Tomographic in vivo microscopy for the study of lung physiology at the alveolar level

Lungs represent the essential part of the mammalian respiratory system, which is reflected in the fact that lung failure still is one of the leading causes of morbidity and mortality worldwide. Establishing the connection between macroscopic observations of inspiration and expiration and the processes taking place at the microscopic scale remains crucial to understand fundamental physiological and pathological processes. Here we demonstrate for the first time in vivo synchrotron-based tomographic imaging of lungs with pixel sizes down to a micrometer, enabling first insights into high-resolution lung structure. We report the methodological ability to study lung inflation patterns at the alveolar scale and its potential in resolving still open questions in lung physiology. As a first application, we identified heterogeneous distension patterns at the alveolar level and assessed first comparisons of lungs between the in vivo and immediate post mortem states.

[1]  Frank Bergner,et al.  Low-dose cardio-respiratory phase-correlated cone-beam micro-CT of small animals. , 2011, Medical physics.

[2]  H. Krapp,et al.  In Vivo Time-Resolved Microtomography Reveals the Mechanics of the Blowfly Flight Motor , 2014, PLoS biology.

[3]  Marco Stampanoni,et al.  A robust tool for photon source geometry measurements using the fractional Talbot effect. , 2014, Optics express.

[4]  William Thomlinson,et al.  Quantitative measurement of regional lung gas volume by synchrotron radiation computed tomography , 2005, Physics in medicine and biology.

[5]  Kentaro Uesugi,et al.  Murine pulmonary acinar mechanics during quasi-static inflation using synchrotron refraction-enhanced computed tomography. , 2013, Journal of applied physiology.

[6]  V. Semenenko,et al.  Irradiation of varying volumes of rat lung to same mean lung dose: a little to a lot or a lot to a little? , 2008, International journal of radiation oncology, biology, physics.

[7]  S. Wilkins,et al.  Simultaneous phase and amplitude extraction from a single defocused image of a homogeneous object , 2002, Journal of microscopy.

[8]  Jung Il Lee,et al.  Development of a small animal model to simulate clinical stereotactic body radiotherapy-induced central and peripheral lung injuries , 2014, Journal of radiation research.

[9]  H. Suhonen,et al.  Differences in the time course of proximal and distal airway response to inhaled histamine studied by synchrotron radiation CT. , 2006, Journal of applied physiology.

[10]  D. Cooper,et al.  In vivo imaging of rat cortical bone porosity by synchrotron phase contrast micro computed tomography , 2015, Physics in medicine and biology.

[11]  Froma P. Roth,et al.  Unresolved Mysteries , 1996 .

[12]  Stuart B Hooper,et al.  Synchrotron-based dynamic computed tomography of tissue motion for regional lung function measurement , 2012, Journal of The Royal Society Interface.

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

[14]  Heikki Suhonen,et al.  Imaging of lung function using synchrotron radiation computed tomography: what's new? , 2008, European journal of radiology.

[15]  Maria Drangova,et al.  Optimization of a retrospective technique for respiratory-gated high speed micro-CT of free-breathing rodents , 2007, Physics in Medicine and Biology.

[16]  A R Sovijärvi,et al.  Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent. , 2001, Physics in medicine and biology.

[17]  Robert C. Wolpert,et al.  A Review of the , 1985 .

[18]  J. Tinevez,et al.  Irradiation damage to frog inner ear during synchrotron radiation tomographic investigation , 2009 .

[19]  M. Stampanoni,et al.  Automated computer-assisted quantitative analysis of intact murine lungs at the alveolar scale , 2017, PloS one.

[20]  P. Davis,et al.  Establishing Functional Residual Capacity at Birth: The Effect of Sustained Inflation and Positive End-Expiratory Pressure in a Preterm Rabbit Model , 2009, Pediatric Research.

[21]  Edmund Koch,et al.  Alveolar dynamics in acute lung injury: Heterogeneous distension rather than cyclic opening and collapse* , 2009, Critical care medicine.

[22]  Andreas H. Jacobs,et al.  Imaging in Neurology Research I: Neurooncology , 2011 .

[23]  Jason H T Bates,et al.  The role of time and pressure on alveolar recruitment. , 2009, Journal of applied physiology.

[24]  Bernd J. Pichler,et al.  Small animal imaging : basics and practical guide , 2011 .

[25]  Holger G. Krapp,et al.  Four-dimensional in vivo X-ray microscopy with projection-guided gating , 2015, Scientific Reports.

[26]  Maria Drangova,et al.  Prospective respiratory-gated micro-CT of free breathing rodents. , 2005, Medical physics.

[27]  Bram van Ginneken,et al.  Automated segmentation of pulmonary structures in thoracic computed tomography scans: a review , 2013 .

[28]  Marco Stampanoni,et al.  A multi-purpose imaging endstation for high-resolution micrometer-scaled sub-second tomography. , 2016, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[29]  K K W Siu,et al.  Dynamic imaging of the lungs using x-ray phase contrast , 2005, Physics in medicine and biology.

[30]  Kamel Fezzaa,et al.  Tracheal Respiration in Insects Visualized with Synchrotron X-ray Imaging , 2003, Science.

[31]  M. Flentje,et al.  A Little to a Lot or a Lot to a Little? , 2003, Strahlentherapie und Onkologie.

[32]  Kentaro Uesugi,et al.  Imaging lung aeration and lung liquid clearance at birth , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  Robert D. Kirch,et al.  In vivo visualization of gold-loaded cells in mice using x-ray computed tomography. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[34]  Marco Stampanoni,et al.  Dose optimization approach to fast X-ray microtomography of the lung alveoli , 2013, Journal of applied crystallography.

[35]  J. Jassem,et al.  Functional evaluation of postradiation lung injury , 1996 .

[36]  Wayne Mitzner,et al.  Viewpoint: unresolved mysteries. , 2012, Journal of applied physiology.

[37]  Y Seppenwoolde,et al.  Partial irradiation of the lung. , 2001, Seminars in radiation oncology.

[38]  M. Anscher,et al.  Radiation-induced lung injury. , 2003, Seminars in radiation oncology.

[39]  Andreas Fouras,et al.  The past, present, and future of x-ray technology for in vivo imaging of function and form , 2009 .

[40]  S. Hooper,et al.  Inspiration regulates the rate and temporal pattern of lung liquid clearance and lung aeration at birth. , 2009, Journal of applied physiology.

[41]  Tilo Baumbach,et al.  X-ray phase-contrast in vivo microtomography probes new aspects of Xenopus gastrulation , 2013, Nature.

[42]  Bram van Ginneken,et al.  Automated segmentation of pulmonary structures in thoracic computed tomography scans: a review , 2013, Physics in medicine and biology.

[43]  Masaki Yamamoto,et al.  Tracking X-ray microscopy for alveolar dynamics in live intact mice , 2013, Scientific Reports.

[44]  M. Stampanoni,et al.  Regridding reconstruction algorithm for real-time tomographic imaging , 2012, Journal of synchrotron radiation.

[45]  J. L. Bas,et al.  High-Resolution Blood–Brain Barrier Permeability and Blood Volume Imaging Using Quantitative Synchrotron Radiation Computed Tomography: Study on an F98 Rat Brain Glioma , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[46]  Kentaro Uesugi,et al.  Development of high-resolution 4D in vivo-CT for visualization of cardiac and respiratory deformations of small animals , 2008, Physics in medicine and biology.

[47]  T. Schilcher,et al.  Assessing noise sources at synchrotron infrared ports , 2011, Journal of synchrotron radiation.