Method and apparatus for determining information about arterial characteristics of a subject

Abstract

According to one aspect, a method for determining information about arterial properties of an artery of a subject is provided, the method comprising the steps of generating (103) volumetric oscillations at a first oscillation frequency in a first cuff at a first location on the limb of the subject, the volumetric oscillations being generated at a plurality of cuff pressures in the first cuff, measuring (105) the pressure in the first cuff during generation of the volumetric oscillations to generate a first cuff pressure signal, and measuring a dV art =(P cuff -P abs )*C cuff -dV osc determining (107) a first arterial volume response representing the arterial volume response to the volume oscillation at each cuff pressure using art is the first arterial volume response, and P cuff is the first cuff pressure signal, and P abs are the respective cuff pressures in the first cuff, and C cuff is the cuff compliance of the first cuff, and dV osc The method includes determining (107) a first arterial volume response, which is a signal representative of a change in volume in the cuff due to the generated volume oscillations, and determining (109) information about the subject's arterial characteristics from the first arterial volume response.

Description

[Technical Field]

[0001] This disclosure relates to a method and apparatus for determining information about the arterial characteristics of a subject, and more particularly to a method for determining this information non-invasively. [Background technology]

[0002] U.S. Patent Application Publication No. 2014135634(A1) provides a system and method for automatically generating accurate central blood pressure measurements.

[0003] U.S. Patent Application Publication No. 2011263990(A1) relates to a method and apparatus for non-invasive determination of blood pressure.

[0004] EP3705033A1 relates to a blood pressure measuring device, particularly a blood pressure measuring device that can be attached to the body, and a method for constructing such a device.

[0005] Early detection of critical conditions in patients is a critical need in clinical settings such as hospitals. Commonly used signals, such as heart rate, can be extremely vague or delayed in indicating changes in a patient's condition (e.g., blood pressure (BP)). For example, a hypotension (low blood pressure) phase may be detected with a delay when only blood pressure is observed. This is illustrated with reference to Figure 1. The plot in Figure 1 concerns a hypotension phase in a patient in the intensive care unit (ICU) approaching a critically low systolic BP (SBP) of 80 mmHg. The systolic BP over time is shown at the top of Figure 1. However, the heart rate (shown at the bottom of Figure 1) responds quickly but vaguely, increasing to compensate for the decrease in BP. The pulse wave arrival time (PAT) (plotted in the middle of Figure 1) changes with the change in BP in this case, but the change in PAT does not predict BP.

[0006] Therefore, there is a need for new or better means to respond quickly, sensitively, and clearly to the patient's condition, which can be easily and unobtrusively monitored or evacuated.

[0007] An undervalued and underutilized information source in current clinical practice is vascular (arterial) compliance, which plays a fundamental role in circulatory integrity. Arterial compliance adapts to changes in blood pressure, circadian rhythms, physical activity, and stress, as well as to long-term changes caused by age, lifestyle, and other factors. Compliance, particularly arterial compliance, can reveal a significant amount of information about the health status of a patient or subject. Traditionally, arterial compliance has been measured using imaging solutions such as vascular ultrasound or MRI (magnetic resonance imaging), but this makes it impossible to continuously measure arterial compliance for most patients (e.g., patients in the ICU).

[0008] Beyond arterial compliance, or the elastic properties of the arterial wall (which enable contraction / expansion), novel regulatory mechanisms of the circulatory system have been discovered, such as the nonlinear properties of the arterial wall, viscosity, damping properties, the existence of cutoff frequencies, and the strain-dependent activation of smooth muscle tone. For this reason, methods have been developed to observe and measure these compensatory mechanisms. However, to date, proposed methods for obtaining such complex regulatory measurements involve invasive measurements, in vitro studies of arteries, or inferences through complex physiological models with uncertainties and assumptions. Some of these methods are described in "Arterial wall mechanics as a function of heart rate: role of vascular smooth muscle" by Fernando Pablo Salvucci et al., 2007 J.Phys.:Conf. Ser.90 012010, and "Beat to Beat Modulation of Arterial Pulse Wave Velocity Induced by Vascular Smooth Muscle Tone" by LJCymberknop et al., 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Berlin, Germany, 2019, pp. 5030-5033.

[0009] Arterial compliance represents the ability of an artery to expand and contract in response to changes in pressure. Therefore, (C a Arterial compliance (as shown in the equation) can be expressed as shown in Equation 1 below.

number

[0010] In Equation 1, V art P is arterial volume, and Ptm is transmural pressure across the arterial wall. tm Equation 2 P tm = P art - P ext (2) is given by, where P art is the arterial pressure and P ext is the pressure outside the artery (e.g., atmospheric pressure), or, when the cuff is placed on the arm or limb, the pressure inside the cuff (referred to as the "cuff pressure"). The maximum value of P art is the systolic blood pressure, and the minimum value of P art is the diastolic blood pressure (DBP), and C a , i.e., arterial compliance, is a highly non-linear subject-specific function of the transmural pressure P tm (i.e., the pressure across the arterial wall).

[0011] In principle, arterial volume can be measured by high-resolution imaging (e.g., ultrasound) that can represent changes in arterial diameter as arterial pressure varies between systolic and diastolic values. In practice, however, the procedure is not automated (as described in "Venous occlusion plethysmography in cardiovascular research: methodology and clinical applications" by Wilkinson IB and Webb DJ, Br. J. Clin. Pharmacol. 2001;52:631 - 646), which requires a highly skilled operator and is error-prone, causing difficulties. In addition to this, when information about arterial properties over a wider range of transmural pressures is required, imaging technology must be incorporated into the cuff setting, making the measurement even more complex.

[0012] Different methods of arterial volume measurement involve the use of existing BP cuffs (i.e., cuffs used when measuring blood pressure). Pressure oscillations inside the cuff represent changes in arterial volume due to the pulsating nature of systemic blood pressure. However, accurate knowledge of arterial pressure is necessary to extract arterial properties from this signal. Such accuracy can be obtained invasively via the arterial pathway. For non-invasive measurements, blood pressure values ​​can be obtained via common cuff-based oscillometric measurements. However, oscillometric measurements have been shown to be inaccurate in some patient groups (such as hypotensive and hypertensive patients). In addition to this, BP can change within very short time spans, especially in hemodynamically unstable patients, and there are variations in heart rate intervals caused by respiration. Therefore, measuring blood pressure at one time and measuring changes in arterial volume at different times may not yield correct arterial property values.

[0013] For the purpose of better detecting deterioration in a patient's condition, estimated arterial compliance or viscosity characteristics can be used in several ways. The simplest method is the quantification of changes in arterial compliance, arterial collapse, or viscosity values. These changes can be made available to clinicians through additional scores displayed on operating room (OR) / ICU monitors in a similar manner to cardiac pressure and blood pressure values. Another method is based on incorporating arterial compliance and viscosity information into physiological models for the purpose of estimating overall system parameters such as cardiac output or peripheral resistance.

[0014] Knowledge of arterial compliance can provide more continuous and non-invasive BP estimations by enabling accurate calibration of BP surrogates. For example, PAT can be a good indicator of changes in systolic blood pressure, as shown in Figure 1. To utilize this, a calibration step is required to link changes in PAT to changes in BP. A good approximation of arterial compliance can bring multiple benefits to this calibration step in terms of the accuracy and range of transwall pressures considered in the BP-PAT function. Furthermore, information about arterial compliance reduces the need for empirical assumptions in the calibration of BP surrogates and supports a more physiologically-based interpretation.

[0015] One relevant application is the assessment of endothelial function, i.e., the artery's ability to adjust lumen size to maintain homeostasis. This assessment is typically performed by measuring arterial dimensions after several minutes of vascular occlusion (known as flow-mediated dilation). Short-term changes in blood flow result in changes in arterial lumen size, which in turn reveal information about the patient's stability (such as the presence of sepsis) or the progression of cardiovascular disease. "Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis" by Ras, RT et al., Int J Cardiol 168,344-351; "Influence of respiratory rate on the variability of blood volume pulse characteristics" by Selvaraj N et al., J Med Eng Technol.2009;33(5):370-375; "Assessment of Vascular Health With Photoplethysmographic Waveforms From the Fingertip" by Wu HT et al., IEEE J Biomed Health Inform.2017 Mar; 21(2):382-386; and "Finger photoplethysmogram pulse amplitude changes induced by flow-mediated dilation" by Zahedi E, Physiol Ultrasound, photoplethysmogram (PPG), or PAT-based techniques, such as those described in Meas.2008;29:625-37, are currently employed in the evaluation of arterial dimensional adjustment. While these current techniques face limitations, such as obvious challenges regarding arterial imaging, other PPG and PAT-based techniques cannot overcome the need for occlusion (which can be traumatic for the patient) to occur for several minutes to produce a detectable change in arterial size.Information on compliance or viscosity could benefit endothelial response assessment by potentially enabling more accurate and comfortable (faster) measurements of changes in arterial size compared to current practices. [Overview of the project] [Problems that the invention aims to solve]

[0016] Therefore, arterial properties such as arterial compliance and / or arterial viscosity are useful in monitoring the health status of subjects. Thus, it is desirable to provide improved methods for non-invasively estimating information about these and other arterial properties of subjects. [Means for solving the problem]

[0017] The present invention is defined by the independent claims. The dependent claims define advantageous embodiments.

