Multicomponent diagnostic systems and methods of use thereof

Abstract

The present disclosure relates to computer-implemented methods and systems for assessing an anatomical region of subject. Fluorescence images and temperature data for the anatomical region may be received, the fluorescence images may be analysed to determine one or more haemodynamic parameters, and the temperature data and the result of the analysis may displayed on a display device. The system includes one or more processor(s) and optional elements suitable for carrying out the disclosed methods.

Description

MULTICOMPONENT DIAGNOSTIC SYSTEMS AND METHODS OF USE THEREOFFIELD OF THE INVENTION

[0001] The present disclosure relates to the field of diagnostic and prognostic systems and methods. In particular, the present disclosure relates to a multi-modal system and method for assessing the condition of an anatomical region of a subject based on haemodynamic and temperature data.BACKGROUND

[0002] Diagnostic systems and methods have an important role in clinical care During surgery and other time-sensitive procedures, it is essential to obtain diagnostic and clinical assessment data quickly and reliably. Such information is critical for informed decision-making and optimal patient outcomes.

[0003] Diagnostic systems and associated methods are also used to monitor a patient's status over time, such as monitoring a response to treatment. For example, diagnostic systems are used to collect data along a continuum, at multiple time points, to support assessment of disease progression or recovery Data collection using a diagnostic system approach may also help direct a treatment pathway, inform clinical decisionmaking including the altering of a treatment approach.

[0004] Diagnostic systems often include multiple components that detect and / or monitor different physiological parameters. The components are selected to provide overlapping or complementary data that allows a medical professional to make a more informed treatment pathway in a given clinical or surgical situation.

[0005] There remains a need for diagnostic systems that allow for the collection of data reliably and rapidly, including longitudinal and repeatable measurements over a long period of time to provide the data that medical professionals need to help them make more informed clinical and surgical decisions.SUMMARY

[0006] The disclosure describes clinical diagnostic systems and methods of using the systems. The systems include at least one system component that provides diagnosticdata to a medical professional, patient, or caregiver for the diagnosis of a disease or injury in a patient.

[0007] In preferred embodiments, the disclosed systems and methods provide a first system component that uses fluorescence to image the circulatory system or the lymphatic system or both the circulatory and lymphatic systems. The first component may also be used for tissue perfusion. The systems have a second system component to image skin temperature over a desired area of tissue. In further embodiments, systems of the disclosure may have additional components for detecting other physiological parameters.

[0008] The use of the first and second system components together provides a reliable, non-invasive system to diagnose and monitor patients whose circulatory or lymphatic systems are compromised by injury or disease. Additionally, the systems allow for, repeatable and extended monitoring over time which enhances the accuracy and reliability of clinical data, and provides valuable insights for diagnosing and treating the patient's physiological condition.

[0009] The systems may include further system components for imaging as required.The systems include at least one controller for controlling the system components and include at least one display for presenting image data.

[0010] According to one aspect of the present disclosure, there is provided a computer-implemented method for assessing an anatomical region of a subject, comprising: receiving fluorescence images of a fluorescent contrast agent in the anatomical region, analysing the images to determine one or more haemodynamic parameters, receiving temperature data corresponding to the anatomical region, and displaying, on a display device, a result of the analysis and the temperature data for the anatomical region

[0011] Optionally, the method further comprises selecting or receiving a selection of a plurality of regions of interest (ROI) in the fluorescence images, wherein at least one of the ROIs is defined to be a reference area.

[0012] Optionally, the method further comprises determining, from the fluorescence images, the haemodynamic parameter(s) for each ROI.

[0013] Optionally, the method further comprises determining a temperature variation between at least the reference area and another ROT based on the temperature data.

[0014] Optionally, the ROIs include a micro-vascular area and a macro-vascular area

[0015] Optionally, the ROIs include a healthy tissue area and an unhealthy tissue area.

[0016] Optionally, the method further comprises computing, for each ROI, a perfusion score based on the determined parameter(s) of the ROI and a comparison to the reference area.

[0017] Optionally, displaying the result of the analysis and the temperature data for the anatomical region includes providing a visual indication of the selected ROIs.

[0018] Optionally, the method further comprises the visual indication of the selected ROIs comprises a labelled image of the anatomical region.

[0019] Optionally, the method further comprises storing in memory the result of the analysis and the temperature data for the anatomical region.

[0020] Optionally, the method further comprises repeating, at a subsequent time, the steps of receiving fluorescence images for the anatomical region, analysing the fluorescence images to determine one or more haemodynamic parameters, and receiving temperature data corresponding to the anatomical region; and comparing the results and / or the temperature data to historical values stored in memory for the same subject.

[0021] Optionally, the method further comprises identifying, based on the comparison, one or more trends related to the haemodynamic parameters) and providing a notification on the display.

[0022] Optionally, the method further comprises identifying, based on the comparison, one or more correlations or discrepancies between the haemodynamic parameter(s) and the temperature data and providing a notification on the display.

[0023] Optionally, the haemodynamic parameter(s) include one or more of fluorescence intensity, temporal change in fluorescence intensity, a time-to-peak fluorescence intensity, a perfusion slope, a wash-in characteristic, a wash-out characteristic, and a flow rate.

[0024] Optionally, the anatomical region comprises a foot.

[0025] Optionally, the fluorescent contrast agent comprises indocyanine green (ICG).

[0026] According to a further aspect of the present disclosure, there is provided a computer-readable medium comprising instructions stored thereon which, when executed by one or more processors, cause the processor(s) to carry out the methods disclosed herein for assessing an anatomical region of a subject.

[0027] According to a further aspect of the present disclosure there is provided a system at least comprising one or more processors configured to carry out a method for assessing the condition of an anatomical region of a subject, the method comprising the steps of: receiving fluorescence images of a fluorescent contrast agent in the anatomical region, analysing the fluorescence images to determine one or more haemodynamic parameters, receiving temperature data corresponding to the anatomical; and communicating with a display device to display the temperature data and a result of analysing the fluorescence images.

[0028] Optionally, the system further comprises means for delivering one or a series of boluses of the fluorescent contrast agent to the subject.

[0029] Optionally, the system further comprises a first system component comprising an image capture device suitable to capture the fluorescence images of the fluorescent contrast agent in the anatomical region.

