System and method for illumination and imaging of target

Abstract

To provide an illumination module used by an imaging system having an imaging field of view for imaging a target.SOLUTION: An imaging device may include: a first illumination port illuminating a target by outputting first light having a first illumination distribution at the target; and a second illumination port which illuminates the target by outputting second light having a second illumination distribution at the target and in which the second illumination distribution is substantially similar to the first illumination distribution at the target, the second illumination port being spaced apart from the first illumination port, the first and second illumination distributions being simultaneously provided to the target, and overlapping each other at the target. The illumination from the first and second ports may be matched to the same aspect ratio and field of view coverage as the imaging field of view.SELECTED DRAWING: Figure 7

Description

Technical Field

[0001] Reference to Related Applications This application claims the benefit of priority of U.S. Provisional Patent Application No. 62 / 255,024, filed on November 13, 2015, entitled "SYSTEMS AND METHODS FOR ILLUMINATION AND FMAGING OF A TARGET", the entire disclosure of which is incorporated herein by reference.

[0002] The present disclosure is mainly related to the fields of illumination and imaging. In particular, the present disclosure is related to the illumination and imaging of a target substance.

Background Art

[0003] Illumination is an important component of imaging systems, such as broadband imaging systems with self-sufficient illumination. In many applications of imaging systems, such as medical imaging, it is difficult to provide illumination of sufficient intensity to produce a sufficiently strong imaging signal while obtaining uniform full-field illumination of the imaging field. Adapting the illumination profile to match the imaging field is one way to save power in illumination, while uniform illumination across the field may be provided by using multiple illumination ports. Conventional illumination projections in imaging systems may feature anamorphic projections for matching the imaging field, but often feature only a single illumination port and are not configured for close working distances. In a single-port illumination system, when illuminating complex shapes such as human anatomical structures or other biological materials, regions that are substantially shadowed and lack visibility occur. Existing designs of surgical field imaging and illumination devices minimize shadow regions by using multiple illumination ports such as ring light surrounding the imaging optics. However, these designs waste illumination outside the field of view and have not achieved uniform illumination of the field across the range of working distances.

Summary of the Invention

[0004] One or more embodiments are directed to a lighting module for use in an imaging system having an imaging field of view for imaging a target, the lighting module including a first lighting port that illuminates the target by outputting a first light beam having a first lighting distribution at the target, and a second lighting port that illuminates the target by outputting a second light beam having a second lighting distribution at the target. The second lighting distribution is substantially similar to the first lighting distribution at the target, the second lighting port is spaced apart from the first lighting port, the first and second lighting distributions are provided simultaneously to the target and overlap at the target, and the lighting from the first and second ports may be matched to the same aspect ratio and field coverage as the imaging field of view.

[0005] The light from the first and second lighting ports may overlap with each other to provide uniform lighting over the target field of view.

[0006] The lighting module may include a steering driver that simultaneously steers the first and second lighting ports through different fields of view.

[0007] Each of the first and second lighting ports may include a lens module having at least one fixed lens, a steerable housing, and at least one lens attached to the steerable housing, and the steerable housing communicates with the steering driver.

[0008] The lighting module may include a housing that houses the first and second lighting ports and the steering driver.

[0009] The housing may be a handheld housing and may include a control surface that includes an activation device for controlling the steering driver.

[0010] Each of the first and second illumination distributions may be a rectangular illumination distribution.

[0011] Each of the first and second illumination ports may include a lens module having two sets of cylindrical lenses.

[0012] The first and second illumination ports may be symmetrically offset from the center line of the longitudinal dimension of the rectangular illumination distribution.

[0013] One or more embodiments are directed to an imaging device having an imaging field of view, the imaging device including a first illumination port that illuminates a target by outputting a first light having a first illumination distribution at the target, and a second illumination port that illuminates the target by outputting a second light having a second illumination distribution at the target, wherein the second illumination distribution is substantially similar to the first illumination distribution at the target, the second illumination port is spaced apart from the first illumination port, the first and second illumination distributions are provided simultaneously to the target and overlap at the target, the illumination from the first and second ports is matched to the same aspect ratio and field of view as the imaging field of view, a second illumination port, and a sensor that detects light from the target.

[0014] The imaging device may include a housing that houses the first and second illumination ports and the sensor.

[0015] The imaging device may include a steering driver that simultaneously steers the first and second illumination ports through different fields of view.

[0016] The imaging device may include an imaging element that focuses light on the sensor, and the steering driver is for moving the imaging element in synchronization with the steering of the first and second illumination ports.

[0017] The steering driver may be within the housing, and the housing may include a control surface that includes an activation device for controlling the steering driver.

[0018] The housing may have a handheld housing having a form factor that enables a user to control the control surface with one hand and control illumination of the target from a plurality of orientations.

[0019] The imaging device may include an illumination source that outputs light to the first and second illumination ports, and the illumination source may be outside the housing.

[0020] The illumination source may output visible light and / or excitation light to the first and second illumination ports.

[0021] The sensor may be a single sensor for detecting light from the target that is generated by illumination with visible light and excitation light.

[0022] The imaging device may include a wavelength-dependent aperture upstream of the sensor, and the wavelength-dependent aperture blocks visible light outside a central region.

[0023] The imaging device may include a video processor box outside the housing.

[0024] The illumination source may be integrated with the video processor box.

[0025] One or more embodiments are directed to a method of examining a target, the method comprising simultaneously illuminating the target with a first light output having a first illumination distribution at the target and a second light output having a second illumination distribution at the target, the second illumination distribution being substantially similar to the first illumination distribution, the first and second illumination distributions overlapping at the target, and the illumination on the target being matched to the same aspect ratio and field of view coverage as the imaging field of view.

[0026] The method may include simultaneously steering the first and second light outputs through different fields of view.

[0027] The method may include receiving light from the target and focusing the light onto a sensor using an imaging element, the imaging element being moved in synchronization with the simultaneous steering of the first and second light outputs.

[0028] One or more embodiments are directed to a drape for use in an imaging device, the drape including a barrier material that encloses the imaging device, a drape window frame that defines an opening in the barrier material, a drape lens within the opening in the barrier material, and an interface integrated with the drape window frame that secures the drape lens to the window frame of the imaging device.

[0029] The drape may be insertable into the window frame of the imaging device.

[0030] The interface may include two clamps symmetrically incorporated on opposite sides of the drape window frame.

[0031] The two clamps are at the top and bottom of the drape window frame.

[0032] One or more embodiments are directed to a processor that images a target. The processor, within a period, generates an excitation pulse for illuminating the target by activating an excitation light source, and generates a white pulse for illuminating the target by activating a white light source such that the white pulse does not overlap the excitation pulse and the white pulse is generated at least twice within the period. During the fluorescence exposure time within the excitation pulse, the processor exposes an image sensor, and during the visible exposure time within at least one white pulse, the processor exposes the image sensor. The processor also detects an output from the image sensor, corrects for ambient light, and outputs a resulting image.

[0033] To correct for ambient light, the processor may expose a first set of sensor pixel rows of the image sensor for a portion of the fluorescence exposure time and expose a second set of sensor pixel rows of the image sensor for the entire fluorescence exposure time, where the first and second sets are for detecting at least one color different from each other.

[0034] The portion may be 1 / 2.

[0035] The processor may determine the fluorescence signal F using the following formula. F = 2 * Exp2 - Exp1 Here, Exp1 is the signal output during the portion of the fluorescence exposure time, and Exp2 is the signal output during the entire fluorescence exposure time.

[0036] The portion of the exposure time may be equal to the width of the excitation pulse.

[0037] The visible exposure time may be longer than the width of the at least one white pulse.

[0038] The visible exposure time may be for one white pulse within the period.

[0039] The visible exposure time may be for two white pulses within the period.

[0040] To correct for ambient light, the processor may expose the image sensor during the background exposure time if the target is not illuminated at least once during the period.

[0041] One or more embodiments are directed to a method for imaging a target. The method includes generating an excitation pulse for illuminating the target within a period, generating a white pulse for illuminating the target such that the white pulse does not overlap the excitation pulse and such that the white pulse is generated at least twice within the period, exposing an image sensor during a fluorescence exposure time within the excitation pulse, exposing the image sensor during a visible exposure time within at least one white pulse, detecting an output from the image sensor, correcting for ambient light, and outputting a resulting image.

[0042] Correcting for ambient light may include exposing a first set of sensor pixel rows of the image sensor for a portion of the fluorescence exposure time and exposing a second set of sensor pixel rows of the image sensor for the entire fluorescence exposure time, the first and second sets being for detecting at least one color different from each other.

[0043] Correcting for ambient light may include exposing the image sensor during a background exposure time if the target is not illuminated at least once during the period.

[0044] Generating the excitation pulse may include providing uniform and anamorphic illumination to the target.

[0045] Providing uniform and anamorphic illumination to the target involves superimposing illumination from at least two illumination ports.

[0046] One or more embodiments are directed to a method of displaying fluorescence intensity in an image. The method includes displaying a target reticle covering an area of the image, calculating a normalized fluorescence intensity within the target reticle, and displaying the normalized fluorescence intensity in a display area associated with the target.

[0047] The display area may be projected onto the target.

[0048] The normalized fluorescence intensity may include a single numerical value and / or a history plot of the normalized fluorescence intensity.

[0049] One or more embodiments are directed to a kit. The kit includes an illumination module including at least two illumination ports spaced apart from each other, wherein a first and a second illumination distribution are simultaneously provided to a target and overlap at the target, and an imaging module including a sensor for detecting light from the target.

[0050] The kit may include a housing surrounding the illumination module and the imaging module.

