WO2023117451A1

WO2023117451A1 - Minimally invasive perfusion monitoring

Info

Publication number: WO2023117451A1
Application number: PCT/EP2022/084918
Authority: WO
Inventors: Tobias WISSEL; Sven KRÖNKE-HILLE
Original assignee: Koninklijke Philips N.V.
Priority date: 2021-12-20
Filing date: 2022-12-08
Publication date: 2023-06-29

Abstract

A device for interactively measuring perfusion includes an infrared heating source, a controller and an imaging device. The infrared heating source remotely heats a limb. The controller includes a memory that stores instructions and a processor that executes the instructions. The controller controls the heating source to remotely heat the limb. The imaging device images dynamic perfusion response to heating of the limb. The controller measures the perfusion dynamically responsive to the heating of the limb and generates a time-series of measurements of perfusion maps as heating is applied to the limb and after the heating ceases.

Description

2021PF00735

MINIMALLY INVASIVE PERFUSION MONITORING

BACKGROUND

[0001] Peripheral vascular disease (PVD) is a progressive circulation disorder that causes vessels outside of the heart and brain to constrict, reducing blood flow to limbs. PVD may be of functional origin or organic origin. Functional PVD relates to a disturbed vasomotor mechanism. An example of a disturbed vasomotor mechanism is an impeded hypoxia-mediated vasodilation/constriction due to disturbed endothelial nitric oxide production or a thermoregulation disorder due to degenerated nerves. Organic PVD is caused by lesions of stenotic plaques which build up to narrow blood vessels or to total occlusions which completely block blood vessels. Differentiating between a functional origin or organic origin as categories of root causes of PVD, including when the two categories coexistence, is crucial for choosing appropriate diagnostic means, tailoring therapy, assessing outcomes of interventions and providing long-term prognoses. Moreover, given organic root causes, assessing the spatial extent and severity of lesions is crucial for therapy planning and monitoring success of therapy. Outcome assessments of interventions are typically based on angiographies or ankle-brachial index (AB I) measurements.

[0002] In current clinical routines, only static perfusion / oxygenation is measured or monitored. Thereby, the depth of insight into the disease state is limited and does not cover several aspects. Perfusion of blood refers to the passage of blood through the circulatory system or lymphatic system. Perfusion is measured as the rate at which blood is delivered to tissue, or volume of blood per unit time per unit tissue mass. As a person gets sick, the body of the person may shift perfusion by shifting blood away from the periphery and to the core organs such as the brain, heart and lungs to protect the core organs.

[0003] Current clinical routines do not currently cover detecting vasomotor paralysis, i.e. maximal vessel dilation due to a lack of oxygen downstream such that there is no room for further vasodilation for e.g. thermoregulation or to tackle hypoxia in case of exercise: Regions of vasomotor paralysis indicate that the vessel structure is at the limit of compensating for a lack of oxygen, which provides valuable insights into the severity and spatial extent of the PVD. Such an analysis gives complementary information to static perfusion / oxygenation measurements. Currently clinical routines also do not currently cover detecting functional disorder of vasodilation / constriction. Such dysfunctions include impeded thermoregulation due to degeneration of nerves, pathway disturbances for hypoxia induced vasomotor response and other signal pathway issues. An example of hypoxia induced vasomotor response is nitric oxide production pathway in the endothelial cells.

[0004] A root cause analysis addressing the above aspects not currently covered by clinical routines inherently requires measuring reactive perfusion parameters. A single measurement of a perfusion response to external stimuli cannot directly differentiate these aspects. Examples of external stimuli include application of a thermal load or occlusion.

[0005] In the research context, various methods have been employed to measure reactive perfusion parameters after applying an external stimulus. Here, mainly ultrasound such as duplex ultrasound is used for measuring the diameter of large arteries or the flow velocity, which would have a significant impact on workflow if used in clinical routine. Dynamical perfusion measurements by near-infrared spectroscopy involving contact have also been documented, along with recent efforts involving laser speckle contrast imaging. Research has also been conducted to investigate the clinical value of various reactive perfusion parameters, along with the predictive value for cardiovascular events.

[0006] The severity of critical limb ischemia and the impact of revascularization can be detected by the slope of the laser speckle contrast signal after applying a thermal load. However, these measurements lack spatial resolution due to the contact-based local heating and the applied analysis. A commercial product known as AngioDefender focuses on analyzing reactive hyperemia using a cuff plus mainly contact-based measurements of hemodynamic parameters. However, AngioDefender does not provide spatially resolved measurements of reactive perfusion parameters, does not measure static perfusion properties, and necessarily involves contact-based measurement.

SUMMARY

[0007] According to an aspect of the present disclosure, a method for interactively measuring perfusion includes controlling an infrared heating source to remotely heat a limb; measuring, via an optical imaging device, dynamic perfusion response to heating of the limb, and generating a time-series of measurements of perfusion maps as heating is applied to the limb and after the heating ceases.

[0008] According to another aspect of the present disclosure, a device for interactively measuring perfusion includes an infrared heating source, a controller and an optical imaging device. The infrared heating source remotely heats a limb. The controller includes a memory that stores instructions and a processor that executes the instructions. The controller controls the heating source to remotely heat the limb. The optical imaging device images dynamic perfusion response to heating of the limb. The controller measures the perfusion dynamically responsive to the heating of the limb and generates a time-series of measurements of perfusion maps as heating is applied to the limb and after the heating ceases.

[0009] According to another aspect of the present disclosure, a contactless system for interactively measuring perfusion includes an infrared heating source, a controller and an optical imaging device. The infrared heating source remotely heats a limb. The controller includes a memory that stores instructions and a processor that executes the instructions. The controller controls the infrared heating source to remotely heat the limb. The optical imaging device performs imaging of dynamic perfusion response to heating of the limb. The controller measures the perfusion dynamically responsive to the heating of the limb and generates a time-series of measurements of perfusion maps as heating is applied to the limb and after the heating ceases.

BRIEF DESCRIPTION OF THE DRAWINGS

[0010] The example embodiments are best understood from the following detailed description when read with the accompanying drawing figures. It is emphasized that the various features are not necessarily drawn to scale. In fact, the dimensions may be arbitrarily increased or decreased for clarity of discussion. Wherever applicable and practical, like reference numerals refer to like elements.

[0011] FIG. 1 A illustrates a system for minimally invasive perfusion monitoring, in accordance with a representative embodiment.

[0012] FIG. IB illustrates a controller for minimally invasive perfusion monitoring, in accordance with a representative embodiment.

[0013] FIG. 2A illustrates a device for minimally invasive perfusion monitoring, in accordance with a representative embodiment.

[0014] FIG. 2B illustrates another system for minimally invasive perfusion monitoring, in accordance with a representative embodiment.

[0015] FIG. 3 illustrates a visualization of anatomical regions with perfusion characteristics, according to an aspect of the present disclosure.

