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

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

Theoretical basis for time 0 correction in the rebreathing analysis

The uptake of a soluble gas during rebreathing is simulated in a compartmental model. The lung is assumed to consist of two parallel units, each one divided into three compartments: a personal dead space, an alveolar space, and a tissue volume. These units are connected to the rebreathing bag via a common dead space. Gas exchange is incorporated into the model for a given cardiac output. Inert and soluble gas concentrations are computed as a function of time in the various compartments by means of differential equations. Using different initial conditions, we simulate time-dependent concentration traces 'at the mouth' and estimate the errors made by traditional analysis of the end-tidal gas concentrations with respect to the 'time 0' correction method as was first proposed by Sackner et al. (Am. Rev. Respir. Dis. 111: 157-165, 1975). We provide a theoretical basis for this correction method and outline the conditions that need to be fulfilled for its application. We show that the tissue volume and cardiac output estimates are less affected by ventilation and perfusion inhomogeneities when the time 0 correction method is used. This is particularly relevant for the expected increase in tissue volume in microgravity where ventilation and perfusion inhomogeneities are expected to be attenuated.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Last Word on Viewpoint: Could lobar flow sequencing account for convection-dependent ventilation heterogeneity in normal man?

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Determinants of the long-range apparent diffusion coefficient in the human lung: Collateral channels or intra-acinar branching?

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Effective axial diffusion in an expansile alveolar duct model

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Dual gas techniques for peripheral airway function: Diffusing the issues

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Link between numbers, pictures, and physiological tests

SCOPUS: le.jinfo:eu-repo/semantics/publishe