Cardio-chemical exchange saturation transfer magnetic resonance imaging reveals molecular signatures of endogenous fibrosis and exogenous contrast media

Circ Cardiovasc Imaging. 2014 Dec 30;8(1):e002180. doi: 10.1161/CIRCIMAGING.114.002180. Print 2015 Jan.

Abstract

Background: Application of emerging molecular MRI techniques, including chemical exchange saturation transfer (CEST)-MRI, to cardiac imaging is desirable; however, conventional methods are poorly suited for cardiac imaging, particularly in small animals with rapid heart rates. We developed a CEST-encoded steady state and retrospectively gated cardiac cine imaging sequence in which the presence of fibrosis or paraCEST contrast agents was directly encoded into the steady-state myocardial signal intensity (cardioCEST).

Methods and results: Development of cardioCEST: A CEST-encoded cardiac cine MRI sequence was implemented on a 9.4T small animal scanner. CardioCEST of fibrosis was serially performed by acquisition of a series of CEST-encoded cine images at multiple offset frequencies in mice (n=7) after surgically induced myocardial infarction. Scar formation was quantified using a spectral modeling approach and confirmed with histological staining. Separately, circulatory redistribution kinetics of the paramagnetic CEST agent Eu-HPDO3A were probed in mice using cardioCEST imaging, revealing rapid myocardial redistribution, and washout within 30 minutes (n=6). Manipulation of vascular tone resulted in heightened peak CEST contrast in the heart, but did not alter redistribution kinetics (n=6). At 28 days after myocardial infarction (n=3), CEST contrast kinetics in infarct zone tissue were altered, demonstrating gradual accumulation of Eu-HPDO3A in the increased extracellular space.

Conclusions: cardioCEST MRI enables in vivo imaging of myocardial fibrosis using endogenous contrast mechanisms, and of exogenously delivered paraCEST agents, and can enable multiplexed imaging of multiple molecular targets at high-resolution coupled with conventional cardiac MRI scans.

Keywords: magnetic resonance imaging; magnetization transfer contrast imaging; myocardial infarction.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiac-Gated Imaging Techniques
  • Contrast Media* / pharmacokinetics
  • Disease Models, Animal
  • Equipment Design
  • Feasibility Studies
  • Fibrosis
  • Gadolinium / pharmacokinetics
  • Heterocyclic Compounds* / pharmacokinetics
  • Image Interpretation, Computer-Assisted
  • Magnetic Resonance Imaging, Cine* / instrumentation
  • Male
  • Mice, Inbred C57BL
  • Molecular Imaging / instrumentation
  • Molecular Imaging / methods*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology*
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Organometallic Compounds* / pharmacokinetics
  • Predictive Value of Tests
  • Ventricular Remodeling

Substances

  • Contrast Media
  • Heterocyclic Compounds
  • Organometallic Compounds
  • gadoteridol
  • Gadolinium