[0016] FIG. 4 illustrates a method for minimally invasive perfusion monitoring, in accordance with a representative embodiment.

[0017] FIG. 5 illustrates a computer system, on which a method for minimally invasive perfusion monitoring is implemented, in accordance with another representative embodiment.

DETAILED DESCRIPTION

[0018] In the following detailed description, for the purposes of explanation and not limitation, representative embodiments disclosing specific details are set forth in order to provide a thorough understanding of an embodiment according to the present teachings. Descriptions of known systems, devices, materials, methods of operation and methods of manufacture may be omitted so as to avoid obscuring the description of the representative embodiments. Nonetheless, systems, devices, materials and methods that are within the purview of one of ordinary skill in the art are within the scope of the present teachings and may be used in accordance with the representative embodiments. It is to be understood that the terminology used herein is for purposes of describing particular embodiments only and is not intended to be limiting. The defined terms are in addition to the technical and scientific meanings of the defined terms as commonly understood and accepted in the technical field of the present teachings.

[0019] It will be understood that, although the terms first, second, third etc. may be used herein to describe various elements or components, these elements or components should not be limited by these terms. These terms are only used to distinguish one element or component from another element or component. Thus, a first element or component discussed below could be termed a second element or component without departing from the teachings of the inventive concept.

[0020] The terminology used herein is for purposes of describing particular embodiments only and is not intended to be limiting. As used in the specification and appended claims, the singular forms of terms ‘a’, ‘an’ and ‘the’ are intended to include both singular and plural forms, unless the context clearly dictates otherwise. Additionally, the terms "comprises", and/or "comprising," and/or similar terms when used in this specification, specify the presence of stated features, elements, and/or components, but do not preclude the presence or addition of one or more other features, elements, components, and/or groups thereof. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

[0021] Unless otherwise noted, when an element or component is said to be “connected to”, “coupled to”, or “adjacent to” another element or component, it will be understood that the element or component can be directly connected or coupled to the other element or component, or intervening elements or components may be present. That is, these and similar terms encompass cases where one or more intermediate elements or components may be employed to connect two elements or components. However, when an element or component is said to be “directly connected” to another element or component, this encompasses only cases where the two elements or components are connected to each other without any intermediate or intervening elements or components.

[0022] The present disclosure, through one or more of its various aspects, embodiments and/or specific features or sub-components, is thus intended to bring out one or more of the advantages as specifically noted below. For purposes of explanation and not limitation, example embodiments disclosing specific details are set forth in order to provide a thorough understanding of an embodiment according to the present teachings. However, other embodiments consistent with the present disclosure that depart from specific details disclosed herein remain within the scope of the appended claims. Moreover, descriptions of well-known apparatuses and methods may be omitted so as to not obscure the description of the example embodiments. Such methods and apparatuses are within the scope of the present disclosure. [0023] As described herein, a monitoring device and/or a monitoring system may be used to spatially resolve measurements of reactive perfusion parameters such as reactive hemodynamic parameters which respond to application of stimulus. As one result, differential diagnosis of both static perfusion and dynamical perfusion may be made possible.

[0024] FIG. 1 A illustrates a system for minimally invasive perfusion monitoring, in accordance with a representative embodiment.

[0025] The system 100 in FIG. 1A is a contactless system for minimally invasive perfusion monitoring and includes components that may be provided together or that may be distributed. The system 100 includes a controller 150, an infrared heating source 160, a thermal camera 174, an optical camera 176 and a display 180. The system 100 in FIG. 1A includes elements that may be distributed among one or more devices, even if the elements are otherwise local to one another such as by being present in the same room and connected to the same local communication network. Two or more of the elements of the system 100 may be also connected to one another physically, such as via circuitry, or wirelessly, such as via wireless interfaces. [0026] In some embodiments, the infrared heating source 160 and the thermal camera 174 are provided in a system.

[0027] The controller 150 is further depicted in FIG. IB, and includes at least a memory 151 that stores instructions and a processor 152 that executes the instructions. A computer that can be used to implement the controller 150 is depicted in FIG. 5, though a controller 150 may include more or fewer elements than depicted in FIG. IB or in FIG. 5.

[0028] The controller 150 may process image data from the optical camera 176 and the thermal camera 174, and may control the infrared heating source 160 to emit infrared heat. For example, the controller 150 may control stimulation for identifying perfusion regions with perfusion lower than a predetermined threshold. The term “hemodynamics” refers to properties of blood flow, such as dynamic properties of blood flow that change over time and even quasi-static properties of blood flow. The controller 150 may analyse image data from the optical camera 176 and measure, based on the image data, one or more hemodynamic parameter(s) to identify perfusion regions with perfusion lower than the predetermined threshold. The optical camera 176 may measure perfusion before stimulus is applied to determine static hemodynamic parameters and may measure perfusion as and/or after the stimulus is applied to determine reactive hemodynamic parameters that react to the application of stimulus. The reactive hemodynamic parameters may be determined via a spatially resolved parameter map. The reactive hemodynamic parameter may be measured based on the time-series of image data from the optical camera 176. The controller 150 calculates and analyses the reactive perfusion parameters in a spatially resolved manner. A reactive hemodynamic parameter may also comprise a parameter map, such as when a parameter map is necessary for checking whether a vasomotor dysfunction might stem from systemic causes.

[0029] The controller 150 may receive image data from the optical camera 176, measure perfusion dynamically responsive to stimulation of the limb from the image data and generate a time-series of measurements of perfusion maps before, during and after the stimulation is applied. A perfusion map is a spatially resolved distribution of perfusion and may include or otherwise reflect one or more perfusion parameters. In embodiments using the infrared heating source 160 for the stimulus, the controller 150 may also receive image data from the thermal camera 174, measure temperature from the image data and generate a time-series of measurements of temperature maps before, during and after the stimulation is applied by the infrared heating source 160. A temperature map is a spatially resolved distribution of temperature and may include or otherwise reflect temperature measurements. The time-series of measurements of perfusion maps may include measurements of the perfusion at the same locations at different times, and/or may include the differences between such measurements at one time (e.g., a first time) and at another time (e.g., a second time).

[0030] The infrared heating source 160 may be referred to herein as an “IR heater” and emits infrared signals to directly heat a limb in the manner described herein. The infrared heating source 160 is a source of stimulation controlled by the controller 150. When the infrared heating source 160 is provided on the same device as the controller 150, the infrared heating source 160 is a source of stimulation which is controlled to heat the limb and to cease remotely heating the limb. When the infrared heating source 160 and the controller 150 are provided on the same device, or separate devices which are attached to one another directly, the infrared heating source is locally controlled to remotely heat the limb. In other embodiments, the controller 150 and the infrared heating source 160 are not necessarily provided on the same device or directly attached to one another, and are instead provided as separate components so that control is provided via a wired or wireless connection between the controller 150 and the infrared heating source 160. An example of an infrared heating source 160 is a heating lamp for which heating power can be adjusted.

