Validating the sensitivity of inhomogeneous magnetization transfer (ihMT) MRI to myelin with fluorescence microscopy

Neuroimage. 2019 Oct 1;199:289-303. doi: 10.1016/j.neuroimage.2019.05.061. Epub 2019 May 26.

Abstract

Inhomogeneous Magnetization Transfer (ihMT) is a development from the MT MRI technique. IhMT can be considered as a dipolar order relaxation time (T1D) weighted imaging modality whose signal has shown an enhanced selectivity for myelin-rich structures. However, a formal validation of the ihMT sensitivity relative to a gold standard myelin density measurement has not yet been reported. To address this need, we compared ihMT MRI with green fluorescence protein (GFP) microscopy, in a study performed on genetically-modified plp-GFP mice, considered as a reference technique for myelin-content assessment. Various ihMT protocols consisting of variable T1D-filtering and radiofrequency power temporal distributions, were used for comparison with fluorescence microscopy. Strong and significant linear relationships (r2 (0.87-0.96), p < 0.0001) were found between GFP and ihMT ratio signals across brain regions for all tested protocol variants. Conventional MT ratios showed weaker correlations (r2 (0.24-0.78), p ≤ 0.02) and a much larger signal fraction unrelated to myelin, hence corresponding to a much lower specificity for myelin. T1D-filtering reduced the ihMT signal fraction not attributed to myelin by almost twofold relative to zero filtering suggesting that at least half of the unrelated signal has a substantially shorter T1D than myelin. Overall, these results strongly support the sensitivity of ihMT to myelin content.

Keywords: Fluorescence microscopy; Inhomogeneous magnetization transfer; MRI; Myelin imaging; ihMT; plp-GFP.

Publication types

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

MeSH terms

  • Animals
  • Data Interpretation, Statistical
  • Gray Matter / diagnostic imaging*
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Imaging / standards*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence / standards*
  • Myelin Sheath*
  • Sensitivity and Specificity
  • White Matter / diagnostic imaging*