Neonatal Ventricles Research Articles

New reference nomograms for the study of ventricular size in preterm infants

IntroductionTransfontanellar brain ultrasound is an essential tool for monitoring the size of the ventricles in preterm neonates and has many advantages over other alternative diagnostic techniques, including its accessibility and non-use of ionizing radiation. When considering the normal ventricular size, it is essential to have reference measurements based on age-matched populations. The objective of this article is to present our reference measures, based on a sample of preterm infants that we have studied. MethodsA retrospective observational study was conducted. Measurements of the Levene index, frontal horn thickness, and Evans index were obtained in preterm neonates from 25 to 45 weeks, over a period of 5 years, between January 2016 and December 2020. After applying the exclusion criteria, a sample of 199 patients and 350 ultrasound scans were obtained. The independent samples t-test and the Mann–Whitney test were used for the comparison of samples. ResultsThe distribution of the right and left Levene indices was normal (Shapiro–Wilk test with p = 0.16 and 0.05, respectively), unlike the thickness distribution of the frontal horns (p < 0.05 on both sides). No significant differences were detected between the sexes (p = 0.08). A linear correlation was found between the biparietal diameter and the Levene index. ConclusionFrom the results obtained in our study, we present reference tables for ventricular size, with the 3rd, 25th, 50th, 75th, and 97th, being the first ones made in our country.

Semi-supervised learning framework with shape encoding for neonatal ventricular segmentation from 3D ultrasound.

Three-dimensional (3D) ultrasound (US) imaging has shown promise in non-invasive monitoring of changes in the lateral brain ventricles of neonates suffering from intraventricular hemorrhaging. Due to the poorly defined anatomical boundaries and low signal-to-noise ratio, fully supervised methods for segmentation of the lateral ventricles in 3D US images require a large dataset of annotated images by trained physicians, which is tedious, time-consuming, and expensive. Training fully supervised segmentation methods on a small dataset may lead to overfitting and hence reduce its generalizability. Semi-supervised learning (SSL) methods for 3D US segmentation may be able to address these challenges but most existing SSL methods have been developed for magnetic resonance or computed tomography (CT) images. To develop a fast, lightweight, and accurate SSL method, specifically for 3D US images, that will use unlabeled data towards improving segmentation performance. We propose an SSL framework that leverages the shape-encoding ability of an autoencoder network to enforce complex shape and size constraints on a 3D U-Net segmentation model. The autoencoder created pseudo-labels, based on the 3D U-Net predicted segmentations, that enforces shape constraints. An adversarial discriminator network then determined whether images came from the labeled or unlabeled data distributions. We used 887 3D US images, of which 87 had manually annotated labels and 800 images were unlabeled. Training/validation/testing sets of 25/12/50, 25/12/25 and 50/12/25 images were used for model experimentation. The Dice similarity coefficient (DSC), mean absolute surface distance (MAD), and absolute volumetric difference (VD) were used as metrics for comparing to other benchmarks. The baseline benchmark was the fully supervised vanilla 3D U-Net while dual task consistency, shape-aware semi-supervised network, correlation-aware mutual learning, and 3D U-Net Ensemble models were used as state-of-the-art benchmarks with DSC, MAD, and VD as comparison metrics. The Wilcoxon signed-rank test was used to test statistical significance between algorithms for DSC and VD with the threshold being p<0.05 and corrected to p<0.01 using the Bonferroni correction. The random-access memory (RAM) trace and number of trainable parameters were used to compare the computing efficiency between models. Relative to the baseline 3D U-Net model, our shape-encoding SSL method reported a mean DSC improvement of 6.5%, 7.7%, and 4.1% with a 95% confidence interval of 4.2%, 5.7%, and 2.1% using image data splits of 25/12/50, 25/12/25, and 50/12/25, respectively. Our method only used a 1GB increase in RAM compared to the baseline 3D U-Net and required less than half the RAM and trainable parameters compared to the 3D U-Net ensemble method. Based on our extensive literature survey, this is one of the first reported works to propose an SSL method designed for segmenting organs in 3D US images and specifically one that incorporates unlabeled data for segmenting neonatal cerebral lateral ventricles. When compared to the state-of-the-art SSL and fully supervised learning methods, our method yielded the highest DSC and lowest VD while being computationally efficient.

