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2.
Comput Biol Med ; 175: 108501, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703545

RESUMO

The segmentation of the fetal head (FH) and pubic symphysis (PS) from intrapartum ultrasound images plays a pivotal role in monitoring labor progression and informing crucial clinical decisions. Achieving real-time segmentation with high accuracy on systems with limited hardware capabilities presents significant challenges. To address these challenges, we propose the real-time segmentation network (RTSeg-Net), a groundbreaking lightweight deep learning model that incorporates innovative distribution shifting convolutional blocks, tokenized multilayer perceptron blocks, and efficient feature fusion blocks. Designed for optimal computational efficiency, RTSeg-Net minimizes resource demand while significantly enhancing segmentation performance. Our comprehensive evaluation on two distinct intrapartum ultrasound image datasets reveals that RTSeg-Net achieves segmentation accuracy on par with more complex state-of-the-art networks, utilizing merely 1.86 M parameters-just 6 % of their hyperparameters-and operating seven times faster, achieving a remarkable rate of 31.13 frames per second on a Jetson Nano, a device known for its limited computing capacity. These achievements underscore RTSeg-Net's potential to provide accurate, real-time segmentation on low-power devices, broadening the scope for its application across various stages of labor. By facilitating real-time, accurate ultrasound image analysis on portable, low-cost devices, RTSeg-Net promises to revolutionize intrapartum monitoring, making sophisticated diagnostic tools accessible to a wider range of healthcare settings.


Assuntos
Cabeça , Sínfise Pubiana , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Cabeça/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Sínfise Pubiana/diagnóstico por imagem , Aprendizado Profundo , Feto/diagnóstico por imagem
3.
Med Biol Eng Comput ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722478

RESUMO

The accurate selection of the ultrasound plane for the fetal head and pubic symphysis is critical for precisely measuring the angle of progression. The traditional method depends heavily on sonographers manually selecting the imaging plane. This process is not only time-intensive and laborious but also prone to variability based on the clinicians' expertise. Consequently, there is a significant need for an automated method driven by artificial intelligence. To enhance the efficiency and accuracy of identifying the pubic symphysis-fetal head standard plane (PSFHSP), we proposed a streamlined neural network, PSFHSP-Net, based on a modified version of ResNet-18. This network comprises a single convolutional layer and three residual blocks designed to mitigate noise interference and bolster feature extraction capabilities. The model's adaptability was further refined by expanding the shared feature layer into task-specific layers. We assessed its performance against both traditional heavyweight and other lightweight models by evaluating metrics such as F1-score, accuracy (ACC), recall, precision, area under the ROC curve (AUC), model parameter count, and frames per second (FPS). The PSFHSP-Net recorded an ACC of 0.8995, an F1-score of 0.9075, a recall of 0.9191, and a precision of 0.9022. This model surpassed other heavyweight and lightweight models in these metrics. Notably, it featured the smallest model size (1.48 MB) and the highest processing speed (65.7909 FPS), meeting the real-time processing criterion of over 24 images per second. While the AUC of our model was 0.930, slightly lower than that of ResNet34 (0.935), it showed a marked improvement over ResNet-18 in testing, with increases in ACC and F1-score of 0.0435 and 0.0306, respectively. However, precision saw a slight decrease from 0.9184 to 0.9022, a reduction of 0.0162. Despite these trade-offs, the compression of the model significantly reduced its size from 42.64 to 1.48 MB and increased its inference speed by 4.4753 to 65.7909 FPS. The results confirm that the PSFHSP-Net is capable of swiftly and effectively identifying the PSFHSP, thereby facilitating accurate measurements of the angle of progression. This development represents a significant advancement in automating fetal imaging analysis, promising enhanced consistency and reduced operator dependency in clinical settings.

