US20210244347A1

US20210244347A1 - Fusion signal processing for maternal uterine activity detection

Info

Publication number: US20210244347A1
Application number: US17/168,999
Authority: US
Inventors: Muhammad Mhajna
Original assignee: Nuvo Group Ltd
Current assignee: Nuvo Group Ltd
Priority date: 2020-02-05
Filing date: 2021-02-05
Publication date: 2021-08-12
Also published as: IL295417A; EP4099906A4; JP2023513678A; WO2021156675A1; US20230301581A1; KR20220150901A; CN115315214A; CA3170821A1; US20210267535A1; EP4099906A1; AU2021217206A1; US11324437B2

Abstract

A computer-implemented method includes providing, by at least one computer processor, a plurality of signal channels, wherein the plurality of signal channels includes a plurality of electrical uterine monitoring signal channels and a plurality of acoustic uterine monitoring signal channels; determining, by the at least one computer processor, a plurality of channel weights, wherein each of the channel weights corresponds to a particular one of the signal channels; and generating, by the at least one computer processor, a combined uterine monitoring signal channel by calculating a weighted average of the signal channels based on the channel weight for each of the signal channels.

Description

CROSS-REFERENCE TO RELATED APPLICATION

This application is a Section 111(a) application relating to and claiming the benefit of commonly-owned, co-pending U.S. Provisional Patent Application No. 62/970,585, filed on Feb. 5, 2020 and entitled “FUSION SIGNAL PROCESSING FOR MATERNAL UTERINE ACTIVITY DETECTION,” the contents of which are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

The invention relates generally to monitoring of expectant mothers. More particularly, the invention relates to analysis of sensed bio-potential data and/or acoustic data to produce computed representations of uterine activity, such as uterine contractions.

BACKGROUND

A uterine contraction is a temporary process during which the muscles of the uterus are shortened and the space between muscle cells decreases. These structural changes in the muscle cause an increase in uterine cavity pressure to allow pushing the fetus downward in a lower position towards delivery. During a uterine contraction, the structure of myometrial cells (i.e., cells of the uterus) changes and the uterine wall becomes thicker. FIG. 1A shows an illustration of a relaxed uterus, in which the muscular wall of the uterus is relaxed. FIG. 1B shows an illustration of a contracted uterus, in which the muscular wall of the uterus contracts and pushes the fetus against the cervix.
Uterine contractions are monitored to evaluate the progress of labor. Typically, the progress of labor is monitored through the use of two sensors: a tocodynamometer, which is a strain gauge-based sensor positioned on the abdomen of an expectant mother, and an ultrasound transducer, which is also positioned on the abdomen. The signals of the tocodynamometer are used to provide a tocograph (“TOCO”), which is analyzed to identify uterine contractions, while the signals of the ultrasound transducer are used to detect fetal heart rate, maternal heart rate, and fetal movement. However, these sensors can be uncomfortable to wear, and can produce unreliable data when worn by obese expectant mothers.

SUMMARY

In some embodiments, the present invention provides a specifically programmed computer system, including at least the following components: a non-transient memory, electronically storing computer-executable program code; and at least one computer processor that, when executing the program code, becomes a specifically programmed computing processor that is configured to perform at least the following operations: receiving a plurality of bio-potential signals collected at a plurality of locations on the abdomen of a pregnant mother; detecting R-wave peaks in the bio-potential signals; extracting maternal electrocardiogram (“ECG”) signals from the bio-potential signals; determining R-wave amplitudes in the maternal ECG signals; creating an R-wave amplitude signal for each of the maternal ECG signals; calculating an average of all the R-wave amplitude signals; and normalizing the average to produce an electrical uterine monitoring (“EUM”) signal. In some embodiments, the operations also include identifying at least one uterine contraction based on a corresponding at least one peak in the EUM signal.
In some embodiments, the present invention provides a method including receiving a plurality of bio-potential signals collected at a plurality of locations on the abdomen of a pregnant mother; detecting R-wave peaks in the bio-potential signals; extracting maternal ECG signals from the bio-potential signals; determining R-wave amplitudes in the maternal ECG signals; creating an R-wave amplitude signal for each of the maternal ECG signals; calculating an average of all the R-wave amplitude signals; and normalizing the average to produce an EUM signal. In some embodiments, the method also includes identifying at least one uterine contraction based on a corresponding at least one peak in the EUM signal.
In an embodiment, a computer-implemented method receiving, by at least one computer processor, a plurality of raw bio-potential inputs, wherein each of the raw bio-potential inputs being received from a corresponding one of a plurality of electrodes, wherein each of the plurality of electrodes is positioned so as to measure a respective one of the raw bio-potential inputs of a pregnant human subject; generating, by the at least one computer processor, a plurality of signal channels from the plurality of raw-bio-potential inputs, wherein the plurality of signal channels includes at least three signal channels; pre-processing, by the at least one computer processor, respective signal channel data of each of the signal channels to produce a plurality of pre-processed signal channels, wherein each of the pre-processed signal channels includes respective pre-processed signal channel data; extracting, by the at least one computer processor, a respective plurality of R-wave peaks from the pre-processed signal channel data of each of the pre-processed signal channels to produce a plurality of R-wave peak data sets, wherein each of the R-wave peak data sets includes a respective plurality of R-wave peaks; removing, by the at least one computer processor, from the plurality of R-wave peak data sets, at least one of: (a) at least one signal artifact or (b) at least one outlier data point, wherein the at least one signal artifact is one of an electromyography artifact or a baseline artifact; replacing, by the at least one computer processor, the at least one signal artifact, the at least one outlier data point, or both, with at least one statistical value determined based on a corresponding one of the R-wave peak data sets from which the at least one signal artifact, the at least one outlier data point, or both was removed; generating, by the at least one computer processor, a respective R-wave signal data set for a respective R-wave signal channel at a predetermined sampling rate based on each respective R-wave peak data set to produce a plurality of R-wave signal channels; selecting, by the at least one computer processor, at least one first selected R-wave signal channel and at least one second selected R-wave signal channel from the plurality of R-wave channels based on at least one correlation between (a) the respective R-wave signal data set of at least one first particular R-wave signal channel and (b) the respective R-wave signal data set of at least one second particular R-wave signal channel; generating, by the at least one computer processor, electrical uterine monitoring data representative of an electrical uterine monitoring signal based on at least the respective R-wave signal data set of the first selected R-wave signal channel and the respective R-wave signal data set of the second selected R-wave signal channel.
In an embodiment, a computer-implemented method also includes sharpening, by the at least one computer processor, the electrical uterine monitoring data to produce a sharpened electrical uterine monitoring signal. In an embodiment, the sharpening step is omitted if the electrical uterine monitoring data is calculated based on a selected one of the electrical uterine monitoring signal channels that is a corrupted electrical uterine signal monitoring channel. In an embodiment, a computer-implemented method also includes post-processing the sharpened electrical monitoring signal data to produce a post-processed electrical uterine monitoring signal. In an embodiment, the sharpening step includes identifying a set of peaks in the electrical uterine monitoring signal data; determining a prominence of each of the peaks; removing, from the set of peaks, peaks having a prominence that is less than at least one threshold prominence value; calculating a mask based on remaining peaks of the set of peaks; smoothing the mask based on a moving average window to produce a smoothed mask; and adding the smoothed mask to the electrical uterine monitoring signal data to produce the sharpened electrical uterine monitoring signal data. In an embodiment, the at least one threshold prominence value includes at least one threshold prominence value selected from the group consisting of an absolute prominence value and a relative prominence value calculated based on a maximal prominence of the peaks in the set of peaks. In an embodiment, the mask includes zero values outside areas of the remaining peaks and nonzero values inside areas of the remaining peaks, wherein the nonzero values are calculated based on a Gaussian function
In an embodiment, the at least one filtering step of the pre-processing step includes applying at least one filter selected from the group consisting of a DC removal filter, a powerline filter, and a high pass filter.
In an embodiment, the extracting step includes receiving a set of maternal ECG peaks for the pregnant human subject; and identifying R-wave peaks in each of the pre-processed signal channels within a predetermined time window before and after each of the maternal ECG peaks in the set of maternal ECG peaks as the maximum absolute value in each of the pre-processed signal channels within the predetermined time window.
In an embodiment, the step of removing at least one of a signal artifact or an outlier data point includes removing at least one electromyography artifact by a process including identifying at least one corrupted peak in one of the plurality of R-wave peaks data sets based on the at least one corrupted peak having an inter-peaks root mean square value that is greater than a threshold; and replacing the corrupted peak with a median value, wherein the median value is either a local median or a global median.
In an embodiment, the step of removing at least one of a signal artifact or an outlier data point includes removing at least one baseline artifact by a process including: identifying a change point in R-wave peaks in one of the plurality of R-wave peaks data sets; subdividing the one of the plurality of R-wave peaks data sets into a first portion located prior to the change point and a second portion located subsequent to the change point; determining a first root-mean-square value for the first portion; determining a second root-mean-square value for the second portion; determining an equalization factor based on the first root-mean-square value and the second root-mean-square value; and modifying the first portion by multiplying R-wave peaks in the first portion by the equalization factor.
In an embodiment, the step of removing at least one of a signal artifact or an outlier point includes removing at least one outlier in accordance with a Grubbs test for outliers.
In an embodiment, the step of generating a respective R-wave data set based on each respective R-wave peak data set includes interpolating between the R-wave peaks of each respective R-wave peak data set, and wherein the interpolating between the R-wave peaks includes interpolating using an interpolation algorithm that is selected from the group consisting of a cubic spline interpolation algorithm and a shape-preserving piecewise cubic interpolation algorithm.
In an embodiment, the step of selecting at least one first one of the R-wave signal channels and at least one second one of the R-wave signal channels includes selecting candidate R-wave signal channels from the R-wave signal channels based on a percentage of prior intervals in which each of the R-wave signal channels experienced contact issues; grouping the selected candidate R-wave signal channels into a plurality of couples, wherein each of the couples includes two of the selected candidate R-wave channels that are independent from one another; calculating a correlation value of each of the couples; and selecting, as the selected at least one first one of the R-wave signal channels and the selected at least one second one of the R-wave signal channels, the candidate R-wave signal channels of at least one of the couples based on the at least one of the couples having a correlation value that exceeds a threshold correlation value.
In an embodiment, the step of calculating the electrical uterine monitoring signal includes calculating a signal that is a predetermined percentile of the selected at least one first one of the R-wave signal channels and the selected at least one second one of the R-wave signal channels. In an embodiment, the predetermined percentile is an 80^thpercentile.
In an embodiment, the statistical value is one of a local median, a global median, or a mean.
In some embodiments, a computer-implemented method includes providing, by at least one computer processor, a plurality of signal channels, wherein the plurality of signal channels includes a plurality of electrical uterine monitoring signal channels and a plurality of acoustic uterine monitoring signal channels; determining, by the at least one computer processor, a plurality of channel weights, wherein each of the channel weights corresponds to a particular one of the signal channels; and generating, by the at least one computer processor, a combined uterine monitoring signal channel by calculating a weighted average of the signal channels based on the channel weight for each of the signal channels.
In some embodiments, the plurality of channel weights are determined based on a machine learning algorithm. In some embodiments, the machine learning algorithm includes a gradient descent optimization process.
In some embodiments, the plurality of channel weights are determined by a process including: defining, by the at least one computer processor, a plurality of channel sets, each of the plurality of channel sets including at least some of the plurality of signal channels; defining, by the at least one computer processor, a plurality of initial weight sets, wherein each of the plurality of initial weight sets corresponds to a particular one of the plurality of channel sets; optimizing, by the at least one computer processor, the plurality of initial weight sets to generate a plurality of optimized weight sets, wherein each of the plurality of optimized weight sets corresponds to a particular one of the plurality of channel sets; and selecting, by the at least one computer processor, a best one of the plurality of optimized weight sets as the plurality of channel weights.
In some embodiments, the step of optimizing the plurality of initial weight sets includes a gradient descent process.
In some embodiments, the step of selecting the best one of the plurality of optimized weight sets is performed by a process including: generating, by the at least one computer processor, a plurality of interim uterine activity traces, wherein each of the plurality of interim uterine activity traces corresponds to a particular one of the plurality of optimized weight sets; calculating, by the at least one computer processor, for each of plurality of optimized weight sets, (a) signal-to-noise ratio of the particular one of the interim uterine activity traces that corresponds to each of the plurality of optimized weight sets; (b) a cost function; (c) a contraction confidence measure; and (d) a difference index; calculating, by the at least one computer processor, for each particular one of the plurality of optimized weight sets, an optimized weight set mean that is a mean of (a) the signal-to-noise ratio of the particular one of the optimized weight sets, (b) the cost function of the particular one of the optimized weight sets, (c) the contraction confidence measure of the particular one of the optimized weight sets, and (d) the difference index of the particular one of the optimized weight sets; and selecting, by the at least one computer processor, a one of the plurality of optimized weight sets having a best optimized weight set mean as the best one of the plurality of optimized weight sets.
In some embodiments, the computer-implemented method also includes generating, by the at least one computer processor, a first interim uterine activity trace and a second interim uterine activity trace corresponding to a particular one of the plurality of channel sets, wherein the first interim uterine activity trace corresponds to a first one of the plurality of optimized weight sets for the particular one of the plurality of channel sets, and wherein the second interim uterine activity trace corresponds to a second one of the plurality of optimized weight sets for the particular one of the plurality of channel sets; calculating, by the at least one computer processor, for the first one of the plurality of optimized weight sets, (a) signal-to-noise ratio of the first interim uterine activity trace; (b) a cost function; (c) a contraction confidence measure; and (d) a difference index; calculating, by the at least one computer processor, for the second one of the plurality of optimized weight sets, (a) signal-to-noise ratio of the second interim uterine activity trace; (b) a cost function; (c) a contraction confidence measure; and (d) a difference index; calculating, by the at least one computer processor, for the first one of the plurality of optimized weight sets, a first mean that is a mean of (a) the signal-to-noise ratio of the first interim uterine activity trace; (b) the cost function of the first one of the plurality of optimized weight sets; (c) a contraction confidence measure of the first one of the plurality of optimized weight sets; and (d) a difference index of the first one of the plurality of optimized weight sets; calculating, by the at least one computer processor, for the second one of the plurality of optimized weight sets, a second mean that is a mean of (a) the signal-to-noise ratio of the second interim uterine activity trace; (b) the cost function of the second one of the plurality of optimized weight sets; (c) a contraction confidence measure of the second one of the plurality of optimized weight sets; and (d) a difference index of second first one of the plurality of optimized weight sets; selecting, by the at least one computer processor, the first one of the plurality of weight sets as a best weight set for the particular one of the plurality of channel sets, based on a determination that the first mean is better than the second mean; and selecting, by the at least one computer processor, the second one of the plurality of weight sets as a best weight set for the particular one of the plurality of channel sets, based on a determination that the second mean is better than the first mean. In some embodiments, the computer-implemented method also includes enhancing, by the at least computer processor, the plurality of channel sets prior to the step of selecting, by the at least one computer processor, the best one of the plurality of optimized weight sets as the plurality of channel weights.
In some embodiments, the step of defining the plurality of channel sets includes defining a contraction-based channel set, and wherein the contraction-based channel set is determined by a process including: identifying, by the at least one computer processor, a set of contractions in each of the plurality of signal channels; extracting, by the at least one computer processor, contraction features for each of the plurality of signal channels based on the set of contractions identified for each of the plurality of signal channels; clustering, by the at least one computer processor, the plurality of signal channels into a plurality of clusters; and selecting a best one of the plurality of clusters as the contraction-based channel set. In some embodiments, the step of defining the plurality of channel sets further includes: improving, by the at least one computer processor, the best one of the plurality of clusters. In some embodiments, wherein the step of defining the plurality of channel sets also includes adding, by the at least one computer processor, to the best one of the plurality of clusters, a portion of one of the signal channels that is not included in the best one of the plurality of clusters. In some embodiments, the step of identifying the set of contractions in each of the plurality of signal channels is performed by a process that includes, for each one of the plurality of signal channels: generating, by the at least one computer processor, an enhanced version of the one of the plurality of signal channels; detecting, by the at least one computer processor, a candidate set of contractions in the enhanced one of the plurality of signal channels, wherein the candidate set of contractions includes a plurality of candidate contractions; calculating, by the at least one computer processor, a plurality of confidence measures for each candidate contraction; and removing, by the at least one computer processor, at least one of the candidate contractions from the set of candidate contractions based on the confidence measures corresponding to the at least one eliminated one of the candidate contractions, thereby producing the set of contractions.
In some embodiments, the step of defining, by the at least one computer processor, the plurality of initial weight sets includes generating, by the at least one computer processor, for each of the channel sets, a channel-voting weight set and a born-equal weight set.
In some embodiments, the step of providing the plurality of signal channels includes generating, by the at least one computer processor, at least one of the plurality of electrical uterine monitoring signal channels, and wherein the at least one of the plurality of electrical uterine monitoring signal channels is generated by a process including receiving, by the at least one computer processor, a plurality of raw bio-potential inputs, wherein each of the raw bio-potential inputs being received from a corresponding one of a plurality of electrodes, and wherein each of the plurality of electrodes is positioned so as to measure a respective one of the raw bio-potential inputs of a pregnant human subject; generating, by the at least one computer processor, a plurality of signal channels from the plurality of raw-bio-potential inputs, wherein the plurality of signal channels includes at least three signal channels; pre-processing, by the at least one computer processor, respective signal channel data of each of the signal channels to produce a plurality of pre-processed signal channels, wherein each of the pre-processed signal channels includes respective pre-processed signal channel data; extracting, by the at least one computer processor, a respective plurality of R-wave peaks from the pre-processed signal channel data of each of the pre-processed signal channels to produce a plurality of R-wave peak data sets, wherein each of the R-wave peak data sets includes a respective plurality of R-wave peaks; removing, by the at least one computer processor, from the plurality of R-wave peak data sets, at least one of: (a) at least one signal artifact or (b) at least one outlier data point, wherein the at least one signal artifact is one of an electromyography artifact or a baseline artifact; replacing, by the at least one computer processor, the at least one signal artifact, the at least one outlier data point, or both, with at least one statistical value determined based on a corresponding one of the R-wave peak data sets from which the at least one signal artifact, the at least one outlier data point, or both was removed, to produce a plurality of interpolated R-wave peak data sets; generating, by the at least one computer processor, a respective R-wave signal data set for a respective R-wave signal channel at a predetermined sampling rate based on each respective interpolated R-wave peak data set to produce a plurality of R-wave signal channels; selecting, by the at least one computer processor, at least one first selected R-wave signal channel and at least one second selected R-wave signal channel from the plurality of R-wave signal channels based on at least one correlation between (a) a respective R-wave signal data set of at least one first particular R-wave signal channel and (b) a respective R-wave signal data set of at least one second particular R-wave signal channel; and generating, by the at least one computer processor, electrical uterine monitoring data representative of an electrical uterine monitoring signal based on at least the respective R-wave signal data set of the first selected R-wave signal channel and the respective R-wave signal data set of the second selected R-wave signal channel, thereby producing the at least one electrical uterine monitoring signal channel.
In some embodiments, the step of providing the plurality of signal channels includes generating, by the at least one computer processor, at least one of the plurality of acoustic uterine monitoring signal channels, and wherein the at least one of the plurality of acoustic uterine monitoring signal channels is generated by a process including: receiving, by the at least one computer processor, a plurality of raw acoustic inputs, wherein each of the raw acoustic inputs being received from a corresponding one of a plurality of acoustic sensors, and wherein each of the plurality of acoustic sensors is positioned so as to measure a respective one of the raw acoustic inputs of a pregnant human subject; generating, by the at least one computer processor, a plurality of signal channels from the plurality of raw acoustic inputs, wherein the plurality of signal channels includes at least three signal channels; pre-processing, by the at least one computer processor, respective signal channel data of each of the signal channels to produce a plurality of pre-processed signal channels, wherein each of the pre-processed signal channels includes respective pre-processed signal channel data; extracting, by the at least one computer processor, a respective plurality of S1-S2 peaks from the pre-processed signal channel data of each of the pre-processed signal channels to produce a plurality of S1-S2 peak data sets, wherein each of the S1-S2 peak data sets includes a respective plurality of S1-S2 peaks; removing, by the at least one computer processor, from the plurality of S1-S2 peak data sets, at least one of: (a) at least one signal artifact or (b) at least one outlier data point, wherein the at least one signal artifact is one of a movement-related artifact or a baseline artifact; replacing, by the at least one computer processor, the at least one signal artifact, the at least one outlier data point, or both, with at least one statistical value determined based on a corresponding one of the S1-S2 peak data sets from which the at least one signal artifact, the at least one outlier data point, or both was removed, to produce a plurality of interpolated S1-S2 peak data sets; generating, by the at least one computer processor, a respective S1-S2 signal data set for a respective S1-S2 signal channel at a predetermined sampling rate based on each respective interpolated S1-S2 peak data set to produce a plurality of S1-S2 signal channels; selecting, by the at least one computer processor, at least one first selected S1-S2 signal channel and at least one second selected S1-S2 signal channel from the plurality of S1-S2 signal channels based on at least one correlation between (a) a respective S1-S2 signal data set of at least one first particular S1-S2 signal channel and (b) a respective S1-S2 signal data set of at least one second particular S1-S2 signal channel; and generating, by the at least one computer processor, acoustic uterine monitoring data representative of an acoustic uterine monitoring signal based on at least the respective S1-S2 signal data set of the first selected S1-S2 signal channel and the respective S1-S2 signal data set of the second selected S1-S2 signal channel, thereby producing the at least one acoustic uterine monitoring signal channel.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a representative uterus in a non-contracted state.

