Integrating 1H MRS and deuterium labeled glucose for mapping the dynamics of neural metabolism in humans

Cember, Abigail; Wilson, Neil; Rich, Laurie J.; Bagga, Puneet; Nanga, Ravi Prakash Reddy; Swago, Sophia; Swain, Anshuman; Thakuri, Deepa; Elliot, Mark A.; Schnall, Mitchell D.; Detre, John A.; Reddy, Ravinder

doi:10.1016/j.neuroimage.2022.118977

Cited by 16 publications

(27 citation statements)

References 33 publications

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“…Therefore, no test-retest repeatability, reproducibility and control measurements were performed in this study. The enrichment of labeled Glx4 in our study is in good agreement with literature (6,(8)(9)(10)20).…”

Section: Discussionsupporting

confidence: 93%

“…In contrast to a direct detection of labeled substrates using DMI ( 2 H-MRS/MRSI), 13 C-MRS, or [ 18 F]FDG-PET the indirect 1 H-based QELT approach allows for simultaneous detection of labeled and unlabeled metabolites to quantify an extended neurochemical profile and requires no additional hardware or radioactive tracers (8)(9)(10). In comparison to recent publications presenting QELT MRSI results in animals (9) and humans (7,8,10) at ultra-high field(≥7T) research systems, our approach provides motion-corrected 3D metabolite maps with high temporal stability (26), which were acquired with high spatial and temporal resolution on widely available clinical 3T MR scanners. Further improvements in spatial and temporal stability can be anticipated considering the wide range of stateof-the-art undersampling or super-resolution techniques in MRSI (27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

“…Deuterium metabolic imaging (DMI) (5,6) and quantitative exchanged label turnover (QELT) (7)(8)(9)(10) are novel magnetic resonance techniques to non-invasively image Glc metabolism in animals and the human brain using deuterium-labeled Glc as tracer, which are able to separate healthy oxidative from pathologic anaerobic pathways, by simultaneously detecting the respective metabolic products glutamate+glutamine and lactate (4). DMI detects deuterium enrichment in the brain tissue directly via 2 H-MRS, while, indirectly, QELT detects a decrease of signal intensities in conventional 1 H-MR spectra due to deuterium-to-proton exchange in the respective molecule.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, DMI has been translated to clinical field strength of 3T (11) with a nominal isotropic resolution of 33 ml and an acquisition time of 10 min for each 3D dataset. QELT features higher SNR and spatial resolution (0.12 ml) with shorter acquisition times (~3 min( 7)) compared to DMI, while additionally detecting non- is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) labeled metabolites, but so far has been applied in humans only at non-clinical field strength of 7T (7,8).…”

Section: Introductionmentioning

confidence: 99%

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Non-invasive three-dimensional 1H-MR Spectroscopic Imaging of human brain glucose and neurotransmitter metabolism using deuterium labeling at 3T

Niess

Hingerl

Strasser

et al. 2022

Preprint

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Objectives Non-invasive, affordable, and reliable mapping of brain glucose metabolism is of critical interest for clinical research and routine application as metabolic impairment is linked to numerous pathologies e.g., cancer, dementia and depression. A novel approach to map glucose metabolism non-invasively in the human brain and separate normal oxidative from pathologic anaerobic pathways has been presented recently on experimental MR scanners using direct or indirect detection of deuterium-labeled glucose and downstream metabolites such as glutamate, glutamine and lactate. The aim of this study was to demonstrate the feasibility to non-invasively detect deuterium labeled downstream glucose metabolites indirectly in the human brain via 3D proton (1H) MR spectroscopic imaging on a clinical 3T MR scanner without additional hardware. Materials and Methods This prospective, institutional review board approved study was performed in seven healthy volunteers (mean age, 31+-4 years, 5 m/ 2 f) following written informed consent. After overnight fasting and oral deuterium-labeled glucose administration 3D metabolic maps were acquired every 4 min with 0.24 ml isotropic spatial resolution using real-time motion-, shim- and frequency-corrected echo-less 3D 1H-MR Spectroscopic Imaging. Time courses were analyzed using linear regression and non-parametric statistical tests. Deuterium labeled glucose and downstream metabolites were detected indirectly via their respective signal decrease in dynamic 1H MR spectra due to deuterium to proton exchange in the molecules. Results Sixty-five minutes after deuterium-labeled glucose administration, glutamate+glutamine (Glx) signal intensities decreased in gray/white matter (GM,WM) by -15+-2%,(p=0.02)/-14+-3%,(p=0.02), respectively. Strong negative correlation between Glx and time was observed in GM/WM (r=-0.71 p<0.001)/(r=-0.67,p<0.001) with 38+-18% (p=0.02) steeper slopes, indicating faster metabolic activity in GM compared to WM. Other non-labeled metabolites showed no significant changes. Conclusion Our approach translates deuterium metabolic imaging to widely available clinical routine MR scanners without specialized hardware offering a safe, affordable, and versatile (other substances than glucose can be labeled) approach for non-invasive imaging of glucose and neurotransmitter metabolism in the human brain.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Non-invasive three-dimensional 1H-MR Spectroscopic Imaging of human brain glucose and neurotransmitter metabolism using deuterium labeling at 3T

