WO2023245124A1 - Wound detection and management using molecular chemical imaging - Google Patents

Wound detection and management using molecular chemical imaging Download PDF

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Publication number
WO2023245124A1
WO2023245124A1 PCT/US2023/068521 US2023068521W WO2023245124A1 WO 2023245124 A1 WO2023245124 A1 WO 2023245124A1 US 2023068521 W US2023068521 W US 2023068521W WO 2023245124 A1 WO2023245124 A1 WO 2023245124A1
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wound
pathogen
image data
wavelengths
light
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PCT/US2023/068521
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French (fr)
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Patrick J. Treado
Matthew P. Nelson
Monica Jo TOMASZEWSKI
Adam Evan SALTMAN
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Chemimage Corporation
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
    • C12Q1/10—Enterobacteria
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
    • C12Q1/14—Streptococcus; Staphylococcus
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
    • G01J3/4406—Fluorescence spectrometry
    • G—PHYSICS
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    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N2021/6417—Spectrofluorimetric devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/3563—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing solids; Preparation of samples therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/359—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using near infrared light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6456—Spatial resolved fluorescence measurements; Imaging
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/02—Mechanical
    • G01N2201/022—Casings
    • G01N2201/0221—Portable; cableless; compact; hand-held
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • G01N2201/12—Circuits of general importance; Signal processing
    • G01N2201/129—Using chemometrical methods
    • G01N2201/1296—Using chemometrical methods using neural networks

Abstract

Systems and methods for detecting and monitoring wounds and pathogens in wounds via molecular chemical imaging are described herein. The systems may include an image sensor configured to collect image data from interacted photons from a wound that is illuminated with a plurality of wavelengths of light, a processor configured to analyze the image data and identify one or more of a pathogen amount, a pathogen identity, a perfusion state, or a fluid state of a wound based on the image data.

Description

WOUND DETECTION AND MANAGEMENT USING MOLECULAR CHEMICAL IMAGING
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to U.S. Provisional Application Serial No. 63/352,584 filed on June 15, 2022, the entirety of which is incorporated by reference herein.
FIELD
[0002] The present disclosure is related to systems and methods for detecting and monitoring wound pathogens that are found within bodily wounds and wound health overall.
BACKGROUND
[0003] People and animals are frequently injured in ways that lacerate, break, or otherwise damage bodily membranes such as the skin When people and animals are wounded, there is a probability that the wound will become infected by wound pathogens, and such infections and sepsis are a leading cause of mortality. The causes of wounding are not limited and may include combat, accidents, bums, trauma, and related events. To maximize the likelihood of recovery from the wound and to avoid sepsis, the wound must be constantly monitored to quickly identify wound pathogens.
[0004] Additionally, there is a substantial difference in the recovery from wounds from patient to patient. Some people or animals, referred to herein as patients when they have a wound or are suspected of having a wound, recover quickly and without complication. However, other patients take longer to recover and have complications. These complications greatly increase the suffering, mental anguish, and pain experienced by the patient, and place significant monetary and emotional cost on those caring for the patient. In severe examples, such complications will lead to sepsis and death. There is a need for systems and methods of detecting and monitoring patients that are wounded.
SUMMARY
[0005] Systems and methods for detecting wound pathogens in wounds via hyperspectral imaging are described herein.
[0006] In one embodiment, a wound detection and monitoring apparatus includes a light source, an image sensor, and a processor, wherein during operation: the image sensor collects image data from interacted photons from a wound that is illuminated with a plurality of wavelengths of light, a processor analyzes the image data to identify one or more of the plurality of wavelengths resulting in contrast in the image data, and the processor identifies one or more of a pathogen amount, a pathogen identity, a perfusion state, or a fluid state of a wound based on the contrast in the image data.
[0007] In one embodiment, a method of detecting wound pathogens includes: illuminating, with a light source, a w ound with a plurality of wavelengths of light, collecting, with an image sensor, image data from interacted photons from a wound, analyzing, with a processor, the image data to identify one or more of the plurality of w avelengths of light and outputting in contrast in the image data, and identifying, with a processor, one or more of a pathogen amount, a pathogen identity, a perfusion state, or a fluid state of a wound based on the contrast in the image data.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 depicts an exemplary wound pathogen detection apparatus that is configured to monitor at least one of tissue oxygenation, tissue perfusion, or fluid accumulation.
[0009] FIG. 2 depicts several components of the wound pathogen detection apparatus.
[0010] FIG. 3 depicts a flowchart in accordance with an embodiment of the disclosure.
[0011] FIG. 4 A depicts a photograph of P. aeruginosa that was cultured on a Brain- Heart Nutrient Agar plate in accordance with the disclosure.
[0012] FIG. 4B depicts a photograph of S. aureus that was cultured on a Nutrient Agar plate in accordance with the disclosure.
[0013] FIG. 4C depicts the fluorescence spectra of the P. aeruginosa and S. aureus bacteria from the photographs of FIG. 4A and FIG. 4B in accordance with the disclosure.
[0014] FIG. 5A depicts ex vivo porcine tissue that was used as a wound model in accordance with an embodiment of the disclosure. [0015] FIG. 5B depicts ex vivo porcine tissue that was used as a wound model in accordance with an embodiment of the disclosure following incubation at 37°C for 22 hours after inoculation.
[0016] FIG. 5C depicts ex vivo porcine tissue that was used as a wound model in accordance with an embodiment of the disclosure following incubation at 37°C for 22 hours after inoculation and includes an overlay of fluorescent hypercubes and principal component analysis (PCA).
[0017] FIG. 6A depicts the hyperspectral emissions emanating from different regions of a porcine tissue sample in accordance with the disclosure.
[0018] FIG. 6B depicts the hyperspectral emission profile for each concentration for P. aeruginosa in accordance with the disclosure.
[0019] FIG. 6C depicts the hyperspectral emissions emanating from different regions of a porcine tissue sample in accordance with the disclosure.
[0020] FIG. 6D depicts the hy perspectral emission profile for each concentration for 5. aureus in accordance with the disclosure.
DETAILED DESCRIPTION
[0021] This disclosure is not limited to the particular systems, devices and methods described, as these may vary. The terminology used in the description is for the purpose of describing the particular versions or embodiments only, and is not intended to limit the scope.
[0022] As used in this document, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. Nothing in this disclosure is to be construed as an admission that the embodiments described in this disclosure are not entitled to antedate such disclosure by virtue of prior invention. As used in this document, the term “comprising” means “including, but not limited to.”
[0023] As used herein, the term “about” means plus or minus 10% of the numerical value of the number with which it is being used. Therefore, about 50% means in the range of 45%-55%. [0024] As used herein, the term “wound pathogen” means a bacterium, virus, or other microorganism that can cause disease when located within a wound, examples of which are ESKAPEE pathogens, which are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli.
[0025] Each of the following patents and patent publications are incorporated by reference herein in their entirety: U.S. Patent Application Publication No. 2021/0393149, U.S. Patent No. 8,269,174.
[0026] The wound pathogen detection apparatus 150 can in certain embodiments detect and monitor tissue perfusion. To do so, the light source emits wavelengths in the visible near infrared (VIS-NIR) or shortwave infrared (SWIR) regions. In some embodiments, the light source emits wavelengths in the ultraviolet (UV), visible (VIS), or infrared (IR) regions. In other embodiments, the wound pathogen detection apparatus 1 0 can detect and monitor tissue fluid levels, such as by NIR or SWIR. And in still other embodiments, the wound pathogen detection apparatus 150 can detect and monitor pathogen identities and amount, such as by illuminating a wound with ultraviolet (UV) light.
[0027] Referring to FIG. 1, an illustrative environment with an exemplary wound pathogen detection apparatus 150 that is configured to monitor at least one of tissue oxygenation, tissue perfusion, or fluid accumulation. The environment includes at least one light source 110 configured to generate photons to illuminate a wound 120, an image sensor 130 positioned to collect interacted photons 135, and a wound pathogen detection apparatus 150 coupled to an image sensor via one or more communications networks 140, although the environment can include other types and/or numbers of devices or systems coupled in other manners. This technology provides a number of advantages including providing methods, non-transitory computer readable media, and tissue perfusion monitoring computing devices that provide improved tissue perfusion monitoring. In particular, certain implementations of this technology provide a real-time, reagentless, and non-contact method for monitoring wounds.