4.
Sci Data ; 11(1): 436, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698003

RESUMO

During the process of labor, the intrapartum transperineal ultrasound examination serves as a valuable tool, allowing direct observation of the relative positional relationship between the pubic symphysis and fetal head (PSFH). Accurate assessment of fetal head descent and the prediction of the most suitable mode of delivery heavily rely on this relationship. However, achieving an objective and quantitative interpretation of the ultrasound images necessitates precise PSFH segmentation (PSFHS), a task that is both time-consuming and demanding. Integrating the potential of artificial intelligence (AI) in the field of medical ultrasound image segmentation, the development and evaluation of AI-based models rely significantly on access to comprehensive and meticulously annotated datasets. Unfortunately, publicly accessible datasets tailored for PSFHS are notably scarce. Bridging this critical gap, we introduce a PSFHS dataset comprising 1358 images, meticulously annotated at the pixel level. The annotation process adhered to standardized protocols and involved collaboration among medical experts. Remarkably, this dataset stands as the most expansive and comprehensive resource for PSFHS to date.


Assuntos
Inteligência Artificial , Cabeça , Sínfise Pubiana , Ultrassonografia Pré-Natal , Humanos , Sínfise Pubiana/diagnóstico por imagem , Feminino , Gravidez , Cabeça/diagnóstico por imagem , Feto/diagnóstico por imagem
5.
Artigo em Inglês | MEDLINE | ID: mdl-38739504

RESUMO

Accurate segmentation of the fetal head and pubic symphysis in intrapartum ultrasound images and measurement of fetal angle of progression (AoP) are critical to both outcome prediction and complication prevention in delivery. However, due to poor quality of perinatal ultrasound imaging with blurred target boundaries and the relatively small target of the public symphysis, fully automated and accurate segmentation remains challenging. In this paper, we propse a dual-path boundary-guided residual network (DBRN), which is a novel approach to tackle these challenges. The model contains a multi-scale weighted module (MWM) to gather global context information, and enhance the feature response within the target region by weighting the feature map. The model also incorporates an enhanced boundary module (EBM) to obtain more precise boundary information. Furthermore, the model introduces a boundary-guided dual-attention residual module (BDRM) for residual learning. BDRM leverages boundary information as prior knowledge and employs spatial attention to simultaneously focus on background and foreground information, in order to capture concealed details and improve segmentation accuracy. Extensive comparative experiments have been conducted on three datasets. The proposed method achieves average Dice score of 0.908 ±0.05 and average Hausdorff distance of 3.396 ±0.66 mm. Compared with state-of-the-art competitors, the proposed DBRN achieves better results. In addition, the average difference between the automatic measurement of AoPs based on this model and the manual measurement results is 6.157 °, which has good consistency and has broad application prospects in clinical practice.

6.
Front Cardiovasc Med ; 10: 1059211, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37621563

RESUMO

Background: This study aims to compare the fetal heart rate (FHR) baseline predicted by the cardiotocograph network (CTGNet) with that estimated by clinicians. Material and methods: A total of 1,267 FHR recordings acquired with different electrical fetal monitors (EFM) were collected from five datasets: 84 FHR recordings acquired with F15 EFM (Edan, Shenzhen, China) from the Guangzhou Women and Children's Medical Center, 331 FHR recordings acquired with SRF618B5 EFM (Sanrui, Guangzhou, China), 234 FHR recordings acquired with F3 EFM (Lian-Med, Guangzhou, China) from the NanFang Hospital of Southen Medical University, 552 cardiotocographys (CTG) recorded using STAN S21 and S31 (Neoventa Medical, Mölndal, Sweden) and Avalon FM40 and FM50 (Philips Healthcare, Amsterdam, The Netherlands) from the University Hospital in Brno, Czech Republic, and 66 FHR recordings acquired using Avalon FM50 fetal monitor (Philips Healthcare, Amsterdam, The Netherlands) at St Vincent de Paul Hospital (Lille, France). Each FHR baseline was estimated by clinicians and CTGNet, respectively. And agreement between CTGNet and clinicians was evaluated using the kappa statistics, intra-class correlation coefficient, and the limits of agreement. Results: The number of differences <3 beats per minute (bpm), 3-5 bpm, 5-10 bpm and ≥10 bpm, is 64.88%, 15.94%, 14.44% and 4.74%, respectively. Kappa statistics and intra-class correlation coefficient are 0.873 and 0.969, respectively. Limits of agreement are -6.81 and 7.48 (mean difference: 0.36 and standard deviation: 3.64). Conclusion: An excellent agreement was found between CTGNet and clinicians in the baseline estimation from FHR recordings with different signal loss rates.

