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Improved spatial resolution for in vivo deuterium metabolic imaging using 2H 3D-FID-MRSI with concentric ring trajectories.
Fabian Niess1, Bernhard Strasser1, Lukas Hingerl1, Viola Bader1, Sabina Frese1, William T Clarke2, Stanislav Motyka1,3, Eva Niess1,3, Martin Krssak4, Siegfried Trattnig1,5, Thomas Scherer4, Rupert Lanzenberger6, and Wolfgang Bogner1,3
1Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria, 2Wellcome Centre for Integrative Neuroimaging, FMRIB,Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, 3Christian Doppler Laboratory for MR Imaging Biomarkers (BIOMAK), Vienna, Austria, 4Department of Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria, 5Institute for Clinical Molecular MRI, Karl Landsteiner Society, Vienna, Austria, 6Department of Psychiatry and Psychotherapy, Comprehensive Center for Clinical Neurosciences and Mental Health (C3NMH), Medical University of Vienna, Vienna, Austria

Synopsis

Keywords: Deuterium, Deuterium, Deuterium Metabolic Imaging, 7T, human brain, Magnetic Resonance Spectroscopic Imaging

Motivation: Sufficiently high spatial resolution for metabolic mapping of brain glucose metabolism is crucial as regional differences are present in many severe brain diseases, such as dementia, tumors and schizophrenia.

Goal(s): To increase spatial resolution for whole brain deuterium metabolic imaging without prolonging scan times.

Approach: Implement density-weighted concentric ring trajectory for 2H FID-MRSI readout to achieve 2.5-fold increase in spatial resolution while maintaining sufficient SNR.

Results: Contrast-enhanced metabolic maps were acquired using CRT with significantly higher (+33%,p<0.01) Glx concentrations in GM regions compared to WM, while no differences were observed using lower resolution phase-encoded MRSI.

Impact: Increased spatial resolution for dynamic deuterium metabolic imaging is crucially needed as many severe brain pathologies feature regional differences in brain glucose metabolism. However, prolonged scan times ultimately limit the achievable spatial resolution using conventional methods for whole brain DMI.

Introduction

Deuterium Metabolic Imaging (DMI) is an emerging Magnetic Resonance technique, which offers non-invasive insight into brain glucose (Glc) uptake and additionally downstream metabolism such as neurotransmitter synthesis of combined glutamate+glutamine (Glx) and lactate production(1-3). Regional differences in glucose metabolism in the brain can be observed in various brain pathologies, such as Alzheimer’s disease, cancer, epilepsy or schizophrenia(4-6). Therefore, sufficiently high spatial resolution is crucial. However, prolonged acquisition times of phase encoded MRSI (chemical shift imaging,CSI) approaches ultimately limit the achievable spatial resolution. Spatial-spectral acquisition schemes e.g., concentric ring trajectories (CRT) can accelerate scan times up to 100-fold compared to phase encoding alone, which allows for acquiring data with higher spatial resolution(7-9). This study aims to implement spatial-spectral sampling schemes for whole-brain 2H FID-MRSI to assess metabolic maps with increased spatial resolution and contrast. Results are compared to lower resolution DMI maps, acquired within the same protocol using CSI.

