Measurement of hemodynamic parameters

Abstract

A method for deriving one or more hemodynamic parameters, including one or more measurements of blood pressure, based on obtaining a series of sample pulse wave signals at a series of applied pressures using a tissue pressure sensor integrated between a user's body and a pressure applicator, wherein the hemodynamic parameters are derived based on identifying characteristic points in the derived plots that indicate changes in pulse waveform morphology as a function of applied pressure.

Description

[Technical Field]

[0001] The present invention relates to a method for measuring hemodynamic parameters such as blood pressure. [Background technology]

[0002] Monitoring hemodynamic parameters plays an important role in patient monitoring, especially for critically ill patients. Hemodynamic monitoring allows for monitoring tissue perfusion and oxygenation while maintaining an adequate mean arterial pressure in the patient. In most clinical practice, such monitoring is only available in intensive care settings because currently available techniques are invasive.

[0003] In recent years, non-invasive hemodynamic monitoring techniques have been developed.

[0004] One area of ​​interest is the possibility of non-invasively determining various measurements of arterial pressure, such as mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as estimates of central hemodynamic parameters, such as cardiac output (CO), stroke volume (SV) and stroke volume variation (SVV), using measurement data acquired using inflatable measurement cuffs typically used for measuring blood pressure (i.e., sphygmomanometer systems).

[0005] US Patent Application Publication No. 2019 / 298188 relates to systems and methods for non-invasive blood pressure measurement.

[0006] US Patent Application Publication No. 2017 / 360313 relates to methods and devices for measuring blood pressure.

[0007] US Pat. No. 4,427,013 relates to a blood pressure measuring device that measures arterial pressure by the oscillometric method.

[0008] An example of a system that has been developed for non-invasive hemodynamic monitoring is the device detailed in EP 2953528 A1.

[0009] This describes a blood pressure measurement system that includes a separate sensor for measuring the pressure between a user's body part (e.g., arm) and the cuff. This is called a tissue pressure sensor. This is provided in addition to a sensor for sensing the pressure inside the inflatable cuff. This tissue pressure sensor makes it possible, under certain circumstances, to obtain a quasi-continuous pressure signal that approximates the patient's invasively obtained pulse waveform signal. This allows various hemodynamic parameters to be derived.

[0010] U.S. Patent Application Publication No. 2015 / 0320364 describes an example of an algorithm that allows for the conversion of acquired pressure signals into an approximation of a pulse waveform signal. It is generally advantageous to be able to measure a patient's pulse waveform noninvasively, preferably continuously, to avoid the use of an invasive arterial line. Previous methods in the art are only able to obtain peripheral (non-central) pulse waveform measurements, which suffer from accuracy issues. For example, previously known methods include volume clamping, which uses a finger cuff and controls the finger cuff to maintain a constant transmural pressure and maintain a constant blood volume within the artery.

[0011] US Patent Application Publication No. 2015 / 0320364 proposes instead to use measurements taken using a pressure sensor located within a blood pressure cuff.

[0012] However, in principle, it is not possible to directly use the directly measured pressure oscillation signal obtained from the pressure sensor readings of a blood pressure cuff, because the relationship between the measured pulse signal (as a function of time) and the true arterial pulse signal (as a function of time) is, in principle, nonlinear with respect to the applied pressure, and as a result, the shape of the measured pulse signal cannot generally be expected to match the shape of the arterial pulse wave.

[0013] This is believed to be because arterial wall compliance affects the linearity of pressure transmission between arterial pressure and the pressure measured by the sensor.

[0014] However, despite the above principles, it has been recognized that there exists a value of applied clamping pressure at which the relationship between the measured pulse signal as a function of time and the true arterial pressure is substantially linear, and therefore the shape of this pulse signal more reliably reflects the shape of the arterial pulse waveform.

[0015] This clamping pressure is considered to be equal to the mean arterial pressure because this value is the applied clamping pressure at which the bias / stress on the arterial wall is minimal, eg, substantially zero.

[0016] The concept in US Patent Application Publication No. 2015 / 0320364 is to calculate a weighted average of a series of pulse wave signals acquired at different respective clamping pressures over a range, where the weighting is related to or correlated to the clamping pressure value of a given signal being pressure-wise close to a specific clamping pressure, defined as the clamping pressure at which the internal actual mean arterial pressure is equal to a certain percentage of the applied clamping pressure.

[0017] However, this specific pressure value cannot be determined, and instead, US Patent Application Publication No. 2015 / 0320364 proposes an iterative method for determining the weighting.

[0018] Scaling was applied after determining the general shape of the pulse waveform using the weighted average signal. Scaling was based on measurements of SBP and DPB, and the pulse waveform shape was amplitude scaled so that its maximum value corresponded to SBP and its minimum value corresponded to DPB.

[0019] As a further extension of this method, an additional auxiliary continuous blood pressure measurement device (e.g., volume clamp finger method) was used to obtain a continuous central blood pressure waveform rather than just intermittent discrete measurements, and the continuous waveform output from this auxiliary sensor was adjusted or calibrated according to the intermittent pulse waveform measurements obtained using the more complex method described above.

[0020] However, the algorithm in US Patent Application Publication No. 2015 / 0320364 is very complex. Summary of the Invention [Problem to be solved by the invention]

[0021] Therefore, a simplified approach for deriving pulse wave signals and / or for deriving hemodynamic parameters using continuous pressure signals is desirable. [Means for solving the problem]

[0022] The invention is defined by the claims.

[0023] According to an example in accordance with one aspect of the present invention, there is provided a method for use in measuring blood pressure with a blood pressure measurement device, the blood pressure measurement device having a pressure applicator for use in applying a variable pressure to tissue of a body part overlying a blood vessel, and further including a tissue pressure sensor configured to sense pressure between a surface of a user's body part overlying a blood vessel and the pressure applicator. The tissue pressure sensor may, for example, comprise a pressure sensor pad positioned between the body part and the pressure applicator during operation. The tissue pressure sensor may, for example, be external to the pressure applicator and / or separate from the pressure applicator.

[0024] The method includes using a blood pressure measurement device to acquire a series of tissue pressure signals (from a tissue pressure sensor), each tissue pressure signal acquired at a different applied pressure value across a sequence of incrementally increasing or decreasing applied pressure values. The method further includes deriving a candidate or sample pulse wave signal from each tissue pressure signal based on extracting an AC component of each tissue pressure signal, thereby deriving a series of candidate pulse wave signals, each candidate pulse wave signal corresponding to a different applied pressure value across the sequence of applied pressure values. The method includes deriving a plot showing changes in pulse wave waveform morphology as a function of applied pressure based on a comparative analysis applied to waveforms of the series of candidate pulse wave signals, identifying applied pressure values ​​that match each of a set of one or more predetermined characteristic features of the plot, and deriving one or more arterial pressure measurements for the subject based on the one or more identified applied pressure values ​​and based on a predetermined mapping / relationship between the applied pressure values ​​at which the characteristic features of the plot occur and one or more arterial pressure measurements.

[0025] Optionally, the method may further comprise generating a data output indicative of one or more arterial pressure measurements.

[0026] The inventors have recognized that the morphology of a measured pulse wave signal changes as a function of applied cuff pressure. This is due to the relationship between transmural pressure and arterial wall compliance. Through experimentation and simulation, the inventors have surprisingly found that identifiable characteristic features in a plot of the change in morphology of the pulse wave waveform as a function of applied pressure are reliably associated with applied pressures equal to certain important blood pressure values, such as systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP). The inventors have therefore recognized that this fact can be used to work backwards: to obtain a plot of the change in morphology as a function of applied pressure, and from this plot, to calculate the applied pressure values ​​at which the characteristic features occur, and to infer that these pressure values ​​must correspond to the associated blood pressure values.

[0027] For example, in some embodiments, the comparative analysis may include performing a waveform comparison procedure that includes comparing the waveform morphology of each of the plurality of candidate pulse wave signals with the waveform morphology of at least one other of the plurality of pulse wave signals to measure changes in waveform morphology as a function of applied pressure.

[0028] This provides a novel and highly accurate method for measuring certain hemodynamic parameter measurements, including various measurements of blood pressure.

[0029] The AC component of each tissue pressure signal provides a pseudo-pulse wave signal (referred to herein as a candidate or sample pulse wave signal). As explained above, in general, a measured pressure signal only accurately corresponds to the waveform shape of a pulse wave signal within a specific range of applied pressure. Thus, each measured tissue pressure signal is, in fact, a candidate for a true pulse wave signal.

[0030] In some embodiments, the one or more characteristic features include one or more inflection or turning points and / or zero crossing points of the plot, which indicate a change in the morphology of the pulse waveform as a function of applied pressure.

[0031] In the context of this disclosure, an inflection point refers to a point where a waveform changes direction, otherwise known as a turning point. Additionally or alternatively, an inflection point refers to a point where the curvature of a waveform changes sign. A zero-crossing point refers to a point where a waveform crosses the zero amplitude line, e.g., a point where a waveform crosses a horizontal axis.

[0032] In some embodiments, the tissue pressure signal is from a tissue pressure sensor having a pressure sensor pad positioned between the body part and the pressure applicator during operation. The tissue pressure sensor may be external to and / or separate from the pressure applicator, for example.

[0033] In some embodiments, the body part is an arm of a patient.

[0034] In some embodiments, the comparison procedure involves using one of the measured tissue pressure signals as a reference pulse wave signal, and comparing each of the other pulse wave signals to this reference pulse wave signal.

[0035] For example, in some embodiments, acquiring the series of tissue pressure signals includes acquiring a reference tissue pressure signal within a defined applied pressure range and acquiring the series of tissue pressure signals over a sequence of incrementally increasing or decreasing applied pressure values ​​outside the defined applied pressure range. Deriving the series of candidate pulse wave signals includes deriving reference candidate pulse wave signals from the reference tissue pressure signals based on extracting AC components, and deriving a respective candidate pulse wave signal for each tissue pressure signal acquired outside the applied pressure range. The method may include performing a predetermined comparison procedure for each candidate pulse wave waveform of the series of signals outside the predetermined range, the comparison comprising comparing a waveform morphology of the respective pulse wave signal with a waveform morphology of a reference pulse wave signal, deriving respective values ​​of a waveform disparity metric for the pulse wave signals, and plotting the waveform disparity metric as a function of applied tissue pressure to derive the plot indicative of changes in pulse waveform morphology as a function of applied pressure.

[0036] In some embodiments, the one or more characteristic features include one or more inflection or turning points and / or zero crossing points in a plot of the waveform disparity metric.

[0037] Thus, in this exemplary set of one or more embodiments, one of the acquired pulse wave signals is used as a reference, and a waveform disparity metric is derived for each of the other acquired pulse wave signals based on comparison to the reference, which is then plotted as a function of applied pressure.

[0038] The particular defined pressure range within which the reference pulse wave signal is acquired may be quantitatively defined in advance or may be dynamically determined during the measurement process.