[0051] One or more embodiments are directed to imaging agents, such as fluorescence imaging agents used in the imaging devices and methods described herein. In one or more embodiments, their use may include blood flow imaging, tissue perfusion imaging, lymphatic imaging, or combinations thereof, which may occur during invasive surgery, minimally invasive surgery, non-invasive surgery, or combinations thereof. The fluorescence imaging agent may be included in the kit described herein. The fluorescence imaging agent may include only ICG, or ICG may be combined with other imaging agents.

[0052] In one or more embodiments, the invasive surgery may include cardiac-related surgery or reconstructive surgery. The cardiac-related surgery may include coronary artery bypass graft (CABG) surgery, which may be on-pump and / or off-pump.

[0053] In one or more embodiments, the minimally invasive surgery or the non-invasive surgery may include wound treatment surgery.

[0054] In one or more embodiments, the lymph imaging may include identification of lymph nodes, lymph node drainage, lymph mapping, or combinations thereof. The lymph imaging may also relate to the female reproductive system. BRIEF DESCRIPTION OF THE DRAWINGS

[0055] The features will become apparent to those skilled in the art by describing exemplary embodiments in detail with reference to the accompanying drawings.

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Embodiments for Carrying Out the Invention

[0077] Exemplary embodiments will be described in more detail with reference to the accompanying drawings below. However, the exemplary embodiments can be implemented in different manners and should not be considered limited to those described herein. Rather, these embodiments are provided so that this disclosure will be thorough and will fully convey exemplary implementations to those skilled in the art. Various devices, systems, methods, processors, kits, and imaging agents are described herein. At least two variations of the devices, systems, methods, processors, kits, and imaging agents are described, but other variations can include any suitable combination of the aspects of the devices, systems, methods, processors, kits, and imaging agents described herein and can have all or some combination of the aspects described.

[0078] Generally, corresponding or like reference numerals will be used where possible throughout the drawings to refer to the same or corresponding members.

[0079] Spatially relative terms, such as "under", "below", "lower", "above", "upper", etc., may be used herein to facilitate description of the relationship of one element or feature to another shown in the figures. It will be understood that spatially relative terms are intended to encompass different arrangements of the device in use or operation in addition to the arrangement shown in the figures. For example, if the device in the figures is turned over, elements described as "under" or "below" other elements or features will then be arranged "above" the other elements or features. Thus, the exemplary term "lower" can encompass both upward and downward arrangements. The device may be otherwise arranged (such as rotated 90 degrees or in other arrangements), and the spatially relative descriptors used herein may be interpreted accordingly.

[0080] FIG. 1 shows a schematic diagram of an illumination and imaging system 10 according to an embodiment. As shown in FIG. 1, the system 10 may include an illumination module 11, an imaging module 13, and a video processor / illuminator (VPI) 14. The VPI 14 may include an illumination source 15 for providing illumination to the illumination module 11, and a processor assembly 16 that transmits control signals and receives data about light from a target 12 illuminated by light output by the illumination module 11 and detected by the imaging module 13. The illumination source 15 may output light in different wavelength band regions, such as, for example, white (RGB) light or excitation light for inducing fluorescence in the target 12, depending on the characteristics of the object under investigation and the material of the target 12. The light in different wavelength bands may be output simultaneously or sequentially by the illumination source. The illumination and imaging system 10 may be used, for example, to facilitate surgery. The target 12 may be a target having a complex shape. For example, it may be a biological object including tissues, anatomical structures, or other objects with contours and shapes that create shadows during illumination. The VPI 14 may record, process, and display the resulting images and related information.

[0081] FIG. 2 shows a schematic perspective view of the illumination module 11 of FIG. 1 according to an embodiment. As shown in FIG. 2, the illumination module 11 may include at least two illumination ports that direct illumination from an illumination source 23, which may be included in the VPI box 14, to, for example, a rectangular target field 24. Each illumination port is for providing illumination on the target field 24 such that, for example, light substantially or completely overlaps at the target material 12 (shown in FIG. 1). More than two illumination ports may be used. The illumination distributions are substantially similar and substantially overlapping at the target, thereby providing uniform illumination of the target 12. By using at least two illumination ports, it is possible to reduce the influence of shadows caused by anatomical shapes and help provide uniform illumination on the target field 24. By directing illumination from the illumination module 11 to the rectangular target field 24, the illumination area can be matched to the rectangular imaging field, thereby helping to provide uniform illumination and increasing the efficiency of the illumination module by reducing wasted illumination. The matching of the illumination field and the imaging field also provides a useful reference for the position and extent of the anatomical region currently being imaged.

[0082] In one embodiment, by using an optical pipe, it is possible to achieve mixing of illumination light to produce a uniform illumination profile. Mixing of the illumination light by the optical pipe can remove the influence of the structure of the light source on the illumination profile. Such influence, if not removed, can adversely affect the uniformity of the illumination profile. For example, by using an optical pipe to mix the illumination light output from the optical fiber light guide, the image of the structure of the individual optical fibers can be removed from the illumination profile. In one embodiment, a rectangular optical pipe may be used to match the illumination profile to the rectangular imaging field while preserving the illumination power. In one embodiment, when an optical pipe material having a high refractive index for both visible light and near-infrared light, such as the optical glass material N-SF11, is used, the efficiency of illumination power transmission can be increased.

[0083] According to one embodiment, a rectangular light pipe with an aspect ratio matching the aspect ratio of the imaging field of view (e.g., both aspect ratios are 16:9) may be used in cooperation with a rotationally symmetric illumination optical element.

[0084] According to one embodiment, a rectangular light pipe with an aspect ratio different from that of the imaging field of view (e.g., a 16:9 imaging field of view aspect ratio for a square light pipe) may be used in cooperation with a cylindrical illumination optical element. By using the cylindrical optical element, one or both dimensions of the rectangular illumination profile can be individually adapted to match the aspect ratio of the imaging field of view.

[0085] Depending on the desired system requirements regarding the working distance range and illumination uniformity, various approaches can be used to match the illumination to the rectangular imaging field of view. For example, an application with high requirements regarding the working distance range and illumination uniformity may require the use of a dynamically steered illumination optical system to fully match the illumination and the imaging field of view, while a fixed illumination optical system for matching the illumination and the field of view may be used for applications with lower requirements.

[0086] In one embodiment, a driver may rotate one or more illumination optical elements to steer the illumination.

[0087] In one embodiment, a driver may move one or more illumination optical elements perpendicular to the imaging optical axis to steer the illumination.

[0088] In one embodiment, one or more illumination optical elements may be configured to provide some distortion in the illumination profile to compensate for the inherent distortion of the associated imaging system.

[0089] In one embodiment, uniform illumination of the imaging field over a specified working distance range can be achieved at a fixed position and orientation of the illumination optical system. The offset distance of the illumination optical system from the imaging optical axis, along with the orientation of the illumination optical system, optimizes the matching between the illumination profile and the imaging field at a certain working distance within the specified working distance range while maintaining substantial matching between the illumination profile and the imaging field at other working distances within the specified range.

[0090] As shown in FIG. 2, each illumination port may include a lens module 20, a connection cable 22 connecting to an illumination light source 23, and an optical pipe 21 that adapts the large numerical aperture of the connection cable 22 to the smaller numerical aperture of the lens module 20. The lens module 20 may be steerable, as will be detailed later. In one scenario, acceptable performance can be achieved without steering. In other words, it may be sufficient to provide an illumination module having a rectangular form factor that matches the field of view of an imaging system using at least two illumination ports, where each port generates a gradient of illumination in its field of view and the sum of the illumination light beams thereof at the object plane is substantially the same at each point of the illumination field (e.g., provides uniform illumination across the imaging field), and an imaging device including the same.

[0091] FIGS. 3A and 3B respectively show a side view and a plan view of the lens module 20. The lens module 20 may include a lens attached to a steerable lens housing 30. As used herein, a lens is any optical element having optical power, whether implemented by refractive elements or diffractive elements. For simplicity of illustration, other elements not essential for understanding, such as the cover surrounding the lens module (see FIG. 2), are not shown.

[0092] In a specific example shown in this specification, the lens may include a pair of horizontal-axis cylindrical lenses 31-32 and a pair of vertical-axis cylindrical lenses 33-34. A prism element 35 that can align the output optical axis for intended illumination light is also shown. In particular, according to an embodiment, in order to make the device more compact, the prism element 35 may correct the angle introduced by the light pipe 21. The mounting design of each lens element 31-35 may enable adjustment of the magnification and focus of the illumination optical system. According to this embodiment, the steerable lens housing 30 houses and steers three cylindrical lenses 31, 33, 34 and the prism lens element 35 as a group, for example. This example of the lens is for illustrative purposes only, and the lens of the lens module 20 may be changed as appropriate.

[0093] In this particular embodiment, the base portion of the steerable housing 30 is pinned, using, for example, a pin 46 (see FIG. 6B) inserted into the housing hole 37, around the pivot point 36, to a fixed housing frame 90 (see FIG. 6A) and a mechanical linkage 40 (see FIGS. 4A to 4C), each of which will be described in detail later. On the other hand, the lens 32 is firmly connected to the housing 90 (i.e., not connected to the housing 30) (see FIG. 6B).

[0094] Figure 4A is a schematic diagram showing the directions of movement provided by the various components of linkage 40. Linkage 40 may include a drive cam 41, illumination cams 45a, 45b (one for each illumination port), and an imaging cam 43. The drive cam 41 receives an input from the user (see FIG. 6) and converts that input, via corresponding housing 30 and pins 46, into synchronous movement of corresponding lens modules 20a, 20b attached to corresponding illumination cams 45a, 45b, and also, via cam follower pins, into synchronous movement of imaging lens 51 and imaging sensor 52 (see FIGS. 5A and 5B) attached to imaging cam 43. Here, imaging lens 51 is depicted as a single field-of-view lens, but additional and / or alternative lenses may be used to focus light from target 20 onto imaging sensor 52. Each port has its own associated illumination cams 45A and 45B, which are depicted here as being to the left and right of an input window for receiving light from target 12.

