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WO2022112804A1 - Dispositif et procédé de surveillance non invasive de condition humaine - Google Patents

Dispositif et procédé de surveillance non invasive de condition humaine Download PDF

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Publication number
WO2022112804A1
WO2022112804A1 PCT/GB2021/053125 GB2021053125W WO2022112804A1 WO 2022112804 A1 WO2022112804 A1 WO 2022112804A1 GB 2021053125 W GB2021053125 W GB 2021053125W WO 2022112804 A1 WO2022112804 A1 WO 2022112804A1
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WIPO (PCT)
Prior art keywords
signal
doppler shift
motion
biological tissue
rbc
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PCT/GB2021/053125
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English (en)
Inventor
Ilya RAFAILOV
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Aston Medical Technology Ltd
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Aston Medical Technology Ltd
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/026—Measuring blood flow
    • A61B5/0261—Measuring blood flow using optical means, e.g. infrared light
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
    • A61B5/414—Evaluating particular organs or parts of the immune or lymphatic systems
    • A61B5/418—Evaluating particular organs or parts of the immune or lymphatic systems lymph vessels, ducts or nodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7203—Signal processing specially adapted for physiological signals or for diagnostic purposes for noise prevention, reduction or removal
    • A61B5/7207—Signal processing specially adapted for physiological signals or for diagnostic purposes for noise prevention, reduction or removal of noise induced by motion artifacts
    • A61B5/721—Signal processing specially adapted for physiological signals or for diagnostic purposes for noise prevention, reduction or removal of noise induced by motion artifacts using a separate sensor to detect motion or using motion information derived from signals other than the physiological signal to be measured

Definitions

  • the present invention relates to devices for non-invasive monitoring of a body.
  • embodiments of the present invention relate to optical monitoring of tissue, optionally human tissue.
  • Embodiments of the invention provide a monitoring device and a method of monitoring.
  • the monitoring device may be a wearable device, for example by attachment to a limb such as a subject's wrist.
  • the device may be suitable for simultaneous detection of red blood cell and lymph microcirculations.
  • the monitoring device may also monitor metabolic biomarker fluorescence of the skin.
  • the device may monitor optically an illuminated region of tissue.
  • Some embodiments of the present invention provide a monitoring device for non-invasive detection of flow properties of both red blood cells (RBC) and/or lymph contrast objects (which may also be referred to as 'lymph scatterers') using Doppler flowmetry.
  • a device is provided that detects non-invasively flow properties of both RBC and/or lymph contrast objects using Doppler flowmetry. Measurements in respect of both blood microcirculation and lymph microcirculation are useful because the combination provides better (richer) diagnostic information.
  • the device may also function as a fluorimeter, exciting and detecting autofluorescent signals from biomarkers in irradiated tissue.
  • a non-invasive human condition monitoring apparatus comprising a monitoring device arranged to be worn by a user, the monitoring device comprising: a source of infrared radiation arranged to emit infrared radiation onto biological tissue associated with a subject; a photodetector module for detecting a first signal and a second signal, the first signal and the second signal corresponding to portions of the infrared illumination reflected from the biological tissue; a processing module arranged to analyse the first signal and the second signal to independently determine: a first Doppler shift associated with the first signal, the first Doppler shift being indicative of red blood cell (RBC) flow velocity in the biological tissue, and a second Doppler shift associated with the second signal, the second Doppler shift being indicative of lymph scatterer flow velocity in the biological tissue, wherein the device comprises a motion sensor (140) configured to generate a motion signal responsive to movement of the device (100), wherein the apparatus is configured to determine a motion parameter indicative of motion of the device based on the motion signal, where
  • the apparatus is therefore able to compensate for an effect of motion of the device on one or both of the first and second signals by ignoring data acquired by the device in respect of the first and second signals when motion of the device is such that the measured first and second signals are considered not representative of a physiological condition of a wearer of the device.
  • the apparatus may be configured, by reference to the motion signal, to:
  • the motion signal comprises information in respect of angular velocity of the motion sensor (140) in each of three mutually orthogonal (x, y, z) directions, the apparatus being configured to:
  • the time period may be a period of 100ms, 200ms, 500ms or any other suitable value.
  • the apparatus may be configured to compensate for an effect of motion of the device on one or both of the first and second signals at least in part by ignoring information corresponding to time periods in which the value of M exceeds a threshold value Mth.
  • a non-invasive human condition monitoring apparatus comprising a monitoring device optionally arranged to be worn by a user, the monitoring device comprising: a source of infrared radiation arranged to emit infrared radiation onto biological tissue associated with a subject; a photodetector module for detecting a first signal and a second signal, the first signal and the second signal corresponding to portions of the infrared illumination reflected from the biological tissue; a processing module arranged to analyse the first signal and the second signal to independently determine: a first Doppler shift associated with the first signal, the first Doppler shift being indicative of red blood cell (RBC) flow velocity in the biological tissue, and a second Doppler shift associated with the second signal, the second Doppler shift being indicative of lymph scatterer flow velocity in the biological tissue, wherein the device comprises a motion sensor (140) configured to generate a motion signal responsive to movement of the device (100), the apparatus being configured to compensate for an effect of motion of the device on one or both of the first and second signals
  • the device may be arranged to be worn by a user by being fixed to an area of interest (such as fingers, toes, forearms, upperarms, ankles or legs).
  • the device may be secured using attachment means, optionally a strap, optionally a strap comprising hook and loop material such as Velcro (RTM).
  • attachment means optionally a strap, optionally a strap comprising hook and loop material such as Velcro (RTM).
  • adhesive may be employed to attach the device to a user. It is to be understood that in some embodiments the device may be secured such that the device does not compress the portion of the body under inspection in such a way as to occlude blood flow excessively.
  • the apparatus may be configured to compensate for an effect of motion by reference to the motion signal at least in part by ignoring information in respect of the first and second signals corresponding to time periods in which one or more characteristics of motion of the device exceeded one or more threshold conditions.
  • the apparatus may ignore such information when performing analysis of the information, for example analysis to determine information in respect of one or more physiological conditions of a user such as blood microcirculation and lymph microcirculation, for example to gain information in respect of user health.
  • the apparatus may be configured to compensate for an effect of motion of the device on one or both of the first and second signals at least in part by ignoring information in respect of the first and second signals corresponding to time periods in which a parameter indicative of rate of acceleration of the device exceeded a predetermined rate.
  • the motion signal may comprise information in respect of rate of acceleration of the device.
  • the motion signal may comprise information in respect of rate of acceleration of the device in a plurality of respective directions.
  • the motion signal may provide information in respect of rate of acceleration of the device along mutually orthogonal axes, optionally along three mutually orthogonal (x, y, z) axes.
  • the apparatus may be configured, by reference to the motion signal, to:
  • the motion signal comprises information in respect of angular velocity of the motion sensor (140) in each of three mutually orthogonal (x, y, z) directions, the apparatus being configured to:
  • the time period may be a period of 100ms, 200ms, 500ms or any other suitable value.
  • the apparatus may be configured to compensate for an effect of motion of the device on one or both of the first and second signals at least in part by ignoring information corresponding to time periods in which the value of M exceeds a threshold value Mth.
  • the value of Mth may correspond to a multiple of a value of M that corresponds to a rest state of the device, for example with the device placed on a stationary state such as a multiple of 2, 5, 10, 20, 50, 100 or any other suitable multiple. It is to be understood that the value of M calculated based on a signal output by the motion sensor may have a non-zero value even with the motion sensor in a rest state. This value of M may be referred to as a background value. It is to be understood that an average value of M over a period of time with the device at rest may be determined, and the value of Mth set to a multiple of this value of M.
  • an average modulus (magnitude) of M over a predetermined period of time with the device at rest such as 100ms, 200ms, 500ms, Is, 10s, 100s or any other suitable value may be measured and the value of Mth set to a multiple of the value of M.