[0039] For example, in some embodiments, the predetermined applied pressure range within which the reference tissue pressure signal is acquired is 0 to 50 mmHg (= 0 to 6666 Pa), e.g., 0 to 40 mmHg (= 0 to 5332 Pa), e.g., 10 to 40 mmHg (= 1333 to 5332 Pa). Through experiments and simulations, the inventors have found that a tissue pressure signal acquired within this particular range closely approximates a true invasively acquired patient pulse pressure waveform. This value should be greater than zero and less than the defined upper limit of the range.

[0040] In some embodiments, the method further comprises generating a data output indicative of the reference pulse wave signal, which provides an output representative of the patient's pulse waveform.

[0041] To increase the SNR of the acquired reference pulse wave signal, in some embodiments, acquiring the reference tissue pressure signal comprises sampling the tissue pressure signal over multiple cardiac cycles at a constant applied pressure value and calculating an average tissue pressure signal over the multiple cardiac cycles as the reference tissue pressure signal. Optionally, the amplitude and duration of each pulse can be normalized before averaging to obtain a cleaner averaged pulse.

[0042] In some embodiments, instead of a fixed numerical range, the defined applied pressure range is defined according to a characteristic feature or characteristic of the tissue pressure signal that occurs in accordance with the applied pressure range. The characteristic feature or characteristic may be, for example, the amplitude of the AC component of the tissue pressure signal that is at or near a maximum. In other words, the reference pulse wave signal is selected as the pulse wave signal having the largest AC amplitude of the acquired pulse wave signals.

[0043] As the applied pressure increases, the maximum amplitude of the AC component is expected to occur in a range of applied pressures around the mean arterial pressure (MAP). As will be explained later, experiments and simulations have shown that at applied pressures approximately equal to the mean arterial pressure, the waveform disparity relative to the patient's true pulse wave is zero or close to zero. The maximum does not necessarily occur exactly at the MAP, but occurs in a range close to the MAP.

[0044] In some examples, the reference candidate pulse wave signal is selected based on identifying a pulse wave signal from among the candidate pulse wave signals that has a distinctive feature or characteristic after the entire measurement sequence is completed.

[0045] There are various possible options for performing the comparison process to calculate the waveform disparity metric.

[0046] According to at least one set of embodiments, a waveform disparity metric for a given pulse wave signal is calculated as the integral of the difference between the respective pulse wave signal and the reference pulse wave signal over the period of the pulse wave, an example of this waveform disparity metric is referred to herein as M1.

[0047] In this case, the one or more characteristic features of the plot of the waveform disparity metric (M1) include a zero crossing point of the plot, and wherein deriving the one or more blood pressure measurements includes deriving a value of mean arterial pressure (MAP) based on the applied pressure value at which the zero crossing point occurs in the plot.

[0048] Additionally or alternatively, in some embodiments, one or more characteristic features of the plot of the waveform disparity metric (M1) can include a maximum point of the plot, and deriving one or more blood pressure measurements includes deriving a value of diastolic blood pressure (DBP) based on the applied pressure value at which the maximum point in the plot occurs. This referenced maximum point of the plot can be the peak point of a rising edge or rising phase of the waveform. It can be the point at which the waveform changes from a rising edge or phase to a falling edge or phase.

[0049] Additionally or alternatively, in some embodiments, the one or more characteristic features of the plot of the waveform disparity metric (M1) can include a first inflection or turning point in the plot after a zero crossing point, and deriving the one or more blood pressure measurements includes deriving a value of systolic blood pressure (SBP) based on the applied pressure value at which the inflection point occurs in the plot, which can be the point at which the waveform changes from a falling edge or phase to a plateau.

[0050] The reasoning behind each of the characteristic features of the plots proposed above will become clear by reference to the simulation data presented later in the detailed description.

[0051] According to a further set of embodiments, a waveform disparity metric for a given pulse wave signal is calculated as the integral of the square of the difference between the respective pulse wave signal and a reference pulse wave signal over the period of the pulse wave. An example of this waveform disparity metric is referred to herein as M2.

[0052] According to this set of embodiments, the one or more characteristic features of the plot of the waveform disparity metric (M2) may include a first maximum point of the plot, and deriving one or more blood pressure measurements includes deriving a value of diastolic blood pressure (DBP) based on the applied pressure value at which the first maximum point occurs in the plot. The referenced first maximum may be the peak point of the first rising edge or rising phase of the waveform. It may be the point at which the waveform changes from the first rising edge or phase to the first falling edge or phase.

[0053] Additionally or alternatively, in some embodiments, the one or more characteristic features of the plot of the waveform disparity metric (M2) include a first minimum point subsequent to a first maximum of the plot of the waveform disparity metric, and deriving the one or more blood pressure measurements includes deriving a value of mean arterial pressure (MAP) based on the applied pressure value at which the minimum point occurs in the plot. The referenced first minimum point can be a turning point where a first falling edge or phase of the waveform changes to a second rising edge or phase of the waveform. It can also be a trough or minimum point at the base of the first falling edge or phase of the waveform.

[0054] Additionally or alternatively, in some embodiments, the one or more characteristic features of the plot of the waveform disparity metric (M2) include a last inflection point of the plot (or an inflection point following the first minimum after a maximum), and deriving the one or more blood pressure measurements includes deriving a value of systolic blood pressure (SBP) based on the applied pressure value at which the inflection point in the plot occurs. This referenced point can be a turning point or inflection point where the waveform changes from a second rising edge or phase of the waveform to a plateau.

[0055] The reasoning behind each of the characteristic features of the plots proposed above will become clear by reference to the simulation data presented later in the detailed description.

[0056] According to a further set of embodiments, the comparative analysis comprises a process of comparing the waveform of each candidate pulse wave signal with the waveform of the preceding candidate pulse wave signal, this approach avoiding the need to measure the reference pulse wave signal separately since each signal is compared with the preceding signal.

[0057] Thus, in this set of embodiments, the method comprises performing a predetermined comparison procedure for each candidate pulse wave signal in the series of candidate pulse wave signals, comprising comparing the waveform morphology of the respective candidate pulse wave signal with the waveform morphology of the immediately preceding candidate pulse wave signal in the series of candidate pulse wave signals, deriving a respective value of a waveform disparity metric (M3) for the pulse wave signal, and plotting the waveform disparity metric as a function of applied pressure, deriving the plot showing the change in waveform morphology of the pulse wave as a function of applied pressure.

[0058] According to this set of embodiments, the one or more characteristic features of the plot of the waveform disparity metric (M3) may include a zero-crossing point of the plot, and deriving the one or more blood pressure measurements includes deriving a value of diastolic blood pressure (DBP) based on the applied pressure value at which the zero-crossing point occurs in the plot, which may be the first zero-crossing point after the first peak or maximum of the waveform / plot.

[0059] Additionally or alternatively, in some embodiments, one or more characteristic features of the plot of the waveform disparity metric (M3) include a first minimum point in the plot after a zero-crossing point, and deriving one or more blood pressure measurements includes deriving a value of mean arterial pressure (MAP) based on the applied pressure value at which the minimum point occurs in the plot. For example, the waveform may have a first rising edge that changes to a first falling edge at a peak point (first maximum point). The first falling edge may include a zero-crossing point. The first falling edge may end at a trough or minimum point where the waveform changes upward and becomes a second rising edge. The first minimum point referred to above may be a minimum point at the base of the first falling edge of the waveform.

[0060] Additionally or alternatively, in some embodiments, one or more characteristic features of the plot of the waveform disparity metric (M3) include a first minimum point in the plot after a zero-crossing point and an inflection point after the minimum point, and deriving one or more blood pressure measurements includes deriving a systolic blood pressure (SBP) value based on the applied pressure value at which the inflection point in the plot occurs. For example, the waveform may have a first rising edge that changes to a first falling edge at a peak point (first maximum point). The first falling edge may include a zero-crossing point. The first falling edge may end at a trough or minimum point where the waveform changes upward and becomes a second rising edge. The referenced inflection point may be the inflection point or inflection point at which the waveform changes from the second rising edge to a plateau.

[0061] The reasoning behind each of the characteristic features of the plots proposed above will become clear by reference to the simulation data presented later in the detailed description.

[0062] In some embodiments, the method includes controlling a tissue pressure cycle of the blood pressure measuring device in which the tissue pressure is increased or decreased in steps over a range of applied pressures to achieve a sequence of different applied pressures.

[0063] In some embodiments, a plot showing the change in pulse waveform morphology as a function of applied pressure is calculated progressively in real time as an applied pressure cycle progresses, and the applied pressure cycle terminates when all of a set of characteristic features of one or more plots have been detected. This has the advantage of minimizing the time required for the measurement process, as the process simply terminates when all of the required plot features have been detected.

[0064] A completed applied pressure cycle means, for example, that the pressure is released and the applied pressure returns to zero or to a minimum applied pressure.

[0065] In some embodiments, the blood pressure measurement device includes a cuff for wrapping around a portion of a user's body, the cuff containing a pressure applicator, the pressure applicator being a pneumatic actuator in the form of an inflatable bladder.

[0066] Here, the pressure application cycle comprises an inflation / deflation cycle of the cuff.

[0067] In some embodiments, deriving each candidate pulse wave signal further includes scaling the extracted AC component of the tissue pressure signal, which includes, for each individual pulse in the signal, increasing the scale of the waveform while maintaining its shape / morphology, so that its maximum point corresponds to a previously measured SBP value and its minimum point corresponds to a previously measured DBP value. This achieves scaling. Scaling may also be performed in the time domain, such that the duration of each individual pulse in the pulse wave signal is scaled to a predetermined time period, e.g., 1 second. These operations effectively normalize each pulse in the signal in both the amplitude and time domains. The terms "scaling and normalization" herein may refer to this pair of operations.

[0068] Here, the measured SBP and DBP values ​​are stored in memory, and these values ​​may be obtained from a previous measurement or a current measurement, and therefore may be historical values.

[0069] The invention may also be implemented in software form. Thus, another aspect of the invention is a computer program product having computer program code configured, when executed on a processor operatively coupled to a blood pressure measuring device, to cause the processor to perform a method according to any embodiment described herein or in any claim of the present application.

[0070] The present invention can also be implemented in hardware.

[0071] Accordingly, another aspect of the present invention is a processing device for use in measuring blood pressure with a blood pressure measurement apparatus having a pressure applicator for use in applying a variable pressure to tissue of a body part overlying a blood vessel, and further including a tissue pressure sensor configured to sense pressure between a surface of a user's body part overlying a blood vessel and said pressure applicator.