Niess

Hingerl

Strasser

et al. 2022

Preprint

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show abstract

“…In contrast to a direct detection of labeled substrates using DMI ( 2 H-MRS/MRSI), 13 C-MRS, or [ 18 F]FDG-PET the indirect 1 H-based QELT approach allows for simultaneous detection of labeled and unlabeled metabolites to quantify an extended neurochemical profile and requires no additional hardware or radioactive tracers. [8][9][10] In comparison with recent publications presenting QELT MRSI results in animals 9 and humans 7,8,10 at ultrahigh field(≥7T) research systems, our approach provides motion-corrected 3D metabolite maps with high temporal stability, 33 which were acquired with high spatial and temporal resolution on widely available clinical 3T MR scanners. Further improvements in spatial and temporal stability can be anticipated considering the wide range of state-of-the-art undersampling or super-resolution techniques in MRSI.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive 3-Dimensional 1H-Magnetic Resonance Spectroscopic Imaging of Human Brain Glucose and Neurotransmitter Metabolism Using Deuterium Labeling at 3T

et al. 2023

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Objectives Noninvasive, affordable, and reliable mapping of brain glucose metabolism is of critical interest for clinical research and routine application as metabolic impairment is linked to numerous pathologies, for example, cancer, dementia, and depression. A novel approach to map glucose metabolism noninvasively in the human brain has been presented recently on ultrahigh-field magnetic resonance (MR) scanners (≥7T) using indirect detection of deuterium-labeled glucose and downstream metabolites such as glutamate, glutamine, and lactate. The aim of this study was to demonstrate the feasibility to noninvasively detect deuterium-labeled downstream glucose metabolites indirectly in the human brain via 3-dimensional (3D) proton (1H) MR spectroscopic imaging on a clinical 3T MR scanner without additional hardware. Materials and Methods This prospective, institutional review board–approved study was performed in 7 healthy volunteers (mean age, 31 ± 4 years, 5 men/2 women) after obtaining written informed consent. After overnight fasting and oral deuterium-labeled glucose administration, 3D metabolic maps were acquired every ∼4 minutes with ∼0.24 mL isotropic spatial resolution using real-time motion-, shim-, and frequency-corrected echo-less 3D 1H-MR spectroscopic Imaging on a clinical routine 3T MR system. To test the interscanner reproducibility of the method, subjects were remeasured on a similar 3T MR system. Time courses were analyzed using linear regression and nonparametric statistical tests. Deuterium-labeled glucose and downstream metabolites were detected indirectly via their respective signal decrease in dynamic 1H MR spectra due to exchange of labeled and unlabeled molecules. Results Sixty-five minutes after deuterium-labeled glucose administration, glutamate + glutamine (Glx) signal intensities decreased in gray/white matter (GM/WM) by −1.63 ± 0.3/−1.0 ± 0.3 mM (−13% ± 3%, P = 0.02/−11% ± 3%, P = 0.02), respectively. A moderate to strong negative correlation between Glx and time was observed in GM/WM (r = −0.64, P < 0.001/r = −0.54, P < 0.001), with 60% ± 18% (P = 0.02) steeper slopes in GM versus WM, indicating faster metabolic activity. Other nonlabeled metabolites showed no significant changes. Excellent intrasubject repeatability was observed across scanners for static results at the beginning of the measurement (coefficient of variation 4% ± 4%), whereas differences were observed in individual Glx dynamics, presumably owing to physiological variation of glucose metabolism. Conclusion Our approach translates deuterium metabolic imaging to widely available clinical routine MR scanners without specialized hardware, offering a safe, affordable, and versatile (other substances than glucose can be labeled) approach for noninvasive imaging of glucose and neurotransmitter metabolism in the human brain.