[0018] Solutions for non-invasively measuring arterial properties can be developed from techniques for measuring blood pressure using external perturbation (known as external pressure non-invasive BP (NIBP) measurement). Using an external perturbation configuration, arterial volume can be measured as a response to a clear external pressure change that produces a change in transwall pressure. In this case, knowledge of internal arterial pressure is unnecessary. Information about arterial compliance can be derived from this arterial volume response. Furthermore, arterial responses to different frequencies (above heart rate) can be measured via external perturbation. This provides information about the viscosity characteristics of the arteries.

[0019] According to a first particular embodiment, a method is provided for determining information about the arterial characteristics of a subject's arteries. The method includes (a) generating volume vibrations at a first vibration frequency in a first cuff at a first location on the limb of a subject, wherein the volume vibrations are generated in the first cuff at a plurality of cuff pressures; (b) measuring the pressure in the first cuff during the generation of volume vibrations to generate a first cuff pressure signal; and (c) dV art =(P cuff -P abs )*C cuff -dV osc A step of determining a first arterial volume response that represents the arterial volume response to volume oscillations at each cuff pressure, wherein dV art This is the first arterial volume response, P cuff This is the first cuff pressure signal, P abs is the respective cuff pressure in the first cuff, C cuff This is the first cuff's cuff compliance, and DV osc (d) the step of determining a first arterial volume response, which is a signal representing the change in volume in the cuff due to the generated volume oscillation, and (d) the step of determining information about the subject's arterial characteristics from the first arterial volume response. This embodiment has the advantage that arterial characteristics can be measured non-invasively without requiring knowledge of internal arterial pressure.

[0020] In some embodiments, step (c) further comprises band-pass filtering a first cuff pressure signal to obtain a signal component corresponding to a first vibration frequency of volume vibration, and determining a first arterial volume response based on the band-pass filtered first cuff pressure signal. These embodiments offer the advantage that the signal component due to heartbeat is not taken into account when determining the first arterial volume response.

[0021] In some embodiments, the first vibration frequency of volume vibration is set to a frequency different from the subject's heart rate. In these embodiments, the first vibration frequency of volume vibration may be in the range of 1 Hz to 3 Hz. In these embodiments, it is possible to filter out and remove volume vibration caused by the heart rate.

[0022] In alternative embodiments, the method may further include, prior to step (a), a step of inflating a second cuff at a second location on the subject to a occlusion cuff pressure, which is a cuff pressure exceeding the subject's systolic blood pressure, wherein the second location is on the same limb as the first location, upstream of the first location, and the second cuff at the second location on the subject is inflated to a occlusion cuff pressure, which is a cuff pressure exceeding the subject's systolic blood pressure, and steps (a) and (b) are performed while the second cuff is inflated to the occlusion cuff pressure. These embodiments have the advantage that volume oscillations due to blood flow are stopped, thereby simplifying subsequent processing of the first cuff pressure signal. In these embodiments, step (d) may include a step of determining a function of arterial volume response to transwall pressure from a first arterial volume response, and a step of determining information about arterial characteristics from the determined function.

[0023] In some embodiments, arterial characteristics include arterial compliance. In these embodiments, the method may further include the steps of determining the cuff pressure at which maximum arterial compliance occurs in the first cuff from a function of arterial volume response to transwall pressure, and determining the mean systemic filling pressure (MSFP) for the subject as the cuff pressure at which maximum arterial compliance occurs in the first cuff. These embodiments provide a simple method for non-invasively determining MSFP without the need to measure arterial pressure.

[0024] In some embodiments, the method further comprises (e) repeating steps (a) and (b) for one or more additional vibration frequencies for volume vibration to generate one or more additional cuff pressure signals, and (f) determining an additional arterial volume response for each of the one or more additional vibration frequencies, wherein the additional arterial volume response represents the arterial volume response to volume vibration at each cuff pressure, and the arterial volume response is determined based on one or more additional cuff pressure signals, the cuff compliance of the first cuff, and each volume vibration signal relating to each vibration frequency of volume vibration generated in the first cuff, and step (d) determining information about the arterial characteristics of the subject from the first arterial volume response and the additional arterial volume response. These embodiments have the advantage that they provide information about arterial volume response at different frequencies.

[0025] In these embodiments, steps (a), (b), and (e) may include (g) inflating a first cuff to a first cuff pressure; (h) generating volume oscillations in the first cuff at a first oscillation frequency and measuring the pressure in the first cuff while generating the volume oscillations; (i) repeating step (h) for one or more further oscillation frequencies in the first cuff; (j) inflating the first cuff to a second pressure; and (k) repeating steps (h) and (i) while the first cuff is inflated to the second pressure. Thus, these embodiments specify that information regarding arterial volume response at different frequencies can be obtained from a single cuff inflation procedure.

[0026] In the embodiments described above, the arterial characteristic may be arterial viscosity. In these embodiments, step (d) may include determining information about arterial viscosity from a comparison of a first arterial volume response with a further arterial volume response.

[0027] In the above embodiment, the first vibration frequency and one or more further vibration frequencies may be in the range of 1 Hz to 25 Hz.

[0028] In some embodiments, the volumetric vibration at the first vibration frequency has an amplitude in the range of 5 ml to 20 ml.

[0029] In some embodiments, the method further comprises the step of determining the cuff compliance of a first cuff. In some embodiments, cuff compliance may be determined prior to step (c) by generating volume vibrations in the first cuff at a second vibration frequency when the first cuff is inflated to a third cuff pressure; measuring the pressure in the first cuff while generating volume vibrations at the second vibration frequency to generate a third cuff pressure signal; bandpass filtering the third cuff pressure signal to obtain a signal component corresponding to the vibration frequency of the second volume vibration; and determining the cuff compliance of the first cuff from the filtered third cuff pressure signal. These embodiments have the advantage that the cuff compliance does not need to be known before the above method is performed, and that the method can be performed with any particular cuff (for example, having a cuff size determined according to the subject's age / size).

[0030] In these embodiments, the step of determining cuff compliance may include dividing the amplitude of volume vibration at a second vibration frequency by the amplitude of a filtered third cuff pressure signal. In these embodiments, the amplitude of volume vibration at a second vibration frequency may be smaller than the amplitude of volume vibration at a first vibration frequency. In these embodiments, the amplitude of volume vibration at a second vibration frequency may be in the range of 0.1 ml to 5 ml.

[0031] A second embodiment provides a computer program product having computer-readable code (including, for example, a computer-readable medium) implemented therein, wherein the computer-readable code is configured such that, when executed by a suitable computer or processing unit, the computer or processing unit is caused to perform the method according to the first embodiment or any embodiment thereof. In some embodiments, the computer or processing unit is configured to connect to or interface with a pump or other vibrator component to perform step (a), and / or to connect to or interface with a cuff pressure sensor to perform step (b).

[0032] According to a third specific embodiment, a device is provided for determining information about the arterial characteristics of a subject's arteries. The device includes (a) the act of initiating the generation of volume vibrations at a first vibration frequency in a first cuff at a first location on the subject's limb, wherein the volume vibrations should be generated at multiple cuff pressures in the first cuff; (b) the act of obtaining a first cuff pressure signal including a measurement of the pressure in the first cuff during the generation of volume vibrations; and (c) dV art =(P cuff -P abs )*C cuff -dV osc The act of determining a first arterial volume response that represents the arterial volume response to volume oscillations at each cuff pressure, where dV art This is the first arterial volume response, P cuff This is the first cuff pressure signal, P abs is the respective cuff pressure in the first cuff, C cuff This is the first cuff's cuff compliance, and DV osc(d) The procedure involves determining a first arterial volume response, which is a signal representing the change in volume within the cuff due to the generated volume oscillation, and determining information about the subject's arterial characteristics from the first arterial volume response. This configuration has the advantage of being able to measure arterial characteristics non-invasively without requiring knowledge of internal arterial pressure.

[0033] In some embodiments, act (c) further includes band-pass filtering a first cuff pressure signal to obtain a signal component corresponding to a first vibration frequency of volume vibration, and determining a first arterial volume response based on the band-pass filtered first cuff pressure signal. These embodiments offer the advantage that the signal component due to heartbeat is not taken into account when determining the first arterial volume response.

[0034] In some embodiments, the first vibration frequency of volume vibration is set to a frequency different from the subject's heart rate. In these embodiments, the first vibration frequency of volume vibration may be in the range of 1 Hz to 3 Hz. In these embodiments, it is possible to filter out and remove volume vibration caused by the heart rate.

[0035] In alternative embodiments, the device may, prior to action (a), initiate inflation of a second cuff at a second location on the subject to a occlusion cuff pressure, which is a cuff pressure exceeding the subject's systolic blood pressure, and further, initiate inflation of a second cuff at a second location on the subject, which is on the same limb as the first location and upstream of the first location, to a occlusion cuff pressure, which is a cuff pressure exceeding the subject's systolic blood pressure, and actions (a) and (b) are performed while the second cuff is inflated to the occlusion cuff pressure. These embodiments have the advantage that volume oscillations due to blood flow are stopped, thereby simplifying subsequent processing of the first cuff pressure signal. In these embodiments, action (d) may include determining a function of the arterial volume response to transwall pressure from the first arterial volume response and determining information about arterial characteristics from the determined function.

[0036] In some embodiments, arterial characteristics include arterial compliance. In these embodiments, the device may further determine the cuff pressure at which maximum arterial compliance occurs in the first cuff from a function of arterial volume response to transwall pressure, and determine the mean systemic filling pressure (MSFP) for the subject as the cuff pressure at which maximum arterial compliance occurs in the first cuff. These embodiments provide a simple method for non-invasively determining MSFP without the need to measure arterial pressure.