7.
Int J Comput Assist Radiol Surg ; 18(8): 1489-1500, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36853584

RESUMO

PURPOSE: In recent years, breast cancer has become the greatest threat to women. There are many studies dedicated to the precise segmentation of breast tumors, which is indispensable in computer-aided diagnosis. Deep neural networks have achieved accurate segmentation of images. However, convolutional layers are biased to extract local features and tend to lose global and location information as the network deepens, which leads to a decrease in breast tumors segmentation accuracy. For this reason, we propose a hybrid attention-guided network (HAG-Net). We believe that this method will improve the detection rate and segmentation of tumors in breast ultrasound images. METHODS: The method is equipped with multi-scale guidance block (MSG) for guiding the extraction of low-resolution location information. Short multi-head self-attention (S-MHSA) and convolutional block attention module are used to capture global features and long-range dependencies. Finally, the segmentation results are obtained by fusing multi-scale contextual information. RESULTS: We compare with 7 state-of-the-art methods on two publicly available datasets through five random fivefold cross-validations. The highest dice coefficient, Jaccard Index and detect rate ([Formula: see text]%, [Formula: see text]%, [Formula: see text]% and [Formula: see text]%, [Formula: see text]%, [Formula: see text]%, separately) obtained on two publicly available datasets(BUSI and OASUBD), prove the superiority of our method. CONCLUSION: HAG-Net can better utilize multi-resolution features to localize the breast tumors. Demonstrating excellent generalizability and applicability for breast tumors segmentation compare to other state-of-the-art methods.


Assuntos
Neoplasias da Mama , Processamento de Imagem Assistida por Computador , Humanos , Feminino , Processamento de Imagem Assistida por Computador/métodos , Ultrassonografia Mamária , Redes Neurais de Computação , Neoplasias da Mama/diagnóstico por imagem , Diagnóstico por Computador
8.
Front Physiol ; 14: 1027076, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36776975

RESUMO

Cardiac magnetic resonance imaging (MRI) segmentation task refers to the accurate segmentation of ventricle and myocardium, which is a prerequisite for evaluating the soundness of cardiac function. With the development of deep learning in medical imaging, more and more heart segmentation methods based on deep learning have been proposed. Due to the fuzzy boundary and uneven intensity distribution of cardiac MRI, some existing methods do not make full use of multi-scale characteristic information and have the problem of ambiguity between classes. In this paper, we propose a dilated convolution network with edge fusion block and directional feature maps for cardiac MRI segmentation. The network uses feature fusion module to preserve boundary information, and adopts the direction field module to obtain the feature maps to improve the original segmentation features. Firstly, multi-scale feature information is obtained and fused through dilated convolutional layers of different scales while downsampling. Secondly, in the decoding stage, the edge fusion block integrates the edge features into the side output of the encoder and concatenates them with the upsampled features. Finally, the concatenated features utilize the direction field to improve the original segmentation features and generate the final result. Our propose method conducts comprehensive comparative experiments on the automated cardiac diagnosis challenge (ACDC) and myocardial pathological segmentation (MyoPS) datasets. The results show that the proposed cardiac MRI segmentation method has better performance compared to other existing methods.

9.
Med Biol Eng Comput ; 61(5): 1017-1031, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36645647

RESUMO

The generalization ability of the fetal head segmentation method is reduced due to the data obtained by different machines, settings, and operations. To keep the generalization ability, we proposed a Fourier domain adaptation (FDA) method based on amplitude and phase to achieve better multi-source ultrasound data segmentation performance. Given the source/target image, the Fourier domain information was first obtained using fast Fourier transform. Secondly, the target information was mapped to the source Fourier domain through the phase adjustment parameter α and the amplitude adjustment parameter ß. Thirdly, the target image and the preprocessed source image obtained through the inverse discrete Fourier transform were used as the input of the segmentation network. Finally, the dice loss was computed to adjust α and ß. In the existing transform methods, the proposed method achieved the best performance. The adaptive-FDA method provides a solution for the automatic preprocessing of multi-source data. Experimental results show that it quantitatively improves the segmentation results and model generalization performance.


Assuntos
Cabeça , Ultrassonografia Pré-Natal , Feminino , Gravidez , Humanos , Ultrassonografia , Cabeça/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos
10.
Front Physiol ; 13: 969052, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531165

RESUMO

CTG (cardiotocography) has consistently been used to diagnose fetal hypoxia. It is susceptible to identifying the average fetal acid-base balance but lacks specificity in recognizing prenatal acidosis and neurological impairment. CTG plays a vital role in intrapartum fetal state assessment, which can prevent severe organ damage if fetal hypoxia is detected earlier. In this paper, we propose a novel deep feature fusion network (DFFN) for fetal state assessment. First, we extract spatial and temporal information from the fetal heart rate (FHR) signal using a multiscale CNN-BiLSTM network, increasing the features' diversity. Second, the multiscale CNN-BiLSM network and frequently used features are integrated into the deep learning model. The proposed DFFN model combines different features to improve classification accuracy. The multiscale convolutional kernels can identify specific essential information and consider signal's temporal information. The proposed method achieves 61.97%, 73.82%, and 66.93% of sensitivity, specificity, and quality index, respectively, on the public CTU-UHB database. The proposed method achieves the highest QI on the private database, verifying the proposed method's effectiveness and generalization. The proposed DFFN combines the advantages of feature engineering and deep learning models and achieves competitive accuracy in fetal state assessment compared with related works.

11.
Front Physiol ; 13: 940150, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531181

RESUMO

Background: Accurate assessment of fetal descent by monitoring the fetal head (FH) station remains a clinical challenge in guiding obstetric management. Angle of progression (AoP) has been suggested to be a reliable and reproducible parameter for the assessment of FH descent. Methods: A novel framework, including image segmentation, target fitting and AoP calculation, is proposed for evaluating fetal descent. For image segmentation, this study presents a novel double branch segmentation network (DBSN), which consists of two parts: an encoding part receives image input, and a decoding part composed of deformable convolutional blocks and ordinary convolutional blocks. The decoding part includes the lower and upper branches, and the feature map of the lower branch is used as the input of the upper branch to assist the upper branch in decoding after being constrained by the attention gate (AG). Given an original transperineal ultrasound (TPU) image, areas of the pubic symphysis (PS) and FH are firstly segmented using the proposed DBSN, the ellipse contours of segmented regions are secondly fitted with the least square method, and three endpoints are finally determined for calculating AoP. Results: Our private dataset with 313 transperineal ultrasound (TPU) images was used for model evaluation with 5-fold cross-validation. The proposed method achieves the highest Dice coefficient (93.4%), the smallest Average Surface Distance (6.268 pixels) and the lowest AoP difference (5.993°) by comparing four state-of-the-art methods. Similar results (Dice coefficient: 91.7%, Average Surface Distance: 7.729 pixels: AoP difference: 5.110°) were obtained on a public dataset with >3,700 TPU images for evaluating its generalization performance. Conclusion: The proposed framework may be used for the automatic measurement of AoP with high accuracy and generalization performance. However, its clinical availability needs to be further evaluated.

12.
Comput Math Methods Med ; 2022: 5192338, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092792

RESUMO

The angle of progression (AoP) for assessing fetal head (FH) descent during labor is measured from the standard plane of transperineal ultrasound images as the angle between a line through the long axis of pubic symphysis (PS) and a second line from the right end of PS tangentially to the contour of the FH. This paper presents a multitask network with a shared feature encoder and three task-special decoders for standard plane recognition (Task1), image segmentation (Task2) of PS and FH, and endpoint detection (Task3) of PS. Based on the segmented FH and two endpoints of PS from standard plane images, we determined the right FH tangent point that passes through the right endpoint of PS and then computed the AoP using the above three points. In this paper, the efficient channel attention unit is introduced into the shared feature encoder for improving the robustness of layer region encoding, while an attention fusion module is used to promote cross-branch interaction between the encoder for Task2 and that for Task3, and a shape-constrained loss function is designed for enhancing the robustness to noise based on the convex shape-prior. We use Pearson's correlation coefficient and the Bland-Altman graph to assess the degree of agreement. The dataset includes 1964 images, where 919 images are nonstandard planes, and the other 1045 images are standard planes including PS and FH. We achieve a classification accuracy of 92.26%, and for the AoP calculation, an absolute mean (STD) value of the difference in AoP (∆AoP) is 3.898° (3.192°), the Pearson's correlation coefficient between manual and automated AoP was 0.964 and the Bland-Altman plot demonstrates they were statistically significant (P < 0.05). In conclusion, our approach can achieve a fully automatic measurement of AoP with good efficiency and may help labor progress in the future.


Assuntos
Apresentação no Trabalho de Parto , Ultrassonografia Pré-Natal , Feminino , Feto/diagnóstico por imagem , Humanos , Redes Neurais de Computação , Gravidez , Reprodutibilidade dos Testes , Ultrassonografia Pré-Natal/métodos
13.
Front Physiol ; 13: 957604, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111152

RESUMO

Atrial fibrillation (AF) with multiple complications, high morbidity and mortality, and low cure rates, has become a global public health problem. Although significant progress has been made in the treatment methods represented by anti-AF drugs and radiofrequency ablation, the therapeutic effect is not as good as expected. The reason is mainly because of our lack of understanding of AF mechanisms. This field has benefited from mechanistic and (or) statistical methodologies. Recent renewed interest in digital twin techniques by synergizing between mechanistic and statistical models has opened new frontiers in AF analysis. In the review, we briefly present findings that gave rise to the AF pathophysiology and current therapeutic modalities. We then summarize the achievements of digital twin technologies in three aspects: understanding AF mechanisms, screening anti-AF drugs and optimizing ablation strategies. Finally, we discuss the challenges that hinder the clinical application of the digital twin heart. With the rapid progress in data reuse and sharing, we expect their application to realize the transition from AF description to response prediction.

14.
Ann Transl Med ; 10(13): 740, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35957704

RESUMO

Background: Complete electronic health records (EHRs) are not often available, because information barriers are caused by differences in the level of informatization and the type of the EHR system. Therefore, we aimed to develop a deep learning system [deep learning system for structured recognition of text images from unstructured paper-based medical reports (DeepSSR)] for structured recognition of text images from unstructured paper-based medical reports (UPBMRs) to help physicians solve the data-sharing problem. Methods: UPBMR images were firstly preprocessed through binarization, image correction, and image segmentation. Next, the table area was detected with a lightweight network (i.e., the proposed YOLOv3-MobileNet model). In addition, the text of the table area was detected and recognized with the model based on differentiable binarization (DB) and convolutional recurrent neural network (CRNN). Finally, the recognized text was structured according to its row and column coordinates. DeepSSR was trained and validated on our dataset with 4,221 UPBMR images which were randomly split into training, validation, and testing sets in a ratio of 8:1:1. Results: DeepSSR achieved a high accuracy of 91.10% and a speed of 0.668 s per image. In the system, the proposed YOLOv3-MobileNet model for table detection achieved a precision of 97.8% and a speed of 0.006 s per image. Conclusions: DeepSSR has high accuracy and fast speed in structured recognition of text based on UPBMR images. This system may help solve the data-sharing problem due to information barriers between hospitals with different EHR systems.

