Modular system for multi-modal imaging and analysis

Abstract

To provide a portable, modular handheld imaging system suited for collecting data about biochemical, biological and non-biological substances such as in wound care.SOLUTION: An optical housing portion 140 is removable from a substrate portion 110 and includes at least one excitation light source. A first filter is configured to detect selected optical signals and permit passage of the signals responsive to illumination with the excitation light to a first image sensor. A second filter is configured to detect selected optical signals and permit passage of the signals responsive to illumination of a target surface with white light to a second image sensor. The substrate portion is configured to releasably receive the optical housing portion, and includes a display and a processor configured to receive a detected fluorescent and white light optical signals and to output a representation of the target surface to the display based on the detected optical signals.SELECTED DRAWING: Figure 5A

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority to Provisional Application No. 62 / 793,842, filed on January 17, 2019, entitled "Modular Systems for Multimodal Imaging and Analysis", the entire content of which is incorporated herein by reference.

[0002] Technical Field Systems for multimodal imaging and analysis are disclosed. In particular, the systems and methods may be suitable for collecting data regarding biochemical, biological, and / or non - biological substances. The data may include, for example, one or more of white - light data, fluorescence data, thermal data, infrared data in applications such as wound care, for both human and animal use.

Background Art

[0003] Background Art Wound care is a major clinical challenge. Healing and chronic non-healing wounds are associated with many biological tissue changes, including inflammation, proliferation, connective tissue remodeling, and bacterial infection, which is a common major concern. The rate of wound infection is not clinically apparent and is contributing to the increasing economic burden associated with wound care, especially in the elderly population. Currently, the gold standard for wound assessment includes direct visual inspection of the wound site under white light combined with the indiscriminate collection of bacterial swabs and tissue biopsies, which is delayed, costly, and often results in insensitive bacteriological results. This can affect the timing and effectiveness of treatment. Qualitative and subjective visual evaluations only provide an overall picture of the wound site and do not provide information on the underlying biological and molecular changes occurring at the tissue and cellular levels. A relatively simple and complementary method that utilizes "biological and molecular" information to improve the early identification of such potential changes is desirable in clinical wound management. Early recognition of high-risk wounds can lead to therapeutic intervention and provide monitoring of responses over time, thus significantly reducing both morbidity and mortality, especially due to chronic wounds.

[0004] Wound care and management are major clinical challenges that present a significant burden and problem for healthcare worldwide [Bowler et al., Clin Microbiol Rev., 2001, 14:244-269; Cutting et al., Journal of Wound Care. 1994, 3: 198 - 201, Dow et al., Ostomy / Wound Management. 1999, 45: 23 - 40]. Wounds are generally classified into wounds without tissue loss (e.g., in surgery), and wounds with tissue loss as a result of burns, trauma, abrasions, or as a secondary event in chronic diseases (e.g., venous stasis, diabetic ulcers or pressure sores and iatrogenic wounds such as skin graft donor sites and skin detachment, folliculitis, non - healing surgical wounds and chronic ulcerative wounds). Wounds are also classified by the layers involved, superficial wounds include only the epidermis, partial - thickness wounds include only the epidermis and dermis, and full - thickness wounds include subcutaneous fat or deeper tissues as well as the epidermis and dermis. The restoration of tissue continuity after injury is a natural phenomenon, but infections, the quality of healing, the rate of healing, fluid loss, and other complications that prolong the healing time are major clinical challenges. Most wounds heal without any complications. However, chronic non - healing wounds with increasing tissue loss pose a major challenge to wound care specialists and researchers. Unlike surgical incisions with relatively little tissue loss that generally heal without major complications, chronic wounds often disrupt the normal healing process that is essentially insufficient to effect repair. The delay in healing is generally the result of a decline in wound physiology [Winter (1962) Nature. 193: 293 - 294], typically occurring with venous stasis and diabetic ulcers, or long - term local pressure such as in immunosuppressed and immobilized elderly individuals. These chronic conditions increase the cost of care and decrease the quality of life of the patient. As the number of these groups increases, the need for advanced wound care products will increase.

[0005] Conventional clinical assessment methods for acute and chronic wounds are still sub - optimal. They are usually based on a qualitative and subjective clinical assessment using a complete patient history, simple visual evaluation using ambient white light and the "naked eye", and may include the use of color photographs to capture the general appearance of the wound area under white light illumination [Perednia (1991) J Am Acad Dermatol. 25:89 - 108]. Regular reassessment of progress towards healing and appropriate modification of interventions are also needed. The terminology for wound assessment is heterogeneous, many questions surrounding wound assessment remain unresolved, there is still no consensus on the important wound parameters to be measured in clinical practice, and the accuracy and reliability of available wound assessment techniques vary. Visual assessment is often combined with swab collection and / or tissue biopsy for bacteriological culture for diagnosis. Bacterial swabs are collected during wound examination and have the significant advantage of providing identification of specific bacterial / microbial species [Bowler, 2001; Cutting, 1994; Dow, 1999; Dow G. Krasner et al. eds Chronic Wound Care: A Clinical Source Book for Healthcare Professionals, 3rd ed., Wayne, Pennsylvania, HMP Communications, 2001, 343 - 356]. However, in many cases, multiple swabs and / or biopsies are randomly collected from the wound site, and some swabbing techniques actually spread microorganisms with the wound during the collection process and can thus affect the patient's healing time and morbidity [Dow, 1999]. This can be a problem, especially in large chronic (non - healing) wounds where the detection yield of bacterial presence using current swabbing and biopsy protocols is sub - optimal (diagnostically insensitive) despite many swabs being collected. Thus, current methods for obtaining swabs or tissue biopsies from the wound site for subsequent bacteriological culture are based on non - standardized or "blind" swabbing or punch biopsy approaches and are not optimized to minimize trauma to the wound or to maximize the diagnostic yield of bacteriological testing.Furthermore, obtaining swabs and biopsy samples for bacteriology is cumbersome, invasive, painful, costly, and more importantly, bacteriological culture results often take about two to three days to return from the laboratory and may not be definitive [Serena et al. (2008) Int J Low Extrem Wounds. 7(1):32-5, Gardner et al., (2007) WOUNDS. 19(2):31-38], thus delaying accurate diagnosis and treatment [Dow, 1999]. Therefore, bacterial swabs do not provide real-time detection of the infection status of the wound site. Although wound swab collection may seem simple, if not performed correctly, it can lead to inappropriate treatment, increased patient morbidity, and length of hospital stay [Bowler, 2001; Cutting, 1994; Dow, 1999; Dow, 2001]. The lack of a non-invasive method to objectively and rapidly assess wound repair at the biological level (which can be more detailed than simply based on appearance or morphology) and to assist in the targeting of swabs and tissue biopsy sample collections for bacteriology is a major obstacle in clinical wound assessment and treatment. An alternative method is highly desirable.

[0006] As wounds (chronic and acute) heal, several important biological changes occur at the tissue and cellular levels at the wound site [Cutting, 1994]. Wound healing involves a complex and dynamic interplay of biological processes that can be divided into four overlapping phases that affect the pathophysiology of wound healing, namely hemostasis, inflammation, cell proliferation, and the maturation or remodeling of connective tissue [Physiological basis of wound healin g. Developments in wound care, PJB Publications Ltd., 5 - 17, 1994]. The main common complications that can occur during the wound healing process, which can range from several days to several months, are infections caused by bacteria and other microorganisms [Cutting, 1994; Dow, 1999]. This can pose a significant obstacle to the healing process and lead to serious complications. All wounds contain bacteria at levels ranging from contamination to colonization, critical colonization to infection, and the diagnosis of a 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, more recently, critical colonization. Wound contamination refers to the presence of bacteria within the wound without a host response [Ayton M. Nurs Times, 1985, 81(46): Suppl 16-19], wound colonization refers to the presence of bacteria within the wound that are either growing or initiating a host response [Ayton, 1985], critical colonization refers to the growth of bacteria that causes a delay in wound healing and is usually accompanied by an exacerbation of pain not previously reported, but without an obvious host response yet [Falanga et al., J Invest Dermatol, 1994, 102(1): 125-27; Kingsley A, Nurs Stand, 2001, 15(30): 50-54, 56, 58]. Wound infection refers to the deposition and growth of bacteria within the tissue with an associated host response [Ayton, 1985]. In practice, the term "critical colonization" can be used to describe wounds that are thought to be transitioning from colonization to local infection. However, the challenge in the clinical setting is to ensure that this situation is recognized quickly and reliably, and perhaps by the use of topical antimicrobials, to reduce the bacterial bioburden as soon as possible. Potential wound pathogens can be classified into different groups such as bacteria, fungi, spores, protozoa, and viruses according to their structure and metabolic capabilities [Cooper et al., Wound Infection and Microbiology.: Medical Communications (UK) Ltd for Johnson & Johnson Medical, 2003]. Viruses generally do not cause wound infections, but bacteria can infect skin lesions formed during the course of certain viral diseases. Such infections can occur in several settings including healthcare (hospitals, clinics) and the home or chronic care facilities. The control of wound infection is becoming increasingly complex, but treatment is not always guided by microbiological diagnosis. The diversity of microorganisms and the high incidence of polymicrobial flora in most chronic and acute wounds give credibility to the value of identifying one or more bacterial pathogens from wound cultures.By early recognition of the causative factors of wound infection, wound care experts can be assisted in performing appropriate treatments. Furthermore, incomplete collagen formation results from an increased bacterial load, leading to an overvascularized and fragile granulation tissue that is free and usually results in wound breakdown [Sapico et al. (1986) Diagn Microbiol Infect Dis. 5: 31-38].

[0008] Accurate and clinically appropriate wound assessment is an important clinical tool, but this process currently remains a significant challenge. Current visual assessments in clinical practice only provide an overall picture of the wound site (e.g., the presence of purulent material and eschar formation). Current best clinical practices are unable to appropriately utilize critically important objective information regarding the fundamental biological changes occurring at the tissue and cellular levels (e.g., contamination, colonization, infection, matrix remodeling, inflammation, bacterial / microbial infection, and necrosis), because such indicators are i) not readily available during wound examination and ii) currently not integrated into conventional wound management processes. The direct visual assessment of wound health using white light relies on the detection of color and topographical / textural changes in and around the wound, and thus is unable to detect subtle changes in tissue remodeling and may be unreliable in that task. More importantly, since bacteria are not visible under white light illumination, the presence of bacterial infection is often undetectable by direct visual assessment of the wound. Infection is clinically diagnosed by microbiological tests used to identify organisms and their antibiotic sensitivities. Physical signs of bacterial infection can be readily observed in most wounds using white light (e.g., purulent exudate, eschar formation, swelling, erythema), but this is often significantly delayed and patients are already at high risk of morbidity (and other complications associated with infection) and mortality. Thus, standard white light direct visualization cannot detect the early presence of bacteria themselves or identify the types of bacteria within the wound. Since bacteria are not visible under white light illumination, the presence of bacterial infection is often undetectable by direct visual assessment of the wound. Infection is clinically diagnosed by microbiological tests used to identify organisms and their antibiotic sensitivities. Physical signs of bacterial infection can be readily observed in most wounds using white light (e.g., purulent exudate, eschar formation, swelling, erythema), but this is often significantly delayed and patients are already at high risk of morbidity (and other complications associated with infection) and mortality. Thus, standard white light direct visualization cannot detect the early presence of bacteria themselves or identify the types of bacteria within the wound.