[0037] In some embodiments, the apparatus further determines further arterial volume responses, where the arterial volume response is determined based on each of the one or more further cuff pressure signals, the cuff compliance of the first cuff, and each volume vibration signal relating to each vibration frequency of the volume vibration generated in the first cuff, and the arterial volume response is determined based on each of the one or more further cuff pressure signals, the cuff compliance of the first cuff, and each volume vibration signal relating to each vibration frequency of the volume vibration generated in the first cuff, and the act (d) includes determining information about the arterial characteristics of the subject from the first arterial volume response and the further arterial volume responses. These embodiments have the advantage that they provide information about arterial volume responses at different frequencies.

[0038] In these embodiments, actions (a), (b), and (e) may include (g) initiating inflation of the first cuff to a first cuff pressure, (h) initiating the generation of volume oscillations at a first vibration frequency within the first cuff and measuring the pressure within the first cuff while the volume oscillations are being generated, (i) repeating action (h) for one or more further vibration frequencies in the first cuff, (j) initiating inflation of the first cuff to a second pressure, and (k) repeating actions (h) and (i) while the first cuff is inflated to the second pressure. Thus, these embodiments specify that information regarding arterial volume response at different frequencies can be obtained from a single cuff inflation procedure.

[0039] In the embodiments described above, the arterial characteristic may be arterial viscosity. In these embodiments, action (d) may include determining information about arterial viscosity from a comparison of a first arterial volume response with a further arterial volume response.

[0040] In the above embodiment, the first vibration frequency and one or more further vibration frequencies may be in the range of 1 Hz to 25 Hz.

[0041] In some embodiments, the volumetric vibration at the first vibration frequency has an amplitude in the range of 5 ml to 20 ml.

[0042] In some embodiments, the apparatus further performs the determination of the cuff compliance of the first cuff. In some embodiments, cuff compliance may be determined by, before action (c), initiating the generation of volume vibrations in the first cuff at a second vibration frequency when the first cuff is inflated to a third cuff pressure; obtaining a third cuff pressure signal including a measurement of the pressure in the first cuff during the generation of volume vibrations at the second vibration frequency; bandpass filtering the third cuff pressure signal to obtain a signal component corresponding to the vibration frequency of the second volume vibration; and determining the cuff compliance of the first cuff from the filtered third cuff pressure signal. These embodiments have the advantage that the cuff compliance does not need to be known before the above process is performed, and that the process can be performed using any particular cuff (for example, with a cuff size determined according to the subject's age / size).

[0043] In these embodiments, the device may be configured to determine cuff compliance by dividing the amplitude of volume vibration at a second vibration frequency by the amplitude of a filtered third cuff pressure signal. In these embodiments, the amplitude of volume vibration at the second vibration frequency may be smaller than the amplitude of volume vibration at the first vibration frequency. In these embodiments, the amplitude of volume vibration at the second vibration frequency may be in the range of 0.1 ml to 5 ml.

[0044] These and other embodiments will become apparent from the embodiments described below, and will be clarified by referring to those embodiments.

[0045] The above embodiments therefore provide an improved method for non-invasively determining information about arterial properties (such as arterial compliance and arterial viscosity), which can be performed using existing equipment or devices used for patient monitoring. Detecting changes in actively regulated arterial properties can reveal the activation of compensatory regulatory mechanisms in the body, for example, preceding hypotensive events. Furthermore, because the above embodiments utilize external pressure vibration, improved information about arterial properties can be obtained without requiring arterial pressure measurement (whether invasive or non-invasive).

[0046] Since changes in arterial viscoelastic properties can precede large changes in blood pressure and hemodynamic instability, information on arterial properties can be used for the early detection of deterioration in a patient's condition. Since the measurement of arterial viscoelastic properties can play a role in assessing the progression of cardiovascular disease and the response to treatment, information on arterial properties can be used similarly or alternatively for the diagnosis and treatment of cardiovascular disease. Information on arterial properties can also be used similarly or alternatively to achieve improved accuracy in the calibration of blood pressure surrogate measures, such as pulse wave arrival time and pulse wave morphological characteristics. Furthermore, since arterial viscoelasticity is an important factor in better identifying different patient groups, for example, in relation to medication response, improved, voluntary, and continuous measurement of arterial properties can enable the development of personalized medical treatments and interventions.

[0047] Next, an exemplary embodiment will be described simply as an example, with reference to the following drawings. [Brief explanation of the drawing]

[0048] [Figure 1] This graph shows heart rate, pulse wave arrival time, and systolic blood pressure measurements for subjects experiencing a period of hypotension. [Figure 2] This is a block diagram of an apparatus that may be used to carry out the techniques described herein. [Figure 3]This is an explanatory diagram illustrating an exemplary measurement setup on a subject according to one embodiment. [Figure 4] This graph shows the oscillation of arterial volume below the cuff when the cuff inflates. [Figure 5] This flowchart shows a method for determining information about one or more arterial characteristics according to various embodiments. [Figure 6] This figure shows a graph illustrating the change in arterial pressure over time, and another graph illustrating the artificial volume oscillations generated inside the cuff over time. [Figure 7(a)] This graph shows the cuff pressure signal obtained from a cuff undergoing volume oscillation, as shown in Figure 6(b), when arterial flow beneath the cuff is not occluded. [Figure 7(b)] This graph shows the cuff pressure signal obtained from the cuff undergoing volume oscillation, as shown in Figure 6(b), when blood flow is blocked using a different cuff. [Figure 8] This figure shows the arterial volume response obtained from the cuff pressure signal in Figure 7(a). [Figure 9] This figure shows a more detailed portion of the graph in Figure 8. [Figure 10] This figure shows a more detailed portion of the graph in Figure 9. [Figure 11] This graph shows arterial volume as a function of transwall pressure. [Modes for carrying out the invention]

[0049] As described above, an individual's arterial characteristics, such as arterial compliance and / or arterial viscosity, are useful for monitoring their health status. These characteristics can be useful for the early detection of deterioration in an individual's health, for example, if changes in these characteristics precede changes in more regularly monitored characteristics, such as heart rate and blood pressure. These characteristics can also be useful in the diagnosis and treatment of cardiovascular disease, and / or they can be used when calibrating blood pressure surrogate measures.

[0050] Embodiments of the techniques described herein enable more accurate non-invasive measurement of arterial compliance. These techniques do not require knowledge of blood pressure, which is generally the most prominent source of error in measuring arterial properties. Embodiments of the techniques described herein enable non-invasive measurement of arterial viscosity. Conventionally, arterial viscosity has only been measured invasively via in vitro measurements or by inference via physiological models. Further embodiments enable non-invasive measurement of mean body circulatory filling pressure (MSFP) using measured arterial compliance.

[0051] These techniques are based on a new understanding of how commonly used cuffs in blood pressure measurement can be used for both applying a clear external pressure to the artery and simultaneously measuring the arterial volume response to changes in external pressure without the need for additional volume sensors such as ultrasonic sensors.

[0052] In the following, various parameters are used to describe and illustrate the present invention. These parameters are defined in Table 1 below for convenience.

[0053] [Table 1]

[0054] Figure 2 shows a block diagram of a system 2 that can be used to estimate arterial characteristics according to various embodiments of the technique described herein. System 2 comprises a cuff 4 (also called the “first cuff 4”), a pump 6 connected to the cuff 4 (e.g., via a connecting tube 7), and a cuff pressure sensor 8 for measuring the pressure in the cuff 4. The cuff 4 should be positioned around a body part of the subject, for example, around a limb such as an arm or leg, and the pump 6 is controllable to selectively inflate the cuff 4. The pump 6 is also capable of selectively deflating the cuff 4 and / or is provided with a valve (not shown) to enable selective deflation of the cuff 4.

[0055] Volume oscillations are generated inside the cuff 4 while the cuff 4 is inflated to a certain pressure level. For example, volume oscillations can be generated by adding air to the cuff 4 and then removing the air from the cuff 4. In some embodiments, the pump 6 can generate volume oscillations inside the cuff 4. In alternative embodiments, system 2 may include a separate vibrator component (not shown in Figure 2) connected to the pump 6, cuff 4 and / or connecting pipe 7, which is used to generate volume oscillations inside the cuff 4. As will be further described below, the magnitude of the volume oscillations is relatively small relative to the volume of the cuff 4 (for example, the oscillations have an amplitude of up to 25 milliliters (ml), while the typical inflated volume of the cuff 4 is in the range of 100 ml to 300 ml).

[0056] The cuff pressure sensor 8 measures the pressure in the cuff 4 at least when the cuff 4 is stimulating an artery located beneath the cuff 4, for example, during inflation of the cuff 4, during deflation of the cuff 4, and / or while the pressure in the cuff 4 is maintained at a specific level, as well as while the pump 6 is generating volumetric oscillations in the cuff 4. The cuff pressure sensor 8 outputs a cuff pressure signal that represents or relates to the measured pressure in the cuff 4 over time. The cuff pressure signal is P cuff This is shown as, and in this specification, is also referred to as the first cuff pressure signal. P cuff It should also be noted that this may refer to the instantaneous measurement of the pressure in the first cuff 4 by the cuff pressure sensor 8 (wherein the instantaneous measurement is referred to as the cuff pressure measurement in this specification).

