Modular System for Multimodal Imaging and Analysis

Abstract

A portable, modular, handheld imaging system is disclosed. The modular system includes a first housing portion and a second housing portion. The first housing portion includes at least one excitation light source. A first filter is configured to detect and allow selected optical signals to pass through a first image sensor in response to illumination with the excitation light. A second filter is configured to detect and allow selected optical signals to pass through a second image sensor in response to illumination of a target surface with white light. The second housing portion is configured to releasably receive the first housing portion. The second housing portion includes a display and a processor configured to receive the detected fluorescent and white light optical signals and output a representation of the target surface to the display based on the detected optical signals.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to Provisional Application No. 62 / 793,842, filed January 17, 2019, entitled “MODULAR SYSTEM FOR MULTI-MODALIMAGING AND ANALYSIS,” the entire contents of which are incorporated herein by reference. Technical Field

[0002] A system for multimodal imaging and analysis is disclosed. Specifically, the system and method are applicable to collecting data related to biochemical, biological, and / or non-biological substances. For example, the data may include one or more of white light data, fluorescence data, thermal data, and infrared data, such as for wound care applications in humans and animals. Background Art

[0003] Wound care is a significant clinical challenge. Healing and chronic non-healing wounds are associated with numerous biological changes, including inflammation, proliferation, connective tissue remodeling, and, often, bacterial infection. A proportion of wound infections are not clinically apparent and contribute to the growing economic burden associated with wound care, particularly in the elderly population. Currently, the gold standard for wound assessment involves direct visual inspection of the wound site under white light, combined with indiscriminate collection of bacterial swabs and tissue biopsies, resulting in delayed, expensive, and often insensitive bacteriological results. This can impact the timing and effectiveness of treatment. Qualitative and subjective visual assessment provides only a gross overview of the wound site but lacks information on the underlying biological and molecular changes occurring at the tissue and cellular levels. Relatively simple and complementary approaches are needed in clinical wound management that leverage both biological and molecular information to improve the early identification of these insidious changes. Early identification of at-risk wounds can guide therapeutic interventions and provide monitoring of responses over time, thereby significantly reducing morbidity and mortality, particularly in chronic wounds.

[0004] Wound care and management are major clinical challenges that pose a significant burden and challenge to global health care [Bowler et al., Clin Microbiol Rev. 2001, 14:244-269; Cutch et al., Journal of Wound Care. 1994, 3:198-201; Dow et al., Ostomy / Wound Management. 1999, 45:23-40]. Wounds are generally classified as those without tissue loss (e.g., during surgery) and those with tissue loss, such as burns, wounds, abrasions, or wounds secondary to chronic disease (e.g., venous stasis, diabetic ulcers, or pressure sores, and iatrogenic wounds, such as skin graft donor sites and skin abrasions, pilonidal sinuses, non-healing surgical wounds, and chronic cavity wounds). Wounds are also classified by the number of layers involved, with superficial wounds involving only the epidermis, partial-thickness wounds involving only the epidermis and dermis, and full-thickness wounds involving subcutaneous fat or deeper tissues as well as the epidermis and dermis. While restoration of tissue continuity after injury is a natural phenomenon, infection, healing quality, healing speed, fluid loss, and other complications that prolong healing time are major clinical challenges. Most wounds heal without complications. However, chronic, non-healing wounds involve increasing amounts of tissue loss, presenting a significant challenge to wound care practitioners and researchers. Unlike surgical incisions, where tissue loss is relatively minimal and wounds typically heal without significant complications, chronic wounds disrupt the normal healing process and are often insufficient to achieve repair. Delayed healing is often the result of impaired wound physiology [Winter (1962) Nature. 193:293-294], commonly occurring in venous stasis and diabetic ulcers, or in the immunosuppressed and immobile elderly population with prolonged localized pressure. These chronic conditions increase the cost of care and reduce the quality of life of patients. As the number of these populations grows, the demand for advanced wound care products will increase.

[0005] Conventional clinical assessment methods for acute and chronic wounds remain suboptimal. They are typically based on a thorough patient history, qualitative and subjective clinical assessment, and simple visual assessment using ambient white light and the “naked eye” and may sometimes involve the use of color photography to capture the gross appearance of the wound under white light illumination [Perednia (1991) J Am Acad Dermatol. 25:89–108]. Regular reassessment of treatment progress and appropriate modification of interventions are also necessary. Wound assessment terminology is not standardized, many questions surrounding wound assessment remain unanswered, there is no consensus on the key wound parameters that need to be measured in clinical practice, and the accuracy and reliability of existing wound assessment techniques vary. Visual assessment is often combined with swabs for bacterial culture and / or tissue biopsy for diagnosis. Collecting bacterial swabs during wound examination has the significant advantage of providing identification of specific bacterial / microbial species [Bowler, 2001; Cutting, 1994; Dow, 1999; Dow G. In: Krasner et al., eds. Chronic Wound Care: A Clinical Source Book for Healthcare Professionals, 3rd ed., Wayne Pa.: HMP Communications. 2001: 343-356]. However, multiple swabs and / or biopsies are often collected randomly from the wound, and some swab techniques may actually spread microorganisms around the wound during collection, thereby affecting patient healing time and morbidity [Dow, 1999]. This can be a problem, particularly for large, chronic (non-healing) wounds, where current swab and biopsy protocols are not efficient enough to detect the presence of bacteria (diagnostic insensitivity) despite the collection of many swabs. Therefore, current methods for obtaining swabs or tissue biopsies from wound sites for subsequent bacterial culture are based on non-targeted or "blind" swab or punch biopsy methods and have not been optimized to minimize trauma to the wound or maximize the diagnostic yield of bacteriological testing. In addition, obtaining bacteriological swabs and biopsy specimens can be laborious, invasive, painful, expensive, and more importantly, bacterial culture results typically take approximately 2-3 days to return from the laboratory and may be inconclusive [Serena et al. (2008) Int J Low Extrem Wounds. 7(1):32-5.; Gardner et al., (2007) WOUNDS. 19(2):31-38], thereby delaying accurate diagnosis and treatment [Dow, 1999]. Therefore, bacterial swabs cannot provide real-time detection of the infection status of the wound.Although wound swabbing appears simple, it can lead to inappropriate treatment, patient morbidity, and increased length of hospital stay if performed incorrectly [Bowler, 2001; Cutting, 1994; Dow, 1999; Dow, 2001]. The lack of noninvasive imaging methods to objectively and rapidly assess wound repair at the biological level (which may be more detailed than appearance or morphology alone) and to facilitate targeted collection of bacteriological swabs and tissue biopsy specimens is a major obstacle to clinical wound evaluation and treatment. Alternative methods are highly desirable.

[0006] As wounds (chronic and acute) heal, many key biological changes occur at the wound site at the tissue and cellular levels [Cutch, 1994]. Wound healing involves a complex and dynamic interplay of biological processes, organized into four overlapping phases—hemostasis, inflammation, cell proliferation, and connective tissue maturation or remodeling—that influence the pathophysiology of wound healing [Physiological basis of wound healing, in Developments in wound care, PJBPublications Ltd., 5-17, 1994]. A common and major complication of wound healing (lasting from days to months) is infection caused by bacteria and other microorganisms [Cutch, 1994; Dow, 1999]. This can lead to significant impairment of the healing process and result in significant complications. All wounds harbor varying degrees of bacterial presence, ranging from contamination, colonization, and heavy colonization to infection. Diagnosis of bacterial infection is based on clinical symptoms and signs (e.g., visual and odor cues).

[0007] The most commonly used terms for wound infection include wound contamination, wound colonization, wound infection, and most recently, critical colonization. Wound contamination refers to the presence of bacteria in the wound without any host response [Ayton M. Nurs Times 1985, 81(46): suppl 16-19], wound colonization refers to the presence of bacteria in the wound that multiply or elicit a host response [Ayton, 1985], and critical colonization refers to bacterial proliferation leading to delayed wound healing, often associated with increased pain that has not been previously reported but remains in the absence of an apparent host response [Falanga et al., J Invest Dermatol W94, 102(1): 125-27; Kingsley A, Nurs Stand 2001, 15(30): 50-54, 56, 58]. Wound infection refers to the deposition and proliferation of bacteria in tissues, accompanied by a host response [Ayton, 1985]. In practice, the term "critical colonization" can be used to describe wounds that are considered to have transitioned from colonization to local infection. However, the challenge in the clinical setting is ensuring that such conditions are recognized quickly and reliably, and that bacterial biocontamination is minimized as quickly as possible, perhaps through the use of topical antimicrobials. Potential wound pathogens can be divided into different groups based on their structure and metabolic capabilities, such as bacteria, fungi, spores, protozoa, and viruses [Cooper et al., Wound Infection and Microbiology.: Medical Communications (UK) Ltd for Johnson & Johnson Medical, 2003]. Although viruses do not typically cause wound infections, bacteria can infect skin lesions formed during certain viral illnesses. Such infections can occur in a variety of settings, including healthcare settings (hospitals, clinics) and homes or chronic care facilities. The management of wound infections is increasingly complex, but treatment is not always guided by microbiological diagnosis. The high incidence of microbial diversity and polymicrobial flora in most chronic and acute wounds necessitates the identification of one or more bacterial pathogens from wound cultures. Early identification of the pathogen(s) responsible for wound infection can help wound care providers take appropriate action. Furthermore, faulty collagen formation is caused by increased bacterial load and results in loose, overvascularized granulation tissue, often leading to wound breakdown [Sapico et al. (1986) Diagn Microbiol Infect Dis. 5:31-38].

[0008] Accurate and clinically relevant wound assessment is a crucial clinical tool, yet achieving this remains a significant challenge. Current visual assessment in clinical practice provides only a gross view of the wound site (e.g., the presence of purulent material and scabs). Current best clinical practices fail to fully utilize crucial objective information regarding potentially critical biological changes occurring at the tissue and cellular levels (e.g., contamination, colonization, infection, matrix remodeling, inflammation, bacterial / microbial infection, and necrosis) because these indicators are i) not readily available during wound inspection and ii) not currently integrated into routine wound management. Direct visual assessment of wound health using white light relies on the detection of color and topographical / textural changes within and around the wound and can be inadequate and unreliable in detecting subtle changes in tissue remodeling. Furthermore, because bacteria are occult under white light illumination, direct visual assessment of wounds often fails to detect the presence of bacterial infection. Infection is diagnosed clinically through microbiological testing to identify the organism and its susceptibility to antibiotics. While physical signs of bacterial infection (e.g., purulent exudate, crusting, swelling, erythema) can be readily observed in most wounds using white light, this is often significantly delayed, and the patient is already at increased risk of morbidity (and other infection-related complications) and mortality. Therefore, standard white light direct visualization cannot detect the early presence of bacteria themselves or identify the type of bacteria within the wound.

[0009] The implantation and transplantation of stem cells has recently attracted interest, for example, in wound care and therapy. However, tracking the proliferation of stem cells after implantation or transplantation is currently challenging. Tracking and identifying cancer cells is also challenging. Being able to monitor these cells in a minimally or noninvasive manner would be desirable.

[0010] It would also be useful to provide a method for detecting contamination on other target surfaces, including non-biological targets. Summary of the Invention

[0011] The present disclosure may solve one or more of the above problems and / or demonstrate one or more of the above desirable features.Other features and / or advantages will become apparent from the following description.

[0012] According to one aspect of the present disclosure, a portable handheld imaging system is provided. The system includes at least one excitation light source configured to emit excitation light during fluorescence imaging. A first filter is configured to detect and allow an optical signal to pass to a first image sensor, the optical signal being responsive to irradiation of a target surface with excitation light and having a wavelength corresponding to one or more of bacterial fluorescence, bacterial autofluorescence, tissue fluorescence, and tissue autofluorescence. A white light source is configured to emit white light during white light imaging. A second filter is configured to detect and allow an optical signal to pass to a second image sensor, the optical signal being responsive to irradiation of a target surface with white light and having a wavelength within the visible light range. Furthermore, a processor is configured to receive the detected fluorescence and white light optical signals and output a representation of the target surface to a display based on the detected optical signals.