[0072] The processing device has an input / output unit and one or more processors operatively coupled to the input / output unit, the processors comprising: receiving, at said input / output, a series of tissue pressure signals acquired at different applied pressure values ​​over a sequence of incrementally increasing or decreasing applied pressure values ​​from said blood pressure measuring device; deriving a candidate pulse wave signal from each tissue pressure signal based on extracting an AC component of each tissue pressure signal, thereby deriving a series of candidate pulse wave signals, each candidate pulse wave signal corresponding to a different applied pressure value across the sequence of applied pressure values; deriving a plot showing changes in pulse waveform morphology as a function of applied pressure based on the comparative analysis applied to waveforms of the series of candidate pulse wave signals; identifying applied pressure values ​​that correspond with each of a set of one or more predetermined characteristic features of said plot; Deriving one or more arterial pressure measurements based on the one or more identified applied pressure values ​​and based on a predetermined mapping / relationship between the applied pressure values ​​and one or more arterial pressure measurements that results in a characteristic feature of the plot; and Optionally, generating a data output indicative of said one or more arterial pressure measurements, and optionally coupling said data output to an input / output for export. It is configured as follows.

[0073] Another aspect of the invention is a system having a processing device as described above or according to any embodiment recited in this specification or any claim of this application, and a blood pressure measurement apparatus operatively coupled to said processing device, the blood pressure measurement apparatus having a pressure applicator for use in applying a variable pressure to tissue of a body part overlying a blood vessel, and further including a tissue pressure sensor configured to sense pressure between a surface of the user's body part overlying the blood vessel and said pressure applicator.

[0074] The tissue pressure sensor may, in some embodiments, comprise a pressure sensor pad that is positioned between the pressure applicator and the body part during use.

[0075] The pressure sensor pad may comprise a fluid-filled pad, pouch, or bag fluidly coupled to a pressure transducer, which may comprise a shell structure arranged to extend annularly around a body portion of a user for reading pressure between the surface of the body and the pressure applicator. A bargain price can be provided.

[0076] In some embodiments, the shell structure of the blood pressure measurement device can have a cylindrical or broken cylindrical form. The shell structure can be comprised of a sheet of material. When attached to a body part, the sheet of material can be wrapped around the body part. The shell structure can include at least one overlap region that allows portions of the shell structure to overlap circumferentially and slide circumferentially to change the inner diameter of the shell structure's tube. For example, the shell structure can include a curled sheet of material with a circumferential discontinuity such that two circumferential ends of the shell structure can slide circumferentially relative to one another.

[0077] In some embodiments, when the blood pressure measurement device includes a shell structure, the tissue pressure sensor can have a pressure sensor pad that is positioned between the body part and the shell structure during operation, and the pressure applicator is positioned, for example, radially above the shell structure.

[0078] In some embodiments, the pressure applicator may be in the form of an inflatable bladder, although other options are possible.

[0079] These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter. [Brief explanation of the drawings]

[0080] For a better understanding of the present invention, and to show more clearly how the same may be carried into effect, reference will now be made, by way of example only, to the accompanying drawings in which: [Figure 1] FIG. 1 shows an exemplary blood pressure measurement device. [Figure 2] FIG. 2 shows the simulated parameters of the simulated blood pressure measurement. [Figure 3] FIG. 3 shows the simulated parameters of the simulated blood pressure measurement. [Figure 4]FIG. 4 shows the simulated parameters of the simulated blood pressure measurements. [Figure 5] FIG. 5 shows arterial compliance and arterial cross-sectional area as a function of arterial transmural pressure. [Figure 6] FIG. 6 shows a series of comparisons made between the true pulse waveform of a simulated patient and the candidate pulse wave signals obtained from the tissue pressure sensor at each applied pressure value. [Figure 7] FIG. 7 shows a plot of a first exemplary waveform disparity metric M1 as a function of applied pressure. [Figure 8] FIG. 8 shows a plot of a second exemplary waveform disparity metric M2 as a function of applied pressure. [Figure 9] FIG. 9 shows a plot annotated to show three distinctive features of the plot of FIG. 7, where the x values ​​correspond to a range of blood pressure values. [Figure 10] FIG. 10 shows a plot annotated to show three distinctive features of the plot of FIG. 8, where the x values ​​correspond to a range of blood pressure values. [Figure 11] FIG. 11 shows a further exemplary plot of the metric M1. [Figure 12] FIG. 12 shows a further exemplary plot of the metric M2. [Figure 13] FIG. 13 outlines the steps of any exemplary method according to one or more embodiments of the present invention. [Figure 14] FIG. 14 shows an overview of exemplary processing units and system components in accordance with one or more embodiments of the present invention. [Figure 15] FIG. 15 shows a series of signals and parameters acquired from a real patient to illustrate the proposed method according to one or more embodiments of the present invention. [Figure 16] FIG. 16 shows an exemplary plot of applied cuff pressure as a function of time for a first implementation of the method. [Figure 17]FIG. 17 shows an exemplary plot of applied cuff pressure as a function of time for a second implementation of the method. [Figure 18] FIG. 18 shows a plot of a further exemplary waveform disparity metric M3 as a function of applied pressure. [Figure 19] FIG. 19 shows a plot of a further exemplary waveform disparity metric M4 as a function of applied pressure. DETAILED DESCRIPTION OF THE INVENTION

[0081] The present invention will now be described with reference to the drawings.

[0082] While the detailed description and specific examples indicate exemplary embodiments of the devices, systems, and methods, it should be understood that they are for illustrative purposes only and are not intended to limit the scope of the invention. These and other features, aspects, and advantages of the devices, systems, and methods of the present invention will become better understood from the following description, the appended claims, and the accompanying drawings. It should be understood that the drawings are merely schematic and not drawn to scale. It should also be understood that the same reference numerals are used throughout the drawings to indicate the same or similar parts.

[0083] The present invention provides a method for deriving one or more hemodynamic parameters, including one or more measurements of blood pressure, based on obtaining a series of sample pulse wave signals at a series of applied pressures using a tissue pressure sensor integrated between a user's body and a pressure applicator, and the hemodynamic parameters are derived based on identifying characteristic points in the derived plots that indicate changes in pulse waveform morphology as a function of applied pressure.

[0084] By way of background, Figure 1 shows a schematic diagram of an exemplary cuff-based hemodynamic parameter measurement device to which embodiments of the present artifact detection method may be advantageously applied. This device may be used to detect blood pressure and / or other hemodynamic parameter measurements, such as cardiac output or stroke volume.

[0085] The figure shows a cuff attached to a patient's upper arm 10. The patient's artery 8 is shown schematically. The device has a different design from most standard cuff-based blood pressure measurement devices in that it includes a dedicated tissue pressure sensor 4 that acts to apply the cuff to the skin tissue when the cuff is inflated. The cuff includes a pneumatic actuator in the form of an inflatable bladder 2 for use in varying the pressure applied by the cuff to the body part 10. The tissue pressure sensor 4 is positioned to sense the pressure between the surface of the user's body part and the cuff. One or more operating parameters of the pneumatic actuator can be sampled independently of the tissue pressure sensor. For example, the pressure inside the inflatable bladder can be sensed. An actuator activity signal indicative of the pumping capacity level or pumping flow rate of the pneumatic actuator's pump can also be sampled.

[0086] Standard blood pressure cuffs use the air pressure in the bladder as the only measurement signal for sensing blood pressure. By further utilizing a tissue pressure sensor 4, the device shown in FIG. 1 can achieve superior quality results and enables measurement of advanced hemodynamic parameters, such as stroke volume, cardiac output, and fluid responsiveness, in addition to blood pressure. In particular, in standard pneumatic blood pressure cuffs, attenuated air is expected to destroy more than 90% of the tissue pressure pulse wave amplitude and contour. In contrast, by using a dedicated tissue pressure sensor, the design shown in FIG. 1 enables recording of high-fidelity (HiFi) arterial pressure and pulse waveforms.

[0087] The tissue pressure sensor 4 may be implemented, for example, as a fluid-filled bag or pad. This can therefore provide a conformal layer of fluid between the cuff's bladder 2 and the surface of the user's body. In this way, the integrated pneumatic actuator allows fluid coupling between the tissue pressure sensor 4 and the tissue of the upper arm. As blood pulsates in the artery, this creates pressure waves 6 that can be detected by the tissue pressure sensor 4. The tissue pressure sensor 4 can be connected to a pressure transducer via a fluid-filled tube / line. This pressure transducer converts the pressure in the fluid into an electrical signal.

[0088] The operating principle is based on coupling a pressure sensor to a body part (e.g., the arm) and transcutaneously recording tissue pressure pulse waves generated by arterial pulsations (e.g., the brachial artery). Similar to conventional pneumatic arm blood pressure cuffs, the cuff compresses the upper arm using an integrated pneumatic actuator that increases clamping pressure. However, the actual compression is achieved by narrowing the diameter of an annular rigid shell.

[0089] In the example shown in FIG. 1 , the cuff includes a shell portion 3, which is positioned between the pneumatic actuator 2 and the body portion when the cuff is attached to the body portion and surrounds the body portion when the cuff is attached. The tissue pressure sensor 4 is positioned between the shell portion 3 and the body portion when the device is attached to the body portion. The shell structure can be relatively rigid. As a result, the tissue pressure measured by the tissue pressure sensor 4 is measured against a relatively rigid support, which can prevent attenuation of the signal amplitude and shape, thereby improving measurement accuracy. In particular, when the tissue pressure sensor unit 4 is at least partially positioned between the shell portion 3 and the body portion, high accuracy of the signal measured by the tissue pressure sensor unit can be achieved. With such a configuration of the tissue pressure sensor unit, the shell structure does not absorb or attenuate the arterial pressure signal.

[0090] The shell portions 3 can include overlapping sections that can move or slide relative to one another, thereby reducing the diameter of the shell portions in response to increasing pressure applied by the pneumatic actuator.

[0091] As mentioned above, if the tissue pressure sensor uses a fluid-based sensing mechanism, the pressure transducer, which is fluidly coupled to the fluid-filled pad 4 of the pressure sensor, requires an initial calibration in which it is exposed to atmospheric pressure before measurements begin. Calibration or correction to account for hydrostatic pressure differences may also be performed.

[0092] The above-described design allows for non-invasive hemodynamic monitoring, allowing for measurement of blood pressure as well as cardiac output and other hemodynamic parameters. For more extensive details regarding this exemplary hemodynamic parameter measuring device, reference is made to European Patent Application Publication No. EP 2953528 A1, which describes the cuff design in more detail.

[0093] A blood pressure measuring device used as part of or in combination with some embodiments of the present invention may include some or all of the components of the hemodynamic parameter measuring system described in European Patent Application Publication No. EP 2953528 A1.

[0094] Embodiments of the present invention are best understood by first outlining the theoretical background underlying the inventive concept.