[0057] The volume oscillations generated inside cuff 4 during the operation of system 2 may be at a single frequency or at multiple different frequencies (for example, when arterial compliance is the arterial characteristic to be determined). In the latter case, cuff pressure measurements obtained when volume oscillations of different frequencies are generated in cuff 4 may be used to obtain information about arterial viscosity. Alternatively or additionally, cuff pressure measurements obtained when volume oscillations of one frequency are generated in cuff 4 may be used to estimate cuff 4 compliance, and cuff pressure measurements obtained when volume oscillations of other or different frequencies are generated may be used to determine information about arterial compliance. The frequency of the volume oscillations may be in the range of 1 Hz to 25 Hz. As will be further explained below, the frequency of the volume oscillations should be different from the subject's heart rate so that the effect of the volume oscillations generated in cuff 4 can be observed in the cuff pressure measurement separately from the oscillations due to blood flow in the arteries. Typical heart rates are in the range of 0.8 Hz to 3 Hz, and suitable frequencies for volume oscillations may be above or below the heart rate.

[0058] In some embodiments, system 2 includes a second cuff 10. The second cuff 10 should be positioned around the body part of the subject, particularly around the same limb as the first cuff 4, and upstream of the first cuff 4 (i.e., the second cuff 10 is closer to the subject's heart than the first cuff 4; in other words, the second cuff 10 is proximal and the first cuff 4 is distal). The second cuff 10 may be connected to a pump 6 via a connecting tube 11, which is controllable to selectively inflate the second cuff 10. The pump 6 is also capable of selectively deflating the second cuff 10 and / or is provided with a valve (not shown) to enable deflation of the second cuff 10. It should be noted that pump 6 can inflate / deflate the second cuff 10 independently of the first cuff 4. For example, pump 6 can inflate or deflate the second cuff 10 to a specific pressure while the first cuff 4 is unable to inflate or deflate, or is otherwise held at its current pressure. Furthermore, pump 6 (or other vibrator component) can apply volumetric vibration to the first cuff 4 without affecting the pressure or volume in the second cuff 10 (i.e., without applying volumetric vibration to the second cuff 10). In some embodiments, instead of using the first pump 6, a separate pump (not shown in Figure 2) is provided, in particular, for inflating / deflating the second cuff 10.

[0059] As will be further explained below, during the use of System 2, the second cuff 10 can be inflated to a pressure that blocks blood flow in the lower part of the limb (where, for example, the first cuff 4 is located), meaning that no blood flows in the artery below the first cuff 4. Volume oscillations are generated in the first cuff 4 while blood flow is blocked in the artery, and a cuff pressure signal can be obtained. By blocking blood flow in this way, it is possible to simplify the processing of the cuff pressure signal when determining information about arterial characteristics. Furthermore, by blocking blood flow in this way, in some embodiments, it is possible to estimate the mean systemic circulation filling pressure (MSFP) for the subject from the cuff pressure signal.

[0060] System 2 also includes a device 12 that operates according to the techniques described herein to determine information about one or more arterial characteristics of a subject. The device 12 is configured to receive a cuff pressure signal from the cuff pressure sensor 8. In some embodiments, the device 12 is configured to control the operation of the pump 6, thereby initiating inflation of the first cuff 4 at an appropriate time and initiating the generation of volumetric oscillations within the cuff 4.

[0061] The device 12 may be a computing device such as a server, desktop computer, laptop, tablet computer, smartphone, or smartwatch, or a patient monitoring device used to monitor (and optionally display) various physiological characteristics of a subject / patient, including arterial compliance and / or arterial viscosity (e.g., a monitoring device located at the patient's bedside in a clinical setting), or it may be part of such a computing device or other type of device.

[0062] Apparatus 12 includes a processing unit 22 which may be configured to control the operation of apparatus 12 and to perform or implement the methods described herein. The processing unit 22 may be implemented in numerous ways using software and / or hardware to perform the various functions described herein. The processing unit 22 comprises one or more microprocessors or digital signal processors (DSPs) programmed using software or computer program code for performing the required functions and / or for controlling the components of the processing unit 22 to implement the required functions. The processing unit 22 may be implemented as a combination of dedicated hardware for performing certain functions (e.g., amplifiers, preamplifiers, analog-to-digital converters (ADCs) and / or digital-to-analog converters (DACs)) and processors for performing other functions (e.g., one or more programmed microprocessors, controllers, DSPs and associated circuits). Examples of components that may be used in various embodiments of this disclosure include, but are not limited to, conventional microprocessors, DSPs, application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), hardware for implementing neural networks, and / or so-called artificial intelligence (AI) hardware accelerators (i.e., processors or other hardware specifically designed for AI applications that may be used in conjunction with a main processor).

[0063] The processing unit 22 is connected to a memory unit 24 which can store data, information, and / or signals for use by the processing unit 22 when controlling the operation of the device 12 and / or when performing or implementing the methods described herein. In some implementations, the memory unit 24 stores computer-readable code that can be executed by the processing unit 22 so that the processing unit 22 performs one or more functions, including the methods described herein. In certain embodiments, the program code may take the form of an application for a smartwatch, smartphone, tablet, laptop, or computer. The memory unit 24 may include any type of non-temporary machine-readable media, such as cache or system memory, including volatile and non-volatile computer memory, including random access memory (RAM), static RAM (SRAM), dynamic RAM (DRAM), read-only memory (ROM), programmable ROM (PROM), erasable PROM (EPROM), and electrically erasable PROM (EEPROM). The memory unit 24 may be implemented in the form of a solid-state device, including a memory chip, an optical disc (such as a compact disc (CD), digital versatile disc (DVD), or Blu-ray disc), a hard disk, a tape storage solution, or a memory stick, solid-state drive (SSD), or memory card.

[0064] In some embodiments, the device 12 includes a user interface 26 comprising one or more components that enable a user of the device 12 to input information, data and / or commands into the device 12, and / or enable the device 12 to output information or data to the user of the device 12. The information that may be output by the user interface 26 may include any of the following: information about arterial characteristics, values ​​of arterial characteristics, information about arterial compliance, arterial compliance values, information about arterial viscosity, arterial viscosity values, and cuff compliance values. The user interface 26 may include any preferred input components, including, but not limited to, a keyboard, keypad, one or more buttons, switches or dials, a mouse, trackpad, touchscreen, stylus, camera, microphone, etc., and / or the user interface 26 may include any preferred output components, including, but not limited to, a display screen, one or more lights or illuminating elements, one or more loudspeakers, vibration elements, etc.

[0065] It will be understood that the practical implementation of device 12 may include additional components to those shown in Figure 2. For example, device 12 may also include a power source such as a battery, or components that enable device 12 to be connected to a wall outlet. Device 12 may also include interface circuits that enable data connections to and / or data exchange with other devices, including servers, databases, and user devices.

[0066] Figure 3 shows an exemplary measurement setup using a first cuff 4 and a voluntary second cuff 10 on a subject 30. The first cuff 4 is shown on the left arm 32 of the subject 30, and Figure 3 also shows where the second cuff 10 can be positioned in embodiments in which the second cuff 10 is used. As described above, the second cuff 10 should be upstream of the first cuff 4, around the same limb as the first cuff 4. Thus, in this explanatory diagram, the second cuff 10 is on the upper portion of the left arm 32, and the first cuff 4 is on the lower portion of the left arm 32. This arrangement of cuffs 4, 10 allows the first cuff 4 to inflate the second cuff 10 to a pressure that obstructs blood flow into the lower portion of the left arm 32 where it is located. The pressure required in the second cuff 10 to obstruct blood flow is greater than the subject 30's systolic blood pressure.

[0067] Figure 4 shows the change in arterial volume (dV) due to blood flow at different pressures in cuff 4 when there is no artificial volume oscillation. art This is a graph showing the magnitude of ). Figure 4 shows both the arterial volume oscillation (expressed in ml) and the signal envelope for the arterial volume oscillation (the signal envelope shown is the difference between the upper envelope for the volume oscillation signal and the lower envelope for the volume oscillation signal (i.e., signal envelope = upper envelope - lower envelope)).

[0068] It is known that measuring the arterial volume response to external pressure can be performed by generating distinct volume oscillations inside a first cuff 4 positioned on the arm 32 of the subject 30. Measuring the arterial volume response requires only a single cuff (the first cuff 4, although the first cuff 4 may be positioned on either the upper or lower portion of the arm 32). During use, the cuff 4 generates different absolute pressures (P abs It is inflated to ) and, while under various absolute pressures, the volumetric oscillation (dV) occurs within the cuff 4 by the pump 6. oscA volumetric oscillation is artificially generated, and the pressure in the cuff 4 is measured by the cuff pressure sensor 8. In some embodiments, a stepwise inflation / measurement method can be used, for example, by inflating the cuff 4 to a first absolute pressure, generating a volumetric oscillation in the cuff 4, and measuring the pressure in the cuff 4 while the volumetric oscillation is being generated. The pressure in the cuff 4 is then changed to a second absolute pressure (which may be higher or lower than the first absolute pressure), generating a volumetric oscillation in the cuff 4, measuring the pressure in the cuff 4, and so on. In alternative embodiments, a continuous inflation / measurement method can be used, for example, by continuously inflating the cuff 4 (for example, at a constant inflation rate), generating a volumetric oscillation in the cuff 4, and measuring the pressure in the cuff 4 while the volumetric oscillation is being generated. In any embodiment, the pressure in the cuff 4 may be in the range of 0 to 200 mmHg.

[0069] Compliance of the first cuff 4 (C cuff If the condition is clear, the pressure response dP of cuff 4 to artificial volume changes (volume oscillations) osc teeth, dP osc =dV osc / C cuff (3) Known from.