Methods

All measurements were performed on an experimental 7T (Terra-dot-Plus) Siemens MR system using a dual-tuned quadrature birdcage head-coil (Stark Contrasts MRI). Six healthy volunteers were scanned (4m/2f) in the morning after overnight fasting and oral [6,6’]-2H glucose administration (0.8 g/kg body weight). Approximately ∼7min after glucose uptake ten whole brain 2H FID-MRSI scans were measured over ∼70 min to acquire metabolic maps of deuterium labeled water, Glc and Glx, see Figure1. Two datasets (first and last time point) were acquired using elliptical phase encoding (CSI) with ∼2ml isotropic resolution (matrix: 16x16x14, FOV:200x200x175mm)(10). Eight datasets (second to eighth time point) were acquired using density-weighted concentric ring trajectories (CRT) (7) with ∼0.77ml isotropic resolution (matrix: 22x22x21, FOV: 200x200x192, Ncircles=43). Following MRSI acquisitions high-resolution anatomical images were acquired (MP2RAGE) for tissue segmentation considering partial volume effects. Data reconstruction and fitting was performed using in-house post-processing (MATLAB R2021, LCModel, Python3.10). To investigate the dynamics of deuterium labeled substrates, Glc and Glx concentrations were regionally averaged over gray (GM) and white matter (WM) regions (threshold CSI>55%, CRT>65%) and across subjects for each time point. To improve the signal-to-noise-ratio (SNR) for CRT data global low-rank denoising was performed using singular value decomposition with modified data shape. Concentration estimation was performed using natural abundance water as internal reference(11) assuming relaxation times and in vivo concentrations from literature(12,13) (2H: water: T1GM/T1WM/T2=350/290/30ms, GlxT1/T2=150/40ms, GlcT1/T2=67/42ms, 2H water concentration: 17.2mM) and considering 40% label loss for Glx(14).

Results

DMI data acquired using CSI achieved SNR (water amplitude/SD of noise) of 27±2 on average. DMI data acquired using CRT achieved initially an SNR of 12±1 and increased significantly (p<0.01) following denoising to 34±4. Representative sample spectra and 3D metabolic maps of 2H Glx and Glc from the last time point (∼77min after tracer uptake) acquired using CSI and CRT sequences are illustrated in Figure2. Time courses of Glx and Glc concentrations regionally averaged over GM and WM and across subjects for CSI and CRT measurements are shown in Figure3. Significantly higher Glx (+33 %,p<0.01) and Glc (+9%,p<0.01) concentrations were observed in GM compared to WM regions for CRT maps while no significant regional differences were observed for CSI maps. Increased GM/WM contrast for CRT maps of Glx is also visually discernible, see Figure2b.

Discussion and Conclusion

In this study we successfully implemented 3D FID-MRSI with fast concentric ring trajectory readout (CRT) for whole brain DMI. Using CRT, a 2.5-fold higher spatial resolution could be achieved for metabolic maps of Glc, Glx and water compared to conventional CSI approaches for similar scan durations (7min). While CRT maps of Glx and Glc revealed increased regional contrast i.e., higher concentrations in GM compared to WM dominated regions, no significant differences could be observed for CSI maps. Our results are in excellent agreement with literature as faster metabolic activity has been reported in GM compared to WM dominated regions (TCA cycle rates 68% higher)(15-17), while differences of absolute steady-state glucose levels have been reported to be smaller and comparable in GM and WM due to similar ratios of glucose transport and utilization(18,19). Although the spatial resolution has been significantly improved, the point spread function is still not optimal and increases the effective voxel size causing significant partial volume effects. This could explain that GM/WM contrast of Glx reported in this study (33%) is lower than reported in literature. The CRT acquisition scheme allows for even higher spatial resolutions compared to the current protocol, but is ultimately limited by the inherently low SNR of deuterium labeled metabolites. This could be further improved in future studies by more efficient sampling schemes and better denoising algorithms.

Acknowledgements

Austrian Science Fund: KLI 1106, WEAVE I 6037

Christian Doppler Laboratoy for MR Imaging Biomarkers (BIOMAK)

References

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8. Hingerl L, Bogner W, Moser P, Povazan M, Hangel G, Heckova E, Gruber S, Trattnig S, Strasser B. Density-weighted concentric circle trajectories for high resolution brain magnetic resonance spectroscopic imaging at 7T. Magn Reson Med 2018;79(6):2874-2885.

9. Moser P, Eckstein K, Hingerl L, Weber M, Motyka S, Strasser B, van der Kouwe A, Robinson S, Trattnig S, Bogner W. Intra-session and inter-subject variability of 3D-FID-MRSI using single-echo volumetric EPI navigators at 3T. Magn Reson Med 2020;83(6):1920-1929.