16.
Data Brief ; 41: 107904, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35198683

RESUMO

The use of transperineal ultrasound techniques for the assessment of fetal head descent and progression is an adjunct to clinical examination. Automatic identification of parameters based on ultrasound images will greatly reduce the subjectivity and non-repeatability of the clinician's judgment. However, the lack of a pubic symphysis-fetal head dataset hinders the development of algorithms. Here, we present an intrapartum transperineal ultrasound dataset of the Intelligent Fetal Monitoring Lab of Jinan University (named the JNU-IFM dataset), in which intrapartum transperineal ultrasound videos of 78 were recorded from 51 patients. These data were obtained with the Youkey D8 wireless 2D ultrasound probe with its corresponding supporting software by Wuhan Youkey Bio-Medical Electronics Co., Ltd., Wuhan, China. In these videos, 6224 high-quality images with four categories were selected to form the JNU- IFM dataset. These images were labelled using the Pair software and then validated by two experienced radiologists. We hope that this data set can be used in the segmentation of the pubic symphysis-fetal head.

17.
Arch Gynecol Obstet ; 306(4): 1015-1025, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35171347

RESUMO

PURPOSE: This work used a machine learning model to improve the accuracy of predicting postpartum hemorrhage in vaginal delivery. METHODS: Among the 25,098 deliveries in the obstetrics department of the First Hospital of Jinan University recorded from 2016 to 2020, 10,520 were vaginal deliveries with complete study data. Further review selected 850 cases of postpartum hemorrhage (amount of bleeding > 500 mL) and 54 cases of severe postpartum hemorrhage (amount of bleeding > 1000 mL). Indicators of clinical risk factors for postpartum hemorrhage were retrieved from electronic medical records. Features of the uterine contraction curve were extracted 2 h prior to vaginal delivery and modeled using a 49-variable machine learning with 90% of study cases used in the training set and 10% of study cases used in the test set. Accuracy was compared among the assessment table, classical statistical models, and machine learning models used to predict postpartum hemorrhage to assess their clinical use. The assessment table contained 16 high-risk factor scores to predict postpartum hemorrhage. The classical statistical model used was Logistic Regression (LR). The machine learning models were Random Forest (RF), K Nearest Neighbor (KNN), and the one integrated with Lightgbm (LGB) and LR. The effect of model prediction was evaluated by area under the receiver operating characteristic curve (AUC), namely, C-static, calibration curve Brier score, decision curve, F-measure, sensitivity (SE), and specificity (SP). RESULTS: 1: Among the tested tools, the machine learning model LGB + LR has the best performance in predicting postpartum hemorrhage. Its Brier, AUC, and F-measure scores are better than those of other models in each group, and its SE and SP reach 0.694 and 0.800, respectively. The predictive performance of the classical statistical model LR is AUC: 0.729, 95%CI [0.702-0.756]). 2: Verification on the testing set reveals that the features of uterine contraction contribute to the improved accuracy of the model prediction. 3: LGB + LR model suggested that among the 49 indicators for predicting severe postpartum hemorrhage, the importance of the first 10 characteristics in descending order is as follows: hematocrit (%), shock index, frequency of contractions (min-1), white blood cell count, gestational hypertension, neonatal weight (kg), time of second labor (min), mean area of contractions (mmHg s), total amniotic fluid (mL), and body mass index (BMI). The prediction effect is close to that of the model after training with all 49 features. The predictive effect was close to that of the model after training using all 49 features. 4: Contraction frequency and intensity Mean_Area (representing effective contractions) have a high predictive value for severe postpartum hemorrhage. 5: Blood loss amount within 2 h has a high warning effect on postpartum hemorrhage, and the increase in AUC to 0.95 indicates that postpartum bleeding mostly occurs within 2 h after delivery. CONCLUSION: Machine learning models incorporated with uterine contraction features can further improve the accuracy of postpartum hemorrhage prediction in vaginal delivery and provide a reference for clinicians to intervene early and reduce adverse pregnancy outcomes.


