Assessment of Myocardial Fibrosis in Mice Using a T2*-Weighted 3D Radial Magnetic Resonance Imaging Sequence

PLoS One. 2015 Jun 26;10(6):e0129899. doi: 10.1371/journal.pone.0129899. eCollection 2015.

Abstract

Background: Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis.

Objective: To goal of this paper was to explore the use of a T2*-weighted radial sequence for the visualization of fibrosis in mouse heart.

Methods: C57BL/6 mice were studied with MI (n = 20, replacement fibrosis), transverse aortic constriction (TAC) (n = 18, diffuse fibrosis), and as control (n = 10). 3D center-out radial T2*-weighted images with varying TE were acquired in vivo and ex vivo (TE = 21 μs-4 ms). Ex vivo T2*-weighted signal decay with TE was analyzed using a 3-component model. Subtraction of short- and long-TE images was used to highlight fibrotic tissue with short T2*. The presence of fibrosis was validated using histology and correlated to MRI findings.

Results: Detailed ex vivo T2*-weighted signal analysis revealed a fast (T2*fast), slow (T2*slow) and lipid (T2*lipid) pool. T2*fast remained essentially constant. Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts. T2*slow correlated with the presence of diffuse fibrosis in TAC hearts (r = 0.82, P = 0.01). Ex vivo and in vivo subtraction images depicted a positive contrast in the infarct co-localizing with the scar. Infarct volumes from histology and subtraction images linearly correlated (r = 0.94, P<0.001). Region-of-interest analysis in the in vivo post-MI and TAC hearts revealed significant T2* shortening due to fibrosis, in agreement with the ex vivo results. However, in vivo contrast on subtraction images was rather poor, hampering a straightforward visual assessment of the spatial distribution of the fibrotic tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathies / diagnosis*
  • Cardiomyopathies / etiology
  • Cardiomyopathies / pathology*
  • Disease Models, Animal
  • Fibrosis
  • Imaging, Three-Dimensional* / methods
  • Magnetic Resonance Imaging* / methods
  • Male
  • Mice

Grants and funding

This research was performed within the framework of the Center for Translational Molecular Medicine (grant 01C-103), and supported by the Netherlands Heart Foundation. NAB was supported by a grant from the Dutch government to the Netherlands Institute for Regenerative Medicine (grant FES0908). FA was supported by research grants from the Netherlands Heart Foundation (contract 2010.T001), Netherlands Genomics Initiative & ZonMw (contract 40-41300-98-11028).