[0031] The optical camera 176 is representative of optical imaging devices, optical imaging systems and optical imaging components and/or optical imaging elements that perform optical perfusion imaging and which capture dynamic perfusion response to heating of the limb as described herein. The optical camera 176 is representative of devices, systems, components and elements that are contactless, and which perform spatially-resolved perfusion measurement. The perfusion measurement may be optical perfusion measurement, and may be performed via, for example, photoplethysmogram (PPG) imaging, multispectral PPG imaging, hyperspectral PPG imaging, or laser speckle contrast imaging. In one example, the optical camera 176 is an optical imaging device which consists of a broad-band light source emitting light in the visible and / or near-infrared and / or near-ultraviolet domain towards the limb and a standard multispectral camera which can spectrally resolve at least two different frequency bands of incoming light. The multispectral camera may be positioned and oriented such that it can image the light of the broad-band light source being reflected from the surface of the limb. In a further example, the broad-band light source may also include a time-dependent, local amplitude modulation, e.g. via a controllable micro-mirror array. In another example, spectral or polarization filters or prisms are used in the camera. In order to relate the measured reflectance spectra into meaningful perfusion parameter maps, a reconstruction algorithm may be applied. In one example, the reconstruction algorithm may consist of a neural network which was trained to regress perfusion parameters such as blood-content, haemoglobin-content or haemoglobin-oxygenation from a reflectance spectrum of a given pixel. Such a neural network may be trained on a training set of reflectance spectra and corresponding target perfusion parameters. The training set may be generated by Monte-Carlo simulations for the scattering processes of photons of different frequencies in the relevant skin tissue model whose perfusion-related properties (e.g., bloodcontent) can be systematically varied. The optical camera 176 is used to measure perfusion dynamically responsive to stimulation of the limb. The optical camera 176 optically measures perfusion properties that responds to the emission of heat and cessation of the emission of heat. As such, the infrared heating source 160, the thermal camera 174 and the optical camera 176 are configured to provide a contactless, optical, spatially resolved measurement of reactive hemodynamic parameters such as perfusion and blood oxygenation. As the term is used herein, reactive hemodynamic parameters are hemodynamic parameters that change in reaction to stimulus or aspects of perfusion properties that change in reaction to stimulus. The measured reactive hemodynamic parameter may involve, for example, the blood content or the blood oxygenation. As noted above, a reactive hemodynamic parameter may also comprise a parameter map, such as when a parameter map is necessary for checking whether a vasomotor dysfunction might stem from systemic causes.

[0032] In some embodiments, a motion-correction algorithm or a 3-dimensional pose estimation may be used for warping perfusion parameter maps such that spatial stability over measurement frames is achieved. When using multi/hyperspectral imaging, the reflectance spectra maps may be warped as an alternative to warping the perfusion parameter maps which are derived from these spectra. The motion-correction algorithms may also use RGB or grey -value images as a further input, such as when the RGB or grey-value images are obtained from an RGB camera (not shown) or a grey-value camera (not shown) along with the optical perfusion measurement from the image data from the optical camera 176.

[0033] The thermal camera 174 is a thermal sensor that senses temperature of the limb and images the heat signature of the limb before, during and after heat is applied by the infrared heating source 160. A time-series of the temperatures detected from the images of the heat signature may be compared to a time-series of the perfusion characteristics detected from the images from the optical camera 176, to derive one or more relationship(s) between temperatures of the limb and perfusion of the limb. The thermal camera 174 functions to provide thermography.

[0034] In FIG. 1A, the infrared heating source 160, the thermal camera 174 and the optical camera 176 may be provided as a single device for applying stimulus to a limb and detecting effects of the stimulus applied to the limb. When provided as a single device, the device may be powered by batteries or a cord that plugs into an outlet. When provided as a single device, the device may also or alternatively be connected/connectable to a computer or another host, such as to plug in and connect to the computer or another host. Such a device may be one of several individual devices configured to connect to the same host, but which are used for different specific purposes.

[0035] The thermal camera 174 outputs image data to the controller 150, and the controller 150 analyses the image data to measure a reactive hemodynamic parameter. The controller 150 analyses the measured reactive hemodynamic parameter to use in controlling application of heat as stimulus for identifying abnormally low perfused regions. In some embodiments, the heating protocol is fixed before the measurement starts and independent of the achieved temperature. In some embodiments, the heating is coupled to the temperature measurement (i.e. by setting a target temperature). In some embodiments, the perfusion parameter map is used dynamically to adapt the temporal heating protocol. The heat may be applied under the control of the controller 150 using a defined protocol, and the reactive hemodynamic parameter may be simultaneously measured via the thermal camera 174. The analysis by the controller 150 may be performed as the heat is applied and after the heat is no longer applied. In some embodiments, the reactive hemodynamic parameter may be derived only after having performed the whole measurement, such as by taking an integral of a quantity over the course of the whole measurement.

[0036] The display 180 is used to produce a visualization of spatial maps of (i) abnormally low perfused regions and (ii) regions with vasomotor dysfunction. The display 180 may be local to the controller 150 or may be remotely connected to the controller 150. The display 180 may be connected to the controller 150 via a local wired interface such as an Ethernet cable or via a local wireless interface such as a Wi-Fi connection. The display 180 may be interfaced with other user input devices by which users can input instructions, including mouses, keyboards, thumbwheels and so on.

[0037] The display 180 may be a monitor such as a computer monitor, a display on a mobile device, an augmented reality display, a television, an electronic whiteboard, or another screen configured to display electronic imagery. The display 180 may also include one or more input interface(s) that may connect other elements or components to the controller 150, as well as an interactive touch screen configured to display prompts to users and collect touch input from users.

[0038] As shown in FIG. 1 A, a chart of perfusion versus time includes a curve with a baseline designated “healthy patient” and a curve designated “vasoconstriction dysfunction”. The curve for the “healthy patient” may comprise a baseline for all patients, or may comprise a baseline for patients with similar demographic and health characteristics to the patient with the limb being stimulated. A map labelled as “opt. perfusion measurement” is also provided adjacent to the chart, and includes a magnifying glass indicating that the curve stems from aggregating (e.g., summing/averaging) the perfusion parameter (e.g., blood content) of a small region. In the chart, an area where both curves rise corresponds to a heating phase when the infrared heating source 160 is used for the stimulation. The peak perfusion is labelled in the chart by the dotted line. A thermal stimulus is applied for both healthy patients and patients with a vasoconstriction dysfunction. The labels refer to the individual curves illustrating the typical behavior for healthy subjects given a stimulus and the typical behavior for subjects with a vasoconstriction dysfunction given a stimulus. As can be seen directly in the chart, a difference between the “healthy patient” and the patient with the limb being stimulated may be determined from a difference in a first slope for the patient with the limb being stimulated, insofar as the first slope for the patient with the limb being stimulated will differ substantially from the baseline some time after the stimulation ceases. Differences in individual perfusion measurements and the baseline at times may also indicate vasoconstriction dysfunction, such as when the raw difference 30 seconds after perfusion peaks is unmistakably elevated compared to the baseline. Analysis of a dynamic perfusion response to heating is not limited to slopes or absolute differences, and may use and include any kind of parameter that describes reactive hyperemia. For example, an exponential may be fit to a chart of changes in perfusion in order to derive a time constant.

