title: Changes of renal water diffusion coefficient after application of iodinated contrast agents:  effect of viscosity.
abstract: OBJECTIVE
  X-ray contrast agents (CA) possess specific physicochemical properties and are excreted renally by glomerular filtration. Thereby, they may affect the diffusion of water molecules within the kidney. The aim of our preclinical study was to investigate potential changes in the apparent diffusion coefficient (ADC) of the kidney after administration of monomeric, low-osmolar, and dimeric, iso-osmolar CA by using diffusion-weighted magnetic resonance imaging (DWI).
  
  
  METHODS
  First, the relationship between CA viscosity and the ADC of water was assessed by phantom measurements. Subsequently, Han Wistar rats (8 per group) received an intravenous injection of iso-osmolar CA (iodixanol) or low-osmolar CA (iopromide) at a dosage of 4 gI/kg body weight. The control group received saline (0.9% NaCl) at the same volume. The renal ADC was dynamically monitored up to 40 minutes postinjection (p.i.) by DWI using a 1.5-T clinical MR unit. After DWI, the animals were killed and the kidneys were removed for iodine measurements by x-ray fluorescence analysis.
  
  
  RESULTS
  The in vitro measurements yielded an inverse relationship between increasing viscosity and decreasing water diffusion. In vivo, a slight increase in ADC was observed immediately after administration of the low-osmolar iopromide (ΔADC=80±78 μm²/s) and saline (ΔADC=89±53 μm²/s), which normalized to the baseline level at 40 minutes p.i. In contrast, a strong decrease in ADC was observed after administration of the iso-osmolar iodixanol. This was most prominent 12 minutes p.i. (ΔADC=-555±194 μm²/s) and persisted throughout the investigation. Concomitantly, the kidney iodine concentration 50 minutes p.i. was significantly higher after iodixanol (58.6±5.3 mgI/g kidney) compared with iopromide injection (18.4±4.5 mgI/g kidney).
  
  
  CONCLUSIONS
  A significant difference in the renal ADC was observed between the low-osmolar CA/saline and the iso-osmolar CA. The in vitro measurements suggest that the substantial decrease in ADC observed after administration of the iso-osmolar CA is based on the high viscosity of the agent during renal passage. This, in turn, may explain the delayed iodine retention after administration of iso-osmolar CA and demonstrates the importance of the physicochemical properties of CA during their renal elimination.
authors.affiliation: TRG Diagnostic Imaging, Bayer Pharma AG, Berlin, Germany. Gregor.Jost@bayer.com
authors.forename: Gregor
authors.initials: G
authors.lastname: Jost
authors.forename: Diana C
authors.initials: DC
authors.lastname: Lenhard
authors.forename: Martin A
authors.initials: MA
authors.lastname: Sieber
authors.forename: Philipp
authors.initials: P
authors.lastname: Lengsfeld
authors.forename: Joachim
authors.initials: J
authors.lastname: Hütter
authors.forename: Hubertus
authors.initials: H
authors.lastname: Pietsch
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000494:pharmacology*; D004058:Diffusion / Q000187:drug effects; D007472:Iohexol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D014283:Triiodobenzoic Acids / Q000494:pharmacology*; D014783:Viscosity; D014867:Water / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D014283:Triiodobenzoic Acids; D014867:Water; D007472:Iohexol; C038192:iopromide; C044834:iodixanol