[0028] In an embodiment, at least one light source 110 generates photons that are directed to a wound 120 in a human or animal. The at least one light source 110 is not limited and can be any light source that is useful in providing illumination. In an embodiment, the at least one light source 110 can be portable or handheld. Other ancillary requirements, such as power consumption, emitted spectra, packaging, thermal output, and so forth may be determined based on the particular application that the at least one light source 110 is used. In some embodiments, the at least one light source 110 is a light element, which is an individual device that emits light. The light elements are not limited and may include an incandescent lamp, halogen lamp, light emitting diode (LED), chemical laser, solid state laser, organic light emitting diode (OLED), electroluminescent device, fluorescent light, gas discharge lamp, metal halide lamp, xenon arc lamp, induction lamp, or any combination of these light sources. In other embodiments, the at least one light source 110 is a light array, which is a grouping or assembly of more than one light element placed in proximity to each other.
[0029] In some embodiments, the at least one light source 1 10 has a particular wavelength that is intrinsic to the light element or to the light array. In other embodiments, the wavelength of a light source 110 may be modified by filtering or tuning the photons that are emitted by the light source. In still other embodiments, a plurality of light sources 110 having different wavelengths are combined. In one embodiment, the selected wavelength of the at least one light source 110 is in the visible-near infrared (VIS-NIR) or shortwave infrared (SWIR) ranges. These correspond to wavelengths of about 400 nm to about 1100 nm (VIS-NIR) or about 850 nm to about 1800 nm (SWIR). The above ranges may be used alone or in combination of any of the listed ranges. Such combinations include adjacent (contiguous) ranges, overlapping ranges, and ranges that do not overlap.
[0030] In some embodiments, the at least one light source 110 comprises a modulated light source. The choice of modulated light source for the at least one light source 110 and the techniques of modulating the light source are not limited. In some embodiments, the modulated light source is one or more of a filtered incandescent lamp, filtered halogen lamp, tunable LED array, tunable solid state laser array, tunable OLED array, tunable electroluminescent device, filtered fluorescent light, filtered gas discharge lamp, filtered metal halide lamp, filtered xenon arc lamp, filtered induction lamp, or any combination of these light sources. In some embodiments, tuning is accomplished by increasing or decreasing the intensity or duration at which the individual light elements 110 are powered. Alternatively, tuning is accomplished by a fixed or tunable filter that filters light emitted by the individual light elements. In still other embodiments, at least one light source 110 is not tunable. A light source 110 that is not tunable cannot change its emitted light spectra, but it can be turned on and off by the appropriate controls.
[0031] Imaging is performed by filtering and detecting interacted photons 135 that are reflected from a wound 120 using the image sensor 130 and associated optics, such as filters. The image sensor 130 can be any suitable image sensor for molecular chemical imaging (MCI). The techniques and devices for filtering are not limited and include any of fixed filters, multi-conjugate filters, and conformal filters. In fixed filters, the functionality of the filter cannot be changed, though the filtering can be changed by mechanically moving the filter into or out of the light path. In some embodiments, real-time image detection is employed using a dual polarization configuration using either multi-conjugate filters or conformal filters. In some embodiments, the filter is a tunable filter that comprises a multiconjugate filter. The multi-conjugate filter is an imaging filter with serial stages along an optical path in a Sole filter configuration. In such filters, angularly distributed retarder elements of equal birefringence are stacked in each stage with a polarizer between stages.
[0032] A conformal filter can filter a broadband spectra into one or more passbands. Example conformal filters include a liquid crystal tunable filter, an acousto-optical tunable filter, a Lyot liquid crystal tunable filter, an Evans Split-Element liquid crystal tunable filter, a Sole liquid crystal tunable filter, a Ferroelectric liquid crystal tunable filter, a Fabry Perot liquid crystal tunable filter, and combinations thereof.
[0033] In an embodiment, the image is collected by an image sensor 130 that is a camera chip. When the image sensor 130 is a camera chip, such camera chips are not limited but are instead selected depending on the expected spectra that is reflected by the wound and surrounding skin of the patient. In some embodiments, the camera chip is one or more of a charge coupled device (CCD), a complementary metal oxide semiconductor (CMOS), an indium gallium arsenide (InGaAs) camera chip, a platinum silicide (PtSi) camera chip, an indium antimonide (InSb) camera chip, a mercury cadmium telluride (HgCdTe) camera chip, or a colloidal quantum dot (CQD) camera chip. In some embodiments, each or the combination of the above-listed camera chips is a focal plane array (FPA). In some embodiments, each of the above-identified image sensor 130 which can be a camera chip can include quantum dots to tune their bandgaps, thereby altenng or expanding sensitivity to different wavelengths. The visualization techniques are not limited, and include one or more of VIS, NIR, SWIR, autofluorescence, fluorescence, or Raman spectroscopy. Although the image sensor 130 is illustrated as a standalone device, the image sensor could be incorporated in the wound pathogen detection apparatus 150 or in a device with the at least one light source 110.