[0070] arterial volume V art is pressure oscillation dP osc And, (the internal pressure pulsation dP that occurs between systolic and diastolic blood pressure values) art It reacts to the measured cuff pressure signal P. cuff Therefore, dV art and domestic violence osc It is affected by both. The arterial volume response is given by the formula dV art =(P cuff -P abs )*C cuff -dV osc (4) P via cuff This can be obtained from the measurement.

[0071] Equation (4) shows the cuff pressure P cuffIt can be used to determine the arterial volume response for discrete measurements, but more generally, the arterial volume response is, dV art (t)=(P cuff (t)-P abs (t))*C cuff -dV osc (t) (5) It can be derived using, where dV art (t) is the arterial volume response over time, P cuff (t) is the cuff pressure signal.

[0072] Arterial volume (dV art The expected magnitude of the change in dV is on the order of 0.25 ml at low cuff pressures and can be on the order of 1.25 ml when the cuff pressure reaches mean arterial pressure, as shown in Figure 4. In general, dV art The maximum amplitude is expected to be in the range of 1 ml to 3 ml. This volume change results from an arterial pressure change of the order of 40 mmHg (pulse pressure, or the difference between systolic and diastolic blood pressure).

[0073] C cuff Since this is usually unknown before the expansion of cuff 4, in some embodiments, the pressure measurement in cuff 4 due to volumetric oscillations induced by pump 6 is also C cuff =dV osc / dP osc (6) It can also be used to determine cuff compliance.

[0074] An artificial volume oscillating of the order of 1 ml that produces a cuff pressure response of the order of 2 mmHg can be used to measure cuff compliance. A cuff pressure pulsation of the order of 2 mmHg does not cause arterial oscillation. This is especially true when cuff compliance is measured at absolute cuff pressures of 20–40 mmHg or 140–180 mmHg (i.e., above systolic blood pressure). At these pressures, the arterial response to a 2 mmHg pressure change is negligible, on the order of 0.02 ml. osc dP that responds to osc This effectively ensures that the reaction is due to the cuff response, and within this amplitude range (artificial pressure pulsation of 1-2 mmHg), there is no arterial damage.

[0075] The flowchart in Figure 5 illustrates exemplary methods for determining information about one or more arterial characteristics according to various embodiments. Various steps of this method can be performed using a processing unit 22, a first cuff 4, a pump 6, and a cuff pressure sensor 8. In particular, the processing unit 22 can control the operation of the pump 6 to inflate and deflate the first cuff 4. In some embodiments, a second cuff 10 is present to block blood flow in the artery below the first cuff 4 and can be inflated.

[0076] In short, in the method shown in Figure 5, the volume response of the artery below cuff 4 is determined at several different pressures within cuff 4, and information about one or more arterial characteristics is determined from the volume response.

[0077] In the optional first step, step 101, the second cuff 10 is placed on the arm 32 (or other limb) of the subject 30 and inflated (e.g., by pump 6) to a pressure level sufficient to block the flow of blood through the artery in the arm 32. This pressure level is referred to herein as the occlusion cuff pressure and is equal to or greater than the subject 30's systolic blood pressure. In some embodiments, the subject 30's systolic blood pressure is known, for example, from blood pressure measurement performed using conventional blood pressure measurement techniques, but in other embodiments, the occlusion cuff pressure may be reset to a value greater than the systolic blood pressure for the subject's population.

[0078] In embodiments in which a second cuff 10 is used, steps 103 and 105 are performed while the second cuff 10 is inflated to the occluding cuff pressure and blood flow in the artery below the first cuff 4 is stopped. In other cases, the second cuff 10 is not present or used, and steps 103 and 105 are performed while blood is flowing through the artery below the first cuff 4.

[0079] In step 103, volumetric vibrations are generated in the first cuff 4 at a first vibration frequency. The first cuff 4 is located at a first location on the arm 32 (or other limb) of the subject 30 (however, in embodiments where the second cuff 10 is used, on the same limb as the second cuff 10). In step 103, volumetric vibrations are generated in the first cuff 4 for multiple cuff pressures. Volumetric vibrations can be generated by the pump 6 or other vibrator components. The magnitude of the volumetric vibrations is clear, i.e., known. In some embodiments, the magnitude of the volumetric vibrations generated in the first cuff 4 is such that the resulting pressure vibrations in the cuff 4 are in the range of 20 to 50 mmHg. In some embodiments, the magnitude of the volumetric vibrations generated in the cuff 4 may be on the order of 10 ml, for example, in the range of 5 ml to 20 ml. If the compliance of the first cuff 4 is 0.5 ml / mmHg, a volumetric vibration of magnitude 10 ml may produce pressure pulsations on the order of 20 mmHg.

[0080] Generally, the first vibration frequency can be in the range of 1 Hz to 25 Hz. In embodiments where the second cuff 10 is not used, the first vibration frequency should be different from the heart rate of the subject 30. For example, if the heart rate of the subject 30 is 60 beats / minute (bpm), i.e., 1 Hz, the first vibration frequency should be different from 1 Hz. As an example, with a heart rate of 60 bpm, the first vibration frequency may be 3 Hz or higher. As another example, with a heart rate of 180 bpm (i.e., 3 Hz), the first vibration frequency may be 1 Hz or a frequency higher than 3 Hz.

[0081] An example is given with reference to Figure 6. Figure 6(a) shows the arterial pressure over time (P) when there are no cuffs 4 and 10 and no volume oscillations. art This is a graph showing arterial pressure P. art The 'V' represents blood pressure, and Figure 6(a) shows the change between systolic blood pressure (e.g., 120 mmHg) and diastolic blood pressure (e.g., 80 mmHg) according to a heart rate of 1 Hz. Figure 6(b) shows an exemplary artificial volume oscillation (V) at a preferred vibration frequency. osc This is a graph showing the change in volume. Therefore, volume oscillations can have a magnitude of 20 ml (+10 ml to -10 ml) and a frequency of 10 Hz.

[0082] In embodiments where a second cuff 10 is used to block blood flow in the artery below the first cuff 4, the first vibration frequency can be set to any desired value, but below we will assume the use of volume vibration as shown in Figure 6(b).

[0083] In step 105, while volumetric oscillations are being generated in the first cuff 4, the cuff pressure sensor 8 measures the pressure in the cuff 4. The cuff pressure sensor 8 generates a first cuff pressure signal representing the pressure in the cuff 4 over time. The signal output by the cuff pressure sensor 8 is P cuff It is shown as follows.

[0084] As described above, a stepwise inflation / measurement method can be used in which steps 103 and 105 include the steps of inflating the first cuff 4 to a first absolute pressure, generating volumetric vibrations in the cuff 4, and measuring the pressure in the cuff 4 while the volumetric vibrations are being generated. The pressure in the cuff 4 is then changed to a second absolute pressure (which may be higher or lower than the first absolute pressure), generating volumetric vibrations in the cuff 4, measuring the pressure in the cuff 4, and so on. In an alternative embodiment, a continuous inflation / measurement method can be used in which steps 103 and 105 include the steps of continuously generating volumetric vibrations in the cuff 4 while continuously inflating the first cuff 4 (for example, at a constant inflation rate), and measuring the pressure in the cuff 4 while the volumetric vibrations are being generated. In either embodiment, the absolute pressure in the cuff 4 may be in the range of 0 to 200 mmHg.

[0085] Figure 7(a) shows the cuff pressure signal (P) obtained using a continuous inflation / measurement technique when blood is flowing through the artery below the first cuff 4. cuff The cuff pressure signal is obtained by measuring the pressure in the first cuff 4 while the first cuff 4 is continuously inflated, generating the volume oscillations shown in Figure 6(b). In this example, the inflation rate of the first cuff 4 is approximately 3-4 ml / s, but it will be understood that other inflation rates can also be used. With typical inflation rates for cuffs, it may take 10-100 seconds to inflate the cuff from 0 mmHg to above systolic blood pressure. Higher frequency oscillations in the pressure in the first cuff 4 are caused by artificial volume oscillations, and lower frequency oscillations are caused by blood flow, so the effect of heartbeat-induced blood flow on the pressure in the first cuff 4 can be seen from the envelope of the cuff pressure signal in Figure 7(a).

[0086] Figure 7(b) shows the cuff pressure signal (P) obtained using a continuous inflation / measurement technique when blood flow through the artery below the first cuff 4 is stopped by the use of the second cuff 10. cuffThis shows that, similar to Figure 7(a), the cuff pressure signal in Figure 7(b) is obtained by measuring the pressure in the first cuff 4 while the first cuff 4 is continuously inflated, generating the volume oscillations shown in Figure 6(b). In this case as well, it will be understood that, although the inflation rate of the first cuff 4 is approximately 3-4 ml / s in this example, other inflation rates can also be used. In this case as well, with a typical inflation rate for the cuff, it may take 10-100 seconds to inflate the cuff from 0 mmHg to above the systolic blood pressure.

[0087] In the case of a stepwise inflation / measurement method, it will be understood that there may be a separate cuff pressure signal for each pressure "stage" in which cuff pressure measurement is performed on the cuff, in which case these signals can be considered together in the subsequent steps of this method, or there may be a single cuff pressure signal that includes the cuff pressure measurements at each pressure stage (in which case these pressure stages are observable in the cuff pressure signal).