[0030] Optionally, the system further comprises a display device configured to display the temperature data and the result of analysing the fluorescence images

[0031] Optionally, the system processor(s) are further configured to select or receive a selection of a plurality of regions of interest (ROI) in the fluorescence images, wherein at least one of the ROls is defined to be a reference area.

[0032] Optionally, the display device is further configured to permit a user to select an ROI a plurality of regions of interest (ROI) in the fluorescence images, wherein at least one of the ROIs is defined to be a reference area.

[0033] Optionally, the system processor(s) are further configured to determine a temperature variation between at least the reference area and another ROI based on the temperature data.

[0034] Optionally, the ROIs include a micro-vascular area and a macro-vascular area.

[0035] Optionally, the ROIs include a healthy tissue area and an unhealthy tissue area.

[0036] Optionally, the system processor(s) are configured to compute, for each ROI, a perfusion score based on the determined haemodynamic parameter(s) of the ROI and a comparison to the reference ROI

[0037] Optionally, displaying the result of the analysis and the temperature data for the anatomical region includes providing a visual indication of the selected ROIs.

[0038] Optionally, the visual indication of the selected ROIs comprises a labelled image of the anatomical region.

[0039] Optionally, the system further comprises one or more memory modules, and wherein the processor(s) are further configured to store in memory the result of the analysis and the temperature data for the anatomical region.

[0040] Optionally, the system processor(s) are further configured to repeat, at a subsequent time, the steps of receiving fluorescence images for the anatomical region, analysing the fluorescence images to determine one or more haemodynamic parameters, and receiving temperature data corresponding to the anatomical region; andwherein the system processor(s) are further configured to compare the results and / or the temperature data to historical values stored in memory for the same subject.

[0041] Optionally, the system processor(s) are further configured to identify, based on the comparison, one or more trends related to the haemodynamic parameter(s) and providing a notification on the display.

[0042] Optionally, the system processor(s) are further configured to identify, based on the comparison, one or more correlations or discrepancies between the haemodynamic parameter(s) and the temperature data and to communicate a notification for display on the display device.

[0043] Optionally, the haemodynamic parameter(s) include one or more of fluorescence intensity, temporal change in fluorescence intensity, a time-to-peak fluorescence intensity, a perfusion slope, a wash-in characteristic, a wash-out characteristic, and a flow rate.

[0044] Optionally, the system further comprises a second system component comprising a temperature measurement device configured to capture the temperature data.

[0045] Optionally, the first system component comprises a near-infrared camera.

[0046] Optionally, the second system component comprises a thermal camera.

[0047] Optionally, the fluorescent contrast agent used with the system comprises indocyanine green (ICG).

[0048] According to a further aspect of the present disclosure, use of indocyanine green in the methods disclosed herein is provided.BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure l is a flow chart showing an exemplary method according to the disclosure, in which one or more haemodynamic parameters for an anatomical region are determined from the analysis of fluorescence images.

[0050] Figure 2 is a flow chart showing an exemplary method according to the disclosure, in which temperature data is received for an anatomical region.

[0051] Figure 3 is a flow chart showing an exemplary method according to the disclosure, in which one or more haemodynamic parameters and temperature data for an anatomical region are stored in memory.

[0052] Figure 4 is a flow chart showing an exemplary method according to the disclosure, in which one or more haemodynamic parameters and temperature data for an anatomical region are displayed on a display device for review by a clinician.

[0053] Figure 5 is a flow chart showing an exemplary method according to the disclosure, in which one or more haemodynamic parameters and temperature data are compared to historical values.

[0054] Figure 6 is a flow chart showing an exemplary method according to the disclosure, in which one or more haemodynamic parameters and temperature data are analysed to identify any correlation.

[0055] Figure 7 is a flow chart showing an exemplary method according to the disclosure, in which a non-dimensional score is generated based on haemodynamic parameter(s) and / or temperature data.

[0056] Figure 8 is a block diagram showing an exemplary system according to the disclosure.

[0057] Figure 9 is flow chart showing one example of a method according to the disclosure.DETAILED DESCRIPTION OF THE DRAWINGS

[0058] This description provides illustrative examples of various aspects and embodiments of the present disclosure and is intended only to provide an overview orframework for understanding the embodiments. The accompanying drawings are included to provide illustration and a further understanding of the various aspects and embodiments and are incorporated in and constitute a part of this specification. The drawings, together with the specification, serve to explain the described and claimed aspects and embodiments.

[0059] This disclosure relates to medical diagnostic and / or medical monitoring systems and methods of using said disclosed systems. The systems include at least one system component that provides diagnostic data to a medical professional, patient, or caregiver for the diagnosis of a disease or injury in a patient. According to the disclosure, a medical professional, patient or caregiver collects diagnostic data from a patient using the at least one system component. The diagnostic data may be displayed for viewing and may be stored for later retrieval and analysis.

[0060] In preferred embodiments, the disclosure relates to systems and methods for imaging the flow of blood through the circulatory system. The disclosure also relates to systems and methods for imaging the lymphatic system. The disclosure also relates to systems and methods of use for imaging tissue perfusion. In preferred embodiments, the systems are used to assess compromised blood flow in the vasculature or tissue perfusion due to disease or injury.

[0061] For example, and without limitation, systems of the disclosure can be used to make surgical decisions by making real-time assessments in the operating room. For example, the systems may be used in procedures such as flap reconstructions and surgeries involving the vascular system. In preferred embodiments, the systems may be used for the assessment of blood flow or tissue perfusion to diagnose and monitor conditions like peripheral artery disease.

[0062] In preferred embodiments, systems and methods of the disclosure are used to monitor burns, wounds or ulcers on a patient's body by measuring changes in blood flow or tissue perfusion that occur due to the bums, wounds, or ulcers. For example, reduced blood flow over time in a burn area may be associated with poorly healing tissue.

[0063] In particularly preferred embodiments, the systems are used to monitor and assess diabetic foot ulcers. The systems permit the detection of physiological changes associated with infection or detect worsening ischemia prior to the onset of overt clinical signs of symptoms in patients suffering from diabetes..

