250 research outputs found
Forward Electrophysiological Modeling and Inverse Problem for Uterine Contractions during Pregnancy
Uterine contractile dysfunction during pregnancy is a significant healthcare challenge that imposes heavy medical and financial burdens on both human beings and society. In the U.S., about 12% of babies are born prematurely each year, which is a leading cause of neonatal mortality and increases the possibility of having subsequent health problems. Post-term birth, in which a baby is born after 42 weeks of gestation, can cause risks for both the newborn and the mother. Currently, there is a limited understanding of how the uterus transitions from quiescence to excitation, which hampers our ability to detect labor and treat major obstetric syndromes associated with contractile dysfunction. Therefore, it is critical to develop objective methods to investigate the underlying contractile mechanism using a non-invasive sensing technique. This dissertation focuses on the multiscale forward electromagnetic modeling of uterine contractile activities and the inverse estimation of underlying source currents from abdominal magnetic field measurements.
We develop a realistic multiscale forward electromagnetic model of uterine contractions in the pregnant uterus, taking into account current electrophysiological and anatomical knowledge of the uterus. Previous models focused on generating contractile forces at the organ level or on ionic concentration changes at the cellular level. Our approach is to characterize the electromagnetic fields of uterine contractions jointly at the cellular, tissue, and organ levels. At the cellular level, focusing on both plateau-type and bursting-type action potentials, we introduce a generalized version of the FitzHugh-Nagumo equations and analyze its response behavior based on bifurcation theory. To represent the anisotropy of the myometrium, we introduce a random conductivity tensor model for the fiber orientations at the tissue level. Specifically, we divide the uterus into contiguous regions, each of which is assigned a random fiber angle. We also derive analytical expressions for the spiking frequency and propagation velocity of the bursting potential. At the organ level, we propose a realistic four-compartment volume conductor, in which the uterus is modeled based on the magnetic resonance imaging scans of a near-term woman and the abdomen is curved to match the device used to take the magnetomyography measurements. To mimic the effect of the sensing direction, we incorporate a sensor array model on the surface of abdomen. We illustrate our approach using numerical examples and compute the magnetic field using the finite element method. Our results show that fiber orientation and initiation location are the key factors affecting the magnetic field pattern, and that our multiscale forward model flexibly characterizes the limited-propagation local contractions at term. These results are potentially important as a tool for interpreting the non-invasive measurements of uterine contractions.
We also consider the inverse problem of uterine contractions during pregnancy. Our aim is to estimate the myometrial source currents that generate the external magnetomyography measurements. Existing works approach this problem using synthetic electromyography data. Our approach instead proceeds in two stages: develop a linear approximation model and conduct the estimation. In the first stage, we derive a linear approximation model of the sensor-oriented magnetic field measurements with respect to source current dipoles in the myometrium, based on a lead-field matrix. In particular, this lead-field matrix is analytically computed from distributed current dipoles in the myometrium according to quasi-static Maxwell\u27s equations, using the finite element method. In the second stage, we solve a constrained least-squares problem to estimate the source currents, from which we predict the intrauterine pressure. We demonstrate our approach through numerical examples with synthetic data that are generated using our multiscale forward model. In the simulations, we assume that the excitation is located at the fundus of the uterus. We also illustrate our approach using real data sets, one of which has simultaneous contractile pressure measurements. The results show that our method well captures the short-distance propagation of uterine contractile activities during pregnancy, the change of excitation area in subsequent contractions or even in a single contraction, and the timing of uterine contractions. These findings are helpful in understanding the physiological and functional properties of the uterus, potentially enabling the diagnosis of labor and the treatment of obstetric syndromes associated with contractile dysfunction such as preterm birth and post-term birth