[0039] In embodiments based on FIG. 1A or any FIGs. with similar or related features, optical perfusion measurement may be resolved over time without requiring contact with the patient. The optical imaging by the optical camera 176 does not particularly require any specific type of optical perfusion measurement, and can optically measure perfusion via photoplethysmogram imaging, multispectral variants or hyperspectral variants of photoplethysmogram imaging, or laser speckle contrast imaging.

[0040] The optical camera 176 images perfusion dynamically responsive to stimulation of the limb. The controller 150 measures the perfusion which is dynamically responsive to the stimulation of the limb and generates a time-series of measurements of perfusion maps as stimulation is applied to the limb and after the stimulation ceases. The controller 150 analyses one or more reactive hemodynamic parameter(s) measured based on, or otherwise derived from, image data from the optical camera 176.

[0041] FIG. IB illustrates a controller for minimally invasive perfusion monitoring, in accordance with a representative embodiment.

[0042] The controller 150 includes a memory 151 and a processor 152. The memory 151 stores instructions and the processor 152 executes the instructions. When used in a device with the thermal camera 174, the infrared heating source 160 and the optical camera 176, the device with the controller 150 may be a stand-alone device that can be used to stimulate perfusion and to measure reactive hemodynamic parameters. In such embodiments, the minimally invasive perfusion monitoring may be performed without requiring contact with a patient.

[0043] In some embodiments, the controller 150 may be separate from a device with the thermal camera 174, the infrared heating source 160 and the optical camera 176. For example, the controller 150 may be provided in a computer that controls multiple different medical devices and the devices may be configured to connect wirelessly or by wire to the computer with the controller 150. In such embodiments, the minimally invasive perfusion monitoring may still be performed without requiring contact with a patient.

[0044] FIG. 2A illustrates a device for minimally invasive perfusion monitoring, in accordance with a representative embodiment.

[0045] In FIG. 2A, a device 201 includes a controller 250, a first interface 256, a second interface 257, a third interface 258, a fourth interface 259, an infrared heating source 260, a thermal camera 274, an optical camera 276, a display 280 and a handle 290.

[0046] The device 201 is a device for interactively measuring perfusion. The device 201 interacts with tissue by remotely stimulating the tissue with heat, and remotely measuring perfusion responsive to the stimulating of the tissue. The device 201 analyses image data. The interactive measurement of perfusion by the device 201 is fast, dynamic and efficient, and results in measuring perfusion properties dynamically responsive to the heat. The controller 250 may be the same as or similar to the controller 150 in FIG. 1A and FIG. IB. That is, the controller 250 may include at least a memory that stores instructions and a processor that executes the instructions. The controller 250 may perform some of the operations described herein directly and may implement other operations described herein indirectly. For example, the controller 250 may indirectly control other operations such as by generating and transmitting content to be displayed on the display 280. Accordingly, the processes implemented by the controller 250 may include steps not directly performed by the controller 250.

[0047] The first interface 256, the second interface 257, the third interface 258 and the fourth interface 259 may include ports, disk drives, wireless antennas, or other types of receiver circuitry. One or more of these interfaces may be or include a user interface that accepts instructions from a user, such as buttons, knobs and external switches. One or more of these interfaces may also be or include a communications interface that enables communications over a wireless network such as a local wireless network.

[0048] The optical camera 276 is a camera used to capture perfusion before, during and after stimulation is applied to a limb. The infrared heating source 260 emits infrared signals to directly but remotely heat the limb, and the thermal camera 274 captures an image of a heat signature of the limb. The thermal camera 274 and the infrared heating source 260 may captures time-series of images that can be correlated with one another to determine effects of heat on characteristics of perfusion.

[0049] In embodiments based on FIG. 2A or other FIGs. herein, a static perfusion map may be recorded before stimulus is applied. The static perfusion map may be automatically analyzed for abnormally low perfused regions. For example, a convolutional neural network (CNN) may be trained on perfusion maps of healthy individuals and patients with perfusion deficits for a particular purpose, and then applied to static perfusion maps. For example, the CNN may be trained to segment regions of abnormally low perfusion. Regions with detected perfusion may be displayed to the clinician, such as via an overlay on a perfusion map in a graphical user interface of the display 280. The static perfusion maps may be used for a spatially-resolved root-cause analysis of PVD. An example of a perfusion map with overlayed static perfusion and dynamical perfusion is provided in FIG. 3.

[0050] The display 280 may be a display similar to a display on a smartphone or a tablet computer, though the display 280 may be an interactive touch graphical user interface that directly accepts input from a user via touch. The display 280 is configured to produce a visualization of spatial maps of perfused regions with perfusion below a predetermined threshold and regions with vasomotor dysfunction. In some embodiments, all or most pixels of a spatial map are analyzed to identify vasomotor dysfunction. In some embodiments, pixels of different regions in a spatial map are analyzed, to identify variations in dysfunction by region, or an average of dysfunction of multiple regions. For example, the device 201 or the system 100 may analyze perfusion to determine whether a systemic or local effect is likely by evaluating spatial variation of dysfunction over an equivalently heated region.

[0051] In FIG. 2A, the device 201 is an integrated device that stimulates perfusion and captures the perfusion without requiring physical contact with the limb.

[0052] The spatially resolved measurement of reactive perfusion parameters with the device 201 may enable resolution of relevant research questions such as whether and to what extent vasodilation can be hindered. Hindrance of vasodilation may be caused by, for example, local intima thickening due to a potential stiffening of the vessel wall. Having a diagnostic tool such as the device 201 and system 100 described herein provides for measuring and monitoring dynamical perfusion properties in a spatially resolved manner with low impact on clinical workflows. The diagnostic tool provided by the device 201 and the system 100 thus contributes to both clinical knowledge and research perspectives, such as for obtaining more detailed insights into variants of the disease and factors relevant for long-term prognosis.

[0053] The system 100, the controller 150, and the device 201 may be used for monitoring according to the teachings herein. The system 100, the controller 150 and the device 201 may be contactless, and can be used for probing the functionality of vasodilation and vasoconstriction, allowing also for long-term monitoring and distinction between functional root causes of PVD and organic root causes of PVD. By combining optical perfusion measurement techniques such as photoplethysmogram imaging with an infrared heating source 160 and thermography in FIG. 1 A and the infrared heating source 260 and thermography in FIG. 2A, the perfusion reaction to a defined thermal load may be measured in a manner that is spatially resolved. Additionally, all components used for the optical perfusion measurement and the photoplethysmogram may be mounted on a common platform, resulting in a single, compact instance of the device 201.