[0013] According to another aspect of the present disclosure, a portable modular handheld imaging system is provided. The modular system includes a first housing portion and a second housing portion. The first housing portion includes: at least one excitation light source configured to emit excitation light during fluorescence imaging; a first filter configured to detect and allow an optical signal to pass to a first image sensor, the optical signal being responsive to illumination of a target surface with the excitation light and having a wavelength corresponding to one or more of bacterial fluorescence, bacterial autofluorescence, tissue fluorescence, and tissue autofluorescence; a white light source configured to emit white light during white light imaging; and a second filter configured to detect and allow an optical signal to pass to a second image sensor, the optical signal being responsive to illumination of a target surface with white light and having a wavelength in the visible light range. The second housing portion is configured to releasably receive the first housing portion and includes a display and a processor configured to receive the detected fluorescence and white light optical signals and output a representation of the target surface to the display based on the detected optical signals.

[0014] According to another aspect of the present disclosure, a portable, modular, handheld imaging system kit is provided. The kit includes a plurality of optical housing portions and a base housing portion. Each of the plurality of optical housing portions includes: at least one excitation light source configured to emit excitation light during fluorescence imaging; a first filter configured to detect and allow optical signals to pass to a first image sensor, the optical signals responsive to illumination of a target surface with the excitation light and having a wavelength corresponding to one or more of bacterial fluorescence, bacterial autofluorescence, tissue fluorescence, and tissue autofluorescence; a white light source configured to emit white light during white light imaging; and a second filter configured to detect and allow optical signals responsive to illumination of the target surface with the white light and having a wavelength within the visible light range to pass to a second image sensor. The base housing portion is configured to releasably and interchangeably receive each of the plurality of optical housing portions. The base housing portion includes a display; a power supply configured to power the at least one excitation light source and the white light source; and a processor configured to receive the detected fluorescence and white light optical signals and output a representation of the target surface to the display based on the detected optical signals.

[0015] According to yet another aspect of the present disclosure, a method for operating a modular, handheld fluorescence-based imaging device is provided. The method includes selecting an optical housing comprising optical components, the optical components including at least one excitation light source for fluorescence imaging, and connecting the selected optical housing to a base housing of the imaging device to provide power to the optical components in the optical housing from a power source in the base housing. The method also includes illuminating a target with the at least one excitation light source to cause one or more of a portion, component, and biomarker of the illuminated portion of the target to fluoresce, reflect, or absorb light; and filtering optical signals in response to the illumination of the target with the excitation light, wherein filtering the plurality of optical signals includes preventing reflected excitation light from passing through and allowing optical signals having wavelengths corresponding to one or more of bacterial fluorescence, bacterial autofluorescence, tissue autofluorescence, and exogenous tissue fluorescence to pass through a fluorescence filter contained in the optical housing. The method also includes detecting the filtered optical signals with an image sensor contained in the optical housing, and displaying the detected filtered signals on at least one display of the base housing as a composite image of the illuminated portion of the target, the composite image including fluorescent representations of various tissue components present in the illuminated portion of the target. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Can be used alone or with Figure 1 The present disclosure will be understood from the following detailed description. The accompanying drawings are included to provide a further understanding and are incorporated into and constitute a part of this specification. The accompanying drawings illustrate one or more exemplary embodiments of the present disclosure and, together with the description, serve to explain various principles and operations.

[0017] Figure 1 is a front view of a first embodiment of a modular handheld imaging device according to the present disclosure.

[0018] Figure 2 yes Figure 1 Rear view of the modular handheld imaging device.

[0019] Figure 3 yes Figure 1 Front perspective view of a modular handheld imaging device.

[0020] Figure 4 yes Figure 1 Rear perspective view of the modular handheld imaging device.

[0021] Figure 5A is a perspective view of a first optical housing separated from a base housing according to a second embodiment of a modular handheld imaging system of the present disclosure.

[0022] Figure 5B is a perspective view of a second optical housing separated from a base housing according to a third embodiment of a modular handheld imaging system of the present disclosure.

[0023] Figure 6 are examples of white light (WL), fluorescence (FL), and thermal images acquired according to an exemplary embodiment of the modular handheld imaging device of the present disclosure.

[0024] Figure 7 are examples of measurements taken according to an exemplary embodiment of the modular handheld imaging device of the present disclosure.

[0025] Figures 8A to 8D is an example of an image acquired and created during formation of a three-dimensional fluorescent image of a target using an exemplary embodiment of a modular handheld imaging device according to one aspect of the present disclosure.

[0026] Figures 9A to 9E A separate charging station according to the present disclosure is shown. Figures 9A to 9C ), and with the imaging device ( Figure 9D and Figure 9E ) together.

[0027] Figure 10 is an exploded view of an example embodiment of an optical housing of an imaging device according to one aspect of the present disclosure.

[0028] Figure 11 is an example embodiment of a printed circuit board for use in an imaging device according to one aspect of the present disclosure.

[0029] Figure 12A and Figure 12BAn example hardware block diagram for use in the imaging device of the present disclosure is shown.

[0030] 13A to 13F Shown is not connected to ( 13A to 13C ) and connected to ( Figures 13D to 13E ) Example embodiments of a cover cloth for a portable handheld imaging device.

[0031] 14A to 14C The present invention is shown for use with an imaging device ( FIG. 14A to FIG. 14B ) and an example embodiment of a sterile drape for use with an imaging device connected to a darkening drape / imaging drape ( Figure 14C ) on the sterile drape over the imaging unit. DETAILED DESCRIPTION

[0032] Wound progression is currently monitored manually. The National Pressure Ulcer Advisory Panel (NPUAP) developed the Pressure Ulcer Healing Scale (PUSH) tool, which outlines a five-step approach to characterizing pressure ulcers. This tool uses three parameters to determine a quantitative score, which is then used to monitor changes in pressure ulcers over time. Qualitative parameters include wound size, tissue type, amount of exudate or drainage, and thermal readings after dressing removal. Wounds can be further characterized by their odor and color. This assessment of wounds currently does not include key biological and molecular information about the wound. Therefore, all descriptions of the wound are subjective and recorded manually by the attending physician or nurse.

[0033] A robust, cost-effective, noninvasive, and rapid imaging-based method or device is needed to objectively assess wound changes at the biological, biochemical, and cellular levels, and to rapidly, sensitively, and noninvasively detect the early presence of bacteria / microorganisms within wounds. Such a method or device for detecting key biological tissue changes in wounds could complement conventional clinical wound management methods to guide critical clinicopathological decisions in patient care. Such a device would be compact, portable, and capable of real-time, noninvasive and / or contactless interrogation of wounds in a safe and convenient manner. This would allow handheld imaging devices to seamlessly fit into conventional wound management practices and be user-friendly for clinicians, nurses, and wound specialists. Handheld imaging devices could also be used in home care settings (including patient self-use). Furthermore, such image-based devices could provide the ability to monitor wound treatment response and healing in real time by incorporating valuable "bioinformatic" image guidance into the clinical wound assessment process. This could ultimately lead to potential new diagnostics, treatment planning, treatment response monitoring, and "adaptive" intervention strategies, potentially allowing for enhanced wound healing responses at the individual patient level. Precise identification of the systemic, local, and molecular factors underlying wound healing problems in individual patients may allow for better tailored treatment.

[0034] Molecular light i:X The device has made great progress in solving many of the above problems. i:X The device allows clinicians to quickly, safely, and easily visualize bacteria and measure wounds at the point of care. i:X The basis of the device and methods of use are described in U.S. Patent No. 9,042,967, national phase application PCT / CA2009 / 000680, filed internationally on May 20, 2009, which claims the benefit of U.S. Provisional Application No. 61 / 054,780, filed on May 20, 2008, each of which is incorporated herein by reference in its entirety.

[0035] Another imaging device for visualizing cancer is disclosed in U.S. Provisional Application No. 62 / 625,983 (filed February 3, 2018), entitled “Devices, Systems, and Methods for Tumor Visualization and Removal,” and U.S. Provisional Application No. 62 / 625,967 (filed February 3, 2018), entitled “Devices, Systems, and Methods for Tumor Visualization and Removal,” and International Patent Application No. PCT / CA2019 / 000015 (filed February 1, 2019), entitled “Devices, Systems, and Methods for Tumor Visualization and Removal,” each of which is incorporated herein by reference in its entirety. Although disclosed in the context of visualizing cancer, the disclosed systems and methods relate to visualization and imaging of tissue autofluorescence and tissue fluorescence, and details regarding the construction, function, and operation of the exemplary devices described therein may be similar or identical to portions of the systems described herein.

[0036] The molecular light i:X device and the device disclosed in this application utilize tissue autofluorescence imaging, which provides a unique means of obtaining biologically relevant information about normal and diseased tissue in real time, thereby allowing differentiation between normal and diseased tissue states. Autofluorescence imaging devices can be used to rapidly, noninvasively, and contactlessly image wounds in real time to detect and utilize the rich biological information of wounds, overcoming existing limitations and improving clinical care and management.

[0037] This application discloses systems, methods, and devices for fluorescence-based imaging. One embodiment of the device is a portable optical digital imaging device. The device can utilize a combination of white light (WL) imaging, fluorescence (FL) imaging, infrared (IR) imaging, thermal imaging, and / or three-dimensional mapping, and can provide real-time wound imaging, assessment, recording / documentation, monitoring, and / or care management. The device can be handheld, compact, and / or lightweight. For example, the apparatus may include: at least one excitation light source configured to emit excitation light during fluorescence imaging; a first filter configured to detect and allow an optical signal to pass to a first image sensor, the optical signal being responsive to illumination of a target surface with the excitation light and having a wavelength corresponding to one or more of bacterial fluorescence, bacterial autofluorescence, tissue fluorescence, and tissue autofluorescence; a white light source configured to emit white light during white light imaging; a second filter configured to detect and allow an optical signal to pass to a second image sensor, the optical signal being responsive to illumination of the target surface with the white light and having a wavelength within the visible light range; and a processor configured to receive the detected fluorescence and white light optical signals and output a representation of the target surface to a display based on the detected optical signals. The apparatus and method may be applicable to monitoring wounds in humans and animals.

[0038] In another exemplary embodiment, the device can be a modular handheld imaging device. In such an embodiment, the device includes a base portion, also referred to herein as a base portion or base housing, and an optical portion, also referred to herein as an optical housing or optical housing portion. The optical portion is releasably received by the base portion and is interchangeable with other optical portions, each configured for a specific application or to capture specific features and optical information from an imaged object. Thus, a user will select an optical housing based on the imaging capabilities required in a given situation.

[0039] The modular handheld imaging device can be packaged and / or sold as part of a kit, wherein a base portion and two or more optical portions are provided, each optical portion having optical properties that differ from one another and from any other optical housing. Properties that can vary from one optical housing to another include, but are not limited to, the following, which can be included in any combination within each optical housing: the number of image sensors, the number of image sensors configured for white light imaging (i.e., in combination with filters for white light imaging); the number of image sensors configured for fluorescence imaging, wherein different image sensors for fluorescence imaging can be paired with different filters to allow different ranges of fluorescence emissions to pass, wherein each range is configured to capture specific features of a target (e.g., blood vessels or microvessels, collagen, elastin, blood, bone, bacteria, malignant tumors, lymphatic vessels, immune cells, adipose tissue, cartilage, tendon, nerves, gastrointestinal tissue, skin, pre-malignant or benign tissue, body fluids, urine, blood, saliva, tears, mucus, mucosal tissue, dermal tissue, and exogenous fluorescent agents, drugs, etc.).

[0040] The image sensor is configured to capture still images or video.

[0041] The number and type of excitation light sources may also vary between optical housings. The excitation light sources may be configured to emit excitation light having a wavelength of about 350 nm to about 400 nm, about 400 nm to about 450 nm, about 450 nm to about 500 nm, about 500 nm to about 550 nm, about 550 nm to about 600 nm, about 600 nm to about 650 nm, about 650 nm to about 700 nm, about 700 nm to about 750 nm, about 750 nm to about 800 nm, about 800 nm to about 850 nm, about 850 nm to about 900 nm, about 900 nm to about 950 nm, about 950 nm to about 1000 nm, and / or combinations thereof. The shape of the optical housing may also vary from one housing to another, depending on the specific application. For example, a specific shape may be used for specific applications, such as accessing confined anatomical spaces such as the alveoli, oral cavity, nasal cavity, anal area, abdominal area, ear, etc. In this case, the optical housing may be in the form of an endoscope attachment. The materials forming the optical housing can vary from one housing to another. For example, the housing can have a flexible or rigid patient-facing portion, depending on the application in which the imaging device will be used. In some embodiments, the optical housing can be made waterproof or water-resistant. In some embodiments, the housing can be made of a material that is inherently resistant to bacterial growth, or of a material with a surface texture or topology that resists microbial growth, such as a roughened nanosurface. The dimensions of the optical housing can vary depending on the size and number of components contained therein. Various exemplary embodiments of the optical housing can also include, in any combination, features such as ambient light sensors, rangefinders, thermal imaging sensors, structured light emitters, infrared radiation sources and detectors for three-dimensional imaging, lasers for taking measurements, and the like. Additionally or alternatively, the imaging device can also have external channels embedded in the housing to enable the delivery of tools such as biopsy forceps, fiber optic spectroscopy probes, or other tools that require (FL) image-guided targeting for tissue collection, ablation, cauterization, or interrogation of fluorescent tissue.