FIG. 1B shows a representative uterus in a contracted state.

FIG. 2 shows a flowchart of an exemplary method.

FIG. 3 shows an exemplary garment including a plurality of bio-potential sensors, which may be used to sense data that is to be analyzed in accordance with the exemplary method of FIG. 2.

FIG. 4A shows a front view of the positions of ECG sensor pairs on the abdomen of a pregnant woman according to some embodiments of the present invention.

FIG. 4B shows a side view of the positions of the ECG sensor pairs on the abdomen of a pregnant woman according to some embodiments of the present invention.

FIG. 5 shows an exemplary bio-potential signal before and after pre-processing.

FIG. 6A shows an exemplary bio-potential signal after pre-processing and with detected R-wave peaks indicated.

FIG. 6B shows the exemplary bio-potential signal of FIG. 6A after peak re-detection.

FIG. 6C shows a magnified view of a portion of the signal of FIG. 6B.

FIG. 6D shows the exemplary bio-potential signal of FIG. 6B after examination of the detected peaks.

FIG. 7A shows a portion of an exemplary bio-potential signal including identified R-wave peaks.

FIG. 7B shows a portion of an exemplary bio-potential signal having a P-wave, a QRS complex, and a T-wave identified therein.

FIG. 7C shows an exemplary bio-potential signal including mixed maternal and fetal data.

FIG. 7D shows a portion of the signal of FIG. 7C along with an initial template.

FIG. 7E shows a portion of the signal of FIG. 7C along with an adapted template.

FIG. 7F shows a portion of the signal of FIG. 7C along with a current template and a zero-th iteration of an adaptation.

FIG. 7G shows a portion of the signal of FIG. 7C along with a current template, a zero-th iteration of an adaptation, and a first iteration of an adaptation.

FIG. 7H shows a portion of the signal of FIG. 7C along with a current template and a maternal ECG signal reconstructed based on the current template.

FIG. 7I shows the progress of an adaptation expressed in terms of the logarithm of the error signal as plotted against the number of the iteration.

FIG. 7J shows an extracted maternal ECG signal.

FIG. 8 shows an exemplary filtered maternal ECG signal.

FIG. 9 shows an exemplary maternal ECG signal with R-wave peaks annotated therein.

FIG. 10A shows an exemplary R-wave amplitude signal.

FIG. 10B shows an exemplary modulated R-wave amplitude signal.

FIG. 11A shows an exemplary modulated R-wave amplitude signal along with the result of the application of a moving average filter thereto.

FIG. 11B shows exemplary filtered R-wave amplitude signals for multiple channels over a same time window.

FIG. 12A shows a first exemplary normalized electrical uterine signal generated based on the exemplary filtered R-wave amplitude signals shown in FIG. 11B.

FIG. 12B shows a first tocograph signal recorded over the same time period as the exemplary normalized electrical uterine signal with self-reported contractions annotated therein.

FIG. 13 shows a flowchart of a second exemplary method.

FIG. 14A shows a second tocograph signal with self-reported contractions annotated therein.

FIG. 14B shows a second exemplary electrical uterine signal derived from bio-potential data recorded during the same time period as that shown in FIG. 14A.

FIG. 15A shows a third tocograph signal with self-reported contractions annotated therein.

FIG. 15B shows a third exemplary electrical uterine signal derived from bio-potential data recorded during the same time period as that shown in FIG. 15A.

FIG. 16A shows a fourth tocograph signal with self-reported contractions annotated therein.

FIG. 16B shows a fourth exemplary electrical uterine signal derived from bio-potential data recorded during the same time period as that shown in FIG. 16A.

FIG. 17A shows a fifth tocograph signal with self-reported contractions annotated therein.

FIG. 17B shows a fifth exemplary electrical uterine signal derived from bio-potential data recorded during the same time period as that shown in FIG. 17A.

FIG. 18A shows an exemplary raw bio-potential data set.

FIG. 18B shows an exemplary filtered data set based on the exemplary raw data set of FIG. 18A.

FIG. 18C shows an exemplary raw bio-potential data set.

FIG. 18D shows an exemplary filtered data set based on the exemplary raw data set of FIG. 18C.

FIG. 18E shows an exemplary raw bio-potential data set.

FIG. 18F shows an exemplary filtered data set based on the exemplary raw data set of FIG. 18E.

FIG. 18G shows an exemplary raw bio-potential data set.

FIG. 18H shows an exemplary filtered data set based on the exemplary raw data set of FIG. 18G.

FIG. 19A shows an exemplary filtered data set with input peak positions.

FIG. 19B shows the exemplary filtered data set of FIG. 19A with extracted peak positions.

FIG. 20A shows an exemplary filtered data set.

FIG. 20B shows the exemplary filtered data set of FIG. 20A with representations of a corresponding maternal motion envelope and an inter-peaks absolute sum.

FIG. 20C shows an exemplary corrected data set produced by removal of electromyography artifacts from the filtered data set of FIG. 20A.

FIG. 21A shows an exemplary corrected data set including a baseline artifact.

FIG. 21B shows the exemplary corrected data set of FIG. 21A following removal of the baseline artifact.

FIG. 22A shows an exemplary corrected data set including an outlier data point.

FIG. 22B shows the exemplary corrected data set of FIG. 22A following removal of the outlier data point.

FIG. 23A shows an exemplary R-wave peaks signal.

FIG. 23B shows an exemplary R-wave signal generated based on the exemplary R-wave peaks signal of FIG. 23A.

FIG. 24A shows an exemplary set of candidate R-wave signal channels.

FIG. 24B shows an exemplary set of selected signal channels based on the exemplary set of candidate R-wave signal channels of FIG. 24A.

FIG. 25A shows an exemplary electrical uterine monitoring signal generated based on the set of selected signal channels shown in FIG. 24B.

FIG. 25B shows an exemplary corrected electrical uterine monitoring signal generated by applying wandering baseline removal to the exemplary electrical uterine monitoring signal of FIG. 25A.

FIG. 26 shows an exemplary normalized electrical uterine monitoring signal generated based on the exemplary corrected electrical uterine monitoring signal of FIG. 25B.

FIG. 27A shows an exemplary normalized electrical uterine monitoring signal.

FIG. 27B shows an exemplary sharpening mask generated based on the exemplary normalized electrical uterine monitoring signal of FIG. 27A.

FIG. 27C shows an exemplary sharpened electrical uterine monitoring signal generated based on the exemplary normalized electrical uterine monitoring signal of FIG. 27A and the exemplary sharpening mask of FIG. 27B.

FIG. 28 shows an exemplary post-processed electrical uterine monitoring signal.

FIG. 29 shows a tocograph signal corresponding to the exemplary post-processed electrical uterine monitoring signal of FIG. 28.

FIG. 30 shows a flowchart of a third exemplary method.

FIG. 31A shows an exemplary pre-processed data set.

FIG. 31B shows a magnified view of a portion of the exemplary pre-processed data set of FIG. 31A.

FIG. 32A shows extracted R-wave peaks in an exemplary pre-processed data set.

FIG. 32B shows a magnified view of extracted R-wave peaks in an exemplary pre-processed data set.

FIG. 32C shows an exemplary R-wave amplitude signal.

FIG. 32D shows an exemplary R-wave amplitude signal over a larger time window.

FIG. 33 shows an exemplary R-wave amplitude signal after filtering.

FIG. 34 shows four data channels of exemplary R-wave data.

FIG. 35A shows a sixth tocograph signal.

FIG. 35B shows a first exemplary acoustic uterine signal derived from acoustic data recorded during the same time period as that shown in FIG. 35A

FIG. 36A shows a seventh tocograph signal.

FIG. 36B shows a second exemplary acoustic uterine signal derived from acoustic data recorded during the same time period as that shown in FIG. 36A

FIG. 37A shows an eighth tocograph signal.

FIG. 37B shows a third exemplary acoustic uterine signal derived from acoustic data recorded during the same time period as that shown in FIG. 37A

FIG. 38 shows a set of ECG-based EUM processed signals and PCG-based processed signals.

FIG. 39 shows a fusion process to generate a uterine activity signal from ECG-based EUM processed signals and PCG-based processed signals.

FIG. 40 shows a process to generate a weight set for use in generating a uterine activity signal based on electrical uterine monitoring data and acoustic uterine monitoring data.

FIG. 41 shows a process to define an initial channel set for use in the method of FIG. 40.

FIG. 42 shows a process to identify contractions within a data set.

FIG. 43 shows an exemplary uterine monitoring signal and exemplary smoothed and enhanced signals as generated by FIG. 42.

FIG. 44 shows exemplary electrical uterine monitoring data signals, exemplary acoustic uterine monitoring data signals, and an exemplary output uterine monitoring signal generated by the method of FIG. 39.

