Abstract
Since lung diseases adversely affect airflow during breathing, they must also alter normal lung motion, which can be exploited to detect these diseases. However, standard imaging techniques such as CT and MRI imaging during breath-holds provide little or no information on lung motion and cannot detect diseases that cause subtle changes in lung structure. Phase-contrast X-ray imaging provides images of high contrast and spatial resolution with temporal resolutions that allow multiple images to be acquired throughout the respiratory cycle. Using X-ray phase-contrast imaging, coupled with velocimetry, we have measured lung tissue movement and determined velocity fields that define speed and direction of regional lung motion throughout a breath in normal Balb/c nude male mice and mice exposed to bleomycin. Regional maps of lung tissue motion reveal both the heterogeneity of normal lung motion, as well as abnormal motion induced by bleomycin treatment. Analysed histologically, bleomycin treatment caused pathological changes in lung structure that were heterogenous, occupying less than 12% of the lung at 6 days after treatment. Moreover, plethysmography failed to detect significant changes in compliance at either 36 h or 6 days after treatment. Detailed analysis of the vector fields demonstrated major differences (p < 0.001) in regional lung motion between control and bleomycin-treated mice at both 36 h and 6 days after treatment. The results of this study demonstrate that X-ray phase-contrast imaging, coupled with velocimetry, can detect early stage, subtle and non-uniform lung disease.
Similar content being viewed by others
References
Adam, J. F., et al. Quantitative functional imaging and kinetic studies with high-Z contrast agents using synchrotron radiation computed tomography. Clin. Exp. Pharmacol. Physiol. 36(1):95–106, 2009.
Adamson, I. Y. R., and D. H. Bowden. Pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am. J. Pathol. 77(2):185–199, 1974.
Adrian, R. J. Twenty years of particle image velocimetry. Exp. Fluids 39(2):159–169, 2005.
Albert, S. P., et al. The role of time and pressure on alveolar recruitment. J. Appl. Physiol. 106(3):757–765, 2009.
Allen, G. B., et al. Pulmonary impedance and alveolar instability during injurious ventilation in rats. J. Appl. Physiol. 99(2):723–730, 2005.
Black, C. L. B., et al. Relationship between dynamic respiratory mechanics and disease heterogeneity in sheep lavage injury. Crit. Care Med. 35(3):870–878, 2007.
Boulet, L. P., M. Belanger, and G. Carrier. Airway responsiveness and bronchial-wall thickness in asthma with or without fixed air-flow obstruction. Am. J. Respir. Crit. Care Med. 152(3):865–871, 1995.
Castillo, R., et al. Ventilation from four-dimensional computed tomography: density versus Jacobian methods. Phys. Med. Biol. 55(16):4661–4685, 2010.
Christensen, G. E., et al. Tracking lung tissue motion and expansion/compression with inverse consistent image registration and spirometry. Med. Phys. 34(6):2155–2163, 2007.
Dubsky, S., et al. Computed tomographic X-ray velocimetry. Appl. Phys. Lett. 96(2):023702, 2010.
Fouras, A., D. Lo Jacono, and K. Hourigan. Target-free Stereo PIV: a novel technique with inherent error estimation and improved accuracy. Exp. Fluids 44(2):317–329, 2008.
Fouras, A., and J. Soria. Accuracy of out-of-plane vorticity measurements derived from in-plane velocity field data. Exp. Fluids 25(5–6):409–430, 1998.
Fouras, A., et al. Three-dimensional synchrotron X-ray particle image velocimetry. J. Appl. Phys. 102(6):064916, 2007.
Guerrero, T., et al. Quantification of regional ventilation from treatment planning CT. Int. J. Radiat. Oncol. Biol. Phys. 62(3):630–634, 2005.
Guerrero, T., et al. Dynamic ventilation imaging from four-dimensional computed tomography. Phys. Med. Biol. 51(4):777–791, 2006.
Hodgson, M. J., D. K. Parkinson, and M. Karpf. Chest X-rays in hypersensitivity pneumonitis—a metaanalysis of secular trend. Am. J. Ind. Med. 16(1):45–53, 1989.
