Evidence of Neuroinflammation and Excitotoxicity in ME/CFS using Single-Voxel MRS
Presented During:
Friday, June 27, 2025: 11:30 AM - 12:45 PM
Brisbane Convention & Exhibition Centre
Room:
M4 (Mezzanine Level)
Poster No:
1951
Submission Type:
Abstract Submission
Authors:
Kiana Kothe1, Jacob Levenstein1, Richard Kwiatek1, Peter Del Fante1, Vince Calhoun2, Zack Shan1
Institutions:
1Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway, Birtinya, 4557 QLD, Australia, 2Tri-Institutional Center for Translational Research in Neuroimaging & Data Science/GSU/GATech/Emory, Atlanta, GA, USA
First Author:
Kiana Kothe
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway
Birtinya, 4557 QLD, Australia
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway
Birtinya, 4557 QLD, Australia
Co-Author(s):
Jacob Levenstein, PhD
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway
Birtinya, 4557 QLD, Australia
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway
Birtinya, 4557 QLD, Australia
Richard Kwiatek
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway
Birtinya, 4557 QLD, Australia
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway
Birtinya, 4557 QLD, Australia
Peter Del Fante
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway
Birtinya, 4557 QLD, Australia
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway
Birtinya, 4557 QLD, Australia
Vince Calhoun
Tri-Institutional Center for Translational Research in Neuroimaging & Data Science/GSU/GATech/Emory
Atlanta, GA, USA
Tri-Institutional Center for Translational Research in Neuroimaging & Data Science/GSU/GATech/Emory
Atlanta, GA, USA
Zack Shan
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway
Birtinya, 4557 QLD, Australia
Thompson Institute, University of the Sunshine Coast, 12 Innovation Parkway
Birtinya, 4557 QLD, Australia
Introduction:
Neuroinflammation is implicated in various brain pathologies and is proposed as a mechanism underlying Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a condition with largely unknown pathophysiology. The neuroinflammatory response is difficult to image non-invasively. However, magnetic resonance spectroscopy (MRS) offers a suitable approach to address this gap by enabling the measurement of metabolites that can serve as markers of neuroinflammation. Specifically, glutamine and glutamate (combined as Glx) are relevant due to their role in excitotoxicity and neuroinflammatory activation (Velu et al., 2024), while total N-acetylaspartate (tNAA) serves as a marker of neuronal integrity and a mitigating factor regarding inflammatory responses (Felice et al., 2024). Myo-inositol (mI), a recognized glial marker, reflects astrocytic activation and proliferation, central to the neuroinflammatory process (Harris et al., 2015). Total choline (tCho) indicates membrane turnover and is associated with neuroinflammation (Mueller et al., 2024). Additionally, lactate (Lac) may modulate immune responses, potentially affecting the hypothesised neuroinflammatory response in ME/CFS (Manosalva et al., 2022). This study investigated whether neurochemical concentrations of these metabolites are associated with a ME/CFS diagnosis. We hypothesise Glx, tCho, mI and lactate to be elevated, and tNAA to be downregulated in individuals with ME/CFS.
Methods:
This study was approved by the University of the Sunshine Coast Human Research Ethics Committee (A191288), and all participants provided informed written consent. MRI data were acquired at the Thompson Institute using a 3T Siemens Skyra scanner. A T1-weighted MPRAGE scan was used to place the MRS volume of interest (VOI) in the left dorsolateral prefrontal cortex. Single-voxel MRS data were acquired with a PRESS sequence (VOI: 27 × 20 × 12 mm, TR = 2000 ms, TE = 33 ms, averages = 200). Data processing and metabolite fitting were performed using OSPREY (v2.8.1; Oeltzschner et al., 2020). Following visual inspection and evaluation of quality matrices, 102 participants (53 healthy controls, 49 ME/CFS cases) were analysed. Total creatine (tCr) was used as the internal reference for metabolite quantification. Independent samples t-tests and Mann-Whitney U tests were conducted in JASP (v0.19.2; JASP Team, 2024). Bonferroni correction was applied.
Results:
The final cohort had a mean SNR for creatine of 63.479 (SD= 14.711) and a mean FWHM for creatine of 8.041 (SD= 7.699). Preliminary independent samples t-tests and Mann-Whitney U tests revealed significant differences between groups for Glx (U = 808, p = .005, r = -0.378) and tCho (U = 1726.00, p = .02, r = 0.329). Group differences for mI were rendered non-significant following Bonferroni correction. Neither Lac, nor tNAA were significant (ps. ≥ 0.22). The uncorrected p-values and detailed results for mI, lactate and tNAA are provided in Table 1.
·Volume of Interest and Group Mean Spectra Plot
·Results Table and Independent Scatter Plots for each Metabolite
Conclusions:
This preliminary analysis provides evidence of altered neurochemical profiles in ME/CFS, with significant group differences in Glx and tCho, suggesting involvement of excitotoxicity, cellular membrane turnover, and neuroinflammatory activation. The non-significant differences detected for mI, tNAA and Lac provide insights into aspects of pathophysiology that may remain unaffected in ME/CFS. More subtle differences may exist, requiring specifically tailored MRS sequences. These findings underscore the utility of MRS in non-invasively investigating neuroinflammatory markers in ME/CFS, advancing understanding of its pathophysiology and potentially informing diagnostic and therapeutic approaches.
Modeling and Analysis Methods:
Other Methods
Novel Imaging Acquisition Methods:
MR Spectroscopy 1
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
Data analysis
DISORDERS
Glutamate
Infections
Magnetic Resonance Spectroscopy (MRS)
Other - Neuroinflammation
1|2Indicates the priority used for review
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2. Harris, J. L., Choi, I. Y., & Brooks, W. M. (2015). Probing astrocyte metabolism in vivo: proton magnetic resonance spectroscopy in the injured and aging brain. Front Aging Neurosci, 7, 202. https://doi.org/10.3389/fnagi.2015.00202
3. JASP Team. (2024). JASP (Version 0.19.2) [Computer software]. https://jasp-stats.org/
4. Manosalva, C., Quiroga, J., Hidalgo, A. I., Alarcón, P., Anseoleaga, N., Hidalgo, M. A., & Burgos, R. A. (2022). Role of Lactate in Inflammatory Processes: Friend or Foe [Review]. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.808799
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