Evaluation of deep convolutional neural networks for automatic classification of common maternal fetal ultrasound planes

The goal of this study was to evaluate the maturity of current Deep Learning classification techniques for their application in a real maternal-fetal clinical environment. A large dataset of routinely acquired maternal-fetal screening ultrasound images (which will be made publicly available) was collected from two different hospitals by several operators and ultrasound machines. All images were manually labeled by an expert maternal fetal clinician. Images were divided into 6 classes: four of the most widely used fetal anatomical planes (Abdomen, Brain, Femur and Thorax), the mother's cervix (widely used for prematurity screening) and a general category to include any other less common image plane. Fetal brain images were further categorized into the 3 most common fetal brain planes (Trans-thalamic, Trans-cerebellum, Trans-ventricular) to judge fine grain categorization performance. The final dataset is comprised of over 12,400 images from 1,792 patients, making it the largest ultrasound dataset to date. We then evaluated a wide variety of state-of-the-art deep Convolutional Neural Networks on this dataset and analyzed results in depth, comparing the computational models to research technicians, which are the ones currently performing the task daily. Results indicate for the first time that computational models have similar performance compared to humans when classifying common planes in human fetal examination. However, the dataset leaves the door open on future research to further improve results, especially on fine-grained plane categorization

Analysis of maturation features in fetal brain ultrasound via artificial intelligence for the estimation of gestational age

Background: Optimal prenatal care relies on accurate gestational age dating. After the first trimester, the accuracy of current gestational age estimation methods diminishes with increasing gestational age. Considering that, in many countries, access to first trimester crown rump length is still difficult owing to late booking, infrequent access to prenatal care, and unavailability of early ultrasound examination, the development of accurate methods for gestational age estimation in the second and third trimester of pregnancy remains an unsolved challenge in fetal medicine. Objective. This study aimed to evaluate the performance of an artificial intelligence method based on automated analysis of fetal brain morphology on standard cranial ultrasound sections to estimate the gestational age in second and third trimester fetuses compared with the current formulas using standard fetal biometry. Study Design: Standard transthalamic axial plane images from a total of 1394 patients undergoing routine fetal ultrasound were used to develop an artificial intelligence method to automatically estimate gestational age from the analysis of fetal brain information. We compared its performance—as stand alone or in combination with fetal biometric parameters—against 4 currently used fetal biometry formulas on a series of 3065 scans from 1992 patients undergoing second (n=1761) or third trimester (n=1298) routine ultrasound, with known gestational age estimated from crown rump length in the first trimester. Results: Overall, 95% confidence interval of the error in gestational age estimation was 14.2 days for the artificial intelligence method alone and 11.0 when used in combination with fetal biometric parameters, compared with 12.9 days of the best method using standard biometrics alone. In the third trimester, the lower 95% confidence interval errors were 14.3 days for artificial intelligence in combination with biometric parameters and 17 days for fetal biometrics, whereas in the second trimester, the 95% confidence interval error was 6.7 and 7, respectively. The performance differences were even larger in the small-for-gestational-age fetuses group (14.8 and 18.5, respectively). Conclusion: An automated artificial intelligence method using standard sonographic fetal planes yielded similar or lower error in gestational age estimation compared with fetal biometric parameters, especially in the third trimester. These results support further research to improve the performance of these methods in larger studies.The research leading to these results was partially funded by Transmural Biotech S.L. In addition, the research has received funding from “la Caixa” Foundation under grant agreements LCF/PR/GN14/10270005 and LCF/PR/GN18/10310003, the Instituto de Salud Carlos III (PI16/00861, PI17/00675) within the Plan Nacional de I+D+I and cofinanced by Instituto de Salud Carlos III— Subdirección General de Evaluación together with the Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa,” Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, United Kingdom), Cellex Foundation, ASISA Foundation, and Agency for Management of University and Research Grants under grant 2017 SGR number 1531. In addition, E.E. has received funding from the Departament de Salut under grant number SLT008/18/00156.Peer ReviewedPostprint (published version

Comparison of 2D versus M-mode echocardiography for assessing fetal myocardial wall thickness

