The effect of vibrotactile stimulation on hypoxia-induced irregular breathing and apnea in preterm rabbits.

BACKGROUND: Manual tactile stimulation is used to counteract apnea in preterm infants, but it is unknown when this intervention should be applied. We compared an anticipatory to a reactive approach using vibrotactile stimulation to prevent hypoxia induced apneas. METHODS: Preterm rabbit kittens were prematurely delivered and randomized to either group. All kittens breathed spontaneously with a positive airway pressure of 8 cmH2O while they were imaged using phase contrast X-ray. Irregular breathing (IB) was induced using gradual hypoxia. The anticipatory group received stimulation at the onset of IB and the reactive group if IB transitioned into apnea. Breathing rate (BR), heart rate (HR) and functional residual capacity (FRC) were compared. RESULTS: Anticipatory stimulation significantly reduced apnea incidence and maximum inter-breath intervals and increased BR following IB, compared to reactive stimulation. Recovery in BR but not HR was more likely with anticipatory stimulation, although both BR and HR were significantly higher at 120 s after stimulation onset. FRC values and variability were not different. CONCLUSIONS: Anticipated vibrotactile stimulation is more effective in preventing apnea and enhancing breathing when compared to reactive stimulation in preterm rabbits. Stimulation timing is likely to be a key factor in reducing the incidence and duration of apnea. IMPACT: Anticipated vibrotactile stimulation can prevent apnea and stimulate breathing effort in preterm rabbits. Anticipated vibrotactile stimulation increases the likelihood of breathing rate recovery following hypoxia induced irregular breathing, when compared to reactive stimulation. Automated stimulation in combination with predictive algorithms may improve the treatment of apnea in preterm infants.

Sustained inflation improves initial lung aeration in newborn rabbits with a diaphragmatic hernia.

BACKGROUND: Infants with a congenital diaphragmatic hernia (DH) have underdeveloped lungs and require mechanical ventilation after birth, but the optimal approach is unknown. We hypothesised that sustained inflation (SI) increases lung aeration in newborn kittens with a DH. METHODS: In pregnant New Zealand white rabbits, a left-sided DH was induced in two fetal kittens per doe at 24-days gestation (term = 32 days); litter mates acted as controls. DH and control kittens were delivered by caesarean section at 30 days, intubated and mechanically ventilated (7-10 min) with either an SI followed by intermittent positive pressure ventilation (IPPV) or IPPV throughout. The rate and uniformity of lung aeration was measured using phase-contrast X-ray imaging. RESULTS: Lung weights in DH kittens were ~57% of controls. An SI increased the rate and uniformity of lung aeration in DH kittens, compared to IPPV, and increased dynamic lung compliance in both control and DH kittens. However, this effect of the SI was lost when ventilation changed to IPPV. CONCLUSION: While an SI improved the rate and uniformity of lung aeration in both DH and control kittens, greater consideration of the post-SI ventilation strategy is required to sustain this benefit. IMPACT: Compared to intermittent positive pressure ventilation (IPPV), an initial sustained inflation (SI) increased the rate and uniformity of lung aeration after birth. However, this initial benefit is rapidly lost following the switch to IPPV. The optimal approach for ventilating CDH infants at birth is unknown. While an SI improves lung aeration in immature lungs, its effect on the hypoplastic lung is unknown. This study has shown that an SI greatly improves lung aeration in the hypoplastic lung. This study will guide future studies examining whether an SI can improve lung aeration in infants with a CDH.

Printable Perovskite Diodes for Broad-Spectrum Multienergy X-Ray Detection.

Multienergy X-ray detection is critical to effectively differentiate materials in a variety of diagnostic radiology and nondestructive testing applications. Silicon and selenium X-ray detectors are the most common for multienergy detection; however, these present poor energy discrimination across the broad X-ray spectrum and exhibit limited spatial resolution due to the high thicknesses required for radiation attenuation. Here, an X-ray detector based on solution-processed thin-film metal halide perovskite that overcomes these challenges is introduced. By harnessing an optimized n-i-p diode configuration, operation is achieved across a broad range of soft and hard X-ray energies stemming from 0.1 to 10's of keV. Through detailed experimental and simulation work, it is shown that optimized Cs0.1 FA0.9 PbI3 perovskites effectively attenuate soft and hard X-rays, while also possessing excellent electrical properties to result in X-ray detectors with high sensitivity factors that exceed 5 × 103 µ C G y Vac - 1 cm - 2 $\mu {\rm{C}}\;{{\bf Gy}}_{{\rm{Vac}}}^{ - 1}\;{\rm{c}}{{\rm{m}}^{ - 2}}$ and 6 × 104 µC Gy-1 cm-2 within soft and hard X-ray regimes, respectively. Harnessing the solution-processable nature of the perovskites, roll-to-roll printable X-ray detectors on flexible substrates are also demonstrated.

