Feasibility of transabdominal electrohysterography for analysis of uterine activity in nonpregnant women

Purpose: Uterine activity plays a key role in reproduction, and altered patterns of uterine contractility have been associated with important physiopathological conditions, such as subfertility, dysmenorrhea, and endometriosis. However, there is currently no method to objectively quantify uterine contractility outside pregnancy without interfering with the spontaneous contraction pattern. Transabdominal electrohysterography has great potential as a clinical tool to characterize noninvasively uterine activity, but results of this technique in nonpregnant women are poorly documented. The purpose of this study is to investigate the feasibility of transabdominal electrohysterography in nonpregnant women. Methods: Longitudinal measurements were performed on 22 healthy women in 4 representative phases of the menstrual cycle. Twelve electrohysterogram-based indicators previously validated in pregnancy have been estimated and compared in the 4 phases of the cycle. Using the Tukey honest significance test, significant differences were defined for P values below .05. Results: Half of the selected electrohysterogram-based indicators showed significant differences between menses and at least 1 of the other 3 phases, that is the luteal phase. Conclusion: Our results suggest transabdominal electrohysterography to be feasible for analysis of uterine activity in nonpregnant women. Due to the lack of a golden standard, this feasibility study is indirectly validated based on physiological observations. However, these promising results motivate further research aiming at evaluating electrohysterography as a method to improve understanding and management of dysfunctions (possibly) related to altered uterine contractility, such as infertility, endometriosis, and dysmenorrhea

Electrohysterogram signal component cataloging with spectral and time-frequency methods

The Electrohysterogram (EHG) is a new instrument for pregnancy monitoring. It measures the uterine muscle electrical signal, which is closely related with uterine contractions. The EHG is described as a viable alternative and a more precise instrument than the currently most widely used method for the description of uterine contractions: the external tocogram. The EHG has also been indicated as a promising tool in the assessment of preterm delivery risk. This work intends to contribute towards the EHG characterization through the inventory of its components which are: • Contractions; • Labor contractions; • Alvarez waves; • Fetal movements; • Long Duration Low Frequency Waves; The instruments used for cataloging were: Spectral Analysis, parametric and non-parametric, energy estimators, time-frequency methods and the tocogram annotated by expert physicians. The EHG and respective tocograms were obtained from the Icelandic 16-electrode Electrohysterogram Database. 288 components were classified. There is not a component database of this type available for consultation. The spectral analysis module and power estimation was added to Uterine Explorer, an EHG analysis software developed in FCT-UNL. The importance of this component database is related to the need to improve the understanding of the EHG which is a relatively complex signal, as well as contributing towards the detection of preterm birth. Preterm birth accounts for 10% of all births and is one of the most relevant obstetric conditions. Despite the technological and scientific advances in perinatal medicine, in developed countries, prematurity is the major cause of neonatal death. Although various risk factors such as previous preterm births, infection, uterine malformations, multiple gestation and short uterine cervix in second trimester, have been associated with this condition, its etiology remains unknown [1][2][3]

Unsupervised Classification of Uterine Contractions Recorded Using Electrohysterography

Pregnancy still poses health risks that are not attended to by current clinical practice motorization procedures. Electrohysterography (EHG) record signals are analyzed in the course of this thesis as a contribution and effort to evaluate their suitability for pregnancy monitoring. The presented work is a contributes with an unsupervised classification solution for uterine contractile segments to FCT’s Uterine Explorer (UEX) project, which explores analysis procedures for EHG records. In a first part, applied processing procedures are presented and a brief exploration of the best practices for these. The procedures include those to elevate the representation of uterine events relevant characteristics, ease further computation requirements, extraction of contractile segments and spectral estimation. More detail is put into the study of which characteristics should be chosen to represent uterine events in the classification process and feature selection methods. To such end, it is presented the application of a principal component analysis (PCA) to three sets: interpolated contractile events, contractions power spectral densities, and to a number of computed features that attempt evidencing time, spectral and non-linear characteristics usually used in EHG related studies. Subsequently, a wrapper model approach is presented as a mean to optimize the feature set through cyclically attempting the removal and re-addition of features based on clustering results. This approach takes advantage of the fact that one class is known beforehand to use its classification accuracy as the criteria that defines whether the modification made to the feature set was ominous. Furthermore, this work also includes the implementation of a visualization tool that allows inspecting the effect of each processing procedure, the uterine events detected by different methods and clusters they were associated to by the final iteration of the wrapper model