[0095] In particular, movement of drive cam 41 causes imaging cam 43 to move along the x-axis, and then such movement of imaging cam 43 causes imaging cam 43 to move imaging lens 51 and imaging sensor 52 along the z-axis and causes illumination cams 45a, 45b to move, and then such movement of illumination cams 45a, 45b causes corresponding lens modules 20a, 20b to be simultaneously steered about corresponding pivot points 36, with the result that the steering of lens modules 20a, 20b is synchronized with the positioning of imaging lens 51 and imaging sensor 52 to ensure proper focusing of light from the target onto sensor 52. Alternatively, imaging cam 43 may move only imaging lens 51 along the z-axis, or any other combination of imaging optical elements may be moved to ensure proper focusing of light from the target onto sensor 52.

[0096] FIG. 4B shows a bottom view of the linkage 40 according to the embodiment, and FIG. 4C shows a top view of the linkage 40. The drive cam 41 may include two drive parts 41a and 41b, and when steering is included, a third drive part 41c, all of which are depicted here as being rigidly attached to form a rigid drive cam 41. Similarly, the imaging cam 43 may include two imaging parts 43a and 43b. The drive cam 41 receives an input from the user (via the control surface 62) via the first drive part 41a and moves the imaging cam 43 via a cam follower pin within the drive part 41b. As a result, the imaging cam part 43a moves the sensor 52, and the imaging cam part 43b moves the imaging lens 51. When steering is included in the linkage, the third drive part 41c simultaneously steers (rotates) the lens modules 20a, 20b using pins 46 (see FIG. 6B) associated with each of the illumination cam parts 45a and 45b by moving the illumination cam parts 45a and 45b. The pins 46 may be inserted through respective slots 49 of the illumination cams 45a, 45b and corresponding housing holes 37 of the lens modules 20a, 20b. The drive part 41c steers the lens modules 20a, 20b simultaneously such that both still illuminate the same field of view with each other in the target field of view of the target 12.

[0097] FIGS. 5A and 5B respectively show bottom views of the linkage combined with the lens modules 20a, 20b, the imaging field lens 51, and the sensor 52 at a far working distance and a near working distance according to the embodiment. As shown in those figures, the linkage 40 synchronizes the steering of the illumination source with the focusing of the imaging system at two sample working distance illumination steering settings. FIGS. 5A - 5B show the positions of the lens modules 20a, 20b (rotating about the pivot pin 37) as well as the lens 51 and the sensor 52 (moving along the optical axis 55 of the imaging system and along the z - axis) at two focusing positions obtained from user input.

[0098] As shown in FIGS. 5A and 5B, in order to minimize or reduce friction during movement, each member that moves axially within the linkage mechanism 40 may be guided by two fixed rolling elements 47 and one spring-biased rolling element 48. The linkage 40 may also include a drive cam input connection point 42.

[0099] FIGS. 6A and 6B show a perspective top view and a perspective bottom top view of the device 10 according to an embodiment. In FIGS. 6A and 6B, the illumination module 11 and the imaging module 13 are attached to the housing 90. The upper part of the housing 90 is removed for clarity. Also shown is a focus drive mechanism 70 that converts movement from a user input via the drive cam input connection point 42 into movement of the drive cam 41.

[0100] As seen in FIG. 6A, the optical axis 55 of the imaging module 13 passes through the center of the imaging module, and the lens modules 20a, 20b are arranged symmetrically with respect to the imaging optical axis 55. The light to be imaged from the target 12 travels along the optical axis 55 and is incident on the lens 51 and the sensor 52. The wavelength-dependent aperture 53 may include a smaller central aperture that permits transmission of all visible light and fluorescence, such as near-infrared (NIR) light, and a larger surrounding aperture that blocks visible light but permits transmission of fluorescence, and is provided upstream of the lens 51.

[0101] Referring to FIGS. 6B and 4A-4B, the pin 46 connects the lens module 20 and the slot 49 of the linkage 40 through the housing hole 37 of the housing 30. Also, the pivot point pin 44 connects the lens module 20 to the housing 90.

[0102] Figure 7 shows an embodiment of an ergonomic housing 60 that encloses the illumination module 11 and the imaging module 13. The ergonomic housing 60 is designed to be gripped in different usage modes / settings. For example, it is a pistol-style grip (Figure 8A) for forward imaging in a scanning imaging posture, and also a vertical grip (Figure 8B) used when imaging downward in an imaging posture from above. As shown in Figure 7, the housing 60 includes a control surface 62, grip details 64, a window frame 68, and a nose piece 66. The ergonomic housing 60 can be connected to the VPI box 14 via an optical guide cable 67 and a data cable 65, and light is provided to the illumination ports 20a, 20b through the optical guide cable 67. The data cable 65 conveys power, sensor data, and any other (non-optical) connections.

[0103] The control surface 62 includes focus buttons 63a (to reduce the working distance) and 63b (to increase the working distance) for controlling the linkage 40. Other buttons on the control surface 62 may be programmable and may be used for various other functions, such as turning on / off the excitation laser power, selecting a display mode, white balance for white light imaging, saving a screenshot, etc. Alternatively or additionally to the focus buttons, a proximity sensor may be provided on the housing and used to automatically adjust the linkage 40.

[0104] As shown in FIG. 8A, when the housing 60 is held such that the imaging window faces forward, the thumb is placed on the control surface 62 and the other fingers of the operator's hand are loosely wrapped around the bottom of the grip detail 64. As shown in FIG. 8B, when the housing 60 is held such that the imaging window faces downward, the grip detail 64 is between the thumb and the index finger, and the fingers are wrapped around to access the control buttons and switches on the control surface 62. The grip detail 64 is shaped to provide partial support of the weight of the device above the wrist in a vertical grip. In this case, the housing 60 hangs loosely and there is no need to tightly grip the housing 60. Thus, the housing 60 is operable with one hand in a plurality of postures. In various other embodiments, the housing 60 may be supported on a support (e.g., a movable support).

[0105] The window frame 68 (see also FIG. 9) defines different windows of the housing 60. In other words, the window frame 68 defines windows 68a, 68b corresponding to the two lens modules 20a, 20b and also defines a window 68c that functions as an input window for light from the target that is to be incident on the sensor 52.

[0106] As shown in FIG. 9, the housing 60 may be used in cooperation with a drape 80. The drape 80 may be a surgical drape suitable for use during surgery. The drape includes a drape material 81, a drape lens 82, a drape window frame 83 surrounding the drape lens, and an interlock interface 84 integrated with the drape window frame 83. The drape material 81 is for wrapping the device within the housing 60 and covering any other optional items as needed. The drape window frame 83 conforms to the shape of the housing nose piece 66. In this case, the drape window frame 83 may be inserted into the housing nose piece 66 without interfering with windows 68a to 68c. The drape 80 is designed to minimize reflections and image ghosts by ensuring that the drape lens 82 is in the same plane as the imaging and illumination window frame 68, for example, within 0.5 mm. The drape 80 may use the interlock interface 84. This may be locked to be in the same plane by fitting into a recess on the inner surface of the housing nose piece 66.

[0107] One or more interlock interfaces 84 may be used on the inner or outer surface of the housing nose piece 66 to ensure that the drape lens 82 fits tightly and closely against the window frame 68. In the particular embodiment shown, two interfaces 84 are used, one at the top and the other at the bottom of the drape window frame 83, each engaging the inner surface of the housing nose piece 66.

[0108] Figures 10A through 10C show typical illumination distributions (shading) for a rectangular imaging field (outline) for an illumination ring (Figure 10A), a pair of fixed anamorphic projection illumination sources (Figure 10B), and a pair of steerable anamorphic projection illumination sources according to an embodiment (Figure 10C), with working distances of 10 cm (left column), 15 cm (center column), and 20 cm (right column) shown, respectively. Figure 10A shows the use of a ring of illumination ports to minimize shadowing, but does not match the illumination to the imaging field and does not provide uniform illumination at all working distances (e.g., the distribution changes with distance). Figure 10B shows anamorphic projections from two fixed illumination sources (e.g., using an illumination lens configuration featuring cylindrical lenses and machined diffusers), and thus they are well calibrated for uniform illumination that matches the imaging field at a fixed working distance, e.g., 15 cm, but there is no equivalent uniformity and no good matching at other distances, whether greater or less. As described above, such illumination is often acceptable by itself. Figure 10C shows the ability, according to an embodiment, to maintain good uniform illumination and to well limit the illumination to the field by steering the illumination when changing the working distance (and imaging focus).

[0109] As described above, the illumination used may include both white light and, for example, fluorescence excitation illumination from a laser to excite near-infrared (NIR) light from the target. However, there is a possibility that ambient light may interfere with the light from the target.

[0110] Figure 11A shows a timing diagram for white light (RGB) and fluorescence excitation (laser) illumination, and visible (VIS) and NIR fluorescence (FL) imaging sensor exposures configured to enable subtraction of ambient room light from the fluorescence signal with a single sensor. As used herein, the white pulse indicates that white light (RGB) illuminates the target, and the excitation pulse indicates that the laser illuminates the target.

[0111] The exposures of the even (Exp1) and odd (Exp2) sensor pixel rows are shown to be interleaved at different exposure times, thereby facilitating the separation of the evaluation of the environmental room light signal components. Such an interleaved exposure readout mode is provided by certain imaging sensors, such as the "High Dynamic Range Interleaved Read-out" mode provided by the CMOSIS CMV2000 sensor.