[0088] In step 107, the processing unit 22 determines the arterial volume response, which represents the arterial volume response to distinct volume oscillations (at a first oscillation frequency) at different pressures in the first cuff 4. The arterial volume response is determined from the cuff pressure signal obtained in step 105. In some embodiments, the arterial volume response is the cuff compliance (C) of the first cuff 4. cuff The cuff compliance (C) of the first cuff 4 is determined using information about volumetric vibrations generated in the first cuff 4 during cuff pressure measurement. cuff ) is either known or already derived according to optional embodiments further described below. Information about volume vibration may be the maximum amplitude of the generated volume vibration and the frequency of the volume vibration. In some embodiments, information about volume vibration may be a signal representing the change in volume generated in the first cuff 4 (this volume change signal is dV osc(As shown). Information about volume vibration may be a control signal used by the pump 6 or other vibrator components to generate appropriate volume vibration, or may be based on such a control signal. In some embodiments, the arterial volume response is further determined using information indicating the absolute pressure in the first cuff 4 at the time a particular cuff pressure measurement is obtained.

[0089] In some embodiments, the arterial volume response to a distinct volume oscillation is determined using equation (4) or (5) above. Optionally, in these embodiments, (P) in equation (4) or (5) is used. cuff -P abs ) can be derived directly from the cuff pressure signal, for example, by trend fitting of the cuff pressure signal.

[0090] Figure 8 shows the arterial volume response obtained from the cuff pressure signal in Figure 7(a) using equation (4) or (5). In particular, Figure 8 shows the arterial volume response in ml (y axis) to distinct volume oscillations at different pressures (x axis) at mmHg in the first cuff 4 and to internal pressure oscillations at a first oscillation frequency. Figure 9 is a "magnified" view of a portion of the arterial volume response in Figure 8. Figure 10 is a further "magnified" view of a portion of the arterial volume response in Figure 9.

[0091] Preferably, the arterial volume response is determined from a consistent portion of the cuff pressure signal. That is, the arterial volume response is determined from a specific portion of the waveform in the cuff pressure signal. For example, as shown in Figure 10, the arterial volume response may be determined from the maximum value in the cuff pressure signal, i.e., where the cuff pressure signal represents the peak of the arterial pressure pulsation (where the arterial pressure is systolic blood pressure). Alternatively, the arterial volume response may be determined from the minimum value in the cuff pressure signal, i.e., where the cuff pressure signal represents the bottom of the arterial pressure pulsation (where the arterial pressure is diastolic blood pressure).

[0092] In embodiments where blood flows through an artery beneath the first cuff 4 (i.e., embodiments where a second cuff 10 is not used or is not present in the system 2), step 107 may include band-pass filtering the first cuff pressure signal to obtain or extract a signal component corresponding to a first vibration frequency of volume vibration. That is, the first cuff pressure signal includes a signal component (i.e., pressure change) from internally generated pulsations (i.e., blood flow at a frequency corresponding to the subject's heart rate 30) and a signal component (i.e., pressure change) from externally generated volume vibration. Since only the pressure change due to volume vibration is important for determining information about arterial characteristics, the cuff pressure signal is band-pass filtered to extract the signal component generated by volume vibration. Therefore, the band-pass filter should pass through (extract) a frequency band that includes the first vibration frequency, or a frequency band centered on the first vibration frequency, or at least a frequency band that does not include the subject's heart rate 30. The passband of the band-pass filter can be set based on the first vibration frequency. The bandpass filtered cuff pressure signal contains a signal component corresponding to the first oscillation frequency of volume oscillation and is used to determine the arterial volume response as described above. For example, (P in equation (4) cuff -P abs ) can be determined from the bandpass filtered cuff pressure signal by, for example, performing trend fitting of the cuff pressure signal to remove changes due to expansion and trend fitting of the resulting signal to remove internal pressure effects. As another example, (P in equation (4) cuff -P abs Further bandpass filtering can be used to determine the result.

[0093] As explained above, as an alternative to bandpass filtering the cuff pressure signal, time-domain de-trending can be used to extract information about the arterial response to external volume oscillations from the cuff pressure signal when the first oscillation frequency is much higher than the heart rate of subject 30. For example, a slowly changing trend can be fitted to the cuff pressure signal shown in Figure 7(a), and the signal can be obtained as the difference between the signal and the trend in Figure 7(a).

[0094] Finally, in step 109, information about the arterial characteristics of subject 30 is determined from the arterial volume response determined in step 107. Arterial characteristics may be arterial compliance and / or arterial viscosity.

[0095] As the cuff is inflated (from a low pressure, e.g., 0 mmHg), the wall pressure (P) tmWith note that this decreases, information about arterial properties, such as arterial compliance or arterial viscosity, can be determined from a function of the arterial volume response to transwall pressure (i.e., pressure applied across the arterial wall). The paper "Theory of the Oscillometric Maximum and the Systolic and Diastolic Detection Ratios" by G. Drzewiecki et al., Annals of Biomedical Engineering, Vol. 22, pp. 88-96, 1994, describes how transwall pressure relates to the action of arterial collapse. The function of the arterial volume response to transwall pressure is determined from the arterial volume response to the distinct pressure pulsations determined in step 107. Exemplary techniques for determining a function of arterial volume response to transwall pressure from arterial volume response to clear pressure oscillations are described in WO2020 / 126576 ("Control unit for deriving a measure of arterial compliance") and in the paper "A modelling framework for assessment of arterial compliance by fusion of oscillometry and pulse wave velocity information" by Bogatu, LI, Turco, S., Mischi, M., Woerlee, P., Bouwman, A., Korsten, EHHM, and Muehlsteff, J., Computer Methods and Programs in Biomedicine, 2020, 196. Figure 11 is a graph showing arterial volume response (in ml) as a function of transwall pressure (in mmHg). Based on equation (1), the relationship shown in Figure 11 represents arterial compliance as a function of transwall pressure, and therefore, the function of arterial volume response to transwall pressure provides information about the arterial compliance of the subjects 30.

[0096] In embodiments where the arterial characteristic is arterial viscosity, viscosity information can be obtained based on the artery's response to volume vibrations at several different frequencies. In that case, if information about viscosity is desired, steps 103 and 105 are repeated for one or more further vibration frequencies for the volume vibration, as indicated by arrow 111. The one or more further vibration frequencies, unlike the first vibration frequency, can be any frequency in the range of 1 Hz to 25 Hz. Similar to the first vibration frequency, in embodiments where the second cuff 10 is not used, the further vibration frequencies should be different from the heart rate of the subject 30.

[0097] Repeating steps 103 and 105 provides a further cuff pressure signal for each additional vibration frequency. In some embodiments (primarily applicable to continuous inflation / measurement techniques), once steps 103 and 105 are performed for a first vibration frequency, the first cuff 4 is deflated to an initial pressure level, and while the first cuff 4 is inflated again, steps 103 and 105 may be performed for a second vibration frequency. This provides a cuff pressure signal for the second vibration frequency. This can be repeated for each additional vibration frequency. In alternative embodiments (primarily applicable to stepwise inflation / measurement techniques), once a cuff pressure signal for a first vibration frequency at a particular pressure "stage" is obtained, volumetric vibrations at further vibration frequencies may be applied to obtain further cuff pressure signals. This can be repeated for each additional vibration frequency at each pressure "stage".

[0098] Instead of repeating steps 103 and 105 to obtain each further cuff pressure signal for each further vibration frequency, in step 103, instead of applying a volume vibration having a single frequency, a combination of volume vibrations of multiple frequencies may be applied, and a multi-frequency volume vibration may be applied in step 103. For example, a 3 Hz sine wave and a 10 Hz sine wave may be combined, and this combined signal may be used to drive the volume vibration. In this embodiment, it will be understood that it is necessary to process the obtained cuff pressure signals in order to separate the arterial volume response for different vibration frequencies. This can be achieved by using a bandpass filter to extract the signal components for each vibration frequency.

[0099] Regardless of the method used to obtain the cuff pressure signal for each further vibration frequency, the obtained cuff pressure signal is processed according to step 107 to determine the further arterial volume response at each vibration frequency. The further arterial volume response for a particular further vibration frequency is determined, as in step 107 above, based on the respective further cuff pressure signal, the cuff compliance of the first cuff, and the respective volume vibration signal related to the particular further vibration frequency of the volume vibration. As in step 107 above, the arterial volume response may be determined according to equation (4) or equation (5).

[0100] It will be understood that the repetition of steps 103 and 105 can be performed before the repetition of step 107 (for example, before determining the arterial volume response from the cuff pressure signal obtained for the first oscillation frequency).

[0101] In step 109, information about the arterial characteristics of subject 30 (e.g., arterial viscosity) can be determined from a first arterial volume response and further arterial volume responses. In particular, viscosity information can be derived from different arterial volume responses to external volume oscillations at different frequencies.

[0102] As an example, information about viscosity can be given as a comparison of the arterial volume response to volume oscillations at one vibration frequency with the arterial volume response to volume oscillations at one or more other vibration frequencies. For example, the arterial volume response to 10 Hz volume oscillations can be compared with the arterial volume response to 1 Hz volume oscillations. A change in viscosity over time (e.g., due to deterioration or improvement of the subject's health) can be observed by comparing arterial volume responses obtained in different measurement operations. Information about the viscosity of the artery can be stored in the form of a lookup table where each table entry indicates, for example, the arterial volume response at a certain transmural pressure and a certain vibration frequency. Other information about viscosity can be given by the arterial volume response to volume oscillations with low frequencies (which can be considered to describe the viscosity behavior in slow changes of stress) and the arterial volume response to volume oscillations at higher frequencies (which can be considered to indicate how the artery responds to higher load periods, i.e., higher heart rates).