[0009] In recent years, the transplantation of stem cells has attracted attention, for example, for wound care and treatment. However, it is currently difficult to track the proliferation of stem cells after transplantation. Tracking and identifying cancer cells has also been difficult. It would be desirable to be able to monitor such cells in a minimally invasive or non-invasive manner.

[0010] It is also useful to provide a method for detecting contamination of other target surfaces including non-biological targets. SUMMARY OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION

[0011] Summary of the Invention This disclosure can solve one or more of the above problems and / or demonstrate one or more of the above desirable features. Other features and / or advantages may become apparent from the following description. MEANS FOR SOLVING THE PROBLEM

[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 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 the target surface by the excitation light and to enable passage to a first image sensor. A white light source is configured to emit white light during white light imaging. A second filter is configured to detect an optical signal having a wavelength within the visible light range in response to illumination of the target surface by the white light and to enable passage to a second image sensor. And a processor is configured to receive the detected fluorescence optical signal and white optical signal 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 hand-held 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 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 by the excitation light and to enable passage to a first image sensor, a white light source configured to emit white light during white light imaging, and a second filter configured to detect an optical signal having a wavelength within the visible light range in response to illumination of the target surface by the white light and to enable passage to a second image sensor. 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 an additional aspect of the present disclosure, a portable modular hand-held 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 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 by the excitation light and to enable passage to a first image sensor, a white light source configured to emit white light during white light imaging, a second filter configured to detect an optical signal having a wavelength within the visible light range in response to illumination of the target surface by the white light and to enable passage 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 supply power to 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 hand-held fluorescence-based imaging device is provided. The method includes selecting an optical housing that includes 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 supply power from a power source within the base housing to the optical components within the optical housing. The method also includes illuminating a target with at least the excitation light source to cause the target to fluoresce, reflect light, or absorb light in one or more of a portion, component, and biomarker of the illuminated portion of the target, and filtering an optical signal in response to the illumination of the target with the excitation light, wherein filtering the plurality of optical signals includes preventing passage of the reflected excitation light and enabling 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 included in the optical housing. The method further includes detecting the filtered optical signal with an image sensor included in the optical housing, and displaying the detected filtered signal on at least one display of the base housing as a composite image of the illuminated portion of the target, wherein the composite image includes fluorescence representations of various tissue components present in the illuminated portion of the target.

[0016] Brief Description of the Drawings The present disclosure can be understood from the following detailed description, alone or in conjunction with the accompanying drawings. The drawings are included to provide a further understanding and are incorporated in and constitute a part of this specification. The drawings illustrate one or more exemplary embodiments of the present disclosure and serve to explain various principles and operations in conjunction with the description.

Brief Description of the Drawings

[0017]

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[0018] DETAILED DESCRIPTION The progression of wounds is currently monitored manually. The National Pressure Ulcer Advisory Panel (NPUAP) has developed a Pressure Ulcer Scale for Healing (PUSH) tool that outlines a five - stage method for characterizing pressure ulcers. This tool uses three parameters to determine a quantitative score, which is then used to monitor pressure ulcers over time. Qualitative parameters include wound dimensions, tissue type, amount of exudate or drainage, and thermometry values present after dressing removal. The wound can be further characterized by its odor and color. Such an assessment of the wound currently does not include significant biological and molecular information regarding the wound. Thus, all descriptions of the wound are somewhat subjective and are written by hand, either by the attending physician or a nurse.

[0019] A robust, cost-effective, non-invasive and rapid imaging-based method or apparatus for objectively evaluating a wound site for changes at the biological, biochemical, and cellular levels, and for rapidly, sensitively and non-invasively detecting the earliest presence of bacteria / microorganisms within the wound site is desirable. Such a method or apparatus for detecting significant biological tissue changes in a wound site can serve as an adjunct to conventional clinical wound management methods to guide important clinical pathological decisions in patient care. Such an apparatus can be compact and portable, enabling real-time non-invasive and / or non-contact investigation of the wound site in a safe and convenient manner, whereby a handheld imaging device can seamlessly fit into routine wound management operations and be user-friendly for clinicians, nurses, and wound care specialists. The handheld imaging device can also be used in home care environments (including self-use by patients), as well as in military battlefield environments. Furthermore, such an image-based device can provide the ability to monitor wound treatment response and healing in real-time by incorporating "biologically informative" image guidance valuable in the clinical wound assessment process. This may ultimately lead to potential new diagnostics, treatment planning, treatment response monitoring, and thus "adaptive" intervention strategies that can improve wound healing response at the individual patient level. Accurate identification of the systemic, local, and molecular factors underlying wound healing problems in individual patients can enable better-tailored treatment.

[0020] The MolecuLight i:X device has made progress in addressing many of the problems raised above. The MolecuLight i:X device enables clinicians to rapidly, safely and easily visualize bacteria and measure the wound site at the point of care. The basis and method of use of the MolecuLight i:X device are described in U.S. Patent No. 9,042,967, which is the national stage application of PCT / CA2009 / 000680, filed internationally on May 20, 2009, claiming 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.

[0021] Another imaging device disclosed for use in cancer visualization is disclosed in U.S. Provisional Patent Application No. 62 / 625,983, filed February 3, 2018, entitled "Devices, Systems, and Methods for Tumor Visualization and Removal," and U.S. Provisional Patent Application No. 62 / 625,967, filed February 3, 2018, entitled "Devices, Systems, and Methods for Tumor Visualization and Removal," as well as International Patent Application No. PCT / CA2019 / 000015, filed February 1, 2019, entitled "Devices, Systems, and Methods for Tumor Visualization and Removal," the entire contents of each of which are incorporated herein by reference. Although disclosed in the context of cancer visualization, the disclosed systems and methods relate to the visualization and imaging of tissue autofluorescence and tissue fluorescence, and the details regarding the structure, functionality, and operation of the exemplary devices described therein are similar or the same as part of the system described herein. may be similar or the same as part of the system described herein.

[0022] The MolecuLight i:X device and apparatus disclosed in the present application utilize tissue autofluorescence imaging, which provides a unique means of obtaining biologically relevant information of normal and diseased tissues in real time, thus enabling the distinction between normal and diseased tissue states. The autofluorescence imaging device may be useful for rapid, non-invasive, and non-contact real-time imaging of the wound site in order to overcome current limitations and detect and utilize the rich biological information of the wound site to improve clinical care and management.

[0023] In this application, systems, methods, and apparatuses for fluorescence-based imaging are disclosed. One embodiment of the apparatus is a portable optical digital imaging device. The apparatus may utilize a combination of white light (WL) imaging, fluorescence (FL) imaging, infrared (IR) imaging, thermal imaging, and / or three-dimensional mapping, and may provide real-time wound imaging, evaluation, recording / documentation, monitoring, and / or care management. The apparatus may be handheld, small, and / or lightweight. For example, the apparatus includes at least one excitation light source configured to emit excitation light during fluorescence imaging, a first filter configured to detect 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 by the excitation light and to allow passage to a first image sensor, a white light source configured to emit white light during white light imaging, a second filter configured to detect an optical signal having a wavelength within the visible light range in response to illumination of the target surface by the white light and to allow passage to a second image sensor, 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. This apparatus and method may be suitable for monitoring wounds in humans and animals.

[0024] In another exemplary embodiment, the apparatus may be a modular handheld imaging device. In such an embodiment, the apparatus includes a base portion, also referred to herein as a base part or base housing, and an optical portion, also referred to herein as an optical housing or optical housing part. The optical portion is releasably received by the base portion and is interchangeable with other optical portions, and each optical portion is configured for a particular application or to capture particular characteristics of the target being imaged and optical information from the target. Thus, the user selects the optical housing based on the desired capabilities for imaging in a given situation.

[0025] The modular hand-held imaging device can be packaged and / or sold as part of a kit having a base portion and two or more optical portions, and the optical characteristics of each optical portion are different from each other and from any other optical housing. Characteristics that can differ from optical housing to optical housing include the following non-limiting examples, which can be included in any combination within each optical housing. That is, the number of image sensors, the number of image sensors configured for white light imaging (i.e., combined with a filter 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 passage of different ranges of fluorescence emission, each range being configured to capture specific characteristics of a target (e.g., vascular or microvascular system, collagen, elastin, blood, bone, bacteria, malignant tumor, lymph, immune cells, adipose tissue, cartilage, tendon, nerve, gastrointestinal tissue, skin, pre-malignant or benign tissue, body fluid, urine, blood, saliva, tears, mucus, mucosal tissue, skin tissue, and exogenous fluorescent agents, drugs, etc.).

[0026] The image sensor is configured to capture still images or video. The number and type of excitation light sources can also vary between optical housings. The excitation light sources are from about 350 nm to about 400 nm, from about 400 nm to about 450 nm, from about 450 nm to about 500 nm, from about 500 nm to about 550 nm, from about 550 nm to about 600 nm, from about 600 nm to about 650 nm , configured to emit excitation light having a wavelength of 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 housing to housing depending on the particular application. For example, a special shape can be used for specific applications such as accessing limited anatomical spaces such as, for example, recesses, oral cavities, nasal cavities, anal regions, abdominal regions, ears, etc. In such cases, the optical housing may have the form of an endoscope attachment. The material forming the optical housing may be different for each housing. For example, the housing can have a flexible patient-facing portion or a rigid patient-facing portion depending on the application in which the imaging device is used. In some embodiments, the optical housing can be made waterproof or water-resistant. The housing may, in some embodiments, be made of a material that is essentially resistant to bacterial growth, or may have a surface texture or topology that is resistant to microbial growth, such as a roughened nano-surface. The size 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 features such as ambient light sensors, rangefinders, thermal imaging sensors, structured light emitters, infrared radiation sources and detectors used for three-dimensional imaging, lasers for performing measurements, etc. in any combination. Additionally or alternatively, the imaging device may also have an external channel embedded in the housing to enable the delivery of instruments such as biopsy forceps, fiber optic spectroscopy probes or other instruments that require (FL) image-guided targeting to collect tissue, excise tissue, cauterize tissue, or examine fluorescent tissue.

[0027] The base part / housing includes an interface configured to releasably receive the optical housing. The optical housing includes a portion configured to be received within the base part so as to provide a power connection between components within the optical housing and the battery and processor within the base part. The connection enables data transfer between the optical housing and the base, and the base includes a processor configured to receive data from the image sensor. Further, the base can be connected to a PC to store or analyze data from the modular imaging device.

[0028] In various exemplary embodiments, the base part includes a heat sink. In one exemplary embodiment, the heat sink forms a lip around an opening of the base part configured to receive the optical housing.

[0029] In various exemplary embodiments, the modular imaging device includes the following elements in various configurations.