Nuevos normogramas de referencia para el estudio de la talla ventricular en neonatos pretérmino

IntroductionTransfontanellar brain ultrasound is an essential tool for monitoring the size of the ventricles in preterm neonates and has many advantages over other alternative diagnostic techniques, including its accessibility and non-use of ionizing radiation. When considering the normal ventricular size, it is essential to have reference measurements based on age-matched populations. The objective of this article is to present our reference measures, based on a sample of preterm infants that we have studied. MethodsA retrospective observational study was conducted. Measurements of the Levene index, frontal horn thickness, and Evans index were obtained in preterm neonates from 25 to 45 weeks, over a period of 5 years, between January 2016 and December 2020. After applying the exclusion criteria, a sample of 199 patients and 350 ultrasound scans were obtained. The independent samples t-test and the Mann–Whitney test were used for the comparison of samples. ResultsThe distribution of the right and left Levene indices was normal (Shapiro–Wilk test with p = 0.16 and 0.05, respectively), unlike the thickness distribution of the frontal horns (p < 0.05 on both sides). No significant differences were detected between the sexes (p = 0.08). A linear correlation was found between the biparietal diameter and the Levene index. ConclusionFrom the results obtained in our study, we present reference tables for ventricular size, with the 3rd, 25th, 50th, 75th, and 97th, being the first ones made in our country.

The impact of perinatal factors on the neonatal electrocardiogram

Abstract Background Myocardial development is still incomplete by the time of birth making the cardiomyocyte vulnerable in the perinatal period. However, little is known on whether perinatal factors affect the neonatal electrocardiogram, and if so, to what degree these effects persist in the neonatal period. Purpose To investigate the impact of maternal and perinatal factors on the neonatal electrocardiogram in a large unselected cohort of neonates. Methods In a multicentre, prospective, population-based cohort study, neonates underwent cardiac evaluation during the first month of life. Electrocardiograms and echocardiograms were obtained and systematically analysed. Medical and demographic information on the parents, pregnancy, and birth-related factors were registered, and the following perinatal risk factors were evaluated: maternal comorbidities, maternal BMI ≥25, use of assisted reproduction technology, parity, (preterm) premature rupture of membranes, placental disorders, abnormal foetus presentation, induction of labour with synthetic hormone, instrumental induction, administration of nitrous oxide, epidural/spinal administration, labour ≥24h, pushing stage ≥1h, Caesarean section, and instrumental delivery. Results A total of 15,928 singletons with normal echocardiograms were included (52% boys; median age at examination 11 days). The neonates were divided into groups by accumulated number of perinatal risk factors: 0 (n=1,587), 1 (n=3,718), 2 (n=4,026), 3–4 (n=4,998), and ≥5 (n=1,197), and differences in ECG parameters between the groups were analysed. Heart rate, QRS axis, uncorrected QT interval, QTcBazett, QTcFridericia, and maximum amplitudes in R-V1 and R-V6 differed across the five subgroups (all p&amp;lt;0.05). We observed a cumulative effect of perinatal risk factors on ECG parameters with increasing left-shift in the QRS axis, prolongation of the QT interval, and increasing amplitudes in R-V1 and R-V6. The subgroup with ≥5 perinatal risk factors differed the most, and absolute differences between this subgroup and neonates without any perinatal risk factors were 7.6% in maximum amplitudes in R-V6 (940 vs. 874 μV, p&amp;lt;0.01), 4.3% in R-V1 (1,201 vs. 1,152 μV, p&amp;lt;0.05), 5.1% in the QRS axis (111 vs 117°, p&amp;lt;0.0001) and 0.8% in QTcFridericia (366 vs. 363 ms, p&amp;lt;0.01). Conclusion We observed a cumulative effect of perinatal risk factors including a significantly more left-shifted QRS axis, increased values of the QT interval, and higher amplitudes in R-V1 and R-V6 in the subgroup with ≥5 perinatal risk factors. These findings suggest a relatively lower right ventricular dominance pattern, discrete prolongation of the QT interval and increased myocardial mass of the right ventricle in neonates exposed to multiple perinatal risk factors. However, the absolute differences in ECG parameters were relatively small. These findings may be useful for identification of neonates with increased cardiovascular risk. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Department of Cardiology, Herlev-Gentofte Hospital, Internal Funding

Investigating the Paracrine Role of Perinatal Derivatives: Human Amniotic Fluid Stem Cell-Extracellular Vesicles Show Promising Transient Potential for Cardiomyocyte Renewal.

