Fluid reactivity using ultrasound data

Abstract

The present invention provides improved metrics of fluid reactivity derived based on comparing the ratios between blood velocity and vessel diameter before and after fluid administration.

Description

Technical Field

[0001] The present invention relates to a method for evaluating the reactivity of a fluid. Background Art

[0002] US2018 / 0353157 discloses a device for automatically evaluating the functional hemodynamic characteristics of a patient.

[0003] Critically ill patients, such as those in cardiogenic shock or hemorrhagic shock, can benefit from intravenous administration of fluids (e.g., saline, blood) to improve physiological stability and patient prognosis. However, administration of excessive fluids carries the risk of volume overload, which is detrimental to patient prognosis.

[0004] Fluid responsiveness is assessed after fluid administration or after performing a passive leg raise (PLR), which allows blood from the venous circulation in the legs to re-enter the arterial circulation. Changes in cardiac preload due to breathing can also be used as a method to assess whether a patient is likely to be fluid responsive. There are several methods of assessing fluid responsiveness in the art. However, all are based on the same principle of increased stroke volume variation (SVV) or a proxy for SVV after fluid administration (or PLR). This is based on the well-known Frank-Starling mechanism. Hypovolemic patients are on the steep portion of the Frank-Starling curve and will have a greater increase in SVV when fluid is administered relative to normovolemic patients.

[0005] Many known hemodynamic measurement systems (such as PiCCO and FloTrac) measure SVV, and can therefore be used to assess fluid responsiveness. Instead of using SVV, changes in stroke volume (SV) or cardiac output (CO) can also be used directly, using hemodynamic measurement equipment or via direct imaging of the heart or major vessels (e.g., the aorta). Pulse pressure changes (PPV-a proxy for SVV) from a continuously acquired arterial blood pressure signal can also be used. Therefore, standard methods for assessing fluid responsiveness rely on invasive measurements of CO, SV, or blood pressure.

[0006] Therefore, existing methods for assessing fluid responsiveness rely on methods that tend to be invasive, indirect, and often unreliable. For example, PiCCO pulse contour analysis uses changes in blood pressure morphology to determine SVV and is unreliable when assessed at time points far from calibration. FloTrac has the same limitations, and these are persistent because it is an uncalibrated method. Another limitation is that changes in SVV, SV, and CO, which are markers of fluid responsiveness, are only defined for mechanically ventilated patients who receive tidal volumes of, for example, greater than 8 ml / kg body weight through mechanical ventilation. For patients receiving lower tidal volumes or patients who breathe spontaneously, these markers of fluid responsiveness perform poorly. Summary of the invention

[0007] The invention is defined by the independent claims. The dependent claims define advantageous embodiments.

[0008] According to an example according to an aspect of the present invention, a computer-implemented method is provided, comprising: receiving first ultrasound data of a blood vessel of a subject, the first ultrasound data being acquired during a first time period, the first time period occurring before a bolus injection of a fluid is administered into an artery of the subject; receiving second ultrasound data of a blood vessel of the subject, the second ultrasound data being acquired during a second time period, the second time period occurring after the bolus injection of the fluid is administered into an artery of the subject; determining a first measure of a flow velocity of blood in the blood vessel of the subject using the first ultrasound data; determining a first measure of a diameter of the blood vessel using the first ultrasound data; determining a second measure of the flow velocity of the blood in the blood vessel of the subject using the second ultrasound data; determining a second measure of the diameter of the blood vessel using the second ultrasound data; determining a first ratio of blood velocity to blood vessel diameter, or a correlation thereof, using the first blood velocity measure and the first blood vessel diameter measure; determining a second ratio of blood velocity to blood vessel diameter, or a correlation thereof, using the second blood velocity measure and the second blood vessel diameter measure; deriving a fluid responsiveness index of the subject based on a comparison between the first ratio and the second ratio; and generating a data output indicative of the fluid responsiveness index.

[0009] Thus, the proposed concept is to use the ratio of blood velocity to vessel diameter (or vice versa) as a fluid responsiveness index. In particular, a comparison of this ratio between a time point before fluid administration and a time point after fluid administration (e.g., a ratio of this ratio) is used to derive a fluid responsiveness index. As demonstrated later in this document, this index has been found to be more reliable than at least some existing fluid responsiveness indices (particularly non-invasive indices) and can be measured non-invasively and quasi-continuously.

[0010] The first ratio and the second ratio are calculated in the same manner; that is, they are two calculations of the same parameters calculated using the same function.

[0011] The method may employ the use of a predefined mapping between the ratio comparison results and the fluid reactivity index.

[0012] In some embodiments, the artery is preferably the left common carotid artery.

