Processor, method and computer program for determining pressure pulse dicrotic notch location

Abstract

A processor is configured to determine a dicrotic incisura location of a pulse pressure by determining at least one of an incisura determination intersection location, an incisura determination maximum location, and an incisura determination function location. The incisura determines that the intersection location is a location where a displaced tangent of the pressure pulse intersects with the pressure pulse. The incisura determination maximum position is a position where the derivative function of the pressure pulse has a maximum value. A position determination function position is determined by applying the position determination function to a characteristic of the pressure pulse. In this way, the dicrotic incisura position related to diagnosis can be determined very accurately.

Description

Technical Field

[0001] The present invention relates to a processor, a method and a computer program for determining the location of a pressure pulse dicrotic notch. The present invention also relates to an apparatus, a method and a computer program for determining a physiological parameter of a subject using the determined location of the dicrotic notch. Background Art

[0002] US 2013 / 0079657 Al discloses a method for determining respiratory information. A photoplethysmograph (PPG) signal is transformed at least in part based on a continuous wavelet transform to generate a scalogram, wherein a threshold energy level is calculated at least in part based on the scalogram. For a particular time, a scale associated with an energy level greater than the threshold but less than a maximum energy level of the scalogram is identified in the scalogram, and an estimate of respiratory rate is determined based at least in part on the scale.

[0003] The location of the dicrotic notch of the pressure pulse is a characteristic of the pressure pulse that can be very useful when attempting to determine a physiological parameter. However, it is often difficult to ensure the location of the dicrotic notch and therefore to ensure that a physiological parameter determined based on the location of the dicrotic notch is reliably and accurately determined. Summary of the Invention

[0004] It is an object of the present invention to provide a processor, a method and a computer program which allow an improved determination of the location of the pressure pulse dicrotic notch. Another object of the present invention is to provide a device, a method and a computer program which allow an improved determination of a physiological parameter of a subject using the determined location of the dicrotic notch.

[0005] In a first aspect of the present invention, a processor for determining a pressure pulse dicrotic notch position is provided, wherein the processor is configured to determine the dicrotic notch position by determining at least one of: a) a notch determination intersection position, which is a position where a shifted tangent intersects the pressure pulse, wherein the shifted tangent is determined by determining a tangent to the pressure pulse at a position of the pressure pulse where a first derivative of the pressure pulse has a minimum value, and by shifting the tangent by a shift distance in a time-increasing direction, b) a notch determination maximum position, which is a position where a derivative function has a maximum value, wherein the derivative function is determined by determining a first derivative of the pressure pulse, determining a second derivative of the pressure pulse and combining the determined first and second derivatives, and c) a notch determination function position, which is determined by determining a characteristic of the pressure pulse and applying a position determination function to the characteristic, wherein the position determination function provides a relationship between the characteristic and the notch determination function position. The position determination function preferably provides a relationship between the position of the notch determination function and a characteristic, the characteristic comprising: i) a maximum position along the pressure pulse, and ii) at least one of the following characteristics of the pressure pulse: the maximum of the pressure pulse, a first position along the pressure pulse prior to the maximum position and at which the value of the pressure pulse at the first position is a predefined first fraction of the maximum, a second position along the pressure pulse after the maximum position and at which the value of the pressure pulse at the second position is a predefined second fraction of the maximum, the maximum value of the first derivative of the pressure pulse, and the difference between the maximum systolic pressure of the pressure pulse and the pressure at the end-diastolic point of the pressure pulse. A processor configured in this manner allows for better determination of the position of the dicrotic notch.

[0006] The processor is configured to receive a pressure pulse. For example, the pressure pulse can be received from a direct measurement or a memory having stored measurement results. The pressure pulse to which the determination of at least one of the notch-determined intersection position, the notch-determined maximum position, and the notch-determined function position is applied can be a directly measured pressure pulse or a processed measured pressure pulse. The measured pressure pulse is an arterial pressure pulse measured for an artery. The measured pressure pulse can be, for example, a non-invasively measured pressure pulse or an invasively measured pressure pulse. The measured pressure pulse is preferably a pressure pulse of an indicated measured pressure signal and includes a plurality of measured pressure pulses. The minimum of the first-order derivative of the pressure pulse is preferably a global minimum of the first-order derivative of the pressure pulse.

[0007] In an example, the processor is configured to provide a shift distance such that it depends on a characteristic of the pressure pulse. The characteristic can be any characteristic related to the pressure pulse, and the shift distance can depend on one or more of the characteristics. For example, the shift distance can depend on at least one of the following: a) pulse rate (also referred to as heart rate); b) the location of a minimum of the first derivative of the pressure pulse between the maximum systolic pressure of the pressure pulse and the pressure of the pressure pulse at the end-diastolic point and / or between the time of the maximum systolic pressure of the pressure pulse and the time when the pressure pulse ends; c) the minimum of the first derivative; and d) the width of the pressure pulse at a predefined percentage of the difference between the maximum systolic pressure of the pressure pulse and the pressure of the pressure pulse at the end-diastolic point. The predefined percentage is preferably in the range of 50% to 80%. In a preferred embodiment, the predefined percentage is 66%. In an example, the width of the pressure pulse is the difference between the maximum systolic pressure of the pressure pulse and the pressure at the end-diastolic point of the pressure pulse divided by a predefined percentage of the full pulse length (i.e., pulse duration) to determine the shift distance. Specifically, the resulting ratio (which may be referred to as the pulse width ratio) may be used as input to a displacement distance function that provides the displacement distance as output. For example, the displacement distance may be calculated according to the following formula:

[0008] Displacement distance = (pulse width ratio - m) * n, (1)

[0009] Here, m and n are parameters predetermined by calibration.

[0010] Thus, the dependence of the displacement distance on one or more characteristics of the corresponding pulse can be determined during a calibration process, wherein the dependence of the displacement distance on one or more characteristics of the corresponding pulse is determined so that the determined intersection position corresponds to the position of the dicrotic notch known during this calibration process. It has been found that a dependence defining the following relationship provides good results: the higher the position of the minimum of the first derivative between the maximum systolic pressure of the pressure pulse and the pressure of the pressure pulse at the end-diastolic point, the greater the offset distance. It has also been found that a dependence defining the following relationship provides good results: the greater the pulse frequency, the smaller the displacement distance, or the displacement distance decreases with increasing pulse frequency. The displacement distance can also be constant. It has been found that a constant displacement distance can lead to a high-quality determination of the dicrotic notch position, wherein the quality of determining the dicrotic notch position can be further improved if the displacement distance depends on one or more characteristics of the pressure pulse.

[0011] The constant shift distance can be predetermined by statistically analyzing a training data set used in the calibration process, the training data set including the known dicrotic notch position, the tangent line, and therefore the shift distance required to move the tangent line so that the resulting intersection position matches the known dicrotic notch position. In an embodiment, the statistical analysis includes calculating the average of the offset distances found when performing the calibration process. In a preferred embodiment, the constant shift distance is in the range of 10 ms to 50 ms. Preferably, the constant shift distance is 20 ms.

[0012] In an example, the processor is configured to select the last intersection position in time as the notch determination intersection position if there are multiple intersection positions of the shift tangent line and the pressure pulse. It has been found that this can further improve the accuracy of determining the intersection position so that it corresponds to the position of the dicrotic notch.

[0013] Furthermore, in one example, the processor is configured to determine the notch-determined maximum position by determining whether the highest maximum value of the derivative function is greater than the second highest maximum value multiplied by a predefined factor, wherein, if this is the case, the notch-determined maximum position is the position of the highest maximum value, and if not, the notch-determined maximum position is the position of the first maximum value of the derivative function, wherein, preferably, the processor is configured to only consider maxima of the derivative function that are greater than a first predetermined derivative threshold value and / or within a provided search range. The first maximum value of the derivative function is the first (i.e., earliest) maximum value of the derivative function in time. This allows determining the notch-determined derivative position so that it corresponds more accurately to the position of the dicrotic notch of the pressure pulse.

[0014] In an example, the processor is configured to determine that a pressure pulse has an artifact if the derivative function includes at least two maxima greater than a second predefined derivative threshold (particularly within the search range), wherein the second predetermined derivative threshold is greater than the first predetermined derivative threshold. If the derivative function of the corresponding pulse includes at least two maxima greater than the first predetermined derivative threshold, the derivative function has at least two very large maxima, which would not be the case if a regular pressure pulse were present. In other words, if there are at least two very large maxima, then an artifact is likely present.

[0015] The predefined derivative threshold values ​​can be determined again in the calibration process. During the calibration process, it is known whether the corresponding training pressure pulse contains artifacts and, if the corresponding training pressure pulse does not contain artifacts, the position of the dicrotic notch is known. These threshold values ​​are determined so that training pressure pulses with artifacts are identified as well as possible, the position of the dicrotic notch corresponding as well as possible to the position of the corresponding known dicrotic notch for each corresponding training pressure pulse without artifacts. It has been found that predefined derivative threshold values ​​in the range of 0.003 to 0.070 (in particular with a value of 0.015) and in the range of 0.05 to 1.00 (in particular with a value of 0.25) provide good results, wherein these values ​​refer to the use of mmHg as pressure unit and s as time unit in the function (2) to be described below.