DETAILED DESCRIPTION

Among those benefits and improvements that have been disclosed, other objects and advantages of this invention will become apparent from the following description taken in conjunction with the accompanying figures. Detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely illustrative of the invention that may be embodied in various forms. In addition, each of the examples given in connection with the various embodiments of the invention which are intended to be illustrative, and not restrictive.
Throughout the specification and claims, the following terms take the meanings explicitly associated herein, unless the context clearly dictates otherwise. The phrases “in one embodiment,” “in an embodiment,” and “in some embodiments” as used herein do not necessarily refer to the same embodiment(s), though it may. Furthermore, the phrases “in another embodiment” and “in some other embodiments” as used herein do not necessarily refer to a different embodiment, although it may. Thus, as described below, various embodiments of the invention may be readily combined, without departing from the scope or spirit of the invention.
As used herein, the term “based on” is not exclusive and allows for being based on additional factors not described, unless the context clearly dictates otherwise. In addition, throughout the specification, the meaning of “a,” “an,” and “the” include plural references. The meaning of “in” includes “in” and “on.” Ranges discussed herein are inclusive (e.g., a range of “between 0 and 2” includes the values 0 and 2 as well as all values therebetween).
As used herein the term “contact region” encompasses the contact area between the skin of a pregnant human subject and cutaneous contact i.e. the surface area through which current flow can pass between the skin of the pregnant human subject and the cutaneous contact.
In some embodiments, the present invention provides a method for extracting a tocograph-like signal from bio-potential data, that is, data describing electrical potential recorded at points on a person's skin through the use of cutaneous contacts, commonly called electrodes. In some embodiments, the present invention provides a method for detecting uterine contractions from bio-potential data. In some embodiments, bio-potential data is obtained through the use of non-contact electrodes positioned against or in the vicinity of desired points on a person's body.
In some embodiments, the present invention provides a system for detecting, recording and analyzing cardiac electrical activity data from a pregnant human subject. In some embodiments, a plurality of electrodes configured to detect fetal electrocardiogram signals is used to record the cardiac activity data. In some embodiments, a plurality of electrodes configured to detect fetal electrocardiogram signals and a plurality of acoustic sensors are used to record the cardiac activity data.
In some embodiments, a plurality of electrodes configured to detect fetal electrocardiogram signals are attached to the abdomen of the pregnant human subject. In some embodiments, the plurality of electrodes configured to detect fetal electrocardiogram signals are directly attached to the abdomen. In some embodiments, the plurality of electrodes configured to detect fetal electrocardiogram signals are incorporated into an article, such as, for example, a belt, a patch, and the like, and the article is worn by, or placed on, the pregnant human subject. FIG. 3 shows an exemplary garment 300, which includes eight electrodes 310 incorporated into the garment 300 so as to be positioned around the abdomen of a pregnant human subject when the garment 300 is worn by the subject. In some embodiments, the garment 300 includes four acoustic sensors 320 incorporated into the garment 300 so as to be positioned around the abdomen of a pregnant human subject when the garment 300 is worn by the subject. In some embodiments, each of the acoustic sensors 320 is one of the acoustic sensors described in U.S. Pat. No. 9,713,430. FIG. 4A shows a front view of the positions of the eight electrodes 310 on the abdomen of a pregnant woman according to some embodiments of the present invention. FIG. 4B shows a side view of the eight electrodes 310 on the abdomen of a pregnant woman according to some embodiments of the present invention.
FIG. 2 shows a flowchart of an exemplary inventive method 200. In some embodiments, an exemplary inventive computing device, programmed/configured in accordance with the method 200, is operative to receive, as input, raw bio-potential data measured by a plurality of electrodes positioned on the skin of a pregnant human subject, and analyze such input to produce a tocograph-like signal. In some embodiments, the quantity of electrodes is between 2 and 10. In some embodiments, the quantity of electrodes is between 2 and 20. In some embodiments, the quantity of electrodes is between 2 and 30. In some embodiments, the quantity of electrodes is between 2 and 40. In some embodiments, the quantity of electrodes is between 4 and 10. In some embodiments, the quantity of electrodes is between 4 and 20. In some embodiments, the quantity of electrodes is between 4 and 30. In some embodiments, the quantity of electrodes is between 4 and 40. In some embodiments, the quantity of electrodes is between 6 and 10. In some embodiments, the quantity of electrodes is between 6 and 20. In some embodiments, the quantity of electrodes is between 6 and 30. In some embodiments, the quantity of electrodes is between 6 and 40. In some embodiments, the quantity of electrodes is between 8 and 10. In some embodiments, the quantity of electrodes is between 8 and 20. In some embodiments, the quantity of electrodes is between 8 and 30. In some embodiments, the quantity of electrodes is between 8 and 40. In some embodiments, the quantity of electrodes is 8. In some embodiments, the exemplary inventive computing device, programmed/configured in accordance with the method 200, is operative to receive, as input, maternal ECG signals that have already been extracted from raw bio-potential data (e.g., by separation from fetal ECG signals that form part of the same raw bio-potential data). In some embodiments, the exemplary inventive computing device is programmed/configured in accordance with the method 200 via instructions stored in a non-transitory computer-readable medium. In some embodiments, the exemplary inventive computing device includes at least one computer processor, which, when executing the instructions, becomes a specifically-programmed computer processor programmed/configured in accordance with the method 200.
In some embodiments, the exemplary inventive computing device is programmed/configured to continuously perform one or more steps of the method 200 along a moving time window. In some embodiments, the moving time window has a predefined length. In some embodiments, the predefined length is sixty seconds. In some embodiments, the exemplary inventive computing device is programmed/configured to continuously perform one or more steps of the method 200 along a moving time window having a length that is between one second and one hour. In some embodiments, the length of the moving time window is between thirty seconds and 30 minutes. In some embodiments, the length of the moving time window is between 30 seconds and 10 minutes. In some embodiments, the length of the moving time window is between 30 seconds and 5 minutes. In some embodiments, the length of the moving time window is about 60 seconds. In some embodiments, the length of the moving time window is 60 seconds.
In step 210, the exemplary inventive computing device is programmed/configured to receive raw bio-potential data as input and pre-process it. In some embodiments, the raw bio-potential data is recorded through the use of at least two electrodes positioned in proximity to a pregnant subject's skin. In some embodiments, at least one of the electrodes is a signal electrode. In some embodiments at least one of the electrodes is a reference electrode. In some embodiments, the reference electrode is located at a point away from the uterus of the subject. In some embodiments, a bio-potential signal is recorded at each of several points around the pregnant subject's abdomen. In some embodiments, a bio-potential signal is recorded at each of eight points around the pregnant subject's abdomen. In some embodiments, the bio-potential data is recorded at 1,000 samples per second. In some embodiments, the bio-potential data is up-sampled to 1,000 samples per second. In some embodiments, the bio-potential data is recorded at a sampling rate of between 100 and 10,000 samples per second. In some embodiments, the bio-potential data is up-sampled to a sampling rate of between 100 and 10,000 samples per second. In some embodiments, the pre-processing includes baseline removal (e.g., using a median filter and/or a moving average filter). In some embodiments, the pre-processing includes low-pass filtering. In some embodiments, the pre-processing includes low-pass filtering at 85 Hz. In some embodiments, the pre-processing includes power line interference cancellation. FIG. 5 shows a portion of a raw bio-potential data signal both before and after pre-processing.
In step 220, the exemplary inventive computing device is programmed/configured to detect maternal R-wave peaks in the pre-processed bio-potential data resulting from the performance of step 210. In some embodiments, R-wave peaks are detected over 10-second segments of each data signal. In some embodiments, the detection of R-wave peaks begins by analysis of derivatives, thresholding, and distances. In some embodiments, the detection of R-wave peaks in each data signal includes calculating the first derivative of the data signal in the 10-second segment, identifying an R-wave peak in the 10-second segment by identifying a zero-crossing of the first derivative, and excluding identified peaks having either (a) an absolute value that is less than a predetermined R-wave peak threshold absolute value or (b) a distance between adjacent identified R-wave peaks that is less than a predetermined R-wave peak threshold distance. In some embodiments, the detection of R-wave peaks is performed in a manner similar to the detection of electrocardiogram peaks described in U.S. Pat. No. 9,392,952, the contents of which are incorporated herein by reference in their entirety. FIG. 6A shows a pre-processed bio-potential data signal, with R-wave peaks detected as described above indicated with asterisks.
In some embodiments, the detection of R-wave peaks of step 220 continues with a peak re-detection process. In some embodiments, the peak re-detection process includes an automatic gain control (“AGC”) analysis to detect windows with significantly different numbers of peaks. In some embodiments, the peak re-detection process includes a cross-correlation analysis. In some embodiments, the peak re-detection process includes an AGC analysis and a cross-correlation analysis. In some embodiments, an AGC analysis is appropriate for overcoming false negatives. In some embodiments, a cross-correlation analysis is appropriate for removing false positives. FIG. 6B shows a data signal following peak re-detection, with R-wave peaks re-detected as described above indicated with asterisks. FIG. 6C shows a magnified view of a portion of the data signal of FIG. 6B.
In some embodiments, the detection of R-wave peaks of step 220 continues with the construction of a global peaks array. In some embodiments, the global peaks array is created from multiple channels of data (e.g., each of which corresponds to one or more of the electrodes 310). In some embodiments, the signal of each channel is given a quality score based on the relative energy of the peaks. In some embodiments, the relative energy of a peak refers to the energy of the peak relative to the total energy of the signal under processing. In some embodiments, the energy of a peak is calculated by calculating a root mean square (“RMS”) of the QRS complex containing the R-wave peak and the energy of a signal is calculated by calculating the RMS of the signal. In some embodiments, the relative energy of a peak is calculated by calculating a signal-to-noise ratio of the signal. In some embodiments, the channel having the highest quality score is deemed the “Best Lead”. In some embodiments, the global peaks array is constructed based on the Best Lead, with signals from the other channels also considered based on a voting mechanism. In some embodiments, after the global peaks array has been constructed based on the Best Lead, each of the remaining channels “votes” on each peak. A channel votes positively (e.g., gives a vote value of “1”) on a given peak that is included in the global peaks array constructed based on the best lead if it contains such peak (e.g., as detected in the peak detection described above), and votes negatively (e.g., gives a vote value of “0”) if it does not contain such peak. Peaks that receive more votes are considered to be higher-quality peaks. In some embodiments, if a peak has greater than a threshold number of votes, it is retained in the global peaks array. In some embodiments, the threshold number of votes is half of the total number of channels. In some embodiments, if a peak has less than the threshold number of votes, additional testing is performed on the peak. In some embodiments, the additional testing includes calculating a correlation of the peak in the Best Lead channel with a template calculated as the average of all peaks. In some embodiments, if the correlation is greater than a first threshold correlation value, the peak is retained in the global peaks array. In some embodiments, the first threshold correlation value is 0.9. In some embodiments, if the correlation is less than the first threshold correlation value, a further correlation is calculated for all leads with positive votes for the peak (i.e., not just the Best Lead peak). In some embodiments, if the further correlation is greater than a second threshold correlation value, the peak is retained in the global peaks array, and if the further correlation is less than the second threshold correlation value, the peak is excluded from the global peaks array. In some embodiments, the second threshold correlation value is 0.85.
In some embodiments, once created, the global peaks array is examined using physiological measures. In some embodiments, the examination is performed by the exemplary inventive computing device as described in U.S. Pat. No. 9,392,952, the contents of which are incorporated herein in their entirety. In some embodiments, the physiological parameters include R-R intervals, mean, and standard deviation; and heart rate and heart rate variability. In some embodiments, the examination includes cross-correlation to overcome false negatives. FIG. 6D shows a data signal following creation and examination of the global peaks array as described above. In FIG. 6D, peaks denoted by circled asterisks represent R-wave peaks that were detected previously (e.g., as shown in FIG. 6A), and circles with no asterisks represent R-wave peaks detected by cross-correlation to overcome false negatives as described above.
In some embodiments, if an initial step of R-wave detection was unsuccessful (i.e., if no R-wave peaks were detected over a given sample), an independent component analysis (“ICA”) algorithm is applied to the data samples and the earlier portions of step 220 are repeated. In some embodiments, the exemplary ICA algorithm is, for example but not limited to, the FAST ICA algorithm. In some embodiments, the FAST ICA algorithm is, for example, utilized in accordance with Hyvarinen et al., “Independent component analysis: Algorithms and applications,” Neural Networks 13 (4-5): 411-430 (2000).
Continuing to refer to FIG. 2, in step 230, the exemplary inventive computing device is programmed/configured to extract maternal ECG signals from signals that include both maternal and fetal data. In some embodiments, where the exemplary inventive computing device, programmed/configured to execute the method 200, receives maternal ECG signals as input after extraction from mixed maternal-fetal data, the exemplary inventive computing device is programmed/configured to skip step 230. FIG. 7A shows a portion of a signal in which R-wave peaks have been identified, and which includes both maternal and fetal signals. Without intending to be limited to any particular theory, the main challenge involved in the process of extracting maternal ECG signals is that each maternal heartbeat differs from all other maternal heartbeats. In some embodiments, this challenge is addressed by using an adaptive reconstruction scheme to identify each maternal heartbeat. In some embodiments, the extraction process begins by segmenting an ECG signal into a three-sourced signal. In some embodiments, this segmentation includes using a curve length transform to find a P-wave, a QRS complex, and a T-wave. In some embodiments, the curve length transform is as described in Zong et al., “A QT Interval Detection Algorithm Based On ECG Curve Length Transform,” Computers In Cardiology 33:377-380 (October 2006). FIG. 7B shows an exemplary ECG signal including these portions.
Following the curve length transform, step 230 continues by using an adaptive template to extract the maternal signal. In some embodiments, template adaptation is used to isolate the current beat. In some embodiments, the extraction of the maternal signal using an adaptive template is performed as described in U.S. Pat. No. 9,392,952, the contents of which are incorporated herein by reference in their entirety. In some embodiments, this process includes beginning with a current template and adapting the current template using an iterative process to arrive at the current beat. In some embodiments, for each part of the signal (i.e., the P-wave, the QRS complex, and the T-wave), a multiplier is defined (referred to as P_mult, QRS_mult, and T_mult, respectively). In some embodiments, a shifting parameter is also defined. In some embodiments, the extraction uses a Levenberg-Marquardt non-linear least mean squares algorithm, as shown below:
P _k+1 =P _k−[
_k ^T
_k+λ_i·diag(
_k ^T
_k)]⁻¹*
_k ^T[ϕ_c(P _k)−ϕ_m]
In some embodiments, the cost function is as shown below:
E=∥ϕ _m−ϕ_c∥²
In the above expressions, #m represents the current beat ECG and #_crepresents the reconstructed ECG. In some embodiments, this method provides a local, stable, and repeatable solution. In some embodiments, iteration proceeds until the relative remaining energy has reached a threshold value. In some embodiments, the threshold value is between 0 db and −40 db. In some embodiments, the threshold value is between −10 db and −40 db. In some embodiments, the threshold value is between −20 db and −40 db. In some embodiments, the threshold value is between −30 db and −40 db. In some embodiments, the threshold value is between −10 db and −30 db. In some embodiments, the threshold value is between −10 db and −20 db. In some embodiments, the threshold value is between −20 db and −40 db. In some embodiments, the threshold value is between −20 db and −30 db. In some embodiments, the threshold value is between −30 db and −40 db. In some embodiments, the threshold value is between −25 db and −35 db. In some embodiments, the threshold value is about −20 db. In some embodiments, the threshold value is about −20 db.
FIG. 7C shows an exemplary signal including mixed maternal and fetal data. FIG. 7D shows a portion of the signal of FIG. 7C along with an initial template for comparison. FIG. 7E shows the portion of the signal of FIG. 7C along with an adapted template for comparison. FIG. 7F shows a portion of the signal of FIG. 7C, a current template, and a 0th iteration of the adaptation. FIG. 7G shows a portion of the signal of FIG. 7C, a current template, a 0th iteration of the adaptation, and a 1st iteration of the adaptation. FIG. 7H shows a portion of the signal of FIG. 7C, a current template, and an ECG signal (e.g., a maternal ECG signal) reconstructed based on the current template. FIG. 7I shows the progress of the adaptation in terms of the logarithm of the error signal against the number of the iteration. FIG. 7J shows an extracted maternal ECG signal.
Continuing to refer to FIG. 2, in step 240, the exemplary inventive computing device is programmed/configured to perform a signal cleanup on the maternal signals extracted in step 230. In some embodiments, the cleanup of step 240 includes filtering. In some embodiments, the filtering includes baseline removal using a moving average filter. In some embodiments, the filtering includes low pass filtering. In some embodiments, the low pass filtering is performed at between 25 Hz and 125 Hz. In some embodiments, the low pass filtering is performed at between 50 Hz and 100 Hz. In some embodiments, the low pass filtering is performed at 75 Hz. FIG. 8 shows a portion of an exemplary filtered maternal ECG following the performance of step 240.
Continuing to refer to FIG. 2, in step 250, the exemplary inventive computing device is programmed/configured to calculate R-wave amplitudes for the filtered maternal ECG signals resulting from the performance of step 240. In some embodiments, R-wave amplitudes are calculated based on the maternal ECG peaks that were detected in step 220 and the maternal ECG signals that were extracted in step 230. In some embodiments, step 250 includes calculating the amplitude of the various R-waves. In some embodiments, the amplitude is calculated as the value (e.g., signal amplitude) of the maternal ECG signals at each detected peak position. FIG. 9 shows an exemplary extracted maternal ECG signal with R-wave peaks annotated with circles.
Continuing to refer to FIG. 2, in step 260, the exemplary inventive computing device is programmed/configured to create an R-wave amplitude signal over time based on the R-wave amplitudes that were calculated in step 250. In some embodiments, the calculated R-wave peaks are not sampled uniformly over time. Accordingly, in some embodiments, step 260 is performed in order to re-sample the R-wave amplitudes in a way such that they will be uniformly sampled over time (e.g., such that the difference in time between each two adjacent samples is constant). In some embodiments, step 260 is performed by connecting the R-wave amplitude values that were calculated in step 250 and re-sampling the connected R-wave amplitude values. In some embodiments, the re-sampling includes interpolation with defined query points in time. In some embodiments, the interpolation includes linear interpolation. In some embodiments, the interpolation includes spline interpolation. In some embodiments, the interpolation includes cubic interpolation. In some embodiments, the query points define the points in time at which interpolation should occur. FIG. 10A shows an exemplary R-wave amplitude signal as created in step 260 based on the R-wave amplitudes from step 250. In FIG. 10A, the maternal ECG is similar to that shown in FIG. 8, the detected R-wave peaks are shown in circles, and the R-wave amplitude signal is the curve connecting the circles. FIG. 10B shows the modulation of the R-wave amplitude signal over a larger time window.
Continuing to refer to FIG. 2, in step 270, the exemplary inventive computing device is programmed/configured to clean up the R-wave amplitude signal by applying a moving average filter. In some embodiments, the moving average filter is applied to clean the high-frequency changes in the R-wave amplitude signal. In some embodiments, the moving average filter is applied over a predetermined time window. In some embodiments, the time window has a length of between one second and ten minutes. In some embodiments, the time window has a length of between one second and one minute. In some embodiments, the time window has a length of between one second and 30 seconds. In some embodiments, the time window has a length of twenty seconds. FIG. 11A shows the R-wave amplitude signal of FIG. 10B, with the signal resulting from the application of the moving average filter shown in a thick line along the middle of the R-wave amplitude signal. As noted above, in some embodiments, multiple channels of data are considered as input for the method 200. FIG. 11B shows a plot of filtered R-wave amplitude signals for multiple channels over the same time window.
Continuing to refer to FIG. 2, in step 280, the exemplary inventive computing device is programmed/configured to calculate the average signal of all the filtered R-wave signals (e.g., as shown in FIG. 11B) per unit of time. In some embodiments, at each point in time for which a sample exists, a single average signal is calculated. In some embodiments, the average signal is the 80th percentile of all the signals at each point in time. In some embodiments, the average signal is the 85th percentile of all the signals at each point in time. In some embodiments, the average signal is the 90th percentile of all the signals at each point in time. In some embodiments, the average signal is the 95th percentile of all the signals at each point in time. In some embodiments, the average signal is the 99th percentile of all the signals at each point in time. In some embodiments, the result of this averaging is a single signal with uniform sampling over time. In step 290, the exemplary inventive computing device is programmed/configured to normalize the signal calculated in step 280. In some embodiments, the signal is normalized by dividing by a constant factor. In some embodiments, the constant factor is between 2 volts and 1000 volts. In some embodiments, the constant factor is 50 volts. FIG. 12A shows an exemplary normalized electrical uterine signal following the performance of steps 280 and 290. FIG. 12B shows a tocograph signal generated over the same time period, with contractions self-reported by the mother indicated by vertical lines. Referring to FIGS. 12A and 12B, it can be seen that the peaks in the exemplary normalized electrical uterine signal in FIG. 12A coincide with the self-reported contractions shown in FIG. 12B. Accordingly, in some embodiments, a normalized electrical uterine monitoring (“EUM”) signal produced through the performance of the exemplary method 200 (e.g., the signal shown in 12A) is suitable for use to identify contractions. In some embodiments, a contraction is identified by identifying a peak in the EUM signal.
In some embodiments, the present invention is directed to a specifically programmed computer system, including at least the following components: a non-transient memory, electronically storing computer-executable program code; and at least one computer processor that, when executing the program code, becomes a specifically programmed computing processor that is configured to perform at least the following operations: receiving a plurality of bio-potential signals collected at a plurality of locations on the abdomen of a pregnant mother; detecting R-wave peaks in the bio-potential signals; extracting maternal electrocardiogram (“ECG”) signals from the bio-potential signals; determining R-wave amplitudes in the maternal ECG signals; creating an R-wave amplitude signal for each of the maternal ECG signals; calculating an average of all the R-wave amplitude signals; and normalizing the average to produce an electrical uterine monitoring (“EUM”) signal. In some embodiments, the operations also include identifying at least one uterine contraction based on a corresponding at least one peak in the EUM signal.
FIG. 13 shows a flowchart of an exemplary inventive method 1300. In some embodiments, an exemplary inventive computing device, programmed/configured in accordance with the method 1300, is operative to receive, as input, raw bio-potential data measured by a plurality of electrodes positioned on the skin of a pregnant human subject, and analyze such input to produce a tocograph-like signal. In some embodiments, the quantity of electrodes is between 2 and 10. In some embodiments, the quantity of electrodes is between 2 and 20. In some embodiments, the quantity of electrodes is between 2 and 30. In some embodiments, the quantity of electrodes is between 2 and 40. In some embodiments, the quantity of electrodes is between 4 and 10. In some embodiments, the quantity of electrodes is between 4 and 20. In some embodiments, the quantity of electrodes is between 4 and 30. In some embodiments, the quantity of electrodes is between 4 and 40. In some embodiments, the quantity of electrodes is between 6 and 10. In some embodiments, the quantity of electrodes is between 6 and 20. In some embodiments, the quantity of electrodes is between 6 and 30. In some embodiments, the quantity of electrodes is between 6 and 40. In some embodiments, the quantity of electrodes is between 8 and 10. In some embodiments, the quantity of electrodes is between 8 and 20. In some embodiments, the quantity of electrodes is between 8 and 30. In some embodiments, the quantity of electrodes is between 8 and 40. In some embodiments, the quantity of electrodes is 8. In some embodiments, the exemplary inventive computing device, programmed/configured in accordance with the method 1300, is operative to receive, as input, maternal ECG signals that have already been extracted from raw bio-potential data (e.g., by separation from fetal ECG signals that form part of the same raw bio-potential data). In some embodiments, the exemplary inventive computing device is programmed/configured in accordance with the method 1300 via instructions stored in a non-transitory computer-readable medium. In some embodiments, the exemplary inventive computing device includes at least one computer processor, which, when executing the instructions, becomes a specifically-programmed computer processor programmed/configured in accordance with the method 1300.
In some embodiments, the exemplary inventive computing device is programmed/configured to continuously perform one or more steps of the method 1300 along a moving time window. In some embodiments, the moving time window has a predefined length. In some embodiments, the predefined length is sixty seconds. In some embodiments, the exemplary inventive computing device is programmed/configured to continuously perform one or more steps of the method 1300 along a moving time window having a length that is between one second and one hour. In some embodiments, the length of the moving time window is between thirty seconds and 30 minutes. In some embodiments, the length of the moving time window is between 30 seconds and 10 minutes. In some embodiments, the length of the moving time window is between 30 seconds and 5 minutes. In some embodiments, the length of the moving time window is about 60 seconds. In some embodiments, the length of the moving time window is 60 seconds.
In step 1305, the exemplary inventive computing device is programmed/configured to receive raw bio-potential data as input. Exemplary raw bio-potential data is shown in FIGS. 18A, 18C, 18E, and 18G. In some embodiments, the raw bio-potential data is recorded through the use of at least two electrodes positioned in proximity to a pregnant subject's skin. In some embodiments, at least one of the electrodes is a signal electrode. In some embodiments at least one of the electrodes is a reference electrode. In some embodiments, the reference electrode is located at a point away from the uterus of the subject. In some embodiments, a bio-potential signal is recorded at each of several points around the pregnant subject's abdomen. In some embodiments, a bio-potential signal is recorded at each of eight points around the pregnant subject's abdomen. In some embodiments, the bio-potential data is recorded at 1,000 samples per second. In some embodiments, the bio-potential data is up-sampled to 1,000 samples per second. In some embodiments, the bio-potential data is recorded at a sampling rate of between 100 and 10,000 samples per second. In some embodiments, the bio-potential data is up-sampled to a sampling rate of between 100 and 10,000 samples per second. In some embodiments, the steps of the method 1300 between receipt of raw data and channel selection (i.e., step 1310 through step 1335) are performed on each of a plurality of signal channels, wherein each signal channel is generated by the exemplary inventive computing device as the difference between the bio-potential signals recorded by a specific pair of the electrodes. In some embodiments, in which the method 1300 is performed through the use of data recorded at electrodes located as shown in FIGS. 4A and 4B, channels are identified as follows:

- Channel 1: A1-A4
- Channel 2: A2-A3
- Channel 3: A2-A4
- Channel 4: A4-A3
- Channel 5: B1-B3
- Channel 6: B1-B2
- Channel 7: B3-B2
- Channel 8: A1-A3

In step 1310, the exemplary inventive computing device is programmed/configured to pre-process the signal channels determined based on the raw bio-potential data to produce a plurality of pre-processed signal channels. In some embodiments, the pre-processing includes one or more filters. In some embodiments, the pre-processing includes more than one filter. In some embodiments, the pre-processing includes a DC removal filter, a powerline filter, and a high pass filter. In some embodiments, a DC removal filter removes the raw data's mean at the current processing interval. In some embodiments, the powerline filter includes a 10th-order band-stop infinite impulse response (“IIR”) filter that is configured to minimize any noise at a preconfigured frequency in the data. In some embodiments, the preconfigured frequency is 50 Hz and the powerline filter includes cutoff frequencies of 49.5 Hz and 50.5 Hz. In some embodiments, the preconfigured frequency is 60 Hz and the powerline filter includes cutoff frequencies of 59.5 Hz and 60.5 Hz. In some embodiments, high pass filtering is performed by subtracting a wandering baseline from the signal, where the baseline is calculated through a moving average window having a predetermined length. In some embodiments, the predetermined length is between 50 milliseconds and 350 milliseconds. In some embodiments, the predetermined length is between 100 milliseconds and 300 milliseconds. In some embodiments, the predetermined length is between 150 milliseconds and 250 milliseconds. In some embodiments, the predetermined length is between 175 milliseconds and 225 milliseconds. In some embodiments, the predetermined length is about 200 milliseconds. In some embodiments, the predetermined length is 201 milliseconds (i.e., 50 samples at a sampling rate of 250 samples per second) long. In some embodiments, the baseline includes data from frequencies lower than 5 Hz, and thus the signal is high pass filtered at about 5 Hz. Pre-processed data generated based on the raw bio-potential data shown in FIGS. 18A, 18C, 18E, and 18G is shown in FIGS. 18B, 18D, 18F, and 18H, respectively.
Continuing to refer to step 1310, in some embodiments, following application of the filters described above, each data channel is checked for contact issues. In some embodiments, contact issues are identified in each data channel based on at least one of (a) RMS of the data channel, (b) signal-noise ratio (“SNR”) of the data channel, and (c) time changes in peaks relative energy of the data channel. In some embodiments, a data channel is identified as corrupted if it has an RMS value greater than a threshold RMS value. In some embodiments, the threshold RMS value is two local voltage units (e.g., a value of about 16.5 millivolts). In some embodiments, the threshold RMS value is between one local voltage unit and three local voltage units. An exemplary data channel identified as corrupted on this basis is shown in FIGS. 18A and 18B. In some embodiments, a data channel is identified as corrupted if it has a SNR value less than a threshold SNR value. In some embodiments, the threshold SNR value is 50 dB. In some embodiments, the threshold SNR value is between 40 dB and 60 dB. In some embodiments, the threshold SNR value is between 30 dB and 70 dB. An exemplary data channel identified as corrupted on this basis is shown in FIGS. 18C and 18D. In some embodiments, a data channel is identified as corrupted if it has a change in relative R-wave peak energy from one interval to another that is greater than a threshold amount of change. In some embodiments, the threshold amount of change is 250%. In some embodiments, the threshold amount of change is between 200% and 300%. In some embodiments, the threshold amount of change is between 150% and 350%. An exemplary data channel identified as corrupted on this basis is shown in FIGS. 18E and 18F. An exemplary data channel not identified as corrupted for any of the above reasons is shown in FIGS. 18G and 18H.
In step 1315, the exemplary inventive computing device is programmed/configured to extract R-wave peaks from the pre-processed signal channels to produce R-wave peak data sets. In some embodiments, step 1315 uses as input known maternal ECG peaks. In some embodiments, step 1315 uses as input maternal ECG peaks identified in accordance with the techniques described in U.S. Pat. No. 9,392,952. In some embodiments, step 1315 includes using the preprocessed data (e.g., as produced by step 1310) and the known maternal ECG peaks to refine the maternal ECG peak positions. In some embodiments, peak position refinement includes a search for the maximal absolute value in a window of samples before and after the known maternal ECG peaks to ensure the R-wave peak is positioned at the maximum point of the R waves for each one of the filtered signals. In some embodiments, the window includes plus or minus a predetermined length of time. In some embodiments, the predetermined length is between 50 milliseconds and 350 milliseconds. In some embodiments, the predetermined length is between 100 milliseconds and 300 milliseconds. In some embodiments, the predetermined length is between 150 milliseconds and 250 milliseconds. In some embodiments, the predetermined length is between 175 milliseconds and 225 milliseconds. In some embodiments, the predetermined length is about 200 milliseconds. In some embodiments, the window includes plus or minus a number of samples that is in a range between one sample and 100 samples. Illustration of the known maternal ECG peaks and the extracted R-wave peaks in an exemplary R-wave peak data set are shown in FIGS. 19A and 19B, respectively.
In step 1320, the exemplary inventive computing device is programmed/configured to remove electromyography (“EMG”) artifacts from the data, which includes the preprocessed data produced by step 1310 and the R-wave peaks extracted in FIG. 1315. FIG. 20A shows exemplary preprocessed data used as input to step 1320. In some embodiments, removal of EMG artifacts is performed in order to correct for peaks with high amplitude where there is an increase in high frequency energy, which usually, but not always, originates from maternal EMG activity. Other sources of such energy are high powerline noise and high fetal activity. In some embodiments, removal of EMG artifacts includes finding corrupted peaks and replacing them with a median value. In some embodiments, finding corrupted peaks includes calculating inter-peak RMS values based on the following formula:
The first step of correcting this artefact is finding the corrupted peaks. Doing so requires calculating the inter-peaks RMS values thus:
inter peaks RMS(iPeak)=RMS(peaks signal(peak location(iPeak)+1:peak location(iPeak+1)−1))
In the above formula, peaks signal is the signal with R-peaks heights (i.e., the amplitude of the R-wave peaks) and peak location is the signal with R-peaks time-indices found per each channel (i.e., the time index for each of the R-wave peaks). In some embodiments, there are two peaks signal values and two peak location values, one for R-wave peaks found using the filtered data and one found using the opposite signal (i.e., a signal obtained by multiplying the original signal data by −1 to yield a sign-inverted signal).
In some embodiments, finding corrupted peaks also includes finding outlier peaks in a maternal physical activity (“MPA”) data set. In some embodiments, such signals (referred to as “envelope signals” hereinafter) are extracted as follows:
In some embodiments, physical activity data is collected using motion sensors. In some embodiments, the motion sensors include a tri-axial accelerometer and a tri-axial gyroscope. In some embodiments, the motion sensors are sampled 50 times per second (50 sps). In some embodiments, the sensors are located on a same sensing device (e.g., a wearable device) that contains electrodes used to collect bio-potential data for the performance of the method 1300 as a whole (e.g., the garment 300 shown in FIG. 3).
In some embodiments, raw motion data is converted. In some embodiments, raw motion data is converted to g units in the case of accelerometer raw data and degrees per second in the case of gyroscope raw data. In some embodiments, the converted data is examined to distinguish between valid and invalid signals by determining whether the raw signals are saturated (e.g., that they have a constant maximal possible value). In some embodiments, signal envelope is extracted as follows. First, in some embodiments, the data is checked for position change. Since position change is characterized by an increase in accelerometer baseline, in some embodiments a baseline filter is applied whenever a position change occurs. In some embodiments, filtration is performed by employing a high-pass finite impulse response (“FIR”) filter. In some embodiments, the high-pass filter has a filter order of 400 and a frequency of 1 Hertz. In some embodiments, to eliminate any non-physiological movement, a low-pass FIR filter is also applied. In some embodiments, the low-pass filter has a filter order of 400 and a frequency of 12 Hertz. (order 400, fc=12 Hz [1]) is applied as well. In some embodiments, following filtering, the magnitude of the accelerometer vector is calculated in accordance with the below formula:
$AccMagnitudeVector (iSample) = \sqrt{({AccData (x, iSample)}^{2} + {AccData (y, iSample)}^{2}) + {AccData (z, iSample)}^{2}}$
In this formula, AccMagnitudeVector(iSample) represents the square root of the sum of the squares of the three accelerometer axes (e.g., x, y, and z) for sample number iSample. In some embodiments, the magnitude vector of the gyroscope data is calculated in accordance with the following formula:
$GyroMagnitudeVector (iSample) = \sqrt{({GyroData (x, iSample)}^{2} + {GyroData (y, iSample)}^{2}) + {GyroData (z, iSample)}^{2}}$
In this formula, GyroMagnitudeVector(iSample) represents the square root of the sum of the squares of the three gyroscope axes (e.g., x, y, and z) for sample number iSample. In some embodiments, following calculation of both the accelerometer magnitude vector and the gyroscope magnitude vector, envelopes of the gyroscope's magnitude vector and the accelerometer's magnitude vector are extracted by applying an RMS window to the gyroscope's magnitude vector and the accelerometer's magnitude vector, respectively. In some embodiments, the RMS window is 50 samples in length. In some embodiments, following extraction of the envelopes of the gyroscope's magnitude vector and the accelerometer's magnitude vector, the two envelopes are averaged (e.g., mean average, median, etc.) to produce an MPA motion envelope.
In some embodiments, peaks in the MPA motion envelope are defined in accordance with the following steps:
motion envelope peaks=find(motion envelope>P _95%(motion envelope))
motion envelope peaks onset=motion envelope peaks−2·peak width
motion envelope peaks offset=motion envelope peaks+2·peak width
In the above, peak width is defined as the distance between the peak and the first point where the envelope reaches 50% of the peak value and P_95%(x) is the 95th percentile of x. FIG. 20B shows the data signal of FIG. 20A along with a corresponding motion envelope calculated in accordance with the above and an inter-peaks absolute sum (i.e., the sum of the absolute values of all samples falling in between adjacent peaks).
In some embodiments, peaks are determined to be corrupt if they are:

- 1) Peaks with inter-peaks RMS higher than 20 local voltage units
- 2) In case the signal examination stage concluded there is a contact issue in the current processing interval, peaks with inter-peaks RMS higher than 8 local voltage units
- 3) In case the signal examination stage concluded there is a contact issue in the current processing interval, but more than 50% of points have inter-peaks RMS higher than 8 local voltage units, use the 20 local voltage units threshold
- 4) Peaks positioned around the motion envelope onset and offset are suspected to be corrupt. These points' inter-peaks RMS should exceed 6 to conclude they are corrupt.

In some embodiments, if a peak is detected to be a corrupted peak as described above, the amplitude of the peak is replaced with a median value, where local median value around the corrupted peak is calculated as follows:
local median=median(peaks signal(corrupt peak−10:corrupt peak+10))
In some embodiments, the corrupted data points themselves are excluded from the above calculation and replaced with a statistical value (e.g., a global median, a local median, a mean, etc.). In some embodiments, if there are 7 or less values to use after exclusion, use the global median as the local one, where the global median is calculated using standard techniques:
local median=global median=median(signal)
In some embodiments, if the absolute difference between the local median and global median exceeds 0.1, the local median is used in place of the amplitude of the corrupted data point, and otherwise the global median is used as a replacement for the corrupted peaks' amplitude. FIG. 20C shows the exemplary data set of FIGS. 20A and 20B with corrupted peaks replaced as discussed above.
Continuing to refer to FIG. 13, in step 1325, the exemplary inventive computing device is programmed/configured to remove baseline artifacts from the signal formed by the R-wave peaks. In some embodiments, such artifacts are caused by sudden baseline or RMS changes. In some embodiments, such changes are often caused by maternal position changes. FIG. 21A shows an exemplary data signal that includes a baseline artifact.
In some embodiments, such artifacts are found using the Grubbs test for outliers, which is a statistical test performed based on absolute deviation from sample mean. In some embodiments, to correct such artifacts, a point of change should be found at first. In some embodiments, a point of change is a point (e.g., data point) where a change in signal RMS or mean begins; such a point should satisfy the following criteria:
$\begin{matrix} length (peaks signal) - change point > 50 & 1) \\ prctile (peaks signal (change point : end), 10) > 0.01 & 2) \\ 1.5 < \frac{P_{10 %} (peaks signal (1 : change point - 1))}{P_{10 %} (peaks signal (change point : end))} < 2 (where P_{10 %} (x) is the 10^{th} percentile of x) & 3 a) \end{matrix}$

OR

$\begin{matrix} 0 < \frac{P_{1 0 %} (peaks signal (1 : change point - 1))}{P_{1 0 %} (peaks signal (change point : end))} < 0.8 & 3 b) \end{matrix}$
In some embodiments, should the change point satisfy the above-mentioned criteria, the peak signal up to this point is changed based on a statistical value as defined below:
$peaks signal (1 : change point - 1) = \frac{P_{1 0 %} (peaks signal (change point : end))}{P_{1 0 %} (peaks signal (1 : change point - 1))} \cdot peaks signal (1 : change point - 1)$
FIG. 21B shows the exemplary data signal of FIG. 21A after baseline artifact removal has been performed in accordance with step 1330.
Continuing to refer to FIG. 13, in step 1330, the exemplary inventive computing device is programmed/configured to remove outliers from the R-wave peaks signal using an iterative process according to a Grubbs test for outliers. FIG. 22A shows an exemplary R-wave peaks signal that includes an outlier data point, as indicated by a diamond. In some embodiments, the iterative process of step 1330 stops when either of the following two conditions occurs:
$\begin{matrix} Outliers \frac{P_{9 5 %}}{P} > 1.5 & 1) \\ Iteration number > 4 & 2) \end{matrix}$
In some embodiments, this process finds outlier points at each iteration and trims the height of such outlier points to the median value of the local area around the outlier peak. In some embodiments, the local area is defined as a time window of a predetermined number of samples before and after the outlier peak. In some embodiments, the predetermined number of samples is between zero and twenty. In some embodiments, the predetermined number of samples is ten. FIG. 22B shows the exemplary data signal of FIG. 22A following the performance of step 1330. It may be seen that the outlier data point shown in FIG. 22A is no longer present in FIG. 22B. In some embodiments, following signal extraction, more outliers are revealed and removed, as will be described in further detail hereinafter.
Continuing to refer to FIG. 13, in step 1335, the exemplary inventive computing device is programmed/configured to interpolate and extract R-wave signal data from each of the R-wave peaks signal data sets to produce R-wave signal channels In some embodiments, the peaks signal that is output by step 1330 is interpolated in time to provide a 4 samples-per-second signal. FIG. 23A shows an exemplary peaks signal output by step 1330. In some embodiments, interpolation is done using cubic spline interpolation. In some embodiments in cases of large gaps in the interpolated data, erroneous high values are present, and instead the interpolation method is shape-preserving piecewise cubic interpolation. In some embodiments, the shape-preserving piecewise cubic interpolation is piecewise cubic hermite interpolating polynomial (“PCHIP”) interpolation. In some embodiments, following interpolation, the process of extracting an R-wave signal includes identifying further outliers in the interpolated signal. In some embodiments, further outliers are identified in this step as one of the following:

- 1) Signal peaks (i.e., peaks in the R-wave signal after interpolation, not peaks in the raw bio-potential signal) with height larger than 1 local voltage unit and its surroundings
- 2) Points lying between two consecutive R-peaks that are more than 10 seconds apart
- 3) Minutes where a severe contact issue was found during the data examination stage (e.g., during steps 1320, 1335, and 1330)