[0013] In some embodiments, comparing includes calculating a difference between the first ratio and the second ratio.

[0014] In some embodiments, each of the first and second ultrasound data includes Doppler ultrasound data and imaging ultrasound data, such as B-mode ultrasound data or M-mode ultrasound data.

[0015] In some embodiments, the Doppler ultrasound data is pulsed wave Doppler ultrasound data.

[0016] In some embodiments, the first and second vessel diameter measures are calculated using imaging ultrasound data in the corresponding first and second ultrasound data. In some embodiments, the first flow velocity measure and the second flow velocity measure are calculated using Doppler data in the corresponding first and second ultrasound data.

[0017] In some embodiments, each of the first ultrasound data and the second ultrasound data comprises dual-function ultrasound data, wherein the dual-function ultrasound data comprises interleaved B-mode acquisition and Doppler mode acquisition. This is an efficient way to acquire these two types of data in one acquisition process, so that these two metrics can be derived from the component elements of the acquired data.

[0018] In some embodiments, the first and second measures of flow velocity in the blood vessel are measures of peak systolic velocity (PSV) measured during the respective first and second periods. As will be explained below, PSV provides particularly accurate results in the final fluid responsiveness index, comparable to results obtainable by invasive means.

[0019] In some embodiments, the systolic peak flow velocity for each of the first flow velocity metric and the second flow velocity metric is obtained based on sampling the flow velocity of the blood vessel at multiple time points within the corresponding period, and selecting the flow velocity corresponding to the 90th percentile (or about / approximately the 90th percentile) of a graph of the sampled velocity versus time within the period. The inventors proposed the 90th percentile because it has been found to be particularly robust to noise and motion artifacts.

[0020] In some embodiments, the previously mentioned second period is timed to begin after a predefined time interval after administration of the bolus. The calculation of the fluid responsiveness index may assume this time interval.

[0021] In some embodiments, the predefined time interval after administration of the bolus is about 15 minutes.

[0022] In some embodiments, each period has a duration of 120 seconds or less, such as 60 seconds or less, such as between about 20 seconds and about 60 seconds. Thus, the method proposes measuring the periods before and after the fluid bolus and comparing them to obtain a discrete measure of the fluid responsiveness index.

[0023] The index can also be measured continuously (or quasi-continuously) by using a moving window that starts after the bolus has been administered and comparing the ratio value calculated over this window with the pre-bolus ratio value, thus obtaining a continuous or quasi-continuous measurement of the fluid responsiveness index.

[0024] To this end, in some embodiments, the method includes repeating the following steps at regular time intervals: receiving second ultrasound data; determining a second measure of flow velocity; determining a second measure of the diameter of the blood vessel; determining a second ratio of blood velocity to blood vessel diameter; and deriving a fluid responsiveness index of the subject to provide post-bolus monitoring of the fluid responsiveness index. Thus, this provides repeated or cyclical measurements.

[0025] The method may include recording a log of each derived value of the fluid reactivity index and its corresponding measurement time, and determining trend information of the fluid reactivity index as a function of time, and generating a data output indicative of the trend information.

[0026] In some embodiments, the first and second ultrasound data are received from an ultrasound acquisition device.

[0027] In some embodiments, the method includes: generating a first control instruction for communicating with an ultrasound acquisition device to enable the device to acquire first ultrasound data; and generating a second control instruction for communicating with the ultrasound acquisition device to enable the device to acquire second ultrasound data.

[0028] In some embodiments, the method further comprises receiving a user input indicating a timing for administering a bolus of liquid, and wherein the second control instruction is generated to cause the ultrasound acquisition device to acquire the second ultrasound data at a time determined based on the user input.

[0029] Another aspect of the present invention is a computer program product comprising computer code configured to cause a processor to perform a method according to any embodiment described in this document or according to any claim of this application.

[0030] The present invention can also be realized in the form of hardware.

[0031] Therefore, another aspect of the present invention is a processing unit comprising: an input / output portion; and one or more processors configured to perform any of the methods described and / or claimed herein. To this end, one or more processors may be configured to: receive via an input / output first ultrasound data of a blood vessel of a subject, the first ultrasound data being acquired during a first period of time, the first period of time occurring before a bolus of fluid is administered into an artery of the subject; receive via the input / output second ultrasound data of a blood vessel of the subject, the second ultrasound data being acquired during a second period of time, the second period of time occurring after a bolus of fluid is administered into an artery of the subject; determine a first measure of flow velocity of blood in the blood vessel of the subject using the first ultrasound data; determine a first measure of diameter of the blood vessel using the first ultrasound data; determine a second measure of the flow velocity of the blood vessel of the subject using the second ultrasound data; determine a second measure of diameter of the blood vessel using the second ultrasound data; determine a first ratio of blood velocity to blood vessel diameter, or a correlation thereof, using the first blood velocity measure and the first blood vessel diameter measure; determine a second ratio of blood velocity to blood vessel diameter, or a correlation thereof, using the second blood velocity measure and the second blood vessel diameter measure; derive a fluid responsiveness index of the subject based on a comparison between the first ratio and the second ratio; and generate a data output indicative of the fluid responsiveness index, and preferably route the generated data output to the input / output.

