HK40062240A - Devices, systems, and methods for tumor visualization and removal - Google Patents

Description

Devices, systems, and methods for visualizing and removing tumors

Citations to related applications

The present application claims priority of united states provisional application No. 62/793,764 (filed on 1/17/2019) entitled "apparatus, system, and method for visualizing and removing tumors" and united states provisional application No. 62/857,155 (filed on 6/4/2019) entitled "apparatus, system, and method for visualizing and removing tumors," the entire contents of which are incorporated herein by reference.

Technical Field

The present disclosure relates to devices, systems, and methods for visualizing and removing tumors. The disclosed devices, systems, and methods may also be used to stage tumors and assess surgical margins (surgical margins), such as margins of tissue on ex vivo tumors and margins on tissue beds/surgical beds where tumors and/or tissue have been removed. The disclosed devices, systems, and methods may also be used to identify one or more of residual cancer cells, pre-cancerous cells, and satellite lesions, and provide guidance for the removal and/or treatment of these cells.

Background

Surgery is one of the oldest types of cancer treatment and is an effective method of treating multiple types of cancer. Tumor surgery may take different forms depending on the goal of the surgery. For example, tumor surgery may include: biopsy, for diagnosing or determining the type or stage of cancer; tumor removal for removing part or all of a tumor or cancerous tissue; exploratory surgery for locating or identifying tumors or cancerous tissue; tumor reduction surgery to reduce or remove tumors as much as possible without adversely affecting other body structures; palliative surgery is used to address diseases caused by tumors, such as pain or stress of body organs.

In surgery where the goal is to remove tumor or cancerous tissue, surgeons often face uncertainty in determining whether all of the cancer has been removed. The surgical bed (surgical bed) or tissue bed from which the tumor is removed may contain residual cancer cells, i.e., cancer cells remaining in the surgical margin of the removed tumor area. If these residual cancer cells remain in the body, the likelihood of recurrence and metastasis increases. Typically, based on examination of the surgical margin of ex vivo tissue during tumor pathology analysis, residual cancer cells are suspected to be present, resulting in a secondary surgery to remove additional tissue from the surgical margin.

For example, breast cancer, the most prevalent cancer in women, is often treated by Breast Conservation Surgery (BCS), such as breast tumor removal, which removes the tumor while leaving as much healthy breast tissue as possible. The therapeutic effect of BCS depends on complete removal of malignant tissue while leaving enough healthy breast tissue to ensure adequate breast reconstruction, which may be poor if too much breast tissue is removed. Visualization of tumor margins under standard White Light (WL) operating room conditions is challenging due to the low contrast of tumor to normal tissue, resulting in about 23% of early invasive breast cancer patients and 36% of ductal carcinoma in situ patients requiring re-surgery (i.e., secondary surgery). Removals are associated with greater risk of recurrence, poor patient recovery, including cosmetic reduction of the breast and increased healthcare costs. A positive surgical margin (i.e., a margin containing cancer cells) after BCS is also associated with decreased disease-specific survival.

The best practice of BCS today involves palpation and/or specimen radiography, with few intraoperative histopathology to guide removal. Specimen radiography uses x-ray images to assess ex vivo tissue margins, intraoperative histopathology (contact preparation or freezing) to assess small samples of cancer cell specimen tissue, both of which are limited by the time delay they cause (about 20 minutes) and inaccuracy in co-locating the positive margins on the ex vivo tissue to the operating bed. Therefore, there is an urgent clinical need for a real-time intraoperative imaging technique to assess ex vivo specimens and the margins of surgical beds and provide guidance for removing one or more of residual cancer cells, precancerous cells, and satellite lesions.

Disclosure of Invention

The present disclosure may address one or more of the problems set forth above and/or may demonstrate one or more of the desirable features set forth above. Other features and/or advantages may become apparent from the following description.

According to one aspect of the present disclosure, an imaging device includes a body having a first end configured to be held in a hand of a user and a second end configured to direct light onto a surgical edge. The apparatus includes at least one excitation light source configured to excite autofluorescence emission of tissue cells and porphyrin-induced fluorescence emission in tissue cells of the surgical margin. A white light source is configured to illuminate the surgical margin during white light imaging of the surgical margin. The device comprises: an imaging sensor; a first optical filter configured to filter optical signals emitted through the surgical margin in response to excitation light illumination and allow passage of autofluorescence emissions of tissue cells and porphyrin-induced fluorescence emissions in tissue cells to the imaging sensor; a second optical filter configured to filter light signals emitted through the surgical margin in response to illumination with white light and allow white light emissions of tissue in the surgical margin to pass to the imaging sensor.

According to another aspect of the present disclosure, an image forming apparatus includes: a body having a first end configured to be held in a user's hand and a second end configured to direct light onto a surgical edge; a first excitation light source configured to emit excitation light having a first wavelength; a second excitation light source configured to emit excitation light having a second wavelength. An imaging sensor is configured to detect emissions of the surgical margin. A first optical filter is configured to filter optical signals emitted through the surgical edge in response to the first excitation light illuminating the surgical edge. The first filter is configured to allow optical signals having a wavelength corresponding to a first characteristic of the surgical edge to pass through the filter to the imaging sensor. A second optical filter is configured to filter optical signals emitted through the surgical edge in response to the first excitation light illuminating the surgical edge, the second filter configured to allow optical signals having a wavelength corresponding to a second characteristic of the surgical edge to pass through the filter to the imaging sensor, the second characteristic different from the first characteristic.

According to yet another aspect of the present disclosure, a method of imaging tissue at a surgical edge includes: illuminating tissue at the surgical edge with a first excitation light source configured to emit excitation light having a first wavelength; receiving, by a first optical filter in an imaging device, a light signal emitted through tissue at the surgical edge; illuminating tissue at the surgical edge with a second excitation light source configured to emit excitation light having a second wavelength; receiving, by a second optical filter in the imaging device, an optical signal emitted through tissue at the surgical edge.

Drawings

The present disclosure can be understood from the following detailed description, taken alone or in conjunction with the accompanying drawings. The accompanying drawings are included to provide a further understanding and are incorporated in and constitute a part of this specification. The drawings illustrate one or more exemplary embodiments of the disclosure and together with the description serve to explain various principles and operations.

Fig. 1 is a diagram of a system for visualizing a tumor according to the present disclosure.

Fig. 2 is a perspective view of a handheld imaging device for visualizing tumors/cancer cells, in accordance with an embodiment of the present disclosure.

Fig. 3 is an end view of the handheld imaging device of fig. 2.

Fig. 4 is a side view of the handheld imaging device of fig. 2.

Fig. 5 is a perspective view of a distal portion of a handheld imaging device including a drape according to the present disclosure.

Fig. 6 is an end view of a distal portion of a handheld imaging device according to the present disclosure.

Fig. 7 is an exploded view of the distal portion of fig. 6.

Fig. 8 is a plan view of a distal PCB of a handheld imaging device, according to an embodiment of the present disclosure.

Fig. 9 is a schematic diagram of a rotatable optical filter portion of a handheld imaging device, according to an embodiment of the present disclosure.

10-15 are diagrams illustrating exemplary frequency bands configured to detect emissions excited by excitation light and incorporated into various optical filters in embodiments of handheld imaging devices according to the present disclosure.

Fig. 16-18 are exemplary display layouts associated with various imaging modes of the handheld imaging device of the present disclosure.

Fig. 19 is a perspective view of a sterile drape for a handheld imaging device according to the present disclosure.

Fig. 20 is a perspective view of the sterile drape of fig. 19 with a handheld imaging device inserted in the sterile drape.

Fig. 21A is a perspective view of a lens cap portion of the drape of fig. 19.

Fig. 21B is a sectional view of the lens cap portion of fig. 21A.

Fig. 22 is a perspective view of another embodiment of a handheld imaging device according to the present disclosure.

Fig. 23 is a top view of the handheld imaging device of fig. 22.

Fig. 24 is another perspective view of the handheld imaging device of fig. 22 in a partially disassembled state.

Fig. 25 is an end view of the cover portion of the handheld imaging device of fig. 22.

Fig. 26 is a partially disassembled view of the distal portion of the handheld imaging device of fig. 22.

Fig. 27 is another partially disassembled view of the distal portion of the handheld imaging device of fig. 22.

Fig. 28 is an end view of the distal portion of the handheld imaging device of fig. 22.

Fig. 29 is a graph showing ICG emission and ICG absorption wavelengths measured in a 60uM aqueous solution.

Fig. 30 is a block diagram illustrating hardware components of a handheld imaging device according to an exemplary embodiment of the present disclosure.

Fig. 31 is a perspective view of a USB connector according to an exemplary embodiment of the present disclosure.

FIG. 32 is a perspective view of a housing of a handheld device in which a USB port is configured to receive the USB connector of FIG. 31, according to an exemplary embodiment of the present disclosure.

Detailed Description

Existing surgical margin assessment techniques focus on ex vivo samples to determine whether the surgical margin includes residual cancer cells. These techniques are limited in that they do not accurately spatially co-localize the positive margins detected on the ex vivo sample to the operating bed, which the present disclosure overcomes by directly imaging the surgical cavity.

Other non-targeted techniques for reducing removals include studies that combine non-targeted edges with standard of care BCS. While this technique may reduce the total number of removals, this approach includes several potential drawbacks. For example, a larger resection is associated with a poorer cosmetic outcome, and additional tissue that is not targeted for removal contradicts the intent of BCS. Furthermore, the end result using such a technique appears to conflict with the recently updated ASTRO/SSO guideline, which defines the positive margin as "tumor in ink", and does not find the additional benefit of a wider margin. Moran MS (Moran MS), Schnitt SJ (Schmitt SJ), Giulino AE (Verlino AE), Harris JR (Harris JR), Khan SA (sweat SA), Horton J (Hoton J) and the like "Society of Surgical Oncology-consensus guidelines of the American Society of Radiation Oncology for the Surgical margins of full-breast radiotherapy and breast preservation for stage I and II invasive breast cancer (Society of Surgical Oncology-American Society for Radiation Oncology consensus on patients for research-research with little-research Radiation diagnosis in both I and II invasive research)" annual Surgical Oncology (Ann research), 2014.21(3): 716). Recent retrospective studies found no significant difference in re-removal after cavity scraping compared to standard BCS. "extra lumen scraping during Breast preservation Surgery" for improving the Accuracy of the Examination of the Margin Status (Ann Surg Oncol) "by Pata G (PatanG), Bartoli M (Bartoli M), Bianchi A (Bianqi A), Pasini M (Pacini), Roncali S (Longcari S), Ragni F (Lagni F)" surgical oncology annual (Ann Surg Oncol) "2016.23 (9): 2802-. If edge scraping is ultimately found to be effective, FL guided surgery can be used to improve the process by increasing the ability to scrape against targeted specific areas in the surgical edge, thereby converting a non-targeted approach that indiscriminately removes additional tissue to a targeted approach, which is more consistent with the intent of BCS.