[0064] Other clinical applications include, but are not limited to, skin ulcers, flaps, bums or wound monitoring

[0065] According to the disclosure, the systems provide real-time feedback to medical professionals during treatment and / or management of patient care including surgeons and clinicians, and also to the patients themselves and / or their caregivers. The systems and methods allow a medical professional to easily, rapidly and accurately assess and monitor a patient's vascular status and physiological condition over time. According to the disclosure, the systems provide simplified data management and retrieval, enabling seamless integration into clinical workflows.

[0066] In preferred embodiments, systems of the disclosure employ multiple modes of imaging to assess, monitor and even detect issues relating to blood flow or tissue perfusion or a combination of blood flow and tissue perfusion. That is, the systems include components designed to use one or more imaging modes to image or measure physiological parameters in a selected tissue area of a patient.

[0067] In preferred embodiments, systems of the disclosure employ near-infrared (NIR) imaging to image vascular flow or tissue perfusion. In preferred embodiments, systems of the disclosure employ thermal imaging to monitor skin or tissue temperature in an anatomical region or surrounding the anatomical region, such as but not limited to ulcer or wound temperatures in a selected tissue area. In particularly preferred embodiments, the systems employ both NIR imaging and thermal imaging. For example, a medical professional may collect both NIR images and thermal images from the same area of tissue of a patient using one or more system components. In preferred embodiments, the images from NIR and thermal imaging components may be collected almost simultaneously and in any order. Further, NIR and thermal images may be collected over time, such as at multiple patient visits. In this way, medical professionals can monitor blood flow, perfusion or temperature changes over time to assess a patient's vascular status and / or physiological condition.

[0068] In some embodiments, Indocyanine Green (ICG) is injected into a patient such that the ICG flows through the circulatory system. According to the disclosure, the systems include a first system component that utilises fluorescent methods for diagnostic and prognostic procedures. In particularly preferred embodiments, the first system component detects the diagnostic agent ICG fluorescence or fluorescence from molecules structurally similar to ICG, including metabolites of ICG. The absorption and emission spectra for ICG are in the near infrared spectrum. For example, in someapplications, the absorption maximum of ICG is approximately 780-800 nm and the emission maximum is at approximately 820-850 nm.

[0069] To excite the fluorescent ICG, the first system component includes an excitation light source that is placed adjacent to the selected tissue area to be imaged. For example, the excitation light source may be an LED light source that emits near infrared light. In other embodiments, the excitation light source may be a laser emitting in the near infrared range. To detect the fluorescence emitted by ICG, the first system component also includes an emission detector. The emission detector is placed adjacent to the tissue area to be imaged, such that the detector detects the emitted ICG fluorescence. In preferred embodiments, the emission detector is a near infrared (NIR) imaging unit fitted with the appropriate filters to detect the emitted ICG fluorescence. For example, the imaging unit may be a camera such as the IC- Flow (Diagnostic Green, GmbH, Germany). In preferred embodiments, the excitation light source provides light at between 780- 800 nm and the imaging unit detects fluorescence at a range of between 820-850 nm. At a selected timepoint(s) after injection or perfusion of ICG into a patient, an image of emitted ICG fluorescence intensities over the selected tissue area may be obtained, using the imaging unit of the first system component. That is, the NIR imaging unit measures the amount or intensity of ICG fluorescence at points over the selected tissue area, thereby generating a map or image of fluorescence intensity over the selected tissue area.

[0070] In general, the emitted fluorescence intensity from the excited ICG varies approximately with ICG concentration in the selected tissue area. For example, a higher ICG fluorescence intensity in a selected tissue area reflects a higher ICG concentration in that area compared to areas having a lower ICG intensity, where the fluorescence intensities are measured at the same timepoint. A higher fluorescence intensity of ICG indicates that the ICG more readily flows or perfuses to an area and a lower fluorescence intensity indicates that ICG less readily flows to an area of tissue. In this way, ICG fluorescence intensity is correlated with the amount of blood flow or with the amount of perfusion in a selected tissue area.

[0071] Systems of the disclosure also include second system component that utilises thermal imaging. For example, the second system component may include an infrared thermometer which may be used to detect changes in temperature over an affected area of tissue. In preferred embodiments, the infrared thermometer is positioned over the skin or the affected area of tissue to develop an image or map of temperaturevariations over the selected tissue area. For example, the infrared thermometer collects temperature measurements at points over the same area of tissue over which ICG fluorescence is imaged to develop an image of temperature variations that overlaps with the image of ICG fluorescence intensities.

[0072] In some embodiments, a patient or a caregiver is able to collect data in the absence of a medical professional, using the system or using components of the system or similar systems. For example, an infrared thermometer or imaging system may be connected to a patient's personal electronic device, such as a mobile phone, either via cable, connector, or wirelessly. In further embodiments, a compact mobile unit with similar functionality as an infrared thermometer can be used by the patient or a caregiver for convenient monitoring In this way, the patient is able to collect temperature maps or images of the affected area in the comfort of their own home. The temperature maps or images may be sent electronically to the clinician.

[0073] Systems of the disclosure may also include additional system components that measure other physiological parameters. For example, a system component may include a white light source to illuminate a desired area of tissue to provide an image of the entire tissue area. The system may also include components that measure a patient's peripheral capillary oxygen saturation (Sp02) levels

[0074] Systems of the disclosure may include at least one controller where the at least one controller allows the system user to control the parameters of the collected images. For example, a system user is able to adjust contrast or brightness of the image obtained with the first system component using a controller. In some embodiments, a separate controller is used for each system component. In other embodiments, there may be a single controller for all system components.

[0075] The systems of the disclosure include one or more displays, such as computer or television screens or display / visualisation systems e.g. wearable systems or augmented images. Images obtained from the first and second system components may be displayed on separate screens or on one split screen. In some embodiments, two or more images may be displayed as an overlay on one screen. For example, ICG fluorescence images and thermal images may be viewed on a single screen, to provide the medical professional with a summary of the patient's status on one screen. The images obtained by the first and second system components may be presented as a composite image for better visualisation of the treatment site by the medical professionals.

[0076] Systems of the disclosure may integrate images into a unified software platform, including, for example, the UltraGreen Data Systems (United States of America) image management and storage software program where clinicians are easily able to retrieve historical images from the same patient for comparison with newly obtained images.