[0032] Another aspect of the invention provides a system comprising a processing unit as described above or according to any embodiment described in this document, and an ultrasound acquisition device operatively coupled to the processing unit. First and second ultrasound data are received from the ultrasound acquisition device.

[0033] In some advantageous embodiments, the ultrasound acquisition device comprises a wearable ultrasound transducer unit, such as a wearable patch integrating the ultrasound transducer device. This allows continuous non-invasive monitoring in an efficient and non-invasive manner.

[0034] In addition to the above, it should be noted that features between different aspects (system, method, computer program product) of the present invention are intended to be fully compatible, such that features or options recited in the context of one aspect may equally apply to any other aspect.

[0035] These and other aspects of the invention will be apparent from and elucidated with reference to the embodiment(s) described hereinafter. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] For a better understanding of the present invention, and in order to more clearly show how the same may be carried into effect, reference will now be made, by way of example only, to the accompanying drawings, in which:

[0037] Figure 1 The steps of an example method according to one or more embodiments of the present invention are outlined;

[0038] Figure 2 Components of example processing devices and systems are schematically outlined in accordance with one or more embodiments of the present invention;

[0039] Figure 3 illustrates the timing of data acquisition relative to the timing of fluid bolus administration; and

[0040] Figure 4-11 The results of experimental testing illustrating the relative effectiveness of different fluid responsiveness indices are shown graphically, wherein: Fig.11 Results are shown for speed: diameter ratios proposed according to embodiments of the present invention. DETAILED DESCRIPTION

[0041] The present invention will be described with reference to the accompanying drawings.

[0042] It should be understood that the detailed description and specific examples, although indicating exemplary embodiments of the device, system and method, are intended only for illustrative purposes and are not intended to limit the scope of the invention. These and other features, aspects and advantages of the device, system and method of the present invention will be better understood from the following description, the appended claims and the accompanying drawings. It should be understood that the drawings are merely schematic and not drawn to scale. It should also be understood that the same reference numerals are used throughout the drawings to indicate the same or similar components.

[0043] The present invention provides an improved measure of fluid responsiveness derived based on comparing the ratio between blood velocity and vessel diameter before and after fluid administration.

[0044] Maintaining adequate fluid balance is essential to optimize the prognosis of critically ill patients. To this end, clinicians need to identify whether a patient is fluid responsive before administering a large fluid bolus to avoid fluid overload. Existing methods for measuring fluid responsiveness are generally invasive, indirect, and often unreliable. This paper proposes a dynamic index that can be derived from diameter and velocity measurements of arteries using ultrasound. The method is non-invasive and a direct measure of fluid responsiveness.

[0045] Particularly advantageous embodiments may optionally employ the use of a wearable ultrasound acquisition device. This provides a further improvement in non-invasiveness and also increases operator independence of the measurement, as the wearable ultrasound unit can be fixed to the subject at a stable arterial position.

[0046] Figure 1The steps of an example method according to one or more embodiments are summarized in block diagram form.Before further explanation in the form of an example embodiment, the steps will be summarized.

[0047] The method may be implemented by a computer.

[0048] The method 10 includes receiving 12 first ultrasound data of a blood vessel of a subject, the first ultrasound data acquired during a first period of time, the first period of time occurring before a bolus injection of a fluid is administered into an artery of the subject. The method 10 also includes receiving 14 second ultrasound data of the blood vessel of the subject, the second ultrasound data acquired during a second period of time, the second period of time occurring after the bolus injection of the fluid is administered into an artery of the subject. The blood vessel may be, for example, a peripheral blood vessel, such as a peripheral artery, for maximum ease of measurement.

[0049] The method 10 further comprises determining 16 a first measure of flow velocity of blood in a vessel of the subject, or a correlate thereof, using the first ultrasound data. The method 10 further comprises determining 18 a first measure of a diameter of the vessel using the first ultrasound data.

[0050] The method 10 further comprises determining 20 a second measure of flow velocity of blood in a vessel of the subject, or a correlate thereof, using the second ultrasound data. The method 10 further comprises determining 22 a second measure of vessel diameter using the second ultrasound data.

