Comparison of 2-Hydroxyglutarate Detection With sLASER and MEGA-sLASER at 7T

Shams, Zahra; Kemp, Wybe J. M. van der; Emir, Uzay E.; Dankbaar, Jan Willem; Snijders, Tom J.; Vos, Filip Y.F. de; Klomp, Dennis W. J.; Wijnen, Jannie P.; Wiegers, Evita C

doi:10.3389/fneur.2021.718423

Cited by 12 publications

(12 citation statements)

References 32 publications

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“…Non-invasive detection of 2HG was developed through a variety of 1 H magnetic resonance spectroscopy (MRS) techniques [ 11 – 14 ]. These include the short echo time (TE = 30 ms) with spectral fitting [ 13 ]; long TE (97–110 ms) that exploits the unique signal evolution of 2HG’s strongly coupled spin system [ 14 , 15 ]; and spectral editing methods (TE = 68 ms) designed to isolate 2HG from background resonances via coupling patterns [ 11 , 14 ]. Clinical applications of 2HG MRS have shown diagnostic utility in identifying gliomas that express a range of IDH1/2 mutations [ 16 , 17 ] and reliably quantifying concentrations in excess of 1 mM [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic imaging of D-2-hydroxyglutarate and other metabolites in pre-surgical patients with IDH-mutant lower-grade gliomas

et al. 2022

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Purpose Prognostically favorable IDH-mutant gliomas are known to produce oncometabolite D-2-hydroxyglutarate (2HG). In this study, we investigated metabolite-based features of patients with grade 2 and 3 glioma using 2HG-specific in vivo MR spectroscopy, to determine their relationship with image-guided tissue pathology and predictive role in progression-free survival (PFS). Methods Forty-five patients received pre-operative MRIs that included 3-D spectroscopy optimized for 2HG detection. Spectral data were reconstructed and quantified to compare metabolite levels according to molecular pathology (IDH1R132H, 1p/19q, and p53); glioma grade; histological subtype; and T2 lesion versus normal-appearing white matter (NAWM) ROIs. Levels of 2HG were correlated with other metabolites and pathological parameters (cellularity, MIB-1) from image-guided tissue samples using Pearson’s correlation test. Metabolites predictive of PFS were evaluated with Cox proportional hazards models. Results Quantifiable levels of 2HG in 39/42 (93%) IDH+ and 1/3 (33%) IDH– patients indicated a 91.1% apparent detection accuracy. Myo-inositol/total choline (tCho) showed reduced values in astrocytic (1p/19q-wildtype), p53-mutant, and grade 3 (vs. 2) IDH-mutant gliomas (p < 0.05), all of which exhibited higher proportions of astrocytomas. Compared to NAWM, T2 lesions displayed elevated 2HG+ γ-aminobutyric acid (GABA)/total creatine (tCr) (p < 0.001); reduced glutamate/tCr (p < 0.001); increased myo-inositol/tCr (p < 0.001); and higher tCho/tCr (p < 0.001). Levels of 2HG at sampled tissue locations were significantly associated with tCho (R = 0.62; p = 0.002), total NAA (R = − 0.61; p = 0.002) and cellularity (R = 0.37; p = 0.04) but not MIB-1. Increasing levels of 2HG/tCr (p = 0.0007, HR 5.594) and thresholding (≥ 0.905, median value; p = 0.02) predicted adverse PFS. Conclusion In vivo 2HG detection can reasonably be achieved on clinical scanners and increased levels may signal adverse PFS.

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Section: Introductionmentioning

confidence: 99%

Spectroscopic imaging of D-2-hydroxyglutarate and other metabolites in pre-surgical patients with IDH-mutant lower-grade gliomas

et al. 2022

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“…Several of these studies utilize 1 H-MRS/I to specifically evaluate 2-hydroxyglutarate (2HG) due to its up-regulation in patients with an IDH mutation ( 38 , 42 , 43 , 51 ). GBMs with IDH-mutant status have increased NADPH activity which increases the production of 2HG and may subsequently be associated with more favorable outcomes ( 38 , 42 , 43 , 51 , 52 ). Overall, these studies show that enhanced visualization of 2HG can be obtained.…”

