Magnetic resonance imaging of brain cell water

Takashi Watanabe,Zhengguo Tan,Jens Frahm,Xiaoqing Wang

doi:10.1038/s41598-019-41587-2

Takashi Watanabe, Zhengguo Tan + Show 2 more

Open Access

https://doi.org/10.1038/s41598-019-41587-2

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Abstract

In the central nervous system of vertebrates, cell bodies of neurons are often assembled as nuclei or cellular layers that play specific roles as functional units. The purpose of this work was to selectively highlight such cell assemblies by magnetic resonance imaging using signals from water protons that are associated with intracellular paramagnetic ions, while saturating lipid-associated water protons as well as extracellular free water protons. Given the significant correlation between image signal intensity and water proton density, the high signal intensities observed for such cell assemblies must be attributed to their abundant paramagnetic-ion-associated water protons. In the hippocampal formation, the technique visualized cell assemblies that were so far not depicted in human in vivo. In the brainstem, the technique delineated noradrenergic neuron groups such as the locus coeruleus in human and mice in vivo. Their reduced magnetization-transfer ratios together with their prolonged relaxation times compared to other gray matter indicate that the source of their high signal intensity is not the presence of T1-shortening molecules, e.g., neuromelanin, but their high water content. Given the general absence of neuromelanin in noradrenergic neurons of rodents, their high signal intensity in mice in vivo further supports this view.

Highlights

IntroductionIn the central nervous system of vertebrates, cell bodies of neurons are often assembled as nuclei or cellular layers that play specific roles as functional units, e.g. in the hippocampal formation as shown in Fig. 1 (top left, arrowheads)
The deviation of the magnetization transfer4 (MT) ratios of white matter (WM) and cerebrospinal fluid (CSF) from the linear relationship is attributable to their lower R2/R1 ratio (Fig. 2c) and to a weaker direct-saturation effect
With regard to the most concentrated paramagnetic ions in brain, the relaxation enhancement factor[16] of Fe3+ on binding to a macromolecule is only 0.3 while that of Cu2+ is 10 and that of Mn2+ is 8. This is because Fe3+ ion has a much shorter electron relaxation time than Cu2+ or Mn2+ ion[17]. Given their high relaxation enhancement factors as well as their high intracellular concentration[5] which meets their high metabolic demand, it is possible that Cu2+ and Mn2+ together play a role in high MT-Magnetic resonance imaging (MRI) signal intensity of some specific cell assemblies, we showed that the water proton density plays the central role (Fig. 2d–e, Supplementary Fig. 2)

Summary

Introduction

In the central nervous system of vertebrates, cell bodies of neurons are often assembled as nuclei or cellular layers that play specific roles as functional units, e.g. in the hippocampal formation as shown in Fig. 1 (top left, arrowheads). Magnetic resonance imaging (MRI) can readily differentiate large cell assemblies from surrounding tissue We attempt to gain signals selectively from the water protons that are associated with intracellular paramagnetic ions by saturating extracellular free water protons by direct on-resonance irradiation, as well as by eliminating signal contributions from lipid-associated protons by off-resonance irradiation of short T2 lipid protons with broad linewidths The latter method indirectly saturates lipid-associated water protons through magnetization transfer[4] (MT).

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