[0077] Annotations and the integration of images with additional sources of information which may be useful for a more complete picture to support diagnosis and treatment may also be incorporated on the image and data management system, such as UltraGreen Data Systems. These elements may include a patient's peripheral capillary oxygen saturation (Sp02) levels, details of their on-site administration of medications e g. via patches, bandages etc and any other relevant clinical data the clinician would like to include, specific to the patient.

[0078] The steps of receiving and analysing data, which includes one or more of fluorescence images, visible light images, and / or temperature data according to the present disclosure, may be carried out by one or more processors which, in various embodiments, may be located locally and / or remotely with respect to the location where the data is captured. In one embodiment, receiving and analysing data is carried out entirely locally by processor(s) on a computing system in the facility where a medical professional has captured the images and possibly temperature data. In such embodiments, the computer system that analyses the fluorescence images may be the same device that captures the fluorescence images or it may be a separate computer system in wired or wireless communication with the device that captures the fluorescence images. In another embodiment, receiving and analysing images and data are carried out entirely remotely, such as on a cloud-based server. In yet another embodiment, receiving the images and data is carried out locally, and any analysis is carried out remotely after the data has been transferred to the remote server(s).

[0079] The processor(s) will be suitably configured with one or more appropriate software components to carry out the various tasks described herein, such as but not limited to fluorescence image analysis, adaptive or machine learning techniques, mathematical and / or statistical models, and rules-based logic.

[0080] Referring to Figure 1, there is presented an exemplary computer-implemented method for assessing an anatomical region of a subject The term “anatomical region” used in the present disclosure will be understood to mean an anatomical structure or tissue of a subject. The method comprises receiving fluorescence images associatedwith a fluorescent contrast agent in the anatomical region, 110, and analysing the fluorescence images to determine one or more haemodynamic parameters, 120. The fluorescence images may at least comprise one or more frames, or a video feed, containing a fluorescent output signal resulting from the excitation of the fluorescent contrast agent that has been administered to the subject as in the anatomical region, such as in the arteries, veins, or surrounding tissue of the anatomical region. Although not presented in Figure 1, white light or RGB images may optionally also be captured for subsequent digital overlay with the fluorescence images and / or other data types captured according to the methods disclosed herein. In order to analyse the images, one or more suitable image processing software components may be utilised, such as but not limited to Perfusion Works (PerfiisionTech ApS, Denmark).

[0081] In addition, the method of Figure 1 may optionally include the step of capturing the fluorescence images using a first system component comprising a suitably configured image capture device. In order to excite the fluorescent contrast agent, an excitation source may be utilised that is configured to emit light of wavelength in the excitation range of the fluorescent contrast agent.

[0082] The fluorescent contrast agent may be administered to the subject using any means known in the art, such as but not limited to injection including intravenous injection, or topical or oral administration. In some embodiments, more than one type of fluorescent contrast agent may be administered. The fluorescent contrast agent(s) may be selected from the group consisting of: indocyanine green (ICG) or structurally similar molecules, fluorescein sodium, fluorescein isothiocyanate, abenacianine, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde, fluorescamine, porphy somes, cyanine dye, IRDDye800CW, and CLR 1502 combined with a targeting ligand. However, other fluorescent contrast agents may also be used according to the present disclosure. In preferred embodiments the fluorescent contrast agent comprises ICG or a structurally similar molecule.

[0083] The bolus amount, the number of boluses, and, where applicable, the time between boluses will vary dependent on the particular instance including subject age and weight, and the anatomical region being assessed, as well as the fluorescent contrast agent being used, and the methods disclosed herein are not limited by this. In certain embodiments, such as those in which the fluorescent contrast agent comprises ICG, the bolus amount may be between 0.01 and 0.05mg / kg, or may be less than O.Olmg / kg. In other embodiments, such as those in which the fluorescent contrastagent is fluorescein sodium, the bolus amount may be between 1 and 7.5mg / kg or more. Tn some embodiments where multiple boluses are delivered, these may be injected with an interval between 5 and 600 seconds, such as between 15 and 300 seconds, for example between 45 and 210 seconds, such as between 90 and 120 seconds. In other embodiments where multiple boluses are delivered, these may be injected with an interval between 600 and 1800 seconds.

[0084] The haemodynamic parameters determined from the fluorescence images analysis may include but are not limited to: a fluorescence intensity, a temporal change in fluorescence intensity such as a rate of increase or decrease in fluorescence intensity, a time-to-peak fluorescence intensity, a time to a given percentage fluorescence increase or decrease, a perfusion slope, a slope start, a wash-in characteristic, a wash-out characteristic, and a flow rate. The haemodynamic parameters may provide information regarding tissue perfusion, the circulatory system, and / or the lymphatic system. The term “wash-in” refers to in-flow or ingress of the fluorescent contrast agent in to the veins, arteries or surrounding tissue of an anatomical region. The term “wash-out” refers to out-flow or egress of the fluorescent contrast agent from the veins, arteries or surrounding tissue of an anatomical region. Tn order to determine these parameters a suitably configured image processing software component may analyse the fluorescent output signal in the images in individual frames and / or overtime. The identification of haemodynamic parameters facilitates an assessment of perfusion (i.e., blood flow) in the assessed anatomical region of the subject, which is important for assessing the condition of an anatomical region, including the healing or a lack of healing of a wound, a bum, or the like.

[0085] In preferred embodiments, the exemplary methods disclosed herein may comprise selecting a plurality of regions of interest (ROT) of the anatomical region, and determining the haemodynamic parameter(s) for each ROT. In various embodiments, the selection of ROIs may be made from the fluorescence images and / or visible light images of the anatomical region. The selection of ROIs may be performed manually, such as by a clinician using a display device, or semi- automatically involving a computer program-guided process involving the clinician interacting with a display device, or automatically by a computer program.Accordingly, processor(s) configured to carry steps disclosed herein will select and / or receive a selection of ROIs for the anatomical region dependent on the extent of human involvement. Where a clinician is involved in the selection of ROIs, this maybe facilitated by displaying one or more fluorescence images and / or visible light images of the anatomical region under assessment on a display device that is configured for appropriate user interaction, such as that presented in Figure 8.

