Improved Brain Tumor Classification by Sodium MR Imaging: Prediction of<i>IDH</i>Mutation Status and Tumor Progression

Biller, Armin; Badde, Stephanie; Nagel, Armin M.; Neumann, J; Wick, Wolfgang; Hertenstein, Anne; Bendszus, Martin; Sahm, Felix; Benkhedah, Nadia; Kleesiek, Jens

doi:10.3174/ajnr.a4493

Cited by 59 publications

(59 citation statements)

References 47 publications

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“…Previous authors have demonstrated increased TSC within CNS neoplasms such as high-grade glioma, 17,32,39 and that 23 Na MRI can be used as a predictive marker of both tumor grade 32 and prognosis. 17 Within glioma, cellular proliferation and changes in cell membrane ion transporters 17 contribute to elevated intracellular sodium concentrations, but these tumors also display increases in the sodium-rich extravascular-extracellular space secondary to necrosis and loss of normal cellular packing. [10][11][12][13][14] Evidence from in vivo animal studies of temporal 23 Na MRI changes in glioma following chemotherapy treatment suggest that TSC may also serve as an early marker of progression and treatment response in this tumor group.…”

Section: Discussionmentioning

confidence: 99%

“…23 Na MRI has been shown to be sensitive to therapy‐induced changes in both breast and central nervous system tumors . In a recent study, 23 Na MRI outperformed an invasive histological correlate for brain tumor prognostication . 23 Na MRI may therefore allow better assessment of tissue cellularity and may allow treatment to be more personalized as a result of documenting the variety of responses seen within and between tumors.…”

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confidence: 99%

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Measuring tissue sodium concentration: Cross‐vendor repeatability and reproducibility of ²³Na‐MRI across two sites

Riemer

McHugh

Zaccagna

et al. 2019

Magnetic Resonance Imaging

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Background Sodium MRI (23Na‐MRI)‐derived biomarkers such as total sodium concentration (TSC) have the potential to provide information on tumor cellularity and the changes in tumor microstructure that occur following therapy. Purpose To evaluate the repeatability and reproducibility of TSC measurements in the brains of healthy volunteers, providing evidence for the technical validation of 23Na‐MRI‐derived biomarkers. Study Type Prospective multicenter study. Subjects Eleven volunteers (32 ± 6 years; eight males, three females) were scanned twice at each of two sites. Field Strength/Sequence Comparable 3D‐cones 23Na‐MRI ultrashort echo time acquisitions at 3T. Assessment TSC values, quantified from calibration phantoms placed in the field of view, were obtained from white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), based on automated segmentation of coregistered 1H T1‐weighted images and hand‐drawn regions of interest by two readers. Statistical Tests Coefficients of variation (CoVs) from mean TSC values were used to assess intrasite repeatability and intersite reproducibility. Results Mean GM TSC concentrations (52.1 ± 7.1 mM) were ∼20% higher than for WM (41.8 ± 6.7 mM). Measurements were highly repeatable at both sites with mean scan–rescan CoVs between volunteers and regions of 2% and 4%, respectively. Mean intersite reproducibility CoVs were 3%, 3%, and 6% for WM, GM, and CSF, respectively. Data Conclusion These results demonstrate technical validation of sodium MRI‐derived biomarkers in healthy volunteers. We also show that comparable 23Na imaging of the brain can be implemented across different sites and scanners with excellent repeatability and reproducibility. Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1278–1284.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Measuring tissue sodium concentration: Cross‐vendor repeatability and reproducibility of ²³Na‐MRI across two sites

Riemer

McHugh

Zaccagna

et al. 2019

Magnetic Resonance Imaging

View full text Add to dashboard Cite

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“…In recent years, researchers have evaluated the feasibility of applying several MRI techniques to determine IDH status in patients with gliomas (14)(15)(16)(17)(18), including gadoliniumenhanced T 1 -weighted (Gd-T 1 w) images (19), diffusion (20)(21)(22), perfusion (23), sodium MRI (24), and machinelearning algorithms (25,26). Notably, because lab studies have proven that the oncometabolite 2-hydroxyglutarate (2-HG) holds a 100-fold increase in IDH-mutant cells compared to IDH-wildtype type cells (27), recent studies also have shown that significantly higher 2-HG detected by single-voxel MRS can identify patients with IDH1-mutant gliomas with high sensitivity (28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

Predicting IDH mutation status in grade II gliomas using amide proton transfer‐weighted (APTw) MRI

Jiang

Zou

Eberhart

et al. 2017

Magnetic Resonance in Med

131

104

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Purpose To assess the APTw-MRI features of isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant grade-II gliomas and to test the hypothesis that the APTw signal is a surrogate imaging marker for identifying IDH mutation status preoperatively. Methods 27 patients with pathologically confirmed low-grade glioma, who were previously scanned at 3T, were retrospectively analyzed. The Mann-Whitney test was used to evaluate relationships between APTw intensities for IDH-mutant and IDH-wildtype groups, and the receiver-operator-characteristic analysis was used to assess the diagnostic performance of APTw. Results Based on histopathology and molecular analysis, seven cases were diagnosed as IDH-wildtype grade-II gliomas, and 20 cases as IDH-mutant grade-II gliomas. The maximum and minimum APTw values, based on multiple regions of interest, as well as the whole-tumor histogram-based mean and 50th percentile APTw values, were significantly higher in the IDH-wildtype gliomas than in the IDH-mutant groups. This corresponded to the areas under the receiver-operator-characteristic curves of 0.89, 0.76, 0.75, and 0.75, respectively, for the prediction of the IDH mutation status. Conclusions IDH-wildtype lesions were typically associated with relatively high APTw signal intensities, compared with IDH-mutant lesions. The APTw signal could be a valuable imaging biomarker by which to identify IDH1 mutation status in grade-II gliomas.