Comparison of non-invasive electrohysterographic recording techniques for monitoring uterine dynamics

Non-invasive recording of uterine myoelectric activity (electrohysterogram, EHG) could provide an alternative to monitoring uterine dynamics by systems based on tocodynamometer (TOCO). Laplacian recording of bioelectric signals has been shown to give better spatial resolution and less interference than mono and bipolar surface recordings. The aim of this work was to study the signal quality obtaines from monopolar, bipolar and Laplacian techniques in EHG recordings, as well as to assess their ability to detect uterine contractions. Twenty-two recording sessions were carried out on singleton pregnant women during the active phase of labour. In each session the following simultaneous recordings were obtained: internal uterine pressure (IUP), external tension of abdominal wall (TOCO) and EHG signals (5 monopolar and 4 bipolar recordings, 1 discrete aproximation to the Laplacian of the potential and 2 estimates of the Laplacian from two active annular electrodes). The results obtained show that EHG is able to detect a higher number of uterine contractions than TOCO. Laplacian recordings give improved signal quality over monopolar and bipolar techniques, reduce maternal cardiac interference and improve the signal-to-noise ratio. The optimal position for recording EHG was found to be the uterine median axis and the lower centre-right umbilical zone.Research partly supported by the Spanish Ministerio de Ciencia y Tecnologia (TEC2010-16945) and the Universitat Politecnica de Valencia (PAID 2009/10-2298). The translation of this paper was funded by the Universitat Politecnica de Valencia, Spain.Alberola Rubio, J.; Prats Boluda, G.; Ye Lin, Y.; Valero, J.; Perales Marin, AJ.; Garcia Casado, FJ. (2013). Comparison of non-invasive electrohysterographic recording techniques for monitoring uterine dynamics. Medical Engineering and Physics. 35(12):1736-1743. https://doi.org/10.1016/j.medengphy.2013.07.008S17361743351

New electrohysterogram-based estimators of intrauterine pressure signal, tonus and contraction peak for non-invasive labor monitoring

[EN] Background: Uterine activity monitoring is an essential part of managing the progress of pregnancy and labor. Although intrauterine pressure (IUP) is the only reliable method of estimating uterine mechanical activity, it is highly invasive. Since there is a direct relationship between the electrical and mechanical activity of uterine cells, surface electrohysterography (EHG) has become a noninvasive monitoring alternative. The Teager energy (TE) operator of the EHG signal has been used for IUP continuous pressure estimation, although its accuracy could be improved. We aimed to develop new optimized IUP estimation models for clinical application. Approach: We first considered enhancing the optimal estimation of IUP clinical features (maximum pressure and tonus) rather than optimizing the signal only (continuous pressure). An adaptive algorithm was also developed to deal with inter-patient variability. For each optimizing signal feature (continuous pressure, maximum pressure and tonus), individual (single patient), global (full database) and adaptive models were built to estimate the recorded IUP signal. The results were evaluated by computing the root mean square errors (RMSe): continuous pressure error (CPe), maximum pressure error (MPe) and tonus error (TOe). Main results: The continuous pressure global model yielded IUP estimates with Cpe = 14.61mm Hg, MPe = 29.17mm Hg and Toe = 7.8mm Hg. The adaptive models significantly reduced errors to CPe = 11.88, MPe = 16.02 and Toe = 5.61mm Hg. The EHG-based IUP estimates outperformed those from traditional tocographic recordings, which had significantly higher errors (CPe = 21.93, MPe = 26.97, and TOe = 13.96). Significance: Our results show that adaptive models yield better IUP estimates than the traditional approaches and provide the best balance of the different errors computed for a better assessment of the labor progress and maternal and fetal wellbeing.This research project was supported by the Spanish Ministry of Economy and Competitiveness, the European Regional Development Fund (DPI2015-68397-R), and by the projects UPV_ FE-2018-C03 and GV/2018/104.Benalcazar-Parra, C.; Garcia-Casado, J.; Ye Lin, Y.; Alberola-Rubio, J.; López-Corral, A.; Perales Marin, AJ.; Prats-Boluda, G. (2019). New electrohysterogram-based estimators of intrauterine pressure signal, tonus and contraction peak for non-invasive labor monitoring. Physiological Measurement. 40(8):1-12. https://doi.org/10.1088/1361-6579/ab37dbS11240