[0030] FL camera sensor - A camera sensor configured to detect fluorescence wavelengths is used in the fluorescence imaging mode (FL). The light incident on this sensor passes through a dual-band filter to enable visualization and capture of red and green fluorescence signals that may be present, for example, signals generated in response to illumination of a target by excitation light. In some embodiments, the filter can be configured to recognize additional or fewer fluorescence signals.

[0031] WL camera 1 - The first white light (WL) camera sensor is used when the modular imaging device is in the white light (WL) imaging mode. The light incident on this sensor passes through a short-pass filter to enable the sensor to image visible light wavelengths. The short-pass filter blocks infrared (IR) light that may be present in a clinical environment. The short-pass filter also blocks IR emitted by a rangefinder, if present.

[0032] WL camera 2 - The second WL image sensor / camera sensor is for the stereo of the modular imaging device Or it can be used as part of a 3D imaging (target depth) configuration.

[0033] The light incident on this sensor passes through a short - pass filter to enable the sensor to image visible light wavelengths. The short - pass filter blocks infrared (IR) light that may be present in the clinical environment. The short - pass filter also blocks the IR emitted by the rangefinder if present. If present, the second WL camera sensor must be aligned with the first WL camera sensor.

[0034] A high - resolution wide - color - gamut display with a display - touch - screen function can be provided. The touch - screen function enables the user to manipulate the image and also enables the display to function as the primary user interface (UI) for the clinician / device operator, allowing for the input of patient information that can be collated or registered in some way with the captured image, either on the camera or when the information is uploaded to the cloud or other storage.

[0035] A rechargeable battery, such as a rechargeable lithium - ion battery with a battery - integrated gas - gauge function, can be used to power the modular imaging device. As is understood, other types of batteries may be used, or other power sources may be used.

[0036] A speaker on the modular imaging device can be used to communicate with the user and can also generate a camera click sound and / or other sounds to improve the user experience.

[0037] Battery status LED - Indicates the charging status of the battery in low - battery condition and during the charging operation.

[0038] System status LED - Indicates the status of the system by on / off or use of different colors, provides an indication of system OK / operating, or indicates the presence of an internal system problem.

[0039] 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 paper use.

[0040] FL LED - The light source of the modular device can include LEDs. In one example, excitation light such as fluorescence excitation light can be generated by a fluorescence (FL) LED. The fluorescence excitation light can be used to induce fluorescence from bacteria, i.e., as a response to illumination by the excitation light. The LED current is controlled by a closed-loop control where the setpoint of the control loop is managed by the MCU. A nominal FL LED drive current setpoint is established during the device manufacturing process to meet the minimum accurate optical irradiance and uniformity requirements. The optical efficiency of the LED is temperature-dependent. A temperature sensor measures the printed circuit board (PCB) temperature near the LED, which is used as an input to a control loop that adjusts the nominal drive current setpoint to compensate for changes in the radiative efficiency that depend on the LED temperature. As will be understood, other types of fluorescent light sources may be used instead of or in addition to the FL LED.

[0041] The ambient light sensor is provided to monitor the ambient light within 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 the FL imaging mode can be stored in the picture metadata. The light level can be useful during post-analysis. The measured ambient light level is also useful during white light imaging mode to enable or control the intensity of the WL torch and obtain. The ambient light sensor may be configured to indicate to the user when the imaging environment is sufficiently dark to take a fluorescence image. This can take the form of providing an indication that the imaging environment is satisfactory and / or not satisfactory depending on the imaging mode.

[0042] Distance meter - Using a distance meter, the distance between the camera sensor and the imaged target can be measured. The minimum accurate blue light irradiance and uniformity are effective within the range from the camera to the target distance. The distance meter provides feedback to the clinician / user to guide imaging at the correct distance by providing an indication that the appropriate distance has been reached. The target distance can be stored in the picture metadata. The target distance can be useful for a sticker detection algorithm used in the measurement process to determine the minimum and maximum expected sticker sizes within the sensor pixels, which are a function of the distance between the sticker and the camera sensor. In some embodiments, the measured change in the target distance can be used to initiate a focus change operation of the camera sensor.

[0043] Torch LED - One or more white light sources can be provided to illuminate the target during white light imaging mode. The white light source can include one or more white light LEDs. Other white light sources may be used in addition to or instead of the LEDs.

[0044] USB-C port - A USB-C port can be provided for battery charging, factory writing of software, factory testing and calibration of the device, and image download. Additional ports or alternative ports can be provided for information transfer and / or charging.

[0045] Exemplary embodiments of the modular handheld imaging device 100 are shown in FIGS. 1 to 5B. As shown in FIGS. 1 to 5B, in some exemplary embodiments, the base portion 110 of the device 100 can have a generally square or rectangular shape. The front surface of the base portion 110, i.e., the user-facing side surface 115, includes a display screen 120 for displaying images and videos captured by the device. Although shown as square or rectangular, the device can take any shape that reasonably supports a display screen such as a touch screen display. In addition to displaying images captured by the imaging device 100, the display screen also operates as a user interface, enabling the user to control the functions of the device via touch screen input.

[0046] On both sides of the device, on the side surface 125 of the device facing the patient, a handle region 130 may be disposed that is configured to facilitate the user's holding of the device during imaging. As shown in FIG. 4, the handle region can include protrusions or regions that extend sufficiently away from the base portion 110 to allow the user's fingers to grip or wrap around the protrusions. Various other types of handles as well as alternative handle positionings may be used. One consideration in such handle positions is the user's ability to balance the imaging device while using the device for imaging and while entering commands via the touch screen display. The weight distribution of the imaging device is also a consideration for providing a user-friendly and ergonomic device. The patient-facing side surface 125 of the device can also incorporate contacts 135 for wireless charging of the device.

[0047] As shown in FIGS. 11A to 11E, a charging station 136 can be provided for wireless charging of the device 100. As shown in the exemplary embodiment, the charging station 136 can include contacts such as contact pins 137 for wireless charging of the device 100. The contact pins 137 may be spring-biased and may be separated from each other to prevent short circuits due to other objects (i.e., small metal objects) being inadvertently placed on the contact pins 137. In one example, the raised portion on the 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.

[0048] According to one aspect of the present disclosure, the patient-facing side 125 of the device 100 also includes an optical housing 140. The optical housing portion 140 may be removable from the base portion 110, as shown in FIGS. 5A-5B. The optical housing portion 140 is shown as a rectangular housing configured to be received in a rectangular opening 145 on the base portion 110. However, both the optical housing portion 140 and the opening 145 may take other shapes, such as square, rectangular, elliptical, or circular. Further, the optical housing portion 140 may not have the same shape as the opening 145. Instead, a connector element configured to be received in the opening 145 of the base portion 110 or having the same shape may 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 disposed within the opening 145, it may be locked in place so that the optical housing portion 140 is locked to the base portion 110. In this configuration, electrical contacts are formed between the base portion 110 and the optical components received in the optical housing portion 140, and the components within the optical housing portion are powered by a power source such as a battery received in the base portion 110.

[0049] In various exemplary embodiments, the base portion 110 includes a heat sink 150. In an exemplary embodiment, the heat sink 150 forms a lip around the opening 145 of the base portion 110 configured to receive the optical housing portion 140.

[0050] As shown in FIGS. 5A and 5B, the optical housing 140 can take on different shapes or configurations. For example, as shown in FIG. 5A, the optical housing portion 140 has a generally flat rectangular shape. The optical components are arranged generally linearly across the width of the optical housing. FIG. 5B shows a second optical housing 185 that includes an endoscope portion 190. The optical components received in the second optical housing 185, unlike the optical housing portion 140, are received at the distal end 195 of the endoscope portion 190 of the second optical housing 185 and are not arranged linearly. The arrangement of the optical components varies for each optical housing based on the size and shape of the optical housing, as well as the number and type of optical components included in a given housing.

[0051] The optical housing portion 140 can include various optical components configured to facilitate the collection of optical signals from a target to be imaged. Characteristics that can vary from optical housing to optical housing include the following non-limiting examples, which can be included in any combination within each optical housing. Namely, the total number of image sensors, the number of image sensors configured for white light imaging (i.e., combined with a filter for white light imaging), and the number of image sensors configured for fluorescence imaging, where different image sensors for fluorescence imaging may be paired with different filters to allow passage of different ranges of fluorescence emission, with each range being configured to capture specific characteristics of a target (e.g., vascular or microvascular system, collagen, elastin, blood, bone, bacteria, malignant tumors, healthy or diseased cartilage, ligaments, tendons, connective tissue, lymphatic vessels, nerves, muscle, etc.).

[0052] The optical housing portion 140 can include one or more excitation light sources. The excitation light source can provide a single wavelength of excitation light selected to excite autofluorescence emission of tissue and fluorescence emission of induced porphyrins in tumor / cancer cells. Additionally or alternatively The excitation light source may provide an excitation light wavelength selected to excite the autofluorescence emission and / or the exogenous fluorescence emission of one or more of the tissues and bacteria within the wound site. 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.

[0053] Alternatively, the excitation light source may be configured to provide two or more wavelengths of excitation light. The wavelengths of the excitation light may be selected for different purposes, as will be understood by those skilled in the art. For example, by changing the wavelength of the excitation light, the depth to which the excitation light penetrates the surface of a target such as an operating table or a wound site can be changed. As the depth of penetration increases with a corresponding increase in wavelength, it is possible to use light of different wavelengths to excite the tissue beneath the surface of the target. In one example, excitation light having a wavelength in the range of 350 nm to 450 nm, for example 405 nm, and excitation light having a wavelength in the range of 550 nm to 600 nm, for example 572 nm, can penetrate the target tissue to different depths, for example up to about 500 μm to about 1 mm and about 2.5 mm respectively. Thereby, a user of the device, such as a physician, surgeon or pathologist, can visualize the surface of the target and the tissue cells beneath the surface of the target. Additionally or alternatively, excitation light having a wavelength in the near-infrared / infrared range may be used, for example, excitation light having a wavelength of about 750 nm to about 800 nm, for example 760 nm or 780 nm. Further, for penetration into tissue to deeper levels, the use of this type of light source may be combined with a second type of imaging / contrast agent such as an infrared dye (e.g., IRDye800, ICG). Thereby, for example, visualization of angiogenesis, vascular perfusion, and blood pooling within the target tissue becomes possible. Further, the usefulness of visualizing vascular perfusion is to improve anastomosis during reconstruction or to observe wound healing.

[0054] The imaging device 100 can include an additional light source such as a white light source for imaging the white light (WL) of the target surface. The use of white light provides the anatomical context of other images such as fluorescence images. The white light source can include one or more white light LEDs. Other white light sources may be used as needed. As will be understood by those skilled in the art, the white light source should be stable and reliable and should not generate excessive heat during long-term use.

[0055] The base portion 110 of the imaging device 100 can include a control unit for enabling switching between white light imaging and fluorescence imaging. The control unit may also enable the use of various excitation light sources together or separately, in various combinations, and / or sequentially. The control unit may cycle through various different combinations of light sources, may control the light sources sequentially, may strobe the light sources, or may control the timing and duration of the use of the light sources in another way. The control unit may be automatic, manual, or a combination thereof, as will be understood by those skilled in the art. As described above, the touch screen display 120 of the base portion 110 can function as a user interface for enabling control of the imaging device 100. Alternatively, instead of or in addition to the touch screen control unit, a manual operation control unit, such as a separate control unit such as a button, may be used. Such a manual operation control unit can be arranged, for example, on the handgrip 130 so that the control unit can be easily operated while the user is holding and using the imaging device.

[0056] The optical housing portion 140 of the imaging device 100 can also include one or more optical imaging filters configured to prevent the reflected excitation light from passing to the camera sensor. In one example, the optical imaging filter can also be configured to allow the passage of light having wavelengths corresponding to the autofluorescence emission of tissue cells and the fluorescence emission of induced porphyrins in the tissue cells. In another example, the device 100 can include one or more optical imaging filters configured to allow the passage of light corresponding to the autofluorescence emission of bacteria contained in the target and the exogenous fluorescence emission of bacteria by using a contrast agent on the target surface. Imaging device 100 can also include a filter configured to capture the fluorescence and autofluorescence of both bacteria and tissue.

[0057] These optical filters may be selected to detect specific optical signals from the target / tissue / wound surface based on the desired light wavelengths. Spectral filtering of the detected optical signals (e.g., absorption, fluorescence, reflection) can also be achieved using, for example, a liquid crystal tunable filter (LCTF), or an acousto-optic tunable filter (AOTF) which is a solid-state electronically tunable spectral bandpass filter. Spectral filtering can also include the use of a continuously variable filter and / or a manual bandpass optical filter. These filters / filtering mechanisms may be placed in front of the imaging sensor to generate multi-spectral, hyperspectral, and / or wavelength-selective imaging of the tissue. :

[0058] The imaging device 100 can be modified by using an optical or variably oriented polarizing filter (e.g., linear or circular in combination with the use of an optical waveplate) attached in a rational manner to an excitation / illumination light source and an imaging sensor. In this way, using the imaging device 100, the target surface can be imaged with polarized illumination and unpolarized detection or vice versa, or polarized illumination and polarized detection, using either white light reflection and / or fluorescence imaging. This can enable imaging of wounds with minimized specular reflection (e.g., glare from white light imaging), as well as imaging of fluorescence polarization and / or anisotropy-dependent changes in connective tissues (e.g., collagen and elastin) within the wound and surrounding normal tissue. This can provide useful information regarding the spatial orientation and organization of connective tissue fibers related to wound remodeling during healing [Yasui et al., (2004) Appl. Opt. 43:2861 - 2867].

[0059] In one exemplary embodiment shown in FIG. 12, the imaging device 200 includes three camera sensors 260, 265, 270, and each sensor includes a fixed filter 261, 266, 271. For example, first and second white light sensors configured to receive visible optical signals through dedicated filters fixed to each respective sensor can be provided. Further, the sensor for fluorescence imaging may be configured to pass various desired emission wavelengths to the fluorescence camera sensor. As described above, different optical housing portions can include different configurations of sensors, filters, and light sources that are configured together to create an image of a particular characteristic of the target.

[0060] FIG. 12 shows an exploded view of the optical housing 240 of the imaging device 200. As shown in FIG. 12, the base portion 210 can include a heat sink 212 disposed behind the heat sink 250 of the optical housing 240. The optical housing 240 further includes three camera sensors 260, 265, 270, a printed circuit board (PCB) 273, an outer heat sink gasket 252, a camera shroud 244, three optical filters 261, 266, 271, a light diffuser 253 for a white light source, an inner gasket / filter retainer 274, windows 275a, 275b, 275c, an adhesive tape 276 (or other means for fixing the windows), and a lens assembly tip 280 including features that allow for the attachment of accessories.

[0061] As will be understood by those skilled in the art, the arrangement of the components within the optical housing of an imaging device can take many configurations. Such configurations can be determined by the size of the device, the installation area of the device, and the number of components used. However, when arranging the components, functional factors should also be considered. For example, problems such as light leakage from the light source of the device and / or ambient light entering the optical housing can interfere with the proper or optimal operation of the device and can cause undesirable outputs such as image artifacts. The arrangement shown in FIG. 12 isolates the camera sensors to prevent light leakage from the light source and environmental light is an arrangement.

[0062] An exemplary PCB 273 is shown in FIG. 13. As shown, the PCB can include an excitation source 302, such as two fluorescent LEDs, such as a purple / blue LED having a wavelength of, for example, from about 400 nm to about 450 nm, and in one example, having a wavelength of about 405 nm. Additional LEDs having the same wavelength may be provided, or only one LED may be used. Further, it is contemplated that additional excitation sources having different wavelengths can be provided. The PCB 273 may also include two temperature sensors 304, a white light or torch LED 306 that provides white light for white light imaging, an ambient light sensor 308, and a distance meter 312, which may be, for example, a laser-based distance meter.

[0063] When the device 100 or 200 is held above the surface of the target tissue (e.g., a wound) to be imaged, the illumination source irradiates the surface of the tissue / wound with light of a narrow or wide bandwidth purple / blue wavelength or other wavelength or wavelength band, thereby generating a flat and uniform light field within the target area. The light can also illuminate or excite the tissue to a specific shallow depth. This excitation / illumination light can interact with normal and diseased tissue to generate optical signals (e.g., absorption, fluorescence, and / or reflection) within the target tissue, which are then captured by one of the camera sensors.

[0064] By changing the excitation wavelength and emission wavelength accordingly, imaging devices 100 and 200 can examine target tissue components (e.g., connective tissue and bacteria in a wound) at a specific depth within the surface and the target tissue (e.g., a wound site). For example, by changing from purple / blue (about 400 - 500 nm) to green (about 500 - 540 nm) wavelength light, excitation of deeper tissue / bacterial fluorescence sources can be achieved, for example, at a wound site. Similarly, by detecting longer wavelengths, fluorescence emission from tissue and / or deeper bacterial sources in the tissue can be detected at the tissue surface. For wound assessment, the ability to examine surface and / or subsurface fluorescence can be useful, for example, in the detection and potential discrimination of bacterial contamination, colony formation, critical colony formation, and / or infection that can occur on the surface as well as deep within a wound site (e.g., within a chronic non - healing wound site).

[0065] The handheld imaging devices 100 and 200 also include an imaging lens and an image sensor within the optical housing portions 140 and 240 of the devices. The imaging lens or lens assembly may be configured to focus filtered autofluorescence emission and fluorescence emission onto the image sensor. A wide - angle imaging lens or a fish - eye imaging lens is an example of a suitable lens. A wide - angle lens can provide a 180 - degree field of view. The lens can also provide an optical magnification. To enable discrimination between very small cell groups, a very high resolution is desirable for the imaging device. The image sensor is configured to detect filtered autofluorescence emission of tissue cells and fluorescence emission of induced porphyrins in the tissue cells. The image sensor can have 4K video capabilities, as well as autofocus and optical or digital zoom capabilities. A CCD or CMOS imaging sensor can be used. In one example, a CMOS sensor combined with a filter, i.e., a hyperspectral imaging sensor such as those sold by Ximea, can be used.

[0066] Exemplary filters include a visible light filter (https: / / www.ximea.com / en / products / hyperspectral-cameras-based-on-usb3-xispec / mq022hg-im-sm4x4-vis) and an IR filter (https: / / www.ximea.com / en / products / hyperspectral-cameras-based-on-usb3-xispec / mq022hg-im-sm5x5-nir). The handheld devices 100, 200 can also include a processor configured to receive the detected emission and output data regarding the detected filtered autofluorescence and / or exogenous fluorescence emission. The processor can have the ability to execute simultaneous programs seamlessly (including, but not limited to, wireless signal monitoring, battery monitoring and control, temperature monitoring, image reception / compression, and button press monitoring). The processor interfaces with internal storage, physical controls such as buttons, optics, and a wireless module. The processor also has the ability to read analog signals.

[0067] The imaging devices 100, 200 can also include a wireless module and may be configured to operate completely wirelessly. The wireless module can utilize high-throughput wireless signals and have the ability to transmit high-definition video with minimal latency. The device may be compatible with both Wi-Fi for data transmission and Bluetooth for quick connections. The device can utilize 5GHz wireless transmission band operation for separation from other devices. Additionally, the device can operate as a soft access point, which eliminates the need for an Internet connection and continues to connect the device and modules separately from other devices related to patient data security. The device can be configured for wireless charging and can include an inductive charging coil. Additionally or alternatively, the device may include a port configured to receive a charging connection.

[0068] Figures 14A and 14B show alternative embodiments of the hardware block diagrams of apparatuses 100 and 200. Figures 14A and 14B show exemplary block diagrams showing various components of the handheld imaging apparatuses 100 and 200 according to exemplary embodiments of the present disclosure.

[0069] The components of the handheld imaging apparatuses 100 and 200 can be grouped into an optical PCB and an electronics system. In the embodiment of Figure 14B, the optical PCB includes four fluorescence wavelength LEDs, two infrared LEDs, and two white light LEDs. The optical PCB further includes an ambient light sensor, a laser range finder, and a temperature sensor.

[0070] The optical PCB is operably coupled to the electronics system 302. The electronics system can 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 electronics system can further include components and systems that interface with other electronic components of the handheld imaging apparatus. For example, the electronics system can include a CMOS camera interface for an optical filter system and motor drive electronics. The electronics system can also include connectors for a fluorescence camera and a white light camera, respectively, to facilitate switching between the fluorescence imaging mode and the white light imaging mode described herein. Only two cameras, a white light camera and a fluorescence camera, are shown in Figure 14B, but the present disclosure contemplates the use of additional cameras, particularly white light cameras. For example, the exemplary block diagram of Figure 14A discloses the presence of three cameras, two white light cameras, and one fluorescence camera. The addition of further cameras is within the scope of the present disclosure.

[0071] Other supporting electronic device systems and components of the electronic device system can include memories such as flash memory devices, rechargeable batteries such as lithium-ion batteries, and inductive battery charging systems. Some components of the electronic device system can include communication components such as Wi-Fi and / or Bluetooth wireless subsystems, as well as spatial orientation components such as one or more of a magnetometer, an accelerometer, and a gyroscope.

[0072] The electronic device system can include various user control parts such as a power switch, a system status LED, a charging status LED, an image capture switch, a video capture switch, and an imaging mode switch. The various user control parts can interface with other components of the electronic device system via a user interface module that provides signals to the user control part.

[0073] Other components within the electronic system can include drivers for fluorescent, infrared, and white light LEDs, a USB hub for uplink or downlink data signals, and / or power from an external computer system such as a workstation or other computer that can connect the electronic system via the USB hub. The electronic device system can also include one or more devices that provide feedback to the user, such as, but not limited to, a speaker. Other feedback devices can include various auditory and visual indicators, tactile feedback devices, displays, and other devices.