[0095] To illustrate this, we performed simulations of oscillometric measurements. This involved simulating the arterial pressure and volume characteristics of a virtual artery for simulation purposes, and these characteristics are shown in Figures 2-3. Figure 2 shows the simulated arterial transmural pressure (y-axis; [mmHg]) across the arterial wall as a function of the pressure applied to the artery (x-axis; [mmHg]) used for the simulation. Figure 3 shows the corresponding simulated arterial volume (y-axis; [ml]) in the virtual artery as a function of the pressure applied to the artery (x-axis; [mmHg]). This can be seen as follows:

number

[0096] In practical measurements, these volume oscillations result in pressure oscillations measured by the tissue pressure sensor 4 of the above-referenced blood pressure measuring device, i.e., a sensor located between the inflatable cuff (or other pressure applicator) and the tissue. For example, this can be achieved by a fluid-filled pad on the skin acting as a pressure sensor over the brachial artery. This measured tissue pressure signal has an AC component and a DC component. The AC component exhibits the oscillatory structure of a typical pulse in the frequency band of the arterial pulse. The DC component reflects the pressure applied to the tissue by the device, i.e., the "applied pressure" referred to in this disclosure. For this purpose, this DC component is used to represent the ramp or level component P of the tissue pressure. TPL (also called clamping pressure) and is in a frequency range lower than that of a typical arterial pulse.

[0097] An exemplary simulation of the AC component of the tissue pressure signal corresponding to the volume oscillations of FIG. 3 is shown in FIG. 4. The ramp component (P TPL ) and leaving only the AC component. In practice, the extraction of the AC component of the tissue pressure signal can be done by high-pass filtering. Thus, Figure 4 shows the relationship between the applied cuff pressure P exFigure 1 shows simulated recordings of tissue pressure signal oscillations (y-axis; [mmHg]) as a function of applied cuff pressure (x-axis; [mmHg]) increasing from 0 mmHg to values ​​above systolic blood pressure.

[0098] As an approximation, in the following discussion, the DC component of the tissue pressure signal, P TPL is the applied pressure (or external pressure) P applied to the outside of the artery by the device. ex Therefore, the transmural pressure (P T ) is thought to determine

[0099] Average applied pressure P ex Given that changes in pressure are generally slow (~2 mmHg / s) compared to changes in arterial pressure (maximum ~200 mmHg / s), the applied pressure can be assumed to be quasi-static (i.e., constant) over any given pressure pulse.

[0100] Thus, in this case, the amplitude of the volume signal is determined by the transmural pressure. As mentioned above, the change in volume is measured by the AC component of the tissue pressure signal.

[0101] Mathematically, the acquired pulse signal, which is expressed in tissue pressure signals, is determined by the arterial compliance C(P T ), and arterial compliance depends on the transmural pressure P T The transmural pressure is not constant as a function of P T =p A (t)-P ex where p A (t) is the time-dependent arterial pressure.

[0102] Therefore, from the above, The shape of the pulse wave signal measured by the tissue pressure sensor varies depending on arterial compliance; -Arterial compliance varies as a function of transmural pressure, - Transmural pressure is the applied pressure P applied to the arteryex Varies as a function of It is recognized that:

[0103] It will therefore be appreciated that the waveform morphology of the pulse wave signal measured by the tissue pressure sensor will vary as a function of the applied pressure.

[0104] Figure 5 shows the relationship between arterial compliance C (P T The x-axis shows the transmural pressure ([mmHg]) and the cross-sectional area of ​​the artery. The y-axis on the left shows the cross-sectional area ([cm 2 ]), and the right y-axis shows arterial compliance ([cm 2 / mmHg]. Line 12 represents arterial compliance. Line 14 represents cross-sectional area.

[0105] The above-mentioned compliance C(P T ) is P T is the derivative of the arterial volume with respect to

number

[0106] The change in volume is

number

[0107] Equation (3) shows that the change in volume (measured in the AC component of the tissue pressure signal) strongly depends on the characteristics of the arterial compliance C. Considering typical measurement conditions,

number

[0108] The effect of arterial compliance on the measured tissue pressure signal is given by C(P T ) behavior.

[0109] The application of the above considerations to embodiments of the present invention will now be described.

[0110] From the above considerations, the inventors have recognized at least two major implications.

[0111] The first major implication is that by looking at the simulations, it is possible to determine the specific range of transmural pressure, and therefore applied pressure P, where arterial compliance has the least effect on the morphology of the measured pulse wave signal (measured using tissue pressure sensors). ex Therefore, the inventors have recognized that by measuring the AC components of the tissue pressure signal in regions where these effects are minimal, a pulse wave signal can be obtained that most closely matches the true morphology of the patient's actual pulse waveform.

[0112] The second main implication follows from the first implication and is that the applied pressure P ex By plotting the change in pulse wave morphology as a function of pressure, it is possible to identify applied pressure values ​​at which characteristic features occur in the plot, and thereby infer important (key) blood pressure measurements.

[0113] Looking at Figure 5, refer to the area indicated by box 16. This is the area of ​​curve 12 of compliance C at high transmural pressure values. High transmural pressures correspond to low mean applied pressure P ex In this region, compliance has minimal effect because compliance is nearly constant as a function of transmural pressure. Thus, for this region of high transmural pressure and low applied pressure, the tissue pressure signal measured over the pulse period closely matches the individual's true pulse waveform signal.

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[0114] Thus, in this region of low applied pressure, the measured tissue pressure signal is proportional in shape to the arterial pressure signal.

[0115] Thus, the measured tissue pressure signal in this region of low applied pressure closely matches the patient's pulse waveform. As explained below, the inventors have further identified a quantitative range of applied pressure values ​​corresponding to region 16 in FIG. 5. This means that if one samples the tissue pressure signal in this region, the resulting waveform will be an accurate estimate of the patient's pulse waveform. This therefore leads to the first implication mentioned above.

[0116] In contrast, at pressure levels near zero transmural pressure, the compliance function C(P T ) shows a large peak that is highly dependent on the transmural pressure. This region of strong transmural pressure influence is indicated by box 18. In this region, the morphology of the measured tissue pressure waveform is strongly influenced by the transmural pressure.

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[0117] Furthermore, the compliance dependence function peaks around zero transmural pressure, which is defined as the applied pressure P ex This means that the applied pressure region where the morphology of the measured tissue pressure waveform is expected to exhibit peak morphological changes is around the region where the applied pressure is close to at least one measured value of arterial pressure. It will be appreciated that by plotting the change in morphology of the measured tissue pressure signal as a function of applied pressure and looking for certain significant features in the plot of this morphology change (e.g., a maximum, minimum, inflection, or zero crossing), it is possible to identify these particular significant blood pressure measurement values. This is therefore the second implication mentioned above. This has been investigated in more detail by the inventors, as explained further below.

[0118] The effect of arterial pressure on the morphology of the tissue pressure signal was simulated, and an exemplary sample of the results is shown in Figure 6. Each individual graph in Figure 6 shows a comparison of a respective simulated pulse waveform for a simulated arterial pressure having a systolic blood pressure value (SBP) of 123 mmHg and a diastolic blood pressure value (DBP) of 90 mmHg. Thus, all graphs correspond to the same hypothetical arterial pressure wave. However, for each graph, different applied pressure values ​​(P ex ) was simulated, and the corresponding tissue pressure signal was simulated. As a result, each graph shows a comparison of (a) the simulated AC component of the measured tissue pressure signal over a single pulse period for one of a range of values ​​of applied pressure P_ex (ranging from 0 to 150 mmHg) and (b) the simulated true pulse waveform corresponding to an arterial pressure varying between SBP=123 mmHg and DBP=90 mmHg. The x-axis represents time (seconds). The comparison is simply shown by superimposing waveform (a) on waveform (b). For illustrative purposes only, this is shown in FIG. 6.

[0119] To allow for waveform comparison, the simulated signals were normalized and scaled to the range 0001 according to the SBP and DBP values ​​mentioned above. The pulse period was assumed to be constant.

[0120] To calculate the quantification of each comparison, various options are possible.

[0121] As an example, a comparison of scaled and normalized pulse waveforms (per pulse k) is performed for pulses with a period T k =T k_end -T k_start This can be achieved by calculating the waveform disparity metric (M1) as the integral of the difference between the signals over T k is the pulse wave period for pulse k, and T k_start is the time of the start of pulse k, and T k_endis the time of the end of pulse k. As a further example, a comparison of scaled and normalized pulse waveforms (per pulse k) can be calculated using a waveform disparity metric (M2), which is equal to the integral of the square of the difference between the waveforms, again for the duration T of the pulse wave: k =T k_end -T k_start This can be achieved by calculating over These are as follows:

number

number

number

number

[0122] For the simulations performed, for each comparison, s1 corresponds to the simulated tissue pressure signal at one of the applied pressures and s2 corresponds to the simulated true pulse waveform.

[0123] In the above formula, K is the total number of pulses used to determine the disparity metric. For consecutive pulses, it is typically T k+1_start =T k_end holds true, i.e., the end of the previous pulse is the start of the next pulse. This holds true when there are no missing pulses due to false detection, for example. The simulated true pulse wave signal s2(t) ranges from 0 to T k =T k_end -T k_startIn the simplest case, each disparity metric M1 and M2 is calculated for only a single individual pulse, and therefore the summations in equations (7a), (7b) and (8a), (8b) contain only a single element. In this case, equations (7a) and (7b) are the same, and equations (8a) and (8b) are the same. Furthermore, if the duration of each pulse is scaled to a period of the same duration, e.g., 1 second, then for each individual pulse k, the difference T k_end -T k_start is equal to the period of the scaled duration, e.g., 1 second.

[0124] As a variation of the above, the M1 metric is calculated from the absolute difference between s1(t) and s2(t), i.e., (s1(t) - s 2(tT k_start )) instead of |s1(t)-s2(tT k_start Note that the σ is determined by integrating |

[0125] 7 shows an exemplary plot of the first waveform disparity metric M1 (y-axis) as a function of applied pressure (x-axis; [mmHg]), where the summation of M1 includes only a single element, i.e., K=1, and disparity is determined at each applied pressure value for only a single individual pulse. In this case, the two equations given above for M1 are combined into the same equation:

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[0126] FIG. 8 shows a plot of the second waveform disparity metric M2 (y-axis) as a function of applied pressure (x-axis; [mmHg]), where the summation of M2 contains only a single element, i.e., K=1, and disparity is determined at each applied pressure value for only a single individual pulse. In this case, the two equations given above for M2 are combined into the same equation:

number

[0127] In Figure 7, the difference between the pulses is determined directly. In Figure 8, the difference between the pulses is determined after normalizing and scaling for a more accurate comparison. Therefore, the ranges of the vertical axes in Figures 7 and 8 are different.

[0128] Vertical lines are shown on each graph indicating the position along each plot where the applied pressure (x-axis) is equal to the simulated diastolic blood pressure (DBP = 78 mmHg), mean arterial pressure (MAP = 95 mmHg), and systolic blood pressure (SBP = 120 mmHg) of the simulated artery.

[0129] It can be seen that in each graph, the points at which the applied cuff pressure (x-axis) coincides with each of these three blood pressure values ​​correspond to distinctive features of the plots of M1 (FIG. 7) and M2 (FIG. 8), respectively.

[0130] This is more clearly shown in Figures 9 and 10, which show the first (A), second (B), and third (C) features of each plot, respectively, where the first feature of each plot corresponds to an applied pressure value equal to diastolic blood pressure (DBP), the second feature of each plot (B) corresponds to an applied pressure value equal to mean arterial pressure (MAP), and the third feature of each plot (C) corresponds to an applied pressure value equal to systolic blood pressure (SBP). These features follow in order.