Devices, systems, and methods for fluorescence-based visualization of tumors, including in vivo and in vitro visualization and/or assessment of tumors, multifocal diseases and surgical margins, and intra-operative guidance for removal of residual tumors, satellite lesions, precancerous cells, and/or cancerous cells in the surgical margins are disclosed. In certain embodiments, the devices disclosed herein are handheld and configured to be positioned at least partially within a surgical cavity. In other embodiments, the device is portable, without a wired connection. However, it is within the scope of the present disclosure that the device may be larger than the handheld device, but may include a handheld assembly. In such embodiments, it is contemplated that the handheld component may be connected to a larger device housing or system through a wired connection.

Methods of intra-operative in vivo imaging using the devices and/or systems are also disclosed. The imaging device may be multispectral. It is also contemplated that the device may be hyperspectral. In addition to providing information about the type of cells contained within the surgical margin, the disclosed devices and systems also provide information about the location (i.e., anatomical context) of the cells contained within the surgical margin. Further, methods of using the device to provide guidance for intraoperative treatment of a surgical margin, e.g., fluorescence-based image guidance of removal of a surgical margin, are disclosed. The devices, systems, and methods disclosed herein can be used with subjects including humans and animals.

According to one aspect of the present disclosure, some disclosed methods combine the use of the disclosed devices and/or systems with the administration of non-activated, non-targeted compounds configured to induce porphyrins in tumor/cancer cells, precancerous cells, and/or satellite lesions. For example, a diagnostic dose (i.e., not a therapeutic dose) of a compound (imaging/contrast agent), such as the prodrug aminolevulinic acid (ALA), may be administered to a subject. As understood by those of ordinary skill in the art, ALA doses of less than 60mg/kg are generally considered diagnostic, whereas doses of greater than 60mg/kg are generally considered therapeutic. As disclosed herein, a diagnostic dose of ALA may be greater than 0mg/kg and less than 60kg/mg, between about 10mg/kg and about 50mg/kg, between about 20mg/kg and 40mg/kg, and a dose of 5mg/kg, 10mg/kg, 15kg/mg, 20mg/kg, 25mg/kg, 30mg/kg, 35mg/kg, 40mg/kg, 45mg/kg, 50mg/kg or 55mg/kg may be administered to a subject. ALA may be administered orally, intravenously, by aerosol, by immersion, by lavage and/or topically. While diagnostic dosages for visualization of residual cancer cells, precancerous cells, and satellite lesions are contemplated, it is also within the scope of the present disclosure to use the disclosed devices, systems, and methods to provide guidance during treatment and/or removal of such cells and/or lesions. In this case, the surgeon's preferred treatment method may vary based on the preference of the individual surgeon. Such treatment may include, for example, photodynamic therapy (PDT). Where PDT or other light-based therapy is deemed possible, it may be necessary to administer a higher dose of ALA, i.e. it is necessary to administer a therapeutic dose rather than a diagnostic dose. In these cases, the subject may be prescribed an ALA dose of greater than 60 mg/kg.

ALA induces porphyrin formation (protoporphyrin ix (PpIX)) in tumor/cancer cells, which when excited by a suitable excitation light causes cells comprising PpIX to fluoresce red, which enhances the red-green fluorescence contrast between tumor/cancer cell tissue cells imaged using the device and normal tissue cells (e.g. collagen). ALA itself did not fluoresce, but PpIX fluoresced around 630nm, 680nm and 710nm, with 630nm emitting most strongly. Alternatively, the endogenous fluorescence difference between tumor/cancer cells or precancerous cells and normal/healthy cells can be used without imaging/contrast agents.

In exemplary embodiments, a non-activating, non-targeting compound configured to induce porphyrins in tumor/cancer cells, precancerous cells, and/or satellite lesions is administered to a subject between about 15 minutes and about 6 hours prior to surgery, about 1 hour to about 5 hours prior to surgery, about 2 hours to about 4 hours prior to surgery, or about 2.5 hours to about 3.5 hours prior to surgery. These exemplary time ranges allow sufficient time for the conversion of ALA into porphyrins in tumor/cancer cells, precancerous cells, and/or satellite lesions. ALA or other suitable compound may be administered orally, intravenously, by aerosol, by immersion, by lavage and/or topically.

In case the administration of the compound is outside the desired or preferred time frame, PpIX may be further induced (or first induced if the compound is not administered before surgery) e.g. by aerosol composition administration of the compound, i.e. spraying it into the surgical cavity or onto ex vivo tissue (before or after biopsy). Additionally or alternatively, the compound may be administered in liquid form, for example as an irrigation solution for an operative cavity. Additionally or alternatively, for removed specimens, PpIX may be induced in ex vivo specimens if it is immersed in a liquid compound such as liquid ALA almost immediately after removal. The earlier the immersion into the ex vivo tissue, the greater the chance of inducing PpIX or additional PpIX in the ex vivo tissue.

During surgery, the surgeon will remove a tumor, such as a primary, palpable or landmark tumor, if possible. The handheld fluorescence-based imaging device is then used to identify, locate and guide the treatment of any residual cancer cells, pre-cancerous cells and/or satellite lesions in the surgical bed from which the tumor has been removed. The device may also be used to examine ex vivo tumor/tissue specimens to determine the presence of any tumor/cancer cells and/or precancerous cells at the outer margins of the ex vivo specimen. The presence of such cells may indicate a positive margin, which the surgeon takes into account when determining whether to perform further removal of the operating bed. The location of any tumor/cancer cells identified on the outer edges of the ex vivo specimen may be used to identify a corresponding location on the surgical bed that may be targeted for further removal and/or treatment. This may be particularly useful in cases where visualization of the surgical bed itself does not identify any residual tumor/cancer cells, precancerous cells, or satellite lesions. Furthermore, a handheld fluorescence-based imaging device may be used to guide the surgical removal of the primary tumor itself, and then, as described above, look for residual cancerous cells, precancerous cells, and/or satellite lesions in the surgical bed from which the tumor has been removed.

According to one aspect of the present disclosure, a handheld fluorescence-based imaging device for visualizing tumors/cancer cells is provided. The fluorescence-based imaging device may include a body sized and shaped to be held and manipulated by a single hand of a user. Exemplary embodiments of a handheld fluorescence-based imaging device are shown in fig. 2-4. As shown, in some example embodiments, the body may have a generally elongated shape and include a first end configured to be held in a user's hand and a second end configured to direct light onto a surgical margin on an outer surface of an ex vivo tumor, on one or more portions of an ex vivo tumor, or in a surgical cavity where the tumor/tissue has been excised. The second end may also be configured to be positioned in a surgical cavity containing a surgical margin. The body of the device may comprise one or more materials suitable for sterilization such that the body of the device may be subjected to sterilization, for example in an autoclave. One example of a suitable material is polypropylene. One of ordinary skill in the art will be familiar with other suitable materials. Components within the body of the device, such as electronics, that may not withstand autoclave conditions may be secured or otherwise contained in a housing for protection, such as a metal or ceramic housing.

The device may be configured for use with a surgical drape or shield. For example, the inventors have found that the image quality improves when the ambient light and artificial light in the imaging area is reduced. This may be achieved by reducing or eliminating ambient and/or artificial light sources in use. Alternatively, a drape or shield may be used to block at least a portion of the ambient and/or artificial light from the surgical site being imaged. In one exemplary embodiment, the protective cover may be configured to fit over the second end of the device and move over the device toward and away from the surgical cavity to vary the amount of ambient and/or artificial light that may enter the surgical cavity. The shield may be conical or umbrella shaped. Alternatively, the device itself may be enclosed in a drape, with a transparent sheath portion covering the end of the device configured to illuminate the surgical site with excitation light. As one of ordinary skill in the art will appreciate, other variations of drapes configured to reduce or eliminate ambient light and/or artificial light may be used. Additionally or alternatively, the handheld fluorescence-based imaging device may include a sensor configured to identify whether the illumination condition satisfies the imaging. The device may also be used with surgical drapes to maintain sterility of the surgical field and/or to protect the tip of the device from bodily fluids. The surgical drape and the ambient light reducing drape may be combined into a single drape design. Alternatively, a drape may enclose the device, and a drape or shield that reduces ambient light may be positioned over the drape.

The apparatus may also include at least one excitation light source contained within the body of the apparatus, the at least one excitation light source configured to excite autofluorescence emission of tissue cells and induced fluorescence emission of porphyrins in the surgical margin tissue cells. The at least one excitation light source may be positioned on, around and/or near one end of the device. Each light source may include, for example, one or more LEDs configured to emit light of a selected wavelength.

The excitation light source may provide excitation light of a single wavelength selected to excite tissue autofluorescence emission and induce porphyrin fluorescence emission in tumor/cancer cells contained in the surgical margin of the ex vivo tumor/tissue and/or in the surgical margin of the surgical bed from which the tumor/tissue cells have been excised. In one example, the excitation light may have a wavelength in the range of about 350nm to about 600nm, or 350nm to about 450nm and 550nm to about 600nm, or 405nm, for example, or 572nm, for example.

Alternatively, the excitation light source may be configured to provide excitation light of two or more wavelengths. As will be appreciated by those skilled in the art, the wavelength of the excitation light may be selected for different purposes. For example, by changing the wavelength of the excitation light, the depth of penetration of the excitation light through the operating bed can be changed. As the depth of penetration increases with a corresponding increase in wavelength, different wavelengths of light may be used to excite tissue below the surface of the operating bed/surgical margin. In one example, excitation light having a wavelength in the range of 350nm-450nm (e.g., 405nm) and excitation light having a wavelength in the range of 550nm-600nm (e.g., 572nm) may penetrate to different depths of tissue forming the surgical bed/surgical margin, e.g., about 500 μm to about 1mm and about 2.5mm, respectively. This will allow a user of the device, e.g. a surgeon or pathologist, to observe the tumor/cancer cells at and below the surface of the operating bed/operating edge. Additionally or alternatively, excitation light having a wavelength in the near infrared/infrared range may be used, for example, excitation light having a wavelength between about 750nm and about 800nm, such as 760nm, 780nm, or other wavelengths may be used. Furthermore, the use of this type of light source may be used in conjunction with a second type of imaging/contrast agent, such as an infrared dye (e.g., IRDye 800, ICG), in order to penetrate tissue to deeper levels. For example, this will visualize the vascularization, vascular perfusion and blood pooling at the surgical margin/within the surgical bed, and the surgeon can use this information to determine the likelihood of residual tumor/cancer cells remaining in the surgical bed. Furthermore, visualizing the utility of vascular perfusion is to improve anastomosis during reconstruction.