Effect of prenatal diaphragmatic hernia on pulmonary arterial morphology.

Congenital diaphragmatic hernia (CDH) is a major cause of severe lung hypoplasia and pulmonary hypertension in the newborn. While the pulmonary hypertension is thought to result from abnormal vascular development and arterial vasoreactivity, the anatomical changes in vascular development are unclear. We have examined the 3D structure of the pulmonary arterial tree in rabbits with a surgically induced diaphragmatic hernia (DH). Fetal rabbits (n = 6) had a left-sided DH created at gestational day 23 (GD23), delivered at GD30, and briefly ventilated; sham-operated litter mates (n = 5) acted as controls. At postmortem the pulmonary arteries were filled with a radio-opaque resin before the lungs were scanned using computed tomography (CT). The 3D reconstructed images were analyzed based on vascular branching hierarchy using the software Avizo 2020.2. DH significantly reduced median number of arteries (2,579 (8440) versus 576 (442), p = .017), artery numbers per arterial generation, mean total arterial volume (43.5 ± 8.4 vs. 19.9 ± 3.1 µl, p = .020) and mean total arterial cross-sectional area (82.5 ± 2.3 vs. 28.2 ± 6.2 mm2 , p =.036). Mean arterial radius was increased in DH kittens between the eighth and sixth branching generation and mean arterial length between the sixth and 28th branching generation. A DH in kittens resulted in threefold reduction in pulmonary arterial cross-sectional area, primarily due to reduced arterial branching. Thus, the reduction in arterial cross-sectional area could be a major contributor to pulmonary hypertension infants with CDH.

Precise phase retrieval for propagation-based images using discrete mathematics.

The ill-posed problem of phase retrieval in optics, using one or more intensity measurements, has a multitude of applications using electromagnetic or matter waves. Many phase retrieval algorithms are computed on pixel arrays using discrete Fourier transforms due to their high computational efficiency. However, the mathematics underpinning these algorithms is typically formulated using continuous mathematics, which can result in a loss of spatial resolution in the reconstructed images. Herein we investigate how phase retrieval algorithms for propagation-based phase-contrast X-ray imaging can be rederived using discrete mathematics and result in more precise retrieval for single- and multi-material objects and for spectral image decomposition. We validate this theory through experimental measurements of spatial resolution using computed tomography (CT) reconstructions of plastic phantoms and biological tissues, using detectors with a range of imaging system point spread functions (PSFs). We demonstrate that if the PSF substantially suppresses high spatial frequencies, the potential improvement from utilising the discrete derivation is limited. However, with detectors characterised by a single pixel PSF (e.g. direct, photon-counting X-ray detectors), a significant improvement in spatial resolution can be obtained, demonstrated here at up to 17%.

Quantifying lung aeration in neonatal lambs at birth using lung ultrasound.

Background: Lung ultrasound (LUS) is a safe and non-invasive tool that can potentially assess regional lung aeration in newborn infants and reduce the need for X-ray imaging. LUS produces images with characteristic artifacts caused by the presence of air in the lung, but it is unknown if LUS can accurately detect changes in lung air volumes after birth. This study compared LUS images with lung volume measurements from high-resolution computed tomography (CT) scans to determine if LUS can accurately provide relative measures of lung aeration. Methods: Deceased near-term newborn lambs (139 days gestation, term ∼148 days) were intubated and the chest imaged using LUS (bilaterally) and phase contrast x-ray CT scans at increasing static airway pressures (0-50 cmH2O). CT scans were analyzed to calculate regional air volumes and correlated with measures from LUS images. These measures included (i) LUS grade; (ii) brightness (mean and coefficient of variation); and (iii) area under the Fourier power spectra within defined frequency ranges. Results: All LUS image analysis techniques correlated strongly with air volumes measured by CT (p < 0.01). When imaging statistics were combined in a multivariate linear regression model, LUS predicted the proportion of air in the underlying lung with moderate accuracy (95% prediction interval ± 22.15%, r 2 = 0.71). Conclusion: LUS can provide relative measures of lung aeration after birth in neonatal lambs. Future studies are needed to determine if LUS can also provide a simple means to assess air volumes and individualize aeration strategies for critically ill newborns in real time.

