Whole-brain deuterium metabolic imaging (DMI) at 7T: a preliminary healthy volunteer study
Poster No:
1959
Submission Type:
Abstract Submission
Authors:
Jing Liu1, Marisa Lafontaine1, Adam Autry1, Sana Vaziri1, Zanib Naeem1, An Vu1, Andrew Krystal1, Tiffany Ho2, Yan Li1
Institutions:
1University of California San Francisco, San Francisco, CA, 2University of California, Los Angeles, Los Angeles, CA
First Author:
Co-Author(s):
Introduction:
Deuterium metabolic imaging (DMI) is a valuable technique for studying metabolic dynamics after the deuterated glucose (2H-glucose) administration, tracing metabolic conversions from glucose to lactate and detecting glutamate and glutamine (Glx) in tissues. As several neurological and psychiatric disorders are characterized by altered glutamate metabolism, DMI is a valuable neuroimaging technique that may offer important biomarkers for diagnosing and monitoring therapeutic responses. At lower field strengths, DMI has limited spatial resolution. Here, we implemented an interleaved 1H/2H MRS acquisition on 7T scanner following the administration of 2H-glucose in healthy volunteers.
Methods:
Six healthy volunteers (32.0±9.6 years; 2F/4M) participated. Scans were performed on a human whole-body 7T MRI scanner (Siemens, Germany) using a 1H 4-channel/2H 4-channel dual-tuned headcoil (Virtumed LLC, Minnesota, USA). Subjects fasted overnight for >8 hours. Prior to oral administration of [6,6'-2H2]-glucose (0.75 g/kg body weight; max dose: 60g), subjects underwent a baseline DMI scan. Immediately after consuming the glucose solution, volunteers were placed inside the magnet bore for continuous data acquisition (over 10 time points) over 60-90 mins after glucose administration. Two subjects underwent a repeated scan within 3 months.
Whole-brain 3D DMI datasets were acquired using an FID MRSI sequence with interleaved weighted undersampling phase encoding (Niess et al., 2023). Imaging parameters: FOV=20 cm3, BW=1 kHz, 256 sample points, TR=290 ms, acquisition delay=0.1 ms, non-localized rectangular excitation pulse (FA=86 degrees, pulse duration=500 us), two averages, image matrix=10x10x10/16x16x16, and scan time=1:47/7:50 mins. T1-weighted proton MR2RAGE images (FOV=22.4 cm2, matrix=112x112, slice thickness=2 mm, 88 slices, TR/TI1/TI2/TE=5060/900/2750/2.2 ms, pixel bandwidth 300, FA=5 degrees, scan time=4:23 mins) were also acquired along with the serial DMI acquisitions.
DMI reconstruction was performed offline using in-house post-processing pipelines (MATLAB R2023b). Data from each channel were phase-corrected and combined using singular value decomposition (SVD), followed by denoising using SVD with low rank estimation, with rank=8 as used in (Niess et al., 2024), before spectral fitting. 2H MRS parameters were quantified using OXSA-AMARES (Vanhamme et al., 1997) in MATLAB using Lorentzian lineshapes with deuterium water (HDO, 4.8 ppm), glucose (Glc, 3.9 ppm), glutamate + glutamine (Glx, 2.4 ppm), and lactate (Lac, 1.3 ppm). Glc and Glx concentration maps (in mM) were calculated from natural abundance 2H estimated from baseline DMI (Ahmadian et al., 2024).
Whole-brain 3D DMI datasets were acquired using an FID MRSI sequence with interleaved weighted undersampling phase encoding (Niess et al., 2023). Imaging parameters: FOV=20 cm3, BW=1 kHz, 256 sample points, TR=290 ms, acquisition delay=0.1 ms, non-localized rectangular excitation pulse (FA=86 degrees, pulse duration=500 us), two averages, image matrix=10x10x10/16x16x16, and scan time=1:47/7:50 mins. T1-weighted proton MR2RAGE images (FOV=22.4 cm2, matrix=112x112, slice thickness=2 mm, 88 slices, TR/TI1/TI2/TE=5060/900/2750/2.2 ms, pixel bandwidth 300, FA=5 degrees, scan time=4:23 mins) were also acquired along with the serial DMI acquisitions.