[0103] As described, information about arterial characteristics can be presented in several ways. For example, information about arterial compliance is dV art (t) / dP ext (t) (e.g., the relationship shown in FIG. 11), or can be expressed in the form of |max(dV art )| / |max(dP ext )|. As another example, information about the viscosity of the artery is dV art (1Hz,time1) / dV art (10Hz,time1)-dV art (1Hz,time2) / dV art (10Hz,time2) (7) or simply, dV art (10Hz)-dV artIt can be represented in the form of (1 Hz). All the equations contain information regarding the viscosity of the artery. Also, the arterial volume reaction and / or a function of the arterial volume reaction with respect to the transmural pressure can be input into a model that describes the artery via the elastic / viscosity parameters. For example, measurements at different frequencies / transmural pressures can be fitted to the arterial model in order to infer the elastic / viscosity parameters.

[0104] As described above, the arterial volume reaction is determined based on the compliance of the first cuff 4. In some embodiments, the cuff compliance C cuff is known or derived before the method in FIG. 5 is executed. Techniques for deriving the compliance of the cuff are known in the art, for example, in EP3705033(“Blood pressure measurement device and control method”), and in the paper “Insights into oscillometry: An Experimental Study for Improvement of Cuff - Based Blood Pressure Measurement Technology” by Bogatu, L., Muehlsteff, J., Bresch, E., Smink, J., and Woerlee, P.H. in the 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2019 (pp.7068 - 7071).

[0105] In alternative embodiments, the compliance of the first cuff 4 may be determined using System 2 before or as part of the method in Figure 5. This may be useful as it allows cuff compliance to be determined at the start of the arterial characterization technique, and may allow the use of different cuffs using System 2 (e.g., cuffs of different sizes for subjects of different sizes). In either case, cuff compliance is required to determine the arterial volume response in step 107, and therefore cuff compliance should be determined or available before those steps are performed (e.g., before step 101, before steps 103 and 105, or after steps 103 and 105, where applicable). Cuff compliance can also be determined in embodiments in which a second cuff 10 is present and obstructs the flow of blood in the artery, or in embodiments in which the second cuff 10 is omitted or not used (or is used only when obtaining information about arterial characteristics).

[0106] To determine cuff compliance, the first cuff 4 is initially inflated to a specific pressure level (also referred to herein as the third cuff pressure). Any specific pressure level can be used, and in some embodiments, the specific pressure level is 80 mmHg.

[0107] While the pressure in the first cuff 4 is at a specific pressure level, volumetric oscillations are generated in the first cuff 4 by the pump 6 or other vibrator components. These volumetric oscillations generally have a magnitude smaller or much smaller than the volumetric oscillations generated (or to be generated) in step 103. In some embodiments, the magnitude of the volumetric oscillations generated in the first cuff 4 may be on the order of 1 ml or 1 ml, and the frequency of these volumetric oscillations may be 8 Hz or about 8 Hz. The volumetric oscillations generated here are intended to induce a pressure change in the cuff 4 on the order of 2 mmHg, i.e., a pressure change much smaller than the pressure change caused by the volumetric oscillations generated in step 103. The cuff pressure sensor 8 measures the pressure in the first cuff 4 when the volumetric oscillations are generated.

[0108] Next, the cuff pressure signal is band-pass filtered to extract the pressure response in the first cuff 4 due to volumetric oscillations. As in the above embodiment of step 107, the objective is to filter out (i.e. remove) the pressure response due to arterial blood flow having a frequency on the order of 1 Hz (60 BPM). Therefore, the cuff pressure signal is band-pass filtered using a passband centered on or containing the frequency of volumetric oscillations (e.g., 8 Hz) to extract the pressure response due to volumetric oscillations. As a result of band-pass filtering of the second cuff pressure signal, a filtered cuff pressure signal is obtained.

[0109] Next, the cuff compliance of the first cuff 4 can be determined from the filtered cuff pressure signal. In particular, based on equation (3) above, the cuff compliance C cuff To give this, the change in volume in the first cuff 4 due to volume pulsation (i.e., the amplitude of the volume oscillation, e.g., 1 ml) is dV. osc However, the filtered cuff pressure signal (dP oscIt is divided by the amplitude of ). As described above, further details of the derivation of cuff compliance can be found, for example, in EP3705033 and / or in the paper “Insights into oscillometry: An Experimental Study for Improvement of Cuff-Based Blood Pressure Measurement Technology”. This cuff compliance can then be used in step 107 to determine the arterial volume response.

[0110] In addition to determining information about arterial properties such as arterial compliance or arterial viscosity, evaluating fluid reactivity by calculating pressure-mean-body circulating filling pressure (MSFP) is another application that can benefit from the quantification of arterial compliance. As described below, MSFP can be derived by measuring stop-flow arterial equilibrium pressure and stop-flow venous equilibrium pressure. These pressure values ​​can be input into a Guytonian model to infer the mean-body circulating filling pressure and effective vascular volume state, which contribute to the evaluation of fluid reactivity, as described in "Estimation of mean systemic filling pressure in postoperative cardiac surgery patients with three methods" by Maas JJ et al., Intensive Care Med. 2012;38:1452-1460, and "Transient stop-flow arm arterial-venous equilibrium pressure measurement: determination of precision of the technique" by Aya HD et al., J Clin Monit Comput. 2016, 30(1):55-61. Information about arterial compliance can improve the accuracy of model parameters, and therefore lead to improved quantification of fluid reactivity.

[0111] MSFP is defined as the mean pressure present in the circulatory system when there is no blood movement. MSFP is affected by blood volume and smooth muscle tone. MSFP can be derived by measuring stop-flow arterial equilibrium pressure and stop-flow venous equilibrium pressure. Blood flow in the distal part of the limb (e.g., forearm) is stopped by occluding veins and arteries at a specific site (e.g., the upper arm). Traditionally, MSFP is determined by measuring blood pressure at the distal limb site during occlusion.

[0112] However, MSFP can be obtained using System 2 in Figure 2 without the need to measure blood pressure. To determine MSFP, first, information on the arterial compliance of the subject 30 is determined according to the method in Figure 5, with the second cuff 10 inflated to the occlusion cuff pressure so that blood flow in the artery below the first cuff 4 is stopped. Information on arterial compliance may take the form of an arterial volume versus transwall pressure function shown in Figure 11.

[0113] The cuff pressure at which maximum arterial compliance occurs at the first cuff 4 is determined from the function of arterial volume response to transwall pressure. Arterial compliance is given by equation (1), and therefore, arterial compliance at a particular transwall pressure corresponds to the slope of the function shown in Figure 11 at that transwall pressure. Thus, from Figure 11, it can be seen that maximum arterial compliance occurs at a transwall pressure of 0 mmHg. Since there is no blood flow under the first cuff 4 during the measurement of arterial compliance, the cuff pressure required to achieve this transwall pressure of 0 mmHg is equal to MSFP. Therefore, the MSFP for subject 30 is determined as the cuff pressure at which maximum arterial compliance occurs at the first cuff 4. Thus, this embodiment enables non-invasive measurement of MSFP.

[0114] In a further approach, information on arterial compliance can also be used to assess limb blood flow measured by venous occlusion plethysmography. This measurement is also based on employing a model that describes the physiology of the occluded limb, as described by Seagar, AD et al., “Interpretation of venous occlusion plethysmographic measurements using a simple model,” Med. Biol. Eng. Comput. (1984) 22:12. Accurate estimation of the model parameters (e.g., arterial compliance) can help interpret changes in limb volume during this measurement (e.g., detection of venous thrombosis).

[0115] Further details of steps 107 and 109 above are given below. A simulation framework is established to show how the cuff pressure signal is generated in the presence of artificial vibration and the arterial response to the artificial vibration (forward model), and to show how the cuff pressure signal can be processed to obtain the arterial response (inverse model). The simulation framework is given by the following equation P cuff =P abs +(V osc +V art ) / C cuff (8)

number

[0116] In equation (9), V art (P tm This is the arterial volume below the first cuff 4 as a function of transwall pressure across the arterial wall (as shown). Equation (9) can be found in the paper "Theory of the Oscillometric Maximum and the Systolic and Diastolic Detection Ratios" by G. Drzewiecki et al., referenced above.

[0117] Based on equation (2), the transwall pressure P given by the first cuff 4 is calculated. tm P tm =P art -P cuff (10) Using P art This is the arterial pressure that oscillates between systolic and diastolic blood pressure.

[0118] The first cuff 4 expands from 0 mmHg to 200 mmHg (i.e., P abs It is simulated that (it gradually increases). art As shown by the graph in Figure 6(a), the blood flow in the arteries causes it to oscillate between 80 mmHg and 120 mmHg at a frequency of approximately 1 Hz. In this example, V osc As shown in Figure 6(b), it oscillates with an amplitude of 10 ml and at 10 Hz. In this simulation, the cuff compliance is set to 0.5 ml / mmHg.

[0119] P abs As P increases, art and V osc The device vibrates, and the pressure inside the cuff 4 is measured. This generates the cuff pressure signal shown in Figure 7(a). Figure 7(a) shows the obtained wall pressure P tm This shows arterial volume pulsations caused by pulsation. Compared to the signal shown in Figure 4 (which is caused by internal arterial pulsations), the arterial volume pulsations in Figure 7(a) are caused by a combination of internal arterial pressure pulsations and external cuff pressure pulsations. Figures 8 and 9 show the detrenched or bandpass filtered pressure signals from Figure 7(a).