[0016] The processor can be configured to determine the derivative function by dividing a) a second-order derivative function that depends on the second-order derivative by b) a first-order derivative function that depends on the first-order derivative. Dividing by the first-order derivative function can avoid overweighting the derivative function in a range of positions where the first-order derivative has a relatively large negative value. By avoiding overweighting, the notch maximum position can be determined so that it better corresponds to the position of the dicrotic notch of the pressure pulse.

[0017] In a preferred embodiment, the second-order derivative function is a second-order derivative. Specifically, the derivative function can be determined according to the following formula:

[0018] f_2deri=(d 2 P / dt 2 ) / (a+(dP / dt)^b),(2)

[0019] Among them, f_2deri represents the derivative function, d 2 P / dt 2 Denotes the second derivative, dP / dt denotes the first derivative, and a and b denote predefined parameters. The parameters a and b can be predetermined during a calibration process, wherein the corresponding positions of the dicrotic notch are known for several training pressure pulses, and wherein the parameters a and b are determined so that the position of the maximum value of the second derivative determined corresponds as well as possible to the position of the known dicrotic notch. In a preferred embodiment, a is in the range of 0 to 10 and b is in the range of 1 to 2. In particular, a is 1.0 and b is 1.3. These values ​​also refer to the use of mmHg as the unit of pressure and s as the unit of time in formula (2). It has been found that by using the derivative function according to formula (2), the determined notch determines the maximum position that corresponds more accurately to the position of the dicrotic notch of the pressure pulse.

[0020] In an example, the first-order derivative is filtered using a filter (preferably a low-pass filter), wherein, in an embodiment, the filter depends on the heart rate. For example, the processor can be configured so that within a normal heart rate range of, for example, 50 to 90 beats per minute, the first-order derivative is filtered multiple times, for example three times, using a moving average filter, wherein the window width of the moving average filter is, for example, 28 milliseconds. If the actual heart rate exceeds the normal heart rate range, another filter can be used. Preferably, the filtering is performed to reduce noise, and the filter can also be constant, that is, it can also be independent of the heart rate. The derivative function can also be filtered by a constant filter or a filter that depends on the heart rate. Specifically, the derivative function can also be filtered multiple times, for example three times, using a moving average filter, wherein if the heart rate is within the normal heart rate range (e.g., 50 to 90 beats per minute), the window width of the moving average filter is, for example, 28 milliseconds; and if the heart rate is outside the normal heart rate range, another filter is used. It is also preferred that the derivative function is filtered to reduce noise.

[0021] The processor may be further configured to align the derivative function with the pressure pulse. Misalignment may occur due to filter delay, wherein the delay may be corrected by aligning the derivative function with the pressure pulse.

[0022] In an example, the processor is configured to provide a position determination function such that it provides a relationship between the position of the notch determination function and at least one of the following characteristics of the pressure pulse: a maximum value of the pressure pulse, a maximum position along the pressure pulse, a first position along the pressure pulse prior to the maximum position at which the pressure pulse has a value of a predefined first fraction of the maximum value, a second position along the pressure pulse after the maximum position at which the pressure pulse has a value of a predefined second fraction of the maximum value, a maximum value of a first derivative of the pressure pulse, and a difference between the maximum systolic pressure of the pressure pulse and the pressure at the end of diastole of the pressure pulse. Specifically, any combination of two or more of the above characteristics can be used to determine the position of the notch determination function, i.e., the notch determination function can depend on one or any combination of two or more of these characteristics. Specifically, the position of the notch determination function can be determined according to the following formula:

[0023] fp=c*t.dia.pre+d*t.max+e*t.dia.post+f*Pulse.max+

[0024] g*d(Pulse) / dt.max+h*PP+i*PR,(3)

[0025] Wherein, fp represents the determination function position, t.dia.pre represents the first position along the pressure pulse before the maximum position, and at which the value of the pressure pulse is a predefined first fraction of the maximum value, t.max represents the maximum position along the pressure pulse, t.dia.post represents the second position along the pressure pulse after the maximum position, and at which the value of the pressure pulse is a predefined second fraction of the maximum value, Pulse.max represents the maximum value of the pressure pulse, d(Pulse) / dt.max represents the maximum value of the first derivative of the pressure pulse, PP represents the difference between the maximum systolic pressure of the pressure pulse and the pressure at the end-diastolic point of the pressure pulse, and PR represents the pulse rate. In addition to the pulse rate, the pulse duration can also be used in formula (3). It has been found that if the notch determination function position fp is determined in this way, it can correspond very accurately to the position of the dicrotic notch of the pressure pulse.

[0026] Furthermore, the parameters c to i are predefined parameters that can be predetermined by calibration. Specifically, the parameters c to i used in formula (3) can be predetermined during a calibration process, during which the position of the dicrotic notch is known for several training pulses, and the parameters c to i are determined so that the corresponding notch determination function position corresponds as well as possible to the corresponding position of the dicrotic notch. A predefined first fraction of the maximum value and a predefined second fraction of the maximum value can also be determined in this way, that is, these fractions can be determined so that during the calibration process, the function position obtained corresponds as well as possible to the known dicrotic notch position. The predefined first and second fractions are preferably in the range of 70% to 95%.

[0027] In an embodiment, the processor is configured to determine the position of the dicrotic notch only within a provided search range. Specifically, the above-mentioned determination process for determining the notch determination intersection position, the notch determination maximum position and / or the notch determination function position is only applicable within the search range. In an example, the search range can be predetermined based on statistical analysis. Specifically, for a large group of training pressure pulses with known dicrotic notch positions, the average position and standard deviation of the dicrotic notch positions can be determined and used to determine the search range. For example, the center of the search range can be defined by the average value, and the width of the search range can be defined by the standard deviation.

[0028] Preferably, the processor is configured to provide a search range defined by: a) first and second percentages of the difference PP between the maximum systolic pressure of the pressure pulse and the pressure at the end of diastole of the pressure pulse, and / or b) first and second percentages of the pulse duration. For example, the start and end points of the search range may be defined based on a) first and second percentages of the difference PP between the maximum systolic pressure of the pressure pulse and the pressure at the end of diastole of the pressure pulse, and / or b) first and second percentages of the pulse duration. If multiple start points and / or multiple end points are determined, the search range is defined by the latest start point and / or earliest end point, respectively. One or more percentages may be static, i.e., have a predetermined constant value, and / or one or more percentages may be dynamic, i.e., dependent on the corresponding pulse or pulse rate. For example, the start point may be defined by a static first percentage of the pulse duration, e.g., 18% of the pulse duration, and may be defined by a static first percentage of the difference between the maximum systolic pressure of the pressure pulse and the pressure at the end of diastole of the pressure pulse, e.g., 75% of the difference. The endpoint can be defined by a static second percentage of the pulse duration, for example, 65% of the pulse duration, by a static second percentage of the difference between the maximum systolic pressure of the pressure pulse and the pressure of the pressure pulse at the end of diastole, for example, 9% of said difference, and by a dynamic percentage of the pulse duration, wherein the dynamic percentage depends on the pulse rate.

[0029] These percentages are also predefined through calibration, i.e., during a training phase, by analyzing training pressure pulses with known dicrotic notches. The percentages can be determined to ensure sufficient presence of the dicrotic notch so that it can be reliably detected. During the calibration process, the presence of the dicrotic notch is determined for a number of training pressure pulses, allowing its location to be determined. This determination can be performed manually, for example, by an experienced physician or technician. The value range is then determined during this calibration process by determining the range in which training pulses with a detectable dicrotic notch appearance fall relative to the corresponding difference PP. Studies have found that a static first percentage of the difference between the maximum systolic pressure of the pressure pulse and the pressure at the end of diastole of the pressure pulse in the range of 75% to 85%, and a static second percentage of this difference in the range of 5% to 15%, further improves dicrotic notch detection. Searching for the dicrotic notch location within the search range can be achieved by, for example, only determining the dicrotic notch if the pressure pulse is located within the search range at a location where the first derivative of the pressure pulse has a minimum value. This ensures that the processor does not determine an unreliable asserted dicrotic notch location for a pressure pulse where the dicrotic notch location cannot actually be determined. This further increases the reliability of determining the dicrotic notch location.

[0030] Another aspect of the present invention provides an apparatus for determining a physiological parameter of a subject, wherein the apparatus comprises:

[0031] a pressure signal providing unit configured to provide a measured pressure signal of the subject over a period of time, wherein the measured pressure signal is indicative of blood pulsation and comprises a plurality of pressure pulses,

[0032] a processor for determining a corresponding dicrotic notch position for a corresponding pressure pulse in a plurality of pressure pulses, as claimed in any one of claims 1 to 9,

[0033] Wherein, the processor is further configured to determine a physiological parameter based on the dicrotic notch locations determined for the plurality of pressure pulses.

[0034] As described above, the processor can determine the corresponding dicrotic notch position directly based on the corresponding measured pressure pulse or based on the corresponding processed measured pressure pulse. If the dicrotic notch position is determined based on the processed measured pressure pulse, it is preferably processed by the processor. However, it is also possible that it is at least partially performed by the pressure signal providing unit.