[0086] In certain embodiments, processor(s) may be configured to recommend an ROI location, either based on image analysis, or based on analysis of historical RO Is selected for the anatomical region of the subject stored in memory.

[0087] Advantageously, at least one of the ROIs may be defined to be a reference ROI against which the haemodynamic parameters in other ROI(s) can be compared. In some embodiments, the reference ROI corresponds to a healthy tissue region, whilst the further ROI(s) corresponds to one or more areas of concern in the anatomical region. The healthy tissue region may be in the same anatomical region or another anatomical region of the subject. In other embodiments, the reference ROI corresponds to a macro-vascular region and the further ROI(s) correspond to a micro- vascular region. In yet further embodiments, the reference ROI and a further ROI may comprise left and right anatomical regions, or vice versa, respectively.

[0088] By determining haemodynamic parameters at both a reference ROI and one or more areas of concern, it may be possible to perform a quantitative assessment of perfusion in the area(s) of concern. For example, a perfusion slope for the fluorescent contrast agent at an area of concern ROI may be compared to the perfusion slope at a healthy tissue reference ROI, and a quantitative assessment of the area of concern may be completed based on whether the perfusion slope for the area of concern is within the expected range for healthy tissue. If the perfusion slope in the area of concern ROI is significantly less than that determined for the healthy reference ROI, this would suggest there is an underlying problem with the tissue in the area of concern. In some embodiments, this quantitative assessment may form part of the image analysis 120 performed by the processor(s) of a computer system and the result then displayed on a display device for review by a clinician. In other embodiments, the perfusion data may be displayed on a display device for a clinician to complete the quantitative assessment in a guided manner. Embodiments relating to the display of infonnation are best described in relation to Figure 4.

[0089] As another, non-limiting example, the wash-out characteristic may comprise a wash-out start, or a wash-out slope, and the wash-in characteristic may comprise a wash-in start, or a wash-in slope. By comparing a wash-in characteristic at a macro- vascular reference ROI to a wash-out characteristic at a micro-vascular area ofconcern, it may be possible to assist the clinician in their assessment of the health of the anatomical region For example, if the image analysis identifies that the wash-in time for the fluorescent contrast agent at a macro-vascular reference ROI is within the expected range for healthy tissue, but the wash-out time at the micro-vascular ROI is slower than expected for healthy tissue, this may suggest that ulceration or a lack of healing is a possible or even probable progression of the anatomical region under assessment. This is because blood is flowing well to the area of concern, but is not egressing from the area of concern adequately.

[0090] Figure 2 provides an exemplary computer-implemented method for assessing an anatomical region of a subject. The method of Figure 2 is similar to that of Figure 1, but additionally comprises the step of receiving 210 temperature data corresponding to the same anatomical region as the fluorescence images. Preferably, the temperature data comprises one or more thermal images of the anatomical region that have been acquired using a thermal camera device, but it may alternatively comprise a series of discrete temperature measurements acquired using a thermal camera device or any other appropriate temperature measurement device. In certain embodiments, the temperature data is collected by a medical professional, such as a clinician or surgeon in a clinical or surgical setting. In other embodiments, the temperature data is collected by the subject.

[0091] The method of Figure 2 may optionally additionally include the step of acquiring the temperature data, such as using a second system component described herein.

[0092] Where the analysis 120 of the fluorescence images involves selecting multiple ROIs, the temperature data is preferably collected for the same ROIs. In various embodiments, the temperature data may include one or more of absolute temperature values at ROIs, a temperature variation between ROIs, or spatial temperature gradients between ROIs. Temperature variation and / or gradient may be assessed between the reference ROI(s) and area(s) of concern, between left and right anatomical regions, or between regions exhibiting different perfusion characteristics determined according to Figure 1.

[0093] In order to ensure the consistency of ROIs, processor(s) may be configured to spatially reconcile the fluorescence images and / or visible light images with thermal images, using any known image processing technique.

[0094] The comparison of temperature data with haemodynamic parameters determined from fluorescence images, either by the clinician or automatically by a software component, may be useful in assessing the condition of the anatomical region

[0095] Referring to Figure 3, the temperature data and the result of the analysing the fluorescence images, including the determined haemodynamic parameters, may be stored in memory for subsequent review, 310. In certain embodiments the stored temperature data and image analysis results may be used for subsequent assessment of an anatomical region, best described in relation to Figure 5. Storage in memory may comprise using local and / or remotely-based storage systems, including volatile and / or non-volatile storage modules. Tn addition or alternatively, the first and second system components utilised according to the present disclosure may store their respective captured data types.

[0096] In any of the embodiments of the present disclosure, the stored temperature data and image analysis results may be used for one or more of the following: train or update one or more machine learning models for subsequent rounds of analysis 120, refine correlation models, improve predictive accuracy of tissue outcomes, and generate population-level, or multi-site level, insights. In certain embodiments, data stored across multiple patients and / or sites may be collectively utilised in an analysis.

[0097] In addition or alternatively to storing 310, the temperature data and the result of the analysing the fluorescence images may be collectively analysed and / or displayed on a display device for review by a medical professional. In one embodiment, temperature variation and the result of the analysing the fluorescence images are collectively analysed for the existence of any correlation between temperature and perfusion metrics.

[0098] Referring to Figure 4a, an exemplary computer-implemented method is illustrated in which a result of analysing 120 the fluorescence images, and the temperature data, are displayed 410 on a display device for review by a medical professional such as a clinician or surgeon. Whilst Figure 4 only illustrates the steps of Figures 1-2, it will be appreciated that storing 310 the temperature data and image analysis results may additionally be performed in the method of Figure 4. The display device may comprise a single display module, or multiple display modules, that is / area configured to present processed data, scores, maps, or visualisations to aclinician. The display device may comprise a computer monitor, a tablet, a mobile phone, or other appropriately configured display device.

[0099] Displaying temperature data together with haemodynamic parameters for the same anatomical region will give the medical professional an augmented overview of the perfusion metrics in areas of concern. By contextualising perfusion metrics with temperature data, the clinician may be able to make a more informed and accurate assessment of tissue condition, such as whether a wound is healing, whether there is a false positive in the perfusion assessment, or whether an infection or fever is developing in the subject. In some embodiments this augmented display presents spatially and temporally correlated data, allowing comparison across multiple time points, thereby improving interpretation of trends and reducing ambiguity in perfusion assessment. In further embodiments, this augmented display of information assists a clinician in making patient-treatment decisions.