The device may comprise additional light sources, such as white light sources for White Light (WL) imaging of the surgical margin/bed. In at least some instances, such as during BCS such as breast tumor removal, for example, removal of the tumor will result in a cavity containing the operating bed/surgical margin. WL imaging may be used to obtain images or video of the interior of the cavity and/or the surgical margins and provide visualization of the cavity. The white light source may comprise one or more white LEDs. Other white light sources may be used, depending on the circumstances. It will be appreciated by those skilled in the art that a white light source should be stable and reliable and not generate excessive heat during prolonged use.

The body of the device may include controls to allow switching between white light imaging and fluorescence imaging. The control may also enable the various excitation light sources to be used together or separately in various combinations and/or sequences. Control may cycle through various different combinations of light sources, the light sources may be controlled sequentially, the light sources may be strobed or otherwise controlled for time and duration of use of the light sources. As will be appreciated by one of ordinary skill in the art, the control may be automatic, manual, or a combination thereof.

The body of the device may also contain one or more optical imaging optical filters configured to prevent the passage of reflected excitation light and to allow the passage of emissions having wavelengths corresponding to the autofluorescence emission of the tissue cells and the fluorescence emission of induced porphyrins in the tissue cells. In one example embodiment, an apparatus includes one filter for White Light (WL) imaging and Infrared (IR) imaging and another filter for Fluorescence (FL) imaging. The device may be configured to switch between different imaging optical filters based on the desired imaging mode and the excitation light emitted by the handheld device.

The handheld fluorescence-based imaging device also includes an imaging lens and an imaging sensor. The imaging lens or lens assembly may be configured to focus the filtered autofluorescence and fluorescence emissions onto an imaging sensor. A wide-angle imaging lens or a fisheye imaging lens are examples of suitable lenses. A wide angle lens may provide a 180 degree field of view. The lens may also provide optical magnification. Imaging devices require very high resolution so that very small cell populations can be distinguished from one another. This is desirable to achieve the goal of maximizing the amount of healthy tissue retained during surgery while maximizing the likelihood of removing substantially all residual cancer cells, precancerous cells, satellite lesions. The imaging sensor is configured to detect filtered autofluorescence emissions of tissue cells and porphyrin-induced fluorescence emissions in tissue cells of the surgical margin. The imaging sensor may have 4K video functionality as well as auto-focus and optical and/or digital zoom functionality. CCD or CMOS imaging sensors may be used. In one example, a CMOS sensor in combination with a filter, i.e., a hyperspectral imaging sensor, such as those sold by Ximiea Company, may be used. Exemplary filters include visible filters (https:// www.ximea.com/en/products/hyperspectra-cameras-based-on-usb 3-xspec/mq 022hg-im-sm4x4-vis) and IR filters (https:// www.ximea.com/en/products/hyperspectra-cameras-based-on-usb 3-xspec/mq 022hg-im-sm5x 5-nir). The handheld device may also include a processor configured to receive the detected emissions and output data regarding the filtered autofluorescence emissions of the detected tissue cells and the induced porphyrin fluorescence emissions in the tissue cells of the surgical margin. The processor may have the ability to run synchronization programs seamlessly (including but not limited to wireless signal monitoring, battery monitoring and control, temperature monitoring, image acceptance/compression, and button press monitoring). The processor is connected to the internal memory, the buttons, the optics, and the wireless module. The processor also has the capability to read analog signals.

The apparatus may also include a wireless module and be configured for fully wireless operation. Which can utilize high throughput wireless signals and can transmit high definition video with minimal delay. The device may enable both Wi-Fi and bluetooth enabled Wi-Fi for data transfer, bluetooth for quick connection. Devices may operate using the 5GHz wireless transmission band to isolate them from other devices. Further, the device may be able to operate as a soft access point, which eliminates the need to connect to the internet and allows the device and module to maintain connections isolated from other devices related to patient data security. The device may be configured for wireless charging and include an inductive charging coil. Additionally or alternatively, the device may include a port configured to receive a charging connection.

Additional details regarding the construction, function, and operation of the exemplary devices described herein may be found in U.S. provisional application 62/625,983 (filed on 3/2/2018) entitled "devices, systems, and methods for visualizing and removing tumors" and U.S. provisional application 62/625,967 (filed on 3/2/2018) entitled "apparatuses, systems, and methods for visualizing and removing tumors," each of which is incorporated by reference herein in its entirety.

Referring now to fig. 1, a system 102 including a handheld imaging device 100 is shown. The handheld imaging device 100 communicates with the hub 104, such as by wireless transmission (e.g., Wi-Fi, bluetooth, or other wireless RF protocol). The hub 104 transmits imaging data received from the handheld imaging device 100 to the display monitor 106 for display using a protocol such as High Definition Multimedia Interface (HDMI). The hub 104 may also transmit the imaging data to a computer system 108, such as a terminal or network for storing the imaging data.

In accordance with one aspect of the present disclosure, an example embodiment of a handheld imaging device 100 in accordance with the present teachings is shown in fig. 2-4. The handheld device 100 includes a body 110 having a first end 112 and a second end 114. The first end 112 is sized and shaped to be held by a single hand of a user of the device. The first end 112 may include controls 113 configured to actuate the device, switch between and/or otherwise control different light sources, and switch between one or more optical imaging filters. Such controls may include buttons, switches, capacitive discharge sensors, or other devices manipulated by the user.

As shown in fig. 2-4, the second end 114 of the hand-held device 100 may be tapered and/or elongated to facilitate insertion of the distal end or tip 116 of the second end through a 2-3cm size surgical incision and into a surgical cavity from which tumor or cancerous tissue has been removed. Second end 114 may be rigid and positioned at an angle relative to first end 112 to facilitate better access under a flap, or may be configured to be flexible to facilitate imaging of a surgical cavity having complex geometries.

The distal end 116 includes one or more light sources 118, such as Light Emitting Diodes (LEDs) configured to emit light having a particular wavelength. For example, the one or more light sources 118 may be configured to emit wavelengths of 405nm, 760nm, 780nm, or other wavelengths. The distal end 116 also includes an imaging device 120, such as a camera assembly configured to capture images of the surgical cavity illuminated by the one or more light sources 118. As discussed in more detail below in connection with fig. 5, the distal end 116 also includes one or more spectral optical filters positioned to filter light entering the imaging device 120.

The device 100 includes a configuration to facilitate the attachment of a drape (drapee) to support the sterility of the handheld device 100. For example, referring now to fig. 19, a drape 1960 configured for use with the apparatus 100 is shown. The drape 1960 may provide a sterile barrier between the non-sterile devices contained in the drape and the sterile field of the procedure, allowing the non-sterile devices contained entirely in the sterile drape to be used in a sterile environment. The drape may cover the hand-held device 100 and also provide a darkened shield extending from the distal end (e.g., distal end 116) and covering the area near the surgical cavity to protect the surgical cavity area from light penetration from light sources other than the hand-held device 100. The drape may also include or be coupled with a hard optical window, such as a lens cover 1962 (or, in other embodiments, lens cover 524 discussed further below in conjunction with fig. 5) that covers the distal end of the handheld device 100 to ensure accurate transmission of light emitted from the light source 118 and corresponding transmission of light back to the imaging device 120. The body of the drape 1960 may include a polymeric material, such as polyethylene, polyurethane, or other polymeric material. Optionally, the lens cover 1962 may include a different material, such as Polymethylmethacrylate (PMMA) or other rigid, optically transparent polymers, glass, silicone, quartz, or other materials.

Referring now to fig. 20, the device 100 may be inserted within a drape 1960 to protect the device 100 from exposure to the surgical environment and to ensure that non-sterile devices do not contaminate the sterile surgical area. The drape 1960 may be coupled to the apparatus 100 by a retention device. As shown in fig. 4, the distal end 116 of the handset 100 includes a circumferential groove 122 configured to interact with one or more features of the drape 1960 to retain the drape 1960 on the handset. For example, referring now to fig. 21A and 21B, the lens cover 1962 may optionally include features that engage the groove 122 (fig. 4). In the embodiment of fig. 21A and 21B, lens cap 1962 includes a plurality of legs 1964 each having an engagement tang 1966 configured to engage groove 122 (fig. 4) when lens cap 1962 is placed on distal end 116 of device 100. Additionally or alternatively, the drape may include means, such as a retaining ring or band, to retain the drape on the handheld device 100. The retaining ring may be or include an elastic band, snap ring, or similar component.

In some embodiments, handheld device 100 may include a built-in screen instead of or in addition to the link to hub 104 (fig. 1). For example, the built-in screen may eliminate the need for external display devices such as the display 106 and/or the computer system 108, or may provide additional information to the user, such as the mode in which the handheld device 100 is operating. Further, the display information may additionally or alternatively be provided to a head mounted display for Augmented Reality (AR) or Virtual Reality (VR) surgery, including remote and/or robotic surgery, or projected onto a holographic display.

Referring again to fig. 4, in some exemplary embodiments, the hand-held device 100 may include a channel 423 formed in a sidewall of the distal end 116. The channel 423 may be used to facilitate insertion of additional tools such as fiber optics for auxiliary light sources or auxiliary imaging sensors, cauterization tools, biopsy forceps, marking tools (for marking tissue with clips, optical labels, dyes or paints, etc.), or other tools while the handheld device 100 is in place within a surgical site. Alternatively or additionally, some embodiments may include a channel formed within the distal tip 116 of the device 100, i.e., an internal channel within the device, for guiding any of the above-described tools into the surgical site when the handheld device 100 is in use.

The handheld device 100 may also include means to facilitate cradle mounting of the device 100 when in use. For example, while the handheld device 100 may be designed and configured primarily for handheld use, in some instances it may be desirable to place the handheld device 100 on a stand or fixed mount (e.g., during use to acquire different images of the same tissue) to ensure that the environment and location of the images are consistent across multiple images. The handheld device may be coupled to a support such as a gooseneck-type flexible support with a weighted or clip-on mount to hold the assembly in place on a table or operating table. In other embodiments, the stent mount may be cart-based and may be moved outside of the sterile surgical area while holding the device. The bracket mounting allows the user to use the device without holding it in his or her hand. The holder may be configured to hold additional auxiliary light sources, imaging devices, support tools such as biopsy forceps, marking tools, or other devices.

