Saturation transfer MRI is sensitive to neurochemical changes in the rat brain due to chronic unpredictable mild stress

Anna Pankowska,Anna Orzyłowska,Wilfred W Lam,Tymoteusz Słowik,Marta Andres-Mach,Agata Chudzik,Radosław Pietura,Radosław Rola,Greg J Stanisz,Artur Łazorczyk,Katarzyna Kochalska

doi:10.1038/s41598-021-97991-0

Abstract

Chemical exchange saturation transfer (CEST) MRI was performed for the evaluation of cerebral metabolic changes in a rat model of depressive-like disease induced by chronic unpredictable mild stress (CUMS). CEST Z-spectra were acquired on a 7 T MRI with two saturation B1 amplitudes (0.5 and 0.75 µT) to measure the magnetization transfer ratio (MTR), CEST and relayed nuclear Overhauser effect (rNOE). Cerebral cortex and hippocampus were examined in two groups of animals: healthy control (n = 10) and stressed (n = 14), the latter of which was exposed to eight weeks of the CUMS protocol. The stressed group Z-spectrum parameters, primarily MTRs, were significantly lower than in controls, at all selected frequency offsets (3.5, 3.0, 2.0, − 3.2, − 3.6 ppm) in the cortex (the largest difference of ~ 3.5% at − 3.6 ppm, p = 0.0005) and the hippocampus (MTRs measured with a B1 = 0.5 µT). The hippocampal rNOE contributions decreased significantly in the stressed brains. Glutamate concentration (assessed using ELISA) and MTR at 3 ppm correlated positively in both brain regions. GABA concentration also correlated positively with CEST contributions in both cerebral areas, while such correlation with MTR was positive in hippocampus, and nonsignificant in cortex. Results indicate that CEST is sensitive to neurometabolic changes following chronic stress exposure.

Highlights

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) was performed for the evaluation of cerebral metabolic changes in a rat model of depressive-like disease induced by chronic unpredictable mild stress (CUMS)
A resting-state Functional MRI (fMRI) study performed by Meng et al.[10] have shown reduced global network efficiency and an increased characteristic path length in the depressed group, while other r esearch[11] has found functional connectivity strength to be lower in the bilateral ventral medial prefrontal cortex and ventral anterior cingulate cortex regions of depressed brains than in corresponding areas in a healthy group
We evaluated characteristics of the saturation transfer data such as the magnetization transfer ratio (MTR), which is a non-specific measure of T 1/T2 ratio, magnetization transfer (MT) and CEST effects, and CEST and relayed nuclear Overhauser effect contributions to the Z-spectra to investigate brain metabolic changes related to depressive disorder with the use of the chronic unpredictable mild stress (CUMS) rat model

Summary

Introduction

Chemical exchange saturation transfer (CEST) MRI was performed for the evaluation of cerebral metabolic changes in a rat model of depressive-like disease induced by chronic unpredictable mild stress (CUMS). Magnetic resonance spectroscopy (MRS) studies performed in depressive patients show decreased metabolic ratios (NAA/Cr, Cho/Cr and Ins/Cr) in the prefrontal r egion[12] compared to healthy subjects. There has been a growing interest in using chemical exchange saturation transfer (CEST) imaging to probe brain m etabolites[19,20], as it offers improved resolution compared to MRS, at the cost of specificity. Assessing the process of protons exchange between water and such CEST-sensitive compounds as neurotransmitters can become an important factor in predicting later changes in the brain that are responsible for depressive disorders. The exchange of magnetization between aliphatic groups, such as methine, and water can be detected upfield of the water resonance[28,29]

Methods

Results

Conclusion