[0112] When white light illumination is pulsed at 80 Hz, the frequency of the flashing light exceeds the frequencies perceptible to the human eye or frequencies that can trigger epileptic seizures. The visible light image exposure may be, for example, twice as long as the RGB illumination. This ensures an overlap between the 60 Hz exposure frame rate and the 80 Hz RGB illumination pulses. The extra ambient light acquired during the visible exposure may be ignored. This is because the intensity of the RGB illumination pulses and the signal from target 12 is much stronger.

[0113] While setting the NIR fluorescence image exposure times Exp1 and Exp2 to acquire 1 / 2 frame period and 1 / 4 frame period respectively, and driving the excitation laser only in the last 1 / 4 frame every two frames, the even rows (Exp1) record 1 / 2 frame of the environmental room light in addition to 1 / 4 frame of the NIR fluorescence, while the odd rows (Exp2) record 1 / 4 frame of the NIR fluorescence and 1 / 4 frame of the environmental room light. By performing these fragment exposures within each visible or NIR fluorescence frame, the motion blur that could otherwise be caused by additional exposure frames inserted into the frame sequence for environmental room light subtraction can be minimized.

[0114] In such an acquired design, the contribution of the environmental room light to the image signal can be separated by subtracting the Exp2 sensor row of the NIR fluorescence image from the Exp1 sensor row (interpolated to match the Exp2 pixel positions), resulting in an evaluation of a 1 / 4 frame of the environmental room light signal. The evaluation of the 1 / 4 frame of the environmental room light signal is then subtracted from the Exp2 sensor row of the NIR fluorescence image, resulting in an evaluation of the NIR fluorescence signal with the 1 / 4 frame of the environmental room light removed. The control of illumination and exposure may be performed by the VPI box 14.

[0115] In one embodiment, the above-described room light subtraction method may be modified to allow the use of a Bayer pattern color sensor. FIG. 12A shows the Bayer pattern arrangement of color sensor pixels. Therein, the even and odd sensor rows have different filter arrays (e.g., there are no red pixels in the even sensor rows and no blue pixels in the odd sensor rows), so the environmental light recorded in the even rows will not be a good evaluation of the environmental light that reached the odd rows during the same period. However, each and every row contains green pixel signals, which also have sensitivity to NIR fluorescence. By using only the green pixels and performing two-dimensional interpolation from the green pixel signals to other pixel positions, an evaluation of the environmental light signal component can be obtained, and thus, for each of the NIR light image and the visible light image, an evaluation of the NIR fluorescence component and an evaluation of the visible light component can be obtained.

[0116] To calculate the NIR signal value at a given position, the green pixel values of Exp1 (even rows) and Exp2 (odd rows) near that position are calculated, and one or both of those values need to be interpolated. FIG. 12B shows an example, where at the red pixel position, the best evaluation of the green value of Exp1 (even rows) is the average of the green values directly above and below, while the best evaluation of the green value of Exp2 (odd rows) is the average of the green values immediately to the left and right.

[0117] The following mathematical example is useful for explaining an embodiment of the environmental chamber light subtraction method. When A = incident environmental light during a 1 / 4 frame period, and F = incident fluorescence during a 1 / 4 frame period, Exp 1 = 2A + F Exp 2 = A + F Solving for F, F = 2*Exp2 - Exp1

[0118] In a specific example shown in FIG. 11A, the detection period is 3 frames, the white light pulse and the excitation pulse have the same duration or width, but different frequencies, visible light is detected between 2 frames, for example the first two frames, and fluorescence is detected between one frame with two different exposure times, for example the third or last frame. As shown in the figure, the visible exposure time may be twice the duration of the white light pulse, the first fluorescence exposure time may be equal to the duration of the excitation pulse, and the second fluorescence exposure time may be a pulse, for example 2 times longer than the excitation pulse. Further, the visible exposure may have a different frequency from the white light pulse. For example, the visible exposure may not occur with each individual white light pulse, while the fluorescence exposure may have the same frequency as the excitation pulse.

[0119] Alternative timings and exposure diagrams are described below. There, a sensor having rows that are all active during a common exposure duration may be used, but still, environmental light is compensated using a single sensor. For example, when the target is not illuminated, the background light may be directly detected by the sensor. Other variations for pulses, exposures, and detections will be apparent to those skilled in the art.

[0120] Figure 11B shows an alternative timing diagram for white light (RGB) and fluorescence excitation (laser) illumination, and visible (VIS) and NIR fluorescence (FL) imaging sensor exposures configured to enable subtraction of ambient room light from the fluorescence signal with a single sensor. The visible light exposure and the fluorescence exposure are shown in sequence along with the exposure for acquiring the background (BG) image signal due to ambient light. As described above, the white light illumination may be pulse output at 80 Hz. The fluorescence excitation illumination may be pulse output at 20 Hz, and the pulse duration or width may be increased up to, for example, twice the white light pulse duration, thereby enabling a longer corresponding fluorescence exposure. When using an imaging sensor with a global shutter, each sensor exposure must end with a readout period at the end of the imaging frame. The exposure for acquiring the ambient light background image signal may be performed at the end portion of the frame when there is no pulsed white light nor excitation light. As shown in the example of Figure 11B, when acquiring video at a frame rate of 60 Hz, a 1 / 4 frame duration may be used as the white light illumination pulse width, and at this time, a visible light exposure of 1 / 4 frame duration occurs in the frame where the end of the white light illumination pulse aligns with the end of the frame.

[0121] The contribution of ambient light to the fluorescence image may be removed by subtracting the scaled image signal recorded during one or more background exposures from each fluorescence exposure image. For example, the image signal from a 1 / 4 frame duration background exposure may be scaled up by a factor of two and subtracted from the subsequent image signal from a 1 / 2 frame duration fluorescence exposure. As another example, both the image signal of the 1 / 4 frame duration background exposure before the image signal of the 1 / 2 frame duration fluorescence exposure and the second 1 / 4 frame background image signal following the fluorescence exposure may be subtracted from the fluorescence image signal. The scaling of the image signals from the first background exposure and the second background exposure may include predicting the pixel values corresponding to the intermediate time points by interpolation of the pixel values from the first exposure time point and the second exposure time point.

[0122] By using an imaging sensor with fast readout that enables a higher video frame acquisition rate, it becomes possible to allocate additional exposure periods within an illumination and exposure timing scheme for a given white light pulse frequency. For example, while maintaining an 80 Hz white light illumination pulse as described above, by using a sensor with a higher video frame acquisition rate such as 120 Hz, it is possible to add white light exposure, ambient background exposure, or fluorescence exposure within a given period compared to using a slower video frame acquisition rate such as 60 Hz.

[0123] In a specific example shown in FIG. 11B, the detection period is 3 frames, the excitation pulse has a width that is twice the width of the white light pulse, visible light is detected during one frame, for example the first frame, background light is detected during one frame, for example the second frame, and fluorescence is detected during one frame, for example the third or last frame. Here, the visible exposure time may be equal to the duration of the white light pulse, the fluorescence exposure time may be equal to the duration of the white light pulse, and the fluorescence exposure time may be equal to the duration of the excitation pulse. Further, the visible exposure may have a frequency different from that of the white light pulse. For example, the visible exposure may not occur with each individual white light pulse, while the fluorescence exposure may have the same frequency as the excitation pulse. Finally, the fluorescence exposure may occur only once within the period.

[0124] Figure 11C shows an alternative timing diagram for white light (RGB) and fluorescence excitation (laser) illumination, and visible (VIS) and NIR fluorescence (FL) imaging sensor exposures configured to enable subtraction of ambient room light from the fluorescence signal with a single sensor with a 120 Hz video frame acquisition rate. An 80 Hz white light pulse frequency is used, and a 1 / 2 frame duration may be used as the white light illumination pulse width, at which time a 1 / 2 frame duration visible light exposure occurs in a frame where the end of the white light illumination pulse aligns with the end of the frame. Fluorescence excitation illumination is pulsed at 40 Hz and the pulse duration is shown to be 1 frame, thereby increasing the frequency of the corresponding fluorescence exposure. The exposure for acquiring the ambient light background image signal may be performed at the end of the frame when there is no pulsed white light or excitation light. For example, as shown in this exemplary embodiment, a 1 / 2 frame duration exposure may occur in the frame between the fluorescence exposure and the next white light exposure.

[0125] In the specific example shown in FIG. 11C, the detection period is 3 frames, the excitation pulse has a width twice the width of the white light pulse, visible light is detected during one frame, for example the second frame, background light is detected during one frame, for example the first frame, and fluorescence is detected during one frame, for example the third or last frame. Here, the visible exposure time may be equal to the duration of the white light pulse, the background exposure time may be equal to the duration of the white light pulse, and the fluorescence exposure time may be equal to the duration of the excitation pulse. Further, the visible exposure may have a frequency different from that of the white light pulse. For example, the visible exposure may not occur with each individual white light pulse, while the fluorescence exposure may have the same frequency as the excitation pulse. Finally, the fluorescence exposure may occur only once within the period.

[0126] Depending on the intensity of the fluorescence excitation light used, there may be safety considerations that limit the duration and frequency of the excitation light pulse. One approach to reducing the applied excitation light intensity is to reduce the duration of the excitation light pulse and the corresponding fluorescence exposure. Additionally or alternatively, the frequency of the excitation light pulse (and the corresponding fluorescence exposure) may be reduced, or the readout period that would otherwise be used for fluorescence exposure may instead be used for background exposure to improve the measurement of ambient light.

