Myelin mapping in the central nervous system of living mice using contrast-enhanced magnetization transfer MRI

This work compares magnetization transfer (MT) MRI of living mice with contrast-enhanced MT MRI using intraventricular administration of gadopentetate dimeglumine (Gd-DTPA), systemic administration of MnCl2, and both. In MT MRI at 9.4 T, the contrast-to-noise ratio (CNR) between white matter (WM) and gray matter (GM) increased by 85% after Gd-DTPA injection into the lateral ventricle. When applied in conjunction with manganese-enhanced MT MRI (117 μm isotropic resolution, 6 min measuring time), Gd-DTPA boosted the CNR increase from + 56% to + 117%. Additional T1 measurements at 2.35 T revealed that intraventricular Gd-DTPA shortens the T1 of GM much more than that of WM, which corresponds to estimated extracellular spaces of 26% in GM and only 15% in WM. These results explain the additional MT contrast enhancement by Gd-DTPA and demonstrate that the T1 shortening by intracellular Mn2 + is well complemented by extracellular Gd-DTPA. The data suggest a high myelin and low water content to hinder access of hydrophilic paramagnetic agents, so that the resulting differential accumulation effectively reduces the MT saturation in water-rich tissues and thereby facilitates the mapping of myelin-rich tissues. Finally, a 156% CNR increase between GM and WM for contrast-enhanced MT MRI at 9.4 T using both Gd-DTPA and manganese allowed for 60 μm isotropic resolution (102 min measuring time), which delineated myelinated fibers and layers even within GM areas such as the thalamus and cerebellar cortex. Improved MT contrasts were also seen in the cervical spinal cord.

► Intraventricular Gd-DTPA injection improves the magnetization transfer MRI contrast. ► This tissue-specific effect can be enhanced by additional manganese administration. ► A high myelin and low water content hinder access of hydrophilic paramagnetic agents. ► Contrast-enhanced MT MRI delineated myelinated structures even within gray matter. ► MT contrast was also improved in the spinal cord MRI at 60 µm isotropic resolution.