Intermittent CPAP limits hyperoxia-induced lung damage in a rabbit model of bronchopulmonary dysplasia.

A significant proportion of preterm infants develop bronchopulmonary dysplasia (BPD) leading to poor lifelong respiratory health. Limited treatment options exist with continuous positive airway pressure (CPAP) ventilation being one of the few associated with diminished BPD. However, little is known about the effect of the distending pressure of CPAP on the developing lung exposed to hyperoxia. We aimed to identify the functional and structural effects of CPAP in a preterm hyperoxia rabbit model of BPD. Premature rabbit pups were randomized to normoxia, hyperoxia (≥95% O2), or hyperoxia plus 4 h daily CPAP [fraction of inspired oxygen (FiO2) 0.95, 5 cmH2O]. On day 7 postdelivery we performed invasive pressure-volume- and forced oscillation-based pulmonary function tests, before lung harvest for histological evaluation. Alveolar and vascular morphology, airway smooth muscle content, respiratory epithelium height, extracellular matrix components, and inflammatory cytokine expression were quantified. Hyperoxia-reared pups had restrictive lungs: alveolar walls were thickened, with the lung parenchymal tissue, collagen content, and airway smooth muscle content increased. In addition, peripheral pulmonary artery wall thickness was increased. CPAP increased alveolar recruitment and limited the structural effect of hyperoxia on the respiratory epithelium and pulmonary arteries. Additionally, CPAP improved lung function, mitigating hyperoxia-associated changes to respiratory system resistance, tissue damping, and tissue elastance. Hyperoxia disrupted functional and structural lung development. Daily intermittent CPAP limited hyperoxia-associated decreased lung function and attenuated structural changes to pulmonary arteries and respiratory epithelium while having no structural alveolar consequences. The mechanism by which CPAP has these beneficial effects needs further investigation.

Preterm birth impairs postnatal lung development in the neonatal rabbit model.

BACKGROUND: Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits. METHODS: Pups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms. RESULTS: Preterm pups assessed at birth depicted a more rudimentary lung structure (larger alveoli and thicker septations) and a lower expression of surfactant proteins in comparison to term pups. MicroCT and dark field imaging revealed delayed lung aeration in preterm pups, in comparison to term pups. Preterm birth led to smaller pups, with smaller lungs with a lower alveolar surface area on day 7/day 4. Furthermore, preterm birth affected lung function with increased tissue damping, tissue elastance and resistance and decreased dynamic compliance. Expression of vascular endothelial growth factor (VEGFA) was significantly decreased in preterm pups, however in the absence of structural vascular differences. CONCLUSIONS: Preterm birth affects lung structure and function at birth, but also has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on BPD. Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD.

Verification of the accuracy of a hybrid breast imaging simulation framework for virtual clinical trial applications.

Purpose: The impact of system parameters on signal detectability can be studied with simulation platforms. We describe the steps taken to verify and confirm the accuracy of a local platform developed for the use in virtual clinical trials. Approach: The platform simulates specific targets into existing two-dimensional full-field digital mammography and digital breast tomosynthesis images acquired on a Siemens Inspiration system. There are three steps: (1) creation of voxel models or analytical objects; (2) generation of a realistic object template with accurate resolution, scatter, and noise properties; and (3) insertion and reconstruction. Four objects were simulated: a 0.5-mm aluminium (Al) sphere and a 0.2-mm-thick Al sheet in a PMMA stack, a 0.8-mm steel edge and a three-dimensional mass model in a structured background phantom. Simulated results were compared to acquired data. Results: Peak contrast and signal difference-to-noise ratio (SDNR) were in close agreement ( < 5 % error) for both sphere and sheet. The similarity of pixel value profiles for sphere and sheet in the x y direction and the artifact spread function for real and simulated spheres confirmed accurate geometric modeling. Absolute and relative average deviation between modulation transfer function measured from a real and simulated edges showed accurate sharpness modelling for spatial frequencies up to the Nyquist frequency. Real and simulated objects could not be differentiated visually. Conclusions: The results indicate that this simulation framework is a strong candidate for use in virtual clinical studies.

Erratum: verification of the accuracy of a hybrid breast imaging simulation framework for virtual clinical trial applications.

[This corrects the article DOI: 10.1117/1.JMI.7.4.042804.].

Translation from murine to human lung imaging using x-ray dark field radiography: A simulation study.

Recent studies on murine models have demonstrated the potential of dark field (DF) x-ray imaging for lung diseases. The alveolar microstructure causes small angle scattering, which is visualised in DF images. Whether DF imaging works for human lungs is not a priori guaranteed as human alveoli are larger and system settings for murine imaging will probably have to be adapted. This work examines the potential of translating DF imaging to human lungs. The DF contrast due to murine and human lung models was studied using numerical wave propagation simulations, where the lungs were modelled as a volume filled with spheres. Three sphere diameters were used: 39, 60 and 80 µm for the murine model and 200, 300 and 400 µm spheres for the human model. System settings applied for murine lung response modelling were taken from a prototype grating interferometry scanner used in murine lung experiments. The settings simulated for human lung imaging simulations combine the requirements for grating interferometry and conventional chest RX in terms of x-ray energy and pixel size. The DF signal in the simulated murine model was consistent with results from experimental DF data. The simulated linear diffusion coefficient for medium alveoli diameters was found to be (1.31±0.01)⋅10-11 mm-1, 120 times larger than those of human lung tissue ((1.09±0.01)⋅10-13 mm-1). However, as the human thorax is typically a factor 15 times larger than that of murine animals, the overall DF effect in human lungs remains substantial. At the largest lung thickness and for the DF setup simulated, human lungs have an estimated DF response of around 0.31 and murine lungs of 0.23. Dark field imaging can therefore be considered a promising modality for use in human lung imaging.

Suitability of low density materials for 3D printing of physical breast phantoms.

Breast physical phantoms are a basic tool for the assessment and verification of performance standards in daily clinical practice of x-ray breast imaging modalities. They are also invaluable in testing and evaluation of new x-ray breast modalities to be potentially established, e.g. breast computed tomography, dual-energy breast CT and phase-contrast mammography and tomography. Nowadays, there is a lack or there are only a limited number of breast physical phantoms available for this purpose. The aim of this study is to explore a range of 3D printing materials such as resins, PLA, ABS, Nylon etc, to determine their attenuation and refractive properties, and to finally compare them to the properties of the breast tissues: adipose, glandular and skin. To achieve this goal, step-wedge phantoms were computationally modeled and then manufactured using stereolithographic and fused-deposition modeling technologies. X-ray images of the phantoms were acquired, using monochromatic beam at ID17, ESRF, Grenoble for three energies-30 keV, 45 keV and 60 keV. Experimental data were further processed to obtain the linear attenuation coefficients of these materials. Comparison with theoretical data for the linear attenuation coefficients and the refractive indexes for breast tissues was performed. From the studied materials, most of the resins, Nylon, Hybrid, PET-G show absorption properties close to the glandular tissue, while ABS shows absorption characteristics close to these of the adipose tissue. For phase-contrast imaging, it turns out that the ABS combined with resin-based materials to represent the adipose and glandular tissues, respectively may be a good combination for manufacturing of a phantom suitable for these studies. These results can be used for the design and the construction of a new physical anthropomorphic phantom of the breast with improved anatomical and radiological characteristics dedicated for advanced mammography imaging techniques implemented at higher photon energies.