[0042] The base portion / base housing includes an interface configured to releasably receive the optical housing. The optical housing includes a portion configured to be received into the base portion in a manner that provides electrical and power connections between components in the optical housing and a battery and processor in the base portion. This connection enables data transfer between the optical housing and the base, which contains a processor configured to receive data from the image sensor. Furthermore, the base can be connected to a PC to store or analyze data from the modular imaging device.

[0043] In various exemplary embodiments, the base portion includes a heat sink. In one exemplary embodiment, the heat sink forms a lip around an opening in the base portion, the lip being configured to receive the optical housing.

[0044] In various example embodiments, the modular imaging device includes elements in the following various configurations:

[0045] FL Camera Sensor - A camera sensor configured to detect fluorescence wavelengths is used in fluorescence imaging mode (FL). Light incident on this sensor passes through a dual-band filter to allow visualization and capture of red and green fluorescence signals that may be present, such as those generated in response to illumination of a target with excitation light. In some embodiments, the filter can be configured to detect additional or fewer fluorescence signals.

[0046] WL Camera 1—When the modular imaging device is in white light (WL) imaging mode, the first white light (WL) camera sensor is used. Light incident on this sensor passes through a short-pass filter to allow the sensor to image visible wavelengths. The short-pass filter blocks infrared (IR) light that may be present in the clinical environment. The short-pass filter also blocks IR emitted by the rangefinder, if present.

[0047] WL Camera 2 - A second WL image sensor / camera sensor may be used as part of a stereo or 3D imaging (object depth) configuration of the modular imaging device.

[0048] Light incident on this sensor passes through a short-pass filter, allowing the sensor to image visible wavelengths. The short-pass filter blocks infrared (IR) light that may be present in the clinical environment. The short-pass filter also blocks IR emitted by the rangefinder (if present). When present, the second WL camera sensor must be aligned with the first.

[0049] Display - A high-resolution, wide color gamut display with touchscreen functionality may be provided. The touchscreen functionality allows the user to manipulate the image and also allows the display to serve as the primary user interface (UI) for the clinician / device operator, allowing for the entry of patient information that can be collated or registered in some manner with the captured image, either on the camera or when the information is uploaded to the cloud or other storage.

[0050] Batteries - Rechargeable batteries, for example, rechargeable lithium-ion batteries with integrated gas measurement functionality, can be used to power the modular imaging device. As will be appreciated, other types of batteries can be used or other power sources can be used.

[0051] Speaker - The speaker on the modular imaging device can be used to communicate with the user and may also generate camera click sounds and / or other sounds that enhance the user experience.

[0052] Battery Status LED - Indicates low battery status and the battery's charge status during charging operations.

[0053] System Status LED - Indicates system status by using on / off or different colors, providing a system OK / operating indication or indicating that there is an internal system problem.

[0054] Wi-Fi Antenna - Enables Wi-Fi communication. Wi-Fi communication is used for cloud storage of images, field updates of system software, and management of pay-per-use usage.

[0055] FL LED - The light source of the modular device may include an LED. In one example, excitation light, such as fluorescence excitation light, may be generated by a fluorescent (FL) LED. The fluorescence excitation light may be used to elicit fluorescence from bacteria, i.e., in response to illumination with the excitation light. The LED current is controlled using a closed-loop control, wherein the set point of the control loop is managed by the MCU. The nominal FL LED drive current set point is established during the device manufacturing process to meet minimum target optical irradiance and uniformity requirements. The optical efficiency of the LED is temperature dependent. A temperature sensor measures the temperature of a printed circuit board (PCB) near the LED, which is used as an input to a control loop that adjusts the nominal drive current set point to compensate for temperature-related variations in irradiance efficiency of the LED. As will be appreciated, other types of fluorescent light sources may be used in place of or in addition to the FL LED.

[0056] An ambient light sensor is provided to monitor the ambient light in the imaging environment near the imaging target. Fluorescence (FL) imaging requires a sufficiently dark environment to obtain useful images. The ambient light sensor is used to provide feedback to the clinician regarding the ambient light level. The ambient light level before the system enters FL imaging mode can be stored in the image metadata. The light level may be useful in later analysis. During white light imaging mode, the measured ambient light level may also be useful to enable or control the intensity of the WL flashlight. The ambient light sensor can be configured to indicate to the user when the imaging environment is dark enough to capture fluorescence images. This may take the form of providing an indication of whether the imaging environment is satisfactory or unsatisfactory, depending on the imaging mode.

[0057] Rangefinder - The rangefinder can be used to measure the distance between the camera sensor and the target being imaged. Minimum blue light irradiance and uniformity are effective over a range of camera to target distances. The rangefinder provides feedback to the clinician / user to guide them in imaging at the correct distance by providing an indication that the appropriate distance has been achieved. The target distance can be stored in the image metadata. The target distance can be useful to the sticker detection algorithm, which can be used in the measurement process to determine the minimum and maximum expected sticker size in sensor pixels as a function of the distance between the sticker and the camera sensor. In some embodiments, changes in the measured target distance can be used to initiate a camera sensor refocusing action.

[0058] Flashlight LED - During white light imaging mode, one or more white light sources can be provided to illuminate the target. The white light source can include one or more white light LEDs. Other white light sources can be used in addition to or in place of LEDs.

[0059] USB-C Port - A USB-C port is provided for battery charging, factory loading of software, factory testing and calibration of the device, and image downloads.

[0060] Additional or alternative ports may be provided for information transfer and / or billing.

[0061] Figures 1 to 5B An exemplary embodiment of a modular handheld imaging device 100 is shown in FIG. Figures 1 to 5B As shown, in some example embodiments, the base portion 110 of the device 100 can have a generally square or rectangular shape. The front, or user-facing side 115, of the base portion 110 includes a display screen 120 for displaying images and video captured by the device. Although depicted as square or rectangular, the device can take any shape that will reasonably support a display screen, such as a touchscreen display. In addition to displaying images captured by the imaging device 100, the display screen also serves as a user interface, allowing a user to control device functions via touchscreen input.

[0062] Positioned on the opposite side of the device, namely the patient-facing side 125 of the device, may be a handheld area 130 configured to facilitate a user holding the device during imaging. Figure 4 As shown, the hand-held area may include a protrusion or an area extending away from the base portion 110 sufficiently to allow the user's fingers to grasp or wrap around the protrusion. Various other types of hand-held and alternative positioning of the hand-held can be used. One factor to consider in the position of such a hand-held is the user's ability to balance the imaging device while using the imaging device and inputting commands via the touch screen display. The weight distribution of the imaging device will also be a consideration in providing a user-friendly and ergonomic device. The patient-facing side 125 of the device may also include contacts 135 for wireless charging of the device.

[0063] like Figures 9A to 9EAs shown, a charging station 136 can be provided for wirelessly charging the device 100. As shown in an example embodiment, the charging station 136 can include contacts, such as contact pins 137, for wirelessly charging the device 100. The contact pins 137 can be spring-loaded and can be separated from each other in a manner that prevents short circuits caused by inadvertent placement of other objects (i.e., small metal objects) on the contact pins 137. In one example, a raised portion of a surface of the charging station 136, such as a protrusion, can separate the contact pins 137. The charging station 136 can also include an indicator light 138 that engages / illuminates when the device 100 is properly placed on the charging station 136 for charging. Additionally or alternatively, the indicator light 138 can indicate when the device 100 is fully charged.

[0064] According to one aspect of the present disclosure, the patient-facing side 125 of the device 100 further includes an optical housing 140. Figures 5A to 5B As shown, the optical housing 140 can be separated from the base portion 110. The optical housing portion 140 is shown as a rectangular housing configured to be received in a rectangular opening 145 in the base portion 110. However, both the optical housing portion 140 and the opening 145 can take other shapes, such as square, rectangular, oval, or circular. In addition, the optical housing portion 140 need not have the same shape as the opening 145. Instead, a connector element having the same shape as the opening 145 of the base portion 110 or otherwise configured to be received in the opening 145 of the base portion 110 can be used as a bridge to connect the optical housing portion 140 to the base portion 110. The opening 145 is configured to releasably receive the optical housing portion 140. When the optical housing portion 140 is positioned in the opening 145, it can be locked into place, locking the optical housing portion 140 to the base portion 110. In this configuration, electrical contact is made between the base portion 110 and the optical components contained in the optical housing portion 140 , and the components in the optical housing portion are powered by a power source (eg, a battery) contained in the base portion 110 .

[0065] In various exemplary embodiments, the base portion 110 includes a heat sink 150. In one exemplary embodiment, the heat sink 150 forms a lip around the opening 145 in the base portion 110 that is configured to receive the optical housing portion 140.

[0066] like Figure 5A and Figure 5B As shown, the optical housing 140 can take different shapes or configurations. Figure 5A As shown, the optical housing portion 140 has a generally flat rectangular shape. The optical components are arranged in a generally linear manner across the width of the optical housing. Figure 5BA second optical housing 185 is shown, which includes an endoscopic portion 190. Unlike optical housing portion 140, the optical components contained in second optical housing 185 are contained within a distal tip 195 of the endoscopic portion 190 of second optical housing 185 and are not arranged in a linear fashion. The arrangement of the optical components in each optical housing will vary based on the size and shape of the optical housing and the number and type of optical components contained in a given housing.

[0067] The optical housing portion 140 may include various optical components configured to facilitate the collection of optical signals from the target being imaged. Properties that may vary from one optical housing to another include the following non-limiting examples, which may be included in any combination within each optical housing: the total number of image sensors, the number of image sensors configured for white light imaging (i.e., in combination with filters for white light imaging); the number of image sensors configured for fluorescence imaging, where different image sensors for fluorescence imaging may be paired with different filters to allow different ranges of fluorescence emissions to pass, where each range is configured to capture specific features of the target (e.g., blood vessels or microvessels, collagen, elastin, blood, bone, bacteria, malignant tumors, healthy or diseased cartilage, ligaments, tendons, connective tissue, lymphatic vessels, nerves, muscles, etc.).

[0068] The optical housing portion 140 may include one or more excitation light sources. The excitation light source may provide excitation light of a single wavelength, the excitation light being selected to excite tissue autofluorescence emission and fluorescence emission of induced porphyrins in tumor / cancer cells. Additionally or alternatively, the excitation light source may provide excitation light of a wavelength selected to excite bacterial autofluorescence emission and / or exogenous fluorescence emission from one or more of tissue and bacteria in the wound. In one example, the excitation light may have a wavelength in the range of about 350 nm to about 600 nm, or 350 nm to about 450 nm and 550 nm to about 600 nm, or, for example, 405 nm, or, for example, 572 nm.

[0069] Alternatively, the excitation light source can be configured to provide excitation light of two or more wavelengths. As those skilled in the art will appreciate, the wavelength of the excitation light can be selected for different purposes. For example, by varying the wavelength of the excitation light, the depth to which the excitation light penetrates a target surface, such as a surgical bed or wound, can be varied. Since penetration depth increases with increasing wavelength, light of different wavelengths can be used to excite tissue beneath the target surface. 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) can penetrate the target tissue to different depths, for example, approximately 500 pm to approximately 1 mm and approximately 2.5 mm, respectively. This allows the device user, such as a physician, surgeon, or pathologist, to visualize tissue cells at the target surface and beneath the target surface. Additionally or alternatively, excitation light with a wavelength in the near-infrared / infrared range can be used, for example, excitation light with a wavelength between approximately 750nm and approximately 800nm, such as 760nm or 780nm. Furthermore, to penetrate deeper into the tissue, this type of light source can be combined with a second type of imaging / contrast agent, such as an infrared dye (e.g., IRDYE 800, ICG). This would, for example, enable visualization of vascularization, vascular perfusion, and blood pooling within the target tissue. Furthermore, visualization of vascular perfusion could be useful for improving anastomosis during reconstruction or for observing wound healing.