Referring now to fig. 5, a perspective view of the distal end 516 of a handheld device is shown, according to an embodiment of the present disclosure. Distal end 516 may be fitted with a sterile lens cover 524. The lens cover 524 may be coupled with the drape discussed above, and the drape may be configured to cover the body of the handheld device and provide a light shield extending from a distal end of the handheld device to prevent ambient light from entering an area to be imaged by the handheld device. Similar to the embodiment of lens cover 1962 of fig. 21A and 21B discussed above, lens cover 524 may include one or more features configured to engage features of the distal end of the handheld device, such as by engaging groove 122 shown in fig. 4.

As discussed in more detail below, the handheld device includes various electrical subsystems including one or more imaging devices, such as a camera sensor, one or more fluorescent LEDs, one of more infrared LEDs, one or more white light LEDs, and various sensors such as a temperature sensor, an ambient light sensor, and a ranging sensor. Other components may include: one or more LED drivers that generate a drive voltage to drive LEDs as needed to achieve a setpoint drive current; one or more accelerometers and gyroscopes to allow the video stream to be tagged with the position of the handheld device, e.g., to provide spatial localization of features within the surgical cavity; a flash memory to provide local storage of video and still images; a USB hub to provide an interface for factory software loading, testing and calibration of a handheld device; an inductive battery charging system; motor drive electronics for providing automatic switching of the optical filter as described below; a Wi-Fi radio subsystem; a user interface that provides information to a user regarding a device mode; rechargeable batteries (e.g., lithium ion batteries); an audio device, such as a speaker, for providing audible feedback of the system status to the user; and other components. Such components may be operatively coupled with one or more controllers, such as computer processors, housed within the handheld device.

For example, in an embodiment, the handheld device includes one or both of an application processor and a microcontroller unit. The functions that the application processor can perform include, but are not limited to: sending the camera interface and video streams (e.g., still images and motion video) to the wireless transmission function to transmit data to a display or computer terminal; the accelerometer, the gyroscope and the onboard flash memory are connected; is connected with the microcontroller unit; driving a speaker to provide audio feedback to a user; and managing the wireless communication subsystem.

The microcontroller unit may provide the functions of: such as controlling LED drive electronics including temperature compensation loops, communication with temperature sensors, ambient light sensors and rangefinders, and interfacing with an application processor for transmitting and receiving functional and environmental conditions used by the system. The microcontroller unit may also monitor the system for anomalies, control LED indicators, control buttons or other user interface devices, control motor drives to switch between optical filters, monitor wireless battery charge and charge status, and control power management, among other functions.

Referring now to fig. 6, the distal portion 516 of the hand held device shown in fig. 5 is shown in an end view. The handheld device 500 includes an imaging device 520, which may be or include a camera, such as a Charge Coupled Device (CCD), Complementary Metal Oxide Semiconductor (CMOS) device, or other image capture technology such as an imaging device including a hyperspectral imaging sensor module. As shown in fig. 5, the imaging device 520 is in an offset position on the end of the handheld device 500. Although the embodiments of fig. 5 and 6 include a single imaging device 520, other exemplary embodiments of the present disclosure may include two or more separate imaging devices to support additional imaging modalities.

The handheld device 500 also includes a diffuser 522 that diffuses light generated by a light source, such as an LED similar to the LED 118 discussed in connection with the embodiments of fig. 2-4. The diffuser 522 can be configured to ensure that light exiting the handheld device 500 is sufficiently diffuse to uniformly illuminate a target area (e.g., a surgical cavity) and provide uniform excitation of tissue. The diffuser 522 may be made of a polymeric material that scatters light emitted by the LED into a more uniform output. Diffuser 522 may include materials such as, for example, acrylic, polycarbonate, mylar, plastic film, or other materials. The diffuser 522 may be shaped so that it does not block other components at the distal end of the device 100, such as a temperature sensor, a range finder, an ambient light sensor, or other components described below in connection with fig. 8.

The handheld device may include one or more Printed Circuit Board (PCB) components to facilitate manufacture and assembly of the handheld device. For example, referring now to FIG. 7, the distal end 516 of the handheld device 500 is shown in an exploded view, showing a plurality of PCB components for mounting and interconnecting various electronic components. The handheld device 500 includes an LED PCB 726 that may include one or more Light Emitting Diodes (LEDs) 718 and associated electronic components. The LED PCB 726 may be operatively coupled with other electronic systems in the handheld device by wiring (e.g., a bus) and may be connected to a control system of the handheld device 500, such as the controls 113 (fig. 2), a power source such as a battery, and the like. The distal end 516 may include a motor drive system 727 for rotating the optical filter wheel 938 discussed below in connection with fig. 9.

The distal PCB 728 may be positioned adjacent the imaging device 520 and may include components to support the imaging device 520, such as controls 113 (fig. 2) to couple the imaging device 520 with the handheld device 500 and a power source, such as a battery. In some embodiments, the light source 118 (fig. 2) of the handset may be included on the distal PCB 728.

For example, referring now to fig. 8, an exemplary layout of the far side PCB 830 is shown. In the embodiment of fig. 8, PCB 830 includes first and second LED devices 832 and 834. As a non-limiting example, the first and second LED devices 832 may include LEDs configured to emit light having a wavelength of 405nm, while the second LED device 834 may include LEDs configured to emit light having a wavelength of 760nm, 780nm, or other wavelengths. PCB 830 may also include white light LEDs 836 configured to provide visual illumination to the area to be imaged.

As will be appreciated by those skilled in the art, the arrangement of components in the distal end of the imaging device may take on many configurations. Such a configuration may be affected by the size of the device, the footprint of the device, and the number of components used. However, when arranging the components, functional factors should also be taken into account. For example, problems such as light leakage from the light sources of the device and/or ambient light entering the housing may interfere with proper or optimal operation of the device and may, for example, result in a less than ideal output, such as image artifacts. The arrangements shown in fig. 6-8 and elsewhere herein represent example arrangements in which the camera sensor is isolated to prevent light leakage from the light source and ambient light.

The distal PCB may include other components operatively coupled with the control system of the handheld device and configured to provide other information to the control system to support efficient operation of the handheld device. For example, the distal PCB 830 may include a temperature sensor 833 used to provide feedback to the LED setpoint temperature compensation loop to ensure that the system is operating within a safe temperature range and to minimize the effect of temperature variations on the LED radiant flux. The LED radiant flux efficiency at the target optical power as a function of LED drive current is temperature dependent, so the temperature compensation loop adjusts the nominal LED drive set point as a function of temperature to facilitate maintaining a constant radiant flux over a range of temperatures. The temperature control loop may be implemented in software running on the microcontroller unit, entirely in hardware, or a combination of both.

The rangefinder 835 may measure the distance between the camera sensor and the target being imaged and may be used to provide feedback to the user to guide the user in imaging at the correct distance. The change in measured target distance may optionally be used to initiate a camera sensor refocusing action. Because fluorescence imaging is only effective in sufficiently dark environments, the ambient light sensor 837 may provide feedback to the user regarding the ambient light level. During the white light imaging mode, the measured ambient light level may also be useful to activate the white light LED or control its intensity. The distal PCB 830 may be operably coupled with other portions of the handheld device such as the controls 113 (fig. 2), a power source such as a battery, one or more processors or other components such as a microcontroller unit and an application processor.

LED devices 832, 834, and 836 can be controlled by a closed loop system that uses information from a temperature sensor as input to a control loop that adjusts the LED drive current set point. In some embodiments, low-range and high-range LED intensity modes may be supported for different applications. Examples include close-range imaging within a surgical cavity and mammography imaging in a remote pathology suite.

As described above, the handheld device may include one or more optical filters configured to allow certain wavelengths or bands of wavelengths of light to pass while blocking other wavelengths. By placing such an optical filter between the imaging device 520 (fig. 6) and the area to be imaged, a particular wavelength or wavelength band is isolated in the image and allows visualization of the area emitting light in that wavelength or wavelength band. For example, the handset may include one or more of a notch filter configured to pass certain wavelengths, a filter configured to transmit green (about 500-550nm light) and red (about 600-660nm) wavelengths, or other types of spectral filters. Can be selected fromTechnology Corp.,10Imtec Lane, Belllows Falls VT,05101USA, part No.59022m (part No.59022m, metalloceneScience and technology group, usa 05101, belos fowls VT, emmtan street number 10) obtains one example of an optical filter configured to transmit green and red wavelengths. The one or more filters may be configured such that a user may switch between the one or more filters when using different light sources, different compounds or dyes, or the like. This switching of the filter may be performed automatically based on other user-defined settings of the handheld device, such as a user-selected mode.

The device may be modified by using optical or variably oriented polarizing filters (e.g., optical waveplates used in combination linearly or circularly) attached in a reasonable manner to the excitation/illumination light source and the imaging sensor. In this way, the device can be used to image tissue surfaces by polarized light illumination and unpolarized light detection, or vice versa, or polarized light illumination and polarized light detection using white light reflectance and/or fluorescence imaging. This may allow imaging of tissue with minimized specular reflection (e.g., glare for white light imaging) and may enable imaging of fluorescence polarization and/or anisotropy-dependent changes in connective tissue (e.g., collagen and elastin) within the tissue. The ability to use polarizing optical elements in the device can achieve polarization of reflected or fluorescent light from the target. This may provide improved image contrast where the tumor reflects 405nm excitation light differently from normal tissue or emits different polarization information from the emitted 500-550nm and 600-660nm fluorescence.

The handheld device may include components configured to enable rapid switching of the filter in a manual or automatic manner. For example, referring now to fig. 9, a filter wheel 938 in accordance with an embodiment of the present disclosure is shown. The filter wheel may be positioned on the handheld device between the imaging device (e.g., imaging device 520) and the area to be imaged. For example, in the embodiments of fig. 5 and 6, the filter wheel may be distal to the imaging device 520 in the distal end 516 of the handheld device.