[0074] The modular hand-held imaging devices 100, 200 of the present application can be used with various accessories. For example, the devices 100, 200 can be used with a drape 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 configured to fit onto the patient-facing side of the optical housing and isolate and / or separate the optical system of the optical housing from ambient light by forming a barrier therebetween. Examples of the types of drapes used with this device can be found, for example, in U.S. Provisional Patent Application No. 62 / 669,009, filed May 9, 2018, entitled "Light-Reducing Drape, Package for Drape, Method of Use, and Method of Deployment Thereof"; International Patent Application No. PCT / CA2019 / 000061, filed May 9, 2019, entitled "Imaging Drape, Package for Drape, Method of Use of Imaging Drape, and Method of Deployment of Drape"; U.S. Design Patent Application No. 29 / 647,110, filed May 9, 2018, entitled "Light-Reducing Drape"; and Design Application No. 29 / 676,893, filed January 15, 2019, entitled "Adapter for Supporting a Light-Reducing Drape", the entire contents of each of which are incorporated herein by reference.

[0075] According to an exemplary embodiment, a light-reducing drape 500 is disclosed. FIGS. 15A-15C show exemplary embodiments of the imaging drape 500. The imaging drape 500 is shown connected to an imaging device such as imaging devices 100, 200 as previously described in FIGS. 15D-15F herein. The drape 500 can be used in conjunction with any of the imaging devices disclosed herein. The drape 500 includes a connection element 501. In an exemplary embodiment, the connection element 501 includes a protrusion 510 used to form a press-fit or snap-fit connection with the imaging devices 100, 200. Protrusions (described below) on the imaging devices 100, 200 can engage with the protrusion 510 to provide a press-fit or snap-fit connection. Further, one or more protrusions 520 can be configured to engage with the protrusions of the imaging devices 100, 200 to better secure the imaging devices 100, 200 by gripping them with the drape. In some embodiments, the protrusion 520 is a toothed member that engages with the protrusions on the imaging device. When the imaging device is properly aligned and pushed down into the connection element, the protrusion 520 bites into the protrusions on the imaging device to provide a snap-fit connection.

[0076] The connection element 501 can also include an end cup member 550 to help facilitate a snap-fit connection between the connection element 501 and the imaging device. As shown in FIG. 15A, the end cup member 550 can be a smooth member disposed at both ends of an opening 533 formed within the connection element 501. The end cup member 550 can provide guidance for centering / positioning the imaging head / optical head of the imaging device snap-fitted to the connection element 501.

[0077] FIG. 15A shows that the protrusion 520 is disposed on the long side of the rectangular shape, and the end cup A rectangular opening 533 in which the material 550 is disposed is shown. However, it is also contemplated that the protrusion 520 may be disposed on the short side of the rectangular shape, and the end cup member 550 may be disposed on the long side of the rectangular shape. In FIG. 15A, two end cup members 550 are shown, but only one end cup member 550 may be used on one side of the opening 533. Further, in some embodiments, the connection element 501 may not include the end cup member 550. In this embodiment, the protrusion 520 may be disposed around most or all of the perimeter of the opening 533 on the connection element 501. The connection element 501 can be formed of injection molded plastic as described above.

[0078] FIG. 15A shows a top perspective view of the connection element 501 fixed to the drape. FIG. 15B shows a top view of the connection element 501 and an external view of the drape, and FIG. 15C shows a bottom view of the connection element 500 and a view of the portable imaging environment formed by the interior of the drape.

[0079] The connection element 501 can also include an upper flat surface 503, a one-way valve such as a flap valve 555, and a protrusion 554. As shown, the protrusion 554 is disposed on the upper surface of the connection element 501. Thus, the protrusion 554 can be seen in the top view of FIG. 15B, but the protrusion 554 cannot be seen from the interior of the drape in the view of FIG. 15C. The protrusion 554 helps to keep the drape material out of the imaging field of view.

[0080] In the embodiments of FIGS. 15A - 15F, the connection element 501 may be formed of an injection - molded plastic such as polyethylene. Thus, the connection element 501 may be a relatively rigid member. In some embodiments, the connection element 501 has a thickness of about 1.8 mm. The protrusion 554 may be formed of the same material as the rest of the connection element 501, or may be less rigid than the rest of the connection element 501. Thus, the protrusion 554 may be thinner than the rest of the connection element 501. The material of the drape body may be formed of the same material as the connection element 501, but does not have to be injection - molded to be less rigid than the connection element 501 (including the protrusion 554). In some embodiments, the material of the drape body is also thinner than the connection element 501 (including the protrusion 554). The drape body may be formed of a soft material welded to the relatively rigid material of the connection element 501. Thereby, the flap valve 555 can be formed of the material of the drape body and integrated into the drape, and the manufacturing cost can be reduced.

[0081] The connection element 501 also includes an opening 533 to provide FL and / or white - light imaging from the imaging devices 100, 200 within the internal environment of the drape. In the embodiments of FIGS. 15A - 15C, the opening 533 is substantially rectangular in shape. However, it is further contemplated that other shapes may be used.

[0082] FIGS. 15D - 15F show an example of an imaging device 600 fixed to the connection element 501 of the drape shown in FIGS. 15A - 15C. The imaging device 600 can be configured as described with respect to the devices 100, 200 above. The imaging device 600 is firmly fastened to the connection element 501 via a snap - fit connection that prevents / reduces ambient light from entering the interior of the drape through the upper part of the drape. The protrusion 670 of the imaging device 600 can engage with the protrusion 520 and the ridge 510 of the connection element 501 to provide a snap - fit connection, as described above.

[0083] An exemplary embodiment of the modular hand-held imaging device 600 is shown in FIGS. 15G and 15H. The imaging device 600 includes a substantially square or rectangular base portion 610. The front surface of the base portion 610, i.e., the user-facing side surface 615, includes a display screen 620 for displaying images and videos captured by the device. The protrusion 670 protrudes outward from the optical head / optical housing 640, but alternatively, it may be disposed on the base portion 610. FIG 15G shows the protrusion 670 disposed at the top of the base portion 610, but it is also contemplated that the protrusion 670 may be disposed on other sides of the base portion 610 depending on the position of the protrusion 520 on the connection element 501.

[0084] Although shown as square or rectangular, the imaging device 600 can take any shape that reasonably supports a display screen such as a touch screen. In addition to disclosing the images captured by the imaging device 600, the display screen also operates as a user interface, enabling the user to control the functions of the device via touch screen input.

[0085] On both sides of the device, on the side surface 625 facing the patient of the device, a handle region 630 configured to facilitate the user holding the device during imaging may be disposed. The patient-facing side surface of the device can also incorporate contacts 635 for wireless charging of the device.

[0086] According to one aspect of the present disclosure, the patient-facing side surface of the device 600 also includes an optical housing 640. The optical housing 640 may be removable from the base portion 610. The optical housing portion 640 is shown as a rectangular housing configured to be received in an opening of the connection element on the drape.

[0087] The optical housing 640 can take different configurations. For example, as shown in FIG. 15H, the optical housing portion 640 has a generally flat rectangular shape. The optical components for FL and / or white light imaging are arranged generally linearly across the width of the optical housing. The optical components are described in more detail above.

[0088] According to another aspect of the present disclosure, the imaging devices 100, 200, 600 of the present disclosure can be used with a sterile drape. The sterile drape is configured to form a sterile barrier between the imaging devices 100, 200, 600 and the environment in which the imaging device is used. Exemplary embodiments of the sterile drape for use with the imaging device of the present disclosure are shown in FIGS. 16A-16C. As shown in FIG. 16A, the sterile drape 700 may be configured to receive the body of the imaging device 800. When the sterile drape is placed on the imaging device 800, the imaging device can engage with the light reduction drape 500 as described above with respect to FIGS. 15A-15H and as shown in FIGS. 16B and 16C.

[0089] The optical housing may be configured such that a single adapter fits all optical housings to attach the light reduction drape. Alternatively, separate adapters may be provided for engaging each optical housing.

[0090] According to one aspect of the present disclosure, a modular handheld device can be used to acquire a three-dimensional fluorescence image of a target. Systems and methods for acquiring such three-dimensional images are disclosed in U.S. Provisional Application No. 62 / 793,837, filed on January 17, 2019, entitled "Systems, Methods, and Apparatus for Three-Dimensional Imaging, Measurement, and Display of Wounds and Tissue Specimens," the entire contents of which are incorporated herein by reference.

[0091] Other uses of the device may include the following. · Imaging based on clinical and research of small and large (e.g., veterinary) animals.

[0092] · Detection and monitoring of contamination (e.g., bacterial contamination) in the preparation of food / animal products in the meat, poultry, dairy, fish, and agricultural industries.

[0093] · Detection of "surface contamination" (e.g., bacterial or biological contamination) in public (e.g., healthcare) and private environments.

[0094] · Multi - spectral imaging and detection of cancer in human and / or animal patients. · As a research tool for multi - spectral imaging and monitoring of cancer in experimental animal models of human diseases (e.g., wounds and cancer).

[0095] · Forensic detection of latent fingerprints and biological fluids on, for example, non - biological surfaces. · Imaging and monitoring of dental plaque, carriers, and cancer in the oral cavity.

[0096] · Imaging and monitoring devices in clinical microbiology laboratories. · Testing of antibacterial agents (e.g., antibiotics), disinfectants.

[0097] The device can generally include i) one or more excitation / illumination light sources, ii) one or more image sensors that can be combined with one or more emission filters or spectral filtering mechanisms. The device can have a view / control screen (e.g., a touch - sensitive screen), an image capture section, and a zoom control section. The device may also have iii) wired and / or wireless data transfer ports / modules, iv) a power supply and a power / control switch.

[0098] The device can include software that enables a user to control the device, including control of imaging parameters, visualization of images, storage of image data and user information, transfer of images and / or related data, and / or related image analysis (e.g., diagnostic algorithms). The device can further include software for measuring an imaged target and calculating amounts of various items seen in the imaged target. For example, if the target is a wound, the device can include software configured to calculate wound size, wound depth, wound perimeter length, wound area, wound volume, and to identify various types of tissue (collagen, elastic, vascular) within the wound and the percentage of each tissue within the wound. Further, the device can determine the amount or quantity of bacteria within the wound, the bacterial load, distinguish 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, filed February 2, 2019, entitled "Imaging and Analysis of Wounds", and International Patent Application No. PCT / CA2019 / 000002, filed January 15, 2019, entitled "Imaging and Analysis of Wounds", the entire contents of each of which are incorporated herein by reference.

[0099] The device may be configured to overlay a white light image, a fluorescence image, a thermal image, and other images of the target. The device may be configured to create a three-dimensional map of the target. The device may be configured to enhance color differentiation between different tissue types identified within the image. The device may be configured to determine tissue classification of the target based on different colors or image features captured in the fluorescence image. The device can be configured to draw a boundary line between diseased and healthy tissue therein and provide a map for the user to selectively remove diseased tissue while not touching the surrounding healthy tissue in a targeted manner.