[0131] In the plot of M1, the feature of the plot (A) corresponding to an applied pressure equal to DBP is the first maximum of the plot, the feature of the plot (B) corresponding to an applied pressure equal to MAP is the zero crossing point of the plot, and the feature of the plot (C) corresponding to an applied pressure equal to SBP is the first inflection point of the plot after the zero crossing point.

[0132] In the plot of M2, the feature of the plot (A) corresponding to the applied pressure equal to DBP is the first maximum of the plot, the feature of the plot (B) corresponding to the applied pressure equal to MAP is the first minimum of the plot, and the feature of the plot (C) corresponding to the applied pressure equal to SBP is the last inflection point of the plot, i.e., the next inflection point after the first minimum (B).

[0133] A further observation evident from each plot is that for applied pressure values ​​below approximately 40-50 mmHg, each of the disparity metrics M1 and M2 has only a very small, approximately constant value. From this (considering the fact that the M1 and M2 plots in FIGS. 9 and 10 represent the disparity between the simulated true pulse waveform of the patient and the waveform morphology of the respective pulse waveform at a given applied pressure as measured by the tissue pressure sensor), it can be concluded that the sample pulse wave signal as measured by the tissue pressure sensor within this applied pressure range can be expected to closely match the waveform morphology of the patient's true pulse wave signal.

[0134] From the above, the inventors have realised that these technical observations can be applied in reverse to: (a) Obtain a patient's pulse waveform that closely matches the true pulse waveform morphology (i.e., an "A-shaped line-like" waveform) based on obtaining a sample pulse waveform using a tissue pressure sensor within a range of applied pressures where the waveform disparity metric is known to be low (e.g., within the range of 0-40 mmHg or 0-50 mmHg, or near point B, which corresponds to mean arterial pressure). (b) Deriving unknown values ​​of DBP, MAP, and SBP based on generating a plot of a waveform disparity metric, e.g., M1 or M2, from a sequence of sample pulse wave signals acquired at a sequence of different applied pressure values ​​measured using a tissue pressure sensor, each of which is compared to a reference pulse wave signal acquired at an applied pressure value known to have low waveform disparity (e.g., within the range of 0-40 mmHg or 0-50 mmHg, or near point B, which corresponds to mean arterial pressure).

[0135] This was tested and confirmed using a further plot of M1, labeled Plot 1 in FIG. 11. Plot 1 was generated for simulated blood pressure values ​​of DBP=61 mmHg, MBP=75 mmHg, and SBP=95 mmHg. Plot 2 in FIG. 11 shows, for comparison, a plot generated for simulated blood pressure values ​​of DBP=86 mmHg, MBP=100 mmHg, and SBP=120 mmHg. For the lower blood pressure of Plot 1, the curve is shifted to the left. For Plots 1 and 2, it can be seen that the applied pressure values ​​match the simulated DBP, MAP, and SBP values ​​at characteristic features A, B, and C of the same plots, labeled in FIG. 9.

[0136] FIG. 12 shows a further plot of M2, labeled Plot 1 in FIG. 12. Plot 1 was generated for simulated blood pressure values ​​of DBP=61 mmHg, MBP=75 mmHg, and SBP=95 mmHg. For comparison, Plot 2 in FIG. 12 shows a plot generated for simulated blood pressure values ​​of DBP=86 mmHg, MBP=100 mmHg, and SBP=120 mmHg. For the lower blood pressure of Plot 1, the curve is shifted to the left. For Plots 1 and 2, it can be seen that the applied pressure values ​​match the simulated DBP, MAP, and SBP values ​​with characteristic features A, B, and C of the same plots labeled in FIG. 10.

[0137] Our proposal is to apply these considerations in practice, allowing blood pressure values ​​to be inferred by using a tissue pressure sensor to measure a sample pulse wave signal as a function of varying applied pressure and plotting the change in waveform morphology as a function of applied pressure. Using the theoretical findings above, characteristic points in these plots can be used to infer blood pressure values.

[0138] 13 illustrates, in block diagram form, an overview of the steps of an exemplary computer-implemented method 50 according to one or more embodiments. The steps are listed in summary form before being further described in the form of an exemplary embodiment.

[0139] A method 50 is provided for use in measuring blood pressure with a blood pressure measurement device, wherein the blood pressure measurement device has a pressure applicator for use in applying a variable pressure to tissue of a body part overlying a blood vessel, and further includes a tissue pressure sensor positioned to sense pressure between a surface of the user's body part overlying the blood vessel and the pressure applicator.

[0140] The method includes using the blood pressure measurement device to acquire (52) a series of tissue pressure signals, each signal being acquired at a different applied pressure value over a sequence of incrementally increasing or decreasing applied pressure values.

[0141] The method further comprises a step (54) of deriving a candidate (or sample or pseudo) pulse wave signal from each tissue pressure signal based on extracting an AC component of each tissue pressure signal, thereby deriving a series of candidate pulse wave signals corresponding to different applied pressure values ​​across the sequence of applied pressure values.

[0142] The method further includes deriving (56) a plot showing the change in pulse waveform morphology as a function of applied pressure based on the comparative analysis applied to the waveforms of the series of candidate pulse wave signals.

[0143] The method further includes identifying (58) applied pressure values ​​that match each of a set of one or more predetermined characteristic features of the plot.

[0144] The method further includes deriving (60) one or more arterial pressure measurements for the subject based on the one or more identified applied pressure values ​​and based on a predetermined mapping or relationship between the applied pressure values ​​at which the characteristic plot features occurred and one or more arterial pressure measurements.

[0145] The method may preferably further comprise the step of generating (62) a data output indicative of the one or more arterial pressure measurements.

[0146] As mentioned above, the method may also be implemented in the form of hardware, for example in the form of a processing unit configured to perform the method according to any example or implementation described herein or according to any claim of the present application.

[0147] To further aid understanding, Figure 14 presents a schematic diagram of an exemplary processing unit 32 configured to perform methods according to one or more embodiments of the present invention. The processing unit is shown in the context of a system 30 having the processing unit. The processing unit alone represents an aspect of the present invention. The system 30 is another aspect of the present invention. A provided system need not include all of the illustrated hardware components, but may include only a subset thereof.

[0148] The processing unit 32 comprises one or more processors 36 configured to perform the methods as outlined above or according to any embodiment described herein or in any claim of the present application. In the example shown, the processing unit further comprises an input / output section 34.

[0149] 14, system 30 further includes a blood pressure measuring device 72 having a pressure applicator 74 for use in applying a variable pressure to tissue of a body portion overlying a blood vessel, and further including a tissue pressure sensor 76 configured to sense pressure between the surface of the user's body portion overlying the blood vessel and the pressure applicator. The blood pressure measuring device may include a cuff for wear by the patient, where pressure applicator 74 is in the form of a pneumatic actuator having an inflatable bladder, whereby varying the inflation level of the bladder varies the applied pressure.

[0150] In some embodiments, the system 30 further comprises a user interface (not shown) for displaying derived blood pressure values ​​and / or other values ​​or signals.

[0151] The input / output 34 may be adapted to receive the series of tissue pressure signals described above and, optionally, to externally communicate a data output indicative of one or more arterial pressure measurements. Alternatively, the tissue pressure signals may be received from a data store or from an intermediate communication device, such as a hub server or network node.

[0152] For example, the input / output 34 may accommodate wired or wireless connections to one or more external units, which may include blood pressure measuring devices.

[0153] The system 30 further includes a memory 38 for storing computer program code (i.e., computer-executable code) configured to cause one or more processors 36 of the processing unit 32 to perform the method outlined above, or according to any embodiment described in this disclosure, or according to any claim.

[0154] The blood pressure measuring device may optionally be of the type of the blood pressure measuring device detailed in European Patent Application Publication No. EP2953528A1 and described herein above.

[0155] As mentioned above, the present invention can also be implemented in software form. Thus, another aspect of the present invention is a computer program product comprising code means configured to, when executed on a processor, cause said processor to perform a method according to any example or embodiment of the invention described herein, or a method according to any claim of the present patent application.

[0156] Embodiments of the present invention are based on observations made from the simulations outlined in detail above. To test these principles in practice, the proposed method was implemented on real data acquired from real patients.

[0157] By way of example, Figure 15 shows measurement data for an exemplary patient: each graph shows a trace of the relevant quantity (y-axis) as a function of time (x-axis; seconds).

[0158] Graph (a) shows the signal output (y-axis; mmHg) from the tissue pressure (TP) sensor as a function of time as the applied pressure is increased stepwise. The baseline in graph (a) represents the applied pressure value. Graph (b) shows the extracted AC component of the tissue pressure signal of graph (a), i.e., the tissue pressure signal of graph (a) with the baseline (BL) removed. This therefore provides a candidate pulse wave signal across the patient's sequence of individual pulses. For comparison, graph (c) shows the patient's true arterial pressure, measured simultaneously with the tissue pressure signal and derived from an invasive measurement. This signal was not obtained during an actual implementation of the method of the present invention, but rather for proof-of-concept purposes. Graph (d) corresponds to the area under each pulse in normalized versions of graphs (b) and (c), i.e., a plot of the area under each pulse in signal (b) after normalization (labeled TP) and a plot of the area under each arterial pressure pulse after normalization (labeled ABP). Graph (e) shows the calculated waveform disparity metric M1 described above for each of the sequences of candidate pulse wave signals represented by the pulses in graph (b) (after normalization).

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[0159] In FIG. 15, the disparity metric M1 is observed to exhibit a zero crossing at the time when the applied pressure (represented by the baseline in graph (a)) is approximately equal to the MAP value (i.e., approximately 100 mmHg). The first maximum in M1 occurs near the time when the applied pressure is approximately equal to DBP (i.e., approximately 70 mmHg), and the inflection point in M1 occurs near the time when the applied pressure value is approximately equal to SBP (i.e., approximately 125 mmHg). Note that the first maximum and inflection point are somewhat difficult to observe in the separate graphical representations of FIG. 15 due to the use of separate scaling. For ease of reading, vertical lines have been placed along the graph at three distinct points along the plot of M1 where the applied pressure (the baseline in graph (a)) corresponds, from left to right, to the blood pressure measurements DBP, MAP, and SBP, respectively.

[0160] Applying the above technical insights as more general principles, and with reference again to the method outlined in schematic form in FIG. 13, it is proposed by one group of embodiments to perform said method as follows.