The filter wheel 938 includes a first optical filter 940 configured to support white light and infrared (WL/IR) imaging and a second optical filter 942 configured to support Fluorescence (FL) imaging. First optical filter 940 and second optical filter 942 span a rotational axis a about which filter wheel 938 is rotatable_RAre positioned opposite each other. As described above, the imaging device 520 (fig. 6) may be in an offset position such that each of the first optical filter 940 and the second optical filter 942 may be alternately positioned in front of the imaging device 520 according to the user's needs. The filter wheel 938 may be rotated by an internal rotating electromechanical system, such as a motor and pinion that meshes with a gear on the filter wheel 938, or another mechanism configured to rotate the filter wheel 938, which may be controlled by a user. As discussed in more detail below in connection with fig. 10-15, a user may select one of first optical filter 940 and second optical filter 942 based on the compound or dye used and/or the wavelength of the excitation light applied to the surgical cavity. Additionally or alternatively, rotation of the filter wheel 938 may be accomplished manually, such as by providing a circumferential surface on the filter wheel 938 that may be grasped by a user. While the filter wheel 938 shown in FIG. 9 includes two filters, other embodiments of the filter wheel may include three filters, four filters, or any desired number of filtersThe desired filter may be mounted on a filter wheel 938.

In an exemplary embodiment, the first filter 940 includes a notch filter (notch filter) configured to block light having a wavelength from 675nm to 825nm while allowing wavelengths less than 675nm and greater than 825nm to pass. In various embodiments, first filter 940 may include a notch filter configured to block light having a wavelength of 690nm to 840nm while allowing wavelengths less than 690nm and greater than 825nm to pass. The second filter 942 may include an optical filter that transmits green and red light, for example, a filter having the characteristics discussed below in connection with fig. 12-15.

Referring now to fig. 30, a block diagram of various components of a handheld imaging device is shown, according to an exemplary embodiment of the present disclosure. In the diagram of fig. 30, the components are grouped into an optical PCB 3000 and an electronic system 3002. In the embodiment of fig. 30, the optical PCB includes 4 fluorescent wavelength LEDs 3004, 2 infrared LEDs 3006 and two white light LEDs 3008. The optical PCB also includes an ambient light sensor 3010, a laser range finder 3012, and a temperature sensor 3014.

Optical PCB 3000 is operatively coupled with electronic system 3002. The electronic system 3002 may include, for example, but is not limited to, electronic control components such as an application processor module 3016, a real-time microcontroller unit (MCU)3018, and a power management subsystem 3020. The electronic system 3002 may also include components and systems that interface with other electronic components of the handheld imaging device. For example, the electronic system 3002 may include a CMOS camera interface 3022 and motor drive electronics 3024 for an optical filter system. The electronic system may also include connectors 3026 and 3027 for fluorescence and white light cameras, respectively, to facilitate switching between fluorescence and white light imaging modes discussed herein.

Other supporting electronic systems and components of electronic system 3002 may include memory such as flash memory device 3028, rechargeable batteries such as lithium ion battery 3030, and inductive battery charging system 3032. Some components of the electronic system 3002 may include communication components such as Wi-Fi and/or bluetooth radio subsystems 3034, as well as spatial orientation components such as one or more of magnetometers, accelerometers, and gyroscopes 3035.

The electronic system 3002 may include various user controls such as a power switch 3036, a system status LED 3038, a charge status LED 3040, a picture capture switch 3042, a video capture switch 3044, and an imaging mode switch 3046. The various user controls may be connected with other components of the electronic system through a user interface module 3048 that provides signals to and from the user controls.

Other components in the electronic system 3002 may include drivers 3050 for fluorescent, infrared, and white light LEDs, a USB hub 3052 for uplink or downlink data signals, and/or a power supply from an external computer system, such as a workstation or other computer, to which the electronic system 3002 may be connected through the USB hub 3052. The electronic system 3002 may also include one or more devices that provide feedback to the user, such as, but not limited to, a speaker 3054. Other feedback devices may include various audible and visual indicators, tactile feedback devices, displays, and other devices.

Electronic system 3002 (fig. 30) may be operatively coupled to a computer by USB hub 3052 (fig. 30) via a removable USB connection cable 3156 as shown in fig. 31. The cable 3156 may include various features configured to ensure that the cable does not interfere with the surgical field and that the cable is not inadvertently removed from the handheld device during use. While the description herein may refer to a Universal Serial Bus (USB) type connection, it should be understood that the present invention is not limited to any particular connection protocol, and connection protocols other than a variety of USB interfaces are within the scope of the present invention.

Cable 3156 may include a strain relief feature 3158 that is molded to facilitate preventing the cable from interfering with the surgical field. For example, in the embodiment of fig. 31, cable 3156 is configured to plug into a connection port on the back of a handheld device according to the present disclosure. The stress relief feature 3158 is molded to create a substantially 90 degree curvature in the cable 3156 when in an unstressed state. The curvature of cable 3156 facilitates the path of cable 3156 away from the surgical field. The curvature of the cable may be less than or greater than 90 degrees. As an exemplary range, the curvature of the cable may be, but is not limited to, from 70 degrees to 110 degrees. Curvatures of less than 70 degrees or greater than 110 degrees are within the scope of the present disclosure. The particular shape of the cable imparted by the strain relief feature 3158 may depend on the location of the connection port on the handset. For example, for a handheld device with a connection port on the side, the strain relief feature may be straight to direct the cable away from the surgical field.

The cable 3156 may also include a connection interface 3160 configured to electrically and mechanically couple the cable 3156 to a handheld device. The connection interface 3160 may include a locking ring 3162 that provides a secure mechanical engagement between the cable 3156 and the handheld device to prevent the cable 3156 from being inadvertently pulled out of the handheld device during use.

For example, referring now to fig. 32, a portion of a housing 3263 is shown that includes a connection port 3264 configured to receive a connection interface 3160 of a cable 3156. The connection port 3160 includes a surrounding portion having slots 3265 configured to receive corresponding tabs 3266 of the locking ring 3162. After the locking ring 3162 is inserted such that the tabs 3266 of the locking ring 3162 are received in the slots 3265, rotating the locking ring 3162 causes the tabs 3266 to rotate into the circumferentially extending portions 3267 of the slots 3265 and the locking ring 3162 retains the connection interface 3160 within the connection port 3264.

The locking ring 3162 and surrounding portions may comprise a material having sufficient mechanical strength to withstand the forces that may be applied to the connection interface 3160 during use. For example, one or both of the locking ring 3162 and the surrounding portions of the connection port 3264 may include a metal, such as an aluminum alloy, a high strength polymer, a composite material, or other material.

Because the stress relief feature 3158 routes the cable away from the handheld device, applying a force to the cable 3156 and/or the stress relief feature 3158 may create a relatively large torque at the connection interface 3160 due to the stress relief feature 3158 being a moment arm. The connection interface 3160 of the cable 3156 and the corresponding connection port on the housing of the handheld device may include features to: the features are configured to withstand such torque and other forces without applying these forces to the more sensitive electrical contact assembly of the connection interface 3160 and the corresponding connection port.

For example, connection port 3264 may include a pin 3268 extending from a surface of port 3264. The connection interface 3160 of the cable 3156 includes recesses 3269 (only one of which is shown in fig. 32) in which pins 3268 are received. The pin 3268 and the recess 3269 form a mechanical interface between the connection port 3264 and the connection interface 3160 that is mechanically strong enough to withstand the typical forces experienced by the cable 3156 and the connection port 3264 during use and prevent excessive stress from being placed on the electrical interface assembly of the connection port 3264 and the connection interface 3160.

Further, in some exemplary embodiments, one or both of connection port 3264 and connection interface 3160 may include seals to prevent various contaminants, such as biological or therapeutic liquids or substances, from invading the electrical contacts of connection port 3264 and connection interface 3160. For example, in the embodiment of fig. 32, the connection port 3264 includes a gasket 3270 that forms a seal against the connection interface 3160 when the connection interface 3264 is secured in the connection port 3264 by a locking ring 3162. Further, in some embodiments, a washer or other seal may be configured to provide a preload force between the connection port 3264 and the connection interface 3160 that acts to keep the locking ring 3162 fixed in the coupled state of the connection interface 3160 in the connection port 3264. As described above, when in the coupled state, cable 3156 may provide a data and/or power transmission channel for attaching the handheld device to a computer. Further, the cable 3156 may be provided with a sterile sheath configured to attach to a sterile drape 1960 (fig. 19) to maintain a sterile barrier between the handheld device 100 and the surgical area when the cable 3156 is coupled to the connection port 3264.

Fig. 10-15 provide examples of possible usage scenarios for handheld devices according to various embodiments of the present disclosure. Referring now to fig. 10, in this use scenario, tissue is illuminated by a light source (e.g., one or more LEDs 118 of handheld device 100 (fig. 2)) that provides an excitation light wavelength of 760 nm. The tissue is treated with an IR dye such as ICG. The optical filter positioned to filter light entering an imaging device, such as imaging device 520 (fig. 6), includes a 760nm notch filter that filters excitation light from being captured by the imaging sensor. The filter has a notch between 675nm and 825 nm. As can be seen in the graph of fig. 10, the light emitted from the ICG treated tissue has an emission wavelength of 835nm and therefore passes through a notch filter and is captured by an imaging sensor, resulting in an image showing the ICG treated tissue.

Referring now to FIG. 11, tissue is illuminated with a light source having a wavelength of 780 nm. A notch filter having a short pass wavelength of 690nm and a long pass wavelength of 840nm is used to filter the light returning to the imaging device. The tissue is treated with an IR dye such as ICG, which when excited by a 780nm light source emits light with a peak intensity wavelength of 835nm and passes through a notch filter for capture by an imaging device, again displaying the ICG treated tissue in the resulting image.

Fig. 12-15 are example use scenarios in which a handheld device is used for fluoroscopic imaging to improve the contrast of tumor versus normal cells. Referring now to fig. 12, a subject may be administered a diagnostic dose of aminolevulinic acid (ALA) to induce PpIX formation in tumor tissue. The tissue is illuminated with a light source having a wavelength of 405 nm. Transmitting green and red wavelengthsThe filter is used to filter the light captured by the imaging device. As shown in fig. 12, PpIX emits light with a wavelength of 635nm within the red transmission band of the optical filter and can therefore be captured by an imaging device, showing in the resulting image the tissue inducing PpIX formation.

Fig. 13-15 present a similar contrast ratio to the example of fig. 12, with various changes made to the filter used in fig. 12 to improve the contrast ratio of tumor to normal cells. In fig. 13, the filter is modified to reduce the green band transmission by about 50%. In other embodiments, the reduction in green band transmission may be less than or greater than 50%, for example, any amount in the range of about 10% to about 90%, less than 10%, or greater than 90%. In FIG. 14, the filter is modified to widen the red transmission band (from about 600-675nm as shown in FIGS. 12 and 13) to 600-725 nm. In fig. 15, the filter was modified to reduce the green band transmission by 50% and widen the red band transmission to 725 nm.