[0100] In preferred embodiments illustrated in Figures 4b and 4c, the displayed information includes information 420a corresponding to determined haemodynamic parameter(s), and temperature data 420b, for each ROI Information 420a corresponding to determined haemodynamic parameter(s) may include the parameter(s) themselves, a non-dimensional score computed at least part based on the parameter(s), one or more charts or graphs demonstrating a plot of perfusion over time, and / or comparative data between ROls, and so on. In the example embodiment of Figure 4b-c, a visible light image 430a of the anatomical region is presented on the display and is labelled with the regions of interest, in order to assist a clinician in reviewing the perfusion information 420a. Similarly, a thermal image 430b of the same anatomical region is labelled to assist the clinician in reviewing the temperature data 420b and to compare said data 420b with the perfusion information 420a. Also in the example embodiment of Figure 4b, a non-dimensional perfusion score for each ROI is displayed; the discussion of such scores in best presented in relation to Figure 6.

[0101] In various embodiments, different ROIs may be colour-coded or otherwise labelled to assist the clinician in interpreting the data. In certain embodiments, such as that in Figures 4b-c, the ROIs may be visibly labelled on the image 430 of the anatomical region as a reference for comparison with the haemodynamic parameter(s) and temperature data for each ROI. The inventors have found that the visual display of both perfusion data and temperature data for an anatomical region, for the sameROIs, significantly aids the assessment of the anatomical region. For example, the comparison of perfusion metrics and temperature for the same ROIs can help in confirming the accuracy of perfusion metrics, assist in identifying a false positive, and so on. As one example, if a perfusion metric for a given area of concern appears to be within an acceptable range of values, whilst the temperature data is not (such as elevated discrete temperature points at area(s) of concern, and / or significant temperature variation or gradients between ROIs, etc.), this may be suggestive of physiological changes such as inflammation, infection, altered metabolic activity or abnormal healing response, where perfusion metrics alone might indicate improvement.

[0102] Tn certain cases the subject (patient) may return to a medical professional for further assessment. As one non-limiting example, a patient may return to a medical facility to assess the healing progress of wound. Accordingly, the processes in any of Figures 1-4 may be repeated 510 one or more times and the results then compared 520 to historical results for the same anatomical region of the subject, as illustrated by Figure 5. That is, further fluorescence images may be captured and / or received and analysed to determine one or more haemodynamic parameters, and further temperature data may be captured and / or received, for the same anatomical region. In preferred embodiments, the same ROIs may be selected for the further fluorescence images and temperature data as in the previous assessment(s).

[0103] By determining and comparing haemodynamic parameters and temperature data captured at different points in time, it may be possible to detect one or more trends related to the anatomical region such as a trend indicative of healing, deterioration, or ischemia. The determination of the trend may be based on the comparison of two or more sets of data, either measured from a baseline dataset as described herein or from any two or more sets of data acquired according to the disclosed methods. Where a particular trend has been identified, it may be provided on a display device as a notification for a clinician to investigate further.

[0104] The newly determined haemodynamic param eter(s) and / or temperature data may be quantitatively compared 520 to the historical results and data from the patient’s earlier visit(s) that have been stored 310 in memory. The comparison may be completed by one or more processor(s) as described herein, and / or by a clinician reviewing the data on a display device.

[0105] Accordingly, in some embodiments, the newly determined haemodynamic parameter(s) and / or temperature data may be displayed on a display device for review by a medical professional, such as but not limited to the manner illustrated by Figures 4b-c. The displayed information may present prior results and data alongside, or overlaid with, the newly determined image analysis results and temperature data. In addition or alternatively the comparison may comprise computer-led comparison of the historical and new determined image analysis results and temperature data, and the presentation of one or more findings on the display as a visual and / or audible notification for the clinician’s review.

[0106] In certain embodiments it may be advantageous to define a baseline set of haemodynamic parameters and temperature data, for the comparison with subsequent assessments of the anatomical region. Defining the baseline may at least comprise timestamping and storing 310 the result of analysing the fluorescence images, and the temperature data, in memory for subsequent review. In preferred embodiments, defining the baseline comprises generating a non-dimensional score for the anatomical region by correlating the determined haemodynamic parameters and temperature data for the anatomical region. The correlating of determined haemodynamic parameters and temperature data may be performed using rules-based logic, mathematical or statistical models, weighted scoring models, or adaptive or machine-learned models. In some embodiments, the non-dimensional score is normalised relative to the defined baseline and expressed as a relative change, trend, or index value over time, thereby enabling comparison across time points, regions of interest, or subjects, while reducing sensitivity to absolute measurement variability. In certain embodiments, the non-dimensional score is mapped to a visual indicator, scale, or categorical range on a display to facilitate rapid interpretation while preserving access to the underlying haemodynamic and temperature data. This mapping may assist the clinician in assessing an otherwise large and in some cases complex multi-modal dataset, by giving them a summary view of tissue condition.

[0107] In optional embodiments, additional parameters may be factored in to the generation of the score. Additional parameters may include, but are not limited to, local or peripheral oxygen saturation (SpO2), patient-specific data such as diabetes status, glucose levels, or comorbidities, wound characteristics such as size, depth, infection indicators, or complications, and historical patient data.

[0108] Accordingly, referring to Figure 6, an exemplary method is illustrated in which such a non-dimensional score, such as a wound score or a tissue viability score, is generated by correlating 610 determined haemodynamic parameters and temperature data for the anatomical region, and optionally additional parameters described herein. Preferably, the correlation is between determined haemodynamic parameters and a temperature variation for the anatomical region. The score may be assigned a number between 0-100 for each ROI, and defined relative to a score for the reference ROI which may be set to 100.

[0109] In some embodiments, the non-dimensional score may facilitate inference of perfusion data based on temperature variation and a baseline.

[0110] In alternative embodiments, separate non-dimensional scores may be generated for the haemodynamic parameters and / or the temperature data or other parameters measured for the anatomical region. For example, a “perfusion score” for an ROI, such as that presented in Figures 4b-c, may be computed based on determined haemodynamic parameters. The comparison of perfusion scores between ROIs, such as between a reference ROI and an area of concern, may greatly simplify the complex haemodynamic dataset presented to a medical professional and facilitate more rapid and easy clinical decision making.