[0161] Acquiring a series of tissue pressure signals includes acquiring a baseline tissue pressure signal within a defined applied pressure range and acquiring a series of tissue pressure signals over a sequence of incrementally increasing or decreasing applied pressure values ​​outside the applied pressure range. The defined applied pressure range may be a predetermined numerical range (e.g., 0-40 mmHg or 0-50 mmHg) or may be dynamically determined based on identifying a characteristic feature or characteristic (e.g., a maximum amplitude, typically occurring near the MAP) of the tissue pressure signal occurring in accordance with the applied pressure range. This is a range known or estimated to match a measured candidate pulse wave signal that closely matches the morphology of the true pulse wave signal. The simulations described above indicate that one suitable range is, for example, 0-50 mmHg or 0-40 mmHg, which has been found to consistently produce the lowest waveform disparity (M1, M2). Another option is to define the defined applied pressure range according to a characteristic feature or characteristic of the tissue pressure signal occurring in accordance with the applied pressure range, for example, the maximum amplitude of the AC component of the tissue pressure signal. As shown above with reference to Figures 9 and 10, waveform disparity was found to be minimal (zero in Figure 9 and very small in Figure 10) at an applied pressure approximately equal to the mean arterial pressure.

[0162] Deriving a series of candidate pulse wave signals includes deriving candidate pulse wave signals from the tissue pressure signal based on extracting an AC component, and deriving a respective candidate pulse wave signal for each tissue pressure signal obtained outside the range of applied pressure.

[0163] The method may include performing a predetermined comparison procedure for each candidate pulse wave signal in the set of signals outside a predetermined range, comprising comparing a waveform morphology of the respective pulse wave signal with a waveform morphology of a reference pulse wave signal, deriving respective values ​​of waveform disparity metrics (e.g., M1, M2) for the pulse wave signal, and plotting the waveform disparity metrics as a function of applied tissue pressure, deriving the plot showing changes in pulse waveform morphology as a function of applied pressure.

[0164] The defined pressure range from which the reference tissue pressure signal is obtained may be in the range of 0 to 50 mmHg, for example, 0 to 40 mmHg (=0 to 5332 Pa), for example, 10 to 40 mmHg (=1333 to 5332 Pa).

[0165] The method may further comprise generating a data output indicative of the reference pulse wave signal, which may therefore be used as an estimated measure of the patient's true pulse wave (the "A-line" pulse wave signal).

[0166] In some embodiments, deriving each candidate pulse wave signal further comprises scaling the extracted AC component for each candidate pulse wave signal, where scaling comprises maintaining the shape / morphology of the waveform but increasing the scale of the waveform so that a maximum point of the waveform coincides with a measured SBP value and a minimum point coincides with a measured DBP value. The measured SBP and DBP values ​​may be, for example, historical values ​​measured for the patient.

[0167] In some embodiments, accuracy is improved by generating a reference tissue pressure signal based on an average of multiple tissue pressure signal pulses, all acquired at the same applied pressure value. In other words, it is generated by sampling the tissue pressure signal over multiple cardiac cycles at a constant applied pressure value and calculating the average tissue pressure signal over the multiple cardiac cycles as the reference tissue pressure signal. This increases the signal-to-noise ratio. Optionally, the amplitude and period of the pulses can be normalized before averaging to obtain a cleaner averaged pulse.

[0168] According to one set of embodiments, the waveform disparity metric may be metric M1 as described above.

[0169] Thus, here, the waveform disparity metric (M1) for a given pulse wave signal is the difference T between the respective pulse wave signal and the reference pulse wave signal over the pulse wave period of each pulse k. k=T k_end -T k_start This is calculated as the integral (for each pulse k) of

number

number

[0170] As a variation of the above, the M1 metric is calculated from the absolute difference between s1(t) and s2(t), i.e., (s1(t)-s2(tT k_start )) instead of |s1(t)-s2(tT k_start Note that the σ is determined by integrating |

[0171] If the waveform disparity metric is M1, one or more characteristic features of a plot of the waveform disparity metric can include a zero-crossing point of the plot, and deriving one or more blood pressure measurements includes deriving a value of mean arterial pressure (MAP) based on the applied pressure value at which the zero-crossing point occurs in the plot. This may be the first zero-crossing point after the first peak or maximum of the waveform / plot. See Figures 7 and 9 above and the associated discussion for an explanation of this.

[0172] If the waveform disparity metric is M1, one or more characteristic features of the plot of the waveform disparity metric can include a maximum point of the plot (e.g., a first maximum of the plot), and deriving one or more blood pressure measurements can include deriving a value of diastolic blood pressure (DBP) based on the applied pressure value at which the maximum point occurs in the plot. This referenced maximum point of the plot is the peak point of a rising edge or phase of the waveform. This is the point at which the waveform changes from a rising edge or phase to a falling edge or phase. For example, the waveform can include a first rising edge or phase that peaks at a first maximum point. The waveform changes to a first falling edge or phase at the first maximum point. At the base of the first falling edge is a turning point or inflection point where the waveform changes to a plateau. For an explanation of this, see Figures 7 and 9 above and the related discussion.

[0173] If the waveform disparity metric is M1, one or more characteristic features of the plot of the waveform disparity metric can include a first inflection point or turning point in the plot after a zero crossing, and deriving one or more blood pressure measurements includes deriving a value of systolic blood pressure (SBP) based on the applied pressure value at which the inflection point occurs in the plot. This is the point at which the waveform changes from a falling edge or phase to a plateau. See Figures 7 and 9 above and related discussion for an explanation of this.

[0174] According to at least one set of embodiments, the waveform disparity metric may additionally or alternatively be the metric M2 described above.

[0175] Thus, here, the waveform disparity metric M for a given pulse wave signal is the difference T between the respective pulse wave signal and the reference pulse wave signal over the pulse wave period of each pulse k. k =T k_end -T k_start It is calculated as the integral of the square of (per pulse k).

[0176] This is mathematically

number

number

[0177] When the waveform disparity metric is M2, one or more characteristic features of the plot of the waveform disparity metric can include a first maximum point of the plot, and deriving one or more blood pressure measurements includes deriving a value of diastolic blood pressure (DBP) based on the applied pressure value at which the first maximum point occurs in the plot. The referenced first maximum point is the peak point of the first rising edge or phase of the waveform. It may also be the point at which the waveform changes from the first rising edge or phase to the first falling edge or phase. For an explanation of this, see Figures 8 and 10 above and the related discussion.

[0178] When the waveform disparity metric is M2, one or more characteristic features of the waveform disparity metric plot can include a first minimum point after a first maximum point in the waveform disparity metric plot, and deriving one or more blood pressure measurements includes deriving a value of mean arterial pressure (MAP) based on the applied pressure value at which the minimum point occurs in the plot. The referenced first minimum point is the point in the waveform where the first falling edge or phase of the waveform changes to the second rising edge or phase of the waveform. It may also be a trough or minimum point at the base of the first falling edge or phase of the waveform. For an explanation of this, see Figures 8 and 10 above and the related discussion.

[0179] If the waveform disparity metric is M2, one or more characteristic features of the plot of this waveform disparity metric may include a turning point or inflection point after the first minimum (or the last inflection point of the plot), and deriving one or more blood pressure measurements may include deriving a value of systolic blood pressure (SBP) based on the applied pressure value at which the inflection point occurs in the plot. The referenced point may be the turning point or inflection point where the waveform changes from the second rising edge or phase of the waveform to a plateau. See Figures 8 and 10 above and the related discussion for an explanation of this.

[0180] With regard to obtaining the reference candidate pulse wave signal, this can be done at different times relative to the sequence of incrementally increasing or decreasing applied pressure values. One option is to obtain the reference candidate pulse wave signal as a separate step at the beginning of the measurement process, before beginning the sequence of incrementally increasing or decreasing applied pressure values. An appropriate applied pressure can be applied to the body part, and the reference pulse wave signal can be measured.

[0181] This is exemplarily shown in Figure 16. As shown, the method performed involves two phases: a reference applied pressure P ref The first phase is when the reference candidate pulse wave signal is measured, and the applied pressure is P ref Pressure value P above max The first phase can be understood to have a second phase in which the applied pressure is increased to T. During the second phase, each candidate pulse wave signal is measured at a series of applied pressure values ​​along an ascending slope, as described in detail above. The time period spanned by the first phase is T. ref and the time period spanned by the second phase is labeled T ramp As described above, the reference candidate pulse wave signal is measured over multiple pulse periods and averaged over the multiple pulse periods to increase the SNR.

[0182] Another option is to acquire the reference candidate pulse wave signal as part of a sequence of incrementally increasing or decreasing applied pressure values, in other words, it is acquired simply as one of a series of candidate pulse wave signals.

[0183] A further option is to obtain the reference pulse wave signal at the end of the measurement process, after the sequence of applied pressure values ​​has finished. In the latter case, the comparison procedure in which the value of the waveform disparity metric is calculated must be performed "off-line" after the measurement process has finished.

[0184] This is exemplarily shown in Figure 17. Again, this has a first phase and a second phase. However, in this embodiment, the first phase involves increasing the applied pressure from a minimum value (e.g., 0) to an upper pressure value Pmax As previously described, at each of a series of applied pressure values ​​along the ramp, a respective candidate pulse wave signal is measured. During the second phase, the baseline applied pressure P ref The reference candidate pulse wave signal is measured at T ramp and the time period spanning the second phase is labeled T ref and labeled.

[0185] Instead of metrics M1 and M2, an alternative waveform disparity metric based on comparing each acquired candidate pulse wave signal with the preceding candidate pulse wave signal can be used, which avoids the need to acquire a reference pulse wave signal as would be required to calculate M1 or M2.

[0186] Thus, according to one or more embodiments, method 50 includes, for each candidate pulse wave signal in the series of candidate pulse wave signals, performing a predetermined comparison procedure comprising comparing the waveform morphology of the respective candidate pulse wave signal with the waveform morphology of the immediately preceding candidate pulse wave signal in the series of candidate pulse wave signals to derive respective values ​​of waveform disparity metrics (M3, M4) for the pulse wave signal; and plotting the waveform disparity metrics as a function of applied pressure to derive said plot showing changes in pulse wave waveform morphology as a function of applied pressure.

[0187] According to this approach, an example of a waveform disparity metric M3 is as follows: M3 can be understood as the waveform disparity of each candidate pulse wave signal compared to the previous candidate pulse wave signal. It can be calculated as the integral of the difference of pulse wave signal k compared to pulse wave signal k-1. In effect, it corresponds to the derivative of M1 with respect to the applied pressure.

[0188] Thus, here, the waveform disparity metric (M3) for a given pulse wave signal is the difference T between each pulse wave signal and the immediately preceding pulse wave signal over the pulse wave period. k =T k_end -Tk_start It is calculated as the integral of

[0189] This is mathematically

number

number

[0190] The pulse wave signal and the immediately preceding pulse wave signal may be amplitude normalized and time scaled to improve comparison, ensuring that both pulse wave signals last an equally long time.

[0191] Additionally or alternatively, a waveform disparity metric M4 can be used, where M4 is calculated as the integral of the square of the difference of pulse wave signal k compared to pulse wave signal k-1, which is effectively the first derivative of M2 with respect to the applied pressure.