[0054] Additionally, the system 100 and the device 201 may be used to automatically analyze the local perfusion before, while and after applying the thermal load. As a result, the local vasomotor functionality may be quantified and made visualizable for the clinician as a dynamical perfusion parameter map that reflects reactions to application of heat. Due to the spatial resolution, a relatively-global vasomotor dysfunction due to systemic root causes (functional PVD) may be differentiable from a relatively spatially-confined dysfunction due to organic causes.

[0055] The dynamical response can also be used for identifying regions of vasomotor paralysis, such as saturated vasodilation due to a lack of oxygen as a consequence of a stenosis. The identification of such regions provides detailed and, with respect to. static perfusion measurements, complementary information about the region affected by organic PVD. In addition, the static perfusion properties may be assessed by automatically identifying regions of abnormally low perfusion from perfusion maps measured before applying the thermal load.

[0056] Therefore, the teachings herein provide mechanisms to measure both static and dynamical properties of perfusion with minimal impact on the clinical workflow. The teachings herein provide for assessing both the static and the dynamical perfusion functionalities in a spatially resolved manner before and after the intervention, to achieve a detailed view on the functionality of the vessel tree.

[0057] FIG. 2B illustrates another system for minimally invasive perfusion monitoring, in accordance with a representative embodiment.

[0058] In FIG. 2B, the system 200 includes the infrared heating source 260 separate from the controller 250. A device in FIG. 2 may include the optical camera 276, the display 280, the handle 290, the controller 250 and the same interfaces as in FIG. 2A. The device may also include a thermal camera, such as the thermal camera 174 or the thermal camera 274, but the infrared heating source 260 is provided separate from the device even though the infrared heating source 260 may be controlled by the controller 250 of the device. The device with the controller 250 and the interfaces may wirelessly control the infrared heating source 260 to stimulate the limb. Among the interfaces shown in FIG. 2B, a wireless interface may be configured to send a wireless signal to control the infrared heating source 260, and the infrared heating source 260 may be remotely controlled to physically tighten around the limb.

[0059] FIG. 3 illustrates a visualization of anatomical regions with perfusion characteristics, according to an aspect of the present disclosure.

[0060] In FIG. 3, a visualization includes regions with reactive perfusion parameters which are indicative for a local vasomotor dysfunction. The local vasomotor dysfunction may be due to a stiffening of the vessel wall. The visualization in FIG. 3 also includes regions where a low static perfusion is indicative for a stenosis. The visualization in FIG. 3 may be provided as a color map, and may be generated as a video that changes over time.

[0061] In FIG. 3, a spatially resolved map shows vasomotor dysfunction and abnormally low static perfusion, and thus reflects the differential capabilities of the device and/or system described herein. As an example, the vasodilation functionality may be used as a component in differential diagnosis of functional PVD vs. organic PVD, and this may be useful for the subsequent treatment strategy. A functional PVD has systemic root causes which are detectable at a level that is relatively more global than characteristics of organic PVD insofar as organic PVD may feature localized vasodilation dysfunction, such as due to local vessel wall stiffening. Vasomotor paralysis is of organic cause and should be reduced and cured after a successful treatment of stenosis. By comparing the dynamical perfusion parameter map before and after a revascularization, vasomotor paralysis may be differentiated from actual vasodilation / - constriction dysfunctions.

[0062] FIG. 4 illustrates a method for minimally invasive perfusion monitoring, in accordance with a representative embodiment.

[0063] The method of FIG. 4 may be provided by a device such as the device 201 in FIG. 2A. [0064] At S410, an IR heater is activated and controlled to remotely stimulate a limb with heat. The IR heater may be or include the infrared heating source 160 in FIG. 1A, or the infrared heating source 260 in FIG. 2A. The IR heater may be activated before the infrared signals are applied to the limb, or may begin applying the infrared signals to the limb immediately upon activation.

[0065] At S420, an optical camera is activated to image perfusion in the limb. The optical camera may be or include the optical camera 176 in FIG. 1 or the optical camera 276 in FIG. 2A [0066] At S430, a thermal camera is activated to image temperature of the limb. The thermal camera may be or include the thermal camera 174 in FIG. 1A or the thermal camera 274 in FIG. 2A.

[0067] Although S410, S420 and S430 are shown in a specific order, these steps of FIG. 4 may be performed simultaneously or in a different order without departing from the spirit and scope of the teachings herein.

[0068] At S440, perfusion is measured based on the perfusion image. When the method of FIG. 4 is performed by or using a single device, the device analyses image data (e.g., a time-series of measurements of perfusion maps). When the method of FIG. 4 is performed by a system, the device with a controller described herein analyses image data (e.g., a time-series of measurements of perfusion maps) to measure the perfusion. The perfusion may be measured by the controller 150 or the controller 250 executing instructions to analyze the perfusion image obtained at S420.

[0069] At S450, temperatures are measured based on the temperature image. The temperatures may be measured by the controller 150 or the controller 250 executing instructions to analyze the temperature image obtained at S430.

[0070] The temperature measured at S450 is fed back so that the IR heater can be controlled at S410 based on the measured temperature. In other words, the nature of the stimulus applied to a limb may be changed while the perfusion response is being measured. One example of the change based on the measurements is when the stimulus is cut off as a binary result of the temperature reaching a target. Another example of how the stimulus may be changed is as a step function starting from off, so that each cycle the stimulus may be incremented in equal steps until a constant surface temperature set as a target is met. Another example of how the stimulus may be changed is as a variable function based, for example on the difference between the measurement and a target, such as in steps of 25% or 50% of the difference from a measured temperature to a target temperature. For example, if a target temperature is set, the measured temperature from S450 may be used to determine whether to increase, decrease or maintain the temperature of the IR heater at S410. In some embodiments, the IR heater may be modulated by a function that is not a step function, and the perfusion measurements may be analyzed to detect how perfusion dynamically follows the stimulus, if at all. When the IR heater is controlled at S410 based on the measured temperature from S450, the process from S420 to S440 may be repeated, so that the processes from S410 to S450 form a process loop. The controlling of the heating source may therefor include locally controlling the heating source to remotely step-up heating of the limb in steps

[0071] At S460, a time-series of perfusion measurements is generated. The time-series of perfusion measurements may include measurements of perfusion maps taken at the same part(s) of the limb at different times. The time-series of perfusion measurements may be generated by the controller 150 or the controller 250 executing instructions. The time-series of perfusion measurements may be values of derived perfusion parameters. Examples of derived perfusion parameters that may be derived and output include, for example: o a local maximal response of the perfusion over time o slope of the perfusion over time

The time-series of perfusion measurements or perfusion parameters derived from the perfusion parameters may be displayed as a spatial map.