Cardiomyocyte renewal represents an unmet clinical need for cardiac regeneration. Stem cell paracrine therapy has attracted increasing attention to resurge rescue mechanisms within the heart. We previously characterized the paracrine effects that human amniotic fluid–derived stem cells (hAFSC) can exert to provide cardioprotection and enhance cardiac repair in preclinical models of myocardial ischemia and cardiotoxicity. Here, we analyze whether hAFSC secretome formulations, namely, hAFSC conditioned medium (hAFSC-CM) over extracellular vesicles (hAFSC-EVs) separated from it, can induce cardiomyocyte renewal. c-KIT+ hAFSC were obtained by leftover samples of II trimester prenatal amniocentesis (fetal hAFSC) and from clinical waste III trimester amniotic fluid during scheduled C-section procedures (perinatal hAFSC). hAFSC were primed under 1% O2 to enrich hAFSC-CM and EVs with cardioactive factors. Neonatal mouse ventricular cardiomyocytes (mNVCM) were isolated from cardiac tissue of R26pFUCCI2 mice with cell cycle fluorescent tagging by mutually exclusive nuclear signal. mNVCM were stimulated by fetal versus perinatal hAFSC-CM and hAFSC-EVs to identify the most promising formulation for in vivo assessment in a R26pFUCCI2 neonatal mouse model of myocardial infarction (MI) via intraperitoneal delivery. While the perinatal hAFSC secretome did not provide any significant cardiogenic effect, fetal hAFSC-EVs significantly sustained mNVCM transition from S to M phase by 2-fold, while triggering cytokinesis by 4.5-fold over vehicle-treated cells. Treated mNVCM showed disorganized expression of cardiac alpha-actinin, suggesting cytoskeletal re-arrangements prior to cell renewal, with a 40% significant downregulation of Cofilin-2 and a positive trend of polymerized F-Actin. Fetal hAFSC-EVs increased cardiomyocyte cell cycle progression by 1.8-fold in the 4-day-old neonatal left ventricle myocardium short term after MI; however, such effect was lost at the later stage. Fetal hAFSC-EVs were enriched with a short isoform of Agrin, a mediator of neonatal heart regeneration acting by YAP-related signaling; yet in vitro application of YAP inhibitor verteporfin partially affected EV paracrine stimulation on mNVCM. EVs secreted by developmentally juvenile fetal hAFSC can support cardiomyocyte renewal to some extension, via intercellular conveyance of candidates possibly involving Agrin in combination with other factors. These perinatal derivative promising cardiogenic effects need further investigation to define their specific mechanism of action and enhance their potential translation into therapeutic opportunity.

Abstract 9815: Role for Btg1 and Btg2 in Postnatal Cardiomyocyte Cell Cycle Arrest and Maturation

Background: Adult mammalian cardiomyocytes (CM) are predominantly post-mitotic and cannot proliferatively repair the heart following myocardial infarction (MI). Overexpression of the transcription factor Tbx20 in adult mouse CMs promotes proliferative cardiac repair post-MI, via mechanisms including direct repression of anti-proliferative genes p21 , Meis1 , and Btg2 . Btg2 (B-cell translocation gene 2), a tumor suppressor and transcriptional co-regulator, exhibits high structural and functional similarity with Btg1. However, both Btg1 and Btg2 (Btg1/2) are virtually uncharacterized in the heart. Here, we investigate the role of Btg1/2 in postnatal cardiac maturation. Methods and Results: By immunostaining in embryonic, neonatal, and adult C57BL/6 mouse hearts, the highest expression of Btg1/2 was observed in late fetal and early neonatal ventricles, concurrent with upregulation of other CM cell cycle inhibitors. In neonatal mouse CMs in vitro, siRNA-mediated loss of Btg2 leads to increased CM proliferation. In vivo , Btg1/2 constitutive single- and double- knockout (SKO and DKO respectively) mice exhibit normal heart weight-to-body weight ratios compared to age-matched wildtype (WT) controls, at postnatal day (P)7, P30, and 1 year after birth. Interestingly, at P7, DKO mice have significantly higher CM mitotic activity, as indicated by pHH3 staining, compared to WT. In addition, DKO mice also exhibit significantly smaller CM cross-sectional area at P7 compared to WT. However, by P15, CM mitotic activity and cell size are comparable between WT and Btg1/2 KO mice. Currently, siRNA-mediated knockdown of Btg1/2 in neonatal rat ventricular cardiomyocyte cultures and RNAseq studies are being performed, to assess the transcriptional regulatory roles of Btg1/2 in rodent CMs. Conclusions: Here, we highlight two novel regulators of postnatal CM maturation, Btg1 and Btg2, which are upregulated coincident with CM mitotic arrest in mice. Similar to p21 and Meis1, Btg1/2 depletion in mice induces a brief period of increased CM proliferative activity before onset of CM cell cycle arrest. Our results provide evidence for Btg1/2 working in tandem with other cardiac transcription factors and cell cycle regulators, to control CM mitotic arrest after birth.