Full Field X-Ray Scatter Tomography.

In X-ray imaging, photons are transmitted through and absorbed by the target object, but are also scattered in significant quantities. Previous attempts to use scattered X-ray photons for imaging applications used pencil or fan beam illumination. Here we present 3D X-ray Scatter Tomography using full-field illumination for small-animal imaging. Synchrotron imaging experiments were performed on a phantom and the chest of a juvenile rat. Transmitted and scattered photons were simultaneously imaged with separate cameras; a scientific camera directly downstream of the sample stage, and a pixelated detector with a pinhole imaging system placed at 45° to the beam axis. We obtained scatter tomogram feature fidelity sufficient for segmentation of the lungs and major airways in the rat. The image contrast in the scatter tomogram slices approached that of transmission imaging, indicating robustness to the amount of multiple scattering present in our case. This opens the possibility of augmenting full-field 2D imaging systems with additional scatter detectors to obtain complementary modes or to improve the fidelity of existing images without additional dose, potentially leading to single-shot or reduced-angle tomography or overall dose reduction for live animal studies.

Spectral propagation-based x-ray phase-contrast computed tomography.

Purpose: Propagation-based x-ray imaging (PBI) is a phase-contrast technique that is employed in high-resolution imaging by introducing some distance between sample and detector. PBI causes characteristic intensity fringes that have to be processed with appropriate phase-retrieval algorithms, which has historically been a difficult task for objects composed of several different materials. Spectral x-ray imaging has been introduced to PBI to overcome this issue and to potentially utilize the spectral nature of the data for material-specific imaging. We aim to explore the potential of spectral PBI in three-dimensional computed tomography (CT) imaging in this work. Approach: We demonstrate phase-retrieval for experimental high-resolution spectral propagation-based CT data of a simple two-component sample, as well as a multimaterial capacitor test sample. Phase-retrieval was performed using an algorithm based on the Alvarez-Macovski model. Virtual monochromatic (VMI) and effective atomic number images were calculated after phase-retrieval. Results: Phase-retrieval results from the spectral data set show a distinct gray-level for each material with no residual phase-contrast fringes. Several representations of the phase-retrieved data are provided. The VMI is used to display an attenuation-equivalent image at a chosen display energy of 80 keV, to provide good separation of materials with minimal noise. The effective atomic number image shows the material composition of the sample. Conclusions: Spectral photon-counting detector technology has already been shown to be compatible with spectral PBI, and there is a foreseeable need for robust phase-retrieval in high-resolution, spectral x-ray CT in the future. Our results demonstrate the feasibility of phase-retrieval for spectral PBI CT.

Dark-field tomography of an attenuating object using intrinsic x-ray speckle tracking.

Purpose: We investigate how an intrinsic speckle tracking approach to speckle-based x-ray imaging is used to extract an object's effective dark-field (DF) signal, which is capable of providing object information in three dimensions. Approach: The effective DF signal was extracted using a Fokker-Planck type formalism, which models the deformations of illuminating reference beam speckles due to both coherent and diffusive scatter from the sample. Here, we assumed that (a) small-angle scattering fans at the exit surface of the sample are rotationally symmetric and (b) the object has both attenuating and refractive properties. The associated inverse problem of extracting the effective DF signal was numerically stabilized using a "weighted determinants" approach. Results: Effective DF projection images, as well as the DF tomographic reconstructions of the wood sample, are presented. DF tomography was performed using a filtered back projection reconstruction algorithm. The DF tomographic reconstructions of the wood sample provided complementary, and otherwise inaccessible, information to augment the phase contrast reconstructions, which were also computed. Conclusions: An intrinsic speckle tracking approach to speckle-based imaging can tomographically reconstruct an object's DF signal at a low sample exposure and with a simple experimental setup. The obtained DF reconstructions have an image quality comparable to alternative x-ray DF techniques.

Higher CPAP levels improve functional residual capacity at birth in preterm rabbits.