  • the value of Mth is set to a value 10M.
  • the value of Mth is set to a value 100M.
  • the value of Mth may be set to a multiple of an average value of M when the device is worn by a user with the user in a rest state.
  • the rest state may correspond to a state in which a user is seated with the device strapped to a limb with the limb, optionally with the limb resting on a surface.
  • the rest state may correspond to a state in which a user is seated with the device strapped to a wrist of the user with the wrist resting on a surface, optionally resting on a surface with the device at substantially the same vertical level as a heart of a user.
  • the apparatus may be configured to compensate for an effect of motion of the device on one or both of the first and second signals at least in part by ignoring information in respect of the first and second signals corresponding to time periods in which a speed of movement of the device exceeded a predetermined speed.
  • the apparatus may be configured to compensate for an effect of motion on one or both of the first and second signals at least in part by modifying one or both signals before analyzing them to determine the first and second Doppler shifts.
  • the apparatus may be configured to compensate for an effect of motion on one or both of the first and second signals at least in part when determining the first and second Doppler shifts.
  • the source of infrared radiation is arranged to output infrared radiation at a single stable frequency, optionally wherein the infrared radiation has a wavelength in the range 800 to 1100 nm, further optionally wherein the source of infrared radiation comprises a laser diode.
  • the photodetector module comprises a first photodetector for detecting the first signal and a second photodetector for detecting the second signal.
  • the processing module is arranged to filter the first signal to remove frequencies outside an expected RBC Doppler shift frequency band.
  • the expected RBC Doppler shift frequency band corresponds to RBC flow rates in the range 0.1 to 4 mm/s.
  • the processing module is arranged to filter the second signal to remove frequencies outside an expected lymph scatterer Doppler shift frequency band.
  • the expected lymph scatterer Doppler shift frequency band is different from the expected RBC Doppler shift frequency band.
  • the apparatus may include an analysis module arranged to determine one or more microcirculation parameters based on the first Doppler shift and the second Doppler shift.
  • the analysis module is arranged to perform wavelet analysis on the first signal and the second signal to extract information indicative of the one or more microcirculation parameters.
  • the one or more microcirculation parameters include the frequency of at least one selected from amongst myogenic rhythm, endothelial oscillations, pacemaker oscillations, and breathing oscillations.
  • the apparatus may include a source of ultraviolet radiation arranged to emit ultraviolet radiation onto biological tissue associated with a subject, wherein the photodetector module is arranged to detect a fluorescent response from the biological tissue triggered by the ultraviolet radiation.
  • the photodetector module is arranged to detect a plurality of fluorescent responses, each of the plurality of fluorescent responses being associated with a respective biomarker.
  • the photodetector module comprises a plurality of photoreceivers, each photoreceiver being arranged to detect a fluorescent response from a respective biomarker, wherein each photoreceiver has an input filter arranged to remove frequencies outside an expected frequency range associated with the fluorescent response of its respective biomarker.
  • the photodetector module is arranged to detect autofluorescent responses from NADH and FAD, and wherein the apparatus includes an analysis module arranged to calculate a tissue redox ratio based on the detected autofluorescent responses for NADH and FAD, the apparatus being configured to provide an output responsive to the calculated tissue redox ratio.23. Apparatus according to any preceding claim wherein the source of infrared radiation is arranged to emit an infrared illumination pattern onto the biological tissue associated with the subject.
  • the source of ultraviolet radiation is arranged to emit an ultraviolet illumination pattern onto the biological tissue associated with the subject.
  • the apparatus may further comprise a computing device remote from the monitoring device and in data communication therewith, the remote computing device being configured to receive data transmitted by the monitoring device and to process the received data.
  • the analysis module arranged to determine one or more microcirculation parameters based on the first Doppler shift and the second Doppler shift is comprised by the remote computing device.
  • the analysis module arranged to calculate a tissue redox ratio is comprised by remote the computing device.
  • the analysis module arranged to determine one or more microcirculation parameters based on the first Doppler shift and the second Doppler shift is also the analysis module arranged to calculate a tissue redox ratio.
  • This module may be comprised by the remote computing device.
  • the analysis module arranged to determine one or more microcirculation parameters based on the first Doppler shift and the second Doppler shift and/or the analysis module arranged to calculate a tissue redox ratio is comprised by the monitoring device, which is optionally wearable as noted above.
  • the monitoring device may be wearable and portable. It may comprise an integrated power supply such as a battery pack so that it does not require to be tethered to a fixed power supply such as a mains power supply.
  • a method of non-invasively monitoring a human condition by means of an apparatus or device comprising: directing infrared radiation onto biological tissue associated with a subject; detecting a first signal and a second signal, the first signal and the second signal corresponding to portions of the infrared radiation reflected from the biological tissue; analysing the first signal and the second signal to independently determine: a first Doppler shift associated with the first signal, the first Doppler shift being indicative of red blood cell (RBC) flow velocity in the biological tissue, and a second Doppler shift associated with the second signal, the second Doppler shift being indicative of lymph scatterer flow velocity in the biological tissue, the method comprising compensating for an effect of motion of the device on one or both of the first and second signals.
  • RBC red blood cell
  • compensating for an effect of motion comprises ignoring information corresponding to time periods in which one or more characteristics of motion of the apparatus or device exceeded one or more threshold conditions.
  • directing ultraviolet radiation onto biological tissue associated with a subject and detecting a fluorescent response associated with a biomarker from the biological tissue triggered by the ultraviolet radiation comprising detecting autofluorescent responses from NADH and FAD, calculating a tissue redox ratio based on the detected autofluorescent responses for NADH and FAD, and providing an output responsive to the calculated tissue redox ratio.
  • some embodiments of the present invention provide a portable laser microcirculation sensor for non-invasive clinical diagnosis of peripheral blood flow.
  • Some embodments analyse and record data indicative of an index of blood microcirculation, which is proportional to the product of the number of erythrocytes and the average speed of their movement, using laser Doppler shift-based flowmetry.
  • the blood microcirculation index is determined at the sensing area in relative units, as a function of time. This registered index allows to assess the dynamics of blood perfusion in the tissue examined.
  • the device can additionally measure skin temperatures from 15 to 40°C with an error of ⁇ 20%. Some embodiments of the invention are arranged to assess blood microcirculation in the top surface layers of the skin and other biotissues.
  • a non-invasive human condition monitoring device comprising: a source of infrared radiation arranged to emit infrared radiation onto biological tissue associated with a subject; a photodetector module for detecting a first signal and a second signal, the first signal and the second signal corresponding to portions of the infrared illumination reflected from the biological tissue; a processing module arranged to analyse the first signal and the second signal to independently determine: a first Doppler shift associated with the first signal, the first Doppler shift being indicative of red blood cell (RBC) flow velocity in the biological tissue, and a second Doppler shift associated with the second signal, the second Doppler shift being indicative of lymph contrast object flow velocity in the biological tissue, wherein the device is configured to compensate for an effect of motion of the device on one or both of the first and second signals.
  • RBC red blood cell
  • Embodiments of the present invention have the advantage that an effect of motion on measurements of RBC flow velocity and/or lymph contrast object flow velocity may be determined and compensated for. Such compensation can be important in certain applications such as in wearable device technology.
  • a common illumination source may be used to obtain independent signals for RBC flow and lymph contrast object flow.
  • the device may be configured to compensate for an effect of motion by ignoring information corresponding to time periods in which one or more characteristics of motion of the device exceeded one or more threshold conditions.
  • the device may be configured to ignore data corresponding to time periods in which a rate of acceleration of the device exceeded a predetermined rate.
  • the device may be configured to ignore data corresponding to time periods in which a speed of movement of the device exceeded a predetermine speed.