[0127] Figure 11D shows an alternative timing diagram of white light (RGB) and fluorescence excitation (laser) illumination, and visible (VIS) and NIR fluorescence (FL) imaging sensor exposures configured to enable subtraction of ambient room light from the fluorescence signal with a single sensor with a 120 Hz video frame acquisition rate. An 80 Hz white light pulse frequency is used, and a 1 / 2 frame duration may be used as the white light illumination pulse width, at which time a 1 / 2 frame duration visible light exposure occurs in a frame where the end of the white light illumination pulse aligns with the end of the frame. Fluorescence excitation illumination is shown to be pulsed at 20 Hz with a pulse duration of 1 frame. The exposure for acquiring the ambient light background image signal may be performed at the end of the frame when there is no pulsed white light or excitation light. For example, as shown in this exemplary embodiment, a 1 / 2 frame duration background exposure may occur in the frame between the fluorescence exposure and the next first white light exposure, and both a 1 frame duration first background exposure and a 1 / 2 frame duration second background exposure may occur in the frame between the first white light exposure and the next second white light exposure.

[0128] In a particular example shown in FIG. 11D, the detection period is 6 frames, the excitation pulse has a width twice that of the white light pulse width, the visible light is detected between 2 frames, for example the second and fifth frames, the background light is detected between 3 frames, for example the first, third and fourth frames, and the fluorescence is detected between one frame, for example the sixth or last frame. Here, the visible exposure time may be equal to the duration of the white light pulse, the background exposure time may be equal to or twice the duration of the white light pulse, and the fluorescence exposure time may be equal to the duration of the excitation pulse. Further, the visible exposure may have a frequency different from that of the white light pulse. For example, the visible exposure may not occur with each individual white light pulse (e.g., only twice within a period), while the fluorescence exposure may have the same frequency as the excitation pulse. Finally, the background exposure occurs three times within the period, and its total duration may be four times the duration of the white light pulse.

[0129] To improve the performance of the environmental chamber light compensation method as described above, a wavelength-dependent aperture (e.g., element 55 of FIG. 6A) may be used that includes a smaller central aperture that allows all transmission of visible and NIR light and a larger surrounding aperture that blocks visible light but allows transmission of NIR light. By using such a wavelength-dependent aperture, a larger proportion of the NIR signal can be collected relative to the visible light signal, thereby improving the performance of the image signal subtraction for the evaluation and removal of the environmental chamber light component. The wavelength-dependent aperture may also be a larger third aperture that blocks both visible and NIR light and that surrounds the other smaller apertures. As an example, the wavelength-dependent aperture may comprise a film aperture. A film (e.g., a plastic or glass film) of a material that blocks transmission of visible light but allows transmission of NIR light has a central aperture (e.g., a hole) that allows transmission of both visible and NIR light. Such a film aperture may include a material that blocks transmission of visible light through reflection and / or a material that blocks transmission of visible light through absorption. As another example, the wavelength-dependent aperture may comprise a dichroic aperture formed by masked thin film deposition on a single substrate. A thin film that allows transmission of visible and NIR light is formed in the smaller central aperture, and a second thin film that blocks transmission of visible light but allows transmission of NIR light is formed in the larger surrounding aperture. The aperture sizes of the smaller central aperture and the larger surrounding aperture of the wavelength-dependent aperture may be set such that the depth of field of visible light and the depth of field of NIR light are substantially the same during imaging by the imaging system. One or more wavelength-dependent filters may be placed at different positions throughout the device. Therein, rejection of the visible signal and passage of the NIR signal may be optimized. For example, such a wavelength-dependent filter may be in front of the lens 51. As another example, one or more wavelength-dependent filters may be at the pupil plane of the imaging lens.

[0130] If a target reticle is displayed around the area within the imaged field of view and the normalized fluorescence intensity is calculated and displayed within that area, it would be convenient, for example, to more easily compare the fluorescence signals of different areas. Normalization of the measured fluorescence intensity values enables meaningful comparison of multiple images and corresponding values. To correct for variations due to the working distance of the measured fluorescence intensity (e.g., the distance between the imaged anatomical structure and the imaging system), the normalized fluorescence intensity value may be based on the ratio between the measured fluorescence intensity value and the reflected light value within the target reticle area.

[0131] The numerical representation of the normalized fluorescence intensity value within the target reticle area may be displayed in or near the image frame. This makes it easier to compare the values when the target reticle is directed at different positions on the imaged anatomical structure. For example, the numerical representation may be the average value of the normalized fluorescence intensity values across all image pixels within the target reticle area.

[0132] Additionally or alternatively, a time history plot of the numerical representation of the normalized fluorescence intensity value within the target reticle area may be displayed in or near the image frame. This makes it easier to compare the values when the target reticle is directed at different positions on the imaged anatomical structure or at the same position over a series of time points. Such a time history plot can further assist the user in evaluating the fluorescence profile on the imaged tissue surface by scanning across the region of anatomical interest and viewing the relative normalized fluorescence intensity profile plot.

[0133] FIG. 13A shows a diagram of a sample display output from an embodiment of the display method. The target reticle 125 is positioned over an area 122 of the anatomical structure 120 being imaged that has no fluorescence intensity, and a numerical representation 126 of the fluorescence intensity is displayed near the target reticle 125. FIG. 13B shows a diagram of another sample display output. The target reticle 125 is positioned over an area 124 of high relative normalized fluorescence intensity, and shows a corresponding relatively high fluorescence intensity numerical representation 126. FIG. 13C shows a diagram of another sample display output. The target reticle 125 is positioned over an area 124 of medium relative normalized fluorescence intensity, and shows a corresponding relatively medium fluorescence intensity numerical representation 126. FIG. 13D shows a diagram of a sample display output. The target reticle 125 is positioned over an area 124 of medium relative normalized fluorescence intensity, and shows a time history plot 128 of the numerical representation of the normalized fluorescence intensity. This plot 128 is consistent with imaging in sequence an area of zero relative normalized fluorescence intensity, an area of high relative normalized fluorescence intensity, and an area of medium relative normalized fluorescence intensity. Alternatively or additionally to displaying the numerical representation and / or the history plot on the target, for example a display area associated with the target reticle on the device itself or on another display may display this information.

[0134] FIG. 14 shows a recorded image of an anatomical fluorescence imaging phantom that characterizes an embodiment of the display method output for displaying the normalized fluorescence intensity. In particular, the target 110 is illuminated by excitation light according to the embodiment, and the target reticle 115 is positioned over an area 112 of the fluorescence intensity. The numerical representation of the target reticle 115 is displayed in an area 116 associated with the target reticle 115. A time history plot 118 of the numerical representation of the normalized fluorescence intensity resulting from imaging different positions of the reticle 115 may be displayed.

[0135] Such a display method would be useful in various fluorescence imaging systems. Such various fluorescence imaging systems include, for example, endoscopic or laparoscopic fluorescence imaging systems, open field fluorescence imaging systems, and combinations thereof. Such normalization and display of fluorescence intensity values can serve for quantitative comparison of relative fluorescence intensities between image data from various time points within an imaging session. When combined with appropriately standardized fluorescent agent administration and imaging protocols as well as standardized calibration of the imaging device, such normalization and display of fluorescence intensity values can further serve for quantitative comparison of relative fluorescence intensities between image data from different imaging sessions.

[0136] Example

[0137] Fluorescence medical imaging system for acquisition of image data

[0138] In one embodiment, the system for illumination and imaging of a subject may be used in conjunction with a medical imaging system, such as, for example, a fluorescence medical imaging system for acquiring fluorescence medical imaging data, or may be used as a component thereof. An example of such a fluorescence medical imaging system is the fluorescence imaging system 10 schematically shown in FIG. 1. In this embodiment, the fluorescence imaging system 10 is configured to acquire a time series of fluorescence signal intensity data (e.g., images, videos) that capture the passage of a fluorescence imaging agent through tissue.

[0139] The fluorescence imaging system 10 (FIG. 1) includes an illumination source 15 and an illumination module 11 that induce fluorescence emission from a fluorescence imaging agent 17 in the subject's tissue (e.g., in the blood) by illuminating the subject's tissue, an imaging module 13 configured to acquire a time series of fluorescence images from the fluorescence emission, and a processor assembly 16 configured to use the acquired time series of fluorescence images (fluorescence signal intensity data) according to the various embodiments described herein.

[0140] In various embodiments, the illumination source 15 (FIG. 1) includes, for example, a light source 200 (FIG. 15), the light source 200 including a fluorescence excitation source configured to generate excitation light having an intensity and wavelength appropriate for exciting the fluorescence imaging agent 17. The light source 200 of FIG. 15 includes a laser diode 202 (e.g., this may include, for example, one or more fiber-coupled diode lasers) configured to provide excitation light for exciting a fluorescence imaging agent 17 (not shown). Examples of other sources of excitation light that may be used in various embodiments include one or more LEDs, arc lamps, or other illumination techniques having an intensity and appropriate wavelength sufficient to excite the fluorescence imaging agent 17 within the tissue (e.g., within the blood). For example, excitation of the fluorescence imaging agent 17 in the blood (the fluorescence imaging agent 17 being a fluorescent dye with near-infrared excitation characteristics) may be performed using one or more 793 nm, conduction-cooled, single-bar, fiber-coupled laser diode modules available from DILAS Diode Laser Co, Germany.

