CT dose reduction factors in the thousands using X-ray phase contrast

Phase-contrast X-ray imaging can improve the visibility of weakly absorbing objects (e.g. soft tissues) by an order of magnitude or more compared to conventional radiographs. Previously, it has been shown that combining phase retrieval with computed tomography (CT) can increase the signal-to-noise ratio (SNR) by up to two orders of magnitude over conventional CT at the same radiation dose, without loss of image quality. Our experiments reveal that as radiation dose decreases, the relative improvement in SNR increases. We discovered this enhancement can be traded for a reduction in dose greater than the square of the gain in SNR. Upon reducing the dose 300 fold, the phase-retrieved SNR was still almost 10 times larger than the absorption contrast data. This reveals the potential for dose reduction factors in the tens of thousands without loss in image quality, which would have a profound impact on medical and industrial imaging applications

Comparison of Two Respiratory Support Strategies for Stabilization of Very Preterm Infants at Birth: A Matched-Pairs Analysis

Objective: Respiratory support for stabilizing very preterm infants at birth varies between centers. We retrospectively compared two strategies that involved either increasing continuous positive airway pressures (CPAP), or increasing oxygen supplementation.Methods: Matched-pairs of infants (<28 weeks of gestation) were born either at the Leiden University Medical Center [low-pressure: CPAP 5–8 cmH2O and/or positive pressure ventilation (PPV) and fraction of inspired oxygen (FiO2) 0.3–1.0; n = 27], or at the University Hospital of Cologne (high-pressure: CPAP 12–35 cmH2O, no PPV and FiO2 0.3–0.4; n = 27). Respiratory support was initiated non-invasively via facemask at both units. Infants (n = 54) were matched between centers for gestational age and birth weight, to compare physiological and short-term clinical outcomes.Results: In the low-pressure group, 20/27 (74%) infants received 1–2 sustained inflations (20, 25 cm H2O) and 22/27 (81%) received PPV (1:19–3:01 min) using pressures of 25–27 cm H2O. Within 3 min of birth [median (IQR)], mean airway pressures [12 (6–15) vs. 19 (16–23) cmH2O, p < 0.001] and FiO2 [0.30 (0.28–0.31) vs. 0.22 (0.21–0.30), p < 0.001] were different in low- vs. high-pressure groups, respectively. SpO2 and heart rates were similar. After 3 min, higher FiO2 levels [0.62 (0.35–0.98) vs. 0.28 (0.22–0.38), p = 0.005] produced higher SpO2 levels [77 (50–92) vs. 53 (42–69)%, p < 0.001] in the low-pressure group, but SpO2/FiO2 and heart rates were similar. While intubation rates during admission were significantly different (70 vs. 30%, p = 0.013), pneumothorax rates (4 vs. 19%, p = 0.125) and the occurrence of spontaneous intestinal perforations (0 vs. 15%, p = 0.125) were similar between groups.Conclusion: Infants (<28 weeks) can be supported non-invasively at birth with either higher or lower pressures and while higher-pressure support may require less oxygen, it does not eliminate the need for oxygen supplementation. Future studies need to examine the effect of high pressures and pressure titration in the delivery room

High vs. Low Initial Oxygen to Improve the Breathing Effort of Preterm Infants at Birth: Study Protocol for a Randomized Controlled Trial

Background: Although most preterm infants breathe at birth, their respiratory drive is weak and supplemental oxygen is often needed to overcome hypoxia. This could in turn lead to hyperoxia. To reduce the risk of hyperoxia, currently an initial low oxygen concentration (21–30%) is recommended during stabilization at birth, accepting the risk of a hypoxic period. However, hypoxia inhibits respiratory drive in preterm infants. Starting with a higher level of oxygen could lead to a shorter duration of hypoxia by stimulating breathing effort of preterm infants, and combined with subsequent titration based on oxygen saturation, prolonged hyperoxia might be prevented.Study design: This multi-center randomized controlled trial will include 50 infants with a gestational age between 24 and 30 weeks. Eligible infants will be randomized to stabilization with an initial FiO2 of either 1.0 or 0.3 at birth. Hereafter, FiO2 will be titrated based on the oxygen saturation target range. In both groups, all other interventions during stabilization and thereafter will be similar. The primary outcome is respiratory effort in the first 5 min after birth expressed as average minute volume/kg. Secondary outcomes include inspired tidal volumes/kg, rate of rise to maximum tidal volume/kg, percentage of recruitment breaths with tidal volumes above 8 mL/kg, duration of hypoxia and hyperoxia and plasma levels of markers of oxidative stress (8-iso-prostaglandin F2α).Discussion: Current resuscitation guidelines recommend oxygen titration if infants fail to achieve the 25th percentile of the SpO2 reference ranges. It has become clear that, using this approach, most preterm infants are at risk for hypoxia in the first 5 min after birth, which could suppress the breathing effort. In addition, for compromised preterm infants who need respiratory support at birth, higher SpO2 reference ranges in the first minutes after birth might be needed to prevent prolonged hypoxia. Enhancing breathing effort by achieving an adequate level of oxygenation could potentially lead to a lower incidence of intubation and mechanical ventilation in the delivery room, contributing to a lower risk on lung injury in high-risk preterm infants. Measuring 8-iso-prostaglandin F2α could lead to a reflection of the true amount of oxygen exposure in both study groups

Clinical aspects of incorporating cord clamping into stabilisation of preterm infants