OBJECTIVE: M-mode and 2D have been proposed for evaluating fetal myocardial thickness. However, studies comparing the performance of both modalities are lacking. We aimed to compare 2D versus M-mode reproducibility for assessing myocardial wall thicknesses. METHODS: A prospective study including 45 healthy fetuses from low-risk pregnancies evaluated between 18 and 41 weeks of gestation. Left and right ventricular free-wall and septal myocardial thicknesses were measured at end-diastole (ED) and end-systole (ES) in transverse 4-chamber view using 2D and M-mode. Intra- and interobserver reproducibility was evaluated by the concordance correlation coefficient (CCC). Both techniques were compared by t-test of the CCC. RESULTS: 2D and M-mode demonstrated excellent and similar intraobserver repeatability, with the best concordance in ES septal thickness (M-mode CCC 0.956 versus 2D-mode CCC 0.914). Interobserver reproducibility demonstrated also a high concordance, optimal in ES left ventricular free wall (M-mode 0.925 versus 2 D 0.855). Comparison of both techniques demonstrated a high concordance in all measurements, except for ED septal thickness with better reproducibility using M-mode (CCC 0.954 versus 0.847, p = .017). CONCLUSIONS: 2D and M-mode can be used in a reproducible manner for measuring fetal myocardial thickness, with a slightly better performance of M-mode for assessing ED septal wall thickness

Uncomplicated monochorionic twins: two normal hearts sharing one placenta

Cardiovascular dysfunction has been reported in complicated monochorionic diamniotic (MCDA) pregnancies; however, little is known whether hemodynamic changes occur in uncomplicated MCDA twins. A prospective observational study was conducted including 100 uncomplicated MCDA twins matched by gestational age to 200 low-risk singletons. Echocardiography was performed at 26-30 weeks gestation and cord blood B-type natriuretic peptide (BNP) was measured at delivery. In both groups, z-scores for echocardiographic parameters were within normal ranges; however the monochorionic group had larger atrial areas (mean (standard deviation) right atria-to-heart ratio: 17.0 (2) vs. 15.9 (1); p = 0.018; left atria-to-heart ratio: 17.0 (3) vs. 15.8 (2); p < 0.001) and signs of concentric hypertrophy (right relative wall thickness: 0.66 (0.12) vs. 0.56 (0.11); p < 0.001; left relative wall thickness: 0.69 (0.14) vs. 0.58 (0.12); p < 0.001). Longitudinal function was increased in twins, leading to higher tricuspid annular plane systolic excursion (6.9 mm (0.9) vs. 5.9 mm (0.7); p < 0.001) and mitral annular plane systolic excursion (4.9 mm (0.8) vs. 4.4 mm (1.1); p < 0.001. BNP levels at birth were also higher in MCDA twins (median [interquartile range]: 20.81 pg/mL [16.69-34.01] vs. 13.14 pg/mL [9.17-19.84]; p < 0.001). Thus, uncomplicated MCDA fetuses have normal cardiac shape and function, but signs of cardiac adaptation were identified by echocardiographic and biochemical parameters, when compared with singletons

SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation.

Sirtuin 3 (SIRT3) is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress. Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances. In this study, we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells. SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1. Consistent with this, SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-alpha. Notably, these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1. Finally, we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter. These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway. Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy, heart failure, and diabetic cardiomyopathy, our results point to SIRT3 as a potential target for treating these diseases

Cardiovascular assessment in fetuses and children conceived by assisted reproductive technologies