DMI reconstruction was performed offline using in-house post-processing pipelines (MATLAB R2023b). Data from each channel were phase-corrected and combined using singular value decomposition (SVD), followed by denoising using SVD with low rank estimation, with rank=8 as used in (Niess et al., 2024), before spectral fitting. 2H MRS parameters were quantified using OXSA-AMARES (Vanhamme et al., 1997) in MATLAB using Lorentzian lineshapes with deuterium water (HDO, 4.8 ppm), glucose (Glc, 3.9 ppm), glutamate + glutamine (Glx, 2.4 ppm), and lactate (Lac, 1.3 ppm). Glc and Glx concentration maps (in mM) were calculated from natural abundance 2H estimated from baseline DMI (Ahmadian et al., 2024).
Results:
Fig.1 shows representative whole brain 2H Glc and 2H Glx concentration maps across a 90-min time course from two repeated scans, 2.5 months apart. The spectra from two voxels in the anterior cingulate cortex (ACC) and the posterior cingulate cortex (PCC) show similar patterns over time, as shown in the bottom panel of Fig. 1.
Fig. 2A shows the fitting of time courses for averaged 2H Glc and 2H Glx concentrations across the brain in 6 subjects. The slope was 0.016±0.005 mM/min for Glc, and 0.028±0.01 mM/min for Glx, where Glx increased 1.8-fold faster than Glc. Fig. 2B&C show data from repeated scans, where strong correlations (correlation coefficients >0.95) and no significant differences (all p >0.05) indicated good reproducibility of the DMI scans. Preliminary results revealed average concentrations of 1.12±0.33 mM for Glc and 1.96±0.60 mM for Glx. In Fig. 2D, we also observed strong correlations (all r>0.7) between age and the fitted slopes as well as the metabolic quantification at 60 mins after glucose administration.
Fig. 2A shows the fitting of time courses for averaged 2H Glc and 2H Glx concentrations across the brain in 6 subjects. The slope was 0.016±0.005 mM/min for Glc, and 0.028±0.01 mM/min for Glx, where Glx increased 1.8-fold faster than Glc. Fig. 2B&C show data from repeated scans, where strong correlations (correlation coefficients >0.95) and no significant differences (all p >0.05) indicated good reproducibility of the DMI scans. Preliminary results revealed average concentrations of 1.12±0.33 mM for Glc and 1.96±0.60 mM for Glx. In Fig. 2D, we also observed strong correlations (all r>0.7) between age and the fitted slopes as well as the metabolic quantification at 60 mins after glucose administration.
·Fig. 1. Whole-brain 2H Glc and 2H Glx concentration maps from baseline to 90 mins after 2H glucose administration from one subject (A). The spectra time courses in two voxels from ACC and PCC (B).
·Fig. 2. Concentration time course fitting (slopes listed) from six subjects (A), two subjects with repeated scans (B&C), and correlations between subject age and slopes and 60-min concentrations (D).
Conclusions:
Our study presents a streamlined 7T DMI workflow to analyze glucose metabolism in healthy volunteers after deuterated glucose administration. We plan to recruit patients with major depressive disorder and compare their metabolism to that of healthy volunteers.
Novel Imaging Acquisition Methods:
MR Spectroscopy 1
Imaging Methods Other 2
Keywords:
Glutamate
MR SPECTROSCOPY
MRI
1|2Indicates the priority used for review
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Provide references using APA citation style.
Niess, F., Strasser, B., Hingerl, L., Bader, V., Frese, S., Clarke, W. T., Duguid, A., Niess, E., Motyka, S., Krššák, M., Trattnig, S., Scherer, T., Lanzenberger, R., & Bogner, W. (2024). Whole‐brain deuterium metabolic imaging via concentric ring trajectory readout enables assessment of regional variations in neuronal glucose metabolism. Human Brain Mapping, 45(6), e26686. https://doi.org/10.1002/hbm.26686
Niess, F., Strasser, B., Hingerl, L., Niess, E., Motyka, S., Hangel, G., Krššák, M., Gruber, S., Spurny-Dworak, B., Trattnig, S., Scherer, T., Lanzenberger, R., & Bogner, W. (2023). Reproducibility of 3D MRSI for imaging human brain glucose metabolism using direct (2H) and indirect (1H) detection of deuterium labeled compounds at 7T and clinical 3T. NeuroImage, 277, 120250. https://doi.org/10.1016/j.neuroimage.2023.120250
Vanhamme, L., Van Den Boogaart, A., & Van Huffel, S. (1997). Improved Method for Accurate and Efficient Quantification of MRS Data with Use of Prior Knowledge. Journal of Magnetic Resonance, 129(1), 35–43. https://doi.org/10.1006/jmre.1997.1244