Characterization of uterine activity by electrohysterography

A growing number of pregnancies is complicated by miscarriage, preterm delivery, and birth defects, with consequent health problems later in life. It is therefore increasingly important to monitor the health status of mother and fetus, so as to permit timely medical intervention when acute health risks are detected. For timely recognition of complications, quantitative assessment of uterine activity can be fundamental during both pregnancy and delivery. During pregnancy, timely prediction of preterm delivery can improve the effectiveness of the required treatments. Unfortunately, the prognostic techniques employed in current obstetrical practice, namely, uterine contraction measurements using an elastic belt (external tocography), cervical change evaluation, and the use of biomarkers like fetal fibronectin, have been demonstrated to be inaccurate for the prediction of preterm delivery. In the last stage of pregnancy and during labor, contractions are routinely and constantly monitored. Especially when complications occur, e.g., when labor shows poor progress, quantitative assessment of uterine activity can guide the physician to choose a uterine contraction induction or augmentation, a cesarean section, or other therapies. Furthermore, monitoring the fetal heart response to the uterine activity (cardiotography) is widely used as a screening test for timely recognition of fetal distress (e.g. asphyxia). However, in current obstetrical practice, accurate quantitative assessment of the uterine contractions can be provided only invasively and during labor. The current golden standard for contraction monitoring, which is based on the direct internal uterine pressure (IUP) measurement by an intrauterine catheter, can be risky and its use is generally limited to very complicated deliveries. The contractile element of the uterus is the myometrium, which is composed of smooth muscle cells. Uterine contractions are caused by electrical activity in the form of action potentials (AP) that propagate through the myometrium cells. Electrohysterography is the measurement of the uterine electrical activity and can be performedby electrodes placed on the abdomen. Electrohysterographic (EHG) measurements are inexpensive and noninvasive. Moreover, it has been demonstrated that the noninvasively recorded EHG signal is representative of those APs that, by propagating from cell to cell, are the root cause of a uterine contraction. Therefore, in view of the limitation of current obstetrical practice, significant benefits could be expected from the introduction of EHG signal analysis for routine contraction monitoring. Previous studies highlighted the potential prognostic and diagnostic value of EHG signal analysis, but did not investigate the possibility of accurately estimating the IUP from noninvasive EHG recordings. Moreover, important issues like the effect of the tissues interposed between the uterus and the skin (volume conductor) on EHG recordings have not been studied. Besides, EHG signal interpretation has been typically based on single-channel measurements, while the use of multiple electrodes conveys additional information (e.g., distribution and dynamics of the electrical activation) that can possibly be predictive of delivery. In this thesis, we focus on the analysis of the EHG signal as an alternative to existing techniques for predicting preterm delivery and monitoring uterine contractions during both pregnancy and delivery. The main goal of this work is to contribute to the technical basis which is required for the introduction of electrohysterography in everyday clinical practice. A major part of this thesis investigates the possibility of using electrohysterography to replace invasive IUP measurements. A novel method for IUP estimation from EHG recordings is developed in the first part of this thesis. The estimates provided by the method are compared to the IUP invasively recorded on women during delivery and result in a root mean squared error (RMSE) with respect to the reference invasive IUP recording as low as 5 mmHg, which is comparable to the accuracy of the invasive golden standard. Another important objective of this thesis work is to contribute to the introduction of novel techniques for timely prediction of preterm delivery. As the spreading of electrical activity at the myometrium is the root cause of coordinated and effective contractions, i.e., contractions that are capable of pushing the fetus down into the birth canal ultimately leading to delivery, a multichannel analysis of the spatial propagation properties of the EHG signal could provide a fundamental contribution for predicting delivery. A thorough study of the EHG signal propagation properties is therefore carried out in this work. Parameters related to the EHG that are potentially predictive of delivery, such as the uterine area where the contraction originates (pacemaker area) or the distribution and dynamics of the EHG propagation vector, can be derived from the delay by which the signal is detected at multiple locations over the whole abdomen. To analyze the propagation of EHG signals on a large scale (cm), a method is designed for calculating the detection delay among the EHG signals recorded by by electrodes placed on the abdomen. Electrohysterographic (EHG) measurements are inexpensive and noninvasive. Moreover, it has been demonstrated that the noninvasively recorded EHG signal is representative of those APs that, by propagating from cell to cell, are the root cause of a uterine contraction. Therefore, in view of the limitation of current obstetrical practice, significant benefits could be expected from the introduction of EHG signal analysis for routine contraction monitoring. Previous studies highlighted the potential prognostic and diagnostic value of EHG signal analysis, but did not investigate the possibility of accurately estimating the IUP from noninvasive EHG recordings. Moreover, important issues like the effect of the tissues interposed between the uterus and the skin (volume