[eng] BACKGROUND: Approximately, five million children have been born as a result of using assisted reproductive technologies (ART). Although the majority of ART children are born healthy; there are several reports of increased rate of pregnancy complications and worse perinatal outcomes in this population that may contribute to long-term health consequences according to the fetal programming hypothesis. Due to these techniques are relatively new, the effect of ART on later stages of development and adult susceptibility are uncertain. The main hypothesis of this thesis is that fetuses conceived by ART present worse perinatal outcomes together with primary cardiovascular remodeling and dysfunction as compared to those spontaneously conceived (SC), changes that persist postnatally and leads to increased cardiovascular risk in adulthood. METHODS: Cardiovascular morphology and functional assessment was performed in singleton and twin fetuses conceived by ART and spontaneously conceived; together with the presence of adverse perinatal outcomes. Finally, follow-up of these cohorts was made and cardiac and vascular function was assessed in childhood. RESULTS: ART fetuses showed: larger atria, shorter ventricles with lower sphericity index together with thicker myocardial walls. Systolic motion was decreased as measured by M-Mode and tissue Doppler; there were also sings of impaired relaxation, as demonstrated by a longer IRT and decreased deceleration time of E wave. All these changes were independent of the presence of been small for gestational age (SGA) due to these groups showed different cardiac phenotypes. ART children showed persistence of changes in cardiac morphology and function together with vascular remodeling (increased blood pressure and thicker carotid intima media). CONCLUSIONS: Adverse pregnancy outcomes seem to be present in infertile women, regardless of the use of ART. Singleton and twin ART fetuses present cardiovascular remodeling and subclinical dysfunction that persist postnatally in childhood. These changes are independent of the presence of SGA. These findings need to be take into account for further studies regarding higher cardiovascular risks in adulthood in this population[spa] INTRODUCCION: Aproximadamente, 5 millones de niños han nacido en el mundo gracias al uso de las tecnicas de reproduccion asistida (TRA). La mayoría de éstos niños son sanos al nacer; pero diversos estudios mencionan la presencia de peores resultados perinatales en esta población; los cuáles podrían tener consecuencias a largo plazo de acuerdo con la teoría de la programación fetal. Estas técnicas son relativamente nuevas, por lo que sus efectos en la vida adulta aún son desconocidos. La hipótesis principal de ésta tesis es que los fetos concebidos mediante TRA, presentan peores resultados perinatales que aquellos concebidos de manera espontánea (CE), junto con la presencia de cambios cardíacos morfológicos y funcionales que persisten de manera postnatal y que condicionaría un incremento del riesgo cardiovascular en la vida adulta. METODOS: Se llevó a cabo la evaluación cardiovascular morfológica y funcional de fetos únicos y gemelares concebidos por TRA comparados con fetos CE; junto con la presencia de resultados perinatales adversos. Se realiza un seguimiento y evaluación cardiovascular de dichas cohortes hasta la infancia. RESULTADOS: Los fetos TRA presentaron cambios al comparlos con los CE: aurículas más grandes, ventrículos más cortos junto con un menor índice de esfericidad así como paredes engrosadas. presentaron función sistólica disminuída de acuerdo con las mediciones de Doppler tisular y modo-M; también signos de disfunción diastólica demostrado por IRT alargados y disminución del tiempo de deceleración de la onda E. Todos estos cambios fueron independientes de la presencia de fetos pequeños para la edad gestacional (PEG), ya que dichos grupos presentaron fenotipos cardiacos diferentes. En la infancia, los niños TRA mostraron persistencia de dichos cambios cardíacos morfológicos y funcionales subclínicos, junto con remodelado vascular (presion arterial más alta y paredes engrosadas de la intima media de las carótidas). CONCLUSIONES: Las mujeres infértiles presentan resultados perinatales adversos independiente de el método de TRA usado. Los fetos concebidos mediante TRA presentan remodelado cardiovascular el cuál persiste postnatalmente en la infancia. Dichos cambios fueron independientes de la presencia de PEG. Estos hallazgos deben ser tomados en cuentra en futuros estudios del incremento de riesgo cardiovascular en la vida adulta de ésta población

Aortic and carotid intima-media thickness in term small-for-gestational-age newborns and relationship with prenatal signs of severity

Objective To assess carotid and aortic intima–media thickness (IMT) in term small‐for‐gestational‐age (SGA) newborns with and without prenatal signs of severity. Methods This prospective study comprised 67 cases diagnosed prenatally and 134 normally grown newborns. Cases were subclassified into SGA with no signs of severity and those with signs of severity, defined as a birth weight below the 3rd percentile or abnormal uterine artery Doppler or cerebroplacental ratio. Blood pressure and vascular IMT were evaluated. Results SGA newborns showed a non‐significant trend for higher values of blood pressure. IMT values were significantly increased in SGA newborns, with and without signs of severity, compared with controls. The magnitude of the increase was higher in SGA newborns with signs of severity. Conclusions Vascular IMT was increased in SGA newborns, irrespective of the presence or absence of prenatal signs of severity. This finding challenges the notion of ‘constitutionally small’ SGA, and supports the premise that the majority of SGA newborns have true growth restriction and suffer fetal cardiovascular programming.This study was supported by grants from Instituto de Salud Carlos III and Ministerio de Economia y Competitividad (ref. PI11/00051, PI11/01709, PI12/00801 and SAF2012‐37196) cofinanciado por el Fondo Europeo de Desarrollo Regional de la Unión Europea ‘Una manera de hacer Europa’, Spain; Centro para el Desarrollo Técnico Industrial (Ref. cvREMOD 2009‐2012) apoyado por el Ministerio de Economia y Competitividad y Fondo de inversión local para el empleo, Spain; Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and Thrasher Research Fund (Salt Lake City, USA)