Abstract P448: Role For Btg1 And Btg2 In Postnatal Cardiomyocyte Cell Cycle Arrest And Maturation

Background: Adult mammalian cardiomyocytes (CM) are predominantly post-mitotic and cannot proliferatively repair the heart following myocardial infarction (MI). Overexpression of the transcription factor Tbx20 in adult mouse CMs promotes proliferative cardiac repair post-MI, via mechanisms including direct repression of anti-proliferative genes p21 , Meis1 , and Btg2 . Btg2 (B-cell translocation gene 2), a tumor suppressor and transcriptional co-regulator, exhibits high structural and functional similarity with Btg1. However, both Btg1 and Btg2 (Btg1/2) are virtually uncharacterized in the heart. Here, we investigate the role of Btg1/2 in postnatal cardiac maturation. Methods and Results: By immunostaining in embryonic, neonatal, and adult C57BL/6 mouse hearts, the highest expression of Btg1/2 was observed in late fetal and early neonatal ventricles, concurrent with upregulation of other CM cell cycle inhibitors. In neonatal mouse CMs in vitro, siRNA-mediated loss of Btg2 leads to increased CM proliferation. In vivo , Btg1/2 constitutive single- and double- knockout (SKO and DKO respectively) mice exhibit normal heart weight-to-body weight ratios compared to age-matched wildtype (WT) controls, at postnatal day (P)7, P30, and 1 year after birth. Interestingly, at P7, DKO mice have significantly higher CM mitotic activity, as indicated by pHH3 staining, compared to WT. In addition, DKO mice also exhibit significantly smaller CM cross-sectional area at P7 compared to WT. However, by P15, CM mitotic activity and cell size are comparable between WT and Btg1/2 KO mice. Currently, siRNA-mediated knockdown of Btg1/2 in neonatal rat ventricular cardiomyocyte cultures and RNAseq studies are being performed, to assess the transcriptional regulatory roles of Btg1/2 in rodent CMs. Conclusions: Here, we highlight two novel regulators of postnatal CM maturation, Btg1 and Btg2, which are upregulated coincident with CM mitotic arrest in mice. Similar to p21 and Meis1, Btg1/2 depletion in mice induces a brief period of increased CM proliferative activity before onset of CM cell cycle arrest. Our results provide evidence for Btg1/2 working in tandem with other cardiac transcription factors and cell cycle regulators, to control CM mitotic arrest after birth.

Effect of Phototherapy on Cardiac Functions in Neonates with Hyperbilirubinemia. A Prospective Cross-Sectional Study

Background: Phototherapy has been reported to alter cardiovascular function by causing increased peripheral blood flow, diminished cardiac output and increased sympathetic activity that may be of concern, particularly in neonates with hyperbilirubinemia. Aim of work: To assess the myocardial function in neonates with hyperbilirubinemia by using echocardiography, especially tissue Doppler imaging (TDI). Patients and Methods: It was a prospective, cross- sectional study. All participants in this study were full-terms and appropriate for gestational age newborns with hyperbilirubinemia who received phototherapy for jaundice (bilirubin level greater than 15 mg/dl). Myocardial functions were assessed using conventional echocardiography and tissue Doppler imaging techniques. Results: The study population consisted of 110 neonates with hyperbilirubinemia; their mean gestational age was 38.8 ± 1.7 weeks and mean birth weight 2785 ± 652 g. After phototherapy, respiratory rate and heart rate were faster whereas oxygen saturation and systolic blood pressure were lower (p 0.05). Pulsed wave Doppler parameters showed no significant difference in the mitral E velocity, mitral A velocity, and E/A ratio (p > 0.05). Conclusion:Phototherapy had no adverse effects on either systolic or diastolic function of the left ventricle in term neonates with indirect hyperbilirubinemia.

Research on ARKFCM Algorithm Based on Membership Constraint and Bias Field Correction in Neonatal HIE Image Segmentation Method

First, this paper presents the algorithm of adaptively regularized kernel-based fuzzy C-means based on membership constraint (G-ARKFCM). Under the idea of competitive learning based on penalizing opponents, a new membership constraint function penalty item is introduced for each sample point in the segmented image, so that the ARKFCM algorithm is no longer limited to the fuzzy index m = 2. Secondly, the multiplicative intrinsic component optimization (MICO) is introduced into G-ARKFCM to obtain the GM-ARKFCM algorithm, which can correct the bias field when segmenting neonatal HIE images. Compared with other algorithms, the GM-ARKFCM algorithm has better segmentation quality and robustness. The GM-ARKFCM algorithm can more completely segment the neonatal ventricles and surrounding white matter and can retain more information of the original image.