10. Niess F, Strasser B, Hingerl L, Niess E, Motyka S, Hangel G, Krssak M, Gruber S, Spurny-Dworak B, Trattnig S, Scherer T, Lanzenberger R, Bogner W. Reproducibility of 3D MRSI for imaging human brain glucose metabolism using direct ((2)H) and indirect ((1)H) detection of deuterium labeled compounds at 7T and clinical 3T. Neuroimage 2023;277:120250.

11. Gasparovic C, Song T, Devier D, Bockholt HJ, Caprihan A, Mullins PG, Posse S, Jung RE, Morrison LA. Use of tissue water as a concentration reference for proton spectroscopic imaging. Magn Reson Med 2006;55(6):1219-1226.

12. Cocking D, Damion RA, Franks H, Jaconelli M, Wilkinson D, Brook M, Auer DP, Bowtell R. Deuterium brain imaging at 7T during D(2) O dosing. Magn Reson Med 2023;89(4):1514-1521.

13. Seres Roig E, De Feyter HM, Nixon TW, Ruhm L, Nikulin AV, Scheffler K, Avdievich NI, Henning A, de Graaf RA. Deuterium metabolic imaging of the human brain in vivo at 7 T. Magn Reson Med 2023;89(1):29-39.

14. de Graaf RA, Thomas MA, Behar KL, De Feyter HM. Characterization of Kinetic Isotope Effects and Label Loss in Deuterium-Based Isotopic Labeling Studies. ACS Chem Neurosci 2021;12(1):234-243.

15. Hyder F, Fulbright RK, Shulman RG, Rothman DL. Glutamatergic function in the resting awake human brain is supported by uniformly high oxidative energy. J Cereb Blood Flow Metab 2013;33(3):339-347.

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Figures

Figure 1: Schematic illustration of the experimental protocol. After oral administration of [6,6’]2H Glucose the subject is placed into the magnet bore. Following initial preparation ten 3D DMI datasets were acquired dynamically over the course of ∼70 min using two sampling schemes with matched acquisition duration, i.e., elliptical phase encoding with 2 ml isotropic resolution (grey) and concentric ring trajectories with 0.77 ml (blue). High resolution anatomical images were acquired using MP2RAGE scans.

Figure 2: Comparison of 2 ml isotropic resolution for conventional phase encoding (CSI, left column) and 0.77 ml for concentric ring trajectories (CRT, right column). Representative sample spectra (a) of the last DMI scan featuring resonances of 2H water, 2H glucose (Glc) and 2H glutamate+glutamine (Glx). 3D metabolic maps of Glx (b) and Glc (c) from one representative volunteer. Faster metabolism in GM compared to WM, i.e., increased Glx concentrations are more pronounced for CRT maps.

Figure 3: Time courses of 2H labeled glutamate+glutamine (Glx, a) and glucose (Glc, b) regionally averaged over gray (GM) and white matter (WM) and across subjects. Significant differences between GM and WM were observed for higher spatial resolution acquisitions (CRT: 0.77ml voxel size) with 33 % higher Glx (p<0.01) and 9% higher Glc (p<0.01) in GM compared to WM. Lower spatial resolution scans (CSI: 2ml voxel size) showed no significant differences between GM and WM

Figure 4: Representative sample spectra from one voxel at similar position from both sampling schemes. Elliptical phase encoding with 2ml isotropic voxel volume (a) and concentric ring trajectory readout with 0.77 ml isotropic voxel volume before (b) and after (c) denoising using global low rank approximation with singular value decomposition. SNR was calculated from water relative to the standard deviation of the noise.

Proc. Intl. Soc. Mag. Reson. Med. 32 (2024)
3031
DOI: https://doi.org/10.58530/2024/3031