Spatial heterogeneity enhances and modulates excitability in a mathematical model of the myometrium
The muscular layer of the uterus (myometrium) undergoes profound changes in global excitability prior to parturition. Here, a mathematical model of the myocyte network is developed to investigate the hypothesis that spatial heterogeneity is essential to the transition from local to global excitation which the myometrium undergoes just prior to birth. Each myometrial smooth muscle cell is represented by an element with FitzHugh–Nagumo dynamics. The cells are coupled through resistors that represent gap junctions. Spatial heterogeneity is introduced by means of stochastic variation in coupling strengths, with parameters derived from physiological data. Numerical simulations indicate that even modest increases in the heterogeneity of the system can amplify the ability of locally applied stimuli to elicit global excitation. Moreover, in networks driven by a pacemaker cell, global oscillations of excitation are impeded in fully connected and strongly coupled networks. The ability of a locally stimulated cell or pacemaker cell to excite the network is shown to be strongly dependent on the local spatial correlation structure of the couplings. In summary, spatial heterogeneity is a key factor in enhancing and modulating global excitability
Assessment of Features between Multichannel Electrohysterogram for Differentiation of Labors
[EN] Electrohysterogram (EHG) is a promising method for noninvasive monitoring of uterine electrical activity. The main purpose of this study was to characterize the multichannel EHG signals to distinguish between term delivery and preterm birth, as well as deliveries within and beyond 24 h. A total of 219 pregnant women were grouped in two ways: (1) term delivery (TD), threatened preterm labor (TPL) with the outcome of preterm birth (TPL_PB), and TPL with the outcome of term delivery (TPL_TD); (2) EHG recording time to delivery (TTD) 24 h. Three bipolar EHG signals were analyzed for the 30 min recording. Six EHG features between multiple channels, including multivariate sample entropy, mutual information, correlation coefficient, coherence, direct partial Granger causality, and direct transfer entropy, were extracted to characterize the coupling and information flow between channels. Significant differences were found for these six features between TPL and TD, and between TTD 24 h. No significant difference was found between TPL_PB and TPL_TD. The results indicated that EHG signals of TD were more regular and synchronized than TPL, and stronger coupling between multichannel EHG signals was exhibited as delivery approaches. In addition, EHG signals propagate downward for the majority of pregnant women regardless of different labors. In conclusion, the coupling and propagation features extracted from multichannel EHG signals could be used to differentiate term delivery and preterm birth and may predict delivery within and beyond 24 h.This research was funded by the National Key R&D Program, grant number 2019YFC0119700, and the National Natural Science Foundation of China, grant number U20A20388.Zhang, Y.; Hao, D.; Yang, L.; Zhou, X.; Ye Lin, Y.; Yang, Y. (2022). Assessment of Features between Multichannel Electrohysterogram for Differentiation of Labors. Sensors. 22(9):1-18. https://doi.org/10.3390/s2209335211822
Dynamic modeling of uteroplacental blood flow in IUGR indicates vortices and elevated pressure in the intervillous space - a pilot study
Ischemic placental disease is a concept that links intrauterine growth retardation (IUGR) and preeclampsia (PE) back to insufficient remodeling of uterine spiral arteries. The rheological consequences of insufficient remodeling of uterine spiral arteries were hypothesized to mediate the considerably later manifestation of obstetric disease. However, the micro-rheology in the intervillous space (IVS) cannot be examined clinically and rheological animal models of the human IVS do not exist. Thus, an in silico approach was implemented to provide in vivo inaccessible data. The morphology of a spiral artery and the inflow region of the IVS were three-dimensionally reconstructed to provide a morphological stage for the simulations. Advanced high-end supercomputing resources were used to provide blood flow simulations at high spatial resolution. Our simulations revealed turbulent blood flow (high-velocity jets and vortices) combined with elevated blood pressure in the IVS and increased wall shear stress at the villous surface in conjunction with insufficient spiral artery remodeling only. Post-hoc histological analysis of uterine veins showed evidence of increased trophoblast shedding in an IUGR placenta. Our data support that rheological alteration in the IVS is a relevant mechanism linking ischemic placental disease to altered structural integrity and function of the placenta