PSMB4 inhibits cardiomyocyte apoptosis via activating NF-κB signaling pathway during myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion (I/R) injury induces cardiomyocyte apoptosis to deteriorate heart function. Thus, how to inhibit cardiomyocyte apoptosis is the focus of recent researches. Proteasome family member PSMB4 (proteasome subunit beta type-4) promotes cell survival. The relationship between PSMB4 and cardiomyocyte apoptosis during myocardial I/R is unknown. In this study, PSMB4 expression increased in rat myocardial I/R model, positively correlated with cleaved caspase-3 expression, negatively correlated with Bcl-2 expression. In vitro, neonatal ventricle cardiomyocyte hypoxia/reoxygenation (H/R) model was constructed to mimic myocardial I/R. PSMB4 silence promoted cardiomyocyte apoptosis and IκBα expression, inhibited the activation of NF-κB. On the contrary, PSMB4 overexpession inhibited cardiomyocyte apoptosis and IκBα expression, promoted the activation of NF-κB. Additionally, PSMB4-IκBα interaction was identified, suggesting that PSMB4 might participate in the proteasome dependent degradation of IκBα. The data indicates that PSMB4 inhibits cardiomyocyte apoptosis via activating NF-κB signaling pathway during myocardial I/R, which can supply novel molecular target for the treatment of ischemic heart disease.

Abstract 13391: Cardiomyocyte Cell Cycling, Maturation, and Growth by Multinucleation in Postnatal Swine

Background: Rodent cardiomyocytes (CM) undergo mitotic arrest and decline of mononucleated-diploid population post-birth, which are implicated in neonatal loss of heart regenerative potential. However, the dynamics of postnatal CM maturation are largely unknown in swine, despite a similar neonatal cardiac regenerative capacity as rodents. Here, we provide a comprehensive analysis of postnatal cardiac maturation in swine, including CM cell cycling, multinucleation and hypertrophic growth, as well as non-CM cardiac factors such as extracellular matrix (ECM), immune cells, capillaries, and neurons. Our study reveals discordance in postnatal pig heart maturational events compared to rodents. Methods and Results: Left-ventricular myocardium from White Yorkshire-Landrace pigs at postnatal day (P)0 to 6 months (6mo) was analyzed. Mature cardiac sarcomeric characteristics, such as fetal TNNI1 repression and CX43 co-localization to cell junctions, were not evident until P30 in pigs. In CMs, appreciable binucleation is observed by P7, with extensive multinucleation (4-16 nuclei per CM) beyond P15. Individual CM nuclei remain predominantly diploid at all ages. CM mononucleation at ~50% incidence is observed at P7-P15, and CM mitotic activity is measurable up to 2mo. CM cross-sectional area does not increase until 2mo-6mo in pigs, though longitudinal CM growth proportional to multinucleation occurs after P15. RNAseq analysis of neonatal pig left ventricles showed increased expression of ECM maturation, immune signaling, neuronal remodeling, and reactive oxygen species response genes, highlighting significance of the non-CM milieu in postnatal mammalian heart maturation. Conclusions: CM maturational events such as decline of mononucleation and cell cycle arrest occur over a 2-month postnatal period in pigs, despite reported loss of heart regenerative potential by P3. Moreover, CMs grow primarily by multinucleation and longitudinal hypertrophy in older pigs, distinct from mice and humans. These differences are important to consider for preclinical testing of cardiovascular therapies using swine, and may offer opportunities to study aspects of heart regeneration unavailable in other models.

The Relationship Between Clinical Imaging and Neurobehavioral Assessment in Posthemorrhagic Ventricular Dilation of Prematurity.