BACKGROUND: Preterm infants are commonly supported with 4-8 cm H2O continuous positive airway pressures (CPAP), although higher CPAP levels may improve functional residual capacity (FRC). METHODS: Preterm rabbits delivered at 29/32 days (~26-28 weeks human) gestation received 0, 5, 8, 12, 15 cm H2O of CPAP or variable CPAP of 15 to 5 or 15 to 8 cm H2O (decreasing ~2 cm H2O/min) for up to 10 min after birth. RESULTS: FRC was lower in the 0 (6.8 (1.0-11.2) mL/kg) and 5 (10.1 (1.1-16.8) mL/kg) compared to the 15 (18.8 (10.9-22.4) mL/kg) cm H2O groups (p = 0.003). Fewer kittens achieved FRC > 15 mL/kg in the 0 (20%), compared to 8 (36%), 12 (60%) and 15 (73%) cm H2O groups (p = 0.008). While breathing rates were not different (p = 0.096), apnoea tended to occur more often with CPAP < 8 cm H2O (p = 0.185). CPAP belly and lung bulging rates were similar whereas pneumothoraces were rare. Lowering CPAP from 15 to 5, but not 15 to 8 cm H2O, decreased FRC and breathing rates. CONCLUSION: In all, 15 cm H2O of CPAP improved lung aeration and reduced apnoea, but did not increase the risk of lung over-expansion, pneumothorax or CPAP belly immediately after birth. FRC and breathing rates were maintained when CPAP was decreased to 8 cm H2O. IMPACT: Although preterm infants are commonly supported with 4-8 cm H2O CPAP at birth, preclinical studies have shown that higher PEEP levels improve lung aeration. In this study, CPAP levels of 15 cm H2O improved lung aeration and reduced apnoea in preterm rabbit kittens immediately after birth. In all, 15 cm H2O CPAP did not increase the risk of lung over-expansion (indicated by bulging between the ribs), pneumothorax, or CPAP belly. These results can be used when designing future studies on CPAP strategies for preterm infants in the delivery room.

Increased end-expiratory pressures improve lung function in near-term newborn rabbits with elevated airway liquid volume at birth.

Approximately 53% of near-term newborns admitted to intensive care experience respiratory distress. These newborns are commonly delivered by cesarean section and have elevated airway liquid volumes at birth, which can cause respiratory morbidity. We investigated the effect of providing respiratory support with a positive end-expiratory pressure (PEEP) of 8 cmH2O on lung function in newborn rabbit kittens with elevated airway liquid volumes at birth. Near-term rabbits (30 days; term = 32 days) with airway liquid volumes that corresponded to vaginal delivery (∼7 mL/kg, control, n = 11) or cesarean section [∼37 mL/kg; elevated liquid (EL), n = 11] were mechanically ventilated (tidal volume = 8 mL/kg). The PEEP was changed after lung aeration from 0 to 8 to 0 cmH2O (control, n = 6; EL, n = 6), and in a separate group of kittens, PEEP was changed after lung aeration from 8 to 0 to 8 cmH2O (control, n = 5; EL, n = 5). Lung function (ventilator parameters, compliance, lung gas volumes, and distribution of gas within the lung) was evaluated using plethysmography and synchrotron-based phase-contrast X-ray imaging. EL kittens initially receiving 0 cmH2O PEEP had reduced functional residual capacities and lung compliance, requiring higher inflation pressures to aerate the lung compared with control kittens. Commencing ventilation with 8 cmH2O PEEP mitigated the adverse effects of EL, increasing lung compliance, functional residual capacity, and the uniformity and distribution of lung aeration, but did not normalize aeration of the distal airways. Respiratory support with PEEP supports lung function in near-term newborn rabbits with elevated airway liquid volumes at birth who are at a greater risk of suffering respiratory distress.NEW & NOTEWORTHY Term babies born by cesarean section have elevated airway liquid volumes, which predisposes them to respiratory distress. Treatments targeting molecular mechanisms to clear lung liquid are ineffective for term newborn respiratory distress. We showed that respiratory support with an end-expiratory pressure supports lung function in near-term rabbits with elevated airway liquid volumes at birth. This study provides further physiological understanding of lung function in newborns with elevated airway liquid volumes at risk of respiratory distress.

Seeing the fetus from a DOHaD perspective: discussion paper from the advanced imaging techniques of DOHaD applications workshop held at the 2019 DOHaD World Congress.

Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.