[0111] It will be appreciated that a non-dimensional score is only one example output of analysing the haemodynamic parameters and temperature data. Figure 7 illustrates an exemplary computer implemented method in which the haemodynamic parameters and temperature data are analysed 710 together in order to produce an output 720, either provided to storage or to a display device. The output 720 may comprise the non-dimensional score of Figure 6, or it may comprise one or more of a risk classification (e g., low, moderate, high risk), indicators of improvement or deterioration of the assessed anatomical region or ROIs thereof, and visual overlays or maps highlighting areas of concern based on the analysis.

[0112] Figure 8 provides a conceptual view of an exemplary system 800 according to the present disclosure, which at least comprises one or more processor(s) 810 configured to carry out the method steps described in any of Figures 1-7 and 9. The system may be suitable for assessing tissue perfusion, vascular integrity, and tissue viability in patients whose circulatory or lymphatic systems are compromised by injury, disease, or surgical intervention. In various embodiments, the The system may operate in intraoperative environments, outpatient clinics, wound care centres, orremote and home-monitoring settings. Elements which the processor(s) may be configured to communicate with but which are optional are denoted by dash lines, and include one or more memory modules 820, a display device 830, a first system component 840, a second system component 850, and a fluorescent contrast agent delivery means 860. As discussed herein, the processor(s) 810 may be located locally and / or remotely with respect to the point of assessment, e.g. where the fluorescence images are captured and / or where the temperature data and other parameters are captured. With the exception of the first system component 840 and the display device 830, each of the elements in Figure 10 may be located locally or remotely with respect to one another in various embodiments. In addition, each of the elements 820-860 may be excluded whilst the others form part of the system 800.

[0113] The first system component 840 preferably comprises an image capture device with an excitation source such as a laser or lamp, and is configured to capture images of the fluorescent contrast agent in the anatomical region, in order to image the circulatory system, lymphatic system, or tissue perfusion. The first system component 840 will include, or will be operatively communicative with, a controller configured to instruct the capture of fluorescence images of the fluorescent contrast agent in the anatomical region Either the first system component 840, or another image capture device not pictured in Figure 8, may be configured to capture visible light images of the anatomical region.

[0114] The second system component 850 preferably comprises a thermal camera or other suitably configured temperature measurement device. In one embodiment the second system component 850 comprises an infrared camera. The second system component 850 will include, or will be operatively communicative with, a controller configured to instruct the capture of temperature data in the anatomical region.

[0115] The memory module(s) 820 may comprise local and / or cloud storage. Where the memory module(s) 820 comprise local storage, they may be located on the same computer system as any local processor(s) 810, and / or on any of the first or second system components 850 as required.

[0116] The fluorescent contrast agent delivery means 860 may comprise injection means such as an intravenous injection system or a controlled injection pump.Example 1

[0117] This example relates to the application of the systems and methods of the disclosure to improve the prevention, management, and treatment of diabetic foot ulcers, bums, or wounds or even lesions. Current diagnosis methods such as the Ankle-Brachial Index and the Toe-Pressure test often yield inaccurate results leading to an underestimation of the severity of the ulcer. The systems of the disclosure provide a robust tool to assess treatment efficacy and track wound healing and progression of foot ulcers in diabetic patients, patients with bums, wounds or even lesions including patients having undergone major surgery.

[0118] In this example, a system combines ICG fluorescence with NIR imaging and perfusion analytics / software / system to provide a detailed visualisation of microvascular perfusion in and around a diabetic foot ulcer site. In this example, the method may be repeated at each visit of a patient to a medical professional's office. The resulting imaging over time enables clinicians to identify areas of poor perfusion or blood flow that could impede healing. Also, in this example, the system includes thermal imaging or imaging using different light wavelengths. Thermal imaging monitors subtle temperature changes in the ulcer and surrounding tissue. Temperature variations can indicate inflammation, infection, or lack of healing progress or a combination of these effects. In this example, the system may include other components for measurement of other physiological data of the patient such as peripheral capillary oxygen saturation (Sp02).

[0119] Figure 9 shows a flow diagram of a method of using an embodiment of the system of Figure 9 to assess a patient having a diabetic foot ulcer. According to this example, after injection of ICG into the patient, a medical professional positions the first system component 840 over or adjacent to the area affected by the foot ulcer, where the first system component 840 includes an excitation light source and emission detector (for example, an NIR camera). The medical professional uses a controller that communicates with the first system component 840 to acquire an image.

[0120] In this example, the medical professional may acquire a single image, may collect multiple images at different timepoints, may collect one or more video clips of the selected tissue area, or may collect any combination of images or video clips at a single visit by the patient. The images or video clips show fluorescence intensitiesemitted by ICG over the selected tissue area. As ICG fluorescence intensity is correlated with the amount of blood flow, the medical professional gains an understanding of the current status of the patient's condition.

[0121] The second system component 850 performs thermal imaging of the area affected by the foot ulcer. According to this example, a medical professional may utilise thermal imaging using an infrared device 850 before or after obtaining the image or images of ICG fluorescence. The medical professional positions an infrared thermometer 850 over the area affected by the foot ulcer and uses the controller that communicates with the infrared thermometer 850 to collect temperature at various sites over the selected tissue area. The temperature variations over the selected area may be displayed in a single image or map In parallel with the collection of ICG fluorescent intensity images, the medical professional may acquire a single thermal image, may collect multiple thermal images at different timepoints, may collect one or more thermal video clips of the selected tissue area, or may collect any combination of images or video clips at single visit by the patient.

[0122] The images obtained by the first and second system components 840, 850 are displayed for viewing by a medical professional on image displays. The images are also stored 310 for retrieval to compare with images collected at subsequent timepoints. For example, the system may retrieve intensity maps of ICG fluorescence and of temperature variation collected at different patient visits which can be played in temporal sequence to present the medical professional with a visual representation of the changes in perfusion and blood flow in the area of the diabetic foot ulcer.

[0123] According to this example, the data collected from patients may be used to train computer systems for use in diagnostic procedures.