Introduction: Neonatal intraventricular hemorrhage (IVH) and subsequent posthemorrhagic ventricular dilation and hydrocephalus of prematurity are associated with brain injury and neurodevelopmental impairment in the preterm population. Neuroimaging assesses cerebral injury and guides neurosurgical intervention; however, the relationship of head ultrasound (HUS) and magnetic resonance imaging (MRI) parameters to neonatal exams in this group has not been well described. The NICU Network Neurobehavioral Scale (NNNS) is a reproducible, highly reliable battery with motor and cognitive domain scores.Objective: To evaluate the relationship between neonatal neurobehavioral findings on the NNNS and measures of ventricular dilation and associated brain injury on HUS and MRI.Materials and Methods: Neonates with IVH and ventricular dilatation with and without posthemorrhagic hydrocephalus were enrolled. NNNS exams were performed at approximately term age equivalent. HUS indices were measured on the last HUS before initial neurosurgical procedure or that with worst ventriculomegaly if no intervention. The posterior fossa was assessed with MRI at term. Descriptive statistics including medians, interquartile ranges, means, and percentages were performed. Correlations were estimated using Pearson's method.Results: 28 patients had NNNS and HUS, and 18 patients also had an MRI. Ventricle size measures for the cohort were significantly above normal. Motor and cognitive subscores on the NNNS exam varied from established baseline scores for postmenstrual age. Children who required neurosurgical intervention had higher ventricle/brain ratios and worse NNNS habituation scores. Ventricle sizes were modestly correlated with motor abnormalities (0.24–0.59); larger anterior horn width correlated with nonoptimal reflexes, hypertonicity and hypotonicity. Ventricle sizes were modestly correlated with cognitive scores (−0.44 to 0.27); larger ventricular index correlated with worse attention. Periventricular hemorrhagic infarction correlated with worse habituation.Conclusion: For this cohort of preterm infants with IVH, surgical intervention for posthemorrhagic hydrocephalus correlated with both larger degrees of ventriculomegaly and worse NNNS exams. Findings on both HUS and MRI correlated with motor and cognitive abnormalities on neonatal neurobehavioral exam, suggesting that larger neonatal ventricle sizes and white matter injury have detectable correlates on exam. The NNNS exam provides important additional information when assessing posthemorrhagic ventricular dilation and hydrocephalus of prematurity.

Use of prostaglandin E1 to treat pulmonary hypertension in congenital diaphragmatic hernia

Background/PurposeProstaglandin E1 (PGE) has been used to maintain ductus arteriosus patency and unload the suprasystemic right ventricle (RV) in neonates with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension (PH). Here we evaluate the PH response in neonates with CDH and severe PH treated with PGE. MethodsWe performed a retrospective chart review of CDH infants treated at our center between 2011 and 2016. In a subset, PGE was initiated for echocardiographic evidence of severe PH, metabolic acidosis, or hypoxemia. To assess PH response, we evaluated laboratory data, including B-type natriuretic peptide (BNP) and echocardiograms before and after PGE treatment. Categorical and continuous data were analyzed with Fisher's exact tests and Mann–Whitney t-tests, respectively. ResultsFifty-seven infants were treated with PGE a mean 17 ± 2 days. BNP levels declined after 1.4 ± 0.2 days of treatment and again after 5.2 ± 0.6 days. After 6 ± 0.8 days of treatment, echocardiographic estimates of severe PH by tricuspid regurgitation jet velocity, ductus arteriosus direction, and ventricular septum position also improved significantly. Treatment was not associated with postductal hypoxemia or systemic hypoperfusion. ConclusionsIn patients with CDH and severe PH, PGE is well tolerated and associated with improved BNP and echocardiographic indices of PH, suggesting successful unloading of the RV. Type of studyTreatment study. Level of evidenceLevel III.

Automatic Segmentation of Neonatal Ventricles from Cranial Ultrasound for Prediction of Intraventricular Hemorrhage Outcome.

Intraventricular hemorrhage (IVH) followed by post hemorrhagic hydrocephalus (PHH) in premature neonates is one of the recognized reasons of brain injury in newborns. Cranial ultrasound (CUS) is a noninvasive imaging tool that has been used widely to diagnose and monitor neonates with IVH. In our previous work, we showed the potential of quantitative morphological analysis of lateral ventricles from early CUS to predict the PHH outcome in neonates with IVH. In this paper, we first present a new automatic method for ventricle segmentation in 2D CUS images. We detect the brain bounding box and brain mid-line to estimate the anatomical positions of ventricles and correct the brain rotation. The ventricles are segmented using a combination of fuzzy c-means, phase congruency, and active contour algorithms. Finally, we compare this fully automated approach with our previous work for the prediction of the outcome of PHH on a set of 2D CUS images taken from 60 premature neonates with different IVH grades. Experimental results showed that our method could segment ventricles with an average Dice similarity coefficient of 0.8 ± 0.12. In addition, our fully automated method could predict the outcome of PHH based on the extracted ventricle regions with similar accuracy to our previous semi-automated approach (83% vs. 84%, respectively, p-value = 0.8). This method has the potential to standardize the evaluation of CUS images and can be a helpful clinical tool for early monitoring and treatment of IVH and PHH.