[0035] The pressure signal providing unit may be a receiving unit configured to receive a measured pressure signal from, for example, a measuring device and to provide the received pressure signal. However, the pressure signal providing unit may also be a memory in which previously measured pressure signals are stored and from which the pressure signal can be retrieved. The pressure signal providing unit may also be or include a measuring device that measures the pressure signal.

[0036] In an example, the pressure signal providing unit is configured to provide a pressure signal measured using a measuring device as the pressure signal, the measuring device comprising: a) a housing configured to enclose a portion of an object through which blood flows; b) a pressure applicator configured to apply pressure to the housing and thereby to the enclosed portion of the object; and c) a pressure sensor configured to measure the pressure signal on the skin of the enclosed portion of the object, wherein the pressure applicator increases or decreases the applied pressure while measuring the pressure signal. Thus, the pressure signal can be a non-invasively measured pressure signal, wherein, despite this, the physiological parameter can still be determined with high quality. However, as described above, the pressure signal providing unit can also be configured to provide an invasively measured pressure signal.

[0037] If the pressure pulse has been measured non-invasively, the processor is preferably configured to determine the dicrotic notch position by determining the notch determination function position.It has been found that, particularly in case of a non-invasively measured pressure pulse, the notch determination function position corresponds well to the dicrotic notch position.

[0038] Furthermore, in a preferred embodiment, if a pressure pulse is non-invasively measured on the skin of the wrapped portion of the subject using a pressure sensor while the pressure applicator increases or decreases the applied pressure, then preferably only the pressure pulse is used to determine the dicrotic notch location, wherein the pressure pulse is measured when the mean measured pressure (which can also be considered as mean tissue pressure since it is measured on the skin of the subject's tissue) is below the systolic arterial blood pressure (SAP) and above the diastolic arterial blood pressure (DAP) by a predefined percentage. Preferably, the predefined percentage is in the range of 85% to 95%, and particularly preferably, the predefined percentage is 90%. The SAP and DAP values ​​here can be the results of a previous blood pressure measurement.

[0039] The processor may be configured to determine an area ratio TPA1.top / TPA2.top based on partial areas TPA1.top and TPA2.top below the pressure pulse curve. To determine partial areas TPA1.top and TPA2.top, a partial area TPA.top located below the corresponding pressure pulse (i.e., below the corresponding pressure pulse curve) is formed, which is the area of ​​the corresponding pressure pulse curve that is above a predefined percentage of the difference TPP between the maximum and minimum values ​​of the corresponding pressure pulse curve. This corresponds to the area of ​​the corresponding pressure pulse curve above a horizontal line arranged along the predefined percentage of the difference TPP. The predefined percentage is preferably in the range of 30% to 90%, and more preferably, is 50%. A vertical line is then arranged so that it passes through the vertex, i.e., the maximum value, of the corresponding pressure pulse curve. In addition, two straight lines are added, wherein the first of the two straight lines connects the vertex with the first of the intersection points of the horizontal line and the corresponding pressure pulse curve, and the second of the two straight lines connects the vertex with the second of the intersection points of the horizontal line and the corresponding pressure pulse curve. The first straight line, together with the horizontal and vertical lines, encloses the first partial area TPA1.top, and the second straight line, together with the horizontal and vertical lines, encloses the second partial area TPA2.top. These partial areas TPA1.top and TPA2.top are also Figure 6 A and described on page 19, line 36 to page 20, line 8 of WO 2018 / 210931 A1, which is incorporated herein by reference.

[0040] In an embodiment, the processor is configured to determine a moving average of the area ratios TPA1.top / TPA2.top over a predetermined number of pressure pulses. Then, for each corresponding pressure pulse, the difference between the moving average of the area ratios TPA1.top / TPA2.top and the corresponding area ratios TPA1.top / TPA2.top of the corresponding pressure pulse is calculated. Based on the obtained difference, a standard deviation function of the pressure pulse is calculated. The corresponding standard deviation function (TPA1.top / TPA2.top).sd is Figure 6 B and described in WO 2018 / 210931 A1, pages 9, lines 19 to 26, and 20, lines 10 to 23, which are incorporated herein by reference as described above. The processor can be configured to determine the location of the dicrotic notch using only the pressure pulse, which is measured before the standard deviation function reaches a maximum value.

[0041] In the example where the measuring device includes a housing, a pressure applicator, and a pressure sensor, the pressure sensor may be disposed within the housing. However, the pressure sensor may also be disposed in another manner to measure the pressure on the skin of the subject being wrapped. For example, a fluid-filled pressure sensor pad may be disposed within the housing and connected to a pressure sensor outside the housing via a fluid path (i.e., via a fluid-filled conduit) to measure the pressure on the skin of the subject being wrapped.

[0042] The processor can be configured to determine a physiological parameter determination value based on the determined dicrotic notch position for the corresponding pressure pulse, so that several physiological parameter determination values ​​are determined for several pressure pulses occurring at different times, wherein a physiological parameter determination curve is formed for several pressure pulses and therefore for several physiological parameter determination values ​​at several times, and the physiological parameter is determined based on the physiological parameter determination curve.

[0043] The processor can be configured to determine, for the respective pressure pulse, at least one feature that depends on the determined dicrotic notch location, and to determine the respective physiological parameter determination value based on the at least one determined feature, in particular without having to determine the respective physiological parameter determination value based on other features that characterize the respective pressure pulse and are independent of the determined dicrotic notch location. However, the processor can also be configured to determine, for the respective pressure pulse, at least one additional feature that characterizes the respective pressure pulse and is not necessarily dependent on the dicrotic notch location, and to further determine the physiological parameter based on the at least one additional feature. Specifically, the processor can be configured to determine, for the respective pressure pulse, the physiological parameter determination value based on several features, at least one of which is based on the determined dicrotic notch location, and at least one additional feature that also characterizes the respective pressure pulse, but is not necessarily based on the dicrotic notch location, such that for several pressure pulses occurring at different times, several physiological parameter determination values ​​are determined, wherein the several physiological parameter determination values ​​determined for the several pressure pulses, and therefore at different times, form the physiological parameter determination curve. As described above, the processor can be configured to determine the physiological parameter based on the physiological parameter determination curve.

[0044] The processor may be adapted to process several physiological parameter determination values ​​obtained for several pressure pulses to obtain a continuous physiological parameter determination curve. For example, interpolation may be applied and optionally also smoothing may be applied.

[0045] In an example, to determine a corresponding physiological parameter determination value for a corresponding pressure pulse, the processor is configured to determine at least one of the following: a) an area below the corresponding pressure pulse between i) a first location (which is a starting location where the corresponding pressure pulse begins, or a location between the starting location and a determined dicrotic notch location) and ii) the determined dicrotic notch location, and b) a difference between the first location and the dicrotic notch location. It has been found that by using at least one of these features, namely the aforementioned area and / or the aforementioned difference, the determination of the physiological parameter (particularly the respiratory rate) can be further improved.

[0046] In an example, the processor is configured to determine the respiratory rate as the physiological parameter based on a determined physiological parameter determination curve, for example, by determining the frequency of the physiological parameter determination curve, in particular if the physiological parameter determination curve has been determined based on at least one of the area and difference features described in the previous paragraph.

[0047] In an example, the processor is configured to determine, for a corresponding pressure pulse, at least one of the following features as at least one additional feature that characterizes the corresponding pressure pulse and does not necessarily depend on the location of the dicrotic notch: i) a difference between the maximum systolic pressure of the pressure pulse and the pressure of the pressure pulse at the end-diastolic point, ii) an area enclosed by an upper portion of the pressure pulse, wherein a) an upper end of the upper portion is located at the maximum systolic pressure of the pressure pulse and b) a lower end of the upper portion is located between the maximum systolic pressure of the pressure pulse and a pressure value corresponding to a pressure average, iii) a duration of the corresponding pressure pulse, iv) an area of ​​the corresponding pressure pulse, and v) a half-peak width of the corresponding pressure pulse. It has been found that by using at least one of these additional features, the determination of the physiological parameter can be further improved.

[0048] As explained above, the corresponding pressure pulse for which the dicrotic notch is to be determined can be a directly measured pressure pulse or a processed measured pressure pulse, wherein the measured pressure pulse can be one of multiple pressure pulses in the measured pressure signal. For example, the corresponding pressure pulse can be processed by subtracting the average measured pressure from the corresponding pressure pulse. However, the pressure pulse can also be processed in another manner. Furthermore, the physiological parameter determination value, in particular, the characteristic characterizing the corresponding pressure pulse, can be determined directly using the measured pressure pulse or using the processed measured pressure pulse.

[0049] The difference between the maximum systolic pressure of a pressure pulse and the pressure at the end-diastolic point of the pressure pulse is preferably the difference between the maximum and minimum measured pressures of the corresponding pressure pulse. The duration of the corresponding pressure pulse preferably corresponds to the time difference between the end-diastolic point and the subsequent end-diastolic point of the corresponding pressure pulse. The half-peak width corresponds to the width at 50% of the difference between the maximum and minimum pressures of the corresponding pressure pulse. Therefore, it is the width at 50% of the difference between the pressure of the pressure pulse at the maximum systolic point and the pressure of the pressure pulse at the end-diastolic point.