Assuntos
Hemorragia Pós-Parto , Parto Obstétrico/efeitos adversos , Feminino , Humanos , Recém-Nascido , Aprendizado de Máquina , Hemorragia Pós-Parto/diagnóstico , Hemorragia Pós-Parto/etiologia , Gravidez , Fatores de Risco , Contração Uterina
18.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299303

RESUMO

Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. Several major mechanisms cause AF in patients, including genetic predispositions to AF development. Genome-wide association studies have identified a number of genetic variants in association with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription PITX2. Because of the inherent complexity of the human heart, experimental and basic research is insufficient for understanding the functional impacts of PITX2 variants on AF. Linking PITX2 properties to ion channels, cells, tissues, atriums and the whole heart, computational models provide a supplementary tool for achieving a quantitative understanding of the functional role of PITX2 in remodelling atrial structure and function to predispose to AF. It is hoped that computational approaches incorporating all we know about PITX2-related structural and electrical remodelling would provide better understanding into its proarrhythmic effects leading to development of improved anti-AF therapies. In the present review, we discuss advances in atrial modelling and focus on the mechanistic links between PITX2 and AF. Challenges in applying models for improving patient health are described, as well as a summary of future perspectives.


Assuntos
Fibrilação Atrial/etiologia , Fibrilação Atrial/genética , Proteínas de Homeodomínio/genética , Modelos Cardiovasculares , Fatores de Transcrição/genética , Animais , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial/genética , Remodelamento Atrial/fisiologia , Padronização Corporal/genética , Simulação por Computador , Genes Homeobox , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Coração/embriologia , Proteínas de Homeodomínio/fisiologia , Humanos , Canais Iônicos/genética , Canais Iônicos/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Mutação , Fatores de Transcrição/fisiologia , Proteína Homeobox PITX2
20.
Ann Transl Med ; 9(2): 106, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33569408

RESUMO

BACKGROUND: Electrical remodelling as a result of the homeodomain transcription factor 2 (Pitx2)-dependent gene regulation induces atrial fibrillation (AF) with different mechanisms. The purpose of this study was to identify Pitx2-induced changes in ionic currents that cause action potential (AP) shortening and lead to triggered activity. METHODS: Populations of computational atrial AP models were developed based on AP recordings from sinus rhythm (SR) and AF patients. Models in the AF population were divided into triggered and untriggered AP groups to evaluate the relationship between each ion current regulated by Pitx2 and triggered APs. Untriggered AP models were then divided into shortened and unshortened AP groups to determine which Pitx2-dependent ion currents contribute to AP shortening. RESULTS: According to the physiological range of AP biomarkers measured experimentally, populations of 2,885 SR and 4,781 AF models out of the initial pool of 30,000 models were selected. Models in the AF population predicted AP shortening and triggered activity observed in experiments in Pitx2-induced remodelling conditions. The AF models included 925 triggered AP models, 1,412 shortened AP models and 2,444 unshortened AP models. Intersubject variability in IKs and ICaL primarily modulated variability in AP duration (APD) in all shortened and unshortened AP models, whereas intersubject variability in IK1 and SERCA mainly contributed to the variability in AP morphology in all triggered and untriggered AP models. The incidence of shortened AP was positively correlated with IKs and IK1 and was negatively correlated with INa , ICaL and SERCA, whereas the incidence of triggered AP was negatively correlated with IKs and IK1 and was positively correlated with INa , ICaL and SERCA. CONCLUSIONS: Electrical remodelling due to Pitx2 upregulation may increase the incidence of shortened AP, whereas electrical remodelling arising from Pitx2 downregulation may favor to the genesis of triggered AP.

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