Hoffman, E. A., et al. Estimation of regional pleural surface expansile forces in intact dogs. J. Appl. Physiol. 55(3):935–948, 1983.
Hogg, J. C. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 364(9435):709–721, 2004.
Hooper, S. B., et al. Imaging lung aeration and lung liquid clearance at birth. FASEB J. 21(12):3329–3337, 2007.
Hooper, S. B., et al. Imaging lung aeration and lung liquid clearance at birth using phase contrast X-ray imaging. Clin. Exp. Pharmacol. Physiol. 36(1):117–125, 2009.
Hove, J. R., et al. Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421(6919):172–177, 2003.
Hsia, C. C. W., et al. An official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am. J. Respir. Crit. Care Med. 181(4):394–418, 2010.
Im, K. S., et al. Particle tracking velocimetry using fast X-ray phase-contrast imaging. Appl. Phys. Lett. 90(9):3, 2007.
Irvine, S. C., et al. Phase retrieval for improved three-dimensional velocimetry of dynamic X-ray blood speckle. Appl. Phys. Lett. 93(15):153901, 2008.
Jamison, R. A., et al. X-ray velocimetry and haemodynamic forces within a stenosed femoral model at physiological flow rates. Ann. Biomed. Eng. 39(6):1643–1653, 2011.
Kitchen, M. J., et al. On the origin of speckle in X-ray Phase Contrast images of lung tissue. Phys. Med. Biol. 49(18):4335–4348, 2004.
Kitchen, M. J., et al. Phase contrast X-ray imaging of mice and rabbit lungs: a comparative study. Br. J. Radiol. 78(935):1018–1027, 2005.
Kitchen, M. J., et al. Dynamic measures of regional lung air volume using Phase Contrast X-ray Imaging. Phys. Med. Biol. 53(21):6065–6077, 2008.
Kitchen, M. J., et al. A new design for high stability pressure-controlled ventilation for small animal lung imaging. J. Instrum. 5:T02002, 2010.
Lai-Fook, S. J., and R. E. Hyatt. Effects of age on elastic moduli of human lungs. J. Appl. Physiol. 89(1):163–168, 2000.
Lazenby, A. J., et al. Remodeling of the lung in bleomycin-induced pulmonary fibrosis in the rat—an immunohistochemical study of laminin, type-IV collagen, and fibronectin. Am. Rev. Respir. Dis. 142(1):206–214, 1990.
Lee, S. J., and G. B. Kim. X-ray particle image velocimetry for measuring quantitative flow information inside opaque objects. J. Appl. Phys. 94(5):3620–3623, 2003.
Lee, S. J., and G. B. Kim. Synchrotron microimaging technique for measuring the velocity fields of real blood flows. J. Appl. Phys. 97(6):6, 2005.
Lewis, R. A. Medical phase contrast x-ray imaging: current status and future prospects. Phys. Med. Biol. 49(16):3573–3583, 2004.
Lewis, R. A., et al. Dynamic imaging of the lungs using X-ray phase contrast. Phys. Med. Biol. 50(21):5031–5040, 2005.
Maltais, F., et al. Comparison of static and dynamic measurements of intrinsic peep in mechanically ventilated patients. Am. J. Respir. Crit. Care Med. 150(5):1318–1324, 1994.
Manali, E., et al. Static and dynamic mechanics of the murine lung after intratracheal bleomycin. BMC Pulm. Med. 11(1):33, 2011.
Nesbitt, W. S., et al. A shear gradient-dependent platelet aggregation mechanism drives thrombus formation. Nat. Med. 15(6):665–673, 2009.
Onodera, M., et al. Determination of ventilatory volume in mice by whole body plethysmography. Jpn. J. Physiol. 47(4):317–326, 1997.
Pan, T., et al. 4D-CT imaging of a volume influenced by respiratory motion on multi-slice CT. Med. Phys. 31(2):333–340, 2004.