[0034] Referring to FIG. 1 and FIG. 2, the wound pathogen detection apparatus 150 in this example includes one or more processors 210, a memory 220, and/or a communication interface 230, which are coupled together by a bus 240 or other communication link, although the wound pathogen detection apparatus 150 can include other types and/or numbers of elements in other configurations. The one or more processors 210 of the wound pathogen detection apparatus 150 may execute programmed instructions stored in the memory 220 for the any number of the functions described and illustrated herein. The one or more processors 210 of the wound pathogen detection apparatus 150 may include one or more CPUs or general-purpose processors with one or more processing cores, for example, although other types of processors can also be used.
[0035] The memory 220 of the wound pathogen detection apparatus 150 stores these programmed instructions for one or more aspects of the present technology as described and illustrated herein, although some or all of the programmed instructions could be stored elsewhere. A variety of different types of memory storage devices 220, such as randomaccess memory (RAM), read only memory (ROM), hard disk, solid state drives, flash memory, or other computer readable medium which is read from and written to by a magnetic, optical, or other reading and writing system that is coupled to the one or more processors, can be used for the memory.
[0036] Accordingly, the memory 220 of the wound pathogen detection apparatus 150 can store one or more applications that can include executable instructions that, when executed by the one or more processors 210, cause the wound pathogen detection apparatus 150 to perform actions, such as to perform the actions described and illustrated below with reference to FIG. 3. In some embodiments, the one or more applications can be implemented as modules or components of one or more other applications. In some embodiments, the one or more applications can be implemented as operating system extensions, module, plugins, or the like.
[0037] In some embodiments, the one or more applications may be operative in a cloudbased computing environment. In some embodiments, the one or more applications can be executed within or as one or more virtual machines or one or more virtual servers that may be managed in a cloud-based computing environment. In some embodiments, the one or more applications and/or the wound pathogen detection apparatus 150 may be located in one or more virtual servers running in a cloud-based computing environment rather than being tied to one or more specific physical network computing devices. In some embodiments, the one or more applications may run in one or more virtual machines (VMs) executing on the wound pathogen detection apparatus 150. Additionally, in one or more embodiments of this technology, one or more virtual machines running on the wound pathogen detection apparatus 150 may be managed or supervised by a hypervisor.
[0038] In a particular embodiment, the memory' 220 of the wound pathogen detection apparatus 150 includes an image processing module 225, although the memory can include other policies, modules, databases, or applications, for example. The image processing module 225 may be configured to analyze image data from the image sensor 130 to determine tissue perfusion, tissue fluid, or the identity and amount of one or more pathogens of the illuminated wound 120 based on the image data, although the image processing module could perform other functions. By way of example only, the image processing module 225 may apply one or more machine learning techniques such as an image-weighted Bayesian function, logistic regression, linear regression, regression with regularization, partial least squares regression (PLSR), partial least squares discriminant analysis (PLSDA), naive Bayes, classification and regression trees (CART), support vector machines, or a neural network to process the image data.
[0039] The communication interface 230 of the wound pathogen detection apparatus 150 operatively couples and communicates between the wound pathogen detection apparatus 150, the image sensor 130, the additional sensors, the client devices and/or the server devices, which are all coupled together by the one or more illustrated communication networks 140. Other types and/or numbers of communication networks 140 or systems with other types and/or numbers of connections and/or configurations to other devices and/or elements can also be used.
[0040] By way of example only, the communication network(s) 140 shown in FIG. 1 can include one or more local area networks (LANs) and/or one or more wide area networks (WANs), and can use TCP/IP over Ethernet and industry-standard protocols, although other types and/or numbers of protocols and/or communication networks can be used. The one or more communication networks 140 in this example can employ any suitable interface mechanisms and network communication technologies including, for example, teletraffic in any suitable form (e.g., voice, modem, and the like), Public Switched Telephone Networks (PSTNs), Ethernet-based Packet Data Networks (PDNs), combinations thereof, and the like.