  • the device may be configured to compensate for an effect of motion on one or both of the first and second signals at least in part by modifying one or both signals before analyzing them to determine the first and second Doppler shifts.
  • the device may be configured to compensate for an effect of motion on one or both of the first and second signals at least in part when determining the first and second Doppler shifts.
  • the device may adjust a value of the first and/or second Doppler shift determined by the device in order to compensate for an effect of motion once a value of Doppler shift has been calculated.
  • the device may comprise a motion sensor configured to generate a motion signal responsive to movement of the device, optionally wherein the motion signal comprises information in respect of rate of acceleration of the device, further optionally wherein the motion signal comprises information in respect of rate of acceleration of the device in a plurality of respective directions.
  • the motion signal may for example provide information in respect of rate of acceleration of the device along mutually orthogonal axes, optionally along three mutually orthogonal (X, Y, Z) axes.
  • the motion sensor may comprise one or more accelerometer devices, such as one or more gyroscopic accelerometer devices, microelectromechanical system (MEMS) devices or other suitable device(s).
  • accelerometer devices such as one or more gyroscopic accelerometer devices, microelectromechanical system (MEMS) devices or other suitable device(s).
  • MEMS microelectromechanical system
  • the source of infrared radiation is arranged to output infrared radiation at a single stable frequency, optionally wherein the infrared radiation has a wavelength in the range 800 to 1100 nm, further optionally wherein the source of infrared radiation comprises a laser diode.
  • the photodetector module comprises a first photodetector for detecting the first signal and a second photodetector for detecting the second signal.
  • the processing module is arranged to filter the first signal to remove frequencies outside an expected RBC Doppler shift frequency band.
  • the expected RBC Doppler shift frequency band may correspond to RBC flow rates in the range 0.1 to 4 mm/s.
  • the expected RBC Doppler shift frequency band may be 250 to 11,000 Hz.
  • the processing module may be arranged to filter the second signal to remove frequencies outside an expected lymph contrast object Doppler shift frequency band.
  • the expected lymph contrast object Doppler shift frequency band may be different from the expected RBC Doppler shift frequency band.
  • the expected lymph contrast object Doppler shift frequency band may be 0 to 150 Hz. Filtering the signal can remove unwanted noise and reduce the processing burden of subsequent analysis steps.
  • the expected RBC Doppler shift frequency band corresponds to RBC flow rates in the range 0.1 to 4 mm/ s.
  • the processing module is arranged to filter the second signal to remove frequencies outside an expected lymph contrast object Doppler shift frequency band.
  • the expected lymph contrast object Doppler shift frequency band is different from the expected RBC Doppler shift frequency band.
  • the device may include an analysis module arranged to determine one or more microcirculation parameters based on the first Doppler shift and the second Doppler shift.
  • the analysis module is arranged to perform wavelet analysis on the first signal and the second signal to extract information indicative of the one or more microcirculation parameters.
  • the analysis module may be arranged to the perform wavelet analysis on the first signal and the second signal to extract information indicative of the one or more microcirculation parameters after the filtering discussed above.
  • the one or more microcirculation parameters include the frequency of at least one selected from amongst myogenic rhythm, endothelial oscillations, pacemaker oscillations, and breathing oscillations.
  • the device may also provide a fluorimeter function.
  • the device may include a source of ultraviolet radiation arranged to emit ultraviolet radiation onto biological tissue associated with a subject, wherein the photodetector module is arranged to detect a fluorescent response from the biological tissue triggered by the ultraviolet radiation.
  • the photodetector module is arranged to detect a plurality of fluorescent responses, each of the plurality of fluorescent responses being associated with a respective biomarker.
  • the photodetector module comprises a plurality of photoreceivers, each photoreceiver being arranged to detect a fluorescent response from a respective biomarker, wherein each photoreceiver has an input filter arranged to remove frequencies outside an expected frequency range associated with the fluorescent response of its respective biomarker.
  • the photodetector module is arranged to detect autofluorescent responses from NADH and FAD, optionally wherein the device includes an analysis module arranged to calculate a tissue redox ratio based on the detected autofluorescent responses for NADH and FAD.
  • the device may be configured to provide an output responsive to the calculated tissue redox ratio.
  • the output may be in the form of an indication of the value of the tissue redox ratio
  • the device may include a display or indicator for outputting data from the processing module or analysis module.
  • the display may include a screen for providing a graphic illustrative of a parameter determined by the processing module or analysis module.
  • the analysis module may be arranged to compare a determined value or values of the one or more microcirculation parameters with stored values indicative of normal or abnormal conditions in order to generate a diagnostic output.
  • the indicator may be arranged as a simple set of laser diodes/LEDs or the like which provide an indication of the nature of the diagnostic output.
  • the device discussed above may be embodiment in any suitable form. However, it is preferably incorporated into a wearable health monitor.
  • the wearable health monitor may comprise a housing containing the device set out above and a means for holding the housing on the human body. Any suitable strap or clip may be used for this purpose.
  • the components of the device may be distributed between the wearable housing and a remote computer.
  • the processing of the first and second signals need not occur within the wearable unit.
  • the processing module and analysis module discussed above may be embodied in an app or other software running on the remote computer.
  • the source of infrared radiation is arranged to emit an infrared illumination pattern onto the biological tissue associated with the subject.
  • a wearable health monitor comprising: a housing containing a non-invasive human condition monitoring device according to any preceding claim, and means for holding the device on the human body.
  • the means for holding the device is a strap.
  • a health monitoring apparatus comprising a wearable health monitor communicatively coupled to a remote computer, wherein the wearable health monitor comprises: a housing containing: a source of infrared radiation arranged to emit infrared radiation onto biological tissue associated with a subject; a photodetector module for detecting a first signal and a second signal, the first signal and the second signal corresponding to portions of the infrared radiation reflected from the biological tissue; and a communication module for transmitting data relating to the first signal and the second signal to the remote computer, wherein the remote computer comprises: a processing module arranged to analyse the first signal and the second signal to independently determine: a first Doppler shift associated with the first signal, the first Doppler shift being indicative of red blood cell (RBC) flow velocity in the biological tissue, and a second Doppler shift associated with the second signal, the second Doppler shift being indicative of lymph contrast object flow velocity in the biological tissue, wherein the apparatus is configured to compensate for an effect of motion of the
  • the remote computer comprises an analysis module arranged to determine one or more microcirculation parameters based on the first Doppler shift and the second Doppler shift.
  • This distributed apparatus may also provide a fluorimeter function.
  • the wearable health monitor further includes a source of ultraviolet radiation arranged to emit ultraviolet radiation onto the biological tissue associated with a subject, optionally wherein the photodetector module is arranged to detect a fluorescent response from the biological tissue triggered by the ultraviolet radiation.
  • the remote computer may be any suitable computing device such as a smartphone, tablet computer, laptop computer, personal computer or any other suitable computing device.
  • a method of non-invasively monitoring a human condition by means of an apparatus or device comprising: directing infrared radiation onto biological tissue associated with a subject; detecting a first signal and a second signal, the first signal and the second signal corresponding to portions of the infrared radiation reflected from the biological tissue; analysing the first signal and the second signal to independently determine: a first Doppler shift associated with the first signal, the first Doppler shift being indicative of red blood cell (RBC) flow velocity in the biological tissue, and a second Doppler shift associated with the second signal, the second Doppler shift being indicative of lymph contrast object flow velocity in the biological tissue, the method comprising compensating for an effect of motion of the device on one or both of the first and second signals.
  • RBC red blood cell
  • compensating for an effect of motion comprises ignoring information corresponding to time periods in which one or more characteristics of relative motion between the apparatus or device exceeded one or more threshold conditions.
