - 25mm, and, wherein the at least one LED is capable of emitting at least 50mW of optical power; and a controller capable of operatively coupling to the accessory device.

38. The kit of claim 37, further comprising at least one syringe, wherein each syringe contains a substance selected from the group consisting of: a buffer rinse solution, a pretreatment solution, and an aqueous solution comprising a fluorescent molecule.

39. The kit of claim 38, wherein the buffer rinse solution is isotonic saline.

40. The kit of claim 38, wherein the pretreatment solution is n-acetylcysteine.

41. The kit of claim 38, wherein fluorescent molecule is a near-infrared dye.

42. The kit of claim 37, further comprising at least one spray catheter.

Images