[0141] In various embodiments, the light output from the light source 200 of FIG. 15 may be projected through an optical element (e.g., one or more optical elements) to form and direct the output used to illuminate the region of interest of the tissue. The forming optical system may include one or more lenses, light guides, and / or diffractive elements such that a flat field is obtained over substantially the entire field of view of the imaging module 13. In certain embodiments, the fluorescence excitation source is selected to emit at a wavelength close to the maximum absorption of the fluorescence imaging agent 17 (e.g., ICG). For example, referring to the embodiment of the light source 200 of FIG. 15, the output 204 from the laser diode 202 passes through one or more focusing lenses 206 and through a homogenizing light pipe 208, such as a light pipe commonly available from Newport Corporation, USA. Finally, the light passes through an optical diffractive element 214 (e.g., one or more optical diffusers), such as a ground glass diffractive element available from Newport Corporation, USA. The power to the laser diode 202 itself may be provided by, for example, a high current laser driver available from Lumina Power Inc., USA. The laser may optionally operate in pulsed mode during the image acquisition process. In this embodiment, an optical sensor, such as a solid state photodiode 212, is incorporated into the light source 200 to sample the illumination intensity generated by the light source 200 via scattering and diffuse reflection from the various optical elements. In various embodiments, an additional illumination source may be used to provide guidance when aligning and positioning the module over the region of interest. In various embodiments, at least one of the components of the light source 200 shown in FIG. 15 may be a component that includes the illumination source 15 and / or the illumination module 11.

[0142] Referring back to FIG. 1, in various embodiments, the imaging module 13 may be, for example, a component of the fluorescence imaging system 10 and may be configured to obtain a time series (e.g., video) of fluorescence images from the fluorescence emission from the fluorescence imaging agent 17. Referring to FIG. 16, an exemplary embodiment of the imaging module 13 comprising a camera module 250 is shown. As shown in FIG. 16, the camera module 250 uses a system of imaging optics (e.g., front element 254, rejection filter 256, dichroic 260, and rear element 262) to focus the fluorescence emission onto an image sensor assembly 264 including at least one two-dimensional solid-state image sensor, so as to obtain an image of the fluorescence emission 252 from the fluorescence imaging agent 17 (not shown) within the tissue (e.g., in the blood). The rejection filter 256 may be, for example, a notch filter used to reject the wavelength band corresponding to the excitation light. The dichroic 260 may be, for example, a dichroic mirror used to selectively pass a certain subset of the incoming light wavelength spectrum and direct the remaining wavelengths away from the optical path for rejection or redirect them towards a separate image sensor. The solid-state image sensor may be a charge-coupled device (CCD), a CMOS sensor, a CID, or similar two-dimensional sensor technology. The charge obtained from the optical signal converted by the image sensor assembly 264 is converted into an electronic video signal including both digital video signals and analog video signals by appropriate readout and amplification electronics within the camera module 250.

[0143] According to one embodiment, in conjunction with the NIR-compatible optics for ICG fluorescence imaging, an excitation wavelength of about 800 nm + / - 10 nm and an emission wavelength of > 820 nm are used. Those skilled in the art will understand that other excitation and emission wavelengths may be used for other imaging agents.

[0144] Returning to FIG. 1, in various embodiments, the processor assembly 16 may include, for example, the following. A processor module (not shown) configured to perform various processing operations, including executing instructions held in a computer-readable medium, the instructions causing one or more of the systems described herein to perform the methods and techniques described herein. A data storage module (not shown) for recording and holding data from operations and, in some embodiments, for holding instructions executable by a processor module, the instructions for implementing the methods and techniques disclosed herein.

[0145] In various embodiments, the processor module includes any computer or computing means such as, for example, a tablet, laptop, desktop, network computer, or dedicated stand-alone microprocessor. Input is obtained, for example, from the image sensor 264 of the camera module 250 shown in FIG. 16, from the solid-state photodiode of the light source 200 of FIG. 15, and from any of the external control hardware such as a foot switch or remote control. Output is provided to the laser diode driver and the optical aligner. In various embodiments, the processor assembly 16 (FIG. 1) may have a data storage module with the ability to store the time series of input data (e.g., image data) in a tangible non-transitory computer-readable medium such as an internal memory (e.g., hard disk or flash memory), thereby enabling data recording and processing. In various embodiments, the processor module may have an internal clock, thereby enabling control of various elements and ensuring the correct timing of illumination and sensor shutters. In various other embodiments, the processor module may provide a graphical display of user input and output. The fluorescence imaging system may optionally include a video display (not shown). This video display may display the image when the image is being acquired or during playback after being recorded, or may visualize the data generated at various stages of the method as described above.

[0146] During operation, and continuing to refer to the exemplary embodiments of FIGS. 1, 15, and 16, the subject is positioned at an imaging position such that the area of interest of the anatomy of the subject is placed under both the illumination module 11 and the imaging module 13. As a result, a substantially uniform illumination field is generated over substantially the entire area of interest. In various embodiments, an image of the area of interest may be acquired for background removal before administering the fluorescent imaging agent 17 to the subject. For example, to do this, the operator of the fluorescent imaging system 10 of FIG. 1 may start the acquisition of a time series (e.g., video) of fluorescent images by pressing a remote switch or foot control, or via a keyboard (not shown) connected to the processor assembly 16. As a result, the illumination source 15 is turned on and the processor assembly 16 begins recording the fluorescent image data provided by the image acquisition assembly 13. It will be understood that in certain embodiments, the illumination source 15 may comprise a radiation source that remains continuously on during the image acquisition sequence, instead of the pulse mode described above. When operating in the pulse mode of the embodiment, the image sensor 264 of the camera module 250 (FIG. 16) is synchronized to collect the fluorescent radiation following the laser pulse generated by the diode laser 202 of the light source 200 (FIG. 15). By doing so, the maximum fluorescent radiation intensity is recorded and the signal-to-noise ratio is optimized. In this embodiment, the fluorescent imaging agent 17 is administered to the subject and carried to the area of interest via arterial flow. The acquisition of the time series of fluorescent images is started, for example, immediately after the administration of the fluorescent imaging agent 17, and the time series of fluorescent images from substantially the entire area of interest is acquired through the arrival of the fluorescent imaging agent 17. The fluorescent radiation from the area of interest is collected by the collection optics of the camera module 250. Residual ambient excitation light and reflected excitation light are attenuated by subsequent optical elements of the camera module 250 (e.g., the optical element 256 of FIG. 16, which may be a filter). As a result, the fluorescent radiation can be acquired by the image sensor assembly 264 with minimal interference from light from other sources.

[0147] In various embodiments, the processor communicates with or is a component of the imaging system. The program code means or other computer-readable instructions according to various embodiments can be described and / or held in any suitable programming language and can be provided to the processor in many forms. Such many forms include, for example, information permanently held in a non-writable holding medium (e.g., read-only memory devices such as ROMs and CD-ROM disks), information changeably held in a writable holding medium (e.g., hard drives), information passed to the processor via a temporary medium (e.g., signals), information carried to the processor through communication media such as local area networks, public networks such as the Internet, or any type of medium suitable for holding electronic instructions, but are not limited thereto. In various embodiments, the tangible non-transitory computer-readable media include all computer-readable media. In one embodiment, the computer-readable instructions for performing one or more of the methods or techniques described herein may be held in the non-transitory computer-readable media alone.

[0148] In one embodiment, the illumination and imaging system may be a component of a medical imaging system, such as the fluorescence medical imaging system 10 that acquires medical imaging data. In an embodiment where the illumination and imaging system is a component of an imaging system such as the above-described fluorescence imaging system, the light source, illumination module, imaging module, and processor of the medical imaging system may function as the camera assembly and processor of the illumination and imaging system. Those skilled in the art will understand that imaging systems other than the fluorescence imaging system may be used for use in an illumination and / or imaging system such as those described above, depending on the type of imaging performed.

[0149] Exemplary imaging agents used in generating image data

[0150] According to one embodiment, in a fluorescence medical imaging application, the imaging agent is a fluorescence imaging agent such as indocyanine green (ICG) dye. When ICG is administered to a subject, it binds to blood proteins and circulates in the tissue together with the blood. The fluorescence imaging agent (e.g., ICG) may be administered to the subject as a bolus (e.g., into a vein or artery) at a concentration suitable for imaging. In this case, the bolus circulates through the vascular system and passes through the capillary system. In other embodiments where multiple fluorescence imaging agents are used, such multiple agents may be administered simultaneously (e.g., as a single bolus) or sequentially (e.g., as separate boluses). In one embodiment, the fluorescence imaging agent may be administered by a catheter. In one embodiment, the fluorescence imaging agent may be administered to the subject within one hour prior to measuring the signal intensity generated from the fluorescence imaging agent. For example, the fluorescence imaging agent may be administered to the subject within thirty minutes prior to performing the measurement. In yet other embodiments, the fluorescence imaging agent may be administered at least thirty seconds prior to performing the measurement. In yet other embodiments, the fluorescence imaging agent may be administered simultaneously with performing the measurement.

[0151] According to certain embodiments, the fluorescent imaging agent may be administered at various concentrations to achieve a desired circulating blood concentration. For example, in embodiments where the fluorescent imaging agent is ICG, a circulating blood concentration of about 5 μM to about 10 μM may be achieved by administering it at a concentration of about 2.5 mg / mL. In various embodiments, the upper limit concentration for administration of the fluorescent imaging agent is the concentration at which the fluorescent imaging agent becomes clinically toxic in the circulating blood, and the lower limit concentration is the limit of the device for obtaining signal intensity data resulting from the fluorescent imaging agent circulating with the blood to detect the fluorescent imaging agent. In various other embodiments, the upper limit concentration for administration of the fluorescent imaging agent is the concentration at which the fluorescent imaging agent becomes self-inactivating. For example, the circulating concentration of ICG may be in the range of about 2 μM to about 10 mM. Thus, in one aspect, the method includes a step of administering an imaging agent (e.g., a fluorescent imaging agent) to a subject and a step of obtaining signal intensity data (e.g., a video) before processing the signal intensity data according to various embodiments. In other aspects, the method may exclude the step of administering the imaging agent to the subject.

