High-Resolution Phase-Contrast Imaging of Submicron Particles in Unstained Lung Tissue

Abstract

Abstract.To access the risks and chances of deposition of submicron particles in the gas-exchange area of the lung, a precise three-dimensional (3D)-localization of the sites of deposition is essential-especially because local peaks of deposition are expected in the acinar tree and in individual alveoli. In this study we developed the workflow for such an investigation. We administered 200-nm gold particles to young adult rats by intratracheal instillation. After fixation and paraffin embedding, their lungs were imaged unstained using synchrotron radiation x-ray tomographic microscopy (SRXTM) at the beamline TOMCAT (Swiss Light Source, Villigen, Switzerland) at sample detector distances of 2.5 mm (absorption contrast) and of 52.5 mm (phase contrast). A segmentation based on a global threshold of grey levels was successfully done on absorption-contrast images for the gold and on the phase-contrast images for the tissue. The smallest spots containing gold possessed a size of 1-2 voxels of 370-nm side length. We conclude that a combination of phase and absorption contrast SRXTM imaging is necessary to obtain the correct segmentation of both tissue and gold particles. This method will be used for the 3D localization of deposited particles in the gas-exchange area of the lung.

Feasibility of a surface-coated lung model for the quantification of active agent deposition for preclinical studies

“…For in vivo models, imaging techniques such as gamma scintigraphy, positron emission tomography (PET), single-photon emission computed tomography (SPECT), or magnetic resonance imaging (MRI) measure particle deposition directly in living animals using radionuclides or non-ionizing radiation, as shown by Conway 11 . Schittny et al 27 used phase contrast imaging to determine the deposition of 200 nm gold particles injected into the lungs of young adult rats by intratracheal instillation. The deposition of particles can also be analysed on the basis of tissue examinations, as reported by Yanamala et al 36 In summary, it can be stated that, to the best of our knowledge, there are no models available that simulate the flow field and the particle deposition in the respiratory tract of a realistic human lung geometry simultaneously.…”

Image-based modelling of skeletal muscle oxygenation

“…Another advantage of synchrotron radiation includes the fact that the X-ray beam is monochromatic and is delivered at a high flux, both of which are not essential for propagation-based phase contrast imaging [108], but avoid beam hardening effects and reduce scanning time significantly, respectively. Phase-contrast mCT has successfully been used to image sub-micrometre particles in unstained lung tissue with a voxel size of 370 nm [109].…”