Ex Vivo Perfusion-Simulation Measurements of Microbubbles as a Scattering Contrast Agent for Grating-Based X-Ray Dark-Field Imaging

PLoS One. 2015 Jul 2;10(7):e0129512. doi: 10.1371/journal.pone.0129512. eCollection 2015.

Abstract

The investigation of dedicated contrast agents for x-ray dark-field imaging, which exploits small-angle scattering at microstructures for contrast generation, is of strong interest in analogy to the common clinical use of high-atomic number contrast media in conventional attenuation-based imaging, since dark-field imaging has proven to provide complementary information. Therefore, agents consisting of gas bubbles, as used in ultrasound imaging for example, are of particular interest. In this work, we investigate an experimental contrast agent based on microbubbles consisting of a polyvinyl-alcohol shell with an iron oxide coating, which was originally developed for multimodal imaging and drug delivery. Its performance as a possible contrast medium for small-animal angiography was examined using a mouse carcass to realistically consider attenuating and scattering background signal. Subtraction images of dark field, phase contrast and attenuation were acquired for a concentration series of 100%, 10% and 1.3% to mimic different stages of dilution in the contrast agent in the blood vessel system. The images were compared to the gold-standard iodine-based contrast agent Solutrast, showing a good contrast improvement by microbubbles in dark-field imaging. This study proves the feasibility of microbubble-based dark-field contrast-enhancement in presence of scattering and attenuating mouse body structures like bone and fur. Therefore, it suggests a strong potential of the use of polymer-based microbubbles for small-animal dark-field angiography.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiography / instrumentation
  • Angiography / methods*
  • Animals
  • Contrast Media / chemistry
  • Ferric Compounds / chemistry
  • Iopamidol / chemistry
  • Light
  • Mice
  • Microbubbles / veterinary*
  • Molecular Imaging / instrumentation
  • Molecular Imaging / methods*
  • Perfusion
  • Polyvinyl Alcohol / chemistry
  • Scattering, Small Angle
  • Tomography, X-Ray Computed / instrumentation
  • Tomography, X-Ray Computed / methods*

Substances

  • Contrast Media
  • Ferric Compounds
  • ferric oxide
  • Polyvinyl Alcohol
  • Iopamidol

Grants and funding

The authors acknowledge financial support through the DFG Cluster of Excellence Munich-Centre for Advanced Photonics (MAP, grant no. DFG EXC-158), the DFG Gottfried Wilhelm Leibniz program, the European Research Council (ERC, FP7, StG 240142) and the Siemens AG. This work was carried out with the support of the Karlsruhe Nano Micro Facility (KNMF, www.kit.edu/knmf), a Helmholtz Research Infrastructure at Karlsruhe Institute of Technology (KIT, www.kit.edu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.