conductor) on EHG recordings have not been studied. Besides, EHG signal interpretation has been typically based on single-channel measurements, while the use of multiple electrodes conveys additional information (e.g., distribution and dynamics of the electrical activation) that can possibly be predictive of delivery. In this thesis, we focus on the analysis of the EHG signal as an alternative to existing techniques for predicting preterm delivery and monitoring uterine contractions during both pregnancy and delivery. The main goal of this work is to contribute to the technical basis which is required for the introduction of electrohysterography in everyday clinical practice. A major part of this thesis investigates the possibility of using electrohysterography to replace invasive IUP measurements. A novel method for IUP estimation from EHG recordings is developed in the first part of this thesis. The estimates provided by the method are compared to the IUP invasively recorded on women during delivery and result in a root mean squared error (RMSE) with respect to the reference invasive IUP recording as low as 5 mmHg, which is comparable to the accuracy of the invasive golden standard. Another important objective of this thesis work is to contribute to the introduction of novel techniques for timely prediction of preterm delivery. As the spreading of electrical activity at the myometrium is the root cause of coordinated and effective contractions, i.e., contractions that are capable of pushing the fetus down into the birth canal ultimately leading to delivery, a multichannel analysis of the spatial propagation properties of the EHG signal could provide a fundamental contribution for predicting delivery. A thorough study of the EHG signal propagation properties is therefore carried out in this work. Parameters related to the EHG that are potentially predictive of delivery, such as the uterine area where the contraction originates (pacemaker area) or the distribution and dynamics of the EHG propagation vector, can be derived from the delay by which the signal is detected at multiple locations over the whole abdomen. To analyze the propagation of EHG signals on a large scale (cm), a method is designed for calculating the detection delay among the EHG signals recorded by multiple electrodes. Relative to existing interelectrode delay estimators, this method improves the accuracy of the delay estimates for interelectrode distances larger than 5-10 cm. The use of a large interelectrode distance aims at the assessment of the EHG propagation properties through the whole uterine muscle using a limited number of sensors. The method estimates values of velocity within the physiological range and highlights the upper part of the uterus as the most frequent (65%) pacemaker area during labor. Besides, our study suggests that more insight is needed on the effect that tissues interposed between uterus and skin (volume conductor) have on the EHG signal. With the aim of improving the current interpretation and measurement accuracy of EHG parameters with potential clinical relevance, such as the conduction velocity (CV), a volume conductor model for the EHG signal is introduced and validated. The intracellular AP at the myometrium is analytically modeled in the spatial domain by a 2-parameter exponential in the form of a Gamma variate function. The unknown atomical parameters of the volume conductor model are the thicknesses of the biological tissues interposed between the uterus and the abdominal surface. These model parameters can be measured by echography for validation. The EHG signal is recorded by an electrode matrix on women with contractions. In order to increase the spatial resolution of the EHG measurements and reduce the geometrical and electrical differences among the tissues below the recording locations, electrodes with a reduced surface and smaller interelectrode distance are needed relative to the previous studies on electrohysterography. The EHG signal is recorded, for the first time, by a 64-channel (8×8) high-density electrode grid, comprising 1 mm diameter electrodes with 4 mm interelectrode distance. The model parameters are estimated in the spatial frequency domain from the recorded EHG signal by a least mean square method. The model is validated by comparing the thickness of the biological tissues recorded by echography to the values estimated using the mathematical model. The agreement between the two measures (RMSE = 1 mm and correlation coefficient, R = 0.94) suggests the model to be representative of the underlying physiology. In the last part of this dissertation, the analysis of the EHG signal propagation focuses on the CV estimation of single APs. As on a large scale this parameter cannot be accurately derived, the propagation analysis is here carried out on a small scale (mm). Also for this analysis, the EHG signal is therefore recorded by a 3×3 cm2 high-density electrode grid containing 64 electrodes (8×8). A new method based on maximum likelihood estimation is then applied in two spatial dimensions to provide an accurate estimate of amplitude and direction of the AP CV. Simulation results prove the proposed method to be more robust to noise than the standard techniques used for other electrophysiological signals, leading to over 56% improvement of the RMS CV estimate accuracy. Furthermore, values of CV between 2 cm/s and 12 cm/s, which are in agreement with invasive and in-vitro measurements described in the literature, are obtained from real measurements on ten women in labor. In conclusion, this research provides a quantitative characterization of uterine contractions by EHG signal analysis. Based on an extensive validation, this thesis indicates that uterine contractions can be accurately monitored noninvasively by dedicated analysis of the EHG signal. Furthermore, our results open the way to new clinical studies and applications aimed at improving the understanding of the electrophysiological mechanisms leading to labor, possibly reducing the incidence of preterm delivery and improving the perinatal outcome