[0051] The method 10 also includes determining 24 a first ratio of blood velocity to vessel diameter, or a correlation thereof, using the first blood velocity metric and the first vessel diameter metric. The method 10 also includes determining 26 a second ratio of blood velocity to vessel diameter, or a correlation thereof, using the second blood velocity metric and the second vessel diameter metric.

[0052] The method also includes deriving 28 a fluid reactivity index of the object based on the comparison between the first ratio and the second ratio. The method may also include generating 30 a data output indicative of the fluid reactivity index. For example, the data output may be communicated to a data storage device for storage, or to another computer for further processing. The data output may be communicated to a user interface for presentation to a user via the user interface.

[0053] Thus, embodiments of the present invention provide arterial diameter and blood velocity (both obtained from ultrasound data) as inputs to a novel algorithm that converts these measurements into a fluid responsiveness index (based on the ratio between the two or their correlation). This software feature can be enabled on any ultrasound system (including wearable, handheld, etc.) to non-invasively assess fluid responsiveness.

[0054] It should be noted that although the above description indicates measuring the diameter of a blood vessel, it is clear that measuring a parameter related or proportional thereto achieves a completely equivalent effect, such as measuring the radius or circumference, will achieve the same effect.

[0055] As mentioned above, the method may also be implemented in hardware form, for example in the form of a processing device configured to perform the method according to any example or embodiment described in this document or according to any claim of this application.

[0056] To further aid understanding, Figure 2 A schematic representation of an example processing unit 32 configured to perform a method according to one or more embodiments of the present invention is presented. The processing unit is shown in the context of a system 30 that includes the processing unit. The processing unit alone represents one aspect of the present invention. The system 30 is another aspect of the present invention. The system provided need not include all of the hardware components shown; it may include only a subset of them.

[0057] The processing unit 32 includes one or more processors 36 configured to perform the method according to the above summary or according to any embodiment described in this document or any claim of this application. In the example shown, the processing unit also includes an input / output unit 34 or a communication interface. Figure 2 In the example shown, the system 30 also includes an ultrasound acquisition device 42 operatively coupled to the processing unit 32. The aforementioned first and second ultrasound data can be received from the ultrasound acquisition device. Alternatively, the first and second ultrasound data can be received from different sources, such as from a data storage device, or from a central server, or from a communication interface. In some embodiments, ultrasound data can be received from an ultrasound acquisition device external to the provided system.

[0058] The present invention may also be implemented in software. Therefore, another aspect of the present invention is a computer program product comprising computer program code, which is configured to, when running on a processor, cause the processor to perform a method according to the embodiments described in this document or according to any claim of this application.

[0059] Note, refer again Figure 2 The system 30 , system 30 or processing unit 32 may include a memory 38 storing computer program instructions for being executed by one or more processors 36 of the processing unit to cause the one or more processors to perform a method according to any embodiment described in the present disclosure.

[0060] In some embodiments, the method 10 may include steps for controlling the acquisition of the first and second ultrasound data. For example, the method 10 may include: generating a first control instruction for communicating with the ultrasound acquisition device 42 to enable the device to acquire the first ultrasound data; and generating a second control instruction for communicating with the ultrasound acquisition device to enable the device to acquire the second ultrasound data.

[0061] In some embodiments, the method further comprises receiving a user input indicating a timing for administering a bolus of liquid, and wherein a second control instruction is generated to cause the ultrasound acquisition device to acquire second ultrasound data at a time determined based on the user input. This may be received, for example, from a user interface device (not shown).

[0062] With respect to the ultrasound data acquisition device 42, in an advantageous embodiment, this may include a wearable ultrasound transducer unit, such as a wearable patch with an integrated ultrasound transducer device. For example, the wearable unit may carry an ultrasound transducer array. The wearable patch may have an adhesive element to allow the patch to be removably adhered to the user's skin in a manner that acoustically couples the ultrasound transducer array to body tissue. Other forms of wearable units are also possible, such as a band that can be worn by a user or a garment with an integrated transducer device. In operation, the transducer unit may be coupled to the user's body at a position above a vessel of interest (e.g., a peripheral artery, such as a carotid artery, such as a left common carotid artery). The use of wearable ultrasound may facilitate the calculation of a fluid responsiveness index in a manner that is obtained continuously and non-invasively.