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Quantification of Cerebral Glucose Concentrations via Detection of the H1‐α‐Glucose Peak in ¹H MRS at 7 T

Kuribayashi

Urushibata

Imai

et al. 2023

Magnetic Resonance Imaging

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BackgroundSensitive detection and quantification of cerebral glucose is desired.PurposeTo quantify cerebral glucose by detecting the H1‐α‐glucose peak at 5.23 ppm in 1H magnetic resonance spectroscopy at 7 T.Study TypeProspective.SubjectsTwenty‐eight non‐fasted healthy subjects (aged 20–28 years).Field Strength/SequenceShort echo time stimulated echo acquisition mode (short‐TE STEAM) and semi‐localized by adiabatic selective refocusing (semi‐LASER) at 7 T.AssessmentSingle voxel spectra were obtained from the posterior cingulate cortex (27‐mL) using a 32‐channel head coil. The H1‐α‐glucose peak in the spectrum with retrospective removal of the residual water peak was fitted using LCModel with a glucose basis set of only the H1‐α‐glucose peak. Conventional spectral analysis was performed with a glucose basis set of a full spectral pattern of glucose, also. Fitting precision was evaluated with Cramér‐Rao lower bounds (CRLBs). The repeatability of glucose quantification via the semi‐LASER sequence was tested.Statistical TestsPaired or Welch's t‐test were used for normally distributed values. A P value of <0.05 was considered significant. The repeatability of measures was analyzed using coefficient of variation (CV).ResultsRemoval of the residual water peak improved the flatness and stability of baselines around the H1‐α‐glucose peak and reduced CRLBs for fitting the H1‐α‐glucose peak. The semi‐LASER sequence was superior to the short‐TE STEAM in the higher signal‐to‐noise ratio of the H1‐α‐glucose peak (mean ± SD 7.9 ± 2.5, P < 0.001). The conventional analysis overfitted the H1‐α‐glucose peak. The individual CVs of glucose quantification by detecting the H1‐α‐glucose peak were smaller than the corresponding CRLBs.Data ConclusionCerebral glucose concentration is quantitated to be 1.07 mM by detecting the H1‐α‐glucose peak in the semi‐LASER spectra. Despite requiring long scan times, detecting the H1‐α‐glucose peak allows true glucose quantification free from the influence of overlapping taurine and macromolecule signals.Evidence Level2Technical Efficacy Stage1

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Integrating 1H MRS and deuterium labeled glucose for mapping the dynamics of neural metabolism in humans

Cited by 16 publications

References 33 publications

Non-invasive three-dimensional 1H-MR Spectroscopic Imaging of human brain glucose and neurotransmitter metabolism using deuterium labeling at 3T

Non-invasive three-dimensional 1H-MR Spectroscopic Imaging of human brain glucose and neurotransmitter metabolism using deuterium labeling at 3T

Noninvasive 3-Dimensional 1H-Magnetic Resonance Spectroscopic Imaging of Human Brain Glucose and Neurotransmitter Metabolism Using Deuterium Labeling at 3T

Quantification of Cerebral Glucose Concentrations via Detection of the H1‐α‐Glucose Peak in ¹H MRS at 7 T

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Integrating 1H MRS and deuterium labeled glucose for mapping the dynamics of neural metabolism in humans

Cited by 16 publications

References 33 publications

Non-invasive three-dimensional 1H-MR Spectroscopic Imaging of human brain glucose and neurotransmitter metabolism using deuterium labeling at 3T

Non-invasive three-dimensional 1H-MR Spectroscopic Imaging of human brain glucose and neurotransmitter metabolism using deuterium labeling at 3T

Noninvasive 3-Dimensional 1H-Magnetic Resonance Spectroscopic Imaging of Human Brain Glucose and Neurotransmitter Metabolism Using Deuterium Labeling at 3T

Quantification of Cerebral Glucose Concentrations via Detection of the H1‐α‐Glucose Peak in 1H MRS at 7 T

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Quantification of Cerebral Glucose Concentrations via Detection of the H1‐α‐Glucose Peak in ¹H MRS at 7 T