Quantitative material decomposition using linear iterative near-field phase retrieval dual-energy x-ray imaging.

This paper expands the linear iterative near-field phase retrieval (LIPR) formalism to achieve quantitative material thickness decomposition. Propagation-based phase contrast x-ray imaging with subsequent phase retrieval has been shown to improve the signal-to-noise ratio (SNR) by factors of up to hundreds compared to conventional x-ray imaging. This is a key step in biomedical imaging, where radiation exposure must be kept low without compromising the SNR. However, for a satisfactory phase retrieval from a single measurement, assumptions must be made about the object investigated. To avoid such assumptions, we use two measurements collected at the same propagation distance but at different x-ray energies. Phase retrieval is then performed by incorporating the Alvarez-Macovski (AM) model, which models the x-ray interactions as being comprised of distinct photoelectric and Compton scattering components. We present the first application of dual-energy phase retrieval with the AM model to monochromatic experimental x-ray projections at two different energies for obtaining split x-ray interactions. Our phase retrieval method allows us to separate the object investigated into the projected thicknesses of two known materials. Our phase retrieval output leads to no visible loss in spatial resolution while the SNR improves by factors of 2 to 10. This corresponds to a possible x-ray dose reduction by a factor of 4 to 100, under the Poisson noise assumption.

Emphysema quantified: mapping regional airway dimensions using 2D phase contrast X-ray imaging.

We have developed an analyser-based phase contrast X-ray imaging technique to measure the mean length scale of pores or particles that cannot be resolved directly by the system. By combining attenuation, phase and ultra-small angle X-ray scattering information, the technique was capable of measuring differences in airway dimension between lungs of healthy mice and those with mild and severe emphysema. Our measurements of airway dimensions from 2D images showed a 1:1 relationship to the actual airway dimensions measured using micro-CT. Using 80 images, the sensitivity and specificity were measured to be 0.80 and 0.89, respectively, with the area under the ROC curve close to ideal at 0.96. Reducing the number of images to 11 slightly decreased the sensitivity to 0.75 and the ROC curve area to 0.90, whilst the specificity remained high at 0.89.

Improving lung aeration in ventilated newborn preterm rabbits with a partially aerated lung.

Preterm newborns commonly receive intermittent positive pressure ventilation (iPPV) at birth, but the optimal approach that facilitates uniform lung aeration is unknown, particularly in a partially aerated lung. As both inflation time and exogenous surfactant facilitate uniform lung aeration, we investigated whether they can improve lung aeration and lung mechanics in a partially aerated lung immediately after birth. Preterm rabbit kittens (29 days of gestation, term ~32 days) were delivered by caesarean section and partial lung aeration was created by intubating and mechanically ventilating the right lung. The tube was then withdrawn to ventilate both lungs using inflation times of 0.2 s or 1.0 s, with or without exogenous surfactant (200 mg/kg; Curosurf) and a tidal volume (Vt) of 8 mL/kg. Simultaneous phase contrast X-ray imaging and plethysmography were used to measure lung aeration and mechanics. Kittens ventilated with longer inflation times (1.0 s) reached their target Vt with fewer inflations, required lower inflation pressures (28.5 ± 1.1 vs. 33.5 ± 1.3 cmH2O, P = 0.01) and had higher dynamic lung compliances (0.54 ± 0.3 vs. 0.40 ± 0.3 cmH2O·mL-1·kg-1, P = 0.003). Surfactant increased functional residual capacity (FRC; 31.9 ± 3.2 vs. 18.0 ± 3.9 mL/kg, P = 0.02) and the proportion of the Vt entering the previously unaerated lung but had no effect on dynamic lung compliance. Combining early surfactant treatment with longer inflation times increases FRC levels, improves dynamic lung compliance, reduces inflation pressures and markedly increases the proportion of the lungs being ventilated during iPPV in preterm kittens with a partially aerated lung.NEW & NOTEWORTHY Preterm newborns commonly receive intermittent positive pressure ventilation (iPPV) at birth, but the optimal approach that facilitates uniform lung aeration is unknown, particularly in a partially aerated lung. Using phase contrast X-ray imaging, we showed that combining a long inflation time (1.0 s) with surfactant improved lung mechanics and aeration in the immediate newborn period. The current clinical practice of using short inflation times during iPPV might be suboptimal and a different approach is needed.