Feasibility and analysis of bipolar concentric recording of Electrohysterogram with flexible active electrode

The conduction velocity and propagation patterns of Electrohysterogram (EHG) provide fundamental information about uterine electrophysiological condition. The accuracy of these measurements can be impaired by both the poor spatial selectivity and sensitivity to the relative direction of the contraction propagation associated with conventional disc electrodes. Concentric ring electrodes could overcome these limitations the aim of this study was to examine the feasibility of picking up surface EHG signals using a new flexible tripolar concentric ring electrode (TCRE), and to compare it with conventional bipolar recordings. Simultaneous recording of conventional bipolar signals and bipolar concentric EHG (BC-EHG) were carried out on 22 pregnant women. Signal bursts were characterized and compared. No significant differences among channels in either duration or dominant frequency in the Fast Wave High frequency range were found. Nonetheless, the high pass filtering effect of the BC-EHG records resulted in lower frequency content within the range 0.1 to 0.2 Hz than the bipolar ones. Although the BC-EHG signal amplitude was about 5-7 times smaller than that of bipolar recordings, similar signal-to-noise ratio was obtained. These results suggest that the flexible TCRE is able to pick up uterine electrical activity and could provide additional information for deducing uterine electrophysiological condition.The authors are grateful to the Obstetrics Unit of the Hospital Universitario La Fe de Valencia (Valencia, Spain), where the recording sessions were carried out. The work was supported in part by the Ministerio de Ciencia y Tecnologia de Espana (TEC2010-16945), by the Universitat Politecnica de Valencia (PAID SP20120490) and Generalitat Valenciana (GV/2014/029) and by General Electric Healthcare.Ye Lin, Y.; Alberola Rubio, J.; Prats Boluda, G.; Perales Marin, AJ.; Desantes, D.; Garcia Casado, FJ. (2015). 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Characterization of laplacian surface electromyographic signals during isometric contraction in biceps brachii. Conf. Proc. IEEE Eng Med. Biol. Soc. 2013:535–538, 2013.Euliano, T. Y., D. Marossero, M. T. Nguyen, N. R. Euliano, J. Principe, and R. K. Edwards. Spatiotemporal electrohysterography patterns in normal and arrested labor. Am. J. Obstet. Gynecol. 200(1):54–57, 2009.Farina, D., and C. Cescon. Concentric-ring electrode systems for noninvasive detection of single motor unit activity. IEEE Trans. Biomed. Eng. 48(11):1326–1334, 2001.Fele-Zorz, G., G. Kavsek, Z. Novak-Antolic, and F. Jager. A comparison of various linear and non-linear signal processing techniques to separate uterine EMG records of term and pre-term delivery groups. Med. Biol. Eng Comput. 46(9):911–922, 2008.Garfield, R. E., and W. L. Maner. Physiology and electrical activity of uterine contractions. Semin. Cell Dev. Biol. 18(3):289–295, 2007.Garfield, R. E., W. L. Maner, L. B. Mackay, D. Schlembach, and G. R. Saade. Comparing uterine electromyography activity of antepartum patients vs. term labor patients. Am. J. Obstet. Gynecol. 193(1):23–29, 2005.Garfield, R. E., H. Maul, L. Shi, W. Maner, C. Fittkow, G. Olsen, and G. R. Saade. Methods and devices for the management of term and preterm labor. Ann. N. Y. Acad. Sci. 943(1):203–224, 2001.Hassan, M., J. Terrien, C. Muszynski, A. Alexandersson, C. Marque, and B. Karlsson. Better pregnancy monitoring using nonlinear correlation analysis of external uterine electromyography. IEEE Trans. Biomed. Eng. 60(4):1160–1166, 2013.Kaufer, M., L. Rasquinha, and P. Tarjan. Optimization of multi-ring sensing electrode set, Conference proceedings of IEEE Engineering in Medicine and Biology Society, 1990, pp. 612–613.Koka, K., and W. G. Besio. Improvement of spatial selectivity and decrease of mutual information of tri-polar concentric ring electrodes. J. Neurosci. Methods 165(2):216–222, 2007.Lu, C.-C., and P. P. Tarjan. 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Electrohysterography in the diagnosis of preterm birth: a review