[0070] Imaging device 100 may include an additional light source, for example, a white light source for white light (WL) imaging of the target surface. White light is used to provide anatomical context for other images, such as fluorescence images. The white light source may include one or more white light LEDs. Other white light sources may be used as appropriate. As will be understood by those skilled in the art, the white light source should be stable and reliable and should not overheat during extended use.

[0071] The base portion 110 of the imaging device 100 may include controls that allow switching / converting between white light imaging and fluorescence imaging. These controls may also enable the use of various excitation light sources, either together or individually, in various combinations, and / or sequentially. These controls may cycle through various light source combinations, control the light sources sequentially, strobe the light sources, or otherwise control the timing and duration of light source use. As will be appreciated by those skilled in the art, these controls may be automatic, manual, or a combination thereof. As described above, the touchscreen display 120 of the base portion 110 may serve as a user interface to allow control of the imaging device 100. Alternatively, it is contemplated that separate controls, such as manual controls (e.g., buttons), may be used in place of or in addition to the touchscreen controls. For example, such manual controls may be located on the handle 130 to allow the user to easily actuate the controls while holding and using the imaging device.

[0072] The optical housing portion 140 of the imaging device 100 may further include one or more optical imaging filters configured to prevent reflected excitation light from passing through the camera sensor. In one example, the optical imaging filter may further be configured to allow emission having a wavelength corresponding to autofluorescence emission of tissue cells and fluorescence emission of porphyrins induced in tissue cells to pass through. In another example, the device 100 may include one or more optical imaging filters configured to allow emission corresponding to autofluorescence emission of bacteria contained in the target and exogenous fluorescence emission of bacteria generated by the use of a contrast agent on the target surface to pass through. The imaging device 100 may further include a filter configured to capture fluorescence and autofluorescence of both bacteria and tissue.

[0073] These optical filters can be selected to detect specific optical signals from the target / tissue / wound surface based on the desired wavelength of light. For example, liquid crystal tunable filters (LCTFs) or acousto-optic tunable filters (AOTFs), which are solid-state, electronically tunable spectral bandpass filters, can also be used to achieve spectral filtering (e.g., absorption, fluorescence, reflectivity) of the detected optical signals. Spectral filtering can also involve the use of continuously variable filters and / or manually bandpass optical filters. These filters / filtering mechanisms can be placed in front of the imaging sensor to produce multispectral, hyperspectral, and / or wavelength-selective imaging of tissue.

[0074] The imaging device 100 can be modified by using optical or variable-orientation polarization filters (e.g., linear or circular, in combination with waveplates) attached to the excitation / illumination light source and imaging sensor in a suitable manner. In this manner, the imaging device 100 can be used to image a target surface using white light reflectance and / or fluorescence imaging with polarized illumination and unpolarized detection, or vice versa, or with polarized illumination and polarized detection. This can allow wounds to be imaged with minimal specular reflection (e.g., glare from white light imaging), as well as enabling imaging of changes in fluorescence polarization and / or anisotropy in connective tissue (e.g., collagen and elastin) in normal tissue within and surrounding the wound. This can yield useful information about the spatial orientation and organization of connective tissue fibers associated with wound remodeling during the healing process [Yasui et al., (2004) Appl. Opt. 43: 2861-2867].

[0075] exist Figure 10 In one example embodiment shown, imaging device 200 includes three camera sensors 260, 265, and 270, each including a fixed filter 261, 266, and 271. For example, first and second white light sensors may be provided, each configured to receive visible light signals via a dedicated filter fixed to the respective sensor. Alternatively, a sensor for fluorescence imaging may be configured to allow various desired emission wavelengths to pass through to the fluorescence camera sensor. As previously described, different optical housing portions may contain different configurations of sensors, filters, and light sources, which together are configured to create an image of a specific feature of a target.

[0076] Figure 10 2 shows an exploded view of the optical housing 240 of the imaging device 200. Figure 10 As shown, base portion 210 may include a heat sink 212 positioned behind heat sink 250 of optical housing 240. Optical housing 240 may further include three camera sensors 260, 265, 270, a printed circuit board (PCB) 273, an external heat sink spacer 252, a camera cover 244, three filters 261, 266, 271, a light diffuser 253 for a white light source, an internal spacer / filter holder 274, windows 275a, 275b, 275c, tape 276 (or other means for securing the windows), and a lens assembly tip 280, which may include features to allow attachment of accessories.

[0077] As will be appreciated by those skilled in the art, the arrangement of components within the optical housing of an imaging device can take on a variety of configurations. This configuration may be influenced by the size of the device, the device's footprint, and the number of components used. However, functional considerations should also be taken into account when arranging the components. For example, issues such as light leakage from the device's light source and / or ambient light entering the optical housing may interfere with proper or optimal operation of the device and, for example, may result in less than desirable outputs, such as image artifacts. Figure 10 The arrangement shown in is one in which the camera sensor is isolated to prevent light leakage from the light source and ambient light.

[0078] Figure 11 An example PCB 273 is shown in FIG. As shown, the PCB can include an excitation light source 302, such as two fluorescent LEDs, for example, violet / blue LEDs having a wavelength between about 400 nm and about 450 nm, and in one example, about 405 nm. Additional LEDs having the same wavelength can be provided, or only one LED can be used. In addition, it is contemplated that additional excitation light sources having different wavelengths can be provided. The PCB 273 can also include two temperature sensors 304, a white light or flashlight LED 306 that provides white light for white light imaging, an ambient light sensor 308, and a rangefinder 312, which can be, for example, a laser-based rangefinder.

[0079] When device 100 or 200 is held above the target tissue surface (e.g., a wound) to be imaged, an illumination light source can illuminate the tissue / wound surface with narrow-band or broadband violet / blue wavelengths, or other wavelengths or wavelength bands, thereby generating a flat and uniform light field within the region of interest. The light also illuminates or excites the tissue down to a shallow depth. This excitation / illumination light interacts with normal and diseased tissue and can generate an optical signal (e.g., absorption, fluorescence, and / or reflection) within the target tissue, which is then captured by one of the camera sensors.

[0080] By varying the excitation and emission wavelengths accordingly, the imaging devices 100, 200 can interrogate target tissue components (e.g., connective tissue and bacteria within a wound) at both the surface and at specific depths within a target tissue (e.g., a wound). For example, by shifting from violet / blue (approximately 400-500 nm) wavelengths of light to green (approximately 500-540 nm) wavelengths of light, excitation of tissue / bacterial fluorescence sources deeper within a wound can be achieved. Similarly, by detecting longer wavelengths, fluorescence emissions from tissue at the tissue surface and / or bacterial sources deeper within the tissue can be detected. The ability to interrogate surface and / or subsurface fluorescence can be useful for wound assessment, for example, to detect and potentially identify bacterial contamination, colonization, critical colonization, and / or infection, which may occur both at the surface and deep within a wound (e.g., in chronic, non-healing wounds).

[0081] The handheld imaging device 100, 200 also includes an imaging lens and an image sensor in the optical housing portion 140, 240 of the device. The imaging lens or lens assembly can be configured to focus the filtered autofluorescence emission and fluorescent emission on the image sensor. A wide-angle imaging lens or a fisheye imaging lens is an example of a suitable lens. The wide-angle lens can provide a 180-degree field of view. The lens can also provide optical magnification. The imaging device requires very high resolution so that it can distinguish between very small cell populations. The image sensor is configured to detect filtered autofluorescence emission of tissue cells and fluorescent emission of induced porphyrins in tissue cells. The image sensor can have 4K video capability as well as autofocus and optical or digital zoom capabilities. CCD or CMOS imaging sensors can be used. In one example, a CMOS sensor combined with a filter, i.e., a hyperspectral image sensor, such as those sold by Ximea, can be used.

[0082] Example filters include a visible light filter (https: / / www.ximea.com / en / products / hyperspectral-cameras-based-on-usb3-xispec / mq022hq-im-sm4x4-vis) and an infrared filter (https: / / www.ximea.com / en / products / hyperspectral-cameras-based-on-usb3-xispec / mq022hg-im-sm5x5-nir). The handheld device 100, 200 may also include a processor configured to receive detected emissions and output data regarding the detected filtered autofluorescence and / or exogenous fluorescence emissions. The processor may be capable of seamlessly running synchronized programs (including, but not limited to, wireless signal monitoring, battery monitoring and control, temperature monitoring, image acceptance / compression, and button press monitoring). The processor interfaces with internal memory, physical controls (e.g., buttons, optics, and wireless modules). The processor also has the capability to read analog signals.

[0083] The imaging device 100, 200 may also include a wireless module and be configured for fully wireless operation. It can utilize high-throughput wireless signals and has the ability to transmit high-definition video with minimal delay. The device can enable Wi-Fi and Bluetooth simultaneously - Wi-Fi for data transmission and Bluetooth for fast connection. The device can operate using the 5GHz wireless transmission band to be isolated from other devices. In addition, the device is capable of operating as a soft access point, which eliminates the need to connect to the Internet and keeps the device and module isolated from other devices related to patient data security. The device can 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.

[0084] Figure 12A and Figure 12B An alternative embodiment of a hardware block diagram of the apparatus 100 , 200 is shown. Figure 12A and Figure 12B An example block diagram illustrating various components of a handheld imaging device 100 , 200 according to an example embodiment of the present disclosure is shown.

[0085] The components of the handheld imaging device 100, 200 can be grouped in the optical PCB and the electronic system. Figure 12B In an embodiment of the present invention, the optical PCB includes four fluorescent wavelength LEDs, two infrared LEDs, and two white light LEDs. The optical PCB further includes an ambient light sensor, a laser rangefinder, and a temperature sensor.

[0086] The optical PCB is operably coupled to an electronic system 302. The electronic system may include, for example, but not limited to, electronic control components, such as an application processor module, a real-time microcontroller unit (MCU), and a power management subsystem. The electronic system may further include components and systems that interface with other electronic components of the handheld imaging device. For example, the electronic system may include a CMOS camera interface and motor drive electronics for the optical filter system. The electronic system may also include connectors for fluorescence and white light cameras, respectively, to facilitate switching between fluorescence and white light imaging modes as discussed herein. Although in Figure 12B Only two cameras are shown, a white light camera and a fluorescence camera, but the present disclosure contemplates the use of additional cameras, specifically white light cameras. For example, Figure 12A The example block diagram of discloses the presence of three cameras, two white light cameras and one fluorescence camera. The addition of additional cameras is within the scope of the present disclosure.

[0087] Other supporting electronic systems and components of the electronic systems may include memory (e.g., flash memory devices), rechargeable batteries (e.g., lithium-ion batteries), and inductive battery charging systems. Some components of the electronic systems may include communication components (e.g., Wi-Fi and / or Bluetooth radio subsystems), and spatial orientation components, such as one or more of a magnetometer, an accelerometer, and a gyroscope.

[0088] The electronic system may include various user controls, such as a power switch, a system status LED, a charging status LED, a picture capture switch, a video capture switch, and an imaging mode switch. The various user controls may interface with other components of the electronic system through a user interface module, which provides signals to and from the user controls.

[0089] Other components in the electronic system may include drivers for fluorescent, infrared, and white light LEDs, a USB hub for uplink or downlink data signals, and / or a power supply from an external computer system. The electronic system may be connected to an external computer system, such as a workstation or other computer, via a USB hub. The electronic system may also include one or more devices for providing feedback to the user, such as, but not limited to, speakers. Other feedback devices may include various audible and visual indicators, tactile feedback devices, displays, and other devices.