[0072] At S470, a time-series of temperatures measurements is generated. The time-series of temperatures may include measurements of temperature maps taken at the same part(s) of the limb at different times. The time-series of temperature measurements may be generated by the controller 150 or the controller 250 executing instructions. An example of a derived perfusion parameter relating to the temperature measurements over time is: o a measure for the correlation between perfusion and local temperature derived from relative changes of the perfusion and the temperature over time

[0073] At S480, the time-series are output. The time-series may be output individually or together, such as via display on the display 180 or the display 280. The time-series which are output may be a display of perfusion measurements or perfusion parameters derived from the perfusion parameters, and the time-series may be output as a spatial map.

[0074] At S490, an effect of applying the heat is identified. For example, the output at S490 may be evaluated to identify from the spatial variation over an equivalently heated region, whether a systemic effect or a local effect is likely. That is, the time-series may be evaluated to identify from spatial variation whether an effect is more likely to be systemic or local. For example, the controller 150 may analyze a reactive hemodynamic parameter measured based on the image data of the perfusion image(s), and determine from the reactive hemodynamic parameter whether the effect of applying the heat is more likely to be systemic or local. The reactive hemodynamic parameter(s) is/are useful in predicting, for example, how a local vessel diameter is dynamically adapted based on changes in stimulus. The reactive hemodynamic parameter(s) exclude static perfusion properties, and instead indicate how the perfusion changes from stimulus, and particularly from thermal stimulus. In this way, reactive perfusion parameters such as the change in vascular resistance over the change in time, in dependence on the stimulus dynamics (e.g. local temperature T(t)), can be measured.

The static perfusion parameters and characteristics may be obtained by measuring perfusion before the stimulus and after reaching a static or quasi-static state by heating the skin surface to a certain given temperature. The given temperature may be determined from measuring the temperature repeatedly at S450 until the given temperature is obtained, using feedback from the thermal camera 274. The controlling of the heating source may be based on feedback from the measuring of the temperature.

[0075] The measurements of perfusion maps of perfusion and the measurements of temperature maps provide insights into dynamical perfusion properties, such as how the vascular system adapts to different temperatures. From two measurements of static perfusion properties, an observation of dynamical perfusion properties may be generated by e.g. taking the difference of the measurements.

[0076] In embodiments based on FIG. 4, stimulus will cease at some point, but does not necessarily cease immediately when a target is reached. Rather, when a target is met, stimulus may simply be maintained constant.

[0077] In some embodiment based on FIG. 4, using a device 201 as in FIG. 2A, an infrared (IR) heating source and a thermography camera may be mounted on the same platform as the optical imaging device, resulting in a single device which allows for a controlled heating of the limb and spatially resolved measurement of the perfusion reaction to this thermal load. Here, the thermal camera 274 may be used for controlling the IR heating source such that a well-defined mean skin temperature is achieved. In some embodiments, a user-defined heating period for achieving the desired temperature may be realized by automatically analyzing the temporal increase of the skin temperature and adjusting the IR heating power to meet pre-defined temperature requirements across the surface area. Geometric properties and thresholds on the skin temperature can be used to avoid patient harm by overheating. Once the desired mean skin temperature is achieved, the IR heating source may be switched off either abruptly or with a finite rate. During the process, the perfusion parameter(s) is/are measured as the temporal/functional response to the stimulus. [0078] In additional embodiments based on FIG. 4, using a device 201 as in FIG. 2A, the thermography signal may be recorded after heating for directly probing the functionality of the thermoregulation. The perfusion may be locally analyzed. The analysis of the perfusion may be performed along with analysis of the thermography signal. The analysis of the perfusion may be performed after normalizing to the static perfusion measurement as a reference baseline.

[0079] Thermoregulation may be triggered by a vasodilation mechanism triggered via a nervous system if a disease pattern allows. The thermal stimulus initially may lead to an increase of the perfusion signal due to the thermoregulation. The enhancement from thermoregulation diminishes over time after the thermal load is switched off for healthy persons, while the decay time scale is extremely prolonged or absent for patients with a vasomotor dysfunction and indicative for a hindered vasoconstriction. By calculating indicative reactive perfusion parameters such as the slope of the decay, the existence and potentially also the severity of the vasomotor dysfunction may be determined, such as by thresholding or more sophisticated classifiers / regressors. The result can thereafter be visualized as an overlay on e.g., the perfusion map or the simultaneously-acquired RGB / grey-value image. The dynamical perfusion parameter analysis may be combined and overlayed with the result of the static perfusion analysis. As a result, a spatially resolved root-cause analysis for PVD is enabled, which may be used for therapy planning, outcome assessment of e.g., a revascularization intervention, and potentially also long-term prognosis.

[0080] Since a single, compact device such as the system 100 may be used for minimally invasive perfusion monitoring, the system 100 may also be used for long-term monitoring both in hospitals with minimal impact on the workflow and at home, in order to assess the effect of pharmaceutical treatments or a revascularization as well as for assessing cardiovascular risks. [0081] In the method of FIG. 4, using the system 200 of FIG. 2B, reactive hyperemia may be probed. The signal pathways are triggered by hypoxia and also influence vasomotor behavior. The thermal stimulus may be wirelessly controlled Abnormalities both in the static perfusion and the reactive perfusion parameters can be derived and visualized as detailed herein. [0082] FIG. 5 illustrates a computer system, on which a method for minimally invasive perfusion monitoring is implemented, in accordance with another representative embodiment. [0083] Referring to FIG.5, the computer system 500 includes a set of software instructions that can be executed to cause the computer system 500 to perform any of the methods or computer- based functions disclosed herein. The computer system 500 may operate as a standalone device or may be connected, for example, using a network 501, to other computer systems or peripheral devices. In embodiments, a computer system 500 performs logical processing based on digital signals received via an analog-to-digital converter.

[0084] In a networked deployment, the computer system 500 operates in the capacity of a server or as a client user computer in a server-client user network environment, or as a peer computer system in a peer-to-peer (or distributed) network environment. The computer system 500 can also be implemented as or incorporated into various devices, such as an integrated mobile device described herein, whether such an integrated mobile device comprises a mobile computer, a laptop computer, a tablet computer, a stand-alone special purpose medical device, or any other machine capable of executing a set of software instructions (sequential or otherwise) that specify actions to be taken by that machine. The computer system 500 can be incorporated as or in a device that in turn is in an integrated system that includes additional devices. In an embodiment, the computer system 500 can be implemented using electronic devices that provide voice, video or data communication. Further, while the computer system 500 is illustrated in the singular, the term “system” shall also be taken to include any collection of systems or sub-systems that individually or jointly execute a set, or multiple sets, of software instructions to perform one or more computer functions.

