Abstract
In this study, a stimulated-echo (STE) method was employed to robustify the cerebral vessel size estimation near air-tissue, bone-tissue interfaces, and large vessels. The proposed solution is to replace the relaxation rate change from gradient-echo (GRE) with that from STE with long diffusion time after the injection of an intravascular contrast agent, superparamagnetic iron oxide nanoparticles. The corresponding diffusion length of STE is shorter than the length over which the unwanted macroscopic field inhomogeneities but is still longer than the correlation length of the fields induced by small vessels. Therefore, the unwanted field inhomogeneities are refocused, while preserving microscopic susceptibility contrast from cerebral vessels. The mean vessel diameter (dimensionless) derived from the diffusion-time-varying STE method was compared to the mean vessel diameter obtained by a conventional spin-echo (SE) and GRE combination based on Monte-Carlo proton diffusion simulations and in vivo rat experiments at 7 T. The in vivo mean vessel diameter from the MRI experiments was directly compared to available reference mouse brain vasculature obtained by a knife-edge scanning microscope (KESM), which is considered to be the gold standard. Monte-Carlo simulation revealed that SE and GRE-based MR relaxation rate changes (ΔR2 and ΔR2∗, respectively) can be enhanced using single STE-based MR relaxation rate change (ΔRSTE) by regulating diffusion time, especially for small vessels. The in vivo mean vessel diameter from the STE method demonstrated a closer agreement with that from the KESM compared to the combined SE and GRE method, especially in the olfactory bulb and cortex. This study demonstrates that STE relaxation rate changes can be used as consistent measures for assessing small cerebral microvasculature, where macroscopic field inhomogeneity is severe and signal contamination from adjacent large vessels is significant.
Highlights
Measurements of the changes in magnetic resonance (MR) transverse relaxation rates (from the spin-echo (SE) and gradient-echo (GRE) acquisitions) induced by the injection of an intravascular contrast agent enable the morphological quantification of the cerebral microvasculature, such as blood volume fraction (BVF), mean vessel diameter, and vessel size index (VSI, μm) (Boxerman et al, 1995; Dennie et al, 1998; Tropres et al, 2001)
Sensitivity and robustness for quantifying changes in small vessel size can be enhanced. Both increased magnetic field strength (B0) and Δχ worsen the effects of macroscopic field inhomogeneity from the air- and bone-tissue interfaces and large vessel influences based on GRE acquisitions, which critically limits the robustness of conventional magnetic resonance imaging (MRI)
The simulated ΔRSTE value with a long diffusion time (TD) tended to decrease at a large cylinder radius, which supports the in vivo observations that macroscopic field inhomogeneities from large vessels, air-tissue, and bone-tissue interfaces are reduced by the STE method
Summary
Measurements of the changes in magnetic resonance (MR) transverse relaxation rates (from the spin-echo (SE) and gradient-echo (GRE) acquisitions) induced by the injection of an intravascular contrast agent enable the morphological quantification of the cerebral microvasculature, such as blood volume fraction (BVF), mean vessel diameter (mVD, dimensionless), and vessel size index (VSI, μm) (Boxerman et al, 1995; Dennie et al, 1998; Tropres et al, 2001). MR sensitivity and robustness for quantifying changes in small vessel size can be enhanced Both increased B0 and Δχ worsen the effects of macroscopic field inhomogeneity from the air- and bone-tissue interfaces and large vessel influences based on GRE acquisitions, which critically limits the robustness of conventional magnetic resonance imaging (MRI). The division of relaxation rate change maps from separate GRE and SE acquisitions typically needs further adjustments from the inherently different Δχ-dependence and the necessary co-registration of the two acquisitions. These issues are all significantly amplified under strong magnetic fields (>7 T) for small rodent brains, which limits the robust quantification of cerebral vasculatures, especially in the vicinity of the olfactory bulb (OB) and cortex
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