[0041] The wound pathogen detection apparatus 150 can be a standalone device or integrated with one or more other devices or apparatuses, such as, for example, the image sensor 130, one or more of the server devices, or one or more of the client devices. In particular embodiments, the wound pathogen detection apparatus 150 can include or be hosted by one of the server devices or one of the client devices. Other arrangements are also possible.
[0042] Although the exemplary environment with the wound pathogen detection apparatus 150 may be configured to operate as virtual instances on the same physical machine. In other words, one or more of the w ound pathogen detection apparatus 150 client devices, or server devices may operate on the same physical device rather than as separate devices communicating through one or more communication networks 140. Additionally, there may be more or fewer wound pathogen detection apparatus 150 than illustrated in FIG. 1.
[0043] In some embodiments, a plurality of computing systems or devices can be substituted for any one of the systems or devices in any example. Accordingly, principles and advantages of distributed processing, such as redundancy and replication also can be implemented, as desired, to increase the robustness and performance of the devices and systems of the examples. The examples may also be implemented on one or more computer systems that extend across any suitable network using any suitable interface mechanisms and traffic technologies, including, by way of example only, wireless networks, cellular networks, PDNs, the Internet, intranets, and combinations thereof.
[0044] The examples may also be embodied as one or more non-transitory computer readable media (e.g., the memory 220) having instructions stored thereon for one or more aspects of the present technology as described and illustrated by way of the examples herein. The instructions in some examples include executable code that, when executed by one or more processors (e.g., the one or more processors 210), cause the one or more processors to carry out steps necessary to implement the methods of the examples of this technology that are described and illustrated herein.
[0045] An exemplary method of tissue perfusion monitoring will now be described with reference to FIG. 3. As shown in FIG. 3, the wound pathogen detection apparatus 150 may collect image data 310 from the image sensor 130. The image data can be fluorescent image data, VIS image data, or hyperspectral image data, for example. The hypercubes may be analyzed 320 to identify one or more of the plurality' of wavelengths resulting in contrast in the image data.
[0046] The wound pathogen detection apparatus 150 may identify 330 one or more regions in the tissue region with altered perfusion states, fluid states, or pathogen states based on the contrast in the image data. In some embodiments, the pathogen states are one or more of a pathogen amount or a pathogen identity. In some embodiments, the wound pathogen detection apparatus 150 may monitor the preceding perfusion states, fluid states, or pathogen states over time. With the technology disclosed herein, tissue perfusion, tissue fluids, and pathogens can be monitored in a non-contact, reagentless manner.
[0047] The wound pathogen detection apparatus 150 may determine 340 if the altered perfusion states, fluid states, or pathogen states meet a predetermined threshold. In some embodiments, if the wound pathogen detection apparatus 150 determines 340 that the altered perfusion states, fluid states, or pathogen states is above the predetermined threshold, the communication interface 230 may output 350 an alert based on the altered perfusion states, fluid states, or pathogen states. In some embodiments, if the wound pathogen detection apparatus 150 determines 340 that the altered perfusion states, fluid states, or pathogen states is below the predetermined threshold, the wound pathogen detection apparatus 150 may return to the step of collecting image data 310 from the image sensor 130.
EXAMPLES
[0048] While several experimental Examples are contemplated, these Examples are intended to be non-limiting.
Preparation Example
[0049] The spectral emissions of bacteria w ere measured. Solid cultured bacteria grown under optimal conditions were prepared and illuminated with light in 5 nm steps from 400 nm to 720 nm under optimal growth conditions. FIG. 4A is a photograph of P. aeruginosa which was cultured on a Brain-Heart Nutrient Agar plate and FIG. 4B is a photograph of S'. Aureus which was cultured on a Nutrient Agar plate. The images from 400 nm-700 nm were obtained and constructed into a hypercube which would be used for subsequent analysis. The fluorescence spectra of the bacteria are shown in FIG. 4C, which is a graph of the normalized emission intensity of fluorescence spectra plotted against the wavelength, in nanometers (nm), of the emitted spectra. In FIG. 4C, the spectra having its highest intensity , that is, the peak maximum at 510 nm corresponds to P. aeruginosa and the spectra having its highest intensity at 530 nm corresponds to S. aureus. The information obtained from the solid cultured bacteria such as the spectral curves shown in FIG. 4C were used to analyze wounded tissue, described below.