[0085] As illustrated in FIG. 5, the computer system 500 includes a processor 510. The processor 510 may be considered a representative example of the processor 152 of the controller 150 in FIG. IB and executes instructions to implement some or all aspects of methods and processes described herein. The processor 510 is tangible and non-transitory. As used herein, the term “non-transitory” is to be interpreted not as an eternal characteristic of a state, but as a characteristic of a state that will last for a period. The term “non-transitory” specifically disavows fleeting characteristics such as characteristics of a carrier wave or signal or other forms that exist only transitorily in any place at any time. The processor 510 is an article of manufacture and/or a machine component. The processor 510 is configured to execute software instructions to perform functions as described in the various embodiments herein. The processor 510 may be a general -purpose processor or may be part of an application specific integrated circuit (ASIC). The processor 510 may also be a microprocessor, a microcomputer, a processor chip, a controller, a microcontroller, a digital signal processor (DSP), a state machine, or a programmable logic device. The processor 510 may also be a logical circuit, including a programmable gate array (PGA), such as a field programmable gate array (FPGA), or another type of circuit that includes discrete gate and/or transistor logic. The processor 510 may be a central processing unit (CPU), a graphics processing unit (GPU), or both. Additionally, any processor described herein may include multiple processors, parallel processors, or both. Multiple processors may be included in, or coupled to, a single device or multiple devices. [0086] The term “processor” as used herein encompasses an electronic component able to execute a program or machine executable instruction. References to a computing device comprising “a processor” should be interpreted to include more than one processor or processing core, as in a multi-core processor. A processor may also refer to a collection of processors within a single computer system or distributed among multiple computer systems. The term computing device should also be interpreted to include a collection or network of computing devices each including a processor or processors. Programs have software instructions performed by one or multiple processors that may be within the same computing device or which may be distributed across multiple computing devices.

[0087] The computer system 500 further includes a main memory 520 and a static memory 530, where memories in the computer system 500 communicate with each other and the processor 510 via a bus 508. Either or both of the main memory 520 and the static memory 530 may be considered representative examples of the memory 151 of the controller 150 in FIG. IB, and store instructions used to implement some or all aspects of methods and processes described herein. Memories described herein are tangible storage mediums for storing data and executable software instructions and are non-transitory during the time software instructions are stored therein. As used herein, the term “non-transitory” is to be interpreted not as an eternal characteristic of a state, but as a characteristic of a state that will last for a period. The term “non- transitory” specifically disavows fleeting characteristics such as characteristics of a carrier wave or signal or other forms that exist only transitorily in any place at any time. The main memory 520 and the static memory 530 are articles of manufacture and/or machine components. The main memory 520 and the static memory 530 are computer-readable mediums from which data and executable software instructions can be read by a computer (e.g., the processor 510). Each of the main memory 520 and the static memory 530 may be implemented as one or more of random access memory (RAM), read only memory (ROM), flash memory, electrically programmable read only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), registers, a hard disk, a removable disk, tape, compact disk read only memory (CD- ROM), digital versatile disk (DVD), floppy disk, Blu-ray disk, or any other form of storage medium known in the art. The memories may be volatile or non-volatile, secure and/or encrypted, unsecure and/or unencrypted.

[0088] “Memory” is an example of a computer-readable storage medium. Computer memory is any memory which is directly accessible to a processor. Examples of computer memory include, but are not limited to RAM memory, registers, and register files. References to “computer memory” or “memory” should be interpreted as possibly being multiple memories. The memory may for instance be multiple memories within the same computer system. The memory may also be multiple memories distributed amongst multiple computer systems or computing devices. [0089] As shown, the computer system 500 further includes a video display unit 550, such as a liquid crystal display (LCD), an organic light emitting diode (OLED), a flat panel display, a solid-state display, or a cathode ray tube (CRT), for example. Additionally, the computer system 500 includes an input device 560, such as a keyboard/virtual keyboard or touch-sensitive input screen or speech input with speech recognition, and a cursor control device 570, such as a mouse or touch-sensitive input screen or pad. The computer system 500 also optionally includes a disk drive unit 580, a signal generation device 590, such as a speaker or remote control, and/or a network interface device 540.

[0090] In an embodiment, as depicted in FIG. 5, the disk drive unit 580 includes a computer- readable medium 582 in which one or more sets of software instructions 584 (software) are embedded. The sets of software instructions 584 are read from the computer-readable medium 582 to be executed by the processor 510. Further, the software instructions 584, when executed by the processor 510, perform one or more steps of the methods and processes as described herein. In an embodiment, the software instructions 584 reside all or in part within the main memory 520, the static memory 530 and/or the processor 510 during execution by the computer system 500. Further, the computer-readable medium 582 may include software instructions 584 or receive and execute software instructions 584 responsive to a propagated signal, so that a device connected to a network 501 communicates voice, video or data over the network 501. The software instructions 584 may be transmitted or received over the network 501 via the network interface device 540.

[0091] In an embodiment, dedicated hardware implementations, such as application-specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), programmable logic arrays and other hardware components, are constructed to implement one or more of the methods described herein. One or more embodiments described herein may implement functions using two or more specific interconnected hardware modules or devices with related control and data signals that can be communicated between and through the modules. Accordingly, the present disclosure encompasses software, firmware, and hardware implementations. Nothing in the present application should be interpreted as being implemented or implementable solely with software and not hardware such as a tangible non-transitory processor and/or memory.

[0092] In accordance with various embodiments of the present disclosure, the methods described herein may be implemented using a hardware computer system that executes software programs. Further, in an exemplary, non-limited embodiment, implementations can include distributed processing, component/object distributed processing, and parallel processing. Virtual computer system processing may implement one or more of the methods or functionalities as described herein, and a processor described herein may be used to support a virtual processing environment.

[0093] Accordingly, minimally invasive perfusion monitoring enables measurement of reactive perfusion parameters with a single, compact device targeting a monitoring scenario with a minimal amount of extra effort. The single device may be used in diverse contexts such as catheterization laboratories, clinical bedside, and even home use. The device described herein will minimally impact a clinical workflow and can assess both static properties and dynamical properties quickly such as in one run taking seconds. The teachings herein may be implemented as a new diagnostic device in catheter labs for assessing vasomotor function before and after an intervention, or as a long-term monitoring device, including for monitoring at home.

[0094] Although minimally invasive perfusion monitoring has been described with reference to several exemplary embodiments, it is understood that the words that have been used are words of description and illustration, rather than words of limitation. Changes may be made within the purview of the appended claims, as presently stated and as amended, without departing from the scope and spirit of minimally invasive perfusion monitoring in its aspects. Although minimally invasive perfusion monitoring has been described with reference to particular means, materials and embodiments, minimally invasive perfusion monitoring is not intended to be limited to the particulars disclosed; rather minimally invasive perfusion monitoring extends to all functionally equivalent structures, methods, and uses such as are within the scope of the appended claims. [0095] The illustrations of the embodiments described herein are intended to provide a general understanding of the structure of the various embodiments. The illustrations are not intended to serve as a complete description of all of the elements and features of the disclosure described herein. Many other embodiments may be apparent to those of skill in the art upon reviewing the disclosure. Other embodiments may be utilized and derived from the disclosure, such that structural and logical substitutions and changes may be made without departing from the scope of the disclosure. Additionally, the illustrations are merely representational and may not be drawn to scale. Certain proportions within the illustrations may be exaggerated, while other proportions may be minimized. Accordingly, the disclosure and the figures are to be regarded as illustrative rather than restrictive.