  • the method may comprise directing ultraviolet radiation onto biological tissue associated with a subject and detecting a fluorescent response associated with a biomarker from the biological tissue triggered by the ultraviolet radiation, the method comprising detecting autofluorescent responses from NADH and FAD, calculating a tissue redox ratio based on the detected autofluorescent responses for NADH and FAD, and providing an output responsive to the calculated tissue redox ratio.
  • a monitoring device capable of non-invasive simultaneous detection of flow properties of both red blood cells (RBC) and lymph contrast objects using Doppler flowmetry. It is to be understood that measurement of a combination of both blood microcirculation and lymph microcirculation is advantageous because it can provide richer diagnostic information.
  • the device comprises an infrared radiation source, a photodetector module for detecting first and second signals that correspond respectively to portions of an infrared pattern reflected from the biological tissue. The signals are analysed to determine Doppler shifts indicative of RBC flow velocity and lymph contrast object flow velocity.
  • the device may also function as a fluorimeter, i.e. to excite and detect autofluorescent signals from biomarkers in irradiated tissue.
  • a non-invasive human condition monitoring device comprising: a source of infrared radiation arranged to emit infrared radiation onto biological tissue associated with a subject; a photodetector module for detecting a first signal and a second signal, the first signal and the second signal corresponding to portions of the infrared illumination reflected from the biological tissue; a processing module arranged to analyse the first signal and the second signal to independently determine: a first Doppler shift associated with the first signal, the first Doppler shift being indicative of red blood cell (RBC) flow velocity in the biological tissue, and a second Doppler shift associated with the second signal, the second Doppler shift being indicative of lymph contrast object flow velocity in the biological tissue, wherein the device is configured to reduce or substantially eliminate an effect of motion of the device on one or both of the first and second signals.
  • RBC red blood cell
  • a non-invasive human condition monitoring device comprising: a source of infrared radiation arranged to emit infrared radiation onto biological tissue associated with a subject; a photodetector module for detecting a first signal and a second signal, the first signal and the second signal corresponding to portions of the infrared illumination reflected from the biological tissue; a processing module arranged to analyse the first signal and the second signal to independently determine: a first Doppler shift associated with the first signal, the first Doppler shift being indicative of red blood cell (RBC) flow velocity in the biological tissue, and a second Doppler shift associated with the second signal, the second Doppler shift being indicative of lymph contrast object flow velocity in the biological tissue, wherein the device is configured to reduce or substantially eliminate an effect of motion of the device on one or both of the first and second signals by ignoring information corresponding to time periods in which one or more characteristics of motion of the device exceeded one or more threshold conditions.
  • RBC red blood cell
  • FIGURE l shows a wearable monitoring device according to an embodiment of the present invention in (a) side view, (b) top view and (c) bottom view whilst (d) is a top view of a device according to a further embodiment;
  • FIGURE 2 is a schematic view of internal components of the monitoring device of the embodiment of FIG. 1 (a)-(c);
  • FIGURE 3 is a schematic diagram illustrating steps in a process for simultaneously determining flow information for red blood cells (RBC) and lymph contrast objects in a subject's blood as performed by the monitoring device of FIGS. l(a)-(c) and 2;
  • RBC red blood cells
  • FIGURE 4 is a schematic diagram illustrating steps in a process for determining biomarker information from a subject's tissue and determining flow information for red blood cells (RBC) and/or lymph contrast objects in the subject's blood, as implemented by the monitoring device of FIGS. l(a)-(c) and 2;
  • RBC red blood cells
  • FIGURE 5 is a plot of data acquired by apparatus according to an embodiment of the present invention as a function of time (x-axis), in this plot data representing (a) a user's body temperature, (b) the LDF signal and (c) motion as detected by the motion sensor;
  • FIG. 6 is a plot of amplitude as a function of frequency in respect of motion within the wearer's microcirculatory system as determined by apparatus according to an embodiment of the present invention.
  • Some embodiments of the present invention relate to a monitoring device for sensing properties of a subject's tissue, and in particular blood flow.
  • the monitoring device itself is arranged to be carried by a user.
  • it may be provided in the form of a wearable device 100.
  • FIG. 1(a) to (c) illustrates a wearable device 100 according to an embodiment of the present invention suitable for attachment to a limb 102 of a subject, such as a wrist, arm or leg.
  • FIG. 1(a) is a side view of the device 100
  • FIG. 1(b) is a plan view of the device 100
  • FIG. 1(c) shows an underside of the device 100.
  • the wearable device 100 comprises a main body 104 and a strap 106 for maintaining the main body in contact with the subject's skin.
  • a charging port 104P is provided that is connectable to an electrical power source in order to recharge an internal battery of the device 100.
  • the charging port 104P may be omitted and the device 100 may be fitted with a non-rechargeable battery.
  • An underside of the main body 104 has a window 105 through which probing radiation may be transmitted from the device 100 onto a user's body and through which signals to be measured may be received by the device 100. These signals may be referred to as 'measurement signals'.
  • an upper side of the main body 104 has a display 132 provided thereon and, in addition, an on/off button 131.
  • the display 132 is a digital display, in the form of a liquid crystal display (LCD), but other forms of display 132 such as a light emitting diode (LED) display may be provided.
  • one or more discrete indicators such as indicator lamps, such as LED lamps, may be provided.
  • FIG. 1(d) is a plan view of a device 200 according to a further embodiment of the invention having discrete LED indicators 232a-232d.
  • the device of FIG. 1(d) has an underside similar to that of the device 100 as shown in FIG. 1(c).
  • Indicator 232a provides an indication of a state of charge of an internal battery of the device 200; in the embodiment shown, when the device is switched on the indicator 232a is extinguished when the battery is charged, illuminated in green colour when the battery is charging, and flashes yellow when the device requires to be charged; in some embodiments the indicator 232a is illuminated in yellow substantially continually when the battery requires to be charged.
  • FIG. 1(d) is a plan view of a device 200 according to a further embodiment of the invention having discrete LED indicators 232a-232d.
  • the device of FIG. 1(d) has an underside similar to that of the device 100 as shown in FIG. 1(c).
  • Indicator 232a provides an indication of a state
  • the display 132 is arranged to convey information about a current diagnostic state of the user based on the received measurement signals.
  • Devices having one or more indicator lamps instead of or in addition to a digital display may likewise be configured to convey information in respect of a current diagnostic state of the user via the one or more indicator lamps such as lamps 232b-d in the embodiment of FIG. 1(d).
  • other information may be displayed in addition or instead, such as an information indicative of an amount of memory available to store captured data.
  • devices according to embodiments of the present invention may be arranged to transmit the information to a remote computing device 190 such as a smartphone, tablet computer, laptop, PC or any other suitable computing device.
  • a remote computing device 190 such as a smartphone, tablet computer, laptop, PC or any other suitable computing device.
  • the devices 100, 200 are configured to transmit the information via short range radio, in particular via Bluetooth ® .
  • any suitable wireless communications protocol may be used for this purpose, such as another short range radio protocol or longer range radio protocol.
  • the device 100, 200 may be configured to communicate via one or more of Wi-Fi, GSM (Global System for Mobile communication) or any other suitable protocol.
  • the device 100 is configured to transmit data acquired by the device 100 in respect of the received measurement signals to the remote computing device 190 where the data is processed.
  • the data may be processed to obtain information about a current diagnostic state of the user.
  • the monitoring devices 100, 200 resemble in size a wristwatch or the like.
  • FIG. 2 is a schematic view of an internal configuration of the main body 104, 204 of the embodiments of FIG. 1. Although both the devices 100, 200 have a similar internal configuration, the following description will be provided with reference to the device 100 of FIG. l(a)-(c) for brevity.
  • the main body 104 defines a hollow housing in which is provided an electrical power source 110 for powering the device 100.
  • the power source 110 includes a rechargeable battery and a power controller.
  • the power controller is configured to stabilize an output voltage of the power source 110 and to control charging and discharging of the battery.