Example 1
[0050] Fresh porcine tissue was obtained from a local supplier. The tissue was trimmed to fit into a petti dish and was contained therein for the entirety of the experiments. In testing the tissue, a modified wound model based on the description in Andersson MA, Madsen LB, Schmidtchen A, Puthia M. Development of an Experimental Ex Vivo Wound Model to Evaluate Antimicrobial Efficacy of Topical Formulations. International Journal of Molecular Sciences. Published May 10, 2021; 22(9):5045. Wounds were introduced in a pattern on the skin of the porcine tissue by heating a metal tool in flames and subsequently pressing the tool on the skin of the porcine tissue for 20 seconds, thereby wounding the skin. This procedure was repeated for several samples, and the tool was cleaned of debris every 2-3 uses. Samples were allowed to cool prior to inoculation to minimize condensation in the containing plates.
[0051] Following preparation of the wounded porcine tissue, 25 pL (microliters) of media or media plus bacteria were introduced to each wound by slowly pipetting the liquid over the depressions caused by the bums. Liquid was allowed to absorb before the samples were moved. The wound model samples were incubated for 22 hours at 37°C before imaging acquisition and analysis was performed by illuminating the porcine samples with light in 5 nm steps from 400 nm-700 nm.
[0052] The hyperspectral information obtained above in “Preparation” was applied to the hyperspectral results of illuminating the porcine samples as described above. In FIG. 5A, ex vivo porcine tissue was used as a wound model as describes above Example 1. Each wound was inoculated with a concentration of bacteria or control media as described in TABLE 1.
The tissue shown in FIG. 5 A was photographed after inoculation, but prior to incubation.
TABLE 1
Figure imgf000014_0001
[0053] FIG. 5B shows a sample that was incubated at 37°C and imaged 22 hours after inoculation. FIG. 5B depicts noticeable deformation of the tissue, and visible condensation has formed on the plate. FIG. 5C is the same as FIG. 5B but includes an overlay of fluorescent hypercubes and principal component analysis (PCA). In the image overlay shown in FIG. 5C, the cyan colors correspond to the spectral profile of S. aureus, and the magenta colors correspond to the spectral profile of P. aeruginosa. As shown in FIG. 5 A and in TABLE 1, wounds and the bacteria were configured into a grid of different areas of the porcine tissue having different amounts of bacteria in a manner than corresponded to FIG. 5 A and TABLE 1. When swab samples were obtained from the wounds and grown in agar plates, we were able to confirm that the bactenal cultures from the wounds were consistent with the bacterial identified in the principal component analysis by way of comparing the spectral signature of the sampled bacteria with the spectral signatures of the bacteria described in “Preparation.”
[0054] The different regions of the porcine tissue having different concentrations of bacteria were also analyzed to determine whether hyperspectral imaging could discern the different amounts of bacteria. FIG. 6 A is a photograph of the hyperspectral emissions coming from different regions of a porcine tissue sample, and FIG. 6B is the hyperspectral emission profile of each concentration for P. aeruginosa. In FIG. 6B, the topmost peak corresponds to neat region, the second highest peak corresponds to a ratio of 1 :400 (IO-2), the third highest peak corresponds to a ratio of 1 : 1000 (10-3), and the lowest peak corresponds to a ratio of 1: 10000 (10‘4). FIG. 6C and FIG. 6D similarly depict hyperspectral emissions emanating from different regions of the porcine tissue, with the difference being that FIG. 6C and FIG. 6D correspond to S. aureus instead of P. aeruginosa described above. It was found that the peak emission wavelength for P. aeruginosa was slightly higher at 525 nm than that of S. aureus which was 510 nm.
[0055] The present disclosure is not to be limited in terms of the particular embodiments de-scribed in this application, which are intended as illustrations of various aspects. Many modifications and variations can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and apparatuses within the scope of the disclosure, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the appended claims. The present disclosure is to be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled. It is also understood that this disclosure is not limited to particular compositions, methods, apparatus, and articles, as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.
[0056] With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity.
