Quantitative Gd-DOTA-based aerosol deposition mapping in the lungs of asthmatic rats using 3D UTE-MRI

NMR Biomed. 2018 Dec;31(12):e4013. doi: 10.1002/nbm.4013. Epub 2018 Oct 11.

Abstract

Asthma is a chronic respiratory disease, commonly treated with inhaled therapy. Better understanding of the mechanisms of aerosol deposition is required to improve inhaled drug delivery. Three-dimensional ultrashort echo time (UTE) MRI acquisitions at 1.5 T were combined with spontaneous nose-only inhalation of aerosolized gadolinium (Gd) to map the aerosol deposition and to characterize signal enhancement in asthmatic rat lungs. The rats were sensitized to ovalbumin (OVA) to develop asthmatic models and challenged before imaging by nebulization of OVA to trigger asthmatic symptoms. The negative controls were not sensitized or challenged by nebulization of saline. The animal lungs were imaged before and after administration of Gd-based aerosol in freely breathing rats, by using a T1 -weighted 3D UTE sequence. A contrast-enhanced quantitative analysis was performed to assess regional concentration. OVA-sensitized rats had lower signal enhancement and lower deposited aerosol concentration. Their enhancement dynamics showed large inter-subject variability. The signal intensity was homogeneously enhanced for controls while OVA-sensitized rats showed heterogeneous enhancement. Contrast-enhanced 3D UTE was applied with aerosolized Gd to efficiently measure spatially resolved deposition in asthmatic lungs. The small administered dose (around 1 μmol/kg body weight) and the use of standard clinical MRI suggest a potential application for the exploration of asthma.

Keywords: Gd-DOTA; aerosol deposition; asthma; contrast enhancement; lung MRI; ultrashort echo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols / analysis*
  • Animals
  • Asthma / diagnostic imaging*
  • Asthma / pathology*
  • Female
  • Heterocyclic Compounds / chemistry*
  • Imaging, Three-Dimensional*
  • Lung / diagnostic imaging*
  • Lung / pathology*
  • Magnetic Resonance Imaging*
  • Organometallic Compounds / chemistry*
  • Rats, Wistar
  • Respiration
  • Time Factors

Substances

  • Aerosols
  • Heterocyclic Compounds
  • Organometallic Compounds
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate