Fractal analysis reveals functional unit of ventilation in the lung

Ventilation is inhomogeneous in the lungs across species. It has been hypothesized that ventilation inhomogeneity is largely determined by the design of the airway branching network. Because exchange of gases at the alveolar barrier is more efficient when gas concentrations are evenly distributed at subacinar length scales, it is assumed that a 'functional unit' of ventilation exists within the lung periphery, where gas concentration becomes uniform. On the other hand, because the morphology of pulmonary airways and alveoli, and the distribution of inhaled fluorescent particles show self-similar fractal properties over a wide range of length scales, it has been predicted that fractal dimension of ventilation approaches unity within an internally homogeneous functional unit of ventilation. However, the existence of such a functional unit has never been demonstrated experimentally due to lack of in situ gas concentration measurements of sufficient spatial resolution in the periphery of a complex bifurcating network. Here, using energy-subtractive synchrotron radiation tomography, we measured the distribution of an inert gas (Xe) in the in vivo rabbit lung during Xe wash-in breathing manoeuvres. The effects of convective flow rate, diffusion and cardiac motion were also assessed. Fractal analysis of resulting gas concentration and tissue density maps revealed that fractal dimension was always smaller for Xe than for tissue density, and that only for the gas, a length scale existed where fractal dimension approached unity. The length scale where this occurred was seen to correspond to that of a rabbit acinus, the terminal structure comprising only alveolated airways. Key points Gas ventilation is inhomogeneous in the lung of many species. However, it is not known down to what length scales this inhomogeneity persists. It is generally assumed that ventilation becomes homogeneous at subacinar length scales, beyond the spatial resolution of commonly available imaging techniques, hence this has not been demonstrated experimentally. Here we measured the distribution of inhaled Xe gas in the rabbit lung using synchrotron radiation energy-subtractive imaging and used fractal analysis to show that ventilation becomes internally uniform within regions about the size of rabbit lung acini.Peer reviewe

Comparison of fast field-cycling magnetic resonance imaging methods and future perspectives

This article is based upon work from COST Action CA15209, supported by COST (European Cooperation in Science and Technology). M. Bödenler, C. Gösweiner and H. Scharfetter acknowledge the financial support by the European Commission in the frame of the H2020 Future and Emerging Technologies (FET-open) under grant agreement 665172, project ‘CONQUER’. L. de Rochefort acknowledges the France Life Imaging network (Grant ANR-11-INBS-0006) that partially funded the small animal FFC-MRI system. D.J. Lurie, L.M. Broche and P.J. Ross acknowledge funding from the European Union’s H2020 research and innovation programme under grant agreement No 668119, project ‘IDentIFY’.Peer reviewedPublisher PD

Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung

OBJECTIVES:: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. DESIGN:: Experimental animal study. SETTING:: International synchrotron radiation laboratory. SUBJECTS:: Four anesthetized rabbits, ventilated in pressure controlled mode. INTERVENTIONS:: The lung was consecutively imaged at ~ 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end-expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (Fderecruited, Frecruited) were computed based on the comparison of the aerated volumes at successive time points. MEASUREMENTS AND MAIN RESULTS:: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of Fderecruited and Frecruited when mechanical interdependence was included, while its exclusion gave Frecruited values of zero at positive end-expiratory pressure greater than or equal to 3 cm H2O. CONCLUSIONS:: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage

The Effect of Positive End-Expiratory Pressure on Lung Micromechanics Assessed by Synchrotron Radiation Computed Tomography in an Animal Model of ARDS

Modern ventilatory strategies are based on the assumption that lung terminal airspaces act as isotropic balloons that progressively accommodate gas. Phase contrast synchrotron radiation computed tomography (PCSRCT) has recently challenged this concept, showing that in healthy lungs, deflation mechanisms are based on the sequential de-recruitment of airspaces. Using PCSRCT scans in an animal model of acute respiratory distress syndrome (ARDS), this study examined whether the numerosity (ASnum) and dimension (ASdim) of lung airspaces change during a deflation maneuver at decreasing levels of positive end-expiratory pressure (PEEP) at 12, 9, 6, 3, and 0 cmH(2)O. Deflation was associated with significant reduction of ASdim both in the whole lung section (passing from from 13.1 +/- 2.0 at PEEP 12 to 7.6 +/- 4.2 voxels at PEEP 0) and in single concentric regions of interest (ROIs). However, the regression between applied PEEP and ASnum was significant in the whole slice (ranging from 188 +/- 52 at PEEP 12 to 146.4 +/- 96.7 at PEEP 0) but not in the single ROIs. This mechanism of deflation in which reduction of ASdim is predominant, differs from the one observed in healthy conditions, suggesting that the peculiar alveolar micromechanics of ARDS might play a role in the deflation process.Peer reviewe

Nasal High Flow at 25 L/min or Expiratory Resistive Load Do Not Improve Regional Lung Function in Patients With COPD: A Functional CT Imaging Study