[0152] According to one embodiment, a suitable fluorescent imaging agent for generating fluorescent image data in a fluorescence imaging application is capable of circulating with blood (e.g., a fluorescent dye capable of circulating with blood components such as lipoproteins and plasma serum in blood), passing through the vascular system of tissues (i.e., large blood vessels and capillaries), and generating a signal intensity when exposed to appropriate light energy (e.g., excitation light energy or absorption light energy). In various embodiments, the fluorescent imaging agent includes a fluorescent dye, an analog thereof, a derivative thereof, or a combination thereof. The fluorescent dye includes a non-toxic fluorescent dye. In one embodiment, the fluorescent dye optimally fluoresces in the near-infrared spectrum. In one embodiment, the fluorescent dye is or includes a tricarbocyanine dye. In a given embodiment, the fluorescent dye is or includes indocyanine green (ICG), methylene blue, or a combination thereof. In other embodiments, the fluorescent dye is fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, orthophthalaldehyde, fluorescamine, rose bengal, trypan blue, fluorogold, or a combination thereof that can be excited using an excitation light wavelength appropriate for each dye, or includes such. In one embodiment, an analog or derivative of the fluorescent dye may be used. For example, a fluorescent dye analog or derivative includes a fluorescent dye that has been chemically modified but maintains the ability to fluoresce when exposed to light energy of an appropriate wavelength.

[0153] In various embodiments, the fluorescent imaging agent may be provided as a lyophilized powder, solid, or liquid. In certain embodiments, the fluorescent imaging agent may be provided in a vial (e.g., a sterile vial), which may allow reconstitution at an appropriate concentration by preparing a sterile fluid with a sterile syringe. Reconstitution may be performed using a suitable carrier or diluent. For example, the fluorescent imaging agent may be reconstituted with an aqueous diluent immediately prior to administration. In various embodiments, any diluent or carrier that will maintain the fluorescent imaging agent in solution may be used. As an example, ICG is reconstitutable with water. In certain embodiments, once the fluorescent imaging agent is reconstituted, it may be mixed with additional diluents and carriers. In certain embodiments, the fluorescent imaging agent may be complexed with other molecules (e.g., proteins, peptides, amino acids, synthetic polymers, sugars, etc.) to enhance, for example, solubility, stability, imaging properties, or combinations thereof. Additional buffers may be added, including trisaminomethane, HCl, NaOH, phosphate buffers, and / or HEPES.

[0154] One of ordinary skill in the art, having been provided with the details of the fluorescent imaging agent above, will understand that other imaging agents may be used in connection with the systems, methods, and techniques described herein, depending on the optical imaging modality.

[0155] In one embodiment, the fluorescent imaging agent used in combination with the methods and systems described herein may be used for blood flow imaging, tissue perfusion imaging, lymph imaging, or combinations thereof, and they may be performed during invasive surgery, minimally invasive surgery, non-invasive surgery, or combinations thereof. Examples of invasive surgeries that may involve blood flow and tissue perfusion include cardiac-related surgeries (e.g., on-pump or off-pump CABG) and reconstructive surgeries. Examples of non-invasive or minimally invasive surgeries include the treatment and / or management of wounds (e.g., chronic wounds such as pressure ulcers). Examples of lymph imaging include the identification of lymph nodes, lymph node drainage, lymph mapping, or combinations thereof. In one variation, such lymph imaging may relate to the female reproductive system (e.g., uterus, cervix, vulva). In one embodiment, the fluorescent imaging agent may be administered at a concentration sufficient to affect lymphatic imaging and in a suitable manner.

[0156] Tissue perfusion is related to the microcirculatory blood flow per unit tissue volume, where oxygen and nutrients are provided to the capillary bed of the tissue to be perfused and waste products are removed therefrom. Tissue perfusion is a phenomenon separate from, although related to, the blood flow within blood vessels. The quantified blood flow through blood vessels may be expressed in terms defining flow (i.e., volume / time) or in terms defining speed (i.e., distance / time). Tissue blood perfusion defines the movement of blood through capillaries such as arterioles, capillaries, venules, etc. within the tissue volume. Quantified tissue blood perfusion is expressed in terms of the blood flow through the tissue, i.e., in terms of volume / time / tissue volume (or tissue mass). Perfusion is associated with nutritive blood vessels (e.g., capillaries known as capillaries). This nutritive blood vessel includes blood vessels associated with the exchange of metabolites between blood and tissue, rather than non-nutritive blood vessels of larger diameter. In one embodiment, quantification of the target tissue may include calculating or determining a parameter or quantity related to the target tissue, such as rate, size, volume, time, distance / time, and / or volume / time, and / or amount of change. It may relate to any one or more of the aforementioned parameters or quantities. However, compared to the movement of blood through blood vessels of larger diameter, the movement of blood through individual capillaries can be highly irregular. This is mainly due to vasomotion, and the spontaneous oscillation at the vascular beat appears as a pulsation in the movement of red blood cells.

[0157] In summary, one or more embodiments can provide a flat illumination field while allowing for changes in working distance and can match the illumination field to a target imaging field. Thus, accurate quantitative imaging applications are possible. The imaging element that focuses light from the target onto the sensor may be moved in synchronization with the steering of the illumination field. Additionally or alternatively, a drape may be used to ensure a tight fit between the drape lens and the device's window frame. Additionally or alternatively, one or more embodiments can reduce ambient light from the light to be imaged by using a single sensor and controlled timing of illumination and exposure or detection. Additionally or alternatively, one or more embodiments may allow for the display of normalized fluorescence intensity measured within the target reticle region of the image frame.

[0158] In contrast, if the illumination and imaging device do not match the illumination to the target imaging field, or do not provide a flat, i.e., uniform or substantially uniform, illumination field, the illumination and image quality will degrade. A non-uniform illumination field can cause disturbing and inaccurate imaging artifacts, especially when used at various working distances in a hand-held imaging device. Also, extra light outside the imaging field reduces the device's efficiency and can be a nuisance to the user when positioning the device.

[0159] The methods and processes described herein may be executed by a computer, processor, manager, controller, or by code or instructions executed by hardware or other circuitry. Since the algorithms underlying the methods (or the operation of the computer, processor, or controller) have been described in detail, the code or instructions for implementing the operation of the method embodiments may convert the computer, processor, or controller into a dedicated processor for executing the methods described herein.

[0160] Other embodiments may also include a computer-readable medium, such as a non-transitory computer-readable medium, for holding the above-described code or instructions. The computer-readable medium may be volatile or non-volatile memory or other storage device, and it may be removably or fixedly coupled to a computer, processor, or controller, which executes the code or instructions to perform embodiments of the methods described herein.

[0161] Exemplary embodiments are disclosed herein and specific terms are used, but they are used only in a general and illustrative sense and should be construed as such, not for the purpose of limitation. In one example, as would be apparent to one of ordinary skill in the art at the time of filing of this application, features, characteristics, and / or elements described in connection with a particular embodiment may be used alone or, unless otherwise specifically stated, in combination with features, characteristics, and / or elements described in connection with other embodiments. Thus, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the spirit and scope of the invention as defined below.

[0162] Although the present disclosure has been described in connection with the various embodiments detailed above, it is not intended to be limited to the details shown. This is because various modifications and structural variations can be made without departing from the scope of the present disclosure. Without departing from the scope of the present disclosure, various changes can be made to the form, component arrangement, steps, details, and order of operations of the described embodiments, and other embodiments of the present disclosure can also be formed, which will be apparent to those skilled in the art who have touched on the present disclosure. Therefore, since the appended claims fall within the scope of the present disclosure, it is assumed that the appended claims cover such variations and embodiments. For the sake of brevity and clarity, features have been described in this specification as part of the same or different embodiments. However, it will be understood that the scope of the present disclosure includes embodiments having all or some combinations of the described features. For the terms "for example" and "such as" and their grammatical equivalents, unless otherwise specified, the phrase "and non-limitingly" is understood to follow. As used in this specification, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

Claims

1. 1. An illumination module for use in an imaging system having an imaging field of view for imaging a target, comprising: a first illumination port configured to output a first light beam having a first illumination distribution at the target to illuminate the target; and a second illumination port configured to illuminate the target by outputting a second light beam having a second illumination distribution at the target, the second illumination distribution being substantially similar to the first illumination distribution at the target, the second illumination port being spaced apart from the first illumination port, the first and second illumination distributions being provided simultaneously to the target and overlapping at the target, and the illumination from the first and second ports being matched to the same aspect ratio and field coverage as the imaging field.

2. 10. The illumination module of claim 1, wherein light from the first and second illumination ports overlap to provide uniform illumination on a target field of view.

3. 3. The lighting module of claim 1 or 2, comprising a steering driver for simultaneously steering the first and second light ports through different fields of view.

4. Each of the first and second illumination ports comprises: at least one fixed lens; A steerable housing; and 4. The lighting module of claim 3, comprising a lens module having at least one lens mounted to a steerable housing, the steerable housing being in communication with the steering driver.

5. 5. The lighting module of claim 3 or 4, further comprising a housing that houses the first and second lighting ports and the steering driver.

6. The lighting module of claim 5 , wherein the housing is a handheld housing.

7. The lighting module of claim 5 , wherein the handheld housing comprises a control surface including an activation device for controlling the steering wheel driver.

8. 8. The lighting module of claim 1, wherein each of the first and second lighting distributions is a rectangular lighting distribution.

9. The illumination module of claim 8 , wherein each of the first and second illumination ports includes a lens module having two pairs of cylindrical lenses.

10. 9. The illumination module of claim 8, wherein said first and second illumination ports are symmetrically offset from a midline of a long dimension of said rectangular illumination distribution.