Section: Resultsmentioning

confidence: 99%

“…Overall, these studies show that enhanced visualization of 2HG can be obtained. Optimization of 1 H-MRS/I allows for detection of 2HG in concentrations as low as 0.5 mM ( 52 ). Therefore, further optimizations and improvements may achieve higher resolution and better robustness to enable clinical use in diagnostics and prognostics.…”

Section: Resultsmentioning

confidence: 99%

Ultra-High-Field MRI in the Diagnosis and Management of Gliomas: A Systematic Review

et al. 2022

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Importance:Gliomas, tumors of the central nervous system, are classically diagnosed through invasive surgical biopsy and subsequent histopathological study. Innovations in ultra-high field (UHF) imaging, namely 7-Tesla magnetic resonance imaging (7T MRI) are advancing preoperative tumor grading, visualization of intratumoral structures, and appreciation of small brain structures and lesions.ObjectiveSummarize current innovative uses of UHF imaging techniques in glioma diagnostics and treatment.MethodsA systematic review in accordance with PRISMA guidelines was performed utilizing PubMed. Case reports and series, observational clinical trials, and randomized clinical trials written in English were included. After removing unrelated studies and those with non-human subjects, only those related to 7T MRI were independently reviewed and summarized for data extraction. Some preclinical animal models are briefly described to demonstrate future usages of ultra-high-field imaging.ResultsWe reviewed 46 studies (43 human and 3 animal models) which reported clinical usages of UHF MRI in the diagnosis and management of gliomas. Current literature generally supports greater resolution imaging from 7T compared to 1.5T or 3T MRI, improving visualization of cerebral microbleeds and white and gray matter, and providing more precise localization for radiotherapy targeting. Additionally, studies found that diffusion or susceptibility-weighted imaging techniques applied to 7T MRI, may be used to predict tumor grade, reveal intratumoral structures such as neovasculature and microstructures like axons, and indicate isocitrate dehydrogenase 1 mutation status in preoperative imaging. Similarly, newer imaging techniques such as magnetic resonance spectroscopy and chemical exchange saturation transfer imaging can be performed on 7T MRI to predict tumor grading and treatment efficacy. Geometrical distortion, a known challenge of 7T MRI, was at a tolerable level in all included studies.ConclusionUHF imaging has the potential to preoperatively and non-invasively grade gliomas, provide precise therapy target areas, and visualize lesions not seen on conventional MRI.

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“…QUANT) used for automated ex vivo NMR metabolomics. Continuing developments in MR scanner technologies, including higher magnetic field strengths and improved coil array designs, have significantly increased our ability to generate MRS images with greater spatial resolution [ 49 , 50 , 51 , 52 ], as well as investigations of tissue cellular microstructures through diffusion-weighted MR spectroscopy [ 53 ]. Thanks to these improvements, MRS and MRSI are now offering metabolomics researchers and clinicians the ability to monitor detailed metabolic changes at high spatial resolution with good sensitivity in real time, in living organisms or in live patients.…”

Section: Metabolite Imaging In Vivo Nmr and Clinical Nmrmentioning

confidence: 99%

NMR and Metabolomics—A Roadmap for the Future

et al. 2022

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Metabolomics investigates global metabolic alterations associated with chemical, biological, physiological, or pathological processes. These metabolic changes are measured with various analytical platforms including liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). While LC-MS methods are becoming increasingly popular in the field of metabolomics (accounting for more than 70% of published metabolomics studies to date), there are considerable benefits and advantages to NMR-based methods for metabolomic studies. In fact, according to PubMed, more than 926 papers on NMR-based metabolomics were published in 2021—the most ever published in a given year. This suggests that NMR-based metabolomics continues to grow and has plenty to offer to the scientific community. This perspective outlines the growing applications of NMR in metabolomics, highlights several recent advances in NMR technologies for metabolomics, and provides a roadmap for future advancements.

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Comparison of 2-Hydroxyglutarate Detection With sLASER and MEGA-sLASER at 7T

Cited by 12 publications

References 32 publications

Spectroscopic imaging of D-2-hydroxyglutarate and other metabolites in pre-surgical patients with IDH-mutant lower-grade gliomas

Spectroscopic imaging of D-2-hydroxyglutarate and other metabolites in pre-surgical patients with IDH-mutant lower-grade gliomas

Ultra-High-Field MRI in the Diagnosis and Management of Gliomas: A Systematic Review

NMR and Metabolomics—A Roadmap for the Future

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