GluCEST Imaging and Structural Alterations of the Bilateral Hippocampus in First-Episode and Early-Onset Major Depression Disorder.

BACKGROUND: Glutamate dysregulation is one of the key pathogenic mechanisms of major depressive disorder (MDD), and glutamate chemical exchange saturation transfer (GluCEST) has been used for glutamate measurement in some brain diseases but rarely in depression. PURPOSE: To investigate the GluCEST changes in hippocampus in MDD and the relationship between glutamate and hippocampal subregional volumes. STUDY TYPE: Cross-sectional. SUBJECTS: Thirty-two MDD patients (34% males; 22.03 ± 7.21 years) and 47 healthy controls (HCs) (43% males; 22.00 ± 3.28 years). FIELD STRENGTH/SEQUENCE: 3.0 T; magnetization prepared rapid gradient echo (MPRAGE) for three-dimensional T1-weighted images, two-dimensional turbo spin echo GluCEST, and multivoxel chemical shift imaging (CSI) for proton magnetic resonance spectroscopy (1 H MRS). ASSESSMENT: GluCEST data were quantified by magnetization transfer ratio asymmetry (MTRasym ) analysis and assessed by the relative concentration of 1 H MRS-measured glutamate. FreeSurfer was used for hippocampus segmentation. STATISTICAL TESTS: The independent sample t test, Mann-Whitney U test, Spearman's correlation, and partial correlation analysis were used. P < 0.05 was considered statistically significant. RESULTS: In the left hippocampus, GluCEST values were significantly decreased in MDD (2.00 ± 1.08 [MDD] vs. 2.62 ± 1.41 [HCs]) and showed a significantly positive correlation with Glx/Cr (r = 0.37). GluCEST values were significantly positively correlated with the volumes of CA1 (r = 0.40), subiculum (r = 0.40) in the left hippocampus and CA1 (r = 0.51), molecular_layer_HP (r = 0.50), GC-ML-DG (r = 0.42), CA3 (r = 0.44), CA4 (r = 0.44), hippocampus-amygdala-transition-area (r = 0.46), and the whole hippocampus (r = 0.47) in the right hippocampus. Hamilton Depression Rating Scale scores showed significantly negative correlations with the volumes of the left presubiculum (r = -0.40), left parasubiculum (r = -0.47), and right presubiculum (r = -0.41). DATA CONCLUSION: GluCEST can be used to measure glutamate changes and help to understand the mechanism of hippocampal volume loss in MDD. Hippocampal volume changes are associated with disease severity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Glutamate alterations in the premature infant brain during different gestational ages with glutamate chemical exchange saturation transfer imaging: a pilot study.

OBJECTIVES: To elucidate the change in glutamate levels in preterm infants at different gestational ages by glutamate chemical exchange saturated transfer (GluCEST) magnetic resonance imaging and to compare the difference in glutamate levels among different brain regions between very early preterm infants and middle and late preterm infants. METHODS: Fifty-three preterm infants (59% males; median gestational age = 33.6 weeks) underwent MRI, including conventional MRI and GluCEST. The original data were postprocessed in MATLAB. Correlation analysis was used to determine the relationship between the MTRasym and gestational age. The differences in MTRasym signals among different ROIs were statistically analysed by one-way analysis of variance (ANOVA). The MTRasym difference of the bilateral hemispherical ROI was compared by a paired T test. RESULTS: In all ROIs, glutamate concentration was positively correlated with gestational age. The glutamate concentration in the thalamus was higher than that in the frontal lobe in very early, middle and late preterm infants. A difference in glutamate concentration was not found in the bilateral ROIs. CONCLUSIONS: The concentration of glutamate in the brains of preterm infants of different gestational ages increased with gestational age, which may be one of the factors contributing to the higher incidence of neurodevelopmental dysfunction in very early preterm infants compared to that in middle and late preterm infants. Meanwhile, the glutamate concentrations among different brain regions were also diverse. KEY POINTS: • The glutamate concentration was positively correlated with gestational age in preterm infants of the brain. • Glutamate concentrations were dissimilar in different brain regions of preterm infants. • Glutamate concentration during the process of brain development in premature infants was not found to be asymmetric.