BackgroundNasal high flow (NHF) is a non-invasive breathing therapy that is based on the delivery via a large-caliber nasal cannula of heated and humidified air at flow rates that exceed peak inspiratory flow. It is thought that positive airway pressure generated by NHF can help reduce gas trapping and improve regional lung ventilation. There are no data to confirm this hypothesis at flow rates applicable in stable chronic obstructive pulmonary disease (COPD) patients.MethodsIn this study, we used non-rigid registration of computed tomography (CT) images acquired at maximal expiration and inspiration to compute regional lung attenuation changes (ΔHU), and lung displacement (LD), indices of regional lung ventilation. Parametric response maps (Galban et al., 2012) were also computed in each experimental condition. Eight COPD patients were assessed at baseline (BL) and after 5 min of NHF and expiratory resistive loading (ERL).ResultsΔHU was: BL (median, IQR): 85 (67.2, 102.8); NHF: 90.7 (57.4, 97.6); ERL: 74.6 (46.4, 89.6) HU (p = 0.531); and LD: 27.8 (22.3, 39.3); 17.6 (15.4, 27.9); and 20.4 (16.6, 23.6) mm (p = 0.120) in the 3 conditions, respectively. No significant difference in trapping was observed. Respiratory rate significantly decreased with both treatments [BL: 17.3 (16.4, 18.9); NHF: 13.7; ERL: 11.4 (9.6, 13.2) bpm; and p < 0.001].ConclusionNeither NHF at 25 L/min nor ERL significantly improved the regional lung ventilation of stable COPD patients with gas trapping, based on functional lung CT imaging. Further study including more subjects is needed to assess the potential effect of NHF on regional lung function at higher flow rates.Clinical Trial Registrationwww.clinicaltrials.gov/under, identifier NCT03821311

Ventilator associated lung injury studied by Synchrotron imaging

Fréquemment, les patients traités par ventilation mécanique développent des lésions pulmonaires graves pouvant entraîner une hypoxie ou dans le pire des cas une défaillance multisystémique. Cette thèse étudie sur un modèle animal la dynamique des déformations bronchiques et alvéolaires d'un poumon ventilé en pression positive, à l'état normal et après induction d'un œdème pulmonaire de perméabilité. A l'aide d'une technique d'imagerie en contraste de phase utilisant une source de rayon x synchrotron, des phénomènes de collapsus et de réaération alvéolaire ont été identifiées comme se produisant à des intervalles de temps court et malgré un mode ventilatoire à pression contrôlée. Nos résultats montrent que l'application d'une pression de fin d'expiration permet de réduire mais n'annihile pas les instabilités pulmonaires. Afin de tester différentes hypothèses mécanistiques, un modèle mathématique de la mécanique respiratoire saine et lésée a été implémenté dans une structure bronchique morphologiquement réaliste. Les résultats de cette simulation numérique suggèrent que le recrutement cyclique des alvéoles pulmonaires pourrait être dus à la conjonction de deux phénomènes : 1) le collapsus et la réaération sont des phénomènes dynamiques; 2) les alvéoles pulmonaires interagissent mécaniquement entre elles. Le comportement à court et à long terme du modèle exhibe une bonne corrélation avec les données expérimentales lorsque ces deux conditions sont réunies. Ce modèle représente un outil de simulation intéressant pour mettre au point et tester de nouveaux protocoles de ventilation mécanique, permettant de minimiser les phénomènes de recrutement cyclique des alvéoles pulmonairesPatients treated with mechanical ventilation are exposed to lung damage leading to hypoxia or in the worst case multi organ failure. Using x-ray phase contrast synchrotron imaging of an animal model, we study the pulmonary micro-mechanic of the damage parenchyma. The relevance of the study lies in the characterisation of the dynamic of the alveoli and bronchi mechanic under constant pressure control ventilation. Thus, extent and magnitude of potential inflammatory regions were reported based on lung recruitment and derecruitment maps on each CT slice. It appears that lung instabilities remain non negligible despite the addition of a positive end expiratory pressure, which may explain the ineffectiveness of current protective ventilation protocols in intensive care units. One probable assumption is to consider one alveolus structural alteration as a consequence of shared stresses through the surrounding network of neighbouring alveoli. To support this hypothesis, a mathematical model mimicking injured lung ventilation was implemented in a realistic airway tree. The model short and long term behaviour shows a good correlation with experimental data, and provides a useful tool to evaluate new ventilation protocol

Synchrotron X-ray imaging of the onset of ultrasonic horn cavitation

High-power ultrasonic horns operating at low frequency are known to generate a cone-shaped cavitation bubble cloud beneath them. The exact physical processes resulting in the conical structure are still unclear mainly due to challenges associated with their visualization. Herein, we address the onset of the cavitation cloud by exploiting high-speed X-ray phase contrast imaging. It reveals that the cone formation is not immediate but results from a three-step phenomenology: (i) inception and oscillation of single bubbles, (ii) individual cloud formation under splitting or lens effects, and (iii) cloud merging leading to the formation of a bubble layer and, eventually, to the cone structure due to the radial pressure gradient on the horn tip.ISSN:1350-4177ISSN:1873-282

Safety Evaluation of All-Solid-State Batteries: An Innovative Methodology Using In Situ Synchrotron X-ray Radiography

International audienc