Evaluation of deep convolutional neural networks for automatic classification of common maternal fetal ultrasound planes

Abstract The goal of this study was to evaluate the maturity of current Deep Learning classification techniques for their application in a real maternal-fetal clinical environment. A large dataset of routinely acquired maternal-fetal screening ultrasound images (which will be made publicly available) was collected from two different hospitals by several operators and ultrasound machines. All images were manually labeled by an expert maternal fetal clinician. Images were divided into 6 classes: four of the most widely used fetal anatomical planes (Abdomen, Brain, Femur and Thorax), the mother’s cervix (widely used for prematurity screening) and a general category to include any other less common image plane. Fetal brain images were further categorized into the 3 most common fetal brain planes (Trans-thalamic, Trans-cerebellum, Trans-ventricular) to judge fine grain categorization performance. The final dataset is comprised of over 12,400 images from 1,792 patients, making it the largest ultrasound dataset to date. We then evaluated a wide variety of state-of-the-art deep Convolutional Neural Networks on this dataset and analyzed results in depth, comparing the computational models to research technicians, which are the ones currently performing the task daily. Results indicate for the first time that computational models have similar performance compared to humans when classifying common planes in human fetal examination. However, the dataset leaves the door open on future research to further improve results, especially on fine-grained plane categorization

Fetal cardiovascular remodelling persists at 6 months of life in infants with intrauterine growth restriction

Objectives Intrauterine growth restriction is associated with increased cardiovascular risk later in life but the link between fetal disease and postnatal risk is not well‐documented. We evaluated longitudinally the association between cardiovascular remodeling in small‐for‐gestational‐age (SGA) fetuses and at 6 months of age. Methods A cohort of 80 SGA fetuses (defined by estimated fetal and birth weights  34 weeks' gestation was compared with 80 normally grown age‐matched control fetuses, with follow‐up at 6 months of corrected age (i.e. 6 months from estimated date of delivery according to first‐trimester crown–rump length). Cardiovascular evaluation included a comprehensive echocardiographic assessment in both fetuses and infants and blood pressure and aortic intima–media thickness (aIMT) measurement in infants. Parameters were adjusted by linear regression analysis for gender, gestational age at delivery, pre‐eclampsia, prenatal glucocorticoid exposure, Cesarean delivery, admission to neonatal intensive care unit and body surface area. Results Both pre‐ and postnatally, when compared with controls, the SGA group showed a more globular cardiac shape (left sphericity index: controls 2.06 vs SGA 1.87 (P = 0.022) prenatally and 1.92 vs 1.67 (P = 0.007) postnatally), as well as signs of systolic longitudinal dysfunction (systolic annular peak velocity (S′): 7.2 vs 6.3 cm/s (P = 0.003) prenatally and 7.9 vs 6.4 cm/s (P < 0.001) postnatally; tricuspid annular plane systolic excursion: 7.2 vs 6.8 mm (P = 0.015) prenatally and 16.0 vs 14.2 mm (P < 0.001) postnatally) and diastolic dysfunction (left isovolumetric relaxation time: 46 vs 52 ms (P < 0.001) prenatally and 50 vs 57 ms (P = 0.034) postnatally). In addition, infants in the SGA group had increased mean blood pressure (mean: 61 vs 70 mmHg, P < 0.001) and maximum aIMT (0.57 vs 0.66 mm; P < 0.001). Conclusions Primary cardiovascular changes are already present in the SGA fetus and persist at 6 months of age. These data support prenatal cardiovascular remodeling as a mechanistic pathway of increased risk later in life in cases of SGA, regardless of Doppler abnormalities.This work was supported by grants from Instituto de Salud Carlos III (grant numbers PI11/00051, PI12/00801, PI11/01709) and from the Ministerio de Economía y Competitividad (grant number SAF2012‐37196), and cofinanced by the Fondo Europeo de Desarrollo Regional de la Unión Europea ‘Una manera de hacer Europa’, Fundación Mutua Madrileña, Fundació Agrupació Premi Àmbit de la Infància (Spain) and Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK). B.V.A. was supported by Programa de Ayudas Postdoctorales FI Agaur (2013FI_B 00667). M.C.L. and B.V.A. wish to express their gratitude to the Mexican National Council of Science and Technology (CONACyT, Mexico City, Mexico) for partially supporting their predoctoral studies at Hospital Clínic, Barcelona, Spain