In vivo imaging of paraCEST agents using frequency labeled exchange transfer MRI

Magn Reson Med. 2014 Jan;71(1):286-93. doi: 10.1002/mrm.24603. Epub 2013 Mar 6.


Purpose: A main obstacle to in vivo applications of paramagnetic chemical exchange saturation transfer (paraCEST) is interference from endogenous tissue magnetization transfer contrast (MTC). The suitability of excitation-based frequency labeled exchange transfer (FLEX) to separate out such MTC effects in vivo was tested.

Methods: The FLEX sequence measures modulation of the water signal based on the chemical shift evolution of solute proton magnetization as a function of evolution time. Time-domain analysis of this water signal allows identification of different solute components and provides a mechanism to separate out the rapidly decaying MTC components with short effective transverse relaxation time ( T2*) values.

Results: FLEX imaging of paraCEST agents was possible in vitro in phantoms and in vivo in mouse kidneys and bladder. The results demonstrated that FLEX is capable of separating out the MTC signal from tissues in vivo while providing a quantitative exchange rate for the rapidly exchanging paraCEST water protons by fitting the FLEX time-domain signal to FLEX theory.

Conclusions: The first in vivo FLEX images of a paraCEST agent were acquired, which allowed separation of the tissue MTC components. These results show that FLEX imaging has potential for imaging the distribution of functional paraCEST agents in biological tissues.

Keywords: chemical exchange saturation transfer; exchange rate; magnetization transfer; paramagnetic contrast agent.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Water / metabolism*
  • Contrast Media
  • Coordination Complexes / pharmacokinetics*
  • Image Interpretation, Computer-Assisted / methods
  • Kidney / metabolism*
  • Lanthanoid Series Elements / pharmacokinetics
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Imaging / methods*
  • Protons
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Staining and Labeling
  • Urinary Bladder / metabolism*


  • Contrast Media
  • Coordination Complexes
  • Lanthanoid Series Elements
  • Protons
  • europium DOTA-tetraglycinate