[0050] In an example, the processor is configured to determine the position of a maximum of a physiological parameter determination curve and to determine the physiological parameter, in particular blood pressure, based on the determined position and the measured pressure. Specifically, the processor can be configured to determine the blood pressure based on an average value of the pressure measured at the determined maximum position. Determining the physiological parameter based on the determined maximum of the physiological parameter determination curve and depending on, for example, the measured pressure on the skin (i.e., depending on, for example, the tissue pressure) allows for further improving the accuracy of determining the physiological parameter.

[0051] Preferably, the processor is configured to provide a function that receives as input at least one characteristic of the respective pressure pulse (including a characteristic that depends on the location of the dicrotic notch) and outputs a corresponding physiological parameter determination value, which together with the physiological parameter determination values ​​determined for the other pressure pulses forms a physiological parameter determination curve. The function has at least one calibration parameter that can be determined by calibration, wherein a reference physiological parameter is measured very accurately and the at least one calibration parameter is determined such that the device produces a very accurately measured physiological parameter with high statistical precision and accuracy. It should be noted that calibration is preferably performed only during the development phase, i.e. not during actual physiological parameter measurements.

[0052] In another aspect, a method for determining a pressure pulse dicrotic notch location is provided, wherein the dicrotic notch location is determined by a processor by determining at least one of:

[0053] a) determining an intersection position, which is a position where a shift tangent line intersects a pressure pulse, wherein the shift tangent line is determined by determining a tangent line of the pressure pulse at a position where a first derivative of the pressure pulse has a minimum value and shifting the tangent line by a shift distance in a time-increasing direction,

[0054] b) notching a maximum position, which is the position where the derivative function has a maximum value, wherein the derivative function is determined by determining the first derivative of the pressure pulse, determining the second derivative of the pressure pulse, and combining the determined first and second derivatives, and

[0055] c) a notch determination function position determined by determining a characteristic of the pressure pulse and applying a position determination function to the characteristic, wherein the position determination function provides a relationship between the characteristic and the notch determination function position. The position determination function preferably provides a relationship between the notch determination function position and the characteristic, comprising: i) a maximum position along the pressure pulse and ii) at least one of the following characteristics of the pressure pulse: the maximum value of the pressure pulse, a first position along the pressure pulse before the maximum position and at which the value of the pressure pulse at the first position is a predefined first fraction of the maximum value, a second position along the pressure pulse after the maximum position and at which the value of the pressure pulse at the second position is a predefined second fraction of the maximum value, a maximum value of the first derivative of the pressure pulse, and a difference between the maximum systolic pressure of the pressure pulse and the pressure at the end-diastolic point of the pressure pulse.

[0056] In another aspect, the present invention provides a method for determining a physiological parameter of a subject, wherein the method comprises:

[0057] providing a pressure signal of the subject over a period of time by a pressure signal providing unit, wherein the pressure signal indicates blood pulsation and includes a plurality of pressure pulses,

[0058] For a corresponding pressure pulse among the plurality of pressure pulses, the processor determines a corresponding dicrotic notch position according to claim 11,

[0059] The processor further determines the physiological parameter based on dicrotic notch locations determined for the plurality of pressure pulses.

[0060] In another aspect of the present invention, a computer program for determining the location of a pressure pulse dicrotic notch is proposed, wherein the computer program comprises program code means for causing a processor according to any one of claims 1 to 8 to perform the steps of the method according to claim 11.

[0061] In one aspect of the present invention, a computer program for determining a physiological parameter of an object is proposed, wherein the computer program comprises program code means for causing the apparatus for determining a physiological parameter as claimed in claim 9 to perform the steps of the method as claimed in claim 12 .

[0062] The device, the method and the computer program for determining a physiological parameter can be adapted to determine the physiological parameter continuously, ie performing several consecutive physiological parameter measurements, or to determine the physiological parameter discontinuously, ie for example once.

[0063] It shall be understood that the processor arrangement according to claim 1, the apparatus according to claim 9, the methods according to claims 11 and 12 and the computer program according to claim 14 have similar and / or identical preferred embodiments, in particular as defined in the dependent claims.

[0064] It shall be understood that a preferred embodiment of the present invention may also be any combination of the dependent claims or the above-mentioned embodiments with the corresponding independent claim.

[0065] These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter. BRIEF DESCRIPTION OF THE DRAWINGS

[0066] In the following figures:

[0067] Figure 1 Schematically and exemplarily shown are embodiments of an apparatus for determining a physiological parameter of a subject with a pressure cuff of the measuring device in an inflated state, the apparatus comprising a measuring device,

[0068] Figure 2 Schematically and exemplarily, the housing of the measuring device is shown enclosing the upper arm of the subject,

[0069] Figure 3 The device is shown schematically and exemplarily in the case of a deflated pressure cuff,

[0070] Figure 4 Schematically and exemplarily shown are the measured tissue pressure and further values ​​derived from the tissue pressure measurement,

[0071] Figure 5 Schematically and exemplarily illustrating the determination of the dicrotic notch position, which is the intersection position of the displacement tangent and the corresponding pressure pulse,

[0072] Figure 6 Schematically and exemplarily shows the determination of the dicrotic notch position, which is the maximum position of the second derivative, ie the position where the second derivative of the corresponding pressure pulse has a maximum,

[0073] Figure 7 The determination of the search range is schematically and exemplarily illustrated,

[0074] Figure 8 Schematically and exemplarily depicts the determination of the dicrotic notch position as a function of position,

[0075] Figure 9 illustrates the calculation of different features of the pressure pulse for the measured tissue pressure as a function of the determined dicrotic notch position,

[0076] Figures 10 to 13 illustrates the calculation of different additional features of the pressure pulse for the measured tissue pressure, and

[0077] Figure 14 A flow chart exemplarily illustrating an embodiment of a method for determining a physiological parameter of a subject is shown. DETAILED DESCRIPTION

[0078] Figure 1 Schematically and exemplarily, an apparatus 1 for determining a physiological parameter of a subject is shown. The apparatus 1 comprises a housing 4, such as Figure 2 As shown, the housing 4 is configured to surround a portion 5 of the subject through which blood flows. In this embodiment, the portion 5 of the subject is the subject's arm, wherein Figure 2The brachial artery 11 in the arm 5 is shown; the arrow in the brachial artery 11 indicates the direction of blood flow away from the heart. The device 1 also includes a pressure sensor 7, which is arranged inside the housing 4 and is configured to measure the pressure on the external skin of the wrapped subject's arm 5. The measured pressure can also be regarded as tissue pressure (TP). Figure 2 As indicated in FIG, the pulse wave in the brachial artery 11 causes a pressure wave 12 which is transmitted via the tissue of the arm 5 to the pressure sensor 7. For clarity, Figure 1 The housing 4 is not shown.

[0079] The device 1 further comprises a cuff 6 which surrounds the housing 4 and can be inflated using a pump 8 to apply pressure to the housing 4 from outside the housing 4 and thereby to the subject's wrapped arm 5. Since the cuff 6 and the pump 8 together enable pressure to be applied to the housing 4 and thereby to the subject's wrapped arm 5, they can be considered to form pressure applicators 6, 8. Furthermore, the housing 4, the pressure applicators 6, 8 and the pressure sensor 7 can be considered to be part of a measuring device controlled by the processor 3. The housing 4 with the cuff 6 is preferably an anti-kink housing cuff, as described in WO 2014 / 121945 A1.

[0080] Processor 3 is configured to control the measurement device so that pressure applicators 6 and 8 increase the applied pressure during a measurement period that lasts until the measurement end time point, and decrease the applied pressure during a subsequent post-physiological parameter measurement period, and pressure sensor 7 measures the pressure on the skin, i.e., tissue pressure TP, at least during the measurement period. Furthermore, processor 3 is configured to control pressure applicators 6 and 8 so that they increase the applied pressure at a first rate during the pre-measurement period and then increase the applied pressure at a second rate during the measurement period, wherein the first rate is greater than the second rate. Figure 1 The control of the measuring device is illustrated in , so that the cuff 6 is inflated and the applied pressure thereby increases, ie the bold arrow indicates the inflation situation.

[0081] The device 1 includes a valve 20 which, when opened, allows compressed air within the system to escape into the surrounding atmosphere, thereby deflation of the cuff. Figure 3 In FIG, this deflation situation with the pump 8 switched off is indicated by a thick arrow.

[0082] The processor 3 may be considered to comprise a control portion 10 for controlling the pump 8 and valve 20 and a processing portion 11 specifically configured to perform some calculations as will be explained further below. The apparatus 1 may also comprise a display 22 for displaying the determined physiological parameters.

[0083] During the pre-measurement period (which can also be considered a fast inflation period), the processor 3 controls the device 1 so that the valve 20 is closed and the pump 8 inflates the cuff 6 at a first, higher rate. During the subsequent measurement period, the processor 3 also controls the device 1 so that the valve 20 is closed, but controls the pump 8 so that the cuff 6 continues to be inflated at a second, lower rate. Therefore, the measurement period can also be considered a slow inflation period.