[0192] Thus, here, the waveform disparity metric M4 for a given pulse wave signal is the difference T between each pulse wave signal and the immediately preceding pulse wave signal over the pulse wave period. k =T k_end -T k_start It is calculated as the integral of the square of

[0193] This is mathematically

number

number

[0194] The pulse wave signal and the immediately preceding pulse wave signal may be amplitude normalized and time scaled to improve comparison, ensuring that both pulse wave signals last an equally long time.

[0195] FIG. 18 (top) shows an exemplary plot of the waveform disparity metric M3 (y-axis) as a function of applied pressure (x-axis; [mmHg]).

[0196] FIG. 19 (top) shows a plot of the second waveform disparity M4 (y-axis) as a function of applied pressure (x-axis; [mmHg]).

[0197] Each plot was generated based on a simulation using simulated blood pressure values: DBP=78 mmHg, MAP=95 mmHg, SBP=120 mmHg.

[0198] Vertical lines are shown on each graph indicating the position along each plot where the applied pressure (x-axis) is equal to the simulated diastolic blood pressure (DBP = 78 mmHg), mean arterial pressure (MAP = 95 mmHg), and systolic blood pressure (SBP = 120 mmHg) of the simulated artery.

[0199] It can be seen that in each graph, the points at which the applied cuff pressure (x-axis) coincides with each of these three blood pressure values ​​correspond to distinctive features of the plots of M3 and M4, respectively.

[0200] In particular, for M3 (top of Figure 18), it can be seen that the zero crossing point of the plot coincides with an applied pressure value (x-axis) equal to DBP (=78 mmHg), the first minimum point of the plot after the zero crossing point coincides with an applied pressure value equal to MAP (=95 mmHg), and the inflection point after the minimum point coincides with an applied pressure value equal to SBP (=120 mmHg).

[0201] For M4 (FIG. 19, top), it can be seen that the first minimum in the plot corresponds to an applied pressure value (x-axis) equal to DBP (=78 mmHg), the first maximum in the plot after the first minimum corresponds to an applied pressure value equal to MAP (=95 mmHg), and the inflection point after the maximum corresponds to an applied pressure value equal to systolic blood pressure (SBP). The inflection points indicate the points in the signal where the slope changes from negative to substantially flat.

[0202] Following on from the above, for M3, the characteristic features of the plot can be stated more formally as follows:

[0203] The one or more characteristic features of the plot of the waveform disparity metric (M3) can include a zero-crossing point of the plot, and deriving the one or more blood pressure measurements can include deriving a value of diastolic blood pressure (DBP) based on the applied pressure value at which the zero-crossing point occurs in the plot, which can be the first zero-crossing point after the first peak or maximum of the waveform / plot.

[0204] One or more characteristic features of the plot of the waveform disparity metric (M3) may include a first minimum in the plot after a zero-crossing point, and deriving one or more blood pressure measurements may include deriving a value of mean arterial pressure (MAP) based on the applied pressure value at which the minimum occurs in the plot. For example, the waveform may have a first rising edge that changes to a first falling edge at a peak point (first maximum). This first falling edge may include a zero-crossing point. The first falling edge may end at a trough or minimum where the waveform changes upward and becomes a second rising edge. The first minimum referred to above may be a minimum point at the base of the first falling edge of the waveform.

[0205] One or more characteristic features of the plot of the waveform disparity metric (M3) may include a first minimum point in the plot after a zero-crossing point and an inflection point after the minimum point, and deriving one or more blood pressure measurements may include deriving a systolic blood pressure (SBP) value based on the applied pressure value at which the inflection point occurs in the plot. For example, the waveform may have a first rising edge that changes to a first falling edge at a peak point (first maximum point). The first falling edge may include a zero-crossing point. The first falling edge may end at a trough or minimum point where the waveform changes upward to a second rising edge. The referenced inflection point may be a turning point or inflection point where the waveform changes from the second rising edge to a plateau.

[0206] Regarding M4, the distinctive features of the plot are as follows:

[0207] The one or more features of the waveform disparity metric (M4) plot may include a first minimum in the plot, and deriving one or more blood pressure measurements may include deriving a value of diastolic blood pressure (DBP) based on the applied pressure value at which the first minimum occurs in the plot. For example, the plot may have a first rising edge that peaks at a first maximum. The plot transitions at the first maximum into a first falling edge or phase of the plot. The first minimum referenced above may be the point where the first falling edge ends and transitions into a second rising edge or phase of the plot.

[0208] The one or more characteristic features of the plot of the waveform disparity metric (M4) may include a first maximum of the plot after the first minimum, and deriving one or more blood pressure measurements may include deriving a value of mean arterial pressure (MAP) based on the applied pressure value at which the first maximum occurs in the plot. For example, this may be a second maximum of the overall plot. For example, this may be a peak of a second rising edge or phase of the plot. For example, this may be a point at which the plot changes from a second rising edge or phase to a second falling edge or phase of the plot.

[0209] The one or more characteristic features of the plot of the waveform disparity metric (M4) may include a first maximum in the plot after the first minimum and an inflection point after the first maximum, and deriving one or more blood pressure measurements includes deriving a systolic blood pressure (SBP) value based on the applied pressure value at which the inflection point occurs in the plot. The inflection point indicates a point in the signal where the slope changes from negative to substantially flat. In other words, the referenced inflection point may be the inflection point or inflection point at which the second falling edge or phase of the plot changes to a plateau.

[0210] 18 (bottom) and 19 (bottom) also show the first derivative of the respective metric (M3 and M4) with respect to cuff pressure, which helps illustrate characteristic points with respect to the slope in the plots of M3 and M4. In some examples, a set of characteristic points is identified based on, for example, first taking the first derivative (d / dp) of the respective metric (M3 or M4) and then finding the characteristic points in the plot of this derivative. For example, both the maxima and minima of M3 or M4 are shown as zero-crossing points in the respective differentiated signals, while the zero-crossing points in M3 are shown as minima in the derivative d(M3) / dp.

[0211] The accuracy of measurements M3 and M4 can be improved by scaling the pulses in time and amplitude so that they all have a pulse duration of, say, 1 second and an amplitude of, say, 1.

[0212] It should be noted that, according to any of the methods outlined above (M1, M2, M3, M4), interpolation can be applied to the plots of each waveform disparity metric to enable more accurate identification of characteristic features of the associated plot (e.g., local maxima / minima, zero crossings, inflection points). In other words, if a characteristic feature of the associated plot occurs between two points of the plot, interpolation can be applied to identify a more accurate value of applied pressure that coincides with the characteristic feature of the plot. Interpolation can be performed, for example, using cubic spline interpolation or any other interpolation method.

[0213] According to some embodiments, the method may be extended to allow real-time tracking of blood pressure. This can be accomplished by first performing the method 50 described above to derive initial values ​​of DBP, MAP, and SBP, and also to derive measurements of a reference pulse wave signal. Additionally, a plot of M1 or M2 as a function of applied pressure can be derived and stored. At this stage, the method sets the applied cuff pressure to a fixed (constant) value P equal to one of the measured initial values ​​of DBP, MAP, and SBP. fixed The tissue pressure sensor may be used to continuously or repeatedly measure a candidate pulse wave signal s1(t). This measured signal s1(t) may then be used to calculate a value for one of the waveform disparity metrics M1 or M2 described above using a previously acquired reference pulse wave signal s2(t). The acquired M1 or M2 value may be used to find a corresponding plot point along a previously derived and stored plot of M1 or M2 versus applied pressure.

[0214] The value of M1 or M2 can be repeatedly or continuously recalculated using new measured s1 waveforms to monitor any changes in M1 or M2. In response to any detected change in M1 or M2, the pressure applied to the cuff is adjusted to maintain M1 or M2 at its original characteristic plot point along the originally derived and stored plot of M1 or M2 vs. applied pressure. Thus, a feedback loop is implemented whereby the applied pressure is automatically adjusted to maintain the value of M1 or M2 at its original characteristic plot point along the originally derived and stored plot of M1 or M2 vs. applied pressure. The applied pressure value at any given time is then used as a real-time estimate of the blood pressure value (corresponding to the characteristic plot point). As an example, suppose the applied cuff pressure is initially set to a fixed (constant) value P equal to MAP. fixed and the metric M1 is used, the applied pressure is simply continuously or iteratively adjusted to maintain M1=0, and the real-time applied pressure can be read as the real-time value of MAP.

[0215] In other words, based on the measured M1 or M2 plot, first determine a fixed (constant) applied cuff pressure value P that corresponds to a desired characteristic feature of the M1 or M2 plot that corresponds to DBP, MAP, or SBP. fixed is selected. Then, a fixed (constant) applied cuff pressure value P fixed The values ​​of M1 or M2 at 1000 Hz are continuously or iteratively calculated. If any change in the new M1 or M2 value is found, a fixed (constant) applied cuff pressure value P is applied to keep the M1 or M2 value constant at one of the desired characteristic features of the M1 or M2 plot. fixed That is, adjust the cuff pressure P fixed The value of M1 or M2 at fixed is continuously adjusted to keep the value of M1 or M2 constant at the relevant characteristic point along the plot of M1 or M2. This allows the applied cuff pressure P fixedcan be used to track one of the following blood pressure values: DBP, MAP, or SBP.

[0216] In some embodiments, tracking of either DBP, MAP, or SBP using this approach is performed for a limited period of time, after which a new complete inflation / deflation cycle is performed to obtain a new M1 or M2 plot. The limited period of time can be a predetermined amount of time, e.g., 10, 20, or 30 minutes. Alternatively, redetermining a complete M1 or M2 plot can be automatically triggered in response to DBP, MAP, or SBP changing by more than a predetermined threshold from the initial DBP, MAP, or SBP value.

[0217] According to one or more embodiments, the method includes controlling the tissue pressure cycle of the blood pressure measurement device 72 to incrementally increase or decrease the tissue pressure over a range of applied pressures to achieve a sequence of different applied pressures.

[0218] Advantageously, according to some embodiments, a plot showing the change in pulse waveform morphology as a function of applied pressure can be calculated progressively in real time as an applied pressure cycle progresses, with the applied pressure cycle terminating when all of a set of characteristic features of one or more plots are detected.

[0219] A completed applied pressure cycle means, for example, that the pressure is released and the applied pressure returns to zero or to a minimum, which has the advantage of minimizing the period of time that pressure is applied to a patient's body part (e.g., arm).

[0220] For example, referring to FIG. 9, if the method includes plotting a waveform disparity metric M1, once features A, B, and C of the plot are all detected, the applied pressure is reduced back to zero, ending the measurement cycle.

[0221] In some embodiments, the blood pressure measurement device includes a cuff for wrapping around a portion of a user's body, the cuff containing a pressure applicator, the pressure applicator being a pneumatic actuator in the form of an inflatable bladder, where a pressure application cycle includes an inflation / deflation cycle of the cuff.

[0222] The embodiments of the invention described above use one or more processing devices. This processing device can generally have a single processor or multiple processors. It may be located within a single containing device, structure, or unit, or may be distributed among several different devices, structures, or units. Thus, reference to a processing device adapted or configured to perform a particular step or task corresponds to that step or task being performed by any one or more of several processing components, either alone or in combination. Those skilled in the art will understand how such a distributed processing device can be implemented. The processing device may include a communication module or input / output for receiving data and outputting data to further components.

