High-resolution three-dimensional macromolecular proton fraction mapping for quantitative neuroanatomical imaging of the rodent brain in ultra-high magnetic fields

Abstract

A well-known problem in ultra-high-field MRI is generation of high-resolution three-dimensional images for detailed characterization of white and gray matter anatomical structures. T1-weighted imaging traditionally used for this purpose suffers from the loss of contrast between white and gray matter with an increase of magnetic field strength. Macromolecular proton fraction (MPF) mapping is a new method potentially capable to mitigate this problem due to strong myelin-based contrast and independence of this parameter of field strength. MPF is a key parameter determining the magnetization transfer effect in tissues and defined within the two-pool model as a relative amount of macromolecular protons involved into magnetization exchange with water protons. The objectives of this study were to characterize the two-pool model parameters in brain tissues in ultra-high magnetic fields and introduce fast high-field 3D MPF mapping as both anatomical and quantitative neuroimaging modality for small animal applications. In vivo imaging data were obtained from four adult male rats using an 11.7T animal MRI scanner. Comprehensive comparison of brain tissue contrast was performed for standard R1 and T2 maps and reconstructed from Z-spectroscopic images two-pool model parameter maps including MPF, cross-relaxation rate constant, and T2 of pools. Additionally, high-resolution whole-brain 3D MPF maps were obtained with isotropic 170 μm voxel size using the single-point synthetic-reference method. MPF maps showed 3–6-fold increase in contrast between white and gray matter compared to other parameters. MPF measurements by the single-point synthetic reference method were in excellent agreement with the Z-spectroscopic method. MPF values in rat brain structures at 11.7T were similar to those at lower field strengths, thus confirming field independence of MPF. 3D MPF mapping provides a useful tool for neuroimaging in ultra-high magnetic fields enabling both quantitative tissue characterization based on the myelin content and high-resolution neuroanatomical visualization with high contrast between white and gray matter.

Histological validation of fast macromolecular proton fraction mapping as a quantitative myelin imaging method in the cuprizone demyelination model

“…Additionally, the dependence on T 1 makes MTR sensitive to the magnetic field strength and the effect of paramagnetic ions, such as iron, which frequently confounds demyelination, particularly in subcortical GM576061. MPF itself is independent of the presence of paramagnetic substances and field strength22. Alternative semi-empirical indexes describing the MT effect, such as MT saturation62, and MTR difference observed in the recent inhomogeneous MT experimental method63 were proposed to overcome limitations of MTR.…”

Immediate and delayed decrease of long term potentiation and memory deficits after neonatal intermittent hypoxia

“…A novel in vivo quantitative MRI method, macromolecular proton fraction (MPF) mapping, was employed to reconstruct parametric maps of a relative amount of macromolecular protons causing the magnetization transfer effect. In the brain the method estimates proportion of water bound predominantly to myelin relative to the rest of brain water and therefore provides a quantitative biomarker of myelination in neural tissues (Yarnykh, 2016; Naumova et al, 2017). The method has been validated with histological markers of myelin in the normal rat brain (Underhill et al, 2011) and in a murine model of demyelination (Khodanovich et al, 2017).…”

Quantitative Assessment of Normal Fetal Brain Myelination Using Fast Macromolecular Proton Fraction Mapping

“…The parameters R and T 2 B were set according to the previous studies 4,5 due to their independence of the magnetic field. 14 The R 1 T 2 F value for 1.5T was taken from the literature.…”