[0084] Figure 4 The relationship between the measured pressure TP and the time t is shown schematically and exemplarily. In the pre-measurement time period, the first inflation starts with a tissue pressure TP, which is the attachment pressure Patt, i.e. the tissue pressure measured in the uninflated cuff 6. This attachment pressure Patt can range, for example, from 0 to 15 mmHg. It has been shown that an attachment pressure Patt of up to 15 mmHg does not lead to venous congestion for a duration of more than 12 hours, making the assembly of the housing 4 and the cuff 6 most suitable for long-term monitoring. Therefore, preferably, the attachment pressure Patt is not greater than 15 mmHg. Figure 4 In FIG. 1 , arrow 30 indicates the start of the pre-measurement period, i.e., the start of the rapid inflation period. During this pre-measurement period, the portion of the entire tissue pressure range where there is no or substantially no information for determining blood pressure should be passed through as quickly as possible. Therefore, during the pre-measurement period, the inflation rate is preferably as high as possible. For example, the inflation rate relative to the tissue pressure TP may be equal to or greater than 8 mmHg / s. This pre-measurement period with the rapid inflation rate ends at Figure 4 The tissue pressure value indicated by "TPlow" in the figure.

[0085] The tissue pressure value TPlow also indicates the start of a measurement period having a second, slower inflation rate. Figure 4 , the start of the measurement time period (which may also be regarded as a slow inflation period) is indicated by arrow 31 .

[0086] exist Figure 4 , time interval 40 indicates the inflation-deflation period from the start of rapid inflation 30 until the tissue pressure TP drops below 20 mmHg during rapid deflation to allow venous return. Time interval 41 indicates the cycle time, which is the time between the start of one measurement and the start of the next measurement, and time interval 42 indicates the interval time, which is the difference between the inflation-deflation period 40 and the cycle time 41.

[0087] Figure 4Also illustrated is a mean pressure TPcl, which can be viewed as the tissue clamping pressure affecting the tissue when the cuff 6 is attached to the subject's arm 5 (e.g., upper arm). The mean pressure TPcl can be calculated by applying a low-pass filter to the tissue pressure TP, wherein the low-pass filter can be located within the processor 3. The processor 3 is preferably configured to determine the component of change in tissue pressure TPac by subtracting the mean pressure TPcl from the measured tissue pressure TP, i.e., TPac=TP-TPcl. Figure 4 In FIG, the TPac curve is shown magnified 2 times to improve the visibility of the curve.

[0088] During slow inflation, i.e. during the measurement period, a TP pulse curve and / or a TPac pulse curve is recorded, which can be analyzed simultaneously (i.e. online), wherein the TP pulse curve and / or the TPac pulse curve has a tissue pressure waveform (TPW) containing information allowing accurate determination of physiological parameters.

[0089] An important characteristic of the pressure pulse (i.e., the TP pulse curve and the TPac pulse curve) is the location of the dicrotic notch. Figure 5 、 6 As explained in Figures 1 and 7, the processor 3 is configured to determine the position of the dicrotic notch. Specifically, the processor is configured to determine the dicrotic notch position by determining at least one of the following: a) a notch determination intersection position, which is the position where the shifted tangent line 52 intersects the pressure pulse, wherein the shifted tangent line 52 is determined by determining a tangent line 51 of the pressure pulse at the position of the pressure pulse where the first derivative of the pressure pulse has a minimum value and shifting the tangent line 51 in a time-increasing direction by a shift distance t.shift, b) a notch determination maximum position, which is the position where the derivative function f_2deri has a maximum value, wherein the derivative function is determined by determining a first derivative of the pressure pulse, determining a second derivative of the pressure pulse and combining the determined first and second derivatives, and c) a notch determination function position, which is determined by determining a characteristic of the pressure pulse and applying a position determination function to the characteristic, wherein the position determination function provides a relationship between the characteristic and the notch determination function position.

[0090] The processor 3 can be configured to determine one, two, or all of the notch-determined intersection position, the notch-determined maximum position, and the notch-determined function position. If the processor 3 determines two or three of the notch-determined intersection position, the notch-determined maximum position, and the notch-determined function position, the processor can be configured to combine the different positions to obtain a combined position corresponding to the dicrotic notch position. For example, the different positions can be averaged to determine the position of the dicrotic notch.

[0091] For example, before determining the notch intersection location, processor 3 preferably checks whether the pressure pulse has a value at the location where the first derivative of the pressure pulse has a minimum value, and the location is within a search range defined by a first and a second percentage of the difference PP between the maximum systolic pressure of the pressure pulse and the pressure at the end-diastolic point of the pressure pulse. This search range may also be referred to as a first search range. Preferably, the static first percentage of the difference PP is in the range of 75% to 85%, and the static second percentage of the difference PP is in the range of 5% to 15%. For example, this search range may be from 75% of PP to 10% of PP.

[0092] If the pressure pulse has a value at a position where the first derivative of the pressure pulse has a minimum value, said position being within a predetermined search range depending on the difference PP, the processor 3 determines a tangent line 51 along the position where the first derivative of the corresponding pulse 50 has a minimum value. Figure 5 As shown in FIG, the tangent line 51 is shifted by a shift distance t.shift, wherein the intersection position of the shifted tangent line 52 and the pulse 50 corresponds to the dicrotic notch position t.notch. Figure 5 In FIG, the shift is rightward because the direction of increase of time is from left to right in the figure. If there are multiple intersections of the shift tangent line 52 and the pressure pulse, the processor 3 preferably selects the last intersection position in time as the intersection position for determining the dicrotic notch position.

[0093] Processor 3 can be configured to provide the shift distance t.shift such that it depends on a characteristic of the corresponding pressure pulse 50. The characteristic can be any characteristic related to the pressure pulse, and the shift distance can depend on one or more of the characteristics. For example, the shift distance can depend on at least one of the following: a) pulse rate (PR) (also known as heart rate); b) the location of the minimum of the first derivative of the pressure pulse between the maximum systolic pressure of the pressure pulse and the pressure of the pressure pulse at the end-diastolic point and / or between the time of the maximum systolic pressure of the pressure pulse and the time when the pressure pulse ends; c) the minimum of the first derivative; and d) the width of the pressure pulse at a predefined percentage of the difference in width PP. The predefined percentage is preferably in the range of 50% to 80%. In a preferred embodiment, the predefined percentage is 66%. In an example, the width of the pressure pulse is the difference between the maximum systolic pressure of the pressure pulse and the pressure at the end-diastolic point of the pressure pulse divided by a predefined percentage of the full pulse length (i.e., pulse duration) to determine the shift distance. However, the processor 3 may also be configured to provide a constant or static shift distance t.shift, ie for example a shift distance t.shift which is independent of any characteristics of the pressure pulse 50 .

[0094] Figure 5Also shown are the position t.start where the pressure pulse 50 begins and the difference LVET (left ventricular ejection time) between the starting position t.start and the determined intersection position (corresponding to the position of the dicrotic notch t.notch).

[0095] Furthermore, before determining the notch-determined maximum position, processor 3 preferentially checks whether the pressure pulse has a value at a location where the first derivative of the pressure pulse has a minimum value, and this location is within the aforementioned search range defined by the percentage of the difference PP between the maximum systolic pressure of the pressure pulse and the pressure at the end-diastolic point of the pressure pulse. If this is the case, the notch-determined maximum position is determined. Otherwise, the notch-determined maximum position for the pressure pulse cannot be determined, and the process proceeds to the next pressure pulse in the pressure signal.

[0096] In order to determine the position of the maximum value of the notch, the processor 3 can be configured to calculate the position where the derivative function has a maximum value, wherein the derivative function is determined by determining the first-order derivative of the pressure pulse, determining the second-order derivative of the pressure pulse, and combining the determined first-order derivative and second-order derivative. The first-order derivative can be filtered to reduce noise. In particular, different noise reduction filters can be used depending on which heart rate range the actual heart rate is in. In an embodiment, if the heart rate is in the normal heart rate range of 50 to 90 beats per minute, the filter can be a moving average filter, wherein, for example, a filter with a width of 28ms or with other widths can be applied several times, for example three times. The filtered first-order derivative 1st_deriv is in Figure 6 An exemplary diagram is shown in FIG.

[0097] The processor 3 may also be configured to determine a derivative function by dividing a) a second-order derivative function that depends on the second-order derivative by b) a first-order derivative function that depends on the first-order derivative. Preferably, the second-order derivative function is a second-order derivative, and the derivative function is determined according to formula (2). The second-order derivative and the derivative function may also be filtered to reduce noise, as explained above for the first-order derivative. Figure 6 The filter derivative function f_2deri is also illustrated exemplarily.

[0098] The processor 3 may also be configured to define a further search range within which the maximum value of the derivative function should be searched. Specifically, the processor may be configured to use a predefined search range that has been predetermined, for example, by statistical analysis as described above, or determined by a start point and an end point, as described below. This further search range may be considered a second search range.