[0100] Various types of filters, power sources, light sources, excitation light sources, image sensors, and charging configurations may be present in the devices of the present disclosure. Examples of such components are described, for example, in U.S. Patent No. 9,042,967, which is the national stage application of PCT / CA2009 / 000680, filed internationally on May 20, 2009, claiming the benefit of U.S. Provisional Application No. 61 / 054,780, filed on May 20, 2008, the entire content of each of which is incorporated herein by reference. Additional components are described in U.S. Provisional Patent Application No. 62 / 625,983, filed on February 3, 2018, entitled "Devices, Systems, and Methods for Tumor Visualization and Removal", and U.S. Provisional Patent Application No. 62 / 625,967, filed on February 2, 2018, entitled "Devices, Systems, and Methods for Tumor Visualization and Removal", the entire content of each of which is incorporated herein by reference. Additional components are described in U.S. Provisional Patent Application No. 62 / 793,764, filed on January 17, 2019, entitled "Multimodal Systems for Visualization of Disease", and U.S. Provisional Patent Application No. 62 / 857,155, filed on June 4, 2019, entitled "Devices, Systems, and Methods for Tumor Visualization", the entire content of each of which is incorporated herein by reference. (filed). The entire content of each of which is incorporated herein by reference.

[0101] The imaging systems and methods disclosed herein may rely on tissue autofluorescence, bacterial autofluorescence, and autofluorescence of other target materials. Additionally or alternatively, this application contemplates the use of exogenous contrast agents that may be applied locally, ingested, or applied in other ways. Examples of such agents for imaging targets are described, for example, in U.S. Patent No. 9,042,967, which is the national stage application of PCT / CA2009 / 000680, filed internationally on May 20, 2009, claiming 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 Patent Application No. 62 / 625,983, filed on February 3, 2018, entitled "Apparatus, System, and Method for Visualization and Removal of Tumors," and U.S. Provisional Patent Application No. 62 / 625,967, filed on February 2, 2018, entitled "Apparatus, System, and Method for Visualization and Removal of Tumors," 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 "Apparatus, System, and Method for Visualization of Tumors," the entire contents of each of which are incorporated herein by reference.

[0102] The device interface port can support both wired (e.g., USB) or wireless (e.g., Bluetooth, WiFi, and similar modalities) data transfer or third-party add-on modules to various external devices, such as a head-mounted display, an external printer, a tablet computer, a laptop computer, a personal desktop computer, a wireless device that enables transfer of imaging data to a remote site / other device, a global positioning system (GPS) device, a device that enables use of additional memory, and a microphone.

[0103] The device can be used to identify the type of bacteria in order to induce debridement of the wound area and assist in the determination of appropriate treatment / drugs / antibiotics.

[0104] The device may also be attached to a mounting mechanism (e.g., a tripod or stand) for use as a relatively stationary optical imaging device for imaging white light, fluorescence, and reflection of objects, materials, and surfaces (e.g., the human body). Thereby, the device can be used on a desk or table or for imaging of "assembly line" of objects, materials and surfaces. In some embodiments, the mounting mechanism may be movable.

[0105] Other features of this device can include the ability to record digital images and videos, audio, methods for documentation (e.g., using image storage and analysis software), and wired or wireless data transmission for remote telemedicine / E-health needs.

[0106] In addition to providing detection of bacterial strains, the device can be used to distinguish the presence and / or location of different bacterial strains (e.g., Staphylococcus aureus or Pseudomonas aeruginosa) in, for example, the wound area and surrounding tissue. This can be based on different autofluorescence emission signatures of different bacterial strains, including those within the 490 - 550 nm and 610 - 640 nm emission wavelength bands when excited by light such as light of about 405 nm. Combinations of other wavelengths can be used to distinguish other species in the image. This information can be used to select appropriate treatment such as the selection of antibiotics. when excited by light such as light of about 405 nm. Combinations of other wavelengths can be used to distinguish other species in the image. This information can be used to select appropriate treatment such as the selection of antibiotics.

[0107] The device can be scanned above any wound site (e.g., on the body surface) such that the excitation light can illuminate the wound area. The wound can then be examined using the device so that an operator can view the wound in real time, for example via a viewer on an imaging device or via an external display device (e.g., a head-up display, a television display, a computer monitor, an LCD projector, or a head-mounted display). It may also be possible to transmit the images obtained in real time (e.g., via wireless communication) from the device to a remote viewing site for telemedicine purposes, or to directly transmit the images to a printer or a computer memory storage device. Imaging can be performed within the routine clinical evaluation of a patient having the wound.

[0108] Prior to imaging, fiducial markers (e.g., using a non-erasable fluorescent ink pen) can be placed on the skin surface near the wound edge or periphery. For example, four spots of different fluorescent ink colors from separate non-erasable fluorescent ink pens, each of which can be provided to the clinical operator as a kit, can be placed near the wound edge or boundary on the normal skin surface. These colors can be imaged by the device using the excitation light and a multispectral band filter that matches the emission wavelengths of the four ink spots. Image analysis can then be performed by overlaying the fiducial markers for image registration. Thus, the user may not need to align the imaging device between different imaging sessions. This technique can facilitate long-term (i.e., over time) imaging of the wound, and thus, the clinical operator can image the wound over time without the need to align the imaging device each time an image is acquired.

[0109] Furthermore, to assist in the intensity calibration of fluorescence images, a disposable, simple fluorescence standard "strip" can be placed within the field of view during wound imaging (e.g., by using a mild adhesive that temporarily attaches the strip to the skin). The strip can be impregnated with one or several different fluorescent dyes at various concentrations that can generate a predetermined calibrated fluorescence intensity when illuminated by an excitation light source, and the excitation light source can have a single (e.g., 405 nm) or multiple fluorescence emission wavelengths or wavelength bands for image intensity calibration. The disposable strip can also have the above four spots from a separate non-fading fluorescent ink pen (e.g., those of different diameters or sizes, those of different fluorescent ink colors each having a unique black dot arranged adjacent to them). With the strip placed near the wound edge or boundary on the normal skin surface, the device can be used to capture white light and fluorescence images. The strip can provide a convenient way to capture multiple images of a given wound over time and then align the images using image analysis. Also, the fluorescence "intensity calibration" strip may include additional linear measurement devices such as a fixed-length ruler to assist in spatial distance measurement of the wound. Such a strip may be an example of a calibration target that can be used with the device to assist in the calibration or measurement of image parameters (e.g., wound size, fluorescence intensity, etc.), and other similar calibration targets can be used.

[0110] During multiple imaging sessions, the fluorescence intensity of the tissue may change slightly if the distance changes, so it may be desirable to enhance the consistency of the imaging results and reproduce the distance between the device and the wound surface. Thus, in one embodiment, the device may have a rangefinder to determine a fixed or variable distance between the device and the wound surface.

[0111] The device can be used to capture white light images of the entire wound area, including normal surrounding normal tissue, using a measuring device (e.g., a ruler) placed within the imaging field of view. This enables visual evaluation of the wound area, as well as calculation / determination of quantitative parameters such as the area, circumference, diameter, and topographic profile of the wound area. Wound healing can be evaluated by planar measurement of the wound area at multiple time points (e.g., at the time of clinical visit) until wound healing. The time course of wound healing can be compared to the predicted healing time calculated by measuring the reduction in wound radius at multiple time points using the formula R = √A / π (where R is the radius, A is the planar wound area, and π is the constant 3.14). This quantitative information regarding the wound area can be used to track and monitor changes in wound appearance over time in order to evaluate and determine the degree of wound healing caused by natural means or any therapeutic intervention. This data can be electronically stored in the patient's health record for future reference. White light imaging can be performed during the initial clinical evaluation of the patient by the operator.

[0112] The device may be designed to detect all or most of the autofluorescence (AF) of the tissue. For example, using a multispectral band filter, the device can image tissue autofluorescence, as well as blood-related light absorption, from, for example, collagen (types I, II, III, IV, V, and others) that appears green under 405nm excitation, elastin that appears greenish-yellow-orange, reduced nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD) that emits a blue-green autofluorescence signal, and bacteria / microorganisms that mostly appear to have broad (e.g., green and red) autofluorescence emission.

[0113] Image analysis can include calculating the ratio of red to green AF within the image. Intensity calculations can be obtained from regions of interest within the wound area image. The pseudocolored image can be mapped onto the white light image of the wound area.

[0114] The device can map the in-vivo distribution of bacteria on the skin within and around the wound site, and thus assist in targeting specific tissue areas that require swabbing or biopsy for microbiological examination. Further, by using the imaging device, it may be possible to monitor the response of bacterially infected tissue to various medical treatments, including the use of antibiotics and photodynamic therapy (PDT), hyperbaric oxygen therapy (HOT), low-level light therapy, or other therapies such as anti-matrix metalloproteinase (MMP). The device may be useful for visualizing the in-vivo distribution of bacteria on the surface of the wound as well as within the deep tissues, and may also be useful for the surrounding normal tissue. Thus, the device may be useful for showing the spatial distribution of the infection.

[0115] Generally, the device can be used for imaging and / or monitoring targets such as skin targets, tumor targets, wound targets, limited anatomical spaces or cavities, oral targets, otolaryngology targets, eye targets, genital targets, anal targets, and any other suitable targets on the subject.

[0116] The image analysis algorithm can provide one or more of the following features.

[0117] Patient digital image management · Integration of various image acquisition devices · Record all imaging parameters including all exogenous fluorescent contrast agents · Multiple scales and calibration settings · Built-in spectral image unmixing and computational algorithms for quantitatively determining the autofluorescence of tissue / bacteria and the fluorescence signals of exogenous agents · Convenient annotation tools · Digital archive · Web publishing Basic image processing and analysis · A complete set of image processing and quantitative analysis functions The image stitching algorithm enables stitching a series of panoramic images or partially overlapping images of the wound site into a single image, either in automatic mode or manual mode.

[0118] ·Easy-to-use measurement tool ·Intuitive setting of processing parameters ·Convenient manual editor Report generation ·Powerful image report generator with specialized templates that can be integrated into existing clinical report infrastructure or telemedicine / e-health patient medical data infrastructure. Reports can be exported, for example, to PDF, Word, Excel.

[0119] Large library of automation solutions ·Customized automation solutions for various areas of wound assessment, including quantitative image analysis.

[0120] Image analysis algorithms, techniques, or software have been described, but this description also extends to computing devices, systems, and methods for performing this image analysis.

[0121] Image guidance The device may also be useful for providing fluorescence image guidance, for example, in surgical procedures, without the use of dyes or markers. Certain tissues and / or organs may have different fluorescence spectra (e.g., intrinsic fluorescence) when imaged using an imaging device or when viewed under specific excitation light conditions.

[0122] Food applications The imaging device can also be useful for monitoring food (e.g., meat products) for contamination. This can be useful, for example, in the preparation of meat, poultry, dairy products, fish, and food / animal products in the agricultural industry. The device can be used as part of an integrated interdisciplinary approach to analytical laboratory services within this sector, which can provide the ability to include image-based detection of contamination and guidance for obtaining samples for testing. The device can be used for real-time detection, identification, and monitoring of the level of contamination / mixing of meat by bacteria and other microorganisms in food. This can be used for tracking bacterial contamination in a food processing plant environment and thus can provide an image-based method for determining food safety and quality. In embodiments where the device is handheld, compact, and portable, the imaging device can be useful in the food preparation field for determining food safety from bacterial / microbial contamination. The device can also be used, for example, as part of a food safety and quality control inspection process, for relatively rapid detection and analysis of bacteria / microorganisms in meat samples (and preparation surfaces) collected or sampled during processing and in finished food. This device can be used in the meat, horticulture, and aquaculture industries when implementing a food safety inspection / detection process that meets 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. This technology can be useful as a fecal contaminant detection system because the bacteria produce porphyrins that can be easily detected by the device.