[0057] It will be understood by those within the art that, in general, tenns used herein, and especially in the appended claims (for example, bodies of the appended claims) are generally intended as “open” terms (for example, the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” et cetera). While various compositions, methods, and devices are described in terms of “comprising” various components or steps (interpreted as meaning “including, but not limited to”), the compositions, methods, and devices can also “consist essentially of’ or “consist of’ the various components and steps, and such terminology should be interpreted as defining essentially closed-member groups. It will be further under-stood by those within the art that if a specific number of an introduced claim recitation is intend-ed, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present.
[0058] For example, as an aid to understanding, the following appended claims may contain us-age of the introductory phrases "at least one" and "one or more" to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles "a" or "an" limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases "one or more" or "at least one" and indefinite articles such as "a" or "an" (for example, “a” and/or “an” should be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations.
[0059] In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should be interpreted to mean at least the recited number (for example, the bare recitation of "two recitations," without other modifiers, means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, et cetera” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example, “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, et cetera). In those instances where a convention analogous to “at least one of A, B, or C, et cetera” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (for example, “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, et cetera). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.” [0060] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.
[0061] As will be understood by one skilled in the art, for any and all purposes, such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, et cetera. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, et cetera. As will also be understood by one skilled in the art all language such as “up to,” “at least,” and the like include the number recited and refer to ranges that can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 cells refers to groups having 1, 2, or 3 cells. Similarly, a group having 1-5 cells refers to groups having 1, 2, 3, 4, or 5 cells, and so forth.
[0062] Various of the above-disclosed and other features and functions, or alternatives thereof, may be combined into many other different systems or applications. Various presently unforeseen or un-anticipated alternatives, modifications, variations or improvements therein may be subsequently made by those skilled in the art, each of which is also intended to be encompassed by the disclosed embodiments

Claims

1. A wound detection and monitoring apparatus comprising a light source, an image sensor, and a processor, wherein during operation: the image sensor collects image data from interacted photons from a wound that is illuminated with a plurality of wavelengths of light, a processor analyzes the image data to identify one or more of the plurality of wavelengths resulting in contrast in the image data, and the processor identifies one or more of a pathogen amount, a pathogen identity, a perfusion state, or a fluid state of a wound based on the contrast in the image data.
2. The wound detection and monitoring apparatus of claim 1, wherein the plurality of wavelengths are in the ultraviolet (UV), visible (VIS), visible near infrared (VIS-NIR), shortwave infrared (SWIR), or infrared (IR) regions.
3. The wound detection and monitoring apparatus of claim 1, wherein the processor identifies a pathogen amount and a pathogen identity.
4. The wound detection and monitoring apparatus of claim 1, wherein the pathogen identity is one or more of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enter bacter spp., and Escherichia coli.
5. The wound detection and monitoring apparatus of claim 1, wherein the wound detection and monitoring apparatus is handheld.
6. A method of detecting wound pathogens, the method comprising: illuminating, with a light source, a wound with a plurality of wavelengths of light, collecting, with an image sensor, image data from interacted photons from a wound, analyzing, with a processor, the image data to identify one or more of the plurality of wavelengths of light and outputting in contrast in the image data, and identifying, with a processor, one or more of a pathogen amount, a pathogen identity, a perfusion state, or a fluid state of a wound based on the contrast in the image data.
7. The method of claim 6, wherein the plurality of wavelengths are in the ultraviolet (UV), visible (VIS), visible near infrared (VIS-NIR), shortwave infrared (SWIR), or infrared (IR) regions.
8. The method of claim 6, wherein identifying is a pathogen amount and a pathogen identity.
9. The method of claim 6, wherein the pathogen identity is one or more of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130201469A1 (en) * 2010-07-12 2013-08-08 Chemlmage Corporation Method for Analysis of Pathogenic Microorganisms in Biological Samples Using Raman Spectroscopic Techniques
US20180325378A1 (en) * 2013-08-01 2018-11-15 Christopher J. Murphy Method of characterizing wounds with raman spectroscopy

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20130201469A1 (en) * 2010-07-12 2013-08-08 Chemlmage Corporation Method for Analysis of Pathogenic Microorganisms in Biological Samples Using Raman Spectroscopic Techniques
US20180325378A1 (en) * 2013-08-01 2018-11-15 Christopher J. Murphy Method of characterizing wounds with raman spectroscopy

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