[0090] The modular handheld imaging devices 100 and 200 of the present application can be used with a variety of accessories. For example, the devices 100 and 200 can be used with a drape that is configured to darken the area around the target being imaged by blocking or reducing ambient light around the target. The drape can include an adapter that is configured to be mounted on the patient-facing side of the optical housing and is configured to isolate and / or separate the optical components of the optical housing from ambient light by forming a barrier between the optical components of the optical housing. Examples of the types of drapes used with the device can be found, for example, in U.S. Provisional Patent Application No. 62 / 669,009, filed on May 9, 2018, entitled “Darkening Drape, Packaging for Drape, Method of Use and Method for Deploying Drape,” International Patent Application PCT / CA2019 / 000061, filed on May 9, 2019, entitled “IMAGING DRAPES, PACKAGING FOR DRAPES, METHODS OF USE OF IMAGING DRAPES, AND METHODS FOR DEPLOYING DRAPE,” U.S. Design Patent Application No. 29 / 647,110, filed on May 9, 2018, entitled “Darkening Drape,” and Design Application No. 29 / 676,893, filed on January 15, 2019, entitled “Adaptor for Supporting a Darkening Drape.” Drape," each of which is incorporated herein by reference in its entirety.

[0091] According to an example embodiment, a darkening drape 500 is disclosed. 13A to 13C An example embodiment of an imaging drape 500 is shown. The imaging drape 500 is shown connected to an imaging device, such as previously described. Figures 13D to 13F, 200 discussed in . The cover cloth 500 can be used in conjunction with any of the imaging devices disclosed herein. The cover cloth 500 includes a connecting element 501. In an example embodiment, the connecting element 501 includes a ridge 510 that is used to form a press-fit or snap-fit connection with the imaging device 100, 200. Protrusions on the imaging device 100, 200 (described below) can engage with the ridge 510 to provide a press-fit or snap-fit connection. Additionally, one or more protrusions 520 can be configured to engage with the protrusions on the imaging device 100, 200 to grip the imaging device 100, 200 and better secure it to the cover cloth. In some embodiments, the protrusions 520 are tooth-like members that engage with the protrusions on the imaging device. When the imaging device is properly aligned and pressed down into the connecting element, the protrusions 520 clip into the protrusions on the imaging device to provide a snap-fit connection.

[0092] The connecting element 501 may also include an end cup member 550 to help facilitate a snap-fit connection between the connecting element 501 and the imaging device. Figure 13A As shown, end cup member 550 may be a smooth member disposed on either end of opening 533 formed in connecting element 501. End cup member 550 may provide a guide to center / position an imaging head / optical head of an imaging device snap-fitted into connecting element 501.

[0093] Figure 13A The opening 533 is shown as having a rectangular shape, with the protrusion 520 disposed on the long side of the rectangle and the end cup member 550 disposed on the short side of the rectangle. However, it is also conceivable that the protrusion 520 may be disposed on the short side of the rectangle and the end cup member 550 may be disposed on the long side of the rectangle. Figure 13A Two end cup members 550 are shown, but only one end cup member 550 may be used on one side of the opening 533. Furthermore, in some embodiments, the connecting element 501 may not include an end cup member 550. In such an embodiment, the protrusions 520 may be disposed around most or the entire perimeter of the opening 533 in the connecting element 501. As described above, the connecting element 501 may be formed from injection molded plastic.

[0094] Figure 13A A top perspective view of the connecting element 501 secured to the drape is shown. Figure 13B Shows a top view of the connecting element 501 and an external view of the cover cloth, Figure 13C Shown is a bottom view of the connecting element 500 and a view of the portable imaging environment formed by the interior of the cover.

[0095] The connecting element 501 may also include a top flat surface 503, a one-way valve such as a flap valve 555, and a protrusion 554. As shown, the protrusion 554 is arranged on the top surface of the connecting element 501. Thus, the protrusion 554 is Figure 13B The top view is visible, but Figure 13C The projections 554 help keep the drape material out of the imaging field of view.

[0096] exist 13A to 13F In some embodiments, the connecting element 501 may be formed from an injection molded plastic such as polyethylene. Thus, the connecting element 501 can be a relatively rigid member. In some embodiments, the connecting element 501 has a thickness of approximately 1.8 mm. The protrusion 554 may be formed from the same material as the rest of the connecting element 501, but may be less rigid than the rest of the connecting element 501. Thus, the protrusion 554 may be thinner than the rest of the connecting element 501. The material of the drape body may be formed from the same material as the connecting element 501, but may not be injection molded, such that the material of the drape body is not as hard as the connecting element 501 (including the protrusion 554). In some embodiments, the material of the drape body is also thinner than that of the connecting element 501 (including the protrusion 554). The drape body may be formed from a soft material welded to the relatively hard material of the connecting element 501. This may reduce manufacturing costs by allowing the flap valve 555 to be integrated into the drape by being formed from the material of the drape body.

[0097] The connecting element 501 also includes an opening 533 to provide FL and / or white light imaging within the interior environment of the drape from the imaging device 100, 200. 13A to 13C In the embodiment of the present invention, the shape of the opening 133 is generally rectangular. However, it is further contemplated that other shapes may be used.

[0098] Figures 13D to 13F Shown is fixed to 13A to 13C , an example of an imaging device 600 with a connecting element 501 of a drape is shown in . The imaging device 600 can be configured as described with respect to the devices 100, 200 discussed above. The imaging device 600 is securely fastened to the connecting element 501 by a snap fit connection that prevents / reduces any ambient light from entering the interior of the drape through the top of the drape. As described above, the protrusions on the imaging device 600 can engage with the protrusions 520 and ridges 510 on the connecting element 501 to provide a snap fit connection.

[0099] The present disclosure provides an example embodiment of a modular handheld imaging device 600. The imaging device 600 includes a base portion having a generally square or rectangular shape. The front, or user-facing, side of the base portion includes a display screen for displaying images and video captured by the device. A protrusion protrudes outwardly from the optical head / optical housing, although it can alternatively be positioned on the base portion. While the protrusion is positioned on the top of the base portion in the example embodiment, it is also contemplated that the protrusion could be positioned on another side of the base portion, depending on the location of the protrusion 520 on the connecting element 501.

[0100] Although depicted as a square or rectangular, imaging device 600 may take any shape that will reasonably support a display screen such as a touch screen. In addition to disclosing images captured by imaging device 600, the display screen also serves as a user interface, allowing a user to control functions of the device via touch screen input.

[0101] Positioned on the opposite side of the device, ie, the patient-facing side of the device, may be a handheld area configured to facilitate a user holding the device during imaging. The patient-facing side of the device may also contain contacts for wireless charging of the device.

[0102] According to one aspect of the present disclosure, the patient-facing side of the device 600 further includes an optical housing. The optical housing is detachable from the base portion. The optical housing portion is shown as a rectangular housing configured to be received in an opening of the connecting element on the drape.

[0103] The optical housing can be configured in various ways. For example, the optical housing portion can have a generally flat rectangular shape. The optical components for FL and / or white light imaging are arranged in a generally linear manner across the width of the optical housing. The optical components are described in more detail below.

[0104] According to another aspect of the present disclosure, the imaging device 100, 200, 600 of the present disclosure may be used with a sterile drape. The sterile drape is configured to form a sterile barrier between the imaging device 100, 200, 600 and the environment in which the imaging device is used. 14A to 14C An example embodiment of a sterile drape for use with the imaging device of the present disclosure is shown. Figure 14A As shown, the sterile drape 700 can be configured to receive the body of the imaging device 800. When the sterile drape is positioned over the imaging device 800, the imaging device can engage with the darkening drape 500, as described above with respect to FIG. 13A to 13F As discussed and Figure 14B and Figure 14C shown.

[0105] The optical housings may be configured such that a single adapter will fit all optical housings to attach the darkening drape. Alternatively, a separate adapter may be provided to engage each optical housing.

[0106] According to one aspect of the present disclosure, a modular handheld device can be used to obtain a three-dimensional fluorescence image of a target. Systems and methods for obtaining such three-dimensional images are disclosed in U.S. Provisional Application No. 62 / 793,837, filed on January 17, 2019, entitled “Systems Methods, and Devices for Three-Dimensional Imaging, Measurement, and Display of Wounds and Tissue Specimens,” the entire contents of which are incorporated herein by reference.

[0107] Other uses for the device may include:

[0108] • Clinical and research-based imaging of small and large animals (e.g., veterinary).

[0109] •Detect and monitor contamination (e.g., bacterial contamination) during food / animal product preparation in meat, poultry, dairy, fish, and agriculture.

[0110] •Detection of “surface contamination” (e.g., bacterial or biological contamination) in public (e.g., healthcare) and private settings.

[0111] •Multispectral imaging and detection of cancer in human and / or veterinary patients.

[0112] •As a research tool for multispectral imaging and monitoring of cancer in experimental animal models of human disease (e.g., wounds and cancer).

[0113] •Forensic testing, e.g., latent fingerprints and biological fluids on non-biological surfaces.

[0114] •Imaging and monitoring of plaque, carriage, and cancer in the oral cavity.

[0115] •Imaging and monitoring devices for clinical microbiology laboratories.

[0116] •Testing of antimicrobials (e.g., antibiotics), disinfectants.

[0117] The device may generally include: i) one or more excitation / illumination light sources and ii) one or more image sensors, which may be combined with one or more optical emission filters or spectral filtering mechanisms. The device may have a viewing / control screen (e.g., a touchscreen), image capture, and zoom controls. The device may also have: iii) a wired and / or wireless data transmission port / module, and iv) a power supply and power / control switch.

[0118] The device may include software that allows the user to control the device, including control of imaging parameters, visualization of images, storage of image data and user information, transmission of images and / or related data, and / or related image analysis (e.g., diagnostic algorithms). The device may also include software for measuring the imaged target and calculating the quantity of various items found in the imaged target. For example, if the target is a wound, the device may include software configured to calculate wound size, wound depth, wound perimeter, wound area, wound volume, identify various tissue types within the wound (collagen, elastic, vascular), and the percentage of each tissue type within the wound. Furthermore, the device may determine the amount or number of bacteria in the wound, the bacterial load, and differentiate between various types of bacteria within the load and identify relative percentages. Examples of suitable software and methods are described, for example, in U.S. Provisional Patent Application No. 62 / 625,611, entitled “Wound Imaging and Analysis,” filed on February 2, 2019, and International Patent Application No. PCT / CA2019 / 000002, entitled “Wound Imaging and Analysis,” filed on January 15, 2019, the entire contents of each of which are incorporated herein by reference.

[0119] The device can be configured to co-register white light images, fluorescence images, thermal images, and other images of a target. The device can be configured to create a three-dimensional map of the target. The device can be configured to enhance color differentiation between different tissue types identified in the image. The device can be configured to determine the tissue classification of the target based on different colors or image features captured in the fluorescence image. The device can be configured to delineate between diseased tissue and healthy tissue therein, providing a map for a user to selectively remove diseased tissue while preserving surrounding healthy tissue in a targeted manner.

[0120] Various types of filters, power supplies, light sources, excitation light sources, image sensors, and charging configurations may be present in the presently disclosed devices. Examples of such components are described in U.S. Patent No. 9,042,967, national phase application PCT / CA2009 / 000680, filed internationally on May 20, 2009, which claims the benefit of U.S. Provisional Application No. 61 / 054,780, filed on May 20, 2008, the entire contents of each of which are incorporated herein by reference. Additional components are disclosed in U.S. Provisional Application No. 62 / 625,983, entitled “Devices, Systems, and Methods for Tumor Visualization and Removal,” filed on February 3, 2018, and U.S. Provisional Application No. 62 / 625,967, entitled “Devices, Systems, and Methods for Tumor Visualization and Removal,” filed on February 2, 2018, the entire contents of each of which are incorporated herein by reference. Additional components are disclosed in U.S. Provisional Patent Application No. 62 / 793,764, filed on January 17, 2019, entitled “Multimodal System for Visualization of Disease,” and U.S. Provisional Patent Application No. 62 / 857,155, filed on June 4, 2019, entitled “DEVICES, SYSTEMS, AND METHODS FORTUMOR VISUALIZATION,” the entire contents of each of which are incorporated herein by reference.