Material Decomposition Using Spectral Propagation-Based Phase-Contrast X-Ray Imaging.

Material decomposition in X-ray imaging uses the energy-dependence of attenuation to digitally decompose an object into specific constituent materials, generally at the cost of enhanced image noise. Propagation-based X-ray phase-contrast imaging is a developing technique that can be used to reduce image noise, in particular from weakly attenuating objects. In this paper, we combine spectral phase-contrast imaging with material decomposition to both better visualize weakly attenuating features and separate them from overlying objects in radiography. We derive an algorithm that performs both tasks simultaneously and verify it against numerical simulations and experimental measurements of ideal two-component samples composed of pure aluminum and poly(methyl methacrylate). Additionally, we showcase first imaging results of a rabbit kitten's lung. The attenuation signal of a thorax, in particular, is dominated by the strongly attenuating bones of the ribcage. Combined with the weak soft tissue signal, this makes it difficult to visualize the fine anatomical structures across the whole lung. In all cases, clean material decomposition was achieved, without residual phase-contrast effects, from which we generate an un-obstructed image of the lung, free of bones. Spectral propagation-based phase-contrast imaging has the potential to be a valuable tool, not only in future lung research, but also in other systems for which phase-contrast imaging in combination with material decomposition proves to be advantageous.

Material decomposition from a single x-ray projection via single-grid phase contrast imaging.

This study describes a new approach for material decomposition in x-ray imaging, utilizing phase contrast both to increase sensitivity to weakly attenuating samples and to act as a complementary measurement to attenuation, therefore allowing two overlaid materials to be separated. The measurements are captured using the single-exposure, single-grid x-ray phase contrast imaging technique, with a novel correction that aims to remove propagation-based phase effects seen at sharp edges in the attenuation image. The use of a single-exposure technique means that images can be collected in a high-speed sequence. Results are shown for both a known two-material sample and for a biological specimen.

Spectral x-ray imaging: Conditions under which propagation-based phase-contrast is beneficial.

Energy-resolved attenuation data in spectral x-ray imaging enables material decomposition, in which the different materials inside an object can be identified and separated virtually. Material decomposition has the drawback of increased noise in the resulting material images relative to the measured images. Recently, spectral x-ray imaging was combined with propagation-based x-ray phase-contrast imaging, an x-ray technique that has the potential to greatly reduce image noise by utilizing wave-optical effects. The net combined effects on image noise of performing spectral material decomposition with phase-contrast are not yet well understood, and we provide a detailed theoretical investigation of this topic here. In particular, we investigate how the addition of phase-contrast in spectral imaging affects material decomposition compared to using conventional spectral attenuation data. We show how the underlying equations can be rearranged into parts that resemble low- and high-pass filters on the input images, from which we are able to identify different energy-dependent cases where phase-contrast is or is not advantageous. Our results suggest that the benefits of phase-contrast in the context of material decomposition are primarily restricted to x-ray energies under a certain threshold, where that threshold depends on the given material combination, and sits in a region where photoelectric absorption dominates x-ray attenuation. Additionally, we show that decomposition of the electron density using an image basis spanned by functions of the Alvarez-Macovski model benefits from phase-contrast, regardless of the x-ray energies. All our findings are based purely on theoretical considerations, and can, therefore, be used to determine the feasibility and utility of propagation-based phase-contrast in spectral x-ray imaging ahead of any data collection.

Photon-counting, energy-resolving and super-resolution phase contrast X-ray imaging using an integrating detector.

This work demonstrates the use of a scientific-CMOS (sCMOS) energy-integrating detector as a photon-counting detector, thereby eliminating dark current and read-out noise issues, that simultaneously provides both energy resolution and sub-pixel spatial resolution for X-ray imaging. These capabilities are obtained by analyzing visible light photon clouds that result when X-ray photons produce fluorescence from a scintillator in front of the visible light sensor. Using low-fluence monochromatic X-ray projections to avoid overlapping photon clouds, the centroid of individual X-ray photon interactions was identified. This enabled a tripling of the spatial resolution of the detector to 6.71 ± 0.04 µm. By calculating the total charge deposited by this interaction, an energy resolution of 61.2 ± 0.1% at 17 keV was obtained. When combined with propagation-based phase contrast imaging and phase retrieval, a signal-to-noise ratio of up to 15 ± 3 was achieved for an X-ray fluence of less than 3 photons/mm2.

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.