[0063] With regard to the first ultrasound data 12 and the second ultrasound data 14, preferably, in each case, the ultrasound data includes both Doppler ultrasound data and imaging ultrasound data, such as B-mode ultrasound data. The Doppler ultrasound data may be pulsed wave Doppler ultrasound data, but this is not required. The Doppler data may be used to measure the blood flow velocity through a blood vessel. The imaging data (e.g., B-mode data) may be used to measure the diameter of a blood vessel. In other words, the imaging ultrasound data in the corresponding first ultrasound data and the second ultrasound data may be used to calculate the first blood vessel diameter metric and the second blood vessel diameter metric, and the Doppler data in the corresponding first ultrasound data and the second ultrasound data may be used to calculate the first flow velocity metric and the second flow velocity metric.

[0064] "Imaging data" refers to an acquisition of line scan data suitable for reconstructing an image. For example, in other words, multi-line data. In other words, ultrasound data includes scan line data spanning at least one plane. The determination of the vessel diameter may be performed by actually reconstructing an image from the acquired imaging data, or it may be accomplished by lower level methods, such as based on detecting characteristic intensity points in the acquired ultrasound lines (which are believed to correspond to the boundaries of the vessel), and calculating the distances between these points.

[0065] A convenient and technically efficient way to acquire both Doppler ultrasound data and B-mode ultrasound data is to use dual-function ultrasound imaging. Thus, in some embodiments, each of the first ultrasound data and the second ultrasound data comprises dual-function ultrasound data comprising interleaved B-mode acquisition and Doppler mode acquisition. A skilled person will be aware of modules for implementing dual-function imaging.

[0066] The present invention may also be implemented in software. The present invention may also be implemented in software. Therefore, another aspect of the present invention is a computer program product comprising computer program code means, which is configured to, when running on a processor, cause the processor to perform a method according to the embodiments described in this document or according to any claim of this application.

[0067] Embodiments of the invention include the step of measuring the blood flow velocity through the vessel before and after the administration of the fluid. To this end, in a preferred set of embodiments it is proposed to measure the value of the systolic peak blood velocity (PSV) over one or more cardiac cycles spanning the corresponding measurement period. For example, an average value of the systolic peak velocity (PSV) can be calculated over multiple heartbeats. For consistency, an average value of the vessel diameter can also be measured over the same multiple heartbeats. The ratio of blood velocity to vessel diameter can then be calculated as a ratio of the average values.

[0068] In some instances, the raw PSV may be prone to measurement errors. Therefore, in some embodiments, in order to improve robustness, the relevance of the PSV may be measured. For example, in some embodiments, the method includes using the 90th percentile of the blood flow velocity during the relevant measurement period. In other words, more specifically, in some embodiments, the systolic peak velocity (PSV) for each of the first flow velocity measure and the second flow velocity measure may be obtained based on the following operations: sampling the flow velocity of the blood vessel at multiple time points during the corresponding period; and selecting the flow velocity corresponding to the 90th percentile of the curve graph of the sampled velocity over time during the period.

[0069] Furthermore, it should be noted that instead of taking the ratio between speed and diameter, the inverse may be taken instead, which achieves the same effect.

[0070] exist Figure 3 The timing scheme of the method is schematically illustrated in FIG. 1 . Administration of a bolus of fluid into the subject's artery is shown at nominal time t=0. Administration of the bolus is preceded by a pre-bolus period, which is indicated as a period of time at nominal time t -1 Following the bolus administration is the post-bolus period, which is indicated as the post-bolus time t +1End at. By way of example, the pre-bolus period and the post-bolus period may each have a duration of 15 minutes. In each of these periods, at least one measurement of the vessel diameter of the blood flow velocity is performed, the measurement results being obtained using the ultrasound data collected during the corresponding measurement period. A single measurement period will typically be short compared to the entire duration of the pre-bolus or post-bolus period. In practice, multiple measurements may be performed in each of the pre-bolus and post-bolus periods, each measurement being based on ultrasound data collected during the corresponding measurement period. By way of example, for each measurement of the vessel diameter and the blood flow velocity, ultrasound data may be collected during an ultrasound period of, for example, 20-60 seconds duration (this is an example for illustration only). If more than one measurement is to be performed before and / or after fluid administration, an average of multiple measured diameters and flow velocities may be taken and used to calculate a single total ratio for each of the pre-fluid administration and post-fluid administration periods.

[0071] To illustrate the effectiveness of the proposed metric as an indicator of fluid responsiveness, reference will now be made to the statistical results of the tests Figure 4-11 The test process described is used to collect experimental data.

[0072] Testing was performed using a test cohort of 13 patients, with a total of 14 fluid boluses administered in a procedure room setting.

