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In vivo GluCEST MRI: Reproducibility, background contribution and source of glutamate changes in the MPTP model of
Puneet Bagga1, Stephen Pickup2, Rachelle Crescenzi2
1Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States. puneetb@pennmedicine.upenn.edu.
Abstract:
Glutamate Chemical Exchange Saturation Transfer (GluCEST) MRI is a recently developed technique to image glutamate. In the present study, we evaluated the reproducibility and background contamination to the GluCEST and source of the GluCEST changes in a mouse model of Parkinson's disease. Repeated measurements in five mice demonstrated an intra-animal coefficient of variation (CV) of GluCEST signal to be 2.3 ± 1.3% and inter-animal CV of GluCEST to be 3.3 ± 0.3%. Mice were treated with MPTP to create a localized striatal elevation of glutamate. We found an elevation in the GluCEST contrast of the striatum following MPTP treatment (Control: 23.3 ± 0.8%, n = 16; MPTP: 26.2 ± 0.8%, n = 19; p ≤ 0.001). Additionally, the positive association between glutamate concentration measured via 1H MRS and GluCEST signal was used to estimate background contribution to the measured GluCEST. The contribution of signal from non-glutamate sources was found to be ~28% of the total GluCEST. Immunohistochemical analysis of the brain showed co-localization of glutamate with GFAP in the striatum. This suggests that the elevated glutamate present in the striatum in this mouse model reflects astroglial proliferation or reactivity due to the action of MPTP. The potential of GluCEST as a biomarker for imaging inflammation mediated gliosis is discussed.
Insights
Glutamate Chemical Exchange Saturation Transfer (GluCEST) MRI shows reproducible results for imaging glutamate. This technique detected elevated glutamate in a Parkinson
Area of Science:
- Neuroimaging
- Biomarker Development
- Neuroscience
Background:
- Glutamate Chemical Exchange Saturation Transfer (GluCEST) MRI is an emerging technique for visualizing glutamate levels in vivo.
- Understanding the reproducibility and sources of signal variation in GluCEST is crucial for its clinical translation.
- Parkinson's disease models offer a platform to investigate GluCEST's utility in neurological disorders characterized by altered glutamate neurotransmission.
Purpose of the Study:
- To assess the reproducibility of GluCEST measurements in a mouse model.
- To investigate the sources of background signal contamination in GluCEST imaging.
- To evaluate GluCEST as a potential imaging biomarker for neuroinflammation and gliosis in Parkinson's disease.
Main Methods:
- Evaluated intra- and inter-animal variability of GluCEST signals in healthy mice.
- Induced Parkinson's-like pathology using MPTP in mice and measured striatal GluCEST changes.
- Correlated 1H Magnetic Resonance Spectroscopy (MRS) glutamate concentrations with GluCEST signals to estimate background contribution.
- Performed immunohistochemical analysis to identify the cellular source of elevated glutamate.
Main Results:
- Demonstrated high reproducibility of GluCEST measurements with low intra-animal (2.3 ± 1.3%) and inter-animal (3.3 ± 0.3%) coefficients of variation.
- Observed a significant elevation in striatal GluCEST contrast in MPTP-treated mice compared to controls (26.2 ± 0.8% vs. 23.3 ± 0.8%, p ≤ 0.001).
- Estimated background signal from non-glutamate sources to be approximately 28% of the total GluCEST signal.
- Showed co-localization of glutamate with GFAP-positive astrocytes in the striatum, indicating reactive gliosis.
Conclusions:
- GluCEST MRI is a reproducible technique for imaging glutamate.
- MPTP-induced Parkinson's model shows elevated striatal glutamate detectable by GluCEST.
- Elevated GluCEST signal in this model likely reflects MPTP-induced astroglial proliferation or reactivity, suggesting GluCEST's potential for imaging inflammation-mediated gliosis.