[0099] The processor 3 may be configured to determine a start point and an end point of a further search range based on a) the percentage of the difference PP and b) the percentage of the pulse duration. In particular, several start points and several end points may be determined, wherein the further search range may be defined by the latest start point and the earliest end point, wherein the percentages may be static or may depend on the respective pulse or pulse rate. For example, Figure 7 In the diagram, a starting point "Start 1" may be defined by a first static percentage of the pulse duration (e.g. 18%), another starting point "Start 2" may be defined by a first static percentage of the difference PP (e.g. 85%), a first end point "Stop 1" may be defined by a second static percentage of the pulse duration (e.g. 65%), a second end point "Stop 2" may be defined by a second static percentage of the difference PP (e.g. 10%), a third end point "Stop 3" may be defined by a dynamic percentage of the pulse duration, said percentage depending on the pulse rate and, for example, for a pulse rate of 50 bpm, said percentage may be 43%. In Figure 7 , the search range starts from the latest starting point "Start 1" and ends at the earliest ending point "Stop 3".

[0100] Preferably, the processor 3 is configured to determine all maxima of the derivative function f_2deri within the additional search range that are greater than a first predetermined derivative threshold, so as to determine all large maxima of the second-order derivative within the search range. If the highest of the determined maxima is greater than the product of a predefined factor and the second highest maximum within the search range, the position of the highest maximum within the search range is considered to be the notch-determined maximum position, i.e., corresponding to the dicrotic notch position t.notch. Otherwise, the position of the first temporal maximum of the derivative function f_2deri within the search range is considered to be the notch-determined maximum position, i.e., corresponding to the dicrotic notch position t.notch.

[0101] If two maxima are found within the additional search range, which are greater than a second predetermined derivative threshold for determining a large maximum, and which in turn is greater than a first predetermined derivative threshold for determining a large maximum, i.e., if there are two or more very large maxima within the search range, the corresponding pressure pulse is not considered for determining the physiological parameter since it is deemed to have an artifact.

[0102] Furthermore, before determining the notch determination function position, processor 3 may check whether the pressure pulse has a value at a location where the first derivative of the pressure pulse has a minimum value, and this location is within a first search range determined by the difference PP between the maximum systolic pressure of the pressure pulse and the pressure at the end-diastolic point of the pressure pulse. If this is the case, the notch function maximum position is determined. Otherwise, the notch determination function position for the pressure pulse cannot be determined, and the process proceeds to the next pressure pulse in the pressure signal.

[0103] To determine the notch determination function position, the processor 3 may be configured to provide a position determination function such that it defines the following characteristics of the notch determination function position and the corresponding pressure pulse (which are also Figure 8 (partially shown in FIG ) is a relationship between at least one of: a maximum value Pulse.max of the corresponding pressure pulse, a maximum position t.max along the corresponding pressure pulse, a first position t.dia.pre along the corresponding pressure pulse before the maximum position t.max, and at this position, the value of the corresponding pressure pulse is a predefined first fraction p1 of the maximum value Pulse.max, a second position t.dia.post along the corresponding pressure pulse after the maximum position t.max, and at this position, the value of the corresponding pressure pulse is a predefined second fraction p2 of the maximum value Pulse.max, the maximum value d(Pulse) / dt.max of the first-order derivative of the corresponding pressure pulse, and a difference PP between the maximum systolic pressure of the pressure pulse and the pressure of the pressure pulse at the end-diastolic point. Specifically, the processor 3 can be configured to calculate the notch determination function position fp that should correspond to the dicrotic notch position t.notch according to the above formula (3).

[0104] The processor 3 is configured to determine, for the corresponding pressure pulse, at least one corresponding feature characterizing the corresponding pressure pulse based on the corresponding determined dicrotic notch position. Figure 9 Describe this.

[0105] As from Figure 9 As can be seen in FIG, pressure pulse 29 has a notch in its descending slope, where the time at which the notch occurs is denoted by "t.notch." Specifically, pressure pulse 29 extends from t.start to t.stop, and therefore its pulse curve duration is t.stop-t.start, including a systolic period starting at t.start, having a systolic rising slope, and ending with a dicrotic notch at time t.notch in the subsequent descending slope. In this example, the dicrotic notch is characterized by a slight notch. The portion of the pulse curve that further descends from t.notch to t.end can be referred to as the "diastolic period."

[0106] The processor can be adapted to determine the difference between the start (t.start) of the pressure pulse 29 and the position of the notch (t.notch) as a feature for determining the physiological parameter. This difference, i.e. the feature, can be named "systolic time interval" or "left ventricular ejection time" (LVET).

[0107] The processor 3 may also be configured to determine the area TPA.sys under the pressure pulse 29 between the start position t.start and the notch position t.notch. Figure 9 The corresponding areas are indicated schematically and exemplarily. In an embodiment, the processor 3 can be configured to additionally or alternatively determine another feature characterizing the ejection phase, in particular the left ventricular ejection phase of the pressure pulse 29, wherein the further feature also uses the knowledge about the position of the dicrotic notch to define the transition between systole and diastole.

[0108] In an embodiment, the processor 3 is further configured to determine a respiratory pulse variation determination value TPWP_R for each pressure pulse based on at least one feature that characterizes the corresponding pressure pulse and depends on the location of the dicrotic notch, such that a plurality of respiratory pulse variation determination values ​​TPWP_R are determined for a plurality of pressure pulses occurring at different times. The plurality of respiratory pulse variation determination values ​​TPWP_R determined for a plurality of pressure pulses, and therefore for a plurality of times, form a physiological parameter determination curve, which in this example is a respiratory rate determination curve. The respiratory rate determination curve may also be referred to as a respiratory pulse variation signal.

[0109] In a preferred embodiment, the respiratory pulse variation determination value TPWP_R is determined based on at least one of TPA.sys and LVET. Furthermore, in a preferred embodiment, the respiratory pulse variation determination value TPWP_R is identical to or proportional to TPA.sys. Therefore, preferably, the respiratory pulse variation signal is TPA.sys(t). However, as previously described, the respiratory pulse variation determination value TPWP_R can also be determined by combining TPA.sys and LVET, for example, by linearly combining TPA.sys and LVET.

[0110] The processor 3 may also be configured to apply a denoising filter to the respiratory pulse variation signal so that the respiratory rate is retained in the respiratory pulse variation signal. Specifically, a moving average filter with a predetermined filter width is applied once or several times. Preferably, the filter width of the moving average filter is 0.4 seconds, and it is applied to the respiratory pulse variation signal twice.

[0111] In this embodiment, the processor 3 is configured to determine the respiratory rate as a physiological parameter based on the respiratory pulse variation signal. Specifically, the processor 3 is configured to transform the signal from the time domain to the frequency domain and determine the frequency in the frequency domain. In order to transform from the time domain to the frequency domain, a corresponding transformation can be used, such as Fourier transform, in particular fast Fourier transform, wavelet transform, etc. For example, the corresponding frequency at the corresponding maximum value in the frequency domain (in particular, within a predetermined expected frequency range) can be determined as the corresponding respiratory rate. The predefined expected frequency range is the frequency range in which the respiratory rate of the expected subject is expected to be.

[0112] The processor 3 may also be configured to determine additional characteristics of the respective pressure pulse. The determination of additional characteristics for each processed measured pressure pulse 29 will be described below, wherein in this example the respective processed measured pressure pulse 29 is a respective TPac pulse curve.

[0113] For example, the difference TPP between the maximum measured pressure and the minimum measured pressure, ie the difference between the maximum systolic pressure of the pressure pulse (TPsys) and the pressure of the pressure pulse at the end of diastole (TPdia), can be determined, as Figure 10 shown.

[0114] The processor 3 may also be configured to determine the pulse duration (t(Pulse)), which is the time difference between the end-diastolic point of the pressure pulse 29 and the next end-diastolic point. This feature may also be defined as the time difference between the start of the corresponding pulse (t.start) and the end of the corresponding pulse (t.stop). This feature is Figure 11 Instructions.

[0115] The processor 3 may also be adapted to determine the pulse area (TPA) of the corresponding pulse 29, which is the area under the corresponding pulse curve during the time defined by t.start to t.stop, ranging from the pressure pulse pressure at the end-diastolic point TPdia to the maximum systolic pressure TPsys of the pressure pulse. Preferably, the pulse area TPA is scaled to TPP=1, as Figure 11 The scaled pressure pulsation area is named "TPA.norm".

[0116] The processor 3 may also be adapted to determine the half-peak pulse width (W50) of the corresponding pulse 29, such as Figure 12 As indicated in .

[0117] Furthermore, the processor 3 may be adapted to determine the area TPA+.top50 enclosed by the upper part of the pressure pulse 29, such as Figure 13Schematically illustrated in FIG. The upper end of the area TPA+.top50 enclosed by the upper portion is at the maximum systolic pressure TPsys of the pressure pulse 29, and the lower end of the area TPA+.top50 is located between the maximum systolic pressure TPsys of the pressure pulse 29 and the pressure value corresponding to the average value TPcl of the measured pressure TP. Because the pressure pulse 29 has been processed by subtracting the average value TPcl from the measured pressure TP, the pressure value corresponding to the average value TPcl of the measured pressure TP is zero. Preferably, the processor 3 is configured to determine the area TPA+.top50 enclosed by the upper portion of the pressure pulse so that the lower end of the upper portion is at a pressure value corresponding to half the pressure distance TPP+ between the maximum systolic pressure TPsys of the pressure pulse and the pressure value corresponding to the average value TPcl of the measured pressure TP.