Robust Characterization of the Uterine Myoelectrical Activity in Different Obstetric Scenarios
[EN] Electrohysterography (EHG) has been shown to provide relevant information on uterine activity and could be used for predicting preterm labor and identifying other maternal fetal risks. The extraction of high-quality robust features is a key factor in achieving satisfactory prediction systems from EHG. Temporal, spectral, and non-linear EHG parameters have been computed to characterize EHG signals, sometimes obtaining controversial results, especially for non-linear parameters. The goal of this work was to assess the performance of EHG parameters in identifying those robust enough for uterine electrophysiological characterization. EHG signals were picked up in different obstetric scenarios: antepartum, including women who delivered on term, labor, and post-partum. The results revealed that the 10th and 90th percentiles, for parameters with falling and rising trends as labor approaches, respectively, differentiate between these obstetric scenarios better than median analysis window values. Root-mean-square amplitude, spectral decile 3, and spectral moment ratio showed consistent tendencies for the different obstetric scenarios as well as non-linear parameters: Lempel-Ziv, sample entropy, spectral entropy, and SD1/SD2 when computed in the fast wave high bandwidth. These findings would make it possible to extract high quality and robust EHG features to improve computer-aided assessment tools for pregnancy, labor, and postpartum progress and identify maternal fetal risks.This work was supported by the Spanish Ministry of Economy and Competitiveness, the European Regional Development Fund (MCIU/AEI/FEDER, UE RTI2018-094449-A-I00-AR) and the Generalitat Valenciana (AICO/2019/220 & GV/2018/104)Mas-Cabo, J.; Ye Lin, Y.; Garcia-Casado, J.; Díaz-Martínez, MDA.; Perales-Marin, A.; Monfort-Ortiz, R.; Roca-Prats, A.... (2020). Robust Characterization of the Uterine Myoelectrical Activity in Different Obstetric Scenarios. Entropy. 22(7):1-15. https://doi.org/10.3390/e22070743S115227Wagura, P., Wasunna, A., Laving, A., Wamalwa, D., & Ng’ang’a, P. (2018). Prevalence and factors associated with preterm birth at kenyatta national hospital. BMC Pregnancy and Childbirth, 18(1). doi:10.1186/s12884-018-1740-2Liu, L., Johnson, H. 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Uterine contractions clustering based on surface electromyography: an input for pregnancy monitoring
Tese de mestrado em Bioestatística, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, em 2018Inicialmente a investigação da contratilidade uterina recorria à utilização de dois métodos: o tocograma externo e o cateter de pressão intrauterino. Ambos os métodos apresentam limitações ao nível da avaliação do risco de parto prematuro e na monitorização da gravidez. O EHG (Electrohisterograma) é um método alternativo ao tocograma externo e ao cateter de pressão intrauterino. Este método pode ser aplicado de forma invasiva no músculo uterino, ou de forma não invasiva através de elétrodos colocados no abdómen. O EHG tem sido considerado uma ferramenta adequada para a monitorização da gravidez e do parto. O índice de massa corporal tem um impacto quase impercetível no EHG, sendo esta uma das principais características deste método. O EHG pode também ser utilizado para identificar as mulheres que vão entrar em trabalho de parto e ainda auxiliar na tomada de decisão médica quanto à utilização da terapia tocolítica (antagonista da oxitocina), evitando deste modo a ingestão de medicação desnecessária e os consequentes efeitos secundários. Na literatura existem apenas cinco casos publicados em que foi realizada uma separação dos principais eventos do sinal EHG: contrações, movimentos fetais, ondas Alvarez e ondas LDBF (Longue Durée Basse Fréquence). Em três das publicações a separação dos eventos foi feita manualmente e nos restantes casos algoritmos, como redes