[0123] Detection of foodborne pathogens such as Listeria monocytogenes (LM) in food samples and processing lines And accurate identification can be important for both ensuring food quality assurance and tracking the spread of bacterial pathogens within the food supply source. Current detection methods used in food manufacturing and processing facilities typically rely on multiple random surface samplings (e.g., swabbing) of the facility, and subsequent molecular-based diagnostic assays (e.g., real-time polymerase chain reaction, RT-PCR) that can typically provide a quantitative confirmation of the presence of LM within 24 - 72 hours. However, due to given time and cost constraints, typically only randomly selected areas of a given food manufacturing facility are tested for pathogen contamination at one time, and the significant possibility of undersampling during "first pass" surface swabbing of equipment, undetected pathogens can cause devastating health and economic consequences. Furthermore, i) the inability to rapidly sample all surface areas during "first pass" swabbing to identify areas with a high probability of infection, ii) the inability to visually document this initial screening process (e.g., no currently available imaging methods), iii) the time-consuming nature of obtaining experimental results, iv) the high costs associated with current methods, and v) more importantly, the possibility of missing an infection by a deadly pathogen, are driving efforts to improve the cost-effective early and accurate detection of foodborne pathogens.

[0124] The device may be useful for providing a relatively rapid and accurate way to detect such pathogens. The device can be used with an assay of a multi-color fluorescent probe “cocktail” (e.g., a combination of two or more contrast agents) that can clearly identify (and visualize) only viable Listeria bacteria from other Listeria species using highly specific gene probe technology. This enables specific detection of live LMs in real time and potentially minimizes the need for standard time-consuming concentration methods. This method can also be extended to include the detection of other pathogens of interest, including Enterobacter sakazakii, Campylobacter species (C. coli, C. jejuni, and C. lari), coliforms and Escherichia coli species bacteria (including lactose- and indole-negative E. coli), Salmonella, all bacteria belonging to the Staphylococcus aureus species and all bacteria separately belonging to the Staphylococcus genus, and Pseudomonas aeruginosa. Other bacteria may be detectable by selecting appropriate probes or combinations of probes. For example, a combination of two or more contrast agents may be designed to be specific for a particular bacterium and may result in a unique detectable fluorescence signature when imaged using an imaging device.

[0125] The imaging device can be used for relatively rapid “first pass” screening of food preparation and handling surfaces for targeted swab collection and microbiological testing (e.g., including multiplexed targeted probes or combinations of probes when combined with an applied exogenous bacteria-specific contrast agent). This device enables relatively rapid image-based surveys of any surface of equipment and food, and can capture in real time the fluorescence signature of food-derived bacteria / pathogens. The device can be used in combination with, for example, assays (and combinations thereof) of multi-color fluorescence probes “cocktails” that can clearly identify (and visualize) only viable Listeria bacteria from other Listeria species using highly specific gene probe technology as described above. Such probe “cocktails” are known to be sensitive to such pathogens and can be designed to specifically target specific pathogens based on a particular combination of probes known to give a signature fluorescence response. In addition to the detection of such pathogens, the device may be able to distinguish the presence and / or location of different strains based on their different signature fluorescence responses.

[0126] Surface contamination The imaging device can be useful for detecting surface contamination, such as detecting “surface bacterial contamination” in healthcare settings. This device can be used to detect and image the presence of bacteria / microorganisms and other pathogens on various surfaces / materials / instruments (especially those related to surgery) in hospitals, long-term care facilities, and the homes of the elderly, where contamination is a major source of infection. The device can be used in conjunction with standard detection, identification and enumeration of indicator organisms and pathogen strategies. The system and method disclosed herein can form a system as outlined below and can perform a process as outlined below.

[0127] The system and method disclosed herein can form a system as outlined below and can perform a process as outlined below.

[0128] A method | system | apparatus for illuminating a subject with light of calibrated intensity and capturing a close-up fluorescence digital image, - An optical rangefinder, - A digital camera sensor with an optical fluorescence filter, - One or more narrow wavelength band light emitters, - A computing processor with a memory, - A user display screen, - A user input control unit, and Thereby, - The light emitter is turned on, - A preview camera image is presented to the user via the display screen, - The value of the rangefinder is presented to the user via the display screen, - The user can activate the camera to capture an image, Thereby, the user can Set the intensity of the light on the subject by adjusting the height of the apparatus from the subject according to the rangefinder value on the screen, And capture an image.

[0129] A method | system | apparatus for capturing a close-up digital image with a consistent magnification and perspective view, - An optical rangefinder, - One or more similar digital camera sensors, - A computing processor with a memory, - A user display screen, - A user input control unit, and Thereby, - A preview camera image is presented to the user via the display screen, - The value of the rangefinder is presented to the user via the display screen, - The user can activate one of the cameras or another camera to capture an image, Thereby, the user can Set the field of view of the subject by adjusting the height of the apparatus from the subject according to the rangefinder value on the screen, And capture an image.

[0130] A method | system | apparatus for capturing a close - up digital image of a subject when measurement preparation is complete, - An optical rangefinder, - A digital camera sensor, - A computing processor with a memory, - A user display screen, - A user input control unit, and - Image processing software, whereby, - The subject has two visible wound stickers attached, - A preview camera image is presented to the user via the display screen, - The value of the rangefinder is presented to the user via the display screen, - When detected using image processing, the positions of the two stickers are continuously presented to the user via the display screen, - The user can operate the camera to capture an image when a sticker is detected, whereby, the user - Sets the appearance of the subject by adjusting the height of the apparatus from the subject according to the rangefinder value on the screen, - Sets the appearance of the subject by adjusting the position of the apparatus relative to the subject so that a sticker is detected, - Can capture an image.

[0131] Those skilled in the art having the benefits of this disclosure will understand that this disclosure provides various exemplary devices, systems, and methods for intraoperative and / or in - vitro visualization of tumors and / or residual cancer cells on resection margins. Further modifications and alternative embodiments of the various aspects of this disclosure will be apparent to those skilled in the art in view of this description.

[0132] Furthermore, the apparatus and method can include additional components or steps that are omitted from the drawings for purposes of illustration and / or clarity of operation. Accordingly, this description should be construed as illustrative only and is for the purpose of teaching one of ordinary skill in the art a general manner of practicing the present disclosure. It is to be understood that the various embodiments shown and described herein are to be construed as illustrative. After gaining the benefit of the description herein, one of ordinary skill in the art will appreciate that elements and materials, as well as their arrangement, may be substituted for those shown and described herein, parts and processes may be reversed, and particular features of the present disclosure may be utilized independently. Modifications may be made to the elements described herein without departing from the spirit and scope of the appended claims, which include the present disclosure and its equivalents.

[0133] It is to be understood that the specific examples and embodiments described herein are non-limiting and that modifications to the structure, dimensions, materials, and methodologies can be made without departing from the scope of the present disclosure.

[0134] Furthermore, the terminology of this description is not intended to be limiting. For example, spatially relative terms such as "beneath," "below," "lower," "above," "upper," "bottom," "right," "left," "proximal," "distal," "front," etc. can 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 arrangements) of the device in use or operation in addition to the positions and orientations shown in the drawings.

[0135] For the purposes of this specification and the appended claims, unless otherwise indicated, all amounts, percentages or ratios used in this specification and the claims, and all numerical values representing other quantities, should be understood to be modified in all instances by the term "about" if they are not already so. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and the appended claims are approximate values that may vary depending upon the desired properties sought to be obtained by the present disclosure. At a minimum, and not as an attempt to limit the application of the doctrine of equivalents to the claims, each numerical parameter should be construed in light of the reported number of significant digits and by applying ordinary rounding techniques. Rather than an attempt to limit the application of the doctrine of equivalents to the claims, each numerical parameter should at least be construed in light of the reported number of significant digits and by applying ordinary rounding techniques.

[0136] Although the numerical ranges and parameters setting forth the broad scope of the present disclosure are approximations, 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 the respective test measurements. Further, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein.

[0137] 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 singular form of any word, include plural referents unless expressly and specifically limited to one referent. As used herein, the term "include" and its grammatical variations are intended to be non-limiting, so that the listing of items in a list is not to be construed as excluding other like items that may be substituted or added to the listed items.

[0138] Although the present disclosure has been described in detail with respect to various exemplary embodiments, it should be understood that the description is not to be considered as limiting, since many modifications are possible within the broad scope of the appended claims, including equivalents thereof.

Claims

**Claim 1** A portable hand-held imaging system comprising: at least one excitation light source configured to emit excitation light during fluorescence imaging; a first filter configured to detect 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 by the excitation light and to allow passage to a first image sensor; a white light source configured to emit white light during white light imaging; a second filter configured to detect an optical signal having a wavelength within the visible light range in response to illumination of the target surface by the white light and to allow passage to a second image sensor; 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. **Claim 2** The system of claim 1, wherein the at least one excitation light source is 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, and / or combinations thereof. **Claim 3** The system of claim 1 or 2, wherein the at least one excitation light source is configured to emit excitation light having a wavelength of about 400 nm to about 450 nm. **Claim 4** The system of any one of claims 1 to 3, wherein the at least one excitation light source is configured to emit excitation light having a wavelength of about 405 nm ± 10 nm. **Claim 5** The system of any one of claims 1 to 4, wherein the at least one excitation light source is coupled to a housing of the portable hand-held imaging system. **Claim 6** The system of any one of claims 1 to 5, wherein the first filter is further configured to block passage of optical signals having a wavelength of 405 nm ± 10 nm. **Claim 7** The system according to any one of claims 1 to 6, wherein the first filter is configured to allow an optical signal having a wavelength of about 500 nm to about 550 nm and / or an optical signal having a wavelength of about 600 nm to about 660 nm to pass through the first filter and reach the first image sensor.

8. The system according to any one of claims 1 to 7, wherein the at least one excitation light source includes first and second violet / blue LEDs, and each LED is configured to emit light having a wavelength of 405 nm ± 10 nm.

9. The system according to any one of claims 1 to 8, further comprising a housing having a display on a front surface.

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

11. The at least one excitation light source includes first and second violet / blue LEDs, and each LED is configured to emit light having a wavelength of 405 nm ± 10 nm. The system according to any one of claims 1 to 11.

12. The system according to claim 11, wherein the first and second violet / blue LEDs are disposed on both sides of a longitudinal axis of the housing, and 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 detachably attached to the display unit.

15. The system according to claim 14, wherein the at least one excitation light source is included 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 detachably receive the optical unit.

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

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

20. The system according to any one of claims 1 to 19, further comprising a thermal sensor configured to detect thermal information regarding the surface of the target.

21. The system according to any one of claims 1 to 20, further comprising an ambient light sensor configured to indicate when the ambient light conditions are sufficient to enable fluorescence imaging.