In some embodiments, points that are identified as outliers based on meeting any of the three criteria mentioned above are discarded and are replaced by a statistical value (e.g., either a local median or a global median) in accordance with the process described above with reference to step 1320.
Continuing to describe step 1335, in some embodiments, following further outlier detection, signal statistics (e.g., median value, minimum value, and standard deviation) are calculated, and a signal (e.g., a one-minute signal time window for a given channel) is identified as a corrupted signal if any of the following are true:

- 1) After elimination of outlier points, the signal still has peaks with amplitude larger than one local voltage unit and standard deviation greater than 0.1
- 2) The signal has a median value greater than 0.65 and a minimum less than 0.6
- 3) More than 15% of the points comprising the signal have been deleted as outliers

Continuing to describe step 1335, following identification of corrupt signals, a sliding RMS window is applied to the signal. In some embodiments, the RMS window has a size that is in the range of between 25 and 200 samples. In some embodiments, the RMS window has a size of 100 samples. In some embodiments, following application of an RMS window, a first order polynomial function is fitted to the signal and then subtracted from the signal, thereby producing a clean version of the interpolated signal, which may be used for the subsequent steps. FIG. 23B shows an exemplary R-wave signal following interpolation of step 1330.
Continuing to refer to FIG. 13, in step 1340, the exemplary inventive computing device is programmed/configured to perform channel selection, whereby a subset of the exemplary R-wave signal channels is selected for use in generating an electrical uterine monitoring signal. In some embodiments, at the start of channel selection all channels are considered to be eligible candidates, and channels are evaluated for possible exclusion in accordance with the following:

- 1) Exclude any channels with contact issues in more than 10% of the processing intervals up to the present time
- 2) If more than 50% of channels are excluded on the basis of the above, exclude instead all channels with contact issues in more than 15% of the processing intervals

If the above results in all channels being excluded, then, instead, any channels that satisfy both of the following criteria are retained, with the remaining channels excluded:

- 1) Standard deviation of the signal is between 0 and 0.1
- 2) Range of the signal is less than 0.2

If the above still results in all channels being excluded, then only the first above condition relating to standard deviation is used, and the second above condition relating to range is disregarded. FIG. 24A shows an exemplary data set including six data channels, with two data channels having been excluded.
In some embodiments, following removal of some channels as described above, the remaining channels are grouped into couples. In some embodiments, in which channels are defined as described above, a channel couple is any pair of the eight channels discussed above. In some embodiments, only couples that are independent of one another (i.e., couples that have no electrode in common) are considered. In some embodiments, possible couples are as follows:

- 1. channels 1 and 2 (A1-A4 and A2-A3)
- 2. channels 1 and 5 (A1-A4 and B1-B3)
- 3. channels 1 and 6 (A1-A4 and B1-B2)
- 4. channels 1 and 7 (A1-A4 and B3-B2)
- 5. channels 2 and 5 (A2-A3 and B1-B3)
- 6. channels 2 and 6 (A2-A3 and B1-B2)
- 7. channels 2 and 7 (A2-A3 and B3-B2)
- 8. channels 3 and 5 (A2-A4 and B1-B3)
- 9. channels 3 and 6 (A2-A4 and B1-B2)
- 10. channels 3 and 7 (A2-A4 and B3-B2)
- 11. channels 3 and 8 (A2-A4 and A1-A3)
- 12. channels 4 and 5 (A4-A3 and B1-B3)
- 13. channels 4 and 6 (A4-A3 and B1-B2)
- 14. channels 4 and 7 (A4-A3 and B3-B2)
- 15. channels 5 and 8 (B1-B3 and A1-A3)
- 16. channels 6 and 8 (B1-B2 and A1-A3)
- 17. channels 7 and 8 (B3-B2 and A1-A3)

As may be seen, for each of the channel pairs listed above, the two channels forming the pair do not share a common electrode. In some embodiments, the Kendall rank correlation of each couple of channels is calculated using only valid points within the channels. In some embodiments, Kendall correlation counts the matching rank signs of each pair of signals to test their statistical dependency.
In some embodiments, channels are then selected by the following selection criteria. First, if the maximum Kendall correlation value is greater than or equal to 0.7, the selected channels are any independent channels having Kendall correlation values greater than or equal to 0.7. However, if all selected channels were previously identified as corrupted, then the output signal is identified as a corrupted signal. Additionally, if any of the selected channels was previously identified as corrupted, or if any of the selected channels has a range greater than 0.3, then any such channels are excluded from the selected channels.
Second, if none of the channels were selected under the first criterion noted above, then if the maximum Kendall correlation value is greater than or equal to 0.5 but less than 0.7, the selected channels are any independent channels having Kendall correlation values in this range. However, if all selected channels were previously identified as corrupted, then the output signal is identified as a corrupted signal. Additionally, if any of the selected channels was previously identified as corrupted, or if any of the selected channels has a range greater than 0.3, then any such channels are excluded from the selected channels.
Third, if none of the channels were selected under the first or second criteria noted above, then if the maximum Kendall correlation value is greater than zero but less than 0.5, then all channels having Kendall correlation values greater than zero are identified as selected channels. However, if the maximal correlation value is less than 0.3, then the output signal is marked as corrupted and all channels with range greater than 0.3 are excluded.
Fourth, if none of the channels were selected under the first three criteria noted above, then all channels with range greater than 0.3 and all channels with more than 15% deleted points are excluded, the remaining channels are selected, and this output signal is identified as one that should be less sharpened, as will be discussed hereinafter with reference to step 1355.
Fifth, if none of the channels were selected under any of the four criteria noted above, then all channels are selected other than those that have severe contact issues. However, if the number of contact issues in the selected channels exceeds fifteen, then the output signal is flagged as corrupted. FIG. 24B shows an exemplary data set following channel selection of step 1340.
In some embodiments, rather than selecting channels in pairs based on correlation values of the pairs, channels are selected individually.
Continuing to refer to FIG. 13, in step 1345, the exemplary inventive computing device is programmed/configured to calculate a uterine activity signal (which may be referred to as an “electrical uterine monitoring” or “EUM” signal) based on the selected R-wave signal channels selected in step 1340. In some embodiments, for each sample (e.g., set of data points at a given sampling time during the four samples per second sampling interval discussed above, for all selected channels), the 80^thpercentile of the selected channels' signals is calculated in accordance with the following:
combined signal(iSample)=P _80%(interpolated peaks signal(selected channels,iSample))
FIG. 25A shows an 80^thpercentile signal calculated based on the selected data channels shown in FIG. 24B. In some embodiments, a wandering baseline is then removed from the combined 80^thpercentile signal as determined above to produce an EUM signal. In some embodiments, a moving average window is considered to find the baseline. In some embodiments, the moving average window subtracts the mean value during the window from the EUM signal. In some embodiments, the length of the window is between zero minutes and twenty minutes. In some embodiments, the length of the window is ten minutes. FIG. 25B shows the exemplary signal of FIG. 25A following removal of the baseline.
In step 1350, the exemplary inventive computing system is programmed/configured to normalize the EUM signal calculated in step 1345. In some embodiments, normalization consists of multiplying the EUM signal from step 1345 by a constant. In some embodiments, the constant is between 200 and 500. In some embodiments, the constant is between 250 and 450. In some embodiments, the constant is between 300 and 400. In some embodiments, the constant is between 325 and 375. In some embodiments, the constant is about 350. In some embodiments, the constant is 350. In some embodiments, the constant is 1, i.e., the original values of the extracted 80^thpercentile signal are maintained. FIG. 26 shows an exemplary data signal following normalization of the data signal of FIG. 25B in accordance with step 1350.
In step 1355, the exemplary inventive computing system is programmed/configured to sharpen the normalized EUM signal produced by step 1350, thereby producing a sharpened EUM signal. In some embodiments, sharpening is performed only on signals that were not flagged as corrupted in the preceding steps; if all relevant signals are flagged as corrupted, then the sharpening step is not performed. In some embodiments, the objective of the sharpening step is to enhance all areas with suspected contractions. In some embodiments, sharpening proceeds as follows. First, if there are any peaks in the EUM signal exceeding the values of 200 local voltage units, the signal is marked as corrupted. Second, it is determined whether the signal was previously marked as corrupted. Third, the signal baseline is removed. In some embodiments, for baseline removal, if the signal duration exceeds ten minutes then a ten-minute long moving average window is used to estimate the baseline, and otherwise the signal's 10^thpercentile is used to estimate the baseline; in either case, the baseline is then subtracted from the EUM signal. Fourth, the signal baseline is defined as 30 visualization voltage units. In some embodiments, a signal baseline defined in this manner following the normalization step provides for an EUM signal that is within a 0-100 range in a manner similar to the signal provided by a cardiotocograph.
Fifth, peaks are identified in accordance with one of the following:

- If the signal was identified as one that needs less sharpening during step 1340, then peaks are defined as having a minimum height of 35 visualization voltage units and a minimum width of 300 samples.
- If the signal was not so identified, peaks are identified as having a minimum height of 35 visualization units and a minimum width of 220 samples.

In either case, the prominence of each peak is calculated in accordance with the below formula:
peaks prominence=peaks height−P _10%(EUM signal)
Following the calculation of the prominence for all peaks in the sample, each peak is eliminated if either of the below is true for that peak:

- The peak has a prominence less than 12 and a height less than 40 visualization voltage units
- The peak has a prominence less than 65% of the maximum prominence of all of the peaks in the sample.

In some embodiments, additional peaks are identified by identifying any further peaks (e.g., local maxima) with a minimum height of 15 visualization voltage units and a minimum width of 200 samples, and then eliminating all peaks with a prominence higher than 20 visualization voltage units.
Following the above, sharpening is performed only if all of the following are true: (a) the signal is not corrupt (with “corrupt” signals being identified as described above); (b) there are no deleted points in the signal; and (c) at least one peak was identified in the preceding portions of this step. If sharpening is to be performed, then, prior to sharpening, each peak is eliminated if any of the below conditions are true for that peak:

- The peak has a prominence of less than 10 visualization voltage units
- The peak has a prominence of greater than 35 visualization voltage units
- The peak has a width of more than 800 samples (i.e., 200 seconds at 4 samples per second)

Following elimination of any peaks that meet one of the conditions noted above, the following values are calculated for each remaining peak:
$μ = mean (peak start, peak end)$ $σ = \frac{(peak end - peak start)}{2 \sqrt{2 π}}$ $t = peak start : peak end$
Once these values have been calculated, a mask of zero values outside the peak areas and Gaussian functions inside the peak areas is created in accordance with the following formula:
$mask (t_{ith peak}) = \exp (- \frac{{(t_{ith peak} - μ_{ith peak})}^{2}}{2 σ_{ith {peak}^{2}}})$
The mask is then smoothed with a moving average window having a predefined length. In some embodiments, the predefined length is between 10 seconds and 50 seconds. In some embodiments, the predefined length is between 20 seconds and 40 seconds. In some embodiments, the predefined length is between 25 seconds and 35 seconds. In some embodiments, the predefined length is about 30 seconds. In some embodiments, the predefined length is 30 seconds. An exemplary EUM signal is shown in FIG. 27A and an exemplary mask created in the above manner for the exemplary EUM signal of FIG. 27A is shown in FIG. 27B. The mask is then added to the existing EUM signal to produce a sharpened EUM signal. In some embodiments, the addition is performed using simple mathematical addition. An exemplary sharpened EUM signal produced by adding the exemplary mask of FIG. 27B to the exemplary EUM signal of FIG. 27A is shown in FIG. 27C.
Referring back to FIG. 13, in step 1360, post-processing is performed to produce a post-processed EUM signal. In some embodiments, post-processing includes baseline removal. In some embodiments, baseline removal includes removing a signal baseline as described above with reference to step 1355. In some embodiments, for baseline removal, if the signal duration exceeds ten minutes then a ten-minute long moving average window is used to estimate the baseline, and otherwise the signal's 10th percentile is used to estimate the baseline; in either case, the baseline is then subtracted from the EUM signal, and the signal baseline is defined as 30 visualization voltage units. Last, all deleted values are set to a value of −1 visualization voltage unit and all values above 100 visualization voltage units are set to a value of 100 visualization voltage units. FIG. 28 shows an exemplary post-processed signal generated by applying the post-processing of step 1360 to the exemplary sharpened signal of FIG. 27B.
Following step 1360, the method 1300 is complete. As noted above, FIG. 28 shows an exemplary EUM signal calculated in accordance with the method 1300. FIG. 29 shows a representative tocograph signal obtained in accordance with known techniques for the same subject and during the same time period as collection of the bio-potential data based on which the EUM signal of FIG. 28 was calculated. It may be seen that FIGS. 28 and 29 are substantially similar to one another and include the same peaks, which may be understood to represent contractions. Accordingly, it may be seen that the result of the method 1300 is an EUM signal that is usable as a tocograph-like signal to monitor maternal uterine activity, but which can be calculated based on bio-potential signals that are recorded non-invasively.
Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments of the invention in a non-limiting fashion.

EXAMPLES

FIGS. 14A-17B show further examples of comparisons between tocograph data and the output of the exemplary method 200. In each of FIGS. 14A, 15A, 16A, and 17A, a tocograph signal against time is shown, with contractions self-reported by the mother being monitored by the tocograph indicated with vertical lines. In each of FIGS. 14B, 15B, 16B, and 17B, the filtered R-wave signal from each of a plurality of channels is shown in a different color (e.g., similar to the plot shown in FIG. 11), with the calculated normalized average signal shown in a heavy black line (e.g., similar to the plot shown in FIG. 12A). Each of FIGS. 14B, 15B, 16B and 17B is shown adjacent to the corresponding one of FIGS. 14A, 15A, 16A, and 17A for comparison (e.g., FIGS. 14A and 14B show different data recorded for the same mother over the same time interval, and so on for FIGS. 15A through 17B). As discussed above with reference to FIGS. 12A and 12B, it can be seen that the peaks in the exemplary normalized uterine signal correspond to the self-reported contractions.
A study was conducted to evaluate the effectiveness of the exemplary embodiments. The study involved a comparison of EUM and TOCO recordings in pregnant women aged 18-50 years with a BMI of <45 kg/m², carrying a singleton fetus at gestational age >32+0 weeks, without fetal anomalies. EUM was calculated as described above over data samples measured for a minimum of 30 minutes. Analysis of the maternal cardiac R-wave amplitude-based uterine activity index referred to herein as EUM showed promising results as an innovative and reliable method for monitoring maternal uterine activity. The EUM data correlated highly with TOCO data. Accordingly, EUM monitoring may provide data that is similarly useful to TOCO data, while overcoming the shortcomings of traditional tocodynamometry, such as discomfort.
FIGS. 18A through 27B show exemplary data existing at various stages during performance of the exemplary method 1300. In particular, FIGS. 27A and 27B show a comparison of the output signal generated by the exemplary method 1300 to a tocograph signal recorded during the same time interval.
FIGS. 18A-18H show exemplary raw data that is received as input for the exemplary method 1300 (e.g., as received in step 1305) and exemplary filtered raw data produced during the exemplary method 1300 (e.g., as produced by step 1310). In particular, FIGS. 18A, 18C, 18E, and 18G show exemplary raw data, while FIGS. 18B, 18D, 18F, and 18H respectively, show exemplary filtered data. It will be apparent to those of skill in the art that FIGS. 18A-18H represent raw and filtered bio-potential data for a single channel and that, in a practical implementation of the method 1300 as described above, data sets comparable to those shown in FIGS. 18A-18H will be present for each channel of data. Referring to FIG. 18A, it may be seen that there is high powerline noise around sample number 6000. Referring to FIG. 18B, it may be seen that the powerline noise is still high; in some embodiments, this may result in this interval being flagged as having severe contact issues due to a change in relative R-wave peak energy from one interval to another that is greater than the threshold value discussed above with reference to step 1310 of exemplary method 1300. Referring to FIG. 18C, it may be seen that there is high powerline noise around sample number 14000. Referring to FIG. 18D, it may be seen that the powerline noise is still high; in some embodiments, this may result in this interval being flagged as having severe contact issues due to the signal RMS exceeding the threshold discussed above with reference to step 1310 of exemplary method 1300. Referring to FIG. 18E, it may be seen that there is high powerline noise throughout the signal. Referring to FIG. 18F, it may be seen that the powerline noise is still high; in some embodiments, this may result in this interval being flagged as having severe contact issues due to the SNR of this signal failing to meet the threshold SNR discussed above with reference to step 1310 of exemplary method 1300. Referring to FIGS. 18G and 18H, it may be seen a clear signal is visible; in some embodiments, this may result in this interval not being flagged as having contact issues.
Referring now to FIGS. 19A and 19B, extraction of R-wave peaks in accordance with step 1315 is shown. It will be apparent to those of skill in the art that FIGS. 19A and 19B represent R-wave peak extraction from a single channel and that, in a practical implementation of the method 1300 as described above, data sets comparable to those shown in FIGS. 19A and 19B will be present for each channel of data. FIG. 19A shows filtered data (e.g., as produced by step 1310) prior to the performance of step 1315. In FIG. 19A, detected peak positions are represented by asterisks. FIG. 19B shows data with extracted peaks following the performance of step 1315. In FIG. 19B, peak positions are represented by asterisks. It may be seen that, in FIG. 19A, some of the peak locations indicated by asterisks are not located at the maximal value of the peak in the data, and that such positions are correctly indicated by the asterisks in FIG. 19B.
Referring now to FIGS. 20A-20C, removal of EMG artifacts in accordance with step 1320 is shown. It will be apparent to those of skill in the art that FIGS. 20A-20C represent removal of EMG artifacts from a single channel and that, in a practical implementation of the method 1300 as described above, data sets comparable to those shown in FIGS. 20A-20C will be present for each channel of data. FIG. 20A shows exemplary filtered data used as in step 1320 (e.g., as produced by step 1310). FIG. 20B shows same filtered data of FIG. 20A and additionally includes a representation of the motion envelope and the inter-peaks absolute sum. In FIG. 20B, peaks suspected to be corrupted are indicated by diamonds. FIG. 20C shows a corrected signal after EMG artifact correction, as produced by step 1320. In FIG. 20C, the suspect peaks have been removed, with corrected peaks shown circled and the original peak values shown in a contrasting shade.
Referring now to FIGS. 21A and 21B, removal of baseline artifacts in accordance with step 1325 is shown. It will be apparent to those of skill in the art that FIGS. 21A and 21B represent removal of baseline artifacts from a single channel and that, in a practical implementation of the method 1300 as described above, data sets comparable to those shown in FIGS. 21A and 21B will be present for each channel of data. FIG. 21A shows exemplary data prior to baseline artifacts removal that may be received as input to step 1325. In FIG. 21A, a baseline artifact is indicated within a circle. In the data shown in FIG. 21A, the baseline ratio between the circled area and the rest of the signal is less than 0.8. In some embodiments, a corrected signal is provided by dividing the rest of the signal by this factor. FIG. 21B shows an exemplary corrected signal such as may be produced by step 1325. In FIG. 21A, the baseline artifact area is indicated within a circle. It may be seen by comparing FIGS. 21A and 21B that the baseline artifact has been removed.
Referring now to FIGS. 22A and 22B, trimming of outliers and gaps in accordance with step 1330 is shown. It will be apparent to those of skill in the art that FIGS. 22A and 22B represent trimming of outliers and gaps from a single channel and that, in a practical implementation of the method 1300 as described above, data sets comparable to those shown in FIGS. 22A and 22B will be present for each channel of data. FIG. 22A shows exemplary data that may be received as input to step 1330. It may be seen that the input data includes an outlier near sample 450, indicated in FIG. 22A with a diamond. FIG. 22B shows the exemplary data of FIG. 22A after the performance of step 1330 to remove outliers as described above. It may be seen that the outlier shown in FIG. 22A has been removed.
Referring now to FIGS. 23A and 23B, interpolation and extraction of an R-wave peak signal in accordance with step 1330 is shown. It will be apparent to those of skill in the art that FIGS. 23A and 23B represent extraction of an R-wave peak signal from a single channel and that, in a practical implementation of the method 1300 as described above, data sets comparable to those shown in FIGS. 23A and 23B will be present for each channel of data. FIG. 23A shows an exemplary R-wave peaks signal that may be provided as output from step 1330 and received as input to step 1335. FIG. 23B shows an exemplary clean interpolated R-wave signal that may be produced by the performance of step 1335.
Referring now to FIGS. 24A and 24B, channel selection in accordance with step 1335 is shown. In the exemplary data set shown in FIGS. 24A and 24B, channels 3 and 8 were found to be ineligible for channel selection due to the presence of contact issues in more than 10% of time intervals. Accordingly, in FIGS. 24A and 24B, only exemplary channels 1, 2, 4, 5, 6, and 7 are shown. Independent channel pairs of the data shown in FIG. 24A with corresponding Kendall correlation values are shown in the table below:


		Kendall
1^st	2^nd	correlation
Channel	Channel	value

1	5	0.01
1	6	0.49
1	7	0.51
2	5	0.08
2	6	0.39
2	7	0.58
4	5	−0.16
4	6	0.38
4	7	0.58

It may be seen from the above table that the group consisting of channels 1, 2, 4, and 7 demonstrates moderate correlation (e.g., correlation greater than 0.5 but less than 0.7). Accordingly, channels 1, 2, 4 and 7 are selected in step 1340. FIG. 24B shows an exemplary data set output by step 1340 including selected channels 1, 2, 4, and 7.
Referring now to FIGS. 25A and 25B, calculation of an EUM signal based on selected channels in accordance with step 1345 is shown. Channel data shown in FIG. 24B is received as input to step 1345 in order to produce output data shown in FIGS. 25A-25B. Referring to FIG. 25A, this figure shows an 80^thpercentile signal extracted from the signals shown in FIG. 24B. FIG. 25B shows a corrected signal obtained by applying wandering baseline removal to the signal shown in FIG. 25A.
Referring now to FIG. 26, calculation of a normalized EUM signal in accordance with step 1350 is shown. Corrected data as produced by step 1345 and as shown in FIG. 25B is received as input to step 1350 in order to produce a normalized EUM signal as shown in FIG. 26. FIG. 26 shows a normalized signal obtained by normalizing the signal shown in FIG. 25B and setting the baseline value to 30 visualization voltage units. It may be seen in FIG. 26 that three weak peaks are present in the signal.
Referring now to FIGS. 27A-27C, sharpening of an EUM signal in accordance with step 1355 is shown. An exemplary normalized signal as produced by step 1350, such as the exemplary normalized signal shown in FIG. 26 is received as input to step 1355 in order to produce a sharpened EUM signal. FIG. 27A shows an exemplary normalized EUM signal as produced by step 1350. FIG. 27B shows an exemplary enhancement mask generated in accordance with step 1355. FIG. 27C shows an exemplary sharpened EUM signal produced by adding the normalized EUM signal of FIG. 27A to the mask of FIG. 27B.
Referring now to FIG. 28, post-processing of an EUM signal in accordance with step 1360 is shown. The sharpened EUM signal as produced by step 1355 is received as input to step 1360 in order to produce a post-processed EUM signal. FIG. 28 shows an exemplary post-processed EUM signal after removing a wandering baseline as described above with reference to step 1360. It may be seen that the three weak peaks shown in FIG. 26 are more clearly visible in FIG. 28 following the sharpening of step 1355 and the post-processing of step 1360.
Referring now to FIG. 29 a tocograph signal corresponding to the exemplary EUM signal of FIG. 28 is shown. As previously noted, the exemplary EUM signal of FIG. 28 is produced in accordance with the method 1300. The representative tocograph signal of FIG. 29 was captured for the same subject during the same time interval as the data used to generate the exemplary EUM signal of FIG. 28. It may be seen that FIGS. 28 and 29 are substantial matches for one another and include the same three peaks as one another.
In some embodiments, uterine monitoring is performed based on acoustic data collected using one or more acoustic sensors such as the acoustic sensors 320 described above with reference to FIG. 3. In some embodiments, the process for uterine monitoring based on acoustic data is substantially similar to the process for uterine monitoring based on bio-potential data described above with reference to the method 1300 shown in FIG. 13, other than as will be described hereinafter. FIG. 30 shows an exemplary method 3000 for uterine monitoring based on acoustic data. In some embodiments, an exemplary inventive computing device is programmed/configured to execute the method 3000. In some embodiments, the exemplary inventive computing device is programmed/configured in accordance with the method 3000 via instructions stored in a non-transitory computer-readable medium. In some embodiments, the exemplary inventive computing device includes at least one computer processor, which, when executing the instructions, becomes a specifically-programmed computer processor programmed/configured in accordance with the method 3000. In some embodiments, the exemplary inventive computing device is specifically configured to solve the technical problems discussed below by the performance of the method 3000.
In step 3005, the exemplary inventive computing device is specifically configured to receive raw acoustic data as input. In some embodiments, one set of raw acoustic data is received from each of a plurality of acoustic sensors positioned in proximity to the abdomen of a pregnant human subject. In some embodiments, one set of raw acoustic data is received from each of two, or three, or four, or five, or six, or seven, or eight, or nine, or ten, or a greater number of acoustic sensors. In one specific exemplary embodiment that will be discussed in detail in the present description of the method 3000, one set of raw acoustic data is received from each of four acoustic sensors, as shown in FIG. 3.
In step 3010, the exemplary inventive computing device is specifically configured to pre-process the raw acoustic data to produce a plurality of channels of pre-processed acoustic data. In some embodiments, pre-processing includes applying at least one filter (e.g., one filter, or two filters, or three filters, or four filters, or five filters, or six filters, or seven filters, or eight filters, or nine filters, or ten filters, or a greater number of filters) to the raw acoustic data, e.g., applying each of a quantity X of filters to each of a quantity Y of channels of raw data to produce a quantity X times Y of preprocessed data channels. In some embodiments, the filters include bandpass filters. In some embodiments, the filters include DC filters. In some embodiments, the filters include finite impulse response filters, or infinite impulse response (“IIR”) filters such as Butterworth filters or Chebyshev filters, or combinations thereof. In some embodiments, the filters include a lowpass zero phase-lag IIR filter with a 50 Hz cutoff. In some embodiments, the filters include twelfth order Butterworth IIR filters, or third order Butterworth IIR filters, or fifth order Butterworth IIR filters. In one exemplary embodiment, the filters include five twelfth order Butterworth IIR filters having frequencies: 10-50 Hz, 15-50 Hz, 20-50 Hz, 25-50 Hz, and 30-50 Hz. In some embodiments, the application of five IIR filters to four raw data channels produces twenty (20) preprocessed data channels. FIG. 31A shows data in an exemplary preprocessed data channel following step 3010. FIG. 31B shows a magnified view of a small time window of the data shown in FIG. 31A.
In step 3015, the exemplary inventive computing device is specifically configured to extract S1-S2 peaks from the pre-processed data channels. It will be known to those of skill in the art that S1 and S2 refer to the first and second sounds without the cardiac cycle. In some embodiments, the term “S1-S2 peak” refers to the maximal point within a given S1-S2 complex. In some embodiments, the S1-S2 peak extraction of step 3015 is performed in a manner substantially similar to the R-wave peak extraction of step 1315 of the method 1300 as described above. FIG. 32A shows data in an exemplary data channel with annotated R-wave peaks shown therein. FIG. 32B shows a magnified view of a small time window of the data shown in FIG. 32A. FIG. 32C shows an exemplary S1-S2 amplitude signal determined based on the R-wave peaks such as those shown in FIG. 32A. FIG. 32D shows an exemplary R-wave amplitude signal over a larger time window.
In steps 3020, 3025, and 3030, the exemplary inventive computing device is specifically configured to remove artifacts and outliers from the data sets produced in step 3015 in the same manner as described above with reference to steps 1320, 1325, and 1330 of the method 1300. It should be noted that the acoustic data that is analyzed by the exemplary method 3000 does not include electrical noise of the type discussed above with reference to step 1320, but, rather, may typically include movement-related noise that is recorded by the acoustic sensors. However, the process for removing such movement-related noise is substantially similar to the process for removing electrical noise described above. FIG. 33 shows an exemplary data set of an exemplary data channel following the performance of steps 3020, 3025, and 3030.
In step 3035, the exemplary inventive computing device is specifically configured to interpolate and extract S1-S2 signal data from the data sets produced in step 3030 in a manner substantially similar to that described above with reference to step 1335 of the method 1300. FIG. 34 shows extracted S1-S2 data sets for a plurality of channels as calculated in step 3035.
In step 3040, the exemplary inventive computing device is specifically configured to perform channel selection in a manner substantially similar to that described above with reference to step 1340 of the method 1300. However, the channel selection of step 3040 differs from that of step 1340 in one aspect. As discussed above, some of the data channels used in step 1340 are not independent from one another due to the differential nature of the bio-potential sensors, as a result of which only some of the data channels used in step 1340 can be coupled with one another. In contrast, the acoustic sensors that collect the data used in the method 3000 are single-ended, i.e., independent from one another. Consequently, any two channels of data may be properly coupled with one another in step 3040. Thus, for example, in an embodiment in which four raw data channels are processed using five different bandpass filters to produce twenty filtered data channels, there are twenty times nineteen, i.e., 380 possible channel couples.
Following channel selection of step 3040, in step 3045, the exemplary inventive computing device is specifically configured to calculate an acoustic uterine activity signal in a manner substantially similar to that described with reference to step 1345 of the method 1300. In step 3050, the exemplary inventive computing device is specifically configured to normalize the acoustic uterine activity signal in a manner substantially similar to that described above with reference to step 1350 of the method 1300. In step 3055, the exemplary inventive computing device is specifically configured to sharpen the normalized acoustic uterine activity signal in a manner substantially similar to that described above with reference to step 1355 of the method 1300. In step 3060, the exemplary inventive computing device is specifically configured to post-process the sharpened acoustic uterine activity signal in a manner substantially similar to that described above with reference to step 1360 of the method 1300.
In some embodiments, the output of the exemplary method 3000 is an acoustic uterine monitoring signal that is determined non-invasively through the analysis of data that can be obtained by acoustic sensors positioned around the abdomen of a pregnant human subject. In some embodiments, the acoustic uterine monitoring signal generated by the exemplary method 3000 provides uterine monitoring data similar to that generated by a tocodynamometer and an ultrasound transducer, and can be used for monitoring uterine activity such as contractions.
FIGS. 35A-37B show examples of comparisons between tocograph data and the output of the exemplary method 3000. In each of FIGS. 35A, 36A, and 37A, a tocograph signal against time is shown. In each of FIGS. 35B, 36B, and 37B, the output of the performance exemplary method 3000 using acoustic data recorded during the same time intervals is shown. It can be seen that the peaks in the exemplary acoustic-based uterine monitoring signal correspond to the peaks in the tocograph data.
FIG. 38 shows a set of ECG-based EUM processed signals and PCG-based processed signals collected from bio-potential sensors and acoustic sensors respectively. In some embodiments, a uterine monitoring signal can be determined based on data collected both from bio-potential sensors (e.g., as discussed above with reference to the methods shown in FIGS. 2 and 13) and acoustic sensors (e.g., as discussed above with reference to the method shown in FIG. 30). Examples of data collected from bio-potential sensors or ECG-based processed EUM signals are shown at section 3801 (first two rows represent 8 channels) and examples of data collected from acoustic sensors or PCG-based processed signals are shown at 3802 (last five rows represent 20 channels). Each column in section 3802 represents an acoustic channel, and each row in section 3802 represents one of 5 filters in a filter bank. Signals such as the ones shown in FIG. 38 can be combined or fused to generate a single uterine activity signal.
FIG. 39 shows a method 3900 for implementing fusion process to generate a uterine activity signal from ECG-based processed EUM signals and PCG-based processed signals. In some embodiments, ECG-based signals can be received from N number of channels as shown at 3901 in parallel or sequentially PCG-based signals can be received from M number of channels at 3903. Thereafter, machine learning technique can be executed at 3905 to determine optimal weights for each of the channels M and N. The optimal weights determined at 3905 can be used to combine the received ECG-based processed EUM signals and the received PCG-based signals into a signal representing uterine activity. Such a signal can be generated, for example, as a weighted average of the N and M channels wherein each channel is associated with a signal.
In some embodiments, the machine learning channel weighting technique can be implemented as a gradient descent (GD) optimization process. For example, a weight value can be given to each of the 28 channels represented in FIG. 38. The cost function for the gradient descent process can be defined as follow:
In each iteration of the gradient descent optimization process, the final signal output is determined based on the weighted average given to each of the 28 channels. For such final signal output, contractions are identified using a detection algorithm based on change from baseline, which defines the start time-point and end time-point of each contraction in the signal. For each identified contraction, a set of features is calculated. Such a set of features can include contraction rise time, contraction fall time, the ratio between the contraction rise time and contraction fall time, SNR, skewness of contraction, and other suitable features. Thereafter, the average value of each feature is calculated across all contractions in the final signal. Then, for each feature, an optimal target value is determined (e.g., based on a standardized or optimal contraction dataset). The cost function of the GD process can correspond to the difference between the optimal target value and the average of a feature value.
In some embodiments, multiple instances of the gradient descent optimization process can be simultaneously executed with different initial weights assigned to each channel. For example, in a first instance, an equal value or the same value can be assigned to all the channels. In a second instance, weights can be assigned to channels based on the quality of the contraction features detected by such channel. For example, contractions can be identified through each channel and for each contraction a set of features can be calculated, for example, contraction rise time, contraction fall time, the ratio between the contraction rise time and contraction fall time, SNR, skewness of contraction, and other suitable features. Average feature values can be calculated across all contractions identified in the channel. A weight that is inversely proportional to the difference between the average features and optimal feature values can be then assigned to the channel. In a third instance, weights can be assigned to channels using a clustering algorithm. For example, for each channel the SNR and its correlation to all other channels can be determined. Clusters of channels can be defined according to their SNR and correlation to other channels. Thereafter, each cluster can be then combined into a single channel and each combined channel can be given a weight based on quality of contraction features detected by such channel. In some embodiments, the optimal outcome can be selected from the first, second, and third instances of the gradient descent optimization process discussed above. As discussed above, in step 3907, the final output i.e., final uterine activity signal is determined based on the weighted average of all the selected channels. FIG. 44 shows a set of exemplary electrical uterine monitoring signals 4410 as received in accordance with step 3901, a set of exemplary acoustic uterine monitoring signals 4420 as received in accordance with step 3903, weights 4430 assigned to each of the signals in accordance with step 3905 (e.g., as determined by the method 4000 that will be described hereinafter; for clarity, only some of the weights 4430 are specifically noted in FIG. 44), and an exemplary final uterine activity signal 4440 as determined in accordance with step 3907.