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“…SODIUM MAGNETIC RESONANCE (MR) techniques provide valuable information about cell physiology and viability and could be useful as a biomarker in vivo . Tissue sodium levels increase in multiple conditions, such as in stroke, multiple sclerosis, and radiotherapy treatment monitoring . Sodium levels increase within cells, if the sodium‐potassium pump cannot maintain the gradient of intracellular and extracellular sodium by pumping three sodium ions from intracellular space to the extracellular space with two potassium ions being exchanged against the electrochemical gradient (Na int ˜15 mM, Na ext ˜140 mM).…”

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confidence: 99%

²³Na Triple‐quantum signal of in vitro human liver cells, liposomes, and nanoparticles: Cell viability assessment vs. separation of intra‐ and extracellular signal

Hoesl

Kleimaier

et al. 2019

Magnetic Resonance Imaging

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Background Triple‐quantum (TQ) filtered sequences have become more popular in sodium MR due to the increased usage of scanners with field strengths exceeding 3T. Disagreement as to whether TQ signal can provide separation of intra‐ and extracellular compartments persists. Purpose To provide insight into TQ signal behavior on a cellular level. Study Type Prospective. Phantom/Specimen Cell‐phantoms in the form of liposomes, encapsulated 0 mM, 145 mM, 154 mM Na+ in a double‐lipid membrane similar to cells. Poly(lactic‐co‐glycolic acid) nanoparticles encapsulated 154 mM Na+ within a single‐layer membrane structure. Two microcavity chips with each 6 × 106 human HEP G2 liver cells were measured in an MR‐compatible bioreactor. Field Strength/Sequence Spectroscopic TQ sequence with time proportional phase‐increments at 9.4T. Assessment The TQ signal of viable, dead cells, and cell‐phantoms was assessed by a fit in the time domain and by the amplitude in the frequency domain. Statistical Tests The noise variance (σ) was evaluated to express the deviation of the measured TQ signal amplitude from noise. Results TQ signal >20σ was found for liposomes encapsulating sodium ions. Liposomal encapsulation of 0 mM Na+ and 154 mM Na+ encapsulation in the nanoparticles resulted in <2σ TQ signal. Cells under normal perfusion resulted in >9σ TQ signal. Compared with TQ signal under normal perfusion, a 56% lower TQ signal of was observed (25σ) during perfusion stop. TQ signal returned to 92% of the initial signal after reperfusion. Data Conclusion Our measurements indicate that TQ signal in liposomes was observed due to the trapping of ions within the double‐lipid membrane rather than from the intraliposomal space. Transfer to the cell results suggests that TQ signal was observed from motion restriction equivalent to trapping. Level of Evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:435–444.

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Improved Brain Tumor Classification by Sodium MR Imaging: Prediction ofIDHMutation Status and Tumor Progression

Cited by 59 publications

References 47 publications

Measuring tissue sodium concentration: Cross‐vendor repeatability and reproducibility of ²³Na‐MRI across two sites

Measuring tissue sodium concentration: Cross‐vendor repeatability and reproducibility of ²³Na‐MRI across two sites

Predicting IDH mutation status in grade II gliomas using amide proton transfer‐weighted (APTw) MRI

²³Na Triple‐quantum signal of in vitro human liver cells, liposomes, and nanoparticles: Cell viability assessment vs. separation of intra‐ and extracellular signal

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Improved Brain Tumor Classification by Sodium MR Imaging: Prediction ofIDHMutation Status and Tumor Progression

Cited by 59 publications

References 47 publications

Measuring tissue sodium concentration: Cross‐vendor repeatability and reproducibility of 23Na‐MRI across two sites

Measuring tissue sodium concentration: Cross‐vendor repeatability and reproducibility of 23Na‐MRI across two sites

Predicting IDH mutation status in grade II gliomas using amide proton transfer‐weighted (APTw) MRI

23Na Triple‐quantum signal of in vitro human liver cells, liposomes, and nanoparticles: Cell viability assessment vs. separation of intra‐ and extracellular signal

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Measuring tissue sodium concentration: Cross‐vendor repeatability and reproducibility of ²³Na‐MRI across two sites

Measuring tissue sodium concentration: Cross‐vendor repeatability and reproducibility of ²³Na‐MRI across two sites

²³Na Triple‐quantum signal of in vitro human liver cells, liposomes, and nanoparticles: Cell viability assessment vs. separation of intra‐ and extracellular signal