[0121] The imaging systems and methods disclosed herein can rely on tissue autofluorescence and bacterial autofluorescence, as well as autofluorescence of other target materials. Additionally or alternatively, the present application contemplates the use of exogenous contrast agents, which can be applied topically, ingested, or otherwise. Examples of such agents are disclosed in U.S. Patent No. 9,042,967, national phase application PCT / CA2009 / 000680, filed internationally on May 20, 2009, which claims the benefit of U.S. Provisional Application No. 61 / 054,780, filed on May 20, 2008, each of which is incorporated herein by reference in its entirety. Additional components are disclosed in U.S. Provisional Application No. 62 / 625,983, filed on February 3, 2018, entitled “Devices, Systems, and Methods for Tumor Visualization and Removal,” and U.S. Provisional Application No. 62 / 625,967, filed on February 2, 2018, entitled “Devices, Systems, and Methods for Tumor Visualization and Removal,” each of which is incorporated herein by reference in its entirety. Additional components are disclosed in U.S. Provisional Patent Application No. 62 / 793,764, filed on January 17, 2019, entitled “Multimodal System for Visualization of Disease,” and U.S. Provisional Patent Application No. 62 / 857,155, filed on June 4, 2019, entitled “DEVICES, SYSTEMS, AND METHODS FORTUMOR VISUALIZATION,” each of which is incorporated herein by reference in its entirety.

[0122] The device interface ports can support wired (e.g., USB) or wireless (e.g., Bluetooth, WiFi, and similar modes) data transmission to various external devices or third-party add-on modules, such as: head-mounted displays, external printers, tablets, laptops, personal desktop computers, wireless devices that allow imaging data to be transmitted to remote sites / other devices, global positioning system (GPS) devices, devices that allow the use of additional memory, and microphones.

[0123] The device can be used to guide wound debridement and identify bacteria types to help determine appropriate treatment / medication / antibiotics.

[0124] The device can also be attached to a mounting mechanism (e.g., a tripod or stand) to be used as a relatively stationary optical imaging device for white light, fluorescence, and reflectance imaging of objects, materials, and surfaces (e.g., the body). This may allow the device to be used on a desk or table, or for "assembly line" imaging of objects, materials, and surfaces. In some embodiments, the mounting mechanism can be mobile.

[0125] Other features of the device may include digital image and video recording capabilities, audio, documentation methods (e.g., image storage and analysis software), and wired or wireless data transmission for telemedicine / e-health needs.

[0126] In addition to providing detection of bacterial strains, the device can also be used to distinguish the presence and / or location of different bacterial strains (e.g., Staphylococcus aureus or Pseudomonas aeruginosa), for example, within a wound and surrounding tissue. This is likely based on the distinct autofluorescence emission signatures of different bacterial strains, including those within the 490-550 nm and 610-640 nm emission bands when excited by violet / blue light (e.g., light around 405 nm). Other wavelength combinations can be used to distinguish other species within the image. This information can be used to select appropriate treatments, such as antibiotics.

[0127] The device can be scanned over any wound (e.g., on the surface of the body) so that the excitation light illuminates the wound area. The device can then be used to examine the wound, allowing the operator to view the wound in real time, for example, via a viewer on the imaging device or through an external display device (e.g., a heads-up display, television display, computer monitor, LCD projector, or head-mounted display). Images obtained from the device can also be transmitted in real time (e.g., via wireless communication) to a remote viewing site, for example, for telemedicine purposes, or sent directly to a printer or computer storage. Imaging can be performed during routine clinical assessments of patients with wounds.

[0128] Prior to imaging, fiducial markers can be placed on the skin surface near the wound edge or perimeter (e.g., using an indelible fluorescent ink pen). For example, four dots can be placed near the wound edge or border on the surface of normal skin, each with a different fluorescent ink color from a separate indelible fluorescent ink pen, which can be provided to the clinician as a kit. These colors can be imaged by the device using excitation light and a multispectral band filter that matches the emission wavelengths of the four ink dots. Image analysis can then be performed by co-registering the fiducial markers for inter-image alignment. Thus, the user may not have to align the imaging device between different imaging sessions. This technology can facilitate longitudinal (i.e., over time) imaging of wounds, allowing clinicians to image wounds over time without having to align the imaging device during each image acquisition.

[0129] Additionally, to aid intensity calibration of fluorescence images, a disposable, simple fluorescence standard "strip" can be placed into the field of view during wound imaging (e.g., by temporarily adhering the strip to the skin using a mild adhesive). This strip can be impregnated with one or several fluorescent dyes of varying concentrations that produce a predetermined and calibrated fluorescence intensity when illuminated by an excitation light source, which can have a single (e.g., 405 nm) or multiple fluorescence emission wavelengths or wavelength bands used for image intensity calibration. The disposable strip can also have four dots as described above (e.g., each of a different diameter or size, each of a different fluorescent ink color, with a unique black dot placed next to it), drawn from separate, non-erasable fluorescent ink pens. The strip is placed near the wound edge or border on the surface of normal skin, and the device can be used to capture both white light and fluorescence images. This strip can provide a convenient way to capture multiple images of a given wound over time and then align the images using image analysis. Furthermore, the fluorescence "intensity calibration" strip can also incorporate an additional linear measurement device, such as a fixed-length ruler, to facilitate measurement of spatial distances within the wound. Such a strip may be an example of a calibration target that may be used with the device to help calibrate or measure image parameters (eg, wound size, fluorescence intensity, etc.), and other similar calibration targets may be used.

[0130] It may be desirable to increase the consistency of imaging results and to reproduce the distance between the device and the wound, since tissue fluorescence intensity may vary slightly if the distance changes during multiple imaging sessions. Therefore, in embodiments, the device may have a rangefinder to determine a fixed or variable distance between the device and the wound surface.

[0131] The device can be used to capture white-light images of the entire wound with normal surrounding tissue using a measuring device (e.g., a ruler) placed within the imaging field of view. This may allow for visual assessment of the wound and calculation / determination of quantitative parameters such as wound area, perimeter, diameter, and topographic contour. Wound healing can be assessed by taking planimetric measurements of the wound area at multiple time points (e.g., during a clinical visit) until the wound is healed. The time course of wound healing can be compared to the expected healing time calculated from multiple time-point measurements of the decrease in wound radius using the equation R = √A / π (R, radius; A, planimetric wound area; π, a constant of 3.14). This quantitative information about the wound can be used to track and monitor changes in wound appearance over time to assess and determine the extent of wound healing, whether induced by natural means or any therapeutic intervention. This data may be electronically stored in the patient's health record for future reference. White-light imaging can be performed during the operator's initial clinical assessment of the patient.

[0132] The device can be designed to detect all or most tissue autofluorescence (AF). For example, using multispectral band filters, the device can image tissue autofluorescence emitted from the following tissue biomolecules, as well as blood-related optical absorption, for example, under 405 nm excitation: collagen (types I, II, III, IV, V, and others), which appear green; elastin, which appears green-yellow-orange; reduced nicotinamide adenine dinucleotide (NADH); flavin adenine dinucleotide (FAD), which emits a blue-green autofluorescence signal; and bacteria / microorganisms, most of which appear to have a broad (e.g., green and red) autofluorescence emission.

[0133] Image analysis can include calculating the ratio of red and green AF in the image. Intensity calculations can be obtained from regions of interest within the wound image. The pseudo-color image can be mapped onto a white light image of the wound.

[0134] The device maps the biodistribution of bacteria at the wound site and in the surrounding skin, thus enabling microbiological testing to be targeted to specific tissue areas requiring swabs or biopsies. Furthermore, the use of this imaging device allows for monitoring the response of bacterially infected tissue to various drug treatments, including the use of antibiotics and other therapies such as photodynamic therapy (PDT), hyperbaric oxygen therapy (HOT), low-level light therapy, or anti-matrix metalloproteinase (MMP) therapy. The device can be used to visualize bacterial biodistribution at the wound surface and within tissue depth, as well as surrounding normal tissue. Thus, the device can be used to indicate the spatial distribution of infection.

[0135] Generally, the device can be used to image and / or monitor targets, such as skin targets, tumor targets, wound targets, confined anatomical spaces or cavities, oral targets, ear, nose and throat targets, eye targets, genital targets, anal targets, and any other suitable targets on a subject.

[0136] Image analysis algorithms can provide one or more of the following features:

[0137] Patient digital image management

[0138] •Integration of multiple image acquisition devices

[0139] • Record all imaging parameters, including any exogenous fluorescent contrast agents

[0140] • Multiple scale and calibration settings

[0141] •Built-in spectral image unmixing calculation algorithm for quantitative determination of tissue / bacterial autofluorescence and exogenous reagent fluorescence signals

[0142] • Convenient annotation tools

[0143] •Digital Archive

[0144] • Online publishing

[0145] Basic image processing and analysis

[0146] • Complete image processing and quantitative analysis capabilities

[0147] The image stitching algorithm will allow a series of panoramic or partially overlapping wound images to be stitched into a single image in automatic or manual mode.

[0148] • Easy-to-use measuring tools

[0149] • Intuitive setting of processing parameters

[0150] • Convenient manual editor

[0151] Report Generation

[0152] •Powerful image report generator with professional templates that can be integrated into existing clinical reporting infrastructure or telemedicine / e-health patient medical data infrastructure. For example, reports can be exported to PDF, Word, Excel.

[0153] Large library of automation solutions

[0154] •Customized automated solutions for all areas of wound assessment, including quantitative image analysis.

[0155] Although image analysis algorithms, techniques, or software have been described, the description also extends to computing devices, systems, and methods for performing such image analysis.

[0156] Image Guidance

[0157] The device can also be used to provide fluorescence image guidance, for example during surgery, even without the use of dyes or labels. Certain tissues and / or organs may have different fluorescence spectra (e.g., intrinsic fluorescence) when viewed using an imaging device, or, for example, under certain excitation light conditions.

[0158] Food applications

[0159] The imaging device can also be used to monitor food products (e.g., meat products) for contamination. This could be useful, for example, in food / animal product preparation within the meat, poultry, dairy, fish, and agricultural industries. The device can be used as part of a comprehensive, multidisciplinary approach to analytical laboratory services within this sector, offering capabilities including image-based contamination detection and guidance for obtaining samples for testing. The device can be used to detect, identify, and monitor levels of meat contamination / adulteration with bacteria and other microorganisms in real time. It can be used to track bacterial contamination within food processing plant environments, providing an image-based approach to determining food safety and quality. In handheld, compact, and portable embodiments, the imaging device can be used in food preparation areas to ensure food safety and prevent bacterial / microbial contamination. The device can also be used to relatively quickly detect and analyze bacteria / microorganisms in collected or sampled meat samples (and preparation surfaces) during processing and in finished food products, for example, as part of regulatory food safety and quality inspections. The device can be used within the meat, horticulture, and aquaculture industries to implement food safety inspection / testing procedures that meet food safety and quality requirements. The device can be used to detect food contaminants, such as those found in the meat, poultry, dairy, and fish industries. The technology could be used in a fecal contaminant detection system because fecal bacteria produce porphyrins, which can be easily detected by the device.

[0160] Detecting and accurately identifying foodborne pathogens, such as Listeria monocytogenes (LM), in food samples and processing lines can be crucial for ensuring food quality assurance and tracing bacterial pathogen outbreaks in the food supply. Current detection methods used in food production and processing facilities typically rely on multiple random surface sampling of equipment (e.g., swabs) and subsequent molecular-based diagnostic assays (e.g., real-time polymerase chain reaction, RT-PCR). These methods typically provide quantitative confirmation of the presence of LM within 24-72 hours. However, due to time and cost constraints, only randomly selected areas of a given food production facility are typically tested for pathogen contamination at a time. This significant potential for undersampling during "first-pass" surface swabbing of equipment can result in undetected pathogens, with catastrophic health and economic consequences. Furthermore, the inability to i) rapidly sample all surface areas during a “first-pass” swabbing process to identify areas of high probability of infection, ii) visually document this initial screening process (e.g., no imaging methods are available to date), iii) delays in obtaining laboratory results, iv) the high costs associated with current methods, and v) more importantly, the absence of infection with potentially lethal pathogens has prompted efforts to improve the cost-effectiveness of early and accurate detection of foodborne pathogens.

[0161] This device can be used to provide a relatively rapid and precise method for detecting such pathogens. It can be used in conjunction with assays using multicolor fluorescent probe "cocktails" (e.g., a combination of two or more contrast agents), which can unambiguously identify (and visualize) only viable Listeria monocytogenes from other Listeria species using highly specific genetic probe technology. This could allow for the specific detection of live Listeria monocytogenes in real time, potentially minimizing the need for standard, time-consuming enrichment methods. This approach can also be expanded to include the detection of other pathogens of interest, including Enterobacter sakazakii, Campylobacter (E. coli, E. jejuni, and Larii), Escherichia coli and E. coli (including lactose- and indole-negative E. coli), Salmonella, all bacteria belonging to the genus Staphylococcus aureus, all bacteria belonging to the genus Staphylococcus, and Pseudomonas aeruginosa. Other bacteria can be detected by selecting appropriate probes or combinations of probes. For example, a combination of two or more contrast agents can be designed to be specific for a particular bacterium and result in a unique, detectable fluorescent signature when imaged using an imaging device.