Changing from the white light and infrared imaging mode discussed in connection with fig. 10 and 11 to the fluorescence imaging mode discussed in connection with fig. 12-15 may be accomplished, according to embodiments of the present disclosure, by rotating filter wheel 938 (fig. 9) so that the desired optical filter (e.g., a notch filter or a filter that transmits green and red wavelengths) is positioned in front of the imaging device to filter the wavelengths of light returning to the handheld device. Controls on the handheld device, such as control 113 (fig. 2), may include switches, buttons, etc. to switch the light source from 760nm or 780nm LEDs to 405nm LEDs or white light LEDs. In some embodiments of the present disclosure, the filter wheel may be configured to automatically rotate from one filter to another based on a selected mode of the handheld device, for example, input by a user at control 113.

The handheld device may also be configured to provide imaging modes other than those described above. For example, the handheld device may include a mode in which the imaging sensor, light source, and filter are configured to provide 3D imaging for topographic mapping of the imaging surface. Additional details regarding the use of 3D imaging may be found in U.S. provisional application No. 62/793,837 (filed 2019 on 1/17), entitled "system, method and apparatus for three-dimensional imaging, measurement and display of wounds and tissue samples," which is incorporated herein by reference in its entirety.

As an example of another imaging modality, the handheld device may be configured to provide fluorescence lifetime imaging of tissue. Fluorophores such as PpIX have a fluorescence emission decay curve that defines the rate at which visible fluorescence disappears upon removal of the excitation source. Thus, by capturing images shortly after the excitation source is removed or turned off, different fluorophores can be imaged separately by tailoring the image capture time for each unique fluorophore after the excitation source that excited the particular fluorophore is removed. For example, if PpIX and another fluorophore have decay times of 9ns and 5ns, respectively, PpIX can be isolated imaged by capturing an image between 5 and 9ns after removal of the excitation source. In this way, fluorescence lifetime imaging can detect multiple unique fluorophores through their respective fluorescence lifetime characteristics based on differences in fluorescence index decay rates from the fluorophores. Such time resolved fluorescence imaging methods can be implemented by pulsing LEDs of various excitation wavelengths and gating the imaging sensor to detect the fluorophore lifetime of interest. Fluorescence lifetime imaging of tissue can be used to identify and distinguish between different tissue components, including healthy and diseased tissue and other biological components such as microorganisms and intrinsically fluorescent chemical agents or drugs.

Other possible imaging modes may include various combinations of white light imaging, infrared imaging, and fluorescence imaging. For example, in one possible imaging mode, white light and IR light sources are used to illuminate the tissue. An infrared dye such as ICG may be excited by the IR light source and the resulting IR image may be superimposed on the white light image to show the IR image in the anatomical environment.

In another imaging mode, white light illumination is followed by 405nm light illumination. The imaging filter for WL/IR is used during white light illumination and the FL filter is used during 405nm illumination. Successive images of white light and fluorescence are captured and can be superimposed to provide the anatomical environment (white light image) of the tumor location (FL image). For example, as shown in FIG. 16, the display 1600 may be divided into several panels. Panel 1602 displays a static white light image and panel 1604 displays a static fluorescent image. The panel 1606 displays an image with a fluorescence image overlaid on the white light image. The panel 1608 displays a dynamic display that can be switched between white light and fluorescent images as needed. With the dynamic panel 1608 in the fluorescence mode, the user would then scan the lumen/sample to find fluorescent tumor tissue, and possibly mark that tissue with a vascular clamp or the like. The superposition of fluorescence on the white light (static) panel 1606 will give the anatomical environment during this process. If dynamic panel 1608 is in white light mode, the user will scan the chamber or sample to find a location corresponding to static white light panel 1602 and then use the fluorescence image overlaid on the white light image in panel 1606 to determine where tumor tissue is located.

Referring now to fig. 17, a similar arrangement may be provided with white light and infrared images. For example, display 1700 may be divided into panels 1702, 1704, 1706 and 1708. The panel 1702 displays a static white light image. Panel 1704 displays a static infrared image. The panel 1706 provides a static image of the infrared image overlaid on the white light image. Finally, panel 1708 provides a dynamic view that can be switched between white light and infrared images as needed.

If the dynamic panel 1708 is in infrared mode, the user will scan the chamber/sample to match the infrared (static) panel 1704. Infrared coverage on the white light (static) panel 1706 will provide an anatomical background during this process.

If the dynamic panel 1708 is in white light mode, the user will scan the cavity/sample to find a location corresponding to the white light (static) panel 1702 and then use the infrared coverage on the white light (static) panel 1706 to determine the location of the relevant tissue.

Referring now to FIG. 18, another imaging modality is disclosed. The white light image, the infrared image and the fluorescence image after the white light/infrared filter is switched to the fluorescence filter are captured in sequence. The display 1800 is divided into display panels 1802-1816 that include white, infrared, and fluorescent static panels as well as various overlay layers as shown in FIG. 18. The dynamic panel 1816 may display any one of a white light image, an infrared image, and a fluorescent image. If the dynamic panel 1816 is in fluorescence mode, the user will scan the cavity/sample for red fluorescence and possibly mark the tissue with a vascular clamp or the like. During this process, the fluorescence overlay on the white light (static) panel will provide the anatomical background. The fluorescence + infrared (static) panel will show vasculature or other infrared fluorescent tissue components in this field of view co-localized with the green and red fluorescence. If the dynamic panel 1816 is in the white light mode, the user will scan the chamber/sample to find a location corresponding to the white light (static) panel, and then use the fluorescence superposition on the white light (static) panel and the infrared superposition on the white light (static) panel to determine the location of the relevant tissue.

Referring now to fig. 22-28, another embodiment of a handheld device 2200 is shown. Although the embodiments discussed above describe various arrangements of switchable filters, such as filter wheel 938 (fig. 9), other embodiments, such as the embodiments shown in fig. 22-28, include multiple filters and multiple cameras with fixed positions. In such embodiments, the handset 2200 may switch modes simply by activating different light sources and cameras, without requiring a mechanical configuration change to move between modes.

Fig. 22 shows a front perspective view of the handheld device 2200. The handheld device 2200 includes a first end 2212 sized and shaped to fit a user to grasp and hold the handheld device 2200. Opposite the first end 2212 is a second end 2214 that may include one or more optical filters, one or more light sources, and one or more sensors such as imaging sensors, temperature sensors, and proximity sensors, as discussed in the above embodiments.

Referring now to fig. 23, a top view of the hand held device 2200 is shown. The handheld device 2200 includes a control array 2250. In the illustrated embodiment, the control array 2250 includes three buttons 2252. The button 2252 provides an interface for the user to switch between various imaging modes of the handheld device 2200, such as the various infrared and fluorescence imaging modes discussed above in connection with other embodiments of the handheld device. The button 2252 may be sealed around the housing of the handset 2200 to simplify cleaning of the device and to prevent contamination of the internal components of the handset 2200.

Referring now to fig. 24, a perspective view of the first end 2212 of the hand-held apparatus 2200 is shown. In the embodiment of fig. 22-28, the handset 2200 has a removable cover portion 2254 that covers various components of the handset 2200, such as an electrical connection port 2256. In the illustrated embodiment, the electrical connection port 2256 is a Universal Serial Bus (USB) port that facilitates connection of the handheld device 2200 to external devices such as computers (such as PC workstations), tablets, phones, or other devices for various tasks, e.g., updating software or firmware on the handheld device 2200, downloading images saved in memory of the handheld device 2200, etc. Additionally or alternatively, the device may be directly connected to a storage device, such as a usb disk, a usb disk drive, or a thumb drive, to transfer data directly. For example, the handheld device may download data, images, and/or other material to the storage device. In another example, the storage device may be used to load new software or instructions onto the handheld device. Such actions may optionally be accomplished through a wireless communication link between the handheld device 2200 and an external device such as a computer, tablet, telephone, or other device, as discussed above with respect to the previous embodiments. In some embodiments, handheld device 2200 may include USB connection and wireless communication (e.g., Wi-Fi, Bluetooth, etc.) functionality.

Fig. 25 shows a back view of the cover 2254 of the handset 2200. The cover 2254 includes a fastener arrangement 2258 that facilitates removal and installation of the cover 2254 by a user. For example, in the embodiment of fig. 25, the fastener device 2258 is a quarter-turn fastener that locks the cover 2254 in place on the handset 2200. To remove the cover 2254, the user simply rotates the fastener device 2258 a quarter turn and removes the cover 2254 from the handset 2258. The fastener device 2258 may take many other forms as will be appreciated by those of ordinary skill in the art. The cover 2254 may also include a gasket 2260 (fig. 24) that forms a seal between the cover 2254 and the hand-held device 2200 to prevent contamination of the internal components of the hand-held device 2200.

In some implementations, handheld device 2200 may include a removable lens assembly configured to protect components located in second end 2214. Referring now to fig. 26, second end 2214 is shown with lens assembly 2262 removed from handheld device 2200. The lens assembly 2262 may include a lens frame 2264 coupled to a translucent lens 2266. In this embodiment, the lens frame 2264 may comprise a metal or metal alloy material and the translucent lens 2266 may comprise glass or other translucent material, such as acrylic or other polymers. The translucent lens 2266 may be bonded to the lens frame 2264 with an adhesive, such as a biocompatible epoxy or other suitable bonding material. Lens assembly 2262 may be coupled to handheld device 2200 in any suitable manner, such as by screws or other fasteners. In the exemplary embodiment of fig. 26, the lens assembly 2262 includes an opaque barrier 2265 positioned and configured to isolate different portions of the lens assembly 2262. For example, the opaque barrier 2265 is configured to isolate an optical sensor (e.g., the optical sensor discussed in conjunction with fig. 28) from various light sources (e.g., the light sources 2270, 2274, and 2276 discussed in conjunction with fig. 28) located at the second end 2214 of the handheld device 2200.

Fig. 27 shows another exploded view of the handheld device 2200. As shown in fig. 27, handheld device 2200 includes a heat sink 2268 in which second end pieces such as a camera, light source, and various other sensors are contained, as described below. The heat sink 2268 may be hollow to reduce weight while still providing efficient heat transfer from the components in the second end 2214 up to the body of the handheld device 2200. The heat spreader 2268 may include a material having desirable heat transfer characteristics, such as for example, copper, aluminum, other metals or metal alloys, or other thermally conductive materials. When assembled in the handheld device 2200, the heat spreader 2268 can extend from the second end 2214 of the handheld device toward the first end 2212 of the handheld device through the neck 2270 of the handheld device.