[0223] The one or more processors of a processing device can be implemented in various ways using software and / or hardware to perform the various functions required. The processor typically uses one or more microprocessors that are programmed using software (e.g., microcode) to perform the required functions. A processor may also be implemented as a combination of dedicated hardware to perform some functions and one or more programmed microprocessors and associated circuitry to perform other functions.

[0224] Examples of circuitry that may be used in various embodiments of the present disclosure include, but are not limited to, conventional microprocessors, application specific integrated circuits (ASICs), and field programmable gate arrays (FPGAs).

[0225] In various implementations, the processor may be associated with one or more storage media, e.g., volatile and non-volatile computer memory such as RAM, PROM, EPROM, and EEPROM. The storage media may be encoded with one or more programs that, when executed on the one or more processors and / or controllers, perform the required functions. The various storage media may be mounted within the processor or controller, or may be transportable such that the one or more programs stored on the storage media are read by the processor.

[0226] Variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, nor does it exclude a plurality of them if a plurality is not stated.

[0227] A single processor or other unit may fulfill the functions of several items recited in the claims.

[0228] The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.

[0229] The computer program may be stored / distributed on a suitable storage medium, e.g., an optical storage medium or a solid-state medium, supplied together with or as part of other hardware, but may also be distributed in other forms, e.g., via the Internet or other wired or wireless telecommunications systems.

[0230] When the term "adapted for" is used in the claims or the specification, it is meant to be similar to the term "configured to."

[0231] Any reference signs in the claims should not be construed as limiting the scope.

Claims

1. 1. A method for use in measuring blood pressure with a blood pressure measurement device, comprising: The blood pressure measurement device has a pressure applicator for use in applying a variable pressure to tissue of a body part overlying a blood vessel, and further includes a tissue pressure sensor positioned to sense pressure between a surface of the user's body part overlying the blood vessel and the pressure applicator, and the method comprises: acquiring a series of tissue pressure signals using the blood pressure measurement device, each acquired at a different applied pressure value over a sequence of incrementally increasing or decreasing applied pressure values; deriving a candidate pulse wave signal from each tissue pressure signal based on extracting an AC component of each tissue pressure signal, thereby deriving a series of candidate pulse wave signals, each candidate pulse wave signal corresponding to a different applied pressure value across the sequence of applied pressure values; deriving a plot showing the change in pulse waveform morphology as a function of applied pressure based on a comparative analysis applied to waveforms of the series of candidate pulse wave signals; identifying applied pressure values ​​that correspond to each of a set of one or more predetermined characteristic features of said plot; deriving the one or more arterial pressure measurements of the user based on one or more of the identified applied pressure values ​​and based on a predetermined mapping / relationship between the applied pressure values ​​at which characteristic features of the plot occur and one or more arterial pressure measurements; generating a data output indicative of the one or more arterial blood pressure measurements; A method comprising:

2. obtaining the series of tissue pressure signals comprises: obtaining a baseline tissue pressure signal within a defined applied pressure range; acquiring a series of tissue pressure signals over a sequence of incrementally increasing or decreasing applied pressure values ​​outside the applied pressure range; and Deriving the series of candidate pulse wave signals includes: deriving a reference candidate pulse wave signal from the reference tissue pressure signal based on extracting an AC component; deriving a respective candidate pulse wave signal for each tissue pressure signal acquired outside the applied pressure range; and The method comprises: performing a predetermined comparison procedure for each candidate pulse wave signal of the series of tissue pressure signals outside the defined applied pressure range, the comparison comprising comparing a waveform morphology of the respective pulse wave signal with a waveform morphology of the reference pulse wave signal, and deriving respective values ​​of waveform disparity metrics (M1, M2) for the pulse wave signal; plotting the waveform disparity metric as a function of applied pressure to derive a plot showing the change in pulse waveform morphology as a function of applied pressure; 2. The method of claim 1, comprising:

3. The method of claim 2 , wherein the one or more predetermined characteristic features of the plot include one or more inflection or turning points and / or zero crossing points of the waveform disparity metric plot.

4. The method of claim 2 or 3, further comprising generating a data output indicative of the reference pulse wave signal.

5. 5. A method according to any one of claims 2 to 4, wherein the defined applied pressure range from which the reference tissue pressure signal is obtained is in the range of 0 to 50 mmHg (= 0 to 6666 Pa), for example 0 to 40 mmHg (= 0 to 5332 Pa), for example 10 to 40 mmHg (= 1333 to 5332 Pa).

6. 5. The method of claim 2, wherein the defined applied pressure range is defined according to a characteristic feature or characteristic of the tissue pressure signal that occurs in accordance with the applied pressure range, the characteristic feature or characteristic being a maximum amplitude of the AC component of the tissue pressure signal.

7. 7. The method of claim 2, wherein the waveform disparity metric (M1) for a given pulse wave signal is calculated based on an integral of the difference between the respective pulse wave signal and the reference pulse wave signal over a pulse wave period.

8. the one or more characteristic features of the plot of the waveform disparity metric (M1) include zero crossing points of the plot, and deriving the one or more arterial pressure measurements comprises deriving a value of mean arterial pressure (MAP) based on the applied pressure values ​​at which the zero crossing points occur in the plot; and / or the one or more characteristic features of the plot of the waveform disparity metric (M1) include a maximum point of the plot, and deriving the one or more arterial pressure measurements comprises deriving a value of diastolic blood pressure (DBP) based on the applied pressure value at which the maximum point occurs in the plot; and / or the one or more characteristic features of the plot of the waveform disparity metric (M1) include a first inflection point of the plot after the zero crossing point, and deriving the one or more arterial pressure measurements comprises deriving a value of systolic blood pressure (SBP) based on an applied pressure value at which the inflection point occurs in the plot. The method of claim 7.

9. 7. The method of claim 2, wherein the waveform disparity metric (M2) for a given pulse wave signal is calculated based on the integral of the square of the difference between the respective pulse wave signal and the reference pulse wave signal over a pulse wave period.

10. the one or more characteristic features of the plot of the waveform disparity metric (M2) include a first maximum point in the plot, and deriving the one or more arterial pressure measurements comprises deriving a value of diastolic blood pressure (DBP) based on the applied pressure value at which the first maximum point occurs in the plot; and / or the one or more characteristic features of the plot of the waveform disparity metric (M2) include a first minimum point subsequent to the first maximum point of the plot of the waveform disparity metric, and deriving the one or more arterial pressure measurements comprises deriving a value of mean arterial pressure (MAP) based on the applied pressure value at which the minimum point occurs in the plot; and / or the one or more characteristic features of the plot of the waveform disparity metric (M2) include a last inflection point of the plot, and deriving the one or more arterial pressure measurements comprises deriving a value of systolic blood pressure (SBP) based on the applied pressure value at which the last inflection point occurs in the plot.

10. The method of claim 9.

11. The method comprises: performing a predetermined comparison procedure for each candidate pulse wave signal of the series of candidate pulse wave signals, the comparison comprising comparing a waveform morphology of the respective candidate pulse wave signal with a waveform morphology of an immediately preceding candidate pulse wave signal in the series of candidate pulse wave signals, to derive a respective value of a waveform disparity metric (M3) for the pulse wave signal; Plotting the waveform disparity metric as a function of applied pressure to derive a plot showing the change in pulse waveform morphology as a function of applied pressure; 2. The method of claim 1, comprising:

12. the one or more characteristic features of the plot of the waveform disparity metric (M3) include zero crossing points of the plot, and deriving the one or more arterial pressure measurements comprises deriving a value of diastolic blood pressure (DBP) based on the applied pressure values ​​at which the zero crossing points occur in the plot; and / or the one or more characteristic features of the plot of the waveform disparity metric (M3) include a first minimum point in the plot after the zero crossing point, and deriving the one or more arterial pressure measurements comprises deriving a value of mean arterial pressure (MAP) based on the applied pressure value at which the minimum point occurs in the plot; and / or the one or more characteristic features of the plot of the waveform disparity metric (M3) include a first minimum point in the plot after the zero crossing point and an inflection point after the minimum point, and deriving the one or more arterial pressure measurements comprises deriving a value of the systolic blood pressure (SBP) based on the applied pressure value at which the inflection point occurs in the plot. The method of claim 11.

13. the method includes controlling the pressure applied to the tissue of the blood pressure measuring device to achieve a sequence of different applied pressures, the applied pressure values ​​of which increase or decrease stepwise over a range of applied pressures; the plot showing the change in pulse waveform morphology as a function of applied pressure is calculated progressively in real time as an applied pressure cycle progresses, and the applied pressure cycle is terminated when all of a set of characteristic features of the one or more plots are detected.

13. The method according to any one of claims 1 to 12.

14. 14. The method of any one of claims 1 to 13, wherein the blood pressure measuring device includes a cuff for wrapping around a part of a user's body, the cuff containing the pressure applicator, the pressure applicator being a pneumatic actuator in the form of an inflatable bladder.

15. 15. A computer program product comprising computer program code configured, when executed on a processor operatively coupled to a blood pressure measuring device, to cause the processor to perform the method of any one of claims 1 to 14.

16. 1. A processing device for use in measuring blood pressure with a blood pressure measurement device having a pressure applicator for use in applying a variable pressure to tissue of a body part overlying a blood vessel, the blood pressure measurement device further including a tissue pressure sensor positioned to sense pressure between a surface of the user's body part overlying the blood vessel and the pressure applicator; The processing device includes: an input / output unit; one or more processors operatively coupled to said input / output section; wherein the one or more processors receiving, at the input / output section, a series of tissue pressure signals from the blood pressure measurement device, each acquired at a different applied pressure value over a sequence of incrementally increasing or decreasing applied pressure values; deriving a candidate pulse wave signal from each tissue pressure signal based on extracting an AC component of each tissue pressure signal, thereby deriving a series of candidate pulse wave signals each corresponding to a different applied pressure value across the sequence of applied pressure values; deriving a plot showing changes in pulse waveform morphology as a function of applied pressure based on the comparative analysis applied to waveforms of the series of candidate pulse wave signals; identifying applied pressure values ​​that correspond to each of a set of one or more predetermined characteristic features of said plot; Deriving one or more arterial pressure measurements for the user based on the one or more identified applied pressure values ​​and based on a predetermined mapping / relationship between applied pressure values ​​at which characteristic features of the plot occur and one or more arterial pressure measurements; and generating a data output indicative of the one or more arterial pressure measurements; 1. A processing device configured to:

17. A processing device according to claim 16; a blood pressure measuring device operably coupled to the processing device; A system having: The blood pressure measuring device has a pressure applicator for use in applying a variable pressure to tissue of a body part overlying a blood vessel, and further includes a tissue pressure sensor configured to sense pressure between a surface of the user's body part overlying the blood vessel and the pressure applicator.

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