22. The system according to any one of claims 1 to 21, further comprising a rangefinder.

23. The system according to any one of claims 1 to 22, further comprising a third filter configured to detect an optical signal having a wavelength within the visible light range in response to illumination of the surface of the target by the white light and to enable passage to a third image sensor.

24. The system according to claim 23, wherein the processor is further configured to receive image data from the second and third image sensors and output a stereoscopic or three-dimensional image.

25. The system according to any one of claims 1 to 24, further comprising a Wi-Fi and / or Bluetooth antenna.

26. The system according to any one of claims 1 to 25, wherein the processor is configured to transmit and / or receive data wirelessly.

27. The system according to any one of claims 1 to 26, further comprising a power source.

28. The system according to any one of claims 1 to 27, wherein the excitation light source includes a first excitation light source and a second excitation light source.

29. The system according to claim 28, wherein the first excitation light source is 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, and / or combinations thereof.

30. The system according to claim 29, wherein the first excitation light source is configured to emit excitation light having a wavelength of about 400 nm to about 450 nm.

31. The system according to claim 30, wherein the first excitation light source is configured to emit excitation light having a wavelength of about 405 nm ± 10 nm.

32. The system according to claim 28, wherein the second excitation light source is 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, and / or combinations thereof.

33. The system according to claim 32, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 750 nm to 800 nm.

34. The system according to claim 33, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 760 nm to about 780 nm.

35. The system according to claim 34, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 760 nm ± 10 nm.

36. The system according to claim 34, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 770 nm ± 10 nm.

37. The system according to claim 34, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 780 nm ± 10 nm.

38. The system according to any one of claims 1 to 37, wherein each of the first and second image sensors includes a complementary metal oxide semiconductor (CMOS) sensor.

39. The system according to any one of claims 1 to 38, wherein the first filter is fixed to the first image sensor.

40. The system according to any one of claims 1 to 39, wherein the second filter is fixed to the second image sensor.

41. The system according to any one of claims 1 to 40, further comprising an infrared radiation source.

42. The system according to claim 41, 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.

43. The system according to claim 42, wherein the processor is further configured to generate a three-dimensional map of the target surface based on the detected reflected infrared radiation.

44. The system according to claim 43, wherein the processor is further configured to generate a three-dimensional fluorescence image of the target on the surface based on the three-dimensional map, the two-dimensional white light image of the target surface, and the two-dimensional fluorescence image of the target surface.

45. A portable modular hand-held imaging system, a first housing portion, at least one excitation light source configured to emit excitation light during fluorescence imaging, a first filter configured to detect 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 the target surface by the excitation light and to enable passage to a first image sensor, a white light source configured to emit white light during white light imaging, a second filter configured to detect an optical signal having a wavelength within the visible light range in response to illumination of the target surface by the white light and to enable passage to a second image sensor, the first housing portion including: a second housing portion configured to releasably receive the first housing portion, a display, 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, the system including the second housing portion.

46. The system according to claim 45, wherein the at least one excitation light source is 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, and / or combinations thereof.

47. The system according to claim 45 or 46, wherein the at least one excitation light source is configured to emit excitation light having a wavelength of about 400 nm to about 450 nm.

48. The system according to any one of claims 45 to 47, wherein the at least one excitation light source is configured to emit excitation light having a wavelength of about 405 nm ± 10 nm.

49. The system according to any one of claims 45 to 48, wherein the first filter is further configured to block the passage of an optical signal having a wavelength of 405 nm ± 10 nm.

50. The system according to any one of claims 45 to 49, wherein the first filter is configured to allow an optical signal having a wavelength of about 500 nm to about 550 nm and / or an optical signal having a wavelength of about 600 nm to about 660 nm to pass through the first filter and reach the first image sensor.

51. The system according to any one of claims 45 to 50, wherein the at least one excitation light source includes first and second purple / blue LEDs, and each LED is configured to emit light having a wavelength of 405 nm ± 10 nm. to 50.

52. The system according to any one of claims 45 to 51, wherein the second housing portion further includes a power source.

53. The system according to claim 52, wherein the second housing further includes an outer surface having a contact for charging the power source.

54. The system according to any one of claims 45 to 53, wherein the second housing further includes a heat sink.

55. The system according to claim 54, wherein the heat sink defines an opening in the second housing configured to releasably receive the first housing.

56. The system according to any one of claims 45 to 55, wherein the first housing further includes a thermal sensor configured to detect thermal information regarding the target surface.

57. The system according to any one of claims 45 to 56, wherein the first housing further includes an ambient light sensor configured to indicate when ambient light conditions are sufficient to enable fluorescence imaging.

58. The system according to any one of claims 45 to 57, wherein the first housing further includes a rangefinder.

59. The system according to any one of claims 45 to 58, wherein the first housing further includes a third filter configured to detect an optical signal having a wavelength within the visible light range in response to illumination of the target surface by the white light and to allow passage to a third image sensor.

60. The system according to any one of claims 45 to 59, wherein the first housing further includes a second excitation light source 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, and / or combinations thereof.

61. The system according to any one of claims 45 to 60, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 750 nm to 800 nm.

62. The system according to claim 61, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 760 nm to about 780 nm.

63. The system according to claim 62, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 760 nm ± 10 nm.

64. The system according to claim 62, wherein the second excitation light source is configured to emit excitation light having a wavelength of about 770 nm ± 10 nm.

65. The second excitation light source is configured to emit excitation light having a wavelength of about 780 nm ± 10 nm The system according to claim 62.

66. The system according to any one of claims 45 to 65, wherein the first housing further includes a polarizing filter.

67. A portable modular hand-held imaging system kit, comprising a plurality of optical housing parts, each of the plurality of optical housing parts including at least one excitation light source configured to emit excitation light during fluorescence imaging; a first filter configured to detect 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 by the excitation light and to enable passage to a first image sensor; a white light source configured to emit white light during white light imaging; a second filter configured to detect an optical signal having a wavelength within the visible light range in response to illumination of the target surface by the white light and to enable passage to a second image sensor, and a plurality of optical housing parts. A base housing portion configured to releasably and interchangeably receive each of the plurality of optical housing portions, a display, a power supply configured to supply power to the at least one excitation light source and the white light source, a processor configured to receive the detected fluorescence and optical signals of the white light, and output a representation of the target surface to the display based on the detected optical signals, and a base housing portion including the same, a kit.

68. In each of the plurality of optical housing portions, the at least one excitation light source is 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, and / or combinations thereof. The kit according to claim 67.

69. The at least one excitation light source is configured to emit excitation light having a wavelength of about 400 nm to about 450 nm. The kit according to claim 67 or 68.

70. The at least one excitation light source is configured to emit excitation light having a wavelength of about 405 nm ± 10 nm. The kit according to any one of claims 67 to 69.

71. The first filter is configured to allow an optical signal having a wavelength of about 500 nm to about 550 nm and / or an optical signal having a wavelength of about 600 nm to about 660 nm to pass through the first filter and reach the first image sensor. The kit according to any one of claims 67 to 70.

72. The at least one excitation light source includes first and second violet / blue LEDs, and each LED is configured to emit light having a wavelength of 405 nm ± 10 nm. The kit according to any one of claims 67 to 71.

73. One of the plurality of optical housing portions further includes a third filter configured to detect an optical signal having a wavelength within the visible light range in response to illumination of the target surface by the white light and allow passage to a third image sensor. Claims 67 to 72 The kit according to any one of the preceding claims.

74. The kit according to claim 73, wherein the second 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 first excitation light source.

75. The kit according to claim 74, wherein the second of the plurality of optical housing portions is formed as an endoscope housing portion.

76. The kit according to any one of claims 67 to 75, wherein one of the plurality of optical housing portions further includes a distance meter.

77. The kit according to any one of claims 67 to 76, wherein one of the plurality of optical housing portions further includes a thermal sensor configured to detect thermal information regarding the target surface.

78. The kit according to any one of claims 67 to 77, wherein the first housing further includes an ambient light sensor configured to indicate when ambient light conditions are sufficient to enable fluorescence imaging.

79. The kit according to any one of claims 67 to 78, wherein the base housing further includes an outer surface having a contact for charging the power source.

80. The kit according to any one of claims 67 to 79, wherein the base housing further includes a heat sink.

81. The kit according to any one of claims 67 to 80, wherein the heat sink defines an opening in the base housing configured to releasably receive one of the plurality of optical housings.

82. The kit according to any one of claims 67 to 81, further including a dimming drape configured to be attached to one of the plurality of optical housings.

83. The kit according to claim 82, wherein the dimming drape is configured to reduce ambient light within the field of view of the first image sensor.

84. The kit according to claim 82, further including a plurality of dimming drapes, each dimming drape being configured to be attached to each of the plurality of optical housings.

85. The kit according to claim 75, further including a dimming drape configured to be attached to the endoscope optical housing.

86. The kit according to claim 85, wherein the dimming drape is configured to reduce ambient light within the field of view of the first image sensor.

87. The kit according to claim 86, wherein the light-reducing drape is further configured to provide sterility to the surgical field and / or protect the optical housing portion from contaminants.

88. The kit according to any one of claims 67 to 87, wherein one of the plurality of optical housing portions further includes a polarizing filter.

89. The base housing and one of the plurality of optical housing portions together form an imaging device, and further include a sterilizing drape configured to form a sterile barrier between the imaging device and the environment in which the imaging device is used, the kit according to any one of claims 67 to 88.

90. The kit according to any one of claims 67 to 89, further comprising one or more contrast agents.

91. A method of operating a modular hand-held fluorescence-based imaging device, comprising: selecting an optical housing including optical components including at least one excitation light source for fluorescence imaging; connecting the selected optical housing to a base housing of the imaging device to supply power from a power source in the base housing to the optical components in the optical housing; illuminating a target with the at least one excitation light source to cause fluorescence emission, reflection, or absorption of light by one or more of a portion, component, and biomarker of the illuminated portion of the target; filtering an optical signal in response to illumination of the target by the excitation light, wherein filtering the plurality of optical signals includes preventing passage of reflected excitation light and enabling 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 included in the optical housing; detecting the filtered optical signal with an image sensor included in the optical housing; displaying the detected and filtered signal on at least one display of the base housing as a composite image of the illuminated portion of the target, the composite image including fluorescence representations of various tissue components present in the illuminated portion of the target.

92. illuminating a target with a white light source included in the optical housing; Filtering an optical signal in response to the illumination of the target by the white light by means of a visible light filter included in the optical housing; Detecting the filtered optical signal by means of an image sensor included in the optical housing, further comprising: The method according to claim 91. **Claim 93** An imaging system kit, comprising: The imaging system according to any one of claims 1 to 66; A sterile drape configured to form a sterile barrier between the imaging system and the environment in which the imaging system is used. **Claim 94** The kit according to claim 93, further comprising an imaging drape configured to reduce ambient light in the imaging environment of the imaging system. **Claim 95** The kit according to claim 94, wherein the imaging drape includes a connector element configured to receive the optical housing of the imaging system. **Claim 96** The kit according to any one of claims 93 to 95, further comprising one or more contrast agents.

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