Visualization of respiratory flows from 3D reconstructed alveolar airspaces using X-ray tomographic microscopy

A deeper knowledge of the three-dimensional (3D) structure of the pulmonary acinus has direct applications in studies on acinar fluid dynamics and aerosol kinematics. To date, however, acinar flow simulations have been often based on geometrical models inspired by morphometrical studies; limitations in the spatial resolution of lung imaging techniques have prevented the simulation of acinar flows using 3D reconstructions of such small structures. In the present study, we use high-resolution, synchrotron radiation-based X-ray tomographic microscopy (SRXTM) images of the pulmonary acinus of a mouse to reconstruct 3D alveolar airspaces and conduct computational fluid dynamic (CFD) simulations mimicking rhythmic breathing motion. Respiratory airflows and Lagrangian (massless) particle tracking are visualized in two examples of acinar geometries with varying size and complexity, representative of terminal sacculi including their alveoli. The present CFD simulations open the path towards future acinar flow and aerosol deposition studies in complete and anatomically realistic multi-generation acinar trees using reconstructed 3D SRXTM geometries.Graphical Abstract

[1]  J S Fleming,et al.  Study of the three‐dimensional geometry of the central conducting airways in man using computed tomographic (CT) images , 2002, Journal of anatomy.

[2]  E R Weibel,et al.  Morphometry of the human pulmonary acinus , 1988, The Anatomical record.

[3]  J. Crapo,et al.  Three-dimensional reconstruction of the rat acinus. , 1987, Journal of applied physiology.

[4]  Hideo Yokota,et al.  Three-dimensional visualization and morphometry of small airways from microfocal X-ray computed tomography. , 2003, Journal of biomechanics.

[5]  D. Darmofal,et al.  An Analysis of 3D Particle Path Integration Algorithms , 1996 .

[6]  J. Bernaudin,et al.  Ventilatory Responses to Hypercapnia and Hypoxia in Conscious Cystic Fibrosis Knockout Mice Cftr−/− , 2004, Pediatric Research.

[7]  F. S. Henry,et al.  Kinematically irreversible acinar flow: a departure from classical dispersive aerosol transport theories. , 2002, Journal of applied physiology.

[8]  R. Shah Laminar Flow Forced convection in ducts , 1978 .

[9]  E. Weibel,et al.  Alveolar volume-surface area relation in air- and saline-filled lungs fixed by vascular perfusion. , 1979, Journal of applied physiology: respiratory, environmental and exercise physiology.

[10]  K. Hanson,et al.  Limiting configuration in dislocation glide through a random array of point obstacles , 1975 .

[11]  Y C Fung,et al.  A model of the lung structure and its validation. , 1988, Journal of applied physiology.

[12]  E. Weibel,et al.  The postnatal growth of the rat lung. I. Morphometry , 1974, The Anatomical record.

[13]  Thomas Rösgen,et al.  Three-dimensional convective alveolar flow induced by rhythmic breathing motion of the pulmonary acinus. , 2007, Journal of biomechanical engineering.

[14]  Marco Stampanoni,et al.  High resolution X-ray detector for synchrotron-based microtomography , 2002 .

[15]  B. Brunekreef,et al.  Air pollution and health , 2002, The Lancet.

[16]  J. Hildebrandt,et al.  Macroscopic isotropy of lung expansion. , 1974, Respiration physiology.

[17]  J. Schittny,et al.  J Am Soc Nephrol 14: 2288–2296, 2003 Glomerular and Renal Vascular Structural Changes in �8 Integrin-Deficient Mice , 2022 .

[18]  Thomas Rösgen,et al.  Respiratory flow phenomena and gravitational deposition in a three-dimensional space-filling model of the pulmonary acinar tree. , 2009, Journal of biomechanical engineering.

[19]  G. H. Bryant,et al.  Branching pattern of airways and air spaces of a single human terminal bronchiole. , 1975, Journal of applied physiology.

[20]  F. S. Henry,et al.  Chaotic mixing of alveolated duct flow in rhythmically expanding pulmonary acinus. , 1995, Journal of applied physiology.

[21]  D. Aykac,et al.  Segmentation and analysis of the human airway tree from three-dimensional X-ray CT images , 2003, IEEE Transactions on Medical Imaging.

[22]  M. Stampanoni,et al.  Developmental Dynamics , 2020, Differentiating Giftedness from Talent.

[23]  A. Tsuda,et al.  Gravitational deposition in a rhythmically expanding and contracting alveolus. , 2003, Journal of applied physiology.

[24]  P. Burri,et al.  Pre-and Postnatal Lung Development, Maturation, and Plasticity Suppression of Cell Proliferation and Programmed Cell Death by Dexamethasone during Postnatal Lung Development , 2001 .

[25]  P. Paré,et al.  Airway narrowing in excised canine lungs measured by high-resolution computed tomography. , 1992, Journal of applied physiology.

[26]  Marco Stampanoni,et al.  Evidence and structural mechanism for late lung alveolarization. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[27]  Chantal Darquenne,et al.  A realistic two-dimensional model of aerosol transport and deposition in the alveolar zone of the human lung , 2001 .

[28]  M Stampanoni,et al.  Finite element 3D reconstruction of the pulmonary acinus imaged by synchrotron X-ray tomography. , 2008, Journal of applied physiology.

[29]  J E Hansen,et al.  Human air space shapes, sizes, areas, and volumes. , 1975, Journal of applied physiology.

[30]  The effect of flow generated by a rhythmically expanding pulmonary acinus on aerosol dynamics , 1998 .

[31]  Matthias Ochs,et al.  Interactions of nanoparticles with pulmonary structures and cellular responses. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[32]  Joel H. Ferziger,et al.  Computational methods for fluid dynamics , 1996 .

[33]  Bruce W. Knight,et al.  A MORPHOMETRIC STUDY ON THE THICKNESS OF THE PULMONARY AIR-BLOOD BARRIER , 1964, The Journal of cell biology.

[34]  M. ROTH-KLEINER,et al.  Neonatal dexamethasone induces premature microvascular maturation of the alveolar capillary network , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[35]  E A Zerhouni,et al.  In vivo measurements of airway reactivity using high-resolution computed tomography. , 1991, The American review of respiratory disease.

[36]  R Takaki,et al.  A three-dimensional model of the human pulmonary acinus. , 2000, Journal of applied physiology.