[0118] exist Figures 9 to 13 In the examples, the reference numerals used have the initial "T" because, in this example, the measured pressure signal is a tissue pressure signal. However, as described above, in addition to the tissue pressure signal, another pressure signal can be measured that is indicative of blood pulsation and includes multiple pressure pulses. For example, the pressure signal can be measured invasively, and the determination of the dicrotic notch location and physiological parameters described above can be applied to the pressure pulses of the invasively measured pressure signal.

[0119] The processor 3 can also be configured to determine a blood pressure determination value TPWP_M for the corresponding pressure pulse based on at least one determined feature, so that for several pressure pulses occurring at different times, several blood pressure determination values ​​TPWP_M are determined, wherein the several blood pressure determination values ​​TPWP_M determined for several pressure pulses and therefore for several times form a blood pressure determination curve TPW_M-curve. The processor 3 can be configured to determine the blood pressure based on the blood pressure determination curve TPW_M-curve, for example, as explained in WO2018 / 210931A1. Specifically, the processor 3 can be configured to determine the position of the maximum value (TPW_M-curve.max) of the blood pressure determination curve TPW_M-curve, and determine the blood pressure based on the determined position and the measured pressure TP. For example, the processor 3 can be configured to determine the systolic arterial blood pressure (SAPni) based on the average TPcl of the pressure TP measured at the determined maximum position (TPW_M-curve.max) according to the following formula:

[0120] SAPni=α·(TPcl@TPW_M-curve.max),(4)

[0121] The parameter α can be predetermined through calibration.

[0122] In practice, the processor 3 may be configured to determine the position of the maximum value and / or the position of the derivative (such as, for example, the first derivative of the blood pressure determination curve TPW_M-curve) of the blood pressure determination curve TPW_M-curve, and determine the blood pressure based on the determined position and / or the measured pressure TP. For example, the processor 3 may be configured to determine the systolic arterial blood pressure based on the average value TPcl of the pressures TP measured at one or two determined positions according to SAPni=α'·(TPcl@TPW_M-curve.max)+β'·(TPcl@TPW_M-curve'.max), where TPW_M-curve' refers to the derivative of TPW_M-curve, and where the parameters α' and β' may be predetermined by calibration.

[0123] In general, the processor 3 is preferably configured to provide the following functionality: receiving as input at least one characteristic of a respective pressure pulse, the at least one characteristic including a characteristic dependent on the determined dicrotic notch, and outputting a corresponding physiological parameter determination value, the physiological parameter determination value forming, together with the physiological parameter determination values ​​determined for other pressure pulses, a physiological parameter determination curve. The function has at least one parameter that can be determined by calibration, wherein a reference physiological parameter of a training measurement is determined very accurately by other means, and the at least one parameter is determined such that the apparatus produces a very accurately determined reference physiological parameter with high statistical precision and accuracy.

[0124] In an embodiment, the physiological parameter determination curve is a smoothed curve, wherein the smoothing process used in smoothing the physiological parameter determination curve may include, for example, filtering and / or fitting. To smooth the physiological parameter determination curve, a moving average filter, in particular a variable moving average filter, may be used, which is applied to the physiological parameter determination values ​​determined for the pressure pulse. The averaging window may be fixed or variable, wherein in the latter case, its maximum duration is preferably, for example, 8 seconds. The use of a filter may result in a filter delay, wherein the minimum filter delay may be as long as the sum of the durations of several pulses.

[0125] The measurement of physiological parameters is intended to be used in a series of measurements in rapid succession to allow for effective semi-continuous monitoring, thereby minimizing stress on the monitored individual (ie, the monitored subject).

[0126] The following will refer to Figure 14 The flow chart shown in exemplarily describes an embodiment of a method for determining a physiological parameter.

[0127] In step 101, a time-varying measured pressure signal of an object is provided by a pressure signal providing unit, wherein, in this embodiment, the pressure signal is measured by using a measuring device, the measuring device comprising: a) a housing configured to enclose a portion of the object through which blood flows; b) a pressure applicator configured to apply pressure to the housing and thereby to the enclosed portion of the object; and c) a pressure sensor configured to measure a pressure signal on the skin of the enclosed portion of the object, wherein the pressure applicator increases or decreases the applied pressure while measuring the pressure signal, and wherein the measured pressure signal indicates blood pulsation and includes a plurality of pressure pulses. Specifically, using the above reference Figures 1 to 3 A measuring device is described to measure pressure signals.

[0128] In step 102, for each pressure pulse from the plurality of pressure pulses, a corresponding feature characterizing the corresponding pressure pulse is determined, thereby determining a plurality of features for the plurality of pressure pulses. Furthermore, in step 102, a physiological parameter (which in this embodiment is respiratory rate) is determined based on the determined plurality of features. For each pressure pulse, one or more features, i.e., features of one or more different types, may be determined. The one or more features determined for the corresponding individual pressure pulse include at least one feature that depends on the location of the dicrotic notch.

[0129] The dicrotic notch position is determined based on at least one of a notch-determined intersection position, a notch-determined maximum position, and a notch-determined function position, which can be determined for a corresponding pressure pulse. Specifically, the notch-determined intersection position can be determined as the intersection of a shifted tangent on the corresponding pressure pulse, wherein the shifted tangent is determined by determining a tangent to the corresponding pressure pulse at the position of the corresponding pressure pulse (at the position where the first-order derivative of the corresponding pressure pulse is minimum) and shifting the tangent by a shift distance in a time-increasing direction, and the notch-determined maximum position can be determined as the position where the derivative function of the corresponding pressure pulse has a maximum value, wherein for more details in this regard, please refer to the corresponding description provided above. Finally, the position determination function position can be determined by determining a characteristic of the corresponding pressure pulse and applying a position determination function to the characteristic, wherein the position determination function provides a relationship between the characteristic and the notch determination function position. For example, formula (3) can be used to determine the notch determination function position for the corresponding pressure pulse.

[0130] The notch-determined intersection position, the notch-determined maximum position, or the notch-determined function position can be directly the dicrotic notch position to be determined, or at least one of the notch-determined intersection position, the notch-determined maximum position, and the notch-determined function position can be combined, in particular averaged, to determine the dicrotic notch position. In addition, the dicrotic notch position determined for the corresponding pressure pulse can be directly used as a feature, or it can be processed to provide a corresponding feature. For example, as described above with respect to Figure 9 As explained, the determined dicrotic notch position t.notch can be used to determine the characteristic LVET and / or the characteristic TPA.sys.

[0131] The portion of step 102 involving determining the location of the dicrotic notch may also be considered as a step of a method for determining the pressure pulse dicrotic notch.

[0132] In step 103 , the features determined for several pressure pulses are used to determine a respiratory pulse variation determination value TPWP_R, which forms a respiratory pulse variation signal, wherein, as described above, the respiratory rate is determined based on the respiratory pulse variation signal.

[0133] In step 104, it is determined whether a termination criterion is met. If so, the method stops at step 105, otherwise it continues at step 101. Thus, the method can be executed in a loop, continuously monitoring physiological parameters over several measurement cycles until the termination criterion is met. For example, monitoring can be interrupted if a user (e.g., a physician) inputs a corresponding command to the device via an input unit such as a keyboard, a computer mouse, or a touchpad.

[0134] Although in the above-described embodiment, the feature is determined by using the TPac pulse as the processed pressure pulse, the feature can also be determined by directly using the measured pressure pulse (i.e., for example, the TP pulse). It is also possible to process the pressure pulse in another manner, i.e., for example, to determine the TPac pulse without subtracting the average TP value. For example, for each measured pressure pulse, the pressure values ​​at t.start and t.stop can be connected by a straight line, and this straight line can be subtracted from each measured pressure pulse to determine the processed pressure pulse.

[0135] Although in the above embodiment, the pressure signal is a tissue pressure signal measured using a shell cuff, that is, although in the above embodiment, the pressure signal is measured non-invasively, the pressure signal can also be measured invasively. In order to invasively measure the pressure signal, a known corresponding measuring device can be used, such as the measuring device described in the article "How to measure blood pressure using an arterialcatheter: a systematic 5-step approach" by B. Saugel et al. in Critical Care, 24: 172 (2020), which is incorporated herein by reference. Other known techniques can also be used to invasively measure the pressure signal. After determining the dicrotic notch position of the invasively measured pressure pulse, the dicrotic notch position can be used to calculate physiological parameters. For example, as also explained above with respect to the non-invasive measurement of the pulse, LVET and / or TPA.sys can be calculated as physiological parameters and can also be used to calculate other physiological parameters such as respiratory rate. Additionally, the pulse contour stroke volume (PCSV), such as described in WO 2019 / 211210 A1 (which is incorporated herein by reference), can be determined based on the invasive pressure pulse and dicrotic notch location.

[0136] The measured pressure pulse may also be a synthetic measured pressure pulse, such as a pressure pulse comprising a non-invasively measured tissue pressure pulse or an invasively measured tissue pressure pulse. For example, a synthetic pressure pulse may be created from a non-invasive pressure pulse with the aim of generating a pressure pulse equivalent to an invasively measured arterial pressure pulse. Thus, all parameters that can be determined from an invasively measured arterial pressure pulse may also be determined based on the synthetic pressure pulse. In an example, the synthetic pressure pulse may be created by weighting the non-invasive pressure pulses and adding the weighted non-invasive pressure pulses. In particular, the synthetic pressure pulse may be generated by weighted averaging two or more consecutive non-invasive pressure pulses. In an embodiment, the synthetic pressure pulse is generated as described in EP2759258A1, in particular as described in claim 1 of EP2759258A1, which is hereby incorporated herein by reference.