  • the power source 110 provides power for an illumination system 112, 114, an optical detector 122, a motion sensor 140 in the form of an accelerometer device 140, a processor 124, output display 132, and a communications module 134.
  • the communications module is a wireless communications module 134 as noted above.
  • the illumination system 112 is capable of generating an infrared (IR) output 114 and an ultraviolet (UV) output 116.
  • An output optical system 118 is provided that enables optical radiation from each of the IR output 114 and UV output 116 to exit from the housing of the main body 104.
  • the device 100 is configured such that, when worn by a user, optical radiation passing out from the device 100 via the output optical system 118 illuminates a patch of skin of the subject.
  • the output optical system 118 comprises a plurality of lenses and a window through which optical radiation from the IR output 114 and UV output 116 may pass in order to illuminate the subject's skin.
  • the output optical system does not comprise a window separate from the one or more lenses.
  • the output optical system comprises a window and no further lenses.
  • the IR output 114 and output optical system 118 are arranged to emit an illumination pattern suitable for performing Doppler flowmetry (laser Doppler flowmetry, LDF).
  • the IR output 114 comprises a pair of radiation beams that intersect to form an interference pattern outside the main body 104 on the illuminated patch of tissue.
  • the IR output 114 is be arranged to emit optical radiation at a single wavelength, in the range 800 nm to 1100 nm.
  • the IR output 114 has a substantially single frequency laser diode for this purpose.
  • the IR output may be a single radiation beam, or more than two radiation beams.
  • the IR output 114 is provided by an 850nm IR laser diode.
  • the UV output 116 is arranged in conjunction with the output optics 118 to emit a beam of UV radiation to illuminate tissue.
  • the UV output 116 illuminates substantially the same patch of tissue as the IR output 114.
  • the UV output 116 may be configured to illuminate a different patch of tissue 114, optionally a different patch that at least partially overlaps the patch illuminated by the IR output 114.
  • the UV output 116 consists of a single frequency light emitting diode (LED) selected to emit radiation at a wavelength that excites fluorescent effects of biomarkers in the tissue.
  • the LED emits optical radiation having a wavelength of 365 nm.
  • the LED may emit optical radiation of a different wavelength.
  • a laser diode may be used instead of an LED.
  • two separate laser devices are provided that deliver the IR output 114 and UV output 116, respectively.
  • the illumination system 112 includes a laser controller (not shown) arranged to control the irradiation power of the IR output 114 and/or UV output, optionally via a control signal from a processing module 124. It is to be understood that, in some embodiments, a Peltier thermoelectric cooler may be used to control temperature of the laser diode(s) as required.
  • an optical detector in the form of a photodetector module 122 is provided.
  • the module 122 has one or more photodetectors or photoreceivers for sensing an optical signal received by the device 100 from the illuminated tissue.
  • the underside of the main body 104 includes an input optical system 120.
  • the input optical system 120 comprises a transparent window through which the optical signal incident on the underside of the main body 104 from the illuminated tissue enters the device 100.
  • the optical signal then passes through a suitable array of lenses that direct the optical signal into the photodetector module 122.
  • the one or more lenses of the input optical system 120 may be omitted.
  • the window of the input optical system 120 may be omitted.
  • the output and input optical systems 118, 120 may share one or more components in order to save space.
  • the photodetector module 122 comprises a pair of photodetectors for capturing a reflection of the IR illumination pattern from the skin.
  • the pair of photodetectors are arranged to convert the captured image into a pair of electrical signals which are used to determine information relating to RBC flow and lymph contrast object flow, respectively, as discussed in further detail below. It is to be understood that other arrangements may be useful in some embodiments.
  • the photodetector module 122 also comprises one or more filtered optical receivers for detecting specific types of fluorescent excitation radiation in the optical signal received back from the illuminated tissue.
  • filtered optical receiver may mean a suitable semiconductor optical sensor having an optical filter over its detection region to limit the range of wavelengths that it receives.
  • the filters used may be narrowband, to transmit only a certain band of wavelengths corresponding to an expected fluorescence effect.
  • the filters may act to prevent reflected UV or IR radiation from being detected.
  • the photodetector module 122 may comprise filtered optical receivers arranged to sense nicotinamide adenine dinucleotide (NADH) and Flavin-adenine-dinucleotide (FAD) autofluorescence excitation signals.
  • NADH nicotinamide adenine dinucleotide
  • FAD Flavin-adenine-dinucleotide
  • the processor comprises a processing module 124 configured to control the laser system 112 and photodetector module 120.
  • the processing module 124 comprises a set of analysis submodules configured to process signals from the photodetector module 122 to determine information about the illuminated tissue.
  • the analysis submodules are provided within the main body 104.
  • one or more or all of these submodules may be provided by a remote device 190 (e.g. a smartphone or the like).
  • the processing module 124 may control a communications interface to transmit the signals received from the photodetector module to the remote device for further analysis.
  • the functionality of the submodules may be implemented by means of the remote device 190.
  • the accelerometer device 140 is an MPU-6000 device (InvenSense, Sunnyvale, CA, USA).
  • the motion sensor 140 is an MPU-6050 "Six-Axis (Gyro + Accelerometer) MEMS MotionTrackingTM Device” (Invensense, Sunnyvale, CA, USA). Other types of motion sensor may be useful in some embodiments.
  • the device 140 is physically located adjacent the laser system 112, which is in the form of a vertical cavity surface emitting laser (VCSEL), within the casing of the main body 104 of the device 100.
  • VCSEL vertical cavity surface emitting laser
  • the accelerometer device 140 produces three output signals corresponding to angular velocities of the device 140 in a three-dimensional coordinate system x, y, z - cox(t), ioy(t), coz(t). In the present embodiment, these signals are then processed in the processing module 124 of the device 100 in the following order: 1) Calculation of the derivatives of the angular velocities, i.e. acceleration is determined using coordinates.
  • Each derivative's modulus is calculated and an average value of each modulus over a period of 200 milliseconds is determined and stored.
  • the sum of the modulus values, M is stored with a time stamp corresponding to the time at which the 200ms period commenced in order to enable modulus values to be synchronised in time with the LDF signal. This way, a value indicative of a rate of acceleration of the device 140 over a given 200ms time period may be obtained. It is to be understood that other values of length of period may be used in some embodiments such as 100ms, 300ms, 500ms or any other suitable value.
  • a fluorescence detection module 126 there are three analysis submodules: a fluorescence detection module 126, a Doppler flowmetry module 128 and a microcirculation evaluation module 130.
  • the fluorescence detection module 126 is arranged to receive one or more signals from the filtered optical receivers in the photodetector module 122.
  • the fluorescence detection module 126 may be arranged to assess skin NADFI and FAD fluorescence from these signals in a conventional manner.
  • the fluorescence redox ratio may be calculated and output from the device, either via the display 132 on the upper surface of the main body 104 or in a communication signal transmitted wirelessly to a remote device such as device 190.
  • the device is therefore operable as a wearable fluorimeter.
  • the fluorescence detection module 126 does not employ information generated by the accelerometer device 140.
  • the Doppler flowmetry module 128 is arranged to analyse independently each signal from the pair of photodetectors to determine flow properties of RBC and lymph contrast objects respectively.
  • Each signal includes information indicative of variations in intensity of the illumination pattern caused by the flow of RBC or lymph contrast objects.
  • Each signal is filtered to remove frequencies that are outside the expected range of RBC or lymph contrast object flow rates.
  • the signal for RBC detection is filtered to retain only frequencies that correspond to a flow rate of 0.1 to 4 mm/s, e.g. 250 Hz to 11 kHz. Similar filtering can be performed on the signal for lymph contrast object flow detection.
  • the target frequency band here may be different, e.g. 0 to 150 Hz.