[0162] This imaging device can be used (for example, when combined with an applied exogenous bacteria-specific contrast agent, including multiple targeted probes or combinations of probes) for relatively rapid "first-pass" screening of food preparation and handling surfaces for targeted swab and microbiological testing. The device can allow for relatively rapid image-based monitoring of any surface of equipment and food, capturing the fluorescent signatures of foodborne bacteria / pathogens in real time. As described above, the device can be used in conjunction with analyses using, for example, multicolor fluorescent probe "cocktails" (and combinations thereof), which can unambiguously identify (and visualize) only viable Listeria monocytogenes from other Listeria species using highly specific genetic probe technology. Such probe "cocktails" can be designed to specifically target certain pathogens based on specific combinations of probes known to be sensitive to such pathogens and known to produce a characteristic fluorescent response. In addition to detecting these pathogens, the device can also distinguish the presence and / or location of different strains based on their distinct characteristic fluorescent responses.

[0163] Surface contamination

[0164] The imaging device can be used to detect surface contamination, such as for detecting "surface bacterial contamination" in healthcare settings. The device can be used to detect and image the presence of bacteria / microorganisms and other pathogens on various surfaces / materials / instruments (particularly those related to surgery) in hospitals, chronic care facilities, and nursing homes, where contamination is a major source of infection. The device can be used in conjunction with standard detection, identification, and enumeration strategies for indicator organisms and pathogens.

[0165] The systems and methods disclosed herein may form a system as outlined below and may be capable of performing the processes outlined below:

[0166] A method | system | apparatus for illuminating an object with light of a calibrated intensity and for capturing a close-up fluorescent digital image, comprising:

[0167] -Optical rangefinder

[0168] -Digital camera sensor with optical fluorescence filter

[0169] -One or more narrowband optical transmitters

[0170] -Computing processor with memory

[0171] -User display

[0172] - User input control

[0173] thus:

[0174] -The light transmitter is turned on,

[0175] - presenting a preview camera image to the user via a display screen,

[0176] - Presenting the rangefinder value to the user via a display

[0177] -Users can activate the camera to capture images

[0178] This allows users to:

[0179] According to the rangefinder value on the screen, set the light intensity on the object by adjusting the height of the device from the object and capture the image.

[0180] A method | system | apparatus for capturing close-up digital images of consistent magnification and perspective, comprising:

[0181] -Optical rangefinder

[0182] -One or more similar digital camera sensors

[0183] -Computing processor with memory

[0184] -User display

[0185] - User input control

[0186] thus:

[0187] - presenting a preview camera image to the user via a display screen,

[0188] - Presenting the rangefinder value to the user via a display

[0189] - The user can activate one or the other camera to capture an image

[0190] This allows users to:

[0191] Set the view of the object by adjusting the height of the device from the object according to the rangefinder value on the screen, and capture the image.

[0192] A method | system | apparatus for capturing a measurement-ready close-up digital image of an object, comprising:

[0193] -Optical rangefinder

[0194] -Digital camera sensors

[0195] -Computing processor with memory

[0196] -User display

[0197] - User input control

[0198] -Image processing software

[0199] thus:

[0200] -The object has 2 visible wound stickers attached.

[0201] - presenting a preview camera image to the user via a display screen,

[0202] - Presenting the rangefinder value to the user via a display

[0203] - If the position of two stickers is detected using image processing, they are continuously presented to the user via the display

[0204] -When a sticker is detected, the user can activate the camera to capture an image.

[0205] This allows users to:

[0206] - set the view of the object by adjusting the height of the device from the object according to the rangefinder value on the screen,

[0207] - setting the view of the object by adjusting the position of the device relative to the object in order to detect the sticker, and

[0208] -Capture image.

[0209] Those skilled in the art who have benefited from this disclosure will appreciate that the present disclosure provides various exemplary devices, systems, and methods for visualizing tumors and / or residual cancer cells on surgical margins during surgery and / or in vitro. In light of this description, further modifications and alternative embodiments of various aspects of the present disclosure will be apparent to those skilled in the art.

[0210] In addition, the apparatus and method may include additional components or steps that are omitted from the accompanying drawings for clarity of illustration and / or operation. Therefore, this description should only be interpreted as illustrative, and is to teach those skilled in the art to implement the general manner of the present disclosure. It should be understood that the various embodiments shown and described herein will be considered as exemplary. It will be apparent to those skilled in the art after having benefited from the description herein that elements and materials and the arrangement of these elements and materials can replace those illustrated and described herein, can reverse parts and processes, and can independently utilize certain features of the present disclosure. Without departing from the spirit and scope of the present disclosure and the appended claims, including their equivalents, the elements described herein may be changed.

[0211] It is to be understood that the particular examples and embodiments set forth herein are non-limiting and that modifications in structure, dimensions, materials, and methods may be made without departing from the scope of the present disclosure.

[0212] Furthermore, the terminology used in this specification is not intended to limit the present disclosure. For example, spatially relative terms such as "below," "lower," "beneath," "upper," "above," "bottom," "right," "left," "proximal," "distal," "front," and the like may be used to describe the relationship of one element or feature to another element or feature as shown in the figures. 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 positions and orientations shown in the figures.

[0213] For the purposes of this specification and the appended claims, unless otherwise indicated, all numbers expressing amounts, percentages or ratios, as well as other numerical values used in the specification and claims, should in all instances be understood as modified (if not already modified) by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and the appended 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.

[0214] Although the numerical ranges and parameters setting forth the broad scope of the present disclosure are approximate, the numerical values set forth in the specific examples are reported as precisely as possible. However, any numerical value inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Furthermore, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein.

[0215] It should be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the," as well as any use of any word in the singular, include plural referents unless expressly and unequivocally limited to one referent. As used herein, the term "include" and its grammatical variations are intended to be non-limiting, such that reciting items in a list is not to the exclusion of other like items that can be substituted or added to the listed items.

[0216] 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 are possible without departing from the broad scope of the appended claims including their intended scope of equivalents.

Claims

1. A portable handheld imaging system comprising: at least one excitation light source configured to emit excitation light during fluorescence imaging; a first image sensor configured to detect a fluorescence wavelength when the imaging system is in a fluorescence imaging mode; a first filter configured to allow passage of an optical signal having a wavelength corresponding to one or more of bacterial fluorescence, bacterial autofluorescence, tissue fluorescence, and tissue autofluorescence in response to illumination of a target surface with the excitation light, the first filter being fixed to the first image sensor; a white light source configured to emit white light during white light imaging; a second image sensor; a second filter configured to allow optical signals having wavelengths within the visible light range to pass therethrough in response to illumination of the target surface with the white light, the second filter being fixed to the second image sensor, the second image sensor imaging the optical signals having wavelengths within the visible light range that pass through the second filter in response to illumination of the target surface with the white light when the imaging system is in a white light imaging mode; a third image sensor; a third filter configured to allow optical signals having wavelengths within the visible light range to pass therethrough in response to irradiation of the target surface with the white light, the third filter being fixed to the third image sensor, the third image sensor imaging the optical signals having wavelengths within the visible light range that pass through the third filter in response to irradiation of the target surface with the white light when the imaging system is in a white light imaging mode; a thermal sensor configured to detect thermal information about the target surface; as well as a processor configured to receive the detected fluorescent and white light optical signals and output a representation of the target surface to a display based on the detected fluorescent and white light optical signals, The processor is further configured to receive image data from the second image sensor and the third image sensor and output a stereoscopic image or a three-dimensional image.

2. The system according to claim 1, wherein: The at least one excitation light source is configured to emit excitation light having a wavelength of 350nm to 400nm, 400nm to 450nm, 450nm to 500nm, 500nm to 550nm, 550nm to 600nm, 600nm to 650nm, 650nm to 700nm, 700nm to 750nm, 750nm to 800nm, 800nm to 850nm, 850nm to 900nm and / or combinations thereof.

3. A system according to claim 1 or claim 2, wherein: The at least one excitation light source is configured to emit excitation light having a wavelength of 400 nm to 450 nm.

4. The system according to claim 1 or 2, wherein: The at least one excitation light source is configured to emit excitation light having a wavelength of 405 nm±10 nm.

5. The system according to claim 1 or 2, wherein: The at least one excitation light source is coupled to a housing of the portable handheld imaging system.

6. The system according to claim 1 or 2, wherein: The first filter is further configured to block passage of optical signals having a wavelength of 405 nm±10 nm.

7. The system according to claim 1 or 2, wherein: The first filter is configured to allow optical signals having a wavelength between 500 nm and 550 nm and / or optical signals having a wavelength between 600 nm and 660 nm to pass through the first filter to the first image sensor.

8. The system according to claim 1 or 2, wherein: The at least one excitation light source includes first and second violet / blue LEDs, each LED being configured to emit light having a wavelength of 405 nm ± 10 nm.

9. The system of claim 1 or 2, further comprising a housing having a display on a front side of the housing.

10. The system according to claim 9, wherein: The at least one excitation light source is located on the rear side of the housing.

11. The system according to claim 9, wherein: The at least one excitation light source includes first and second violet / blue LEDs, each LED being configured to emit light having a wavelength of 405 nm ± 10 nm.

12. The system according to claim 11, wherein The first and second violet / blue LEDs are located on opposite sides of a longitudinal axis of the housing, wherein the longitudinal axis passes through the top and bottom of the housing.

13. The system according to claim 10, wherein: The housing is a modular housing including a display unit and an optical unit.

14. The system according to claim 13, wherein: The optical unit is releasably attached to the display unit.

15. The system according to claim 14, wherein: The at least one excitation light source is contained in the optical unit.

16. The system according to claim 15, wherein: The white light source is included in the optical unit.

17. The system according to claim 16, wherein: The display unit includes an interface configured to releasably receive an optical unit.

18. The system according to claim 17, wherein: The interface is defined at least in part by a heat sink of the system.

19. The system according to claim 18, wherein: The heat sink surrounds an opening configured to releasably receive the optical unit.

20. The system of claim 1 or 2, further comprising an ambient light sensor configured to indicate when ambient lighting conditions are sufficient to allow fluorescence imaging.

21. The system of claim 1 or 2, further comprising a rangefinder.

22. The system of claim 1 or 2, further comprising a WiFi and / or Bluetooth antenna.

23. The system according to claim 1 or 2, wherein: The processor is configured to transmit and / or receive data wirelessly.

24. The system of claim 1 or 2, further comprising a power source.

25. The system according to claim 1 or 2, wherein: The excitation light source includes a first excitation light source and a second excitation light source.

26. The system of claim 25, wherein: The first excitation light source is configured to emit excitation light having a wavelength of 350nm to 400nm, 400nm to 450nm, 450nm to 500nm, 500nm to 550nm, 550nm to 600nm, 600nm to 650nm, 650nm to 700nm, 700nm to 750nm, 750nm to 800nm, 800nm to 850nm, 850nm to 900nm and / or combinations thereof.

27. The system of claim 26, wherein: The first excitation light source is configured to emit excitation light having a wavelength of 400 nm to 450 nm.

28. The system of claim 27, wherein: The first excitation light source is configured to emit excitation light having a wavelength of 405 nm±10 nm.

29. The system of claim 25, wherein: The second excitation light source is configured to emit excitation light having a wavelength of 350nm to 400nm, 400nm to 450nm, 450nm to 500nm, 500nm to 550nm, 550nm to 600nm, 600nm to 650nm, 650nm to 700nm, 700nm to 750nm, 750nm to 800nm, 800nm to 850nm, 850nm to 900nm and / or combinations thereof.

30. The system of claim 29, wherein: The second excitation light source is configured to emit excitation light having a wavelength of 750 nm to 800 nm.

31. The system of claim 30, wherein: The second excitation light source is configured to emit excitation light having a wavelength between 760 nm and 780 nm.

32. The system of claim 31, wherein: The second excitation light source is configured to emit excitation light having a wavelength of 760 nm±10 nm.

33. The system of claim 32, wherein: The second excitation light source is configured to emit excitation light having a wavelength of 770 nm±10 nm.