neuronais, foram aplicados ao EHG. As ondas Alvarez e as Braxton-Hicks são as mais reconhecidas. As ondas Alvarez foram descritas pela primeira vez nos anos cinquenta e as Braxton-Hicks foram descritas pela primeira vez em 1872 sendo detetadas através de palpação. As ondas Alvarez são ocasionalmente sentidas pela mulher. Estas ondas estão localizadas numa pequena área do tecido uterino sem propagação e podem levar a contrações com maior intensidade e, consequentemente, ao parto pré-termo. As Braxton-Hicks são contrações ineficientes registadas a partir da 20ª semana de gravidez que se tornam mais frequentes e intensas com o decorrer da gravidez. Estas contrações são menos localizadas que as ondas Alvarez e, durante o parto, propagam-se por todo o tecido uterino num curto período de tempo. As Braxton-Hicks estão associadas a uma diminuição do ritmo cardíaco fetal. As ondas LDBF são contrações de longa duração associadas a hipertonia uterina, quando há contração do tecido uterino sem retorno ao relaxamento muscular, o que representa um risco na gravidez. Neste trabalho foram utilizadas duas bases de dados. Na base de dados da Islândia existem 122 registos de 45 mulheres, dos quais apenas 4 correspondem a partos pré-termo. Na base de dados TPEHG (Term-Preterm EHG) existem 300 registos, dos quais 38 correspondem a partos pré-termo. Neste trabalho foram escolhidos canais bipolares, visto que estes reduzem o ruído idêntico, como o ECG (Eletrocardiograma) materno ou movimentos respiratórios. Para ambas as bases de dados os sinais originais de EHG foram processados e filtrados. Na estimação espetral foram considerados dois métodos: paramétricos e não paramétricos. O método Welch foi escolhido pois representa um bom compromisso entre ambos. Este método foi utilizado para calcular o espectro de cada evento detetado no sinal EHG. Para detetar os eventos no sinal EHG foram considerados cinco métodos baseados na energia ou amplitude. O método Wavelet foi o escolhido pois após uma inspeção visual, este era o método que delineava melhor as contrações. Na base de dados da Islândia foram identificadas 3136 contrações e na TPEHG foram encontradas 4622 contrações. O objetivo principal desta tese é obter clusters de contrações detetadas no sinal EHG. No entanto, as contrações são séries temporais não estacionárias, e a sua classificação visual é inviável a longo termo e também difícil de aplicar na prática clínica. Existem vários parâmetros que podem ser extraídos do sinal EHG, mas o espectro das contrações foi o método escolhido visto que este representa o sinal EHG e tem sempre a mesma dimensão, independentemente da duração da contração. As distâncias espetrais têm sido utilizadas com sucesso no reconhecimento áudio. Neste trabalho foi realizada uma aplicação desse método ao processamento do EHG, no qual foram realizados os ajustes necessários. Para comparar os espectros foram estudadas 8 distâncias diferentes: Itakura-Saito, COSH, Itakura, Itakura simétrica, Kullback-Leibler, Jeffrey, Rényi e Jensen-Rényi. Apenas as distâncias simétricas foram selecionadas para um estudo mais detalhado visto que estas são, segundo a literatura, as distâncias mais adequadas aquando do clustering. Após comparação das distâncias simétricas, a divergência de Jeffrey foi a selecionada para a comparação dos espectros. Nesta tese foram avaliados três métodos diferentes de clustering: o linkage, o K-means e o K-medoids. O linkage é um método hierárquico. Os clusters que resultam do agrupamento hierárquico estão organizados numa estrutura chamada dendrograma. No agrupamento hierárquico, não é necessário predeterminar o número de clusters, o que torna este um método ideal na exploração dos dados. O K-means e o K-medoids são métodos de partição, nos quais os dados são separados em k clusters decididos previamente. Os clusters são definidos de forma a otimizar a função da distância. No algoritmo K-means, os clusters baseiam-se na proximidade entre si de acordo com uma distância predeterminada. A diferença entre o K-medoids e o K-means é que o K-medoids escolhe pontos de dados como centros, chamados de medoides, enquanto K-means usa centróides. Após uma comparação dos diferentes métodos de clustering foi escolhido neste trabalho foi o average linkage, visto que este apresentava melhores resultados quer na separação dos espectros quer na silhueta. É então apresentado um método inovador no qual se utiliza todo o espectro das contrações detetadas automaticamente no EHG para o clustering não supervisionado. Esta técnica é uma contribuição para a classificação