Poelma, C., et al. In vivo blood flow and wall shear stress measurements in the vitelline network. Exp. Fluids 45(4):703–713, 2008.
Reinhardt, J. M., et al. Registration-based estimates of local lung tissue expansion compared to xenon CT measures of specific ventilation. Med. Image Anal. 12(6):752–763, 2008.
Robertson, H. T., et al. High-resolution maps of regional ventilation utilizing inhaled fluorescent microspheres. J. Appl. Physiol. 82(3):943–953, 1997.
Schrier, D. J., S. H. Phan, and B. M. McGarry. The effects of the nude (nu/nu) mutation on bleomycin-induced pulmonary fibrosis—a biochemical evaluation. Am. Rev. Respir. Dis. 127(5):614–617, 1983.
Sethi, S., and T. F. Murphy. Current concepts: infection in the pathogenesis and course of chronic obstructive pulmonary disease. N. Engl. J. Med. 359(22):2355–2365, 2008.
Siew, M. L., et al. Inspiration regulates the rate and temporal pattern of lung liquid clearance and lung aeration at birth. J. Appl. Physiol. 106(6):1888–1895, 2009.
Snigirev, A., et al. On the possibilities of X-ray phase contrast microimaging by coherent high-energy synchrotron radiation. Rev. Sci. Instrum. 66(12):5486–5492, 1995.
Sundaram, T. A., and J. C. Gee. Towards a model of lung biomechanics: pulmonary kinematics via registration of serial lung images. Med. Image Anal. 9(6):524–537, 2005.
Sznitman, J., et al. Visualization of respiratory flows from 3D reconstructed alveolar airspaces using X-ray tomographic microscopy. J. Vis. 13(4):337–345, 2010.
Tustison, N. J., et al. Pulmonary kinematics from tagged hyperpolarized helium-3 MRI. J. Magn. Reson. Imaging 31(5):1236–1241, 2010.
Tustison, N. J., et al. Pulmonary kinematics from image data: a review. Acad. Radiol. 18(4):402–417, 2011.
Udalov, S., et al. Effects of phosphodiesterase 4 inhibition on bleomycin-induced pulmonary fibrosis in mice. BMC Pulm. Med. 10:26, 2010.
Westneat, M. W., J. J. Socha, and W.-K. Lee. Advances in biological structure, function, and physiology using synchrotron X-ray imaging. Annu. Rev. Physiol. 70:119–142, 2008.
Westneat, M. W., et al. Tracheal respiration in insects visualized with synchrotron X-ray imaging. Science 299(5606):558–560, 2003.
Wilkins, S. W., et al. Phase-contrast imaging using polychromatic hard X-rays. Nature 384(6607):335–338, 1996.
Yagi, N., et al. Refraction-enhanced X-ray imaging of mouse lung using synchrotron radiation source. Med. Phys. 26(10):2190–2193, 1999.
Yin, Y. B., et al. Simulation of pulmonary air flow with a subject-specific boundary condition. J. Biomech. 43(11):2159–2163, 2010.
Acknowledgments
We thank Charlene Chua for assistance with figures; Melissa Siew for assistance with statistical analysis; David Paganin, Kevin Wheeler, John McDougal, Bruce Thompson and Christopher Stuart-Andrews for discussions. Research is funded by the Australian Research Council (DP110101498), the National Health and Medical Research Council (491103) and supported by beamtime grants from the Japan Synchrotron Radiation Research Institute. We acknowledge travel funding provided by the International Synchrotron Access Program (ISAP) managed by the Australian Synchrotron and funded by the Australian Government.
Author information
Authors and Affiliations
Corresponding author
Additional information
Associate Editor Kenneth R. Lutchen oversaw the review of this article.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Fouras, A., Allison, B.J., Kitchen, M.J. et al. Altered Lung Motion is a Sensitive Indicator of Regional Lung Disease. Ann Biomed Eng 40, 1160–1169 (2012). https://doi.org/10.1007/s10439-011-0493-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10439-011-0493-0