In some embodiments, a process for determining channel weights (e.g., the process of step 3905) is performed in accordance with the exemplary method 4000 shown in FIG. 40. In step 4010, a set of electrical uterine activity signals and a set of acoustic-based/PCG-based uterine activity signals are received. In some embodiments, the set of electrical uterine activity signals are generated in accordance with step 1335 of the method 1300 shown in FIG. 13. In some embodiments, the set of acoustic uterine activity signals are generated in accordance with step 3035 of the method 3000 shown in FIG. 30.
In step 4020, a plurality of channel sets are initialized. In some embodiments, the channel sets each include different combinations of channels (with possible overlap with one another). In some embodiments, in each set of weights, certain channels are attributed non-zero weights and other channels are “zeroed”. For example, if one set of weights is defined as a set of biopotential channels (e.g., electrical uterine activity channels) only, all channels issuing from acoustic data will be assigned weight of 0, and the channels issuing from biopotential data will be attributed weights based on their quality, as will be detailed below. As will be discussed in further detail hereinafter with reference to subsequent steps of the method 4000, after an initial selection of the weights for each set, an optimization stage is performed using gradient descent and enhancement, and at the end of the process the best set of optimized weights will be selected, and the data will be weighted and averaged according to the selected set of weights. In some embodiments, the plurality of weight sets initialized in step 4020 includes four (4) weight sets. In some embodiments, the plurality of channel sets includes:
1. A “Bio-Set”, consisting of data issuing from the biopotential channels only.
2. An “Acoustic-Set”, consisting of data issuing from the acoustic channels only.
3. A ‘Contraction-Based-Set’, where channels are selected based on K-means clustering of contraction features, as will be discussed hereinafter.
4. A “Combined Set”, where all channels are considered.
In some embodiments, for the first two Sets, non-zero weights are attributed to channels based on data type, as described above. In some embodiments, for the Contraction-Based Set, the initial weights are determined in accordance with the method 4100 that will be described hereinafter with reference to FIG. 41.
FIG. 41 shows a flowchart of a method 4100 for initializing a Contraction-Based Set of channels. In step 4110, the method 4100 takes as input a set of electrical uterine monitoring channels and a set of acoustic uterine monitoring channels, as described above with reference to step 4010 of method 4000. In step 4120, contractions are identified in each of the channels. In some embodiments, the contractions are identified in accordance with the method 4200 that will be described hereinafter with reference to FIG. 42.
In step 4130, a plurality of contraction features are determined for each channel. In some embodiments, six (6) contraction features are determined for each channel. In some embodiments, the features determined for each channel include the following:
1. Kurtosis of the signal during contractions, averaged across contractions.
2. Relative Energy: the ratio between the sum of all values during contractions (sig(conts)) and the sum of all channel values, per channel:
$\frac{\sum sig (conts)}{\sum sig}$
3. Relative Time: the total duration of all contractions together, divided by the duration of the entire channel data.
4. Derivative Energy: the ratio between the RMS of the first derivative of the signal during contractions and the RMS of the first derivative of the entire signal.
5. Time skew: the ratio between mean rise and fall times, which in turn are calculated for each contraction as the difference between onset to peak contraction amplitude, and peak amplitude to offset, respectively.
6. Contraction SNR: calculated as the average between two determined SNR: Global SNR and Averaged Contraction SNR. Global SNR is equal to the RMS of the derivative of all contraction activity divided by the RMS of the derivative of all signal located outside contractions, for a given channel. Averaged Contraction SNR is equal to the averaged SNR across individual contractions, given by the RMS of the derivative of contraction activity divided by the RMS of the derivative of activity located in the immediate surroundings of the specific contraction.
In some embodiments, the output of step 4130 is a feature matrix of size N by 6, where N is the number of channels considered and 6 is the number of features determined for each channel. In step 4140, the channels are clustered. In some embodiments, the channels are clustered by performing K-means clustering on the feature matrix output by step 4130. In some embodiments, a different type of clustering method (e.g., K-medoids clustering, hierarchical clustering, etc.) is used to perform clustering on the feature matrix output by step 4130. In some embodiments, the cluster with the largest number of maximal values across features is then retained as the “best cluster”.
In step 4150, the best cluster is improved. In some embodiments, in an iterative process, the best cluster of channels is improved by removing channels that might reduce the inner agreement between the channels in the cluster. In some embodiments, for that purpose, the inner correlation matrix of all channel pairs within the cluster is computed. In some embodiments, linear correlation (e.g., Pearson correlation) is applied to compute the inner correlation matrix. In some embodiments, another correlation method is applied. In some embodiments, a candidate channel having the lowest correlations with the others is preliminarily removed from the cluster, and the inner correlation matrix is recomputed. In some embodiments, if the inner correlation improves above a pre-defined threshold, as a result of preliminary removal of the candidate channel, the candidate channel is removed. In some embodiments, as a second step, all channels that are not part of the best cluster are tested for their cross-correlation with the averaged cluster signal and added to the cluster if the cross-correlation is sufficiently high and with a small lag. In some embodiments, lag is calculated using the cross-correlation function (which provides the cross-correlation coefficients and the lag as one-dimensional arrays), where the final cross-correlation coefficient is taken as the maximum of the calculated cross-correlation coefficients and the lag is taken as the lag value corresponding to the same array element in which the final correlation coefficient is calculated. In some embodiments, this calculation can be represented in pseudo-code as follows:
corr_coefs,lags=cross_correlation(signal1,signal2)
corr_coef,ind_of_corr_coef=max(corr_coefs)
lag=lags[ind_of_corr_coef]
In some embodiments, cross-correlation is sufficiently high if p>0.8. In some embodiments, lag is sufficiently low if the lag is less than a maximum lag threshold. In some embodiments, the maximum lag threshold is between 30 seconds and 60 seconds, or is between 30 seconds and 40 seconds, or is between 30 seconds and 50 seconds, or is between 40 seconds and 60 seconds, or is between 40 seconds and 50 seconds, or is between 50 seconds and 60 seconds, or is less than 60 seconds, or is between 25 seconds and 35 seconds, or is about 30 seconds, or is 30 seconds. In some embodiments, the result of step 4150 is a cluster of channels with very high inner correlation for processing during the weight selection process below.
In step 4160, regions of excluded channels (e.g., channels that are not selected for inclusion in the best cluster after step 4150) are considered for inclusion in the best cluster if such regions belong to contractions which are of high quality. In some embodiments, this “Regional” data inclusion is performed by finding suitable datapoints within non-included channels (e.g., data points having good contraction activity), zeroing all other datapoints of the channel, and including those “treated” channels with good regions as part of the best cluster as well. In some embodiments, good regions in otherwise non-included channels are recognized as follows: If the contraction SNR of a particular channel (e.g., feature #6 of each channel as discussed above) is above a threshold, the contractions of that channel are tested for their individual SNR against the relevant threshold. In some embodiments, both the SNR and the threshold are unitless values. In some embodiments, the threshold is any value greater than zero. In some embodiments, the threshold is between 0.1 and 5, or is between 0.1 and 4, or is between 0.1 and 3, or is between 0.1 and 2, or is between 0.1 and 1, or is 0.5, or is 1, or is 1.5, or is 2, or is 2.5, or is 3, or is 3.5, or is 4, or is 4.5, or is 5. In some embodiments, data from high SNR contractions are retained if the data comes from timepoints during which there is no contraction activity in previously included “best cluster” channels and if it is above a minimal length. In some embodiments, the minimum length is between 1 minute and 9 minutes, or is between 2 minutes and 8 minutes, or is between 3 minutes and 7 minutes, or is between 4 minutes and 6 minutes, or is about 5 minutes, or is 5 minutes. In other words, contraction data is added to the pool of good channel data if SNR is above threshold and if it includes new timepoints that were not part of previously included contractions, and if these new timepoints are not too scarce. In some embodiments, all other timepoints of such a channel are then zeroed, and the channel with the remaining “good” contraction activity is added to the best cluster. The best cluster is output in step 4170 for use as the Contraction-Based Set of channels to assigned weights.
Referring back to FIG. 40, in step 4030, a set of initial weights is defined for each of the channel sets defined in step 4020. In some embodiments, two weight subsets are defined for each channel. In some embodiments, the two weight subsets include (1) a “channel-voting” subset, as will be described hereinafter, and (2) a “born-equal” subset in which the initial weight of each channel within a channel set is 1/N, with N equal to the number of channels within the set.
In some embodiments, initial weights in a channel-voting subset are determined as follows. Voting, used for the creation of the first subset of weights within each set, is a process by which, for each data-point within a channel, the number of other channels that feature a contraction or do not feature a contraction at that same data-point is counted. In other words, all channels “vote” for activity type (e.g., contraction or not a contraction) in all other channels, data-point by data-point. The votes across the data-points are then averaged to calculate a vote count metric for each particular channel, reflecting the degree of agreement, across the set of channels, with the contractions identified on the particular channel. The voting process is repeated with each channel being voted for by all the other channels.
In some embodiments, in addition to voting, the average of the two contraction scores is computed per channel, where the contraction scores are determined in accordance with step 4280 of the method 4200, which will be described hereinafter. Initial weights are then calculated for each channel, as the sum of the following three items:
1. The ratio of vote count to the number of channels in the set.
2. The ratio between the two contraction scores and a pre-defined score threshold.
3. Reliability of contractions, computed as the ratio between the sum of signal values during identified contractions and the sum of the entire signal, divided by the number of contractions.
The resulting weights are then normalized such that weights across channels sum up to 1. In some embodiments, a uterine monitoring process analyzes received data in “frames” of a set, processing data during the course of a given frame and providing output (e.g., a uterine monitoring signal) at the end of the frame. In some embodiments, a frame is 10 minutes in length. In some embodiments, for any recording frame that is not the first one (e.g., beyond the first 10 minutes during which a given patient is being monitored), weights are averaged with the weights of the previous segment to mitigate abrupt weight changes between processing segments. In some embodiments, weighting of each channel is determined as 0.6 times the previous weight of the channel plus 0.4 times the calculated current weight of the channel as discussed above.
In step 4040, the weights are optimized. In some embodiments, the optimization is performed using a gradient descent process. In some embodiments, a gradient descent algorithm adjusts the weights by trying to minimize a cost function in an iterative process. In some embodiments, the iterative process has a configurable maximum number of iterations. In some embodiments, the iterative process has a maximum of 20 iterations. In some embodiments, the iterative process has a maximum of 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 iterations. In some embodiments, the cost function is computed, for each optimization iteration, as follows: the signal of the relevant channels in a given set is averaged to a single timeseries using the current weights (e.g., the initial weights for a first iteration; the weights determined for the previous iteration for each subsequent iteration), resulting in an interim uterine activity trace. In some embodiments, the interim uterine activity trace is a temporary form of a uterine activity trace, since the weights have not yet been optimized and selected. In some embodiments, contractions are identified in the interim uterine activity trace using the contraction detection process that will be described hereinafter with reference to the method 4200 shown in FIG. 42. In some embodiments, the following equation is then applied to extract the cost function from the signal:
$C (w) = \frac{(E_{c o n t} + E_{t o t}) + (A_{c o n t} + R) / R}{2}$
In the above expression, E_contis contraction energy, computed as the sum of all temporary uterine signal values spanning two-thirds of contraction width around its peak, summed across all contractions; E_totis the sum of the entire temporary signal; A_contis the mean contraction amplitude computed for the third of contraction width around its peak, averaged across contractions; R is the range (max-min) of baseline activity amplitude between contractions; and w identifies the given weight under consideration. Note again that all sets of weights have the same length, which is equal to the number of channels. Weights representing channels that are not to be included in the channel set by its definition (e.g., channels originating from bio-potential signals with reference to an acoustic channel set), are equal to zero.
In step 4050, the best subset of weights for each weight set is selected. In some embodiments, after optimization as described above with reference to step 4040, the two weight subsets within each set compete against each other, and the best subset of weights is selected to “represent” the set. At a later stage of the method 4000, the weights of the different sets will compete between them towards a selection of the final weights that will be used in the fusion process. In some embodiments, the selection process between the two competing uterine activity traces within each set (e.g., the two weight subsets within each set) is based on the following measures:
1. The signal-to-noise ratio of the uterine activity traces.
2. Cost function.
3. Contraction confidence measures, as will be defined hereinafter.
4. A “Difference Index”.
In some embodiments, the difference index quantifies the difference between the MUA signal that has been produced so far throughout the session (i.e. from previously analyzed recording frames) and the signal that would have resulted if these previous recording segments had been analyzed using the current weight set only. In some embodiments, the difference index is computed as follows:
Difference Index=1−max{0,r(S _prev ,S _current)}
In the above, r(S_prev, S_current) is the Spearman correlation coefficient between the previously determined uterine activity trace and the uterine activity trace of the current selected set of channels (excluding the currently analyzed data frame, which cannot be compared with previous data). In some embodiments, this index varies from 0 (identical traces) to 1 (any negative correlation between the 2 traces). This cannot be computed for the first analyzed data segment, and thus this step is omitted for the first analyzed data segment.
In some embodiments, the means of the four measures are compared between the two competing subsets and against a threshold, as well their absolute values. In some embodiments, the comparison is based on a relative difference of 10%, or, if the relative difference is not met, an absolute difference greater than zero. If one of the two subsets presents both greater mean of the above four measures than the other, as well as relative to the threshold, it is selected for the channel. If the subset having the better mean is below threshold, a decision tree is activated where each measure has a different importance in the decision process.
In some embodiments, the decision tree is based on cost functions and confidence measures for the two measures, and is performed as follows:

- If conf_1>conf2
  - If cost_2 is not valid (e.g., has an invalid numerical number, such as NaN or Inf), then select method 1.
    - Else if cost_1 is not valid, then select method 2.
  - If both cost_1 and cost_2 are valid, calculate the relative difference between cost_1 and cost_2. If the relative difference is in favor of measure 1 (meaning that the cost function is lower for method 1) by a threshold (e.g., a threshold of 10%), then select measure 1, otherwise, select measure 2.

In the above, cost_1 is the cost function of the first subset in the comparison, cost_2 is the cost function of the second subset in the comparison, conf_1 is the contraction confidence measure of the first subset in the comparison, and conf_2 is the contraction confidence measure of the second subset in the comparison. In some embodiments, an updated uterine activity trace is finally computed using the selected optimized weights, and contractions are re-defined based on the updated uterine activity trace.
In step 4060, the signals in each channel set are enhanced. In some embodiments, two substeps are performed to enhance the signals. In some embodiments, the first substep is to enhance data in channels with marked contractions. In some embodiments, the first substep is performed by computing, for each channel, a measure of similarity with the weighted averaged signal. For this, three metrics are examined: (1) the correlation coefficient between the weighted-average signal and the individual channels that exceeds a threshold (e.g., any value greater than 0.5, such as 0.6, 0.7, 0.75, 0.8, or 0.9); (2) the first parameter of the first-degree polynomial fit between the channel data and the weighted average (the ‘slope’); and (3) the estimated error (delta) of the fit above (e.g., the difference between the first-degree polynomial fit and the channel). In some embodiments, the three metrics noted above are examined against thresholds (e.g., a threshold of 0.55 for the first metric, of 0.1 of the second metric, and of 0.3 for the third metric, with all thresholds configurable as needed), and the weights associated with any channels exceeding the threshold are retained. The remaining weights (e.g., those that did not cross relevant thresholds) are zeroed. The remaining weights are then scaled to sum up to 1. In some embodiments, following this substep, an additional iteration of gradient differential optimization is run on the resulted weights. Next, in some embodiments, among the selected weights, weights of traces having higher power than the weighted average are further upscaled by a factor that is defined as minimizing the Euclidian distance between the weighted channel and the weighted average. In some embodiments, contractions and their scores are then identified on the new weighted averaged uterine activity trace for each channel.
The second substep considers weights from previous recording segments, if they exist. In some embodiments, the current recording segment is assigned a contribution weight (CW) from 0 to 1, and the previous weights are assigned the complementary contribution weight (1−CW). In some embodiments, the contribution weight CW assigned to a given segment that is segment number N is CW=1/N. As more previous segments exist, the current segment will be assigned a lower CW: each additional recording segment adds a 1/segment-number bit of information. Then, weights are adjusted to balance between current and previous sessions according to this weighing method.
In step 4070, a final weight set is determined. As discussed above, prior to step 4070, a subset of weights has been selected for each of the channel sets, thereby providing uterine activity candidates from which to select a final weight set to produce a final uterine activity output. In some embodiments, to select a final weight set, the same four metrics as are used in step 4050 above. In step 4070, as opposed to in step 4050, there are more than two candidates to compare and select from (e.g., the four channels each having a selected weight set as described above). Thus, in step 4070, selection is performed iteratively. The selection of step 4070 starts by comparing the metrics of a first one of the weight sets with the metrics of a second one of the weight sets, and selecting the best among the two. The selected one of the weight sets is compared against the third one of the weight sets, with the selected best one from that comparison then being compared against the fourth one of the weight sets. The best weight set from that comparison is then selected as the final weight set for use in generating a maternal uterine activity signal. As noted above, in some embodiments, the final weight set determined in step 4070 is used as an input at step 3905 of method 3900 to generate a weighted average of the data channels.
Referring now to FIG. 42, a flowchart for a method 4200 for identifying contractions in a uterine activity signal. In some embodiments, the method 4200 is applied during performance of the method 4000 described above. In some embodiments, the method 4200 is applied to an electrical uterine activity signal generated by the method 1300 and/or to an acoustic uterine activity signal generated by the method 3000. In step 4210, the method 4200 receives as input a current uterine activity channel. It will be apparent to those of skill in the art that while the method 4200 is described with reference to a signal uterine activity channel, the method 4200 can also be performed on multiple uterine activity channels, including either sequentially and/or simultaneously.
In step 4220, a smoothed version and an enhanced version of the input signal received in step 4210 are calculated. In some embodiments, the smoothed version is calculated by convolving the first derivative of the signal with a Hamming window and returning the cumulative sum of the result. In some embodiments, convolution is done after padding the signal with its right-left flipped version at both ends (as will be described in further detail with reference to step 4230 hereinafter), creating a continuous padded signal to ensure no edge effects exist at the beginning or at the end of the original channel data trace. In some embodiments, after the smoothing process, the padding is discarded. In some embodiments, the enhanced version is calculated by computing the hyperbolic tangent of the z-score normalized smoothed signal. In some embodiments, the enhanced version produced in this manner is a smoothed, rounded, time-series where transient modulations in heartbeat peak amplitudes are readily manifested and detectable. FIG. 43 shows a plot showing an exemplary input uterine activity channel 4310, a smoothed channel 4320, and an enhanced channel 4330.
In step 4230, peaks are detected. In some embodiments, peaks of contractions, their prominence and their width are detected on the enhanced channel 4330, after right-left flipping of the signal and adding it as padding to both ends. In some embodiments, the padding of the signal by its mirrored version enables the detection of incomplete contractions at edges of the recording as the mirrored signal “completes” half-contractions with their mirrored versions. In some embodiments, peaks, prominence, and width are calculated as described above with reference to step 1355 of method 1300 as shown in FIG. 13. In some embodiments, given the smoothness of the enhanced channel 4330 and the above parameters, there is no clutter of detected peaks. In some embodiments, as peaks located close to the edges of the signal (not considering padding) may be missed, a second iteration of peak detection is performed, with enhanced sensitivity of the peak finder. In some embodiments, sensitivity is enhanced in the second iteration by reducing thresholds applied to peak width and distance between peaks. In some embodiments, in the first iteration the thresholds are 30 seconds for peak width and 60 seconds for distance between peaks, and in the second iteration the thresholds are 20 seconds for peak width and 50 seconds for distance between peaks. It will be apparent to those of skill in the art that different magnitudes of threshold reduction are also possible. In some embodiments, if any new peak is detected in this second iteration, it is considered only if located 160 seconds or less from the signal edge. In some embodiments, as a third iteration, short contractions with high prominence that might have been missed but constitute physiologically valid contractions are identified. In some embodiments, sensitivity is further enhanced in the third iteration by reducing thresholds applied to peak width and distance between peaks. In some embodiments, in the third iteration the thresholds are 20 seconds for peak width and 40 seconds for distance between peaks. In some embodiments, as final contraction peaks are determined, the width of each contraction is computed using a linear interpolation of the left and right points that intercept the signal at half the peaks' prominence.
In step 4240, outlier peaks are identified. In some embodiments, Euclidean distances between each pair of peak prominences are computed, and an error estimate per peak is calculated as the sum of the distances to the other peaks. In some embodiments, outlier error values are detected. In some embodiments, an outlier error value is one that is greater than 3 scaled median absolute deviation (MAD) away from the median. In some embodiments, scaled MAD is calculated as K*MEDIAN(ABS(A-MEDIAN(A))), where A is the value being evaluated and K is a scaling factor. In some embodiments, the scaling factor K is equal to about 1.5. In some embodiments, the scaling factor K is equal to about 1.4826. Additionally, in some embodiments, contraction peak height is compared to a threshold which is determined based on the smoothed channel 4320 that was generated in step 4220. In some embodiments, the threshold is determined by normalizing the smoothed channel 4320 to its maximal value and set at 0.2 after normalization. In some embodiments, outlier peaks and peaks having a maximum value less than the peak height threshold are discarded as peaks.
In step 4250, incomplete contractions are detected. In some embodiments, an incomplete contraction is one that is still ongoing when a current data segment ends. In some embodiments, a contraction is detected as an incomplete contraction if the contraction peak and the contraction offset are separated by less than a minimum required time and if activity levels before and after the contraction differ above a certain threshold. In some embodiments, the minimum required time is one minute. In some embodiments, the threshold is a relative threshold that is a change of 30% between the value at the determined onset and the value at the determined offset. In some embodiments, if a contraction is identified as incomplete, it is marked as such for further use. For example, in some embodiments, contractions marked as incomplete are given lesser weight when calculating the overall quality of a trace (e.g., are weighted by a factor of 0.5 in determining the overall SNR of a trace). In some embodiments, an incomplete contraction is completed by considering data from a subsequent segment.
In step 4260, confidence measures are computed for each contraction. In some embodiments, three (3) confidence measures are computed. In some embodiments, the confidence measures are completed as follows:
1. Contraction relative energy. This is computed by first calculating the energy of contraction as the sum of the datapoints spanning two-thirds of the contraction width around its peak, and then dividing, for each contraction, its energy by the sum of the energy of all contractions.
2. The ratio between the upper third mean activity (e.g., the mean amplitude of one third of the contraction width around its peak) and the range of values between contractions. The range of values between contractions is computed by taking the distribution of all datapoints which are not located within a contraction and finding the difference between the 5^thpercentile and the 95^thpercentile of this distribution.
3. The ratio between the range of values during and between contractions. The range of values between contraction is computed as in item 2 immediately above. The range of values for each contraction is computed by taking the distribution of datapoints composing the contraction data and finding the difference between the 5^thand the 95^thpercentile of this distribution.
In step 4270, noisy contractions and small contractions are eliminated based on the confidence measures determined in step 4260. In some embodiments, the confidence measures are compared against pre-defined thresholds and are used to eliminate noisy contractions. In some embodiments, noisy contractions are contractions having a confidence measure less than or equal to the pre-defined threshold. In some embodiments, the pre-defined threshold is 0.5. Small contractions, as compared to activity between contractions and the surrounding troughs, are eliminated as well. In some embodiments, small contractions are contractions having a normalized peak value less than 0.2 (e.g., less than 0.2 times the maximum peak value contraction).
In step 4280, contraction scores are determined for each contraction. In some embodiments, contraction scores are used, for example, in the determination of initial weights as described above with reference to step 4030 of the method 4000 shown in FIG. 40. In some embodiments, two contraction scores are determined. In some embodiments, the first contraction score is calculated as the difference between the mean activity level before and after a given contraction, normalized by contraction peak amplitude. In some embodiments, the second contraction score is calculated as a normalized prominence, calculated as the difference between contraction peak amplitude and the mean of activity around the contraction, divided by the peak amplitude.
As discussed herein, a technical problem in the field of maternal/fetal care is that existing solutions for monitoring uterine activity (e.g., contractions) through the use of a tocodynamometer and an ultrasound transducer require an expectant mother to wear uncomfortable sensors, and can produce unreliable data when worn by obese expectant mothers (e.g., the sensors may not have sufficient sensitivity to produce usable data). As further discussed herein, the exemplary embodiments present technical solutions to this technical problem through the use of various sensors (e.g., bio-potential sensors and/or acoustic sensors) integrated into a comfortably wearable device and the analysis of data that can be obtained by such sensors (e.g., electrodes and/or acoustic sensors) to produce a signal that can be utilized to monitor uterine activity. A further technical problem in the field of maternal/fetal care is that existing solutions for analysis based on signals that can be obtained by sensors (e.g., bio-potential sensors and/or acoustic sensors) that can be integrated into a comfortably wearable device are limited to analyzing such signals to extract cardiac data. As discussed herein, the exemplary embodiments present a technical solution to this technical problem through the analysis of bio-potential data and/or acoustic data to produce a signal that can monitor uterine activity (e.g., contractions).
Publications cited throughout this document are hereby incorporated by reference in their entirety. Although the various aspects of the invention have been illustrated above by reference to examples and embodiments, it will be appreciated that the scope of the invention is defined not by the foregoing description but by the following claims properly construed under principles of patent law. Further, many modifications may become apparent to those of ordinary skill in the art, including that various embodiments of the inventive methodologies, the inventive systems, and the inventive devices described herein can be utilized in any combination with each other. Further still, the various steps may be carried out in any desired order (and any desired steps may be added and/or any undesired steps in a particular embodiment may be eliminated).

Claims

What is claimed is:

1. A computer-implemented method, comprising:

providing, by at least one computer processor, a plurality of signal channels, wherein the plurality of signal channels includes a plurality of electrical uterine monitoring signal channels and a plurality of acoustic uterine monitoring signal channels;

determining, by the at least one computer processor, a plurality of channel weights, wherein each of the channel weights corresponds to a particular one of the signal channels; and

generating, by the at least one computer processor, a combined uterine monitoring signal channel by calculating a weighted average of the signal channels based on the channel weight for each of the signal channels.

2. The computer-implemented method of claim 1, wherein the plurality of channel weights are determined based on a machine learning algorithm.

3. The computer-implemented method of claim 2, wherein the machine learning algorithm includes a gradient descent optimization process.

4. The computer-implemented method of claim 1, wherein the plurality of channel weights are determined by a process comprising:

defining, by the at least one computer processor, a plurality of channel sets, each of the plurality of channel sets including at least some of the plurality of signal channels;

defining, by the at least one computer processor, a plurality of initial weight sets, wherein each of the plurality of initial weight sets corresponds to a particular one of the plurality of channel sets;

optimizing, by the at least one computer processor, the plurality of initial weight sets to generate a plurality of optimized weight sets, wherein each of the plurality of optimized weight sets corresponds to a particular one of the plurality of channel sets; and

selecting, by the at least one computer processor, a best one of the plurality of optimized weight sets as the plurality of channel weights.

5. The computer-implemented method of claim 4, wherein the step of optimizing the plurality of initial weight sets includes a gradient descent process.

6. The computer-implemented method of claim 4, wherein the step of selecting the best one of the plurality of optimized weight sets is performed by a process comprising:

generating, by the at least one computer processor, a plurality of interim uterine activity traces, wherein each of the plurality of interim uterine activity traces corresponds to a particular one of the plurality of optimized weight sets;

calculating, by the at least one computer processor, for each of plurality of optimized weight sets, (a) signal-to-noise ratio of the particular one of the interim uterine activity traces that corresponds to each of the plurality of optimized weight sets; (b) a cost function; (c) a contraction confidence measure; and (d) a difference index;

calculating, by the at least one computer processor, for each particular one of the plurality of optimized weight sets, an optimized weight set mean that is a mean of (a) the signal-to-noise ratio of the particular one of the optimized weight sets, (b) the cost function of the particular one of the optimized weight sets, (c) the contraction confidence measure of the particular one of the optimized weight sets, and (d) the difference index of the particular one of the optimized weight sets; and

selecting, by the at least one computer processor, a one of the plurality of optimized weight sets having a best optimized weight set mean as the best one of the plurality of optimized weight sets.

7. The computer-implemented method of claim 4, further comprising:

generating, by the at least one computer processor, a first interim uterine activity trace and a second interim uterine activity trace corresponding to a particular one of the plurality of channel sets, wherein the first interim uterine activity trace corresponds to a first one of the plurality of optimized weight sets for the particular one of the plurality of channel sets, and wherein the second interim uterine activity trace corresponds to a second one of the plurality of optimized weight sets for the particular one of the plurality of channel sets;

calculating, by the at least one computer processor, for the first one of the plurality of optimized weight sets, (a) signal-to-noise ratio of the first interim uterine activity trace; (b) a cost function; (c) a contraction confidence measure; and (d) a difference index;

calculating, by the at least one computer processor, for the second one of the plurality of optimized weight sets, (a) signal-to-noise ratio of the second interim uterine activity trace; (b) a cost function; (c) a contraction confidence measure; and (d) a difference index;

calculating, by the at least one computer processor, for the first one of the plurality of optimized weight sets, a first mean that is a mean of (a) the signal-to-noise ratio of the first interim uterine activity trace; (b) the cost function of the first one of the plurality of optimized weight sets; (c) a contraction confidence measure of the first one of the plurality of optimized weight sets; and (d) a difference index of the first one of the plurality of optimized weight sets;

calculating, by the at least one computer processor, for the second one of the plurality of optimized weight sets, a second mean that is a mean of (a) the signal-to-noise ratio of the second interim uterine activity trace; (b) the cost function of the second one of the plurality of optimized weight sets; (c) a contraction confidence measure of the second one of the plurality of optimized weight sets; and (d) a difference index of second first one of the plurality of optimized weight sets;

selecting, by the at least one computer processor, the first one of the plurality of weight sets as a best weight set for the particular one of the plurality of channel sets, based on a determination that the first mean is better than the second mean; and

selecting, by the at least one computer processor, the second one of the plurality of weight sets as a best weight set for the particular one of the plurality of channel sets, based on a determination that the second mean is better than the first mean.

8. The computer-implemented method of claim 7, further comprising:

enhancing, by the at least computer processor, the plurality of channel sets prior to the step of selecting, by the at least one computer processor, the best one of the plurality of optimized weight sets as the plurality of channel weights.

9. The computer-implemented method of claim 4, wherein the step of defining the plurality of channel sets comprises defining a contraction-based channel set, and wherein the contraction-based channel set is determined by a process comprising:

identifying, by the at least one computer processor, a set of contractions in each of the plurality of signal channels;

extracting, by the at least one computer processor, contraction features for each of the plurality of signal channels based on the set of contractions identified for each of the plurality of signal channels;

clustering, by the at least one computer processor, the plurality of signal channels into a plurality of clusters; and

selecting, by the at least one computer processor, a best one of the plurality of clusters as the contraction-based channel set.

10. The computer-implemented method of claim 9, wherein the step of defining the plurality of channel sets further comprises:

improving, by the at least one computer processor, the best one of the plurality of clusters.

11. The computer-implemented method of claim 9, wherein the step of defining the plurality of channel sets further comprises:

adding, by the at least one computer processor, to the best one of the plurality of clusters, a portion of one of the signal channels that is not included in the best one of the plurality of clusters.

12. The computer-implemented method of claim 9, wherein the step of identifying the set of contractions in each of the plurality of signal channels is performed by a process that includes, for each one of the plurality of signal channels:

generating, by the at least one computer processor, an enhanced version of the one of the plurality of signal channels;

detecting, by the at least one computer processor, a candidate set of contractions in the enhanced one of the plurality of signal channels, wherein the candidate set of contractions includes a plurality of candidate contractions;

calculating, by the at least one computer processor, a plurality of confidence measures for each candidate contraction; and

removing, by the at least one computer processor, at least one of the candidate contractions from the set of candidate contractions based on the confidence measures corresponding to the at least one eliminated one of the candidate contractions, thereby producing the set of contractions.

13. The computer-implemented method of claim 4, wherein the step of defining, by the at least one computer processor, the plurality of initial weight sets comprises generating, by the at least one computer processor, for each of the channel sets, a channel-voting weight set and a born-equal weight set.

14. The computer-implemented method of claim 1, wherein the step of providing the plurality of signal channels includes generating at least one of the plurality of electrical uterine monitoring signal channels, and wherein the at least one of the plurality of electrical uterine monitoring signal channels is generated by a process comprising:

receiving, by the at least one computer processor, a plurality of raw bio-potential inputs,

wherein each of the raw bio-potential inputs being received from a corresponding one of a plurality of electrodes,

wherein each of the plurality of electrodes is positioned so as to measure a respective one of the raw bio-potential inputs of a pregnant human subject;

generating, by the at least one computer processor, a plurality of signal channels from the plurality of raw-bio-potential inputs,

wherein the plurality of signal channels comprises at least three signal channels;

pre-processing, by the at least one computer processor, respective signal channel data of each of the signal channels to produce a plurality of pre-processed signal channels,

wherein each of the pre-processed signal channels comprises respective pre-processed signal channel data;

extracting, by the at least one computer processor, a respective plurality of R-wave peaks from the pre-processed signal channel data of each of the pre-processed signal channels to produce a plurality of R-wave peak data sets,

wherein each of the R-wave peak data sets comprises a respective plurality of R-wave peaks;

removing, by the at least one computer processor, from the plurality of R-wave peak data sets, at least one of: (a) at least one signal artifact or (b) at least one outlier data point,

wherein the at least one signal artifact is one of an electromyography artifact or a baseline artifact;

replacing, by the at least one computer processor, the at least one signal artifact, the at least one outlier data point, or both, with at least one statistical value determined based on a corresponding one of the R-wave peak data sets from which the at least one signal artifact, the at least one outlier data point, or both was removed, to produce a plurality of interpolated R-wave peak data sets;

generating, by the at least one computer processor, a respective R-wave signal data set for a respective R-wave signal channel at a predetermined sampling rate based on each respective interpolated R-wave peak data set to produce a plurality of R-wave signal channels;

selecting, by the at least one computer processor, at least one first selected R-wave signal channel and at least one second selected R-wave signal channel from the plurality of R-wave signal channels based on at least one correlation between (a) a respective R-wave signal data set of at least one first particular R-wave signal channel and (b) a respective R-wave signal data set of at least one second particular R-wave signal channel; and

generating, by the at least one computer processor, electrical uterine monitoring data representative of an electrical uterine monitoring signal based on at least the respective R-wave signal data set of the first selected R-wave signal channel and the respective R-wave signal data set of the second selected R-wave signal channel, thereby producing the at least one electrical uterine monitoring signal channel.

15. The computer-implemented method of claim 1, wherein the step of providing the plurality of signal channels includes generating at least one of the plurality of acoustic uterine monitoring signal channels, and wherein the at least one of the plurality of acoustic uterine monitoring signal channels is generated by a process comprising:

receiving, by the at least one computer processor, a plurality of raw acoustic inputs,

wherein each of the raw acoustic inputs being received from a corresponding one of a plurality of acoustic sensors,

wherein each of the plurality of acoustic sensors is positioned so as to measure a respective one of the raw acoustic inputs of a pregnant human subject;

generating, by the at least one computer processor, a plurality of signal channels from the plurality of raw acoustic inputs,

extracting, by the at least one computer processor, a respective plurality of S1-S2 peaks from the pre-processed signal channel data of each of the pre-processed signal channels to produce a plurality of S1-S2 peak data sets,

wherein each of the S1-S2 peak data sets comprises a respective plurality of S1-S2 peaks;

removing, by the at least one computer processor, from the plurality of S1-S2 peak data sets, at least one of: (a) at least one signal artifact or (b) at least one outlier data point,

wherein the at least one signal artifact is one of a movement-related artifact or a baseline artifact;

replacing, by the at least one computer processor, the at least one signal artifact, the at least one outlier data point, or both, with at least one statistical value determined based on a corresponding one of the S1-S2 peak data sets from which the at least one signal artifact, the at least one outlier data point, or both was removed, to produce a plurality of interpolated S1-S2 peak data sets;

generating, by the at least one computer processor, a respective S1-S2 signal data set for a respective S1-S2 signal channel at a predetermined sampling rate based on each respective interpolated S1-S2 peak data set to produce a plurality of S1-S2 signal channels;

selecting, by the at least one computer processor, at least one first selected S1-S2 signal channel and at least one second selected S1-S2 signal channel from the plurality of S1-S2 signal channels based on at least one correlation between (a) a respective S1-S2 signal data set of at least one first particular S1-S2 signal channel and (b) a respective S1-S2 signal data set of at least one second particular S1-S2 signal channel; and

generating, by the at least one computer processor, acoustic uterine monitoring data representative of an acoustic uterine monitoring signal based on at least the respective S1-S2 signal data set of the first selected S1-S2 signal channel and the respective S1-S2 signal data set of the second selected S1-S2 signal channel, thereby producing the at least one acoustic uterine monitoring signal channel.