[0120] During the actual measurement of cuff pressure, the cuff pressure signal in Figure 8 is recorded, and the vibration volume (dV) is recorded. art Arterial volume pulsation can be obtained using equation (4) or equation (6), the recorded cuff pressure signal, and the known volume oscillation amplitude. Figure 10 shows the reconstructed arterial volume oscillation plotted together with the original arterial volume signal.

[0121] As described above, arterial compliance and other arterial collapse characteristics can be obtained by reconstructing the arterial volume response versus transwall pressure function, as shown in Figure 11. As described, this function can be achieved by obtaining the arterial volume response to an artificial pressure oscillation of amplitude 20 mmHg. For example, in Figure 10 (an enlarged view of part of Figure 9), a low-frequency pulsation of a larger amplitude is generated by the internal arterial pressure, i.e., by blood flow. The faster, smaller volume oscillation is the volume oscillation caused by the artificial pressure pulsation of 20 mmHg. In response to the pressure change of 20 mmHg, the arterial volume response dV art This can be obtained at several cuff pressures. To minimize the effects of arterial pressure oscillations, it is useful to process specific parts of the waveform, as shown in Figure 10. In Figure 10, the peak of the arterial pressure pulsation, where the arterial pressure is always at its systolic value, may be the part of the waveform processed to determine arterial compliance. In an alternative embodiment, the trough of the arterial pressure pulsation, where the arterial pressure is always at its diastolic value, may be the part of the waveform processed to determine arterial compliance. Arterial compliance values ​​at different cuff pressures can be determined parametrically or nonparametrically to obtain an arterial volume versus transwall pressure function. Exemplary techniques for determining a function of arterial volume response to transwall pressure are described in WO2020 / 126576, titled "Control unit for deriving a measure of arterial compliance," and in the paper "A modelling framework for assessment of arterial compliance by fusion of oscillometry and pulse wave velocity information."

[0122] Therefore, the techniques described above provide an improved way to non-invasively determine information about arterial properties, such as arterial compliance and arterial viscosity. These techniques do not require blood pressure measurement, which can be a source of measurement errors in conventional techniques. Furthermore, the techniques described can be performed using existing equipment or devices used for patient monitoring.

[0123] Variations of the disclosed embodiments can be understood and implemented by those skilled in the art in carrying out the principles and techniques described herein, based on a study of the drawings, this disclosure, and the appended claims. In the claims, the words “equipped with” or “having” do not exclude other elements or steps, and singular elements do not exclude plural elements. A single processor or other unit performs the functions of several items described in the claims. The mere fact that several means are described in mutually different dependent claims does not imply that combinations of these means cannot be used advantageously. Computer programs may be stored or distributed on a suitable medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunications systems. No reference numeral in the claims should be construed as limiting its scope.

Claims

1. 1. A method for determining information about an arterial characteristic of an artery of a subject, the method comprising: (a) generating volumetric oscillations at a first oscillation frequency in a first cuff at a first location on the subject's limb, the volumetric oscillations being generated at a plurality of cuff pressures in the first cuff; (b) measuring pressure in the first cuff during said generating of said volume oscillations to generate a first cuff pressure signal; (c) dV ａｒｔ = (P ｃｕｆｆ -P ａｂｓ ) *C ｃｕｆｆ -dV ｏｓｃ determining a first arterial volume response representative of a volume response of the artery to the volume oscillations at each cuff pressure using a ａｒｔ is the first arterial volume response, P ｃｕｆｆ is the first cuff pressure signal, P ａｂｓ is the respective cuff pressure in the first cuff, and C ｃｕｆｆ is the cuff compliance of the first cuff, and dV ｏｓｃ determining a first arterial volume response, said first arterial volume response being a signal representative of a change in volume in said first cuff due to said generated volume oscillations; (d) determining the information about the arterial characteristics of the subject from the first arterial volume response; The method comprising:

2. The step (c) bandpass filtering the first cuff pressure signal to obtain a signal component corresponding to the first oscillation frequency of the volume oscillation; determining the first arterial volume response based on the bandpass filtered first cuff pressure signal; The method of claim 1 further comprising:

3. The method comprises: Prior to step (a), inflating a second cuff at a second location on the subject to a cut-off cuff pressure that is a cuff pressure above the systolic blood pressure of the subject, the second location being on the same limb as the first location and upstream of the first location, inflating a second cuff at a second location on the subject to a cut-off cuff pressure that is a cuff pressure above the systolic blood pressure of the subject. and 2. The method of claim 1, wherein steps (a) and (b) are performed while the second cuff is inflated to the cut-off cuff pressure.

4. The step (d) determining a function of arterial volume response to transmural pressure from the first arterial volume response; determining said information about said arterial properties from said determined function; 4. The method of claim 3, comprising:

5. The arterial characteristic comprises arterial compliance, and the method further comprises: determining a cuff pressure at which maximum arterial compliance occurs in said first cuff from a function of arterial volume response to transmural pressure; determining a mean systemic filling pressure (MSFP) for the subject as the cuff pressure at which the maximum arterial compliance occurs in the first cuff; The method of claim 1 , further comprising:

6. The method comprises: (e) repeating steps (a) and (b) for one or more additional oscillation frequencies for the volume oscillation to generate respective one or more additional cuff pressure signals; (f) determining a further arterial volume response for each of the one or more further oscillation frequencies, the further arterial volume response representing a volume response of the artery to the volume oscillations at a respective cuff pressure, the further arterial volume response being determined based on the respective one or more further cuff pressure signals, the cuff compliance of the first cuff, and respective volume oscillation signals related to respective oscillation frequencies of the volume oscillations generated in the first cuff; and 6. The method of claim 1 , wherein step (d) comprises determining the information about the arterial characteristics of the subject from the first arterial volume response and the further arterial volume response.

7. 7. The method of claim 6, wherein the arterial property is viscosity of the artery, and step (d) comprises determining information about the viscosity of the artery from a comparison of the first arterial volume response and the further arterial volume response.

8. The method further comprises, prior to step (c), generating volume oscillations in the first cuff at a second oscillation frequency when the first cuff is inflated to a third cuff pressure; measuring pressure in the first cuff during said generating of said volume oscillations at said second oscillation frequency to generate a third cuff pressure signal; bandpass filtering the third cuff pressure signal to obtain a signal component corresponding to the second oscillation frequency of the volume oscillation; determining the cuff compliance of the first cuff from the filtered third cuff pressure signal; 8. The method of claim 1, further comprising determining the cuff compliance of the first cuff by:

9. A computer program comprising computer readable code configured, when executed by a suitable computer or processing unit, to cause the computer or processing unit to perform a method according to any one of claims 1 to 8.

10. 1. An apparatus for determining information about an arterial characteristic of an artery of a subject, the apparatus comprising: (a) initiating generation of volumetric oscillations at a first oscillation frequency in a first cuff at a first location on the limb of the subject, the volumetric oscillations being generated at a plurality of cuff pressures in the first cuff; (b) obtaining a first cuff pressure signal comprising a measurement of pressure in the first cuff during the generation of the volume oscillations; and (c) dV ａｒｔ = (P ｃｕｆｆ -P ａｂｓ ) *C ｃｕｆｆ -dV ｏｓｃ determining a first arterial volume response representative of a volume response of the artery to the volume oscillations at each cuff pressure using a ａｒｔ is the first arterial volume response, P ｃｕｆｆ is the first cuff pressure signal, P ａｂｓ is the respective cuff pressure in the first cuff, and C ｃｕｆｆ is the cuff compliance of the first cuff, and dV ｏｓｃ determining a first arterial volume response, the first arterial volume response being a signal representative of a change in volume in the first cuff due to the generated volume oscillation; (d) determining the information about the arterial characteristics of the subject from the first arterial volume response; and An apparatus for performing the above.

11. The apparatus comprises: prior to act (a), further initiating inflation of a second cuff at a second location on the subject, on the same limb as the first location and upstream of the first location, to a cut-off cuff pressure, the cuff pressure being above a systolic blood pressure of the subject; 11. The apparatus of claim 10, wherein act (a) and act (b) are performed while the second cuff is inflated to the cut-off cuff pressure.

12. The act (d) determining a function of arterial volume response to transmural pressure from the first arterial volume response; determining said information about said arterial properties from said determined function; and The apparatus of claim 11 , comprising:

13. The arterial characteristic comprises arterial compliance, and the device further comprises: determining a cuff pressure at which maximum arterial compliance occurs in said first cuff from a function of arterial volume response to transmural pressure; determining a mean systemic filling pressure (MSFP) for the subject as the cuff pressure at which the maximum arterial compliance occurs in the first cuff; The apparatus according to claim 10 , further comprising:

14. The apparatus comprises: (e) repeating acts (a) and (b) for one or more additional oscillation frequencies for the volume oscillation to generate respective one or more additional cuff pressure signals; (f) determining a further arterial volume response for each of the one or more further oscillation frequencies, the further arterial volume response representing a volume response of the artery to the volume oscillations at a respective cuff pressure, the further arterial volume response being determined based on the respective one or more further cuff pressure signals, the cuff compliance of the first cuff, and a respective volume oscillation signal related to a respective oscillation frequency of the volume oscillations generated in the first cuff; Further, 14. The apparatus of any one of claims 10 to 13, wherein act (d) comprises determining the information about the arterial characteristics of the subject from the first arterial volume response and the further arterial volume response.

15. 15. The apparatus of claim 14, wherein the arterial characteristic is a viscosity of the artery, and act (d) includes determining information about the viscosity of the artery from a comparison of the first arterial volume response and the further arterial volume response.