34. The system of claim 33, wherein: The second excitation light source is configured to emit excitation light having a wavelength of 780 nm±10 nm.

35. The system of claim 1 or 2, wherein: The first image sensor and the second image sensor each include a complementary metal oxide semiconductor sensor.

36. The system of claim 1 or 2, further comprising an infrared radiation source.

37. The system of claim 36, wherein: The system is configured to project infrared radiation onto the target surface and detect infrared radiation reflected from the target surface and any infrared fluorescence emitted by the target when excited by an appropriate excitation wavelength.

38. The system of claim 37, wherein: The processor is further configured to generate a three-dimensional image of the target surface based on the detected reflected infrared radiation.

39. The system of claim 38, wherein: The processor is further configured to generate a three-dimensional fluorescence image of the target surface based on the three-dimensional image of the target surface, the two-dimensional white light image of the target surface, and the two-dimensional fluorescence image of the target surface.

40. A portable modular handheld imaging system comprising: The first housing portion includes: at least one excitation light source configured to emit excitation light during fluorescence imaging, a first image sensor configured to detect a fluorescence wavelength when the imaging system is in a fluorescence imaging mode; a first filter configured to allow passage of optical signals having wavelengths corresponding to one or more of bacterial fluorescence, bacterial autofluorescence, tissue fluorescence, and tissue autofluorescence in response to illumination of a target surface with the excitation light, the first filter being fixed to the first image sensor, a white light source configured to emit white light during white light imaging, and a second image sensor; a second filter configured to allow optical signals having wavelengths within the visible light range to pass therethrough in response to illumination of the target surface with the white light, the second filter being fixed to the second image sensor, the second image sensor imaging the optical signals having wavelengths within the visible light range that pass through the second filter in response to illumination of the target surface with the white light when the imaging system is in a white light imaging mode; a third image sensor; a third filter configured to allow optical signals having wavelengths within the visible light range to pass therethrough in response to irradiation of the target surface with the white light, the third filter being fixed to the third image sensor, the third image sensor imaging the optical signals having wavelengths within the visible light range that pass through the third filter in response to irradiation of the target surface with the white light when the imaging system is in a white light imaging mode; a thermal sensor configured to detect thermal information about the target surface; and A second housing portion configured to releasably receive the first housing portion and comprising: Display, and a processor configured to receive the detected fluorescent and white light optical signals and output a representation of the target surface to the display based on the detected fluorescent and white light optical signals, The processor is further configured to receive image data from the second image sensor and the third image sensor and output a stereoscopic image or a three-dimensional image.

41. The system of claim 40, wherein: The at least one excitation light source is configured to emit excitation light having a wavelength of 350nm to 400nm, 400nm to 450nm, 450nm to 500nm, 500nm to 550nm, 550nm to 600nm, 600nm to 650nm, 650nm to 700nm, 700nm to 750nm, 750nm to 800nm, 800nm to 850nm, 850nm to 900nm and / or combinations thereof.

42. A system according to claim 40 or claim 41, wherein The at least one excitation light source is configured to emit excitation light having a wavelength of 400 nm to 450 nm.

43. The system of claim 40 or 41, wherein: The at least one excitation light source is configured to emit excitation light having a wavelength of 405 nm±10 nm.

44. The system of claim 40 or 41, wherein: The first filter is further configured to block passage of optical signals having a wavelength of 405 nm±10 nm.

45. The system of claim 40 or 41, wherein: The first filter is configured to allow optical signals having a wavelength between 500 nm and 550 nm and / or optical signals having a wavelength between 600 nm and 660 nm to pass through the first filter to the first image sensor.

46. The system of claim 40 or 41, wherein: The at least one excitation light source includes first and second violet / blue LEDs, each LED being configured to emit light having a wavelength of 405 nm ± 10 nm.

47. The system of claim 40 or 41, wherein: The second housing portion also includes a power source.

48. The system of claim 47, wherein: The second housing portion also includes an outer surface having contacts for charging the power source.

49. The system of claim 40 or 41, wherein: The second housing portion further includes a heat sink.

50. The system of claim 49, wherein: The heat sink defines an opening in the second housing portion, the opening being configured to releasably receive the first housing portion.

51. The system of claim 40 or 41, wherein: The first housing portion also includes an ambient light sensor configured to indicate when ambient lighting conditions are sufficient to allow fluorescence imaging.

52. The system of claim 40 or 41, wherein: The first housing portion also includes a rangefinder.

53. The system of claim 40 or 41, wherein: The first shell portion also includes a second excitation light source, which is configured to emit excitation light having a wavelength of 350nm to 400nm, 400nm to 450nm, 450nm to 500nm, 500nm to 550nm, 550nm to 600nm, 600nm to 650nm, 650nm to 700nm, 700nm to 750nm, 750nm to 800nm, 800nm to 850nm, 850nm to 900nm and / or combinations thereof.

54. The system of claim 53, wherein: The second excitation light source is configured to emit excitation light having a wavelength of 750 nm to 800 nm.

55. The system of claim 54, wherein: The second excitation light source is configured to emit excitation light having a wavelength between 760 nm and 780 nm.

56. The system of claim 55, wherein: The second excitation light source is configured to emit excitation light having a wavelength of 760 nm±10 nm.

57. The system of claim 55, wherein: The second excitation light source is configured to emit excitation light having a wavelength of 770 nm±10 nm.

58. The system of claim 55, wherein: The second excitation light source is configured to emit excitation light having a wavelength of 780 nm±10 nm.

59. The system of claim 40 or 41, wherein: The first housing portion further includes a polarization filter.

60. A portable modular handheld imaging system kit comprising: a plurality of optical housing portions, each of the plurality of optical housing portions comprising: at least one excitation light source configured to emit excitation light during fluorescence imaging, a first image sensor configured to detect a fluorescence wavelength when the imaging system is in a fluorescence imaging mode; a first filter configured to allow passage of optical signals having wavelengths corresponding to one or more of bacterial fluorescence, bacterial autofluorescence, tissue fluorescence, and tissue autofluorescence in response to illumination of a target surface with the excitation light, the first filter being fixed to the first image sensor, a white light source configured to emit white light during white light imaging, and a second image sensor; a second filter configured to allow optical signals having wavelengths within the visible light range to pass therethrough in response to illumination of the target surface with the white light, the second filter being fixed to the second image sensor, the second image sensor imaging the optical signals having wavelengths within the visible light range that pass through the second filter in response to illumination of the target surface with the white light when the imaging system is in a white light imaging mode; a third image sensor; a third filter configured to allow optical signals having wavelengths within the visible light range to pass therethrough in response to irradiation of the target surface with the white light, the third filter being fixed to the third image sensor, the third image sensor imaging the optical signals having wavelengths within the visible light range that have passed through the third filter in response to irradiation of the target surface with the white light when the imaging system is in a white light imaging mode; and a base housing portion configured to releasably and interchangeably receive each of the plurality of optical housing portions and comprising: monitor, a power supply configured to supply power to the at least one excitation light source and the white light source, and a processor configured to receive the detected fluorescent and white light optical signals and output a representation of the target surface to the display based on the detected fluorescent and white light optical signals, The processor is further configured to receive image data from the second image sensor and the third image sensor and output a stereoscopic image or a three-dimensional image.

61. The kit of claim 60, wherein In each of the multiple optical housing portions, the at least one excitation light source is configured to emit excitation light having a wavelength of 350nm to 400nm, 400nm to 450nm, 450nm to 500nm, 500nm to 550nm, 550nm to 600nm, 600nm to 650nm, 650nm to 700nm, 700nm to 750nm, 750nm to 800nm, 800nm to 850nm, 850nm to 900nm and / or combinations thereof.

62. The kit of claim 60 or 61, wherein The at least one excitation light source is configured to emit excitation light having a wavelength of 400 nm to 450 nm.

63. The kit of claim 60 or 61, wherein The at least one excitation light source is configured to emit excitation light having a wavelength of 405 nm±10 nm.

64. The kit of claim 60 or 61, wherein The first filter is configured to allow optical signals having a wavelength between 500 nm and 550 nm and / or optical signals having a wavelength between 600 nm and 660 nm to pass through the first filter to the first image sensor.

65. The kit of claim 60 or 61, wherein The at least one excitation light source includes first and second violet / blue LEDs, each LED being configured to emit light having a wavelength of 405 nm ± 10 nm.

66. The kit of claim 60, wherein A second optical housing portion of the plurality of optical housing portions further includes a second excitation light source configured to emit excitation light having a wavelength different from that of the at least one excitation light source.

67. The kit of claim 66, wherein A second optical housing portion among the plurality of optical housing portions is formed as an endoscope housing portion.

68. The kit of claim 60 or 61, wherein One of the plurality of optical housing portions further includes a rangefinder.

69. The kit of claim 60 or 61, wherein One of the plurality of optical housing portions further includes a thermal sensor configured to detect thermal information about the target surface.

70. The kit of claim 60 or 61, wherein One of the plurality of optical housing portions further includes an ambient light sensor configured to indicate when ambient lighting conditions are sufficient to allow fluorescence imaging.

71. The kit of claim 60 or 61, wherein The base housing portion also includes an outer surface having contacts for charging the power source.

72. The kit of claim 60 or 61, wherein The base housing portion also includes a heat sink.

73. The kit of claim 72, wherein The heat sink defines an opening in the base housing portion, the opening being configured to releasably receive one of the plurality of optical housing portions.

74. The kit of claim 60 or 61 further comprising a darkening drape configured to be attached to one of the plurality of optical housing portions.

75. The kit of claim 74, wherein The darkening cover is configured to reduce ambient light in a field of view of the first image sensor.

76. The kit of claim 75, further comprising a plurality of darkening drapes, each darkening drape being configured to attach to a respective one of the plurality of optical housing portions.

77. The kit of claim 67, further comprising a darkening drape configured to attach to the endoscope housing portion.

78. The kit of claim 77, wherein The darkening cover is configured to reduce ambient light in a field of view of the first image sensor.

79. The kit of claim 78, wherein The darkening drape is also configured to provide sterility in the surgical field and / or protect the endoscope housing portion from contamination.

80. The kit of claim 60 or 61, wherein One of the plurality of optical housing portions further includes a polarization filter.

81. The kit of claim 60 or 61, wherein The base housing portion and one of the plurality of optical housing portions together form an imaging device and further include a sterile drape configured to create a sterile barrier between the imaging device and an environment in which the imaging device is used.

82. The kit of claim 60 or 61, further comprising one or more imaging or contrast agents.

83. A method of operating the portable modular handheld imaging system of any one of claims 40 to 59, comprising: selecting an optical housing comprising optical components including at least one excitation light source for fluorescence imaging and at least one white light source for white light imaging; connecting the selected optical housing to a base housing of an imaging device to provide power from a power source in the base housing to the optical components in the optical housing; illuminating the target with the at least one excitation light source to cause one or more of a portion of an illuminated portion, a component, and a biomarker of the target to fluoresce, reflect, or absorb light, and illuminating the target with the at least one white light source configured to emit white light during the white light imaging; filtering optical signals in response to illumination of the target with the excitation light, wherein filtering the plurality of optical signals comprises preventing reflected excitation light from passing therethrough and allowing optical signals having wavelengths corresponding to one or more of bacterial fluorescence, bacterial autofluorescence, tissue autofluorescence, and exogenous tissue fluorescence to pass through a first filter contained in the optical housing; filtering an optical signal in response to illumination of the target surface with the white light so that an optical signal having a wavelength within the visible light range passes through a second filter and a third filter contained in the optical housing; detecting the filtered optical signal using at least three image sensors contained in the optical housing, wherein the first filter, the second filter, and the third filter are respectively fixed to corresponding sensors among the at least three image sensors; and The detected filtered signals are displayed on at least one display of the base housing as a composite image of the illuminated portion of the object, the composite image including fluorescent representations of various tissue components present in the illuminated portion of the object.

84. An imaging system kit comprising: The imaging system according to any one of claims 1 to 59; as well as A sterile drape is configured to create a sterile barrier between the imaging system and an environment in which the imaging system is used.

85. The kit of claim 84 further comprising an imaging drape configured to reduce ambient light in an imaging environment of the imaging system.

86. The kit of claim 85, wherein The imaging drape includes a connector element configured to receive an optical housing of the imaging system.

87. The kit of any one of claims 84 to 86, further comprising one or more imaging or contrast agents.

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