Normal Reference Range of Lateral Ventricle Parameters in Preterm Neonates by Ultrasonography

Background: Cranial ultrasound is considered as the method of choice for early evaluation of neonatal ventricular system. Since premature neonates are susceptible to intra-ventricular hemorrhage and hydrocephaly, it is essential to have normal values of parameters as reference ranges. Objectives: To provide native information of ventricular sizes in normal premature infants in our area for screening policy. Methods: This Multicenter prospective study was conducted on normal premature babies with a gestational age of 26 to 35 weeks, from February to September 2014, in the South of Iran. Patients were divided into 10 groups according to their weeks of gestational age and each group was separately studied during the first 3 days of life. Statistical package for the Social Sciences version 16.0 software package [SPSS Inc, Chicago, Illinois] was used for statistical analysis. Continuous variables were described by mean with standard deviations (SD) and categorical variables by numbers and percentage appropriately. A 95% confidence interval was supposed for all ventricular parameters (5, 50 and 95 percentile). Each parameter that was above the 95 percentile for GA or birth weight was considered abnormal. Comparison between groups was done by Pearson correlation and Mann-Whitney and Wilcoxon Signed Ranks tests as appropriate. P value ≤ 0.05 was regarded as statistically significant. Results: 177 premature neonates were evaluated. The mean of ventricular index was 11.7 mm ± 1.5 SD. The mean of anterior horn width and thalamo-occipital distance were 1.8 mm ± 0.7 SD and 15 mm ± 2.7 SD, respectively. Ventricular index was gradually increased as the gestational age and birth weight increased, however, there was no obvious relationship between these and 2 other dimensions. There was no significant difference in dimensions between boys and girls, and also between normal vaginal delivery and cesarean section. Conclusions: This study provides native normal reference values for lateral ventricular size in preterm infants in Iran. It helps physicians better understand the normal and abnormal size of the lateral ventricle in preterm neonates and improves both early diagnostic and therapeutic approaches.

Longitudinal Analysis of Pre-Term Neonatal Cerebral Ventricles From 3D Ultrasound Images Using Spatial-Temporal Deformable Registration.

Preterm neonates with a very low birth weight of less than 1,500 grams are at increased risk for developing intraventricular hemorrhage (IVH), which is a major cause of brain injury in preterm neonates. Quantitative measurements of ventricular dilatation or shrinkage play an important role in monitoring patients and evaluating treatment options. 3D ultrasound (US) has been developed to monitor ventricle volume as a biomarker for ventricular changes. However, ventricle volume as a global indicator does not allow for precise analysis of local ventricular changes, which could be linked to specific neurological problems often seen in the patient population later in life. In this work, a 3D+t spatial-temporal deformable registration approachis proposed, which is applied to the analysis of the detailed local changes of preterm IVH neonatal ventricles from 3D US images. In particular, a novel sequential convex/dual optimization algorithm is introduced to extract the optimal 3D+t spatial-temporal deformable field, which simultaneously optimizes the sequence of 3D deformation fieldswhile enjoying both efficiencyand simplicity in numerics. The developed registration technique was evaluated by comparing two manually extracted ventricle surfaces from the baseline and the registered follow-up images using the metrics of Dice similarity coefficient (DSC), mean absolute surface distance (MAD), and maximum absolute surface distance (MAXD). The performed experiments using 14 patients with 5 time-point images per patient show that the proposed 3D+t registration approach accurately recovered the longitudinal deformation of ventricle surfaces from 3D US images. The proposed approach may be potentially used to analyse the change pattern of cerebral ventricles of IVH patients, their response to different treatment options, and to elucidate the deficiencies that a patient could have later in life. To the best of our knowledge, this paper reports the first study on the longitudinalanalysis of neonatal ventricular system from 3D US images.

Bailout shunt/banding for backward left heart failure after adequate neonatal coarctectomy in borderline left hearts.

To determine the outcome of a bailout procedure using the right ventricle to re-assist the left ventricle in neonates after technically adequate coarctectomy but a failing borderline left heart. The surgical procedure was performed on bypass. A 'reversed' 6-mm surgical shunt was inserted between the pulmonary trunk and the descending aorta together with bilateral branch pulmonary artery banding. Over a 10-year period, 89 neonates presented with coarctation and small left hearts. In 9 neonates, a hybrid procedure was performed at the outset. The remaining 80 underwent extended end-to-end coarctectomy. Two of these, despite adequate coarctectomy, developed retrograde cardiac failure with supra-systemic pulmonary hypertension, dilating right ventricles and progressive cardiogenic shock. The progressively dilating right ventricles inhibited left ventricular filling. Reversed surgical shunts were performed at 9 and 7 days post-coarctectomy. Both infants recovered rapidly and could be extubated after 4 and 7 days, respectively. Patient 1 proceeded to a univentricular repair and Patient 2 to a biventricular repair. Reversed surgical shunt with bilateral banding of the branch pulmonary arteries after neonatal coarctectomy can be successfully employed as a bailout procedure in cases where a borderline left heart with growth potential cannot tolerate a biventricular circulation. It may act as an acute life-saving measure as well as a bridge to later repair. If high risk for backward failure exists in a borderline left heart with catch-up growth potential, a primary hybrid procedure is probably a more elegant and predictable strategy.

