Oral 23rd International Society of Magnetic Resonance Conference 2023

The quantification of Glutamate and Glutamine concentrations using MRS and MRSI in MND and controls at 7 Tesla (#108)

Zeinab Eftekhari 1 2 , Thomas B Shaw 1 3 4 , Jin Jin 2 5 , Wolfgang Bogner 6 , Markus Barth 1 2 4
  1. Centre for Advanced Imaging, The University of Queensland, Brisbane, Qld, Australia
  2. ARC Training Centre for Innovation in Biomedical Imaging Technology (CIBIT), The University of Queensland, Brisbane, Qld, Australia
  3. Neurology Department, Royal Brisbane and Women’s Hospital, , Brisbane, Australia
  4. School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Qld, Australia
  5. Siemens Healthcare Pty Ltd, Brisbane, Australia
  6. High-field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria

Introduction:

Motor Neuron Disease (MND; often called Amyotrophic Lateral Sclerosis or ALS) is characterized by motor neuron loss in the motor cortex, brain stem, and spinal cord, resulting in progressive disability and eventual death. Magnetic Resonance Spectroscopy (MRS) offers a unique, non-invasive approach to assess neurochemical changes in MND patients. Prior evidence suggests altered metabolite concentrations in MND, impacting disease progression and heterogeneity [1]. However, limited studies have explored 7T for measuring metabolite changes in MND or utilized MRS/MRSI to quantify Glutamate and Glutamine concentrations longitudinally [2]. This study aimed to quantify metabolite ratios in the motor cortex using 7T MRI. We investigated Glutamate/N-Acetylaspartate (Glu/NAA) and Gamma-Aminobutyric Acid/Glutamate (GABA/Glu) ratios between patients and non-neurodegenerative controls (NCs), which will potentially enable improved diagnostic certainty and progression monitoring in early-stage disease.

 

Method:

We used the following MRS protocols on a 7 Tesla human MRI scanner (Magnetom 7T+, Siemens Healthcare, Erlangen, Germany) to investigate the most optimal approach to accurately estimate Glutamate (Glu) and Glutamine (Gln) concentrations with optimal peak intensity and minimize dephasing of j-coupled metabolites: Short-TE STEAM [3], semi-LASER [4, 5], FID-CRT-MRSI [8]. We acquired data in a spectroscopy phantom (SPECTRE, Gold standard phantoms) and four participants (3 healthy controls (HCs): 3 males aged 30, 31, and 50, and 1 ALS patient: female, 49). The acquired spectra were processed and analyzed using Osprey MRS analysis toolbox [6] in MATLAB (v.R2022a). Metabolite signals were quantified using LCModel (v6.3) [7]. The resulting Glu/NAA and GABA/Glu ratios were reported for all comparisons.

 

Results:

The selected short-TE semi-LASER sequence showed the highest signal-to-noise ratio (1830 in phantom, 490 in humans) and best test-retest reliability (0.9% Coefficient of variation) of j-coupled metabolite concentrations (Glx/tCr in HCs [1.3] and ALS patients [0.94]). The ALS patient exhibited a lower NAA/tCr and higher Glu/NAA and GABA/Glu ratios compared to HCs in line with literature reports [2].

Conclusion:

This study demonstrates the feasibility of acquiring robust single-voxel MRS and MRSI in the motor cortex at 7T. The observed differences in NAA/tCr, Glu/NAA, and GABA/Glu ratios between HCs and the ALS results suggestive of potential metabolic alterations in ALS.

 

 

  1. [1] G. Öz, Magnetic resonance spectroscopy of degenerative brain diseases. Springer, 2016.
  2. [2] F. Christidi et al., "Neurometabolic Alterations in Motor Neuron Disease: Insights from Magnetic Resonance Spectroscopy," Journal of Integrative Neuroscience, vol. 21, no. 3, p. 87, 2022.
  3. [3] M. Marjanska et al., "Region-specific aging of the human brain as evidenced by neurochemical profiles measured noninvasively in the posterior cingulate cortex and the occipital lobe using (1)H magnetic resonance spectroscopy at 7 T," Neuroscience, vol. 354, pp. 168-177, Jun 23 2017, doi: 10.1016/j.neuroscience.2017.04.035.
  4. [4] D. K. Deelchand et al., "Across-vendor standardization of semi-LASER for single-voxel MRS at 3T," NMR Biomed, vol. 34, no. 5, p. e4218, May 2021, doi: 10.1002/nbm.4218
  5. [5] G. Öz and I. Tkáč, "Short‐echo, single‐shot, full‐intensity proton magnetic resonance spectroscopy for neurochemical profiling at 4 T: validation in the cerebellum and brainstem," Magnetic resonance in medicine, vol. 65, no. 4, pp. 901-910, 2011.
  6. [6] G. Oeltzschner et al., "Osprey: Open-source processing, reconstruction & estimation of magnetic resonance spectroscopy data," Journal of neuroscience methods, vol. 343, p. 108827, 2020.
  7. [7] S. W. Provencher, "Estimation of metabolite concentrations from localized in vivo proton NMR spectra," Magnetic resonance in medicine, vol. 30, no. 6, pp. 672-679, 1993.
  8. [8] Hangel, Gilbert, et al. "High-resolution metabolic imaging of high-grade gliomas using 7T- CRT-FID-MRSI." NeuroImage: Clinical 28 (2020): 102433.