Fig. 28 is an enlarged view of the second end 2214 of the hand-held device 2200 and illustrates various components in the second end 2214. The second end 2214 of the handheld device 2200 includes a plurality of excitation light sources 2270 (e.g., emitting excitation light having a wavelength of about 350nm to about 400nm, about 400nm to about 450nm, about 450nm to about 500nm, about 500nm to about 550nm, about 550nm to about 600nm, about 600nm to about 650nm, about 650nm to about 700nm, about 700nm to about 750nm, about 750nm to about 800nm, about 800nm to about 850nm, about 850nm to about 900nm, and/or combinations thereof) and a first optical filter 2272 configured to support fluorescence imaging. In one example embodiment, the excitation light source 2270 is configured to emit excitation light in the blue/violet range, for example, emitting excitation light having a wavelength of about 405 nm. The excitation light source 2270 may be generally located around the first optical filter 2272, and a first optical sensor, such as a camera (not visible), may be located behind the first optical filter 2272. FL imaging is used to visualize, for example, cancer in breast tissue. The cancer in the breast tissue can be observed by irradiating the breast tissue with violet light (405nm) to excite protoporphyrin (PpIX) accumulated in cancer cells after the patient takes in 5-aminolevulinic acid (ALA). Local PpIX within the cancerous tumor absorbs the excitation light (405nm) and then emits light of a longer wavelength (peak at 635nm), allowing visualization of the cancer in the breast tissue. See, for example, fig. 12-15.

The second end 2214 also includes one or more white light sources 2274 (e.g., LEDs) that emit visible white light. A white light source 2274 is positioned adjacent the second optical filter 2278. WL imaging illuminates the entire field of view (FOV) for viewing and capturing images of breast tissue under standard illumination conditions, similar to what exists in an operating room environment.

One or more infrared light sources 2276 (infrared excitation light sources) are also positioned adjacent to the second optical filter 2278. The infrared excitation light source may emit excitation light having a wavelength between about 700nm and about 1 nm. In one example embodiment, the infrared excitation light source may emit an excitation wavelength between about 750nm and about 800 nm. In another example embodiment, the infrared excitation light source may be configured to emit an excitation wavelength between about 760nm and 780 nm. In another exemplary embodiment, the infrared excitation light source may be configured to emit an excitation wavelength of about 760nm ± 15 nm. The second optical filter 2278 may be positioned in front of a second optical sensor, such as a camera (not shown), and the second optical filter 2278 may be configured to support imaging using white light or infrared light as discussed in detail above. IR imaging can be used with indocyanine green (ICG) dye for viewing biological structures such as lymph nodes or blood vessels during breast surgery. ICG is a cyanine dye that is administered to patients intravenously, which binds tightly to beta lipoproteins, particularly albumin. Albumin is a family of globular proteins that are commonly found in plasma and circulatory systems. In addition, ICG accumulates in lymphatic pathways and lymph nodes due to the high protein content in lymph nodes. The accumulation of ICG makes it possible to visualize lymph nodes and vasculature using IR imaging. ICG is a dye that fluoresces when excited by near infrared light, with a peak absorption at 800nm and a peak emission at 835 nm. (see, e.g., fig. 10 and 11). As a further example, fig. 29 shows ICG emission and ICG absorption wavelengths measured in a 60uM aqueous solution.

The second end 2214 may also include other components, such as an ambient light sensor 2280, a range finder 2282, a temperature sensor 2284, and other sensors or components. In an exemplary embodiment, the handheld device 2200 includes a separate optical sensor (e.g., a camera) positioned behind each of the first optical filter 2272 and the second optical filter 2278.

The control array 2250 (fig. 23) may be operatively coupled to various components in the handheld device 2200 by a controller (e.g., one or more microprocessors and associated components) to enable a user to switch between fluorescent, white light, or infrared imaging modes. The configuration of the handset 2200 of fig. 22-28 enables switching between fluorescence and IR/white light imaging modes without any mechanical configuration changes in the handset 2200, thereby facilitating rapid mode changes and potentially reducing the likelihood of mechanical failure of components.

Moreover, the apparatus and methods may include additional components or steps that have been omitted from the figures for clarity of illustration and/or operation. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the general manner of carrying out the disclosure. It should be understood that the various embodiments shown and described herein are to be considered exemplary. Elements and materials, and arrangements of those elements and materials, may be substituted for those shown and described herein, parts and processes may be reversed, and certain features of the disclosure may be utilized independently, all as would be apparent to one skilled in the art after having the benefit of the description herein. Changes may be made in the elements described herein without departing from the spirit and scope of the disclosure and the appended claims, including their equivalents.

It is to be understood that the specific examples and embodiments set forth herein are not limiting and that modifications in structure, size, materials, and method may be made without departing from the scope of the present disclosure.

Furthermore, the terminology of the present specification is not intended to be limiting of the present disclosure. For example, spatially relative terms, such as "lower," "below," "lower," "above," "upper," "bottom," "right," "left," "proximal," "distal," "front," and the like, may be used to describe one element or feature's relationship to another element or feature as illustrated. These spatially relative terms are intended to encompass different positions (i.e., locations) and orientations (i.e., rotational placements) of the device in use or operation in addition to the position and orientation depicted in the figures.

For the purposes of the present specification and appended claims, unless otherwise indicated, all numbers expressing quantities, percentages or proportions, and other numerical values used in the specification and claims, are to be understood as being modified in all instances by the term "about" if they are not already present. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific embodiments are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

Moreover, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein.

It is noted that, as used in this specification and the appended claims, the singular forms "a," "an," and any use of any word include plural referents unless expressly and unequivocally limited to one reference. As used herein, the term "include" and grammatical variations thereof are intended to be non-limiting such that listing an item in a list does not exclude other similar items that may be substituted or added to the listed item.

It should be understood that while the present disclosure has been described in detail with respect to various exemplary embodiments thereof, it should not be considered limited thereto since various modifications can be made without departing from the broader scope of the appended claims, including their equivalents.

Claims (76)

1. An image forming apparatus comprising:

a body having a first end configured to be held in a user's hand and a second end configured to direct light onto a surgical edge;

at least one excitation light source configured to excite autofluorescence emission of tissue cells and porphyrin-induced fluorescence emission in tissue cells of the surgical margin;

a white light source configured to illuminate the surgical margin during white light imaging of the surgical margin;

an imaging sensor;

a first optical filter configured to filter optical signals emitted through the surgical margin in response to excitation light illumination and allow passage of autofluorescence emissions of tissue cells and porphyrin-induced fluorescence emissions in tissue cells to the imaging sensor;

a second optical filter configured to filter light signals emitted through the surgical margin in response to illumination with white light and allow white light emissions of tissue in the surgical margin to pass to the imaging sensor.

2. The imaging device of claim 1, wherein the first optical filter and the second optical filter are configured to be alternately positioned to filter light signals passing through the filters to the imaging sensor.

3. The imaging device of claim 2, wherein the first and second optical filters are positioned on a filter wheel rotatable relative to the imaging sensor.

4. The imaging device of claim 3, wherein the filter wheel is operably coupled with a motor drive configured to rotate the filter wheel between a first position at which the first optical filter filters light signals reaching the imaging sensor through the first filter and a second position at which the second optical filter filters light signals reaching the imaging sensor through the second filter.

5. The imaging apparatus of claim 4, wherein the apparatus further comprises a processor, and the motor driver is in signal communication with the processor.

6. The imaging device of any of claims 3 to 5, wherein the rotatable filter wheel is positioned distal to the imaging sensor.

7. The imaging apparatus of any of claims 1 to 6, wherein the excitation light source comprises a first excitation light source and a second excitation light source.

8. The imaging device of claim 7, wherein the first excitation light source is configured to emit excitation light having a wavelength of about 350nm to about 400nm, about 400nm to about 450nm, about 450nm to about 500nm, about 500nm to about 550nm, about 550nm to about 600nm, about 600nm to about 650nm, about 650nm to about 700nm, about 700nm to about 750nm, about 750nm to about 800nm, about 800nm to about 850nm, about 850nm to about 900nm, and/or combinations thereof.

9. The imaging device of claim 8, wherein the first excitation light source is configured to emit excitation light having a wavelength of about 400nm to about 450 nm.

10. The imaging device of claim 9, wherein the first excitation light source is configured to emit excitation light having a wavelength of about 405nm ± 10 nm.

11. The imaging device of claim 7, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 350nm to about 400nm, about 400nm to about 450nm, about 450nm to about 500nm, about 500nm to about 550nm, about 550nm to about 600nm, about 600nm to about 650nm, about 650nm to about 700nm, about 700nm to about 750nm, about 750nm to about 800nm, about 800nm to about 850nm, about 850nm to about 900nm, and/or combinations thereof.

12. The imaging device of claim 11, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 750nm-800 nm.

13. The imaging device of claim 12, wherein the second excitation light source is configured to emit excitation light having a wavelength between about 760nm and about 780 nm.

14. The imaging device of claim 13, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 760nm ± 10 nm.

15. The imaging device of claim 13, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 770nm ± 10 nm.

16. The imaging device of claim 13, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 780nm ± 10 nm.

17. The imaging device of claim 1, wherein the first optical filter is configured to allow optical signals having a wavelength of about 500nm to about 550nm and/or about 600nm to about 675nm to pass.

18. The imaging device of claim 1, wherein the first optical filter is configured to allow optical signals having a wavelength of about 500nm to about 550nm and/or about 600nm to about 725nm to pass.

19. The imaging device of claim 1, wherein the first optical filter is configured to allow optical signals having a wavelength of about 635nm to pass.

20. The imaging device of claim 17 or 18, wherein the first optical filter is configured to attenuate passage of optical signals having wavelengths of about 500nm to about 550nm by an amount in a range of about 10% to about 90%.

21. The imaging device of claim 1, wherein the second optical filter is configured to allow optical signals having wavelengths below about 675nm and above about 825nm to pass.

22. The imaging device of claim 1, wherein the second optical filter is configured to allow optical signals having wavelengths below about 690nm and above about 840nm to pass.

23. The imaging device of claim 21 or 22, wherein the second optical filter is configured to allow passage of optical signals having a wavelength of about 835 nm.