[0073] According to the above reference Figure 3 The protocol described above, a fluid bolus 62 was administered to each patient at a nominal time t=0. Ultrasound data was collected during ultrasound measurement periods of 20-60 s duration, obtained for the test procedure using a handheld ultrasound probe, before 64 and after 66 bolus administration, over a 15 minute period. In addition, arterial blood pressure (ABP) measurements and PiCCO-based stroke volume variation (SVV), stroke volume (SV), and cardiac output (CO) measurements were obtained for comparison purposes. ABP measurements were collected by invasive measurement means, and SVV, SV, and CO measurements were all collected invasively.

[0074] For the purpose of validating the fluid reactivity index proposed according to embodiments of the present invention, experimental testing requires only these, as will become clear.

[0075] At least one ultrasound measurement is performed in both the pre-bolus 64 and post-bolus time periods 66. If more than one ultrasound measurement period is performed, an average of the ultrasound-derived measurements over the entire time periods 64, 66 is taken. In effect, the pre-bolus period serves as a control period, while the post-bolus period serves as a test period.

[0076] Measures of ABP, SVV, SV and CO are obtained as comparative measures. As described above, stroke volume variation or its proxy is a standard parameter used to measure fluid responsiveness. This is based on the well-known Frank-Starling mechanism. Hypovolemic patients are on the steep part of the Frank-Starling curve and will have a greater increase in SVV when fluid is administered relative to normovolemic patients.

[0077] Stroke volume (SV) and cardiac output (CO) can also be used as indirect measures of fluid responsiveness. Pulse pressure variation (PPV - a proxy for SVV) from a continuously acquired arterial blood pressure signal can also be used.

[0078] exist Figure 4-11 The results of the data obtained for the test process are presented in . Each of the presented graphs relates to the data of one measured parameter (described below). For each parameter, three values ​​are plotted: the value of the parameter measured before fluid application ("before"), the value of the parameter measured after fluid application ("after"), and the difference between the two ("difference"). Two statistical values ​​are also shown for each graph, which attempt to represent the statistical significance of the observed difference between the before value and the after value and the statistical amplitude of the observed difference. This effectively gives an indication of the effectiveness of the corresponding parameter in representing the actual effect of the change in fluid responsiveness. The statistical values ​​are in particular the p-value and the Cohen's-d value. The p-value is a paired t-test, and the Cohen'sd is a measure of the effect size. These are standard statistical measurements used to verify hypotheses for observed data. The p-value measures the probability of obtaining the observed result, assuming that the null hypothesis is true. The lower the p-value, the greater the statistical significance of the observed difference. The Cohen'sd value measures the statistical size of the effect.

[0079] So, in conclusion, Figure 4-11 The graphs presented in allow for comparison of the effectiveness of different measured parameters as indicators / metrics of fluid responsiveness. The lower the p-value and the higher the Cohen's-d value, the more robust the parameter is as an indicator of fluid responsiveness. Since SVV is a standard parameter for assessing fluid responsiveness, it provides a very valuable baseline against which other parameters can be compared.

[0080] The most important thing in this context is Fig.11 , which shows the results of the proposed fluid responsiveness index based on the ratio of blood velocity and vessel diameter.

[0081] In summary, the graph involves the following parameters. Figure 4 The results for SVV are shown (unit: %). Figure 5 Results are shown for SV (unit: ml / beat). Figure 6 Results for CO (unit: L / min) are shown. Figure 7 The results for PPV are shown (unit: %). Figure 8 Results are shown for ABP SSI (see explanation below) (unit: au). Fig. 9 Results are shown for the diameter of the blood vessel ("Dia") (unit: cm). Fig.10 Results are shown for blood flow velocity ("velocity"), specifically peak systolic velocity (in cm / s). Fig.11 Results are shown for the ratio of peak velocity to vessel diameter.

[0082] The parameters SVV, SV and CO are obtained from the PiCCO device. The parameters PPV and ABPSSI are calculated from the invasively measured ABP waveform. The parameters Dia, Velocity and Velocity / Dia are derived from the acquired ultrasound data in the manner already described above.

[0083] More specifically, ABP is used to calculate PPV. Traditionally, PPV is defined as follows:

[0084]

[0085] Here, ABP(max), ABP(min) and ABP(mean) refer to the maximum, minimum and mean values ​​of ABP during the measurement period. For experimental purposes, PPV was calculated in a similar manner, but with the 99th and 1st percentile values ​​of ABP instead of the maximum and minimum values, as these are more robust to noise.

[0086] ABP SSI is a novel ABP-based feature calculated as follows:

[0087]

[0088] Here, the Signal Stability Index (SSI) is an index previously defined in document EP3571991A1. As a brief overview, SSI is a non-parametric method based on kernel density estimation for determining the probability density function of the underlying signal. The probability density is approximated by the superposition of multiple Gaussian kernels centered at multiple equidistant points on the signal segment (here 100 points). The maximum value of the superposition of these Gaussian kernels forms the SSI. If the mean and variance of the underlying Gaussian kernels are comparable, the SSI is high. The ABP SSI feature performs better than the traditional PPV metric and is novel.