  • the same filter may be used for both signals; in some such embodiments the filter may be arranged to allow only frequencies in the range from around 0 to around 10 kHz to pass through. It is to be understood that, in some embodiments, the signals are not filtered to remove frequencies that are outside an expected range of RBC or lymph contrast object flow rates, or other predetermined range. Rather, the signal data is recorded. It is to be understood that data outside an expected range may still be valid data, representative of flow properties in the subject being monitored, provided the data was acquired when the modulus sum value M does not exceed a threshold value Mth (see below).
  • the Doppler flowmetry module 128 is configured not to use data corresponding to the signals from the pair of photodetectors corresponding to time periods for which the modulus sum value M exceeds threshold value Mth.
  • data the value of which may be unreliable due to a relatively high value of M, is not employed to determine the flow properties of RBC and lymph contrast objects.
  • recorded LDF data corresponding to periods during which M exceeds Mth is deleted and not employed to determine the flow properties of RBS and lymph contrast objects.
  • the data is not deleted, but not employed to determine the flow properties.
  • the signals from the pair of photodetectors corresponding to time periods for which the modulus sum value M exceeds threshold value Mth are not recorded.
  • the resulting signal can be used to derive information about the flow rate of RBC or lymph contrast objects in the subject.
  • This information may be calculated and output from the device, either via the display 132 on the upper surface of the main body 104 or in a communication signal transmitted wirelessly to a remote device.
  • the device 100 is therefore operable as a wearable blood flowmeter that can simultaneously output flow rates of RBC and lymph contrast objects.
  • the filtered signals may be normalized by multiplying the output signal by an average RBC or lymph contrast object flow density, i.e. make the signal proportionally correspondent to predetermined (e.g. previously calculated) number of the RBC or lymph contrast objects passing through illuminated tissue volume (typically 2-3 mm A 3) multiplied by an average RBC speed.
  • the average RBC speed may be calculated based on a set of values of a RBC speed microcirculation index, e.g. by sampling this parameter at a frequency of 1 Hz or the like.
  • the microcirculation evaluation module 130 is arranged to extract further information from the filtered signals that are indicative of RBC and lymph contrast object flow rates. After normalizing the signal as discussed above, wavelet analysis of the whole spectrum is performed to determine one or more microcirculation rhythms. The wavelet analysis is sensitive to drift around a baseline value. To reduce or minimise the effect of drift the averaged signals are normalised.
  • a myogenic rhythm (typically in the range 0.05 - 0.145 Hz) for the subject may be detected from either or both of the RBC spectrum and the lymph contrast object spectrum.
  • myogenic rhythm typically in the range 0.05 - 0.145 Hz
  • endothelial oscillations typically in the range 0.005 - 0.015 Hz
  • pacemaker oscillations typically in the range 0.8 - 1.6 Hz
  • breathing oscillations typically in the range 0.2 - 0.4 Hz.
  • the calculated microcirculation rhythms may be compared with stored values that are indicative of various normal or abnormal conditions.
  • the stored values may be in a computer memory associated with the processing module 124.
  • the microcirculation evaluation module 130 may be arranged to output information indicative of a diagnostic condition.
  • the diagnostic condition information may be output from the device, either via the display 132 on the upper surface of the main body 104 or in a communication signal transmitted wirelessly to a remote device.
  • the device 100 is therefore operable as a diagnostic instrument for determining a current condition from RBC and lymph flow rate data.
  • the functionality of one or more or all of the submodules may be provided by a remote device 190 (e.g. a smartphone or the like).
  • Information indicative of a diagnostic condition determined by the remote device 190 may be output by the remote device 190.
  • the data may be transmitted to the device 100 for output to a user, e.g., via the display 132 of the embodiment of FIG. 1(a) or one or more of the LED indicators 232b-d of the embodiment of FIG. 1(d).
  • the wavelet analysis may be performed periodically over a predetermined duration (e.g. 2 minutes), whereby values obtained for the calculated microcirculation rhythms are averaged over the duration before comparison with the stored values.
  • a predetermined duration e.g. 2 minutes
  • the main body 104 includes a display 132 in the form of a screen for displaying the results of the various analysis processes performed by the processing module 124.
  • the display 132 may be configured to display a graphical user interface that shows the various calculated parameters.
  • the diagnostics results are displayed using a three-colour LED indicator or a set of three individual indicators 232b-d as in the embodiment of FIG. 1(d).
  • a green light may be used to indicate normal conditions.
  • a yellow flashing light may be used to indicate functional deviation from the normal condition which can be reversed.
  • a red flashing light may be used to mean deep and serious haemo- and lymph-dynamic deviation.
  • the main body 104 includes a wireless module 134 for communicating with a remote device.
  • the wireless module 134 may be arranged to transmit the raw data from the photodetector module 122 or to transmit the calculated parameters from the processing module 124.
  • the wireless module 134 may receive software updates or values to store in the memory of the processing module.
  • FIG. 3 is a schematic flow diagram illustrating various steps in a method of operating the device 100, in particular to detect RBC and lymph perfusion data.
  • the device 100 irradiates tissue with IR radiation as discussed above.
  • a first detector detects (on a first channel for obtaining RBC flow data) a reflected signal of varying intensity and stores data corresponding to the intensity of the signal at a given moment in time together with a time stamp.
  • the time stamp corresponds to the time at which the optical signal was received by the photodetector module 122.
  • the value of M (being the sum of the values of average modulus of each coordinate obtained from the accelerometer device 140) is calculated.
  • the device 100 associates a time stamp with each value of M, the time stamp corresponding to the time period over which the modulus data was captured.
  • the value of M is synchronized with the RBC flow data provided on the first channel which also has an associated time stamp.
  • the RBC flow data time stamp corresponds to the time at which the corresponding optical signal was received by the photodetector module 122.
  • values of the optical signal detected by the photodetector module 122 (corresponding to RBC flow) having a time stamp corresponding to a moment in time when the value of M exceeds a threshold value Mth are not used in subsequent calculations of RBC flow velocity.
  • the detected signal processed at 204 is filtered to extract an RBC Doppler shift frequency band as discussed above.
  • values of the optical signal detected by the photodetector module 122 (corresponding to RBC flow) having a time stamp corresponding to a moment in time when the value of M exceeds a threshold value Mth are not used in this or subsequent calculations of RBC flow velocity.
  • this signal is used to determine an RBC flow velocity, which is output in step 218.
  • the filtered signal may be normalized in step 208 based on an average RBC flow density, as discussed above.
  • This normalized reflected signal is then subjected to wavelet analysis at step 210 to determine myogenic frequency.
  • the wavelet analysis may be performed on a set of reflected signals that are obtained over a measurement period (e.g. 2 minutes).
  • the determined myogenic frequency may be an average of a plurality of values calculated during the measurement period.
  • a diagnostic condition is determined using the myogenic frequency. This can be done by comparing the calculated myogenic frequency with stored values that correspond to normal and abnormal conditions.
  • the method may conclude by instructing the display 132 to provide information to a user based on the determined diagnostic condition.
  • a similar process for lymph contrast objects can run in parallel.
  • the method may include a step 220 of detecting in a second detector (on a second channel for obtaining lymph flow data) a reflected signal of varying intensity.
  • the motion information generated at step 205 is received by the second detector which ignores lymph flow data on the second channel having a time stamp corresponding to a time period for which M is greater than Mth.
  • the detected signal not having a time stamp corresponding to a time period for which M is greater than Mth is filtered at step 222 to extract a lymph contrast object Doppler shift frequency band as discussed above.
  • this signal is used to determine a lymph contrast object flow velocity, which is output at step 228.
  • the filtered signal generated at step 222 may be normalized at step 224 based on an average lymph contrast object flow density, as discussed above.
  • This normalized reflected signal is then subjected to wavelet analysis at step 210 to determine myogenic frequency or some other microcirculation parameter.