Fetal to neonatal transition is characterised by major pulmonary and haemodynamic changes occurring in a short period of time. In the international neonatal resuscitation guidelines, comprehensive recommendations are available on supporting pulmonary transition and delaying clamping of the cord in preterm infants. Recent experimental studies demonstrated that the pulmonary and haemodynamic transition are intimately linked, could influence each other and that the timing of umbilical cord clamping should be incorporated into the respiratory stabilisation. We reviewed the current knowledge on how to incorporate cord clamping into stabilisation of preterm infants and the physiological-based cord clamping (PBCC) approach, with the infant's transitional status as key determinant of timing of cord clamping. This approach could result in optimal timing of cord clamping and has the potential to reduce major morbidities and mortality in preterm infants

Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP): study protocol

Introduction Timing of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons. Objectives (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA. Methods and analysis Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks’ gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored. Ethics and dissemination Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases

Perinatal stabilisation of infants born with congenital diaphragmatic hernia: A review of current concepts

Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs into the chest. Pulmonary hypertension is a major contributor to both mortality and morbidity, however, treatment modalities are limited. Novel prenatal and postnatal interventions, such as fetal surgery and medical treatments, are currently under investigation. Until now, the perinatal stabilisation period immediately after birth has been relatively overlooked, although optimising support in these early stages may be vital in improving outcomes. Moreover, physiological parameters obtained from the perinatal stabilisation period could serve as early predictors of adverse outcomes, thereby facilitating both prevention and early treatment of these conditions. In this review, we focus on the perinatal stabilisation period by discussing the current delivery room guidelines in infants born with CDH, th

Physiological-based cord clamping in very preterm infants — Randomised controlled trial on effectiveness of stabilisation

Aim: To test whether stabilising very preterm infants while performing physiological-based cord clamping (PBCC) is at least as effective as the standard approach of time-based delayed cord clamping (DCC). Methods: A randomised contr

Increasing Respiratory Effort With 100% Oxygen During Resuscitation of Preterm Rabbits at Birth

Background: Spontaneous breathing is essential for successful non-invasive respiratory support delivered by a facemask at birth. As hypoxia is a potent inhibitor of spontaneous breathing, initiating respiratory support with a high fraction of inspired O2 may reduce the risk of hypoxia and increase respiratory effort at birth. Methods: Preterm rabbit kittens (29 days gestation, term ~32 days) were delivered and randomized to receive continuous positive airway pressure with either 21% (n = 12) or 100% O2 (n = 8) via a facemask. If apnea occurred, intermittent positive pressure ventilation (iPPV) was applied with either 21% or 100% O2 in kittens who started in 21% O2, and remained at 100% O2 for kittens who started the experiment in 100% O2. Respiratory rate (breaths per minute, bpm) and variability in inter-breath interval (%) were measured from esophageal pressure recordings and functional residual capacity (FRC) was measured from synchrotron phase-contrast X-ray images. Results: Initially, kittens receiving 21% O2 had a significantly lower respiratory rate and higher variability in inter-breath interval, indicating a less stable breathing pattern than kittens starting in 100% O2 [median (IQR) respiratory rate: 16 (4–28) vs. 38 (29–46) bpm, p = 0.001; variability in inter-breath interval: 33.3% (17.2–50.1%) vs. 27.5% (18.6–36.3%), p = 0.009]. Apnea that required iPPV, was more frequently observed in kittens in whom resuscitation was started with 21% compared to 100% O2 (11/12 vs. 1/8, p = 0.001). After recovering from apnea, respiratory rate was significantly lower and variability in inter-breath interval was significantly higher in kittens who received iPPV with 21% compared to 100% O2. FRC was not different between study groups at both timepoints. Conclusion: Initiating resuscitation with 100% O2 resulted in increased respiratory activity and stability, thereby reducing the risk of apnea and need for iPPV after birth. Further studies in human preterm infants are mandatory to confirm the benefit of this approach in terms of oxygenation. In addition, the ability to avoid hyperoxia after initiation of resuscitation with 100% oxygen, using a titration protocol based on oxygen saturation, needs to be clarified

Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC):study protocol for a multicentre, randomised controlled trial

Introduction Pulmonary hypertension is a majordeterminant of postnatal survival in infants with acongenital diaphragmatic hernia (CDH). The current careduring the perinatal stabilisation period in these infantsmight contribute to the development of pulmonaryhypertension after birth—in particular umbilical cordclamping before lung aeration. An ovine model ofdiaphragmatic hernia demonstrated that cord clampingafter lung aeration, called physiological-based cordclamping (PBCC), avoided the initial high pressures in thelung vasculature while maintaining adequate blood flow,thereby avoiding vascular remodelling and aggravationof pulmonary hypertension. We aim to investigate if theimplementation of PBCC in the perinatal stabilisation periodof infants born with a CDH could reduce the incidence ofpulmonary hypertension in the first 24 hours after birth.Methods and analysis We will perform a multicentre,randomised controlled trial in infants with an isolatedleft-sided CDH, born at ≥35.0 weeks. Before birth, infantswill be randomised to either PBCC or immediate cordclamping, stratified by treatment centre and severity ofpulmonary hypoplasia on antenatal ultrasound. PBCCwill be performed using a purpose- built resuscitationtrolley. Cord clamping will be performed when the infantis considered respiratory stable, defined as a heartrate >100 bpm, preductal oxygen saturation >85%,while using a fraction of inspired oxygen of <0.5. Theprimary outcome is pulmonary hypertension diagnosedin the first 24 hours after birth, based on clinical andechocardiographic parameters. Secondary outcomesinclude neonatal as well as maternal outcomes.Ethics and dissemination Central ethical approvalwas obtained from the Medical Ethical Committee ofthe Erasmus MC, Rotterdam, The Netherlands (METC2019-0414). Local ethical approval will be obtained bysubmitting the protocol to the regulatory bodies and localinstitutional review boards