[0089] “Dia” and “Velocity” are the diameter and peak systolic velocity derived from the USB mode and PWD signal, respectively.

[0090] " / Dia" is the ratio of the 90th percentile value of the velocity waveform divided by the average value of the diameter over the measurement period. This is a measure of fluid responsiveness proposed according to an embodiment of the present invention.

[0091] review Fig.11 , which relates to the proposed ratio velocity / diameter, with a p-value of 0.03 and a Cohen's-d value of 0.3. It is clear from the results that this metric performs better than the diameter of the peak systolic velocity itself (which obtains a p-value of 0.16 and a Cohen's-d value of -0.25), and performs better than the blood flow velocity itself (p-value = 0.07 and Cohen's = -d 0.18). It is also comparable to the results of the classical SSV parameters (p-value = 0.01 and Cohen's-d = 0.66) and SV parameters (p-value = 0.04 and Cohen's-d = -0.16). In fact, the proposed ratio performs an order of magnitude better in terms of p-values ​​than the classical parameters of CO (p-value = 0.27 and Cohen's-d = -0.09) and PPV (p-value = 0.1 and Cohen's-d = 0.41).

[0092] Thus, the results demonstrate the reliability of the proposed flow velocity:diameter ratio as a basis for calculating the fluid responsiveness index. Furthermore, the proposed ratio can be measured completely non-invasively and very quickly.

[0093] The ultrasound-based feature calculation proposed by the inventors is different from the calculation of SVV, SV, CO and ABP-based features because it can be calculated using data collected only in a short measurement period (e.g., 20-60 s) in the pre-bolus and post-bolus periods, while other features are calculated in a continuous 15-minute measurement period. This makes it faster and easier to obtain measurement results.

[0094] In fact, quasi-continuous measurement is also about the possibility of continuous ultrasound monitoring technology (e.g., wearable ultrasound transducer unit). In addition, if the measurement is performed with a wearable ultrasound device, the repeatability error can be significantly mitigated, thus further improving the performance.

[0095] It should also be noted that the fluid responsiveness metric proposed according to the present invention does not specifically exploit respiratory regulation, and for this reason it is broadly applicable to both ventilated and spontaneously breathing patients.

[0096] The same ratio can actually be applied outside of fluid responsiveness assessment to determine the efficacy of the administration of vasodilators and vasoconstrictors and to titrate that administration.

[0097] The embodiments of the present invention described above adopt processing units. The processing unit can generally include a single processor or multiple processors. It can be located in a single containing device, structure or unit, or it can be distributed between multiple different devices, structures or units. Therefore, the reference to the processing unit being suitable for or configured to perform a specific step or task can correspond to the step or task being performed by any one or more of the multiple processing components individually or in combination. Those skilled in the art will understand how such distributed processing units can be implemented. The processing unit includes a communication module or input / output unit for receiving data and outputting data to other components.

[0098] The one or more processors of the processing unit can be implemented in a variety of ways using software and / or hardware to perform the various functions required. The processors typically employ one or more microprocessors that can be programmed using software (e.g., microcode) to perform the required functions. The processors can be implemented as a combination of dedicated hardware to perform some functions and one or more programmed microprocessors and associated circuits to perform other functions.

[0099] Examples of circuits that may be employed in various embodiments of the present disclosure include, but are not limited to, conventional microprocessors, application specific integrated circuits (ASICs), and field programmable gate arrays (FPGAs).

[0100] In various embodiments, the processor may be associated with one or more storage media, such as volatile and non-volatile computer memory, such as RAM, PROM, EPROM, and EEPROM. The storage media may be encoded with one or more programs that perform the desired functions when run on one or more processors and / or controllers. The various storage media may be fixed within the processor or controller or may be transportable so that one or more programs stored thereon may be loaded into the processor.

[0101] By studying the drawings, the disclosure and the appended claims, those skilled in the art can understand and implement variations of the disclosed embodiments when practicing the claimed invention. In the claims, the word "comprising" does not exclude other elements or steps, and the word "one" or "an" does not exclude a plurality.

[0102] A single processor or other unit may fulfill the functions of several items recited in the claims.

[0103] Measures recited in mutually different dependent claims may advantageously be combined.

[0104] The computer program may be stored / distributed on suitable media, such as optical storage media or solid-state media provided together with or as part of other hardware, but the computer program may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunications systems.

[0105] Any reference signs in the claims should not be construed as limiting the scope.