automática das diferentes contrações, especialmente aquelas mais reconhecidas na literatura: Alvarez e Braxton-Hicks. Era expectável encontrar um cluster isolado com as ondas LDBF, visto que estas representam um risco para o feto. O principal objetivo era juntar num cluster os espectros semelhantes das contrações, e relacioná-lo com o respetivo tipo de contração. Essa tarefa foi concluída através da identificação positiva de Alvarez e Braxton-Hicks. O clustering forneceu ainda algumas pistas sobre ondas Alvarez que não foram encontradas com o algoritmo de deteção de contrações, situação para a qual um método alternativo é apresentado. É sugerido que as ondas Alvarez sejam detetadas com métodos baseados na frequência, como, por exemplo, a frequência instantânea, no entanto este método não foi desenvolvido neste trabalho. Em relação às ondas LDBF, estas foram encontradas no cluster das Braxton-Hicks. É sugerido que a deteção das ondas LDBF seja baseada na sua caraterística mais distinta: a longa duração. Verificou-se que os casos pré-termo e os registos pré-parto não ficaram isolados num cluster, não se tendo encontrado uma relação entre a idade gestacional e o tipo de contração. Conclui-se que as contrações mais curtas apresentam maior amplitude do que as contrações com maior duração. Baseado em estudos anteriores sobre a eletrofisiologia do útero, supõem-se que o início do trabalho de parto pré-termo e termo esteja associado a sequências específicas de diferentes tipos de contrações, nas quais as ondas Alvares desempenham um papel importante. As contrações identificadas como Alvarez e Braxton-Hicks não são usadas como tal na prática clínica apesar de a maioria das contrações detetadas pelo tocograma serem Braxton-Hicks. O interesse pelas ondas Alvarez diminuiu rapidamente visto que estas ondas são praticamente indetetáveis pelo método de referência de deteção de contrações: o tocograma. As capacidades e a resolução do EHG levaram à renovação do estudo das contrações mais subtis, incluindo as Alvarez. Este trabalho é uma contribuição para a investigação nesta área.An innovative technique is introduced wherein where an unsupervised clustering method using as feature the whole spectrum of automatically detected contractions on the EHG (Electrohysterogram) is presented as a contribution to the automatic classification of the different uterine contractions, at least those that have been most recognized in the literature: Alvarez and Braxton-Hicks. It was expected to also be able to cluster the LDBF (Longue Durée Basse Fréquence) components, as these pose a fetal risk. The main task was to have the spectral contractions descriptions clustered and linked to the respective contraction type. That task was completed with positive identification of the Alvarez and Braxton-Hicks. The clustering process also provided clues regarding the missed Alvarez waves in the contraction detection algorithm, for which an alternative technique is suggested but not developed in this work. Regarding the LDBF they were found in the Braxton-Hicks cluster. It is suggested the LDBF´s to be detected based in their most prominent feature: the long duration. It is presented the rationale behind the selection of a cost function to be used in the spectral distance’s algorithm. Spectral distances have been successfully used in audio recognition and this works represents an application to the EHG processing, for which the necessary adjustments have to be implemented. It was found that no single cluster pointed to the preterm cases, or indeed to the pre-labor subject recordings. It is hypothesized, based on previous studies in uterine electrophysiology, that the initiation of pre-term or term labor should be associated with triggering contraction sequences of different types, where the Alvarez waves play a major role. Alvarez and Braxton-Hicks, labeled as such, are not typically used in the clinical environment despite most of the Tocogram detected contractions being the latter. Alvarez waves are not usually detectable by the Tocogram. Alvarez were firstly detected invasively in the early fifties, and Braxton-Hicks in 1872 using routine palpation techniques. The interest in Alvarez components declined rapidly since being practically undetectable by the de facto reference in the contraction detection: the Tocogram. The EHG capabilities and resolution made it possible to revive the research on the most subtle uterine contractions, Alvarez included and this work is a contribution in this research area
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