[0096] One or more embodiments of the disclosure may be referred to herein, individually and/or collectively, by the term “invention” merely for convenience and without intending to voluntarily limit the scope of this application to any particular invention or inventive concept. Moreover, although specific embodiments have been illustrated and described herein, it should be appreciated that any subsequent arrangement designed to achieve the same or similar purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all subsequent adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the description.

[0097] The Abstract of the Disclosure is provided to comply with 37 C.F.R. § 1.72(b) and is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, various features may be grouped together or described in a single embodiment for the purpose of streamlining the disclosure. This disclosure is not to be interpreted as reflecting an intention that the claimed embodiments require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter may be directed to less than all of the features of any of the disclosed embodiments. Thus, the following claims are incorporated into the Detailed Description, with each claim standing on its own as defining separately claimed subject matter.

[0098] The preceding description of the disclosed embodiments is provided to enable any person skilled in the art to practice the concepts described in the present disclosure. As such, the above disclosed subject matter is to be considered illustrative, and not restrictive, and the appended claims are intended to cover all such modifications, enhancements, and other embodiments which fall within the true spirit and scope of the present disclosure. Thus, to the maximum extent allowed by law, the scope of the present disclosure is to be determined by the broadest permissible interpretation of the following claims and their equivalents and shall not be restricted or limited by the foregoing detailed description.

Claims

CLAIMS:

1. A method for interactively measuring perfusion, comprising: controlling an infrared heating source to remotely heat a limb; measuring, via an optical imaging device, dynamic perfusion response to heating of the limb, and generating a time-series of measurements of perfusion maps as heating is applied to the limb and after the heating ceases.

2. The method of claim 1, wherein the infrared heating source is controlled to remotely heat the limb and to cease remotely heating the limb.

3. The method of claim 2, further comprising: measuring, using a thermal camera, a temperature of the limb as the infrared heating source remotely heats the limb and after the infrared heating source ceases remotely heating the limb; and generating a time-series of measurements of temperature maps as the infrared heating source remotely heats the limb and after the infrared heating source ceases remotely heating the limb, and identifying an effect of the heat on the perfusion.

4. The method of claim 3, wherein the controlling of the infrared heating source is based on feedback from the measuring of the temperature.

5. The method of claim 1, wherein the controlling of the infrared heating source comprises locally controlling the infrared heating source to remotely step-up heating of the limb in steps.

6. The method of claim 1, wherein the perfusion maps comprise perfusion parameters derived from the measuring.

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7. The method of claim 1, further comprising: displaying the time-series of measurements of perfusion maps as the heating is applied to the limb and after the heating ceases.

8. The method of claim 1, wherein the measuring comprises: measuring a first slope of the perfusion as the heat is applied and a second slope of the perfusion after the heating ceases.

9. A device for interactively measuring perfusion, comprising: an infrared heating source that remotely heats a limb; a controller with a memory that stores instructions and a processor that executes the instructions, wherein the controller controls the heating source to remotely heat the limb; an optical imaging device that images dynamic perfusion response to heating of the limb, wherein the controller measures the perfusion dynamically responsive to the heating of the limb and generates a time-series of measurements of perfusion maps as heating is applied to the limb and after the heating ceases.

10. The device of claim 9, further comprising: a thermal camera that senses temperature of the limb as the infrared heating source heats the limb and after the infrared heating source ceases heating the limb, wherein the controller generates a time-series of measurements of temperature maps as the heat is applied to the limb and after the heating ceases, and wherein the controller identifies an effect of the heat on the perfusion.

11. The device of claim 10, wherein, when the processor executes the instructions, the device analyses image data from the optical imaging device and measures, based on the timeseries of measurements of perfusion maps, a reactive hemodynamic parameter.

12. The device of claim 9, wherein, when the processor executes the instructions, the device analyses image data from the optical imaging device and measures, based on the timeseries of measurements of perfusion maps, a reactive hemodynamic parameter.

13. The device of claim 9, further comprising: a display which produces a visualization of the perfusion maps comprising perfused regions with perfusion below a predetermined threshold and regions with vasomotor dysfunction.

14. The device of claim 9, wherein, when the processor executes the instructions, the device analyses a reactive hemodynamic parameter measured based on the time-series of measurements of perfusion maps, and controls heating for identifying perfused regions with perfusion lower than a predetermined threshold.

15. The device of claim 9, wherein, when the processor executes the instructions, the device analyses a reactive hemodynamic parameter measured based on the time-series of measurements of perfusion maps from the optical imaging device, and controls heating of the limb based on a defined protocol as the reactive hemodynamic parameter is measured.

16. A contactless system for interactively measuring perfusion, comprising: an infrared heating source that remotely heats a limb; a controller with a memory that stores instructions and a processor that executes the instructions, wherein the controller controls the infrared heating source to remotely heat the limb; and an optical imaging device that performs imaging of dynamic perfusion response to heating of the limb, wherein the controller measures the perfusion dynamically responsive to the heating of the limb and generates a time-series of measurements of perfusion maps as heating is applied to the limb and after the heating ceases.

17. The contactless system of claim 16, further comprising: a thermal camera that senses temperature of the limb as the infrared heating source heats the limb and after the infrared heating source ceases heating the limb, wherein the controller generates a time-series of measurements of temperature maps as the heat is applied to the limb and after the heating ceases, and wherein the controller identifies an effect of the heat on the perfusion.

18. The contactless system of claim 16, wherein, when the processor executes the instructions, the device analyses image data from the optical imaging device and measures, based on the time-series of measurements of perfusion maps, a reactive hemodynamic parameter.

19. The contactless system of claim 16, further comprising: a display which produces a visualization of the perfusion maps comprising perfused regions with perfusion below a predetermined threshold and regions with vasomotor dysfunction.

20. The contactless system of claim 16, wherein, when the processor executes the instructions, the device analyses a reactive hemodynamic parameter measured based on the timeseries of measurements of perfusion maps from the optical imaging device, and controls heating for identifying perfused regions with perfusion lower than a predetermined threshold.

21. The contactless system of claim 16, wherein, when the processor executes the instructions, the device analyses a reactive hemodynamic parameter measured based on the timeseries of measurements of perfusion maps from the optical imaging device, and controls heating of the limb based on a defined protocol as the reactive hemodynamic parameter is measured.

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