[0137] Although respiratory rate and blood pressure have been determined as physiological parameters in the above embodiments, the device can also determine other physiological parameters, such as fluid responsiveness parameters.

[0138] Although in the above embodiment, the area below the corresponding pressure pulse between the starting position where the corresponding pressure pulse begins and the determined dicrotic notch position is used to determine the respiratory rate, other parameters related to the dicrotic notch may also be used to determine the respiratory rate, such as a position below the corresponding pressure pulse between: i) the starting position and the determined dicrotic notch position, for example, the position where the corresponding pressure pulse reaches a maximum value or the position where the increment (i.e., the first-order derivative of the pressure pulse) reaches a maximum value, and ii) the dicrotic notch position.

[0139] Other 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.

[0140] In the claims, the word "comprising" does not exclude other elements or steps, and the word "a" or "an" does not exclude a plurality.

[0141] A single unit or device may fulfill the functions of several items recited in the claims. 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.

[0142] Calculations such as determining pulse characteristics, specific curves, physiological parameters, etc., performed by one or more units or devices may be performed by any other number of units or devices. Calculations and determinations and / or control of a processor according to the method for determining the location of a dicrotic notch and / or control of an apparatus for determining a subject's physiological parameters according to the method for determining a subject's physiological parameters may be implemented as program code units of a computer and / or dedicated hardware.

[0143] The computer program may be stored / distributed on suitable media such as optical storage media or solid-state media provided together with or as part of other hardware, but may also be distributed in other forms such as via the Internet or other wired or wireless telecommunication systems.

[0144] Any reference signs in the claims should not be construed as limiting the scope. Specifically, letters and expressions used as reference signs in parentheses in the claims, such as PP, t.notch, etc., should not be construed as limiting the scope. For example, according to the claims, other features besides those indicated by the reference signs may be used.

[0145] The present invention relates, for example, to a processor configured to determine a dicrotic notch position of a pressure position by determining at least one of a notch-determined intersection position, a notch-determined maximum position, and a notch-determined function position. The notch-determined intersection position is the position where a tangent to the displacement of the pressure pulse intersects the pressure pulse. The notch-determined maximum position is the position where a derivative function of the pressure pulse has a maximum value. The position determination function position is determined by applying a position determination function to a characteristic of the pressure pulse. This allows for highly accurate determination of a diagnostically relevant dicrotic notch position.

Claims

1. A processor for determining the location of a dicrotic notch of a pressure pulse, wherein: The processor is configured to determine the dicrotic notch location by determining at least one of: a) determining an intersection position, which is a position where a shifted tangent line (52) intersects the pressure pulse, wherein the shifted tangent line (52) is determined by determining a tangent line (51) of the pressure pulse at a position of the pressure pulse where a first derivative of the pressure pulse has a minimum value, and shifting the tangent line (51) in a time-increasing direction by a shift distance (t.shift), b) notching a maximum position, which is the position where the derivative function has a maximum value, wherein the derivative function is determined by determining the first derivative of the pressure pulse, determining the second derivative of the pressure pulse, and combining the determined first and second derivatives, and c) a notch determination function position determined by determining a characteristic of the pressure pulse and applying a position determination function to the characteristic, wherein the position determination function provides a relationship between the notch determination function position and the characteristic, the characteristic comprising: i) a maximum position along the pressure pulse, and ii) at least one of the following characteristics of the pressure pulse: the maximum value of the pressure pulse; a first position along the pressure pulse before the maximum position, at which the value of the pressure pulse is a predefined first fraction of the maximum value; a second position along the pressure pulse after the maximum position, at which the value of the pressure pulse is a predefined second fraction of the maximum value; the maximum value of the first derivative of the pressure pulse; and the difference between the maximum systolic pressure of the pressure pulse and the pressure of the pressure pulse at the end-diastolic point.

2. The processor according to claim 1, wherein: The processor is configured to provide the shift distance (t.shift) such that the shift distance depends on a characteristic of the pressure pulse (50).

3. A processor according to any one of the preceding claims, wherein The processor is configured to: if there are several intersection positions of the displacement tangent line and the pressure pulse, select the last intersection position in time as the notch determination intersection position.

4. A processor according to any one of the preceding claims, wherein The processor is configured to determine the notch-determined maximum position by determining whether the highest maximum value of the derivative function is greater than the second highest maximum value of the derivative function multiplied by a predefined factor, wherein if the highest maximum value of the derivative function is greater than the second highest maximum value of the derivative function multiplied by the predefined factor, then the notch-determined maximum position is the position of the highest maximum value, and if the highest maximum value of the derivative function is not greater than the second highest maximum value of the derivative function multiplied by the predefined factor, then the notch-determined maximum position is the position of the first maximum value of the derivative function.

5. A processor according to any one of the preceding claims, wherein The processor is configured to determine that the pressure pulse has an artifact if the derivative function includes at least two maxima that are greater than a second predefined second derivative threshold, wherein the second predefined second derivative threshold is greater than the first predefined second derivative threshold.

6. A processor according to any one of the preceding claims, wherein The processor is configured to determine the derivative function by dividing a) a second-order derivative function that is dependent on the second-order derivative by b) a first-order derivative function that is dependent on the first-order derivative.

7. A processor according to any one of the preceding claims, wherein The processor is configured to determine the dicrotic notch location only within a provided search range.

8. The processor according to claim 7, wherein: The processor is configured to provide the search range such that the search range is defined by: a) a first percentage and a second percentage of a difference (PP) between a maximum systolic pressure of the pressure pulse and a pressure of the pressure pulse at the end-diastolic point and / or b) a first percentage and a second percentage of a pulse duration.

9. An apparatus for determining a physiological parameter of a subject, the apparatus comprising: a pressure signal providing unit configured to provide a measured pressure signal of a subject over a period of time, wherein the measured pressure signal is indicative of blood pulsation and comprises a plurality of pressure pulses (9), A processor according to any one of claims 1 to 8, configured to determine a respective dicrotic notch position for a respective pressure pulse of the plurality of pressure pulses (9), Wherein, the processor is further configured to determine the physiological parameter based on the dicrotic notch locations determined for the plurality of pressure pulses (9).

10. The device according to claim 9, wherein The processor is configured to determine a physiological parameter determination value (TPWP_R) for the corresponding pressure pulse based on the determined dicrotic notch position, so that several physiological parameter determination values ​​(TPWP_R) are determined for several pressure pulses occurring at different times, wherein the several physiological parameter determination values ​​(TPWP_R) determined for the several pressure pulses and therefore for several times form a physiological parameter determination curve, and the processor is configured to determine the physiological parameter based on the physiological parameter determination curve.

11. A method for determining the location of the dicrotic notch of a pressure pulse, wherein: The dicrotic notch location is determined by a processor by determining at least one of: a) determining an intersection position, which is a position where a shifted tangent line (52) intersects the pressure pulse, wherein the shifted tangent line (52) is determined by determining a tangent line (51) of the pressure pulse at a position of the pressure pulse where a first derivative of the pressure pulse has a minimum value, and shifting the tangent line (51) in a time-increasing direction by a shift distance (t.shift), b) notching a maximum position, which is the position where the derivative function has a maximum value, wherein the derivative function is determined by determining the first derivative of the pressure pulse, by determining the second derivative of the pressure pulse, and combining the determined first and second derivatives, and c) a notch determination function position determined by determining a characteristic of the pressure pulse and applying a position determination function to the characteristic, wherein the position determination function provides a relationship between the notch determination function position and the characteristic, the characteristic comprising: i) a maximum position along the pressure pulse, and ii) at least one of the following characteristics of the pressure pulse: the maximum value of the pressure pulse; a first position along the pressure pulse before the maximum position, at which the value of the pressure pulse is a predefined first fraction of the maximum value; a second position along the pressure pulse after the maximum position, at which the value of the pressure pulse is a predefined second fraction of the maximum value; the maximum value of the first derivative of the pressure pulse; and the difference between the maximum systolic pressure of the pressure pulse and the pressure of the pressure pulse at the end-diastolic point.

12. A method for determining a physiological parameter of a subject, the method comprising: providing a measured pressure signal of the subject over a period of time by a pressure signal providing unit, wherein the measured pressure signal is indicative of blood pulsation and comprises a plurality of pressure pulses (9), For a corresponding pressure pulse among the plurality of pressure pulses (9), the processor determines a corresponding dicrotic notch position according to claim 11, Wherein, the processor further determines the physiological parameter based on the dicrotic notch locations determined for the plurality of pressure pulses (9).

13. A computer program for determining the position of the dicrotic notch of a pressure pulse, the computer program comprising program code means for causing a processor according to any one of claims 1 to 8 to perform the steps of the method according to claim 11.

14. A computer program for determining a physiological parameter of a subject, the computer program comprising program code means for causing the apparatus for determining a physiological parameter according to claim 9 to perform the steps of the method according to claim 12.

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