Automatic segmentation approach to extracting neonatal cerebral ventricles from 3D ultrasound images.

Preterm neonates with a very low birth weight of less than 1,500g are at increased risk for developing intraventricular hemorrhage (IVH). Progressive ventricle dilatation of IVH patients may cause increased intracranial pressure, leading to neurological damage, such as neurodevelopmental delay and cerebral palsy. The technique of 3D ultrasound (US) imaging has been used to quantitatively monitor the ventricular volume in IVH neonates, which may elucidate the ambiguity surrounding the timing of interventions in these patients as 2D clinical US imaging relies on linear measurement and visual estimation of ventricular dilation from a series of 2D slices. To translate 3D US imaging into the clinical setting, a fully automated segmentation algorithm is necessary to extract the ventricular system from 3D neonatal brain US images. In this paper, an automatic segmentation approach is proposed to delineate lateral ventricles of preterm neonates from 3D US images. The proposed segmentation approach makes use of phase congruency map, multi-atlas initialization technique, atlas selection strategy, and a multiphase geodesic level-sets (MGLS) evolution combined with a spatial shape prior derived from multiple pre-segmented atlases. Experimental results using 30 IVH patient images show that the proposed GPU-implemented approach is accurate in terms of the Dice similarity coefficient (DSC), the mean absolute surface distance (MAD), and maximum absolute surface distance (MAXD). To the best of our knowledge, this paper reports the first study on automatic segmentation of the ventricular system of premature neonatal brains from 3D US images.

In Vivo Validation of a 3-D Ultrasound System for Imaging the Lateral Ventricles of Neonates

Intra-ventricular hemorrhage, with the resultant cerebral ventricle dilation, is a common cause of brain injury in preterm neonates. Clinically, monitoring is performed using 2-D ultrasound (US); however, its clinical utility in dilation is limited because it cannot provide accurate measurements of irregular volumes such as those of the ventricles, and this might delay treatment until the patient's condition deteriorates severely. We have developed a 3-D US system to image the lateral ventricles of neonates within the confines of incubators. We describe an in vivo ventricle volume validation study in two parts: (i) comparisons between ventricle volumes derived from 3-D US and magnetic resonance images obtained within 24 h; and (ii) the difference between 3-D US ventricle volumes before and after clinically necessary interventions (ventricle taps), which remove cerebral spinal fluid. Magnetic resonance imaging ventricle volumes were found to be 13% greater than 3-D US ventricle volumes; however, we observed high correlations (R2 = 0.99) when comparing the two modalities. Differences in ventricle volume pre- and post-intervention compared with the reported volume of cerebrospinal fluid removed also were highly correlated (R2 = 0.93); the slope was not found to be statistically significantly different from 1 (p < 0.05), and the y-intercept was not found to be statistically different from 0 (p < 0.05). Comparison between 3-D US images can detect the volume change after neonatal intra-ventricular hemorrhage. This could be used to determine which patients will have progressive ventricle dilation and allow for more timely surgical interventions. However, 3-D US ventricle volumes should not be directly compared with magnetic resonance imaging ventricle volumes.

Abnormal Ventricular Development in Preterm Neonates with Visually Normal MRIs.

Children born preterm are at risk for a wide range of neurocognitive and neurobehavioral disorders. Some of these may stem from early brain abnormalities at the neonatal age. Hence, a precise characterization of neonatal neuroanatomy may help inform treatment strategies. In particular, the ventricles are often enlarged in neurocognitive disorders, due to atrophy of surrounding tissues. Here we present a new pipeline for the detection of morphological and relative pose differences in the ventricles of premature neonates compared to controls. To this end, we use a new hyperbolic Ricci flow based mapping of the ventricular surfaces of each subjects to the Poincaré disk. Resulting surfaces are then registered to a template, and a between group comparison is performed using mulitvariate tensor-based morphometry. We also statistically compare the relative pose of the ventricles within the brain between the two groups, by performing a Procrustes alignment between each subject's ventricles and an average shape. For both types of analyses, differences were found in the left ventricles between the two groups.