Developing Smart Nanoparticles Responsive to the Tumor Micro-Environment for Enhanced Synergism of Thermo-Chemotherapy With PA/MR Bimodal Imaging.

With the development of nanotechnology, a theranostics nanoplatform can have broad applications in multimodal image-guided combination treatment in cancer precision medicine. To overcome the limitations of a single diagnostic imaging mode and a single chemotherapeutic approach, we intend to combat tumor growth and provide therapeutic interventions by integrating multimodal imaging capabilities and effective combination therapies on an advanced platform. So, we have constructed IO@MnO2@DOX (IMD) hybrid nanoparticles composed of superparamagnetic iron oxide (IO), manganese dioxide (MnO2), and doxorubicin (DOX). The nano-platform could achieve efficient T2-T1 magnetic resonance (MR) imaging, switchable photoacoustic (PA) imaging, and tumor microenvironment (TME)-responsive DOX release and achieve enhanced synergism of magnetic hyperthermia and chemotherapy with PA/MR bimodal imaging. The results show that IMD has excellent heating properties when exposed to an alternating magnetic field (AMF). Therefore, it can be used as an inducer for tumor synergism therapy with chemotherapy and hyperthermia. In the TME, the IMD nanoparticle was degraded, accompanied by DOX release. Moreover, in vivo experimental results show that the smart nanoparticles had excellent T2-T1 MR and PA imaging capabilities and an excellent synergistic effect of magnetic hyperthermia and chemotherapy. IMD nanoparticles could significantly inhibit tumor growth in tumor-bearing mice with negligible side effects. In conclusion, smart IMD nanoparticles have the potential for tumor diagnosis and growth inhibition as integrated diagnostic nanoprobes.

Glutamate Chemical Exchange Saturation Transfer Imaging and Functional Alterations of Hippocampus in Rat Depression Model: A Pilot Study.

BACKGROUND: Adjusting abnormal glutamate neurotransmission is a crucial mechanism in the treatment of depression. However, few non-invasive techniques could effectively detect changes in glutamate neurotransmitters, and no consensus exists on whether glutamate could affect resting-state function changes in depression. PURPOSE: To study the changes in glutamate chemical exchange saturation transfer (GluCEST) value in the hippocampus of rat model exposed to chronic unpredictable mild stress (CUMS), and to explore the effect of this change on the activity of hippocampal glutamatergic neurons. STUDY TYPE: Prospective animal study. ANIMAL MODEL: Twenty male Sprague-Dawley rats (200-300 g). FIELD STRENGTH/SEQUENCE: 7.0 T scanner. Fat rapid acquisition relaxation enhancement sequence for GluCEST, and echo planner imaging sequence for resting-state functional magnetic resonance imaging (rs_fMRI). ASSESSMENT: Rats were divided into two groups: CUMS group (N = 10) and control group (CTRL, N = 10). The magnetization transfer ratio asymmetry analysis was used to quantify the GluCEST data, and evaluate the rs_fMRI data through the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) analysis. STATISTICAL TESTS: A t-test was used to compare the difference in GluCEST or rs_fMRI between CUMS and CTRL groups. Spearman's correlation was applied to explore the correlation between GluCEST values and abnormal fMRI values in hippocampus. Statistical significance was set at P < 0.05. RESULTS: The GluCEST value in the left hippocampus has changed significantly (3.3 ± 0.3 [CUMS] vs. 3.9 ± 0.4 [CTRL], P < 0.05). In addition, the GluCEST value was significantly positively correlated with the ALFF values (r = 0.5, P < 0. 05, df = 7) and negatively correlated with the ReHo values (r = -0.6, P < 0.05, df = 7). DATA CONCLUSION: GluCEST technique has the feasibility of mapping glutamate changes in rat depression. Glutamate neurotransmitters are important factors affecting the abnormal function of neural activity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.