24. The imaging device of any of claims 1 to 23, wherein the imaging sensor comprises a Complementary Metal Oxide Semiconductor (CMOS) sensor.

25. The imaging device of claim 1, wherein the first filter and the second filter are each in a fixed position relative to a body of the imaging device.

26. The imaging apparatus of claim 25, wherein the excitation light source is adjacent to the first optical filter and the white light source is adjacent to the second optical filter.

27. The imaging apparatus of claim 25, wherein the imaging sensor is a first imaging sensor, the imaging apparatus comprising a second imaging sensor, wherein the first optical filter is positioned to filter light signals entering the first imaging sensor, and wherein the second optical filter is positioned to filter light signals entering the second imaging sensor.

28. The imaging device of claim 1, further comprising a connection port configured to receive a connection cable for connecting the imaging device to an external computer system.

29. The imaging device of claim 28, wherein the connection port includes a feature configured to interact with the connection cable to prevent rotation of the connection cable relative to the connection port.

30. An imaging system, comprising:

the imaging device of any one of claims 1 to 29; and

a sterile drape configured to form a sterile barrier between the imaging device and an environment in which the imaging device is used.

31. The imaging system of claim 30, wherein the sterile drape includes a first portion configured to form a sterile barrier between the imaging device and an environment in which the imaging device is used and a second portion configured to shield a surgical cavity from ambient light.

32. The imaging system of claim 30 or 31, wherein the sterile drape comprises an optically transparent lens cover positioned over the imaging sensor when the sterile drape is installed on the imaging device.

33. The imaging system of claim 32, wherein the lens cover is configured to engage a feature on the second end of the device.

34. The imaging system of claim 33, wherein the feature on the second end of the device comprises a circumferential groove.

35. The imaging system of any of claims 30 and 32 to 34, further comprising a darkening drape configured to reduce ambient light at a surgical edge to be imaged.

36. The imaging system of any of claims 30 to 35, further comprising a connection cable, a portion of the connection cable configured to non-rotatably connect to a connection port of the imaging device.

37. The imaging system of claim 36, further comprising a sterile sheath for the connection cable.

38. An image forming apparatus comprising:

a body having a first end configured to be held in a user's hand and a second end configured to direct light onto a surgical edge;

a first excitation light source configured to emit excitation light having a first wavelength;

a second excitation light source configured to emit excitation light having a second wavelength;

an imaging sensor configured to detect emissions of the surgical margin;

a first optical filter configured to filter optical signals emitted through the surgical edge in response to the first excitation light illuminating the surgical edge, the first filter configured to allow optical signals having a wavelength corresponding to a first characteristic of the surgical edge to pass through the filter to the imaging sensor;

a second optical filter configured to filter optical signals emitted through the surgical edge in response to the first excitation light illuminating the surgical edge, the second filter configured to allow optical signals having a wavelength corresponding to a second characteristic of the surgical edge to pass through the filter to the imaging sensor, the second characteristic different from the first characteristic.

39. The imaging device of claim 38, wherein the first optical filter is configured to be positioned to filter optical sensors passed to the imaging sensor when the first light source is actuated, and the second optical filter is configured to be positioned to filter optical sensors passed to the imaging sensor when the second light source is actuated.

40. The imaging device of claim 39, wherein the first optical filter and the second optical filter are on a filter wheel rotatable relative to the imaging sensor.

41. The imaging device of any one of claims 38 to 40, wherein in a first mode of operation the first light source is actuated to illuminate target tissue and the first optical filter is positioned to filter optical signals emitted through the target tissue in response to illumination and entering the imaging sensor, and in a second mode of operation the second light source is actuated to illuminate target tissue and the second optical filter is positioned to filter light entering the imaging sensor.

42. The imaging device of claim 38, wherein the first optical filter and the second optical filter are each in a fixed position relative to a body of the imaging device.

43. The imaging device of claim 42, wherein the first excitation light source is adjacent to the first optical filter and the second excitation light source is adjacent to the second optical filter.

44. The imaging apparatus of claim 38, wherein the imaging sensor is a first imaging sensor and the imaging apparatus comprises a second imaging sensor, wherein the first optical filter is positioned to filter light signals entering the first imaging sensor, and wherein the second optical filter is positioned to filter light signals entering the second imaging sensor.

45. An imaging system, comprising:

the imaging device of any one of claims 38 to 44;

a sterile drape configured to form a sterile barrier between the imaging device and an environment in which the imaging device is used.

46. The imaging system of claim 45, wherein the sterile drape comprises an optically transparent lens cover positioned over the imaging sensor when the sterile drape is installed on the imaging device.

47. The imaging system of claim 44 or 46, further comprising a darkening drape configured to reduce ambient light at a surgical cavity to be imaged.

48. The imaging system of any of claims 44 to 47, further comprising a connection cable, a portion of the connection cable configured to non-rotatably connect to a connection port of the imaging device.

49. The imaging system of claim 48, further comprising a sterile sheath for the connection cable.

50. A method of imaging tissue at a surgical edge, comprising:

illuminating tissue at the surgical edge with a first excitation light source configured to emit excitation light having a first wavelength;

receiving, by a first optical filter in an imaging device, a light signal emitted through tissue at the surgical edge;

illuminating tissue at the surgical edge with a second excitation light source configured to emit excitation light having a second wavelength;

receiving, by a second optical filter in the imaging device, an optical signal emitted through tissue at the surgical edge.

51. The method of claim 50, further comprising:

based on the signals from the processor:

moving the first optical filter away from a position at which light signals emitted by tissue at the surgical edge are filtered by the first optical filter;

moving the second optical filter to a position where optical signals emitted from tissue at the surgical edge are filtered by the second optical filter.

52. The method of claim 50, wherein moving the first optical filter from a position and the second optical filter to a position comprises: actuating a motor to move the first optical filter and the second optical filter.

53. The method of claim 52, wherein actuating a motor to move the first and second optical filters comprises: actuating the motor to rotate a filter wheel including the first optical filter and the second optical filter.

54. The method of any of claims 50 to 53, wherein illuminating tissue at the surgical edge with a first excitation light source configured to emit excitation light having a first wavelength comprises: the tissue is illuminated with a first excitation light source having a wavelength of about 405nm ± 10 nm.

55. The method of any of claims 52 to 54, wherein illuminating tissue at the surgical edge with a second excitation light source configured to emit excitation light having a second wavelength comprises: the tissue is illuminated with a second excitation light source having a wavelength of about 750nm to 800 nm.

56. The method of any of claims 52 to 55, wherein receiving, by a first optical filter, the optical signal emitted through tissue at the surgical edge comprises: the optical signals emitted by the tissue are filtered by a filter that allows optical signals having wavelengths of about 500nm to about 550nm and/or about 600nm to about 675nm to pass through.

57. The method of any of claims 52 to 55, wherein receiving, by a first optical filter, the optical signal emitted through tissue at the surgical edge comprises: the optical signals emitted by the tissue are filtered by a filter that allows optical signals having wavelengths of about 500nm to about 550nm and/or about 600nm to about 725nm to pass through.

58. The method of any of claims 52 to 57, wherein receiving, by a second optical filter, the optical signal emitted through tissue at the surgical edge comprises: the optical signals emitted by the tissue are filtered by a filter that allows optical signals having wavelengths below about 675nm and above about 825nm to pass through.

59. The method of any of claims 52 to 58, wherein receiving, by a second optical filter, the optical signal emitted through tissue at the surgical edge comprises: the optical signals emitted by the tissue are filtered by a filter that allows the passage of optical signals having wavelengths below about 690nm and above about 840 nm.

60. The method of any of claims 52-59, further comprising: administering ALA to the patient prior to irradiating tissue at the surgical edge.

61. The method of any of claims 52-60, further comprising: administering ICG to the patient prior to irradiating tissue at the surgical edge.

62. The method of any of claims 52-61, further comprising: placing a sterile drape over the imaging device prior to illuminating tissue at the surgical edge.

63. The method of any of claims 52-62, further comprising: reducing ambient light at a surgical site at which the surgical margin is located.

64. The method of claim 63, wherein reducing ambient light comprises: positioning a darkened drape around the surgical site prior to illuminating tissue at the surgical edge such that the surgical edge is positioned within a field of view of the imaging device in an interior of the darkened drape.

65. The method of any of claims 52-64, further comprising: it is determined whether the level of ambient light is sufficient to allow fluorescence imaging.

66. A method of visualizing a breast cancer cell, comprising:

administering one or more imaging agents to the patient, wherein at least one of the imaging agents is configured to induce formation of protoporphyrin in breast cancer cells;

after administering the one or more imaging agents, illuminating breast tissue of the patient with a first excitation light source configured to cause fluorescence of the protoporphyrin;

receiving, by a first optical filter in an imaging device, an optical signal emitted by cells within breast tissue containing protoporphyrin in response to illumination with the first excitation light;

illuminating breast tissue with a white light source;

receiving, by a second optical filter in the imaging device, a light signal emitted through the breast tissue in response to illumination with the white light.

67. The method of claim 66, wherein the step of administering one or more pharmaceutical agents to the patient comprises: administering ALA to the patient.

68. The method of claim 66, wherein the step of administering one or more pharmaceutical agents to the patient comprises: administering ICG to the patient.

69. The method of any one of claims 66 to 68, wherein receiving, by a first optical filter, an optical signal emitted by cells within the protoporphyrin-containing breast tissue in response to illumination with the first excitation light comprises: receiving an optical signal through the first optical filter at a first imaging sensor.

70. The method of claim 69, wherein receiving, by a second optical filter, a light signal emitted through the breast tissue in response to illumination with the white light comprises: receiving a light signal through the second optical filter at a second imaging sensor.

71. The method of any of claims 66-68, further comprising: moving the first optical filter from a first position at which the light signal is filtered by the first optical filter before being received by an imaging device, and moving the second optical filter to the first position.

72. The method of any of claims 66-71, further comprising: the handheld device is operably coupled to an external computer system by a cable connected to a port of the handheld device.

73. The method of any of claims 66-72, further comprising: placing a sterile drape over the imaging device prior to irradiating the patient's breast tissue.

74. The method of any of claims 66-73, further comprising: reducing ambient light at a surgical site where the breast tissue is located.

75. The method of claim 74, wherein reducing ambient light comprises: prior to illuminating breast tissue, positioning a darkening drape about the surgical site such that the breast tissue is positioned within a field of view of the imaging device in an interior of the darkening drape.

76. The method of any of claims 66-75, further comprising: it is determined whether the level of ambient light is sufficient to allow fluorescence imaging.