This is an author-created, un-copyedited versíon of an article published in Physiological Measurement. IOP Publishing Ltd is not responsíble for any errors or omissíons in this versíon of the manuscript or any versíon derived from it. The Versíon of Record is available online at http://doi.org/10.1088/1361-6579/aaad56.[EN] Preterm birth (PTB) is one of the most common and serious complications in pregnancy. About 15 million preterm neonates are born every year, with ratios of 10-15% of total births. In industrialized countries, preterm delivery is responsible for 70% of mortality and 75% of morbidity in the neonatal period. Diagnostic means for its timely risk assessment are lacking and the underlying physiological mechanisms are unclear. Surface recording of the uterine myoelectrical activity (electrohysterogram, EHG) has emerged as a better uterine dynamics monitoring technique than traditional surface pressure recordings and provides information on the condition of uterine muscle in different obstetrical scenarios with emphasis on predicting preterm deliveries. Objective: A comprehensive review of the literature was performed on studies related to the use of the electrohysterogram in the PTB context. Approach: This review presents and discusses the results according to the different types of parameter (temporal and spectral, non-linear and bivariate) used for EHG characterization. Main results: Electrohysterogram analysis reveals that the uterine electrophysiological changes that precede spontaneous preterm labor are associated with contractions of more intensity, higher frequency content, faster and more organized propagated activity and stronger coupling of different uterine areas. Temporal, spectral, non-linear and bivariate EHG analyses therefore provide useful and complementary information. Classificatory techniques of different types and varying complexity have been developed to diagnose PTB. The information derived from these different types of EHG parameters, either individually or in combination, is able to provide more accurate predictions of PTB than current clinical methods. However, in order to extend EHG to clinical applications, the recording set-up should be simplified, be less intrusive and more robust-and signal analysis should be automated without requiring much supervision and yield physiologically interpretable results. Significance: This review provides a general background to PTB and describes how EHG can be used to better understand its underlying physiological mechanisms and improve its prediction. The findings will help future research workers to decide the most appropriate EHG features to be used in their analyses and facilitate future clinical EHG applications in order to improve PTB prediction.This work was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund under grant DPI2015-68397-R.Garcia-Casado, J.; Ye Lin, Y.; Prats-Boluda, G.; Mas-Cabo, J.; Alberola Rubio, J.; Perales Marin, AJ. (2018). Electrohysterography in the diagnosis of preterm birth: a review. Physiological Measurement. 39(2). https://doi.org/10.1088/1361-6579/aaad56S39