Claims

1. A computer-implemented method comprising: Receiving (12) first ultrasound data of a blood vessel of a subject, the first ultrasound data being acquired during a first period of time, the first period of time occurring (t -1) before a bolus of fluid is administered into an artery of the subject; receiving (14) second ultrasound data of a blood vessel of the subject, the second ultrasound data being acquired during a second period of time, the second period of time occurring (t_+1) after a bolus of the fluid is administered into an artery of the subject; using the first ultrasound data to determine (16) a first measure of flow velocity of blood in the blood vessel of the subject; using the first ultrasound data to determine (18) a first measure of a diameter of the blood vessel; using the second ultrasound data to determine (20) a second measure of the flow velocity of the blood in the blood vessel of the subject; using the second ultrasound data to determine (22) a second measure of the diameter of the blood vessel; using the first blood velocity metric and the first blood vessel diameter metric to determine (24) a first ratio of blood velocity to blood vessel diameter or a correlation thereof; determining (26) a second ratio of blood velocity to blood vessel diameter or a correlation thereof using the second blood velocity metric and the second vessel diameter metric; deriving (28) a fluid responsiveness index of the subject based on a comparison between the first ratio and the second ratio; A data output indicative of an index of reactivity of the fluid is generated (30).

2. The method according to claim 1, wherein: The comparing includes calculating a difference between the first ratio and the second ratio.

3. The method according to claim 1 or 2, wherein: Each of the first ultrasound data and the second ultrasound data comprises both Doppler ultrasound data and imaging ultrasound data, such as B-mode ultrasound data, and optionally wherein the Doppler ultrasound data is pulsed wave Doppler ultrasound data.

4. The method according to claim 3, in, calculating the first blood vessel diameter metric and the second blood vessel diameter metric using the imaging ultrasound data in the corresponding first ultrasound data and second ultrasound data; and The first flow velocity quantity and the second flow velocity quantity are calculated using the Doppler data in the corresponding first ultrasound data and second ultrasound data.

5. The method according to any one of claims 3 to 4, wherein: Each of the first ultrasound data and the second ultrasound data includes duplex ultrasound data including interleaved B-mode acquisition and Doppler mode acquisition.

6. The method according to any one of claims 1 to 5, wherein: Each of the first and second measures of flow velocity in the blood vessel is a measure of peak systolic velocity (PSV) measured during respective first and second periods.

7. The method according to claim 6, wherein: The systolic peak flow rate for each of the first flow rate metric and the second flow rate metric is obtained based on the following operations: sampling the flow velocity of the blood vessel at a plurality of time points within a corresponding period, and The flow rate corresponding to the 90th percentile of the plot of sampled velocity versus time for the period is selected.

8. The method according to any one of claims 1 to 7, wherein: The second period is timed to begin after a predefined time interval after administration of the bolus, and optionally wherein the predefined time interval after administration of the bolus is about 15 minutes.

9. The method according to any one of claims 1 to 8, wherein: Each period has a duration of 120 seconds or less, such as 60 seconds or less, such as between about 20 seconds and about 60 seconds.

10. The method according to any one of claims 1 to 9, wherein: The method comprises: Repeat the following steps at regular intervals: receiving the second ultrasound data, determining said second measure of said flow rate; determining said second measure of said diameter of said blood vessel, determining a second ratio of blood velocity to blood vessel diameter, and deriving a fluid responsiveness index for the subject, So as to provide post-bolus monitoring of the fluid responsiveness index.

11. The method according to any one of claims 1 to 10, wherein: The method comprises: generating a first control instruction, wherein the first control instruction is used to communicate with an ultrasound acquisition device to enable the device to acquire the first ultrasound data, and generating a second control instruction, wherein the second control instruction is used to communicate with the ultrasound acquisition device so that the device acquires the second ultrasound data, and Optionally, the method further comprises: receiving a user input indicating a timing for administering the bolus of the liquid, and wherein the second control instruction is generated to cause the ultrasound acquisition device to acquire the second ultrasound data at a time determined based on the user input.

12. A computer program product comprising computer code configured to cause a processor (36) to perform the method according to any one of claims 1-11.

13. A processing unit (32), comprising: Input / output (34); as well as One or more processors (36) configured to perform the method according to any of claims 1-11.

14. A system (30), comprising: The processing unit (32) according to claim 13; as well as an ultrasonic acquisition device (42) operatively coupled to the processing unit, The first ultrasound data and the second ultrasound data are received from the ultrasound acquisition device.

15. The system of claim 14, wherein: The ultrasound collection device includes a wearable ultrasound transducer unit, such as a wearable patch integrating an ultrasound transducer device.

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