Claims

CLAIMSWhat is claimed is:

1. A computer-implemented method for assessing an anatomical region of a subject, comprising:receiving fluorescence images of a fluorescent contrast agent in the anatomical region, analysing the images to determine one or more haemodynamic parameters, receiving temperature data corresponding to the anatomical region, and displaying, on a display device, a result of the analysis and the temperature data for the anatomical region.

2. The method of claim 1, further comprising selecting or receiving a selection of a plurality of regions of interest (RO1) in the fluorescence images, wherein at least one of the ROIs is defined to be a reference area.

3. The method of claim 2, further comprising determining, from the fluorescence images, the haemodynamic parameter(s) for each ROI.

4. The method of claim 2 or claim 3, further comprising determining a temperature variation between at least the reference area and another ROT based on the temperature data.

5. The method of claims 2-4, wherein the ROIs include a micro-vascular area and a macro-vascular area.

6. The method of claims 2-5, wherein the ROIs include a healthy tissue area and an unhealthy tissue area.

7. The method of claims 2-6, further comprising computing, for each ROI, a perfusion score based on the determined parameter(s) of the ROI and a comparison to the reference area.

8. The method of claims 1-7, wherein displaying the result of the analysis and the temperature data for the anatomical region includes providing a visual indication of the selected ROIs.

9. The method of claim 8, wherein the visual indication of the selected ROIs comprises a labelled image of the anatomical region.

10. The method of claims 1-9, further comprising storing in memory the result of the analysis and the temperature data for the anatomical region.

11. The method of claims 1-10, further comprising repeating, at a subsequent time, the steps of receiving fluorescence images for the anatomical region, analysing the fluorescence images to determine one or more haemodynamic parameters, and receiving temperature data corresponding to the anatomical region; and comparing the results and / or the temperature data to historical values stored in memory for the same subject.

12. The method of claim 11, further identifying, based on the comparison, one or more trends related to the haemodynamic parameter(s) and providing a notification on the display13. The method of claim 11 or claim 12, further comprising identifying, based on the comparison, one or more correlations or discrepancies between the haemodynamic parameter(s) and the temperature data and providing a notification on the display.

14. The method of claims 1-13, wherein the haemodynamic parameter(s) include one or more of fluorescence intensity, temporal change in fluorescence intensity, a time-to- peak fluorescence intensity, a perfusion slope, a wash-in characteristic, a wash-out characteristic, and a flow rate.

15. The method of claims 1-14, wherein the anatomical region comprises a foot.

16. The method of claims 1-15, wherein the fluorescent contrast agent comprises indocyanine green (ICG).

17. A computer-readable medium comprising instructions stored thereon which, when executed by one or more processors, cause the processor(s) to carry out the method of claims 1-16.

18. A system at least comprising one or more processors configured to carry out a method for assessing the condition of an anatomical region of a subject, the method comprising the steps of:receiving fluorescence images of a fluorescent contrast agent in the anatomical region,analysing the fluorescence images to determine one or more haemodynamic parameters,receiving temperature data corresponding to the anatomical; and communicating with a display device to display the temperature data and a result of analysing the fluorescence images.

19. The system of claim 18, further comprising means for delivering one or a series of boluses of the fluorescent contrast agent to the subject.

20. The system of claim 18 or claim 19, further comprising a first system component comprising an image capture device suitable to capture the fluorescence images of the fluorescent contrast agent in the anatomical region.

21. The system of claims 18-20, further comprising a display device configured to display the temperature data and the result of analysing the fluorescence images22. The system of claims 18-21, wherein the processor(s) are further configured to select or receive a selection of a plurality of regions of interest (ROI) in the fluorescence images, wherein at least one of the ROls is defined to be a reference area.

23. The system of claim 21, wherein the display device is further configured to permit a user to select an ROI a plurality of regions of interest (ROI) in the fluorescence images, wherein at least one of the ROIs is defined to be a reference area.

24. The system of claim 22, wherein the processors) are further configured to determine a temperature variation between at least the reference area and another ROT based on the temperature data.

25. The system of claims 22-24, wherein the ROIs include a micro-vascular area and a macro-vascular area.

26. The system of claims 22-25, wherein the ROIs include a healthy tissue area and an unhealthy tissue area.

27. The system of claims 22-26, wherein the processor(s) are configured to compute, for each ROT, a perfusion score based on the determined haemodynamic parameter(s) of the ROT and a comparison to the reference ROT.

28. The system of claims 22-27, wherein displaying the result of the analysis and the temperature data for the anatomical region includes providing a visual indication of the selected ROIs.

29. The system of claim 28, wherein the visual indication of the selected ROIs comprises a labelled image of the anatomical region.

30. The system of claims 18-29, further comprising one or more memory modules, and wherein the processor(s) are further configured to store in memory the result of the analysis and the temperature data for the anatomical region.

31. The system of claims 18-30, wherein the processor(s) are further configured to repeat, at a subsequent time, the steps of receiving fluorescence images for the anatomical region, analysing the fluorescence images to determine one or more haemodynamic parameters, and receiving temperature data corresponding to the anatomical region; andwherein the processor(s) are further configured to compare the results and / or the temperature data to historical values stored in memory for the same subject.

32. The system of claim 31, wherein the processors) are further configured to identify, based on the comparison, one or more trends related to the haemodynamic parameter(s) and providing a notification on the display.

33. The system of claim 31 or claim 32, wherein the processor(s) are further configured to identify, based on the comparison, one or more correlations or discrepancies between the haemodynamic parameter(s) and the temperature data and to communicate a notification for display on the display device.

34. The system of claims 1-33, wherein the haemodynamic parameter(s) include one or more of fluorescence intensity, temporal change in fluorescence intensity, a time-to- peak fluorescence intensity, a perfusion slope, a wash-in characteristic, a wash-out characteristic, and a flow rate.

35. The system of claims 18-34, further comprising a second system component comprising a temperature measurement device configured to capture the temperature data.

36. The system of claim 20, wherein the first system component comprises a nearinfrared camera.

37. The system of claim 35, wherein the second system component comprises a thermal camera.

38. The system of claims 18-37, wherein the fluorescent contrast agent comprises indocyanine green (ICG).

39. Use of indocyanine green in the method of claims 1-17.

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