In vivo Metabolic Profiles as Determined by 31P and short TE 1H MR-Spectroscopy

Wenger, Katharina; Hattingen, Elke; Franz, Kea; Steinbach, Joachim P.; Bähr, Oliver; Pilatus, Ulrich

doi:10.1007/s00062-017-0630-8

Cited by 20 publications

(10 citation statements)

References 38 publications

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“…Prior preclinical and clinical studies have discussed possible changes in the phospholipid mechanism related to mutations in IDH genes but were not entirely consistent. 29,41,42,48,49 Phospholipids are synthesized from phosphatidic acid and 1,2-diacylglycerol intermediates in the synthesis of triacylglycerols. The link to lactate production is pyruvate.…”

Section: Changes In Tumor Ph Imentioning

confidence: 99%

“…Statistical significance in pH i between patients with IDHmut and IDHwt gliomas was maintained, excluding the 2 patients pretreated with radiation therapy or chemotherapy from the cohort (P , .001). Further results regarding metabolite ratios obtained from 3D 31 P chemical shift imaging have been published previously 39,41. DISCUSSION…”

mentioning

confidence: 95%

“…pH i in predefined tumor voxels was determined from the chemical shift difference between inorganic phosphate and phosphocreatine, following the approach by Petroff et al 40 as described in our previous publications. 24,41 Statistics Statistical analysis was performed with Statistica (Version 7.1; StatSoft). Lac/Cr signal ratio, absolute Lac and Cr concentrations, as well as pH i were compared using a 2-tailed unpaired t test (IDHmut versus IDHwt; IDHmut WHO II versus IDHmut WHO III [Lac only]; IDH mut and chromosomal losses 1p/19q versus IDHmut without chromosomal losses 1p/19q [Lac only]).…”

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confidence: 99%

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Lower Lactate Levels and Lower Intracellular pH in Patients with IDH-Mutant versus Wild-Type Gliomas

Wenger

Steinbach

Bähr

et al. 2020

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Preclinical evidence points toward a metabolic reprogramming in isocitrate dehydrogenase (IDH) mutated tumor cells with down-regulation of the expression of genes that encode for glycolytic metabolism. We noninvasively investigated lactate and Cr concentrations, as well as intracellular pH using 1 H/phosphorus 31 ( 31 P) MR spectroscopy in a cohort of patients with gliomas.MATERIALS AND METHODS: Thirty prospectively enrolled, mostly untreated patients with gliomas met the spectral quality criteria (World Health Organization IIMR imaging protocol included 3D 31 P chemical shift imaging and 1 H single-voxel spectroscopy (point-resolved spectroscopy sequence at TE ¼ 30 ms and TE ¼ 97 ms with optimized echo spacing for detection of 2-hydroxyglutarate) from the tumor area. Values for absolute metabolite concentrations were calculated (phantom replacement method). Intracellular pH was determined from 31 P chemical shift imaging.RESULTS: At TE ¼ 97 ms, lactate peaks can be fitted with little impact of lipid/macromolecule contamination. We found a significant difference in lactate concentrations, lactate/Cr ratios, and intracellular pH when comparing tumor voxels of patients with IDH-mutant with those of patients with IDH wild-type gliomas, with reduced lactate levels and near-normal intracellular pH in patients with IDH-mutant gliomas. We additionally found evidence for codependent effects of 1p/19q codeletion and IDH mutations with regard to lactate concentrations for World Health Organization tumor grades II and III, with lower lactate levels in patients exhibiting the codeletion. There was no statistical significance when comparing lactate concentrations between IDH-mutant World Health Organization II and III gliomas. CONCLUSIONS:We found indirect evidence for metabolic reprogramming in IDH-mutant tumors with significantly lower lactate concentrations compared with IDH wild-type tumors and a near-normal intracellular pH. ABBREVIATIONS: ATP ¼ adenosine triphosphate; CRLB ¼ Cramer-Rao Lower Bound; 2-HG ¼ 2-hydroxyglutarate; IDHmut ¼ isocitrate dehydrogenase mutant; IDHwt ¼ isocitrate dehydrogenase wild-type; MM ¼ macromolecules; NHE1 ¼ sodium-hydrogen antiporter 1; pH i ¼ intracellular pH; PRESS ¼ pointresolved spectroscopy sequence; SVS ¼ single-voxel spectroscopy; WHO ¼ World Health Organization

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Section: Changes In Tumor Ph Imentioning

confidence: 99%

mentioning

confidence: 95%

mentioning

confidence: 99%

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Lower Lactate Levels and Lower Intracellular pH in Patients with IDH-Mutant versus Wild-Type Gliomas

Wenger

Steinbach

Bähr

et al. 2020

AJNR Am J Neuroradiol

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“…31 P MRS has the potential to reveal important information about energy metabolism, cell membrane turnover, and intra‐ and extracellular pH without the need of an invasive intervention 1 . Potential applications include pH imaging 2,3 as well as imaging of energy and phospholipid metabolism, 4,5 which can be utilized in cancer and neurological and psychiatric disorders. Nevertheless, the potential of phosphorus MRS is limited by a low intrinsic sensitivity.…”

Section: Introductionmentioning

confidence: 99%

3D ³¹P MRSI of the human brain at 9.4 Tesla: Optimization and quantitative analysis of metabolic images