11. 1. An imaging device having an imaging field of view, comprising: a first illumination port configured to output a first light having a first illumination distribution at the target to illuminate the target; a second illumination port for illuminating the target by outputting a second light having a second illumination distribution at the target, the second illumination distribution being substantially similar to the first illumination distribution at the target, the second illumination port being spaced apart from the first illumination port, the first and second illumination distributions being provided simultaneously to the target and overlapping at the target, and the illumination from the first and second ports being matched to the same aspect ratio and field of view as the imaging field of view; and a sensor for detecting light from the target.

12. The imaging device of claim 11 , further comprising a housing that houses the first and second illumination ports and the sensor.

13. 13. The imaging device of claim 11 or 12, further comprising a steering driver for simultaneously steering the first and second illumination ports through different fields of view.

14. an imaging element for focusing light onto the sensor; 14. The imaging device of claim 13, wherein the steering driver is for moving the imaging element synchronously with steering of the first and second illumination ports.

15. The imaging device of claim 14 , wherein the steering driver is within the housing, the housing including a control surface including an activation device for controlling the steering driver.

16. 16. The imaging device of claim 12, wherein the housing is a handheld housing having a form factor that enables the control surface to be controlled with one hand to control the illumination of the target from multiple orientations.

17. 17. The imaging device of claim 12, further comprising an illumination source that outputs light to the first and second illumination ports, the illumination source being outside the housing.

18. 20. The imaging device of claim 17, wherein the illumination source is for outputting visible light and / or excitation light to the first and second illumination ports.

19. 20. The imaging device of claim 18, wherein the sensor is a single sensor for detecting light from the target resulting from illumination with visible light and excitation light.

20. further comprising a wavelength dependent aperture upstream of said sensor; 20. The imaging device of claim 19, wherein the wavelength dependent aperture blocks visible light outside a central region.

21. 21. The imaging device of claim 12, further comprising a video processor box external to the housing.

22. 22. The imaging device of claim 21, wherein the illumination source is integrated with the video processor box.

23. 1. A method for investigating a target, comprising: illuminating the target with a first light output having a first illumination distribution at the target and a second light output having a second illumination distribution at the target, wherein the second illumination distribution is substantially similar to the first illumination distribution, the first and second illumination distributions overlap at the target, and the illumination on the target is matched to the same aspect ratio and field coverage as an imaging field.

24. 24. The method of claim 23, further comprising simultaneously steering the first and second light outputs through different fields of view.

25. receiving light from the target; 25. The method of claim 24, further comprising focusing light onto a sensor with an imaging element, the imaging element being moved synchronously with the simultaneous steering of the first and second light outputs.

26. A drape for use with an imaging device, comprising: a barrier material encasing the imaging device; and a drape window frame defining an opening in the barrier material; a drape lens within the opening in the barrier material; and an interface integral with the drape window frame, the interface securing the drape lens to a window frame of the imaging device.

27. 27. The drape of claim 26, wherein the drape window frame is insertable into the window frame of the imaging device.

28. 28. The drape of claim 26 or 27, wherein the interface includes two clamps symmetrically mounted on each of opposite sides of the drape window frame.

29. 29. The drapery of claim 28, wherein the two clamps are at the top and bottom of the drapery window frame.

30. A processor for imaging a target, the processor comprising: activating an excitation light source to generate an excitation pulse for illuminating the target; generating a white pulse for illuminating the target by activating a white light source such that the white pulse does not overlap with the excitation pulse and such that the white pulse is generated at least twice within the period; exposing an image sensor for a fluorescence exposure time during said excitation pulse; exposing the image sensor during at least one white light pulse for a visible exposure time; detecting an output from the image sensor; Correcting the ambient light, and outputting the resulting image.

31. To perform ambient light compensation, the processor: exposing a first set of sensor pixel rows of the image sensor for a percentage of the fluorescent light exposure time for the first set of sensor pixel rows; and exposing a second set of sensor pixel rows of the image sensor for the entire fluorescent exposure time.

32. 32. The processor of claim 31, wherein the percentage is 1 / 2.

33. 33. The processor of claim 32, wherein the processor is for determining the fluorescent signal F using the formula: F = 2*Exp2 - Exp1 where Exp1 is the signal output during said percentage of the fluorescence exposure time and Exp2 is the signal output during said entire fluorescence exposure time.

34. 32. The processor of claim 31, wherein the percentage of the exposure time is equal to a width of the excitation pulse.

35. 31. The processor of claim 30, wherein the visible exposure time is greater than a width of the at least one white pulse.

36. 31. The processor of claim 30, wherein the visible exposure time is for one white pulse within the period.

37. 31. The processor of claim 30, wherein the visible exposure time is for two white pulses within the period.

38. To perform ambient light compensation, the processor:

31. The processor of claim 30, further comprising exposing the image sensor for a background exposure time if a target is not illuminated at least once within the period of time.

39. 1. A method for imaging a target within a period of time, comprising: generating an excitation pulse to illuminate the target; generating a white pulse for illuminating the target such that the white pulse does not overlap the excitation pulse and such that the white pulse is generated at least twice within the period; exposing an image sensor for a fluorescence exposure time during said excitation pulse; exposing the image sensor during at least one white light pulse for a visible exposure time; detecting an output from the image sensor; Correcting the ambient light, and outputting the resulting image.

40. To correct the ambient light, exposing a first set of sensor pixel rows of the image sensor for a percentage of the fluorescent light exposure time; 40. The method of claim 39, further comprising exposing a second set of sensor pixel rows of the image sensor for the entire fluorescent light exposure time.

41. To correct the ambient light, 40. The method of claim 39, comprising exposing the image sensor for a background exposure time if a target is not illuminated at least once within the period of time.

42. 42. The method of any one of claims 39 to 41, wherein generating the excitation pulse comprises providing uniform, anamorphic illumination to the target.

43. 43. The method of claim 42, wherein providing uniform, anamorphic illumination to the target comprises overlapping illumination from at least two illumination ports.

44. exposing the imaging sensor for the fluorescence exposure time includes providing a wavelength-dependent aperture upstream of the imaging sensor during the exposure; 44. A method according to any one of claims 39 to 43, wherein the wavelength dependent aperture blocks visible light outside a central region.

45. 45. The method of claim 44, wherein the wavelength dependent aperture is configured to produce a substantially similar depth of field at the sensor plane for both visible light and the fluorescent light excited by the excitation pulse.

46. 1. A method for displaying fluorescence intensity in an image, comprising: displaying a target reticle covering an area of ​​the image; Calculating a normalized fluorescence intensity within the target reticle; and displaying the normalized fluorescence intensity in a display area associated with the target.

47. 47. The method of claim 46, wherein the display area is projected onto the target.

48. 48. The method of claim 46 or 47, wherein the normalized fluorescence intensity comprises a single numerical value.

49. 49. The method of any one of claims 46 to 48, wherein the normalized fluorescence intensity comprises a historical plot of normalized fluorescence intensity.

50. an illumination module including at least two illumination ports spaced apart from one another, such that first and second illumination distributions are simultaneously provided to a target and overlap at the target; and an imaging module including a sensor for detecting light from the target.

51. 51. The kit of claim 50, further comprising a housing enclosing the illumination module and the imaging module.

52. 50. A fluorescent imaging agent for use in an imaging device according to any one of claims 11 to 22, a method according to any one of claims 23 to 25, a method according to any one of claims 39 to 45, a method according to any one of claims 46 to 49, or a combination thereof.

53. 50. A fluorescent imaging agent for use during blood flow imaging, tissue perfusion imaging, lymphatic imaging, or a combination thereof, in an imaging device as claimed in any one of claims 11 to 22, a method as claimed in any one of claims 23 to 25, a method as claimed in any one of claims 39 to 45, a method as claimed in any one of claims 46 to 49, or a combination thereof.

54. 54. The fluorescent imaging agent of claim 53, wherein the blood flow imaging, tissue perfusion imaging, and / or lymphatic imaging includes blood flow imaging, tissue perfusion imaging, and / or lymphatic imaging during invasive surgery, minimally invasive surgery, non-invasive surgery, or a combination thereof.

55. 55. The fluorescent imaging agent of claim 54, wherein the invasive surgery comprises heart-related or reconstructive surgery.

56. 56. The fluorescent imaging agent of claim 55, wherein the heart-related procedure comprises a coronary artery bypass graft (CABG) procedure.

57. 57. The fluorescent imaging agent of claim 56, wherein the CABG is on-pump or off-pump.

58. 55. The fluorescent imaging agent of claim 54, wherein the minimally invasive or non-invasive surgery comprises a wound care surgery.

59. 54. The fluorescent imaging agent of claim 53, wherein the lymphatic imaging includes identification of lymph nodes, lymphatic drainage, lymphatic mapping, or a combination thereof.

60. 54. The fluorescent imaging agent of claim 53, wherein said lymphatic imaging relates to the female reproductive system.

61. 5. Use of an imaging device according to any one of claims 11 to 22, a method according to any one of claims 23 to 25, a method according to any one of claims 39 to 45, a method according to any one of claims 46 to 49, or a combination thereof for lymphatic imaging.

62. 50. Use of an imaging device according to any one of claims 11 to 22, a method according to any one of claims 23 to 25, a method according to any one of claims 39 to 45, a method according to any one of claims 46 to 49, or a combination thereof, for blood flow imaging, tissue perfusion imaging, or a combination thereof.

63. 52. A fluorescent imaging agent for use in the kit of claim 50 or 51.

64. 64. The fluorescent imaging agent of any one of claims 52 to 60 or claim 63, wherein the fluorescent imaging agent comprises ICG.

65. 64. The fluorescent imaging agent of any one of claims 52 to 60 or claim 63, wherein the fluorescent imaging agent is ICG.

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