  • the wavelet analysis may be performed on a set of reflected signals that are obtained over a measurement period (e.g. 2 minutes).
  • the determined microcirculation parameter may be an average of a plurality of values calculated during the measurement period.
  • the device 100 does not use all data values acquired by the photodetector module 122 to calculate RBC flow velocity and then ignore values of RBC flow velocity that appear to be outside an expected range. Rather, when calculating RBC flow velocity, the device 100 ignores data acquired by the photodetector module 122 only at times when the value of M exceeds a threshold. It is to be understood that this may be important in cases where a person wearing the device has a medical condition that results in values of RBC flow velocity that are outside of an expected range for a 'healthy' person. The device will not ignore this data provided that the value of M does not exceed the threshold value Mth. This increases a likelihood that a more accurate understanding of a person's true health condition will be gained by use of a device 100 according to embodiments of the present invention.
  • the threshold value Mth used in order to determine whether to ignore data or not may be set at a level where the data would be "ruined” and not useful in determining a metric of user health due to the motion. That is, to a value above which LDF data acquired by the device would not be useful in determining a true metric of user health because of the movement of the device when the LDF data was being acquired.
  • LDF is a relatively sensitive measurement technology and movement of the device 100, attached to a user, during data acquisition may affect the data acquired. Movement of the device 100 as a user moves can readily override the sensitive data LDF can acquire.
  • FIG. 4 is a schematic flow diagram that illustrates various steps in another method 300 of operating the device 100 discussed above, in this case to simultaneously detect RBC and lymph perfusion data together with fluorescence data that permits determination of tissue redox ratio.
  • the method begins with a step 302 of irradiating the tissue separately or simultaneously with UV and IR radiation as discussed above.
  • the method continues at step 304 at which RBC and/or lymph contrast object flow information is determined based on a reflected IR signal following one of more of the steps discussed with reference to FIG. 3 above. Data corresponding to IR signals received during a time period corresponding to a time stamp when the value of M exceeded Mth is ignored at step 304.
  • the determined information signal is output at step 306, e.g. displayed on display 132 or transmitted to a remote device.
  • the method includes a step 308 of detecting a fluorescence excitation signal from the region of irradiated tissue.
  • This step may be performed by one or more filtered photoreceivers as discussed above.
  • the detected fluorescence signal is filtered at step 310 in order to detect a specific biomarker.
  • NADFI or FAD can be detected by selecting the filters to pass wavelengths corresponding to specific fluorescence peaks.
  • NADFI and FAD may be detected simultaneously to permit determination of the tissue redox ratio.
  • the filtered signal is analysed to extract information relating to a detected biomarker.
  • This information is output in step 312, e.g. by being displayed on the display 132 or other indicator or by being transmitted to a remote device 190.
  • embodiments of the present invention are directed to measurement of velocity of substances such as red blood cells in the body, providing information in respect of blood perfusion. This is in contrast to other techniques which are directed to absorption measurements.
  • patients subject to LDF monitoring have been confined to single point measurements such as in a hospital, clinic or other healthcare facility.
  • Embodiments of the present invention enable users to have measurements made away from such facilities and without direct supervision, and whilst not being restricted to a stationary position such as a seated or lying position for the purpose of data acquisition. Rather, the user may go about their regular daily activities.
  • the monitoring device 100 performs the measurements and analysis described herein, useful data being acquired during periods when movement of the device 100 is within an acceptable range of values of speed and/or acceleration as described herein.
  • FIG. 5 is a plot of data acquired by the device 100 as a function of time (x-axis).
  • a temperature signal is indicative of the body temperature of the wearer of the device 100.
  • Temperature is monitored by means of a thermosensor.
  • the thermosensor senses temperature by means of a platinum resistance thermometer (e.g. NCP18WF104D03RB
  • NTC by Murata Manufacturing Co., Ltd., Nagaokakyo, Kyoto, see https://www.murata.com/en- eu/products/productdetail?partno NCP18WF104D03RB).
  • a platinum resistance thermometer e.g. NCP18WF104D03RB
  • NTC by Murata Manufacturing Co., Ltd., Nagaokakyo, Kyoto, see https://www.murata.com/en- eu/products/productdetail?partno NCP18WF104D03RB).
  • the platinum resistance thermometer is physically coupled to a metallic element that is provided on an underside of the device 100, around the output optics 118.
  • temperature may be sensed by means of a metallic element around the input optics 120, or around both the input and output optics 120, 118.
  • Other arrangements may be useful.
  • thermosensor may be used in some embodiments, such as a thermocouple of any other suitable thermosensor.
  • the motion signal is indicative of the value of M calculated by the device as a function of time. In the plot shown, the motion signal remains within acceptable limits, i.e. the value of M does not exceed Mth, for the period indicated in FIG. 5.
  • the software running on the smartphone 190 that receives data acquired by the device 100 may evaluate the data by performing analysis of the data received.
  • the analysis may be performed substantially in real time or offline.
  • FIG. 6 is a plot of amplitude (in arbitrary units, AU) as a function of 1/frequency (1/f) in respect of detected motion within the wearer's microcirculatory system.
  • the software is configured to isolate five rhythmic oscillations from the LDF data, each within a predetermined unique frequency interval, labelled A to E in FIG. 6. The intervals correspond to endothelial oscillations (interval A), neurogenic oscillations (interval B), biogenic oscillations (interval C), respiratory oscillations (interval D) and cardiac (pulse) rhythm or oscillations (interval E).
  • This data may be reviewed by a medical practitioner in order to gain an understanding of the wearer's health condition. It is to be understood that the medical practitioner may review the data using the smartphone 190 or other computing device 190 to which the device 100 may transmit the data. In some embodiments, the smartphone 190 may upload the data, and some or all of the analysis performed by the smartphone 190 and/or device 100, to cloud storage or transmit the data to the medical practitioner, for example by email or other messaging system. The medical practitioner may then review the data offline.
  • a non-invasive human condition monitoring device comprising: a source of infrared radiation arranged to emit infrared radiation onto biological tissue associated with a subject; a photodetector module for detecting a first signal and a second signal, the first signal and the second signal corresponding to portions of the infrared illumination reflected from the biological tissue; a processing module arranged to analyse the first signal and the second signal to independently determine: a first Doppler shift associated with the first signal, the first Doppler shift being indicative of red blood cell (RBC) flow velocity in the biological tissue, and a second Doppler shift associated with the second signal, the second Doppler shift being indicative of lymph scatterer flow velocity in the biological tissue, wherein the device is configured to compensate for an effect of motion of the device on one or both of the first and second signals.
  • RBC red blood cell
  • a device configured to compensate for an effect of motion by ignoring information corresponding to time periods in which one or more characteristics of motion of the device exceeded one or more threshold conditions. 3. A device according to clause 1 or clause 2 configured to ignore data corresponding to time periods in which a rate of acceleration of the device exceeded a predetermined rate.
  • a device configured to ignore data corresponding to time periods in which a speed of movement of the device exceeded a predetermined speed.
  • a device configured to compensate for an effect of motion on one or both of the first and second signals at least in part by modifying one or both signals before analyzing them to determine the first and second Doppler shifts.
  • a device configured to compensate for an effect of motion on one or both of the first and second signals at least in part when determining the first and second Doppler shifts.
  • a device comprising a motion sensor configured to generate a motion signal responsive to movement of the device, optionally wherein the motion signal comprises information in respect of rate of acceleration of the device, further optionally wherein the motion signal comprises information in respect of rate of acceleration of the device in a plurality of respective directions.
  • the motion signal may for example provide information in respect of rate of acceleration of the device along mutually orthogonal axes, optionally along three mutually orthogonal (X, Y, Z) axes.