Ruhm

Dorst

Avdievitch

et al. 2021

Magnetic Resonance in Med

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Purpose To present 31P whole brain MRSI with a high spatial resolution to probe quantitative tissue analysis of 31P MRSI at an ultrahigh field strength of 9.4 Tesla. Methods The study protocol included a 31P MRSI measurement with an effective resolution of 2.47 mL. For SNR optimization, the nuclear Overhauser enhancement at 9.4 Tesla was investigated. A sensitivity correction was achieved by applying a low rank approximation of the γ‐adenosine triphosphate signal. Group analysis and regression on individual volunteers were performed to investigate quantitative concentration differences between different tissue types. Results Differences in gray and white matter tissue 31P concentrations could be investigated for 12 different 31P resonances. In addition, the first highly resolved quantitative MRSI images measured at B0 = 9.4 Tesla of 31P detectable metabolites with high SNR could be presented. Conclusion With an ultrahigh field strength B0 = 9.4 Tesla, 31P MRSI moves further toward quantitative metabolic imaging, and subtle differences in concentrations between different tissue types can be detected.

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“…The MR protocol included a 2D 1 H PRESS sequence, a 3D FID 31 P CSI (reported in a separate publication 27 ) and two single voxel PRESS sequences from identical target positions. For the majority of patients, single voxel volumes of 8 mL (20 × 20 × 20 mm) were selected from the tumor area.…”

Section: Mrimentioning

confidence: 99%

Fitting algorithms and baseline correction influence the results of non‐invasive in vivo quantitation of 2‐hydroxyglutarate with ¹H‐MRS

Wenger¹,

Hattingen

Harter

et al. 2018

NMR in Biomedicine

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1H‐MRS enables non‐invasive detection of 2‐hydroxyglutarate (2‐HG), an oncometabolite accumulating in gliomas carrying mutations in the isocitrate dehydrogenase (IDH) genes. Reliable 2‐HG quantitation requires reproducible post‐processing, deployment of fitting algorithms and quantitation methods. We prospectively enrolled 38 patients with suspected or recently diagnosed gliomas (IDH mutated n = 26). The MRI protocol included a 1H single voxel PRESS sequence with volumes of usually 8 mL or more (20 × 20 × 20 mm3) at TE = 97 ms and 180° pulse spacing. Our aim was to evaluate the reliability of 2‐HG quantitation comparing two frequently used software tools and their respective options of baseline correction (jMRUI with the time domain methods AQSES and QUEST, and LCModel, which analyzes the frequency domain data). For AQSES, degrees of freedom for baseline correction constrains were varied. For LCModel, baseline correction was obtained with and without correction of the unknown background term (predefined macromolecules, lipids). Tissue concentrations were calculated based on the phantom replacement method. Quantitation of 2‐HG levels showed similar mean 2‐HG tissue concentrations for IDH mutated tumors (2.65mM, range 3.06–2.20) for all methods. Bland–Altman plots (difference plots) did not reveal a systematic bias (fixed bias) for any of the algorithms tested, and we were able to show a significant correlation regarding 2‐HG concentration at the same echo time with few statistical outliers (parametric correlation). However, evaluation of outliers suggested that in vivo quantitation of 2‐HG is affected not only by the fitting domain (time or frequency), but also by the baseline correction, which is a major contributing factor to the result of 2‐HG fitting. Clinical application of 2‐HG quantitation as a prognostic or predictive biomarker, particularly in multicenter trials, requires standardized use of fitting methods and baseline correction procedures.

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In vivo Metabolic Profiles as Determined by 31P and short TE 1H MR-Spectroscopy

Abstract: Using 3D-CSI data acquisition, in vivo P MR spectroscopic measurement of phospholipid metabolites could not distinguish between IDHmut and IDHwt.

Cited by 20 publications

References 38 publications

Lower Lactate Levels and Lower Intracellular pH in Patients with IDH-Mutant versus Wild-Type Gliomas

Lower Lactate Levels and Lower Intracellular pH in Patients with IDH-Mutant versus Wild-Type Gliomas

3D ³¹P MRSI of the human brain at 9.4 Tesla: Optimization and quantitative analysis of metabolic images

Fitting algorithms and baseline correction influence the results of non‐invasive in vivo quantitation of 2‐hydroxyglutarate with ¹H‐MRS

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In vivo Metabolic Profiles as Determined by 31P and short TE 1H MR-Spectroscopy

Abstract: Using 3D-CSI data acquisition, in vivo P MR spectroscopic measurement of phospholipid metabolites could not distinguish between IDHmut and IDHwt.

Cited by 20 publications

References 38 publications

Lower Lactate Levels and Lower Intracellular pH in Patients with IDH-Mutant versus Wild-Type Gliomas

Lower Lactate Levels and Lower Intracellular pH in Patients with IDH-Mutant versus Wild-Type Gliomas

3D 31P MRSI of the human brain at 9.4 Tesla: Optimization and quantitative analysis of metabolic images

Fitting algorithms and baseline correction influence the results of non‐invasive in vivo quantitation of 2‐hydroxyglutarate with 1H‐MRS

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Product

Resources

About

3D ³¹P MRSI of the human brain at 9.4 Tesla: Optimization and quantitative analysis of metabolic images

Fitting algorithms and baseline correction influence the results of non‐invasive in vivo quantitation of 2‐hydroxyglutarate with ¹H‐MRS