  • the source of infrared radiation is arranged to output infrared radiation at a single stable frequency, optionally wherein the infrared radiation has a wavelength in the range 800 to 1100 nm, further optionally wherein the source of infrared radiation comprises a laser diode.
  • the photodetector module comprises a first photodetector for detecting the first signal and a second photodetector for detecting the second signal.
  • processing module is arranged to filter the first signal to remove frequencies outside an expected RBC Doppler shift frequency band.
  • processing module is arranged to filter the second signal to remove frequencies outside an expected lymph scatterer Doppler shift frequency band.
  • a device including an analysis module arranged to determine one or more microcirculation parameters based on the first Doppler shift and the second Doppler shift.
  • a device wherein the analysis module is arranged to perform wavelet analysis on the first signal and the second signal to extract information indicative of the one or more microcirculation parameters.
  • microcirculation parameters include the frequency of at least one selected from amongst myogenic rhythm, endothelial oscillations, pacemaker oscillations, and breathing oscillations.
  • a device including a source of ultraviolet radiation arranged to emit ultraviolet radiation onto biological tissue associated with a subject, wherein the photodetector module is arranged to detect a fluorescent response from the biological tissue triggered by the ultraviolet radiation. 18. A device according to clause 17, wherein the photodetector module is arranged to detect a plurality of fluorescent responses, each of the plurality of fluorescent responses being associated with a respective biomarker.
  • the photodetector module comprises a plurality of photoreceivers, each photoreceiver being arranged to detect a fluorescent response from a respective biomarker, wherein each photoreceiver has an input filter arranged to remove frequencies outside an expected frequency range associated with the fluorescent response of its respective biomarker.
  • the photodetector module is arranged to detect autofluorescent responses from NADH and FAD, and wherein the device includes an analysis module arranged to calculate a tissue redox ratio based on the detected autofluorescent responses for NADH and FAD, the device being configured to provide an output responsive to the calculated tissue redox ratio.
  • a device according to any preceding clause wherein the source of infrared radiation is arranged to emit an infrared illumination pattern onto the biological tissue associated with the subject.
  • a device according to clause 17 or any one of clauses 18 to 21 depending through clause 17 wherein the source of ultraviolet radiation is arranged to emit an ultraviolet illumination pattern onto the biological tissue associated with the subject.
  • a method of non-invasively monitoring a human condition by means of an apparatus or device comprising: directing infrared radiation onto biological tissue associated with a subject; detecting a first signal and a second signal, the first signal and the second signal corresponding to portions of the infrared radiation reflected from the biological tissue; analysing the first signal and the second signal to independently determine: a first Doppler shift associated with the first signal, the first Doppler shift being indicative of red blood cell (RBC) flow velocity in the biological tissue, and a second Doppler shift associated with the second signal, the second Doppler shift being indicative of lymph scatterer flow velocity in the biological tissue, the method comprising compensating for an effect of motion of the device on one or both of the first and second signals.
  • RBC red blood cell
  • a method according to clause 23 whereby compensating for an effect of motion comprises ignoring information corresponding to time periods in which one or more characteristics of relative motion between the apparatus or device exceeded one or more threshold conditions.
  • a method according to clause 23 or 24 comprising directing ultraviolet radiation onto biological tissue associated with a subject and detecting a fluorescent response associated with a biomarker from the biological tissue triggered by the ultraviolet radiation, the method comprising detecting autofluorescent responses from NADH and FAD, calculating a tissue redox ratio based on the detected autofluorescent responses for NADH and FAD, and providing an output responsive to the calculated tissue redox ratio.
  • main body 110 power source 112: laser system
  • Accelerometer device 200 Process for simultaneously determining flow information for red blood cells (RBC) and lymph contrast objects in a subject's blood.
  • RBC red blood cells
  • Detection on a first channel for obtaining RBC flow data of reflected signal of varying intensity.
  • 205 The sum of the motion modulus values, M, is calculated together with a time stamp.
  • Step 206 Detected signal from step 204 not having a time stamp corresponding to a time period for which M is greater than Mth is filtered to extract an RBC Doppler shift frequency band.
  • Normalized reflected signal is subjected to wavelet analysis to determine myogenic frequency.
  • Filtered signal from step 206 is used to determine an RBC flow velocity.
  • Detected signal not having a time stamp corresponding to a time period for which M is greater than Mth is filtered to extract a lymph contrast object Doppler shift frequency band.
  • Signal produced at step 222 is used to determine a lymph contrast object flow velocity.
  • Method 300 Method 300 of operating the device 100 to simultaneously detect RBC and lymph perfusion data together with fluorescence data that permits determination of tissue redox ratio.
  • RBC and/or lymph contrast object flow information is determined based on a reflected IR signal. Data corresponding to IR signals received during a time period corresponding to a time stamp when the value of M exceeded Mth is ignored.
  • the RBC and/or lymph flow information determined at step 304 is output.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Physics & Mathematics (AREA)
  • Public Health (AREA)
  • Pathology (AREA)
  • Physiology (AREA)
  • Signal Processing (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
  • Vascular Medicine (AREA)
  • Artificial Intelligence (AREA)
  • Computer Vision & Pattern Recognition (AREA)
  • Psychiatry (AREA)
  • Measuring Pulse, Heart Rate, Blood Pressure Or Blood Flow (AREA)

Abstract

L'invention concerne un dispositif de surveillance non invasive de condition humaine, comprenant : une source de rayonnement infrarouge conçue pour émettre un rayonnement infrarouge sur un tissu biologique associé à un sujet ; un module photodétecteur pour détecter un premier signal et un second signal, le premier signal et le second signal correspondant à des parties de l'éclairage infrarouge réfléchie par le tissu biologique ; un module de traitement agencé pour analyser le premier signal et le second signal pour déterminer indépendamment : un premier décalage Doppler associé au premier signal, le premier décalage Doppler étant indicatif d'une vitesse d'écoulement de globule rouge (GB) dans le tissu biologique, et un second décalage Doppler associé au second signal, le second décalage Doppler étant indicatif de la vitesse d'écoulement de l'objet de contraste lymphatique (ou du "diffuseur lymphatique") dans le tissu biologique, le dispositif étant configuré pour compenser un effet de mouvement du dispositif sur l'un ou les deux des premier et second signaux.
PCT/GB2021/053125 2020-11-30 2021-11-30 Dispositif et procédé de surveillance non invasive de condition humaine Ceased WO2022112804A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB2018858.7 2020-11-30
GBGB2018858.7A GB202018858D0 (en) 2020-11-30 2020-11-30 Monitoring device and method of monitoring

Publications (1)

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WO2022112804A1 true WO2022112804A1 (fr) 2022-06-02

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040034293A1 (en) * 2002-08-16 2004-02-19 Optical Sensors Inc. Pulse oximeter with motion detection
US20040034294A1 (en) * 2002-08-16 2004-02-19 Optical Sensors, Inc. Pulse oximeter
WO2017089479A1 (fr) * 2015-11-26 2017-06-01 Aston University Dispositif de surveillance non invasif d'une affection humaine
US20170172424A1 (en) * 2014-12-22 2017-06-22 Eggers & Associates, Inc. Wearable Apparatus, System and Method for Detection of Cardiac Arrest and Alerting Emergency Response

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040034293A1 (en) * 2002-08-16 2004-02-19 Optical Sensors Inc. Pulse oximeter with motion detection
US20040034294A1 (en) * 2002-08-16 2004-02-19 Optical Sensors, Inc. Pulse oximeter
US20170172424A1 (en) * 2014-12-22 2017-06-22 Eggers & Associates, Inc. Wearable Apparatus, System and Method for Detection of Cardiac Arrest and Alerting Emergency Response
WO2017089479A1 (fr) * 2015-11-26 2017-06-01 Aston University Dispositif de surveillance non invasif d'une affection humaine

Also Published As

Publication number Publication date
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