Myo-Inositol Levels Measured with MR Spectroscopy Can Help Predict Failure of Antiangiogenic Treatment in Recurrent Glioblastoma

El-Abtah, Mohamed E.; Wenke, Michael; Talati, Pratik; Fu, Melanie; Kim, Daniel; Weerasekera, Akila; He, Julian; Vaynrub, Anna; Vangel, Mark; Rapalino, Otto; Andronesi, Ovidiu C.; Arrillaga‐Romany, Isabel; Forst, Deborah; Yen, Yi‐Fen; Rosen, Bruce R.; Batchelor, Tracy T.; González, R Gilberto; Dietrich, Jörg; Gerstner, Elizabeth R.; Ratai, Eva‐Maria

doi:10.1148/radiol.2021210826

Cited by 14 publications

(29 citation statements)

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“…A total of ten studies were performed on patients with recurrent GBM 6 , 12 , 17 , 22 , 25 , 27 , 28 , 29 , 30 , 31 (10/11; 90.9%) and 1 study was performed on patients with newly diagnosed GBM 26 (1/11; 9.1%). All patients underwent surgical resection or biopsy followed by chemoradiation.…”

Section: Resultsmentioning

confidence: 99%

“… 3 , 4 Proposed mechanisms for this include changes in the permeability of the blood brain barrier (BBB) and a non-enhancing AAT-induced brain infiltration driven by vascular co-option. 5 , 6 To that end, there has been much interest in the incorporation of other advanced MRI modalities to investigate markers that differentiate pseudoresponse from true response after initiating AAT.…”

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confidence: 99%

“…mI is an osmoregulator and glial marker that has been shown to be decreased in more aggressive gliomas and in shorter-term survivors of GBM. 6 , 13 Further, it is believed that disruptions to the BBB result in disturbances to osmotic equilibrium, resulting in lower mI concentrations. 6 Although the resonance of glycine (Gly) overlaps with that of mI at short TE, it can be detected in isolation at longer TE due to the cancelation of the mI peak.…”

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confidence: 99%

“… 6 , 13 Further, it is believed that disruptions to the BBB result in disturbances to osmotic equilibrium, resulting in lower mI concentrations. 6 Although the resonance of glycine (Gly) overlaps with that of mI at short TE, it can be detected in isolation at longer TE due to the cancelation of the mI peak. 14 Notably, high concentrations of Gly are observed in high-grade gliomas compared to lower-grade cancers.…”

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confidence: 99%

“…Despite numerous reports on the incorporation of MRSI to investigate metabolic changes after AAT in patients with GBM, 6 , 12 , 22 there remains uncertainty regarding which MRS methodology to use, and how and when to incorporate MRS within the clinical management of patients. This is partly due to heterogeneity in the timing of MRSI acquisition post-AAT initiation, need for technical expertise to methodologic ally implement MRSI, and the lack of consensus on metabolites of interest.…”

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confidence: 99%

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Magnetic resonance spectroscopic imaging for detecting metabolic changes in glioblastoma after anti-angiogenic therapy—a systematic literature review

El-Abtah

Talati

Dietrich

et al. 2022

Neuro-Oncology Advances

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Background The impact of antiangiogenic therapy (AAT) on patients with glioblastoma (GBM) is unclear due to a disconnect between radiographic findings and overall survivorship. MR spectroscopy (MRS) can provide clinically relevant information regarding tumor metabolism in response to AAT. This review explores the use of MRS to track metabolic changes in patients with GBM treated with AAT. Methods We conducted a systematic literature review in accordance with PRISMA guidelines to identify primary research articles that reported metabolic changes in GBMs treated with AAT. Collected variables included single or multi-voxel MRS acquisition parameters, metabolic markers, reported metabolic changes in response to AAT, and survivorship data. Results Thirty-five articles were retrieved in the initial query. After applying inclusion and exclusion criteria, 11 studies with 262 patients were included for qualitative synthesis with all studies performed using multivoxel 1H MRS. Two studies utilized 31P MRS. Post-AAT initiation, shorter-term survivors had increased choline (cellular proliferation marker), increased lactate (a hypoxia marker), and decreased levels of the short echo time (TE) marker, myo-inositol (an osmoregulator and gliosis marker). MRS detected metabolic changes as soon as 1-day after AAT, and throughout the course of AAT, to predict survival. There was substantial heterogeneity in the timing of scans, which ranged from 1-day to 6-9 months after AAT initiation. Conclusions Multivoxel MRS at intermediate and short TE can serve as a robust prognosticator of outcomes of patients with GBM who are treated with AAT.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Magnetic resonance spectroscopic imaging for detecting metabolic changes in glioblastoma after anti-angiogenic therapy—a systematic literature review

El-Abtah

Talati

Dietrich

et al. 2022

Neuro-Oncology Advances

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Metabolic signatures derived from whole-brain MR-spectroscopy identify early tumor progression in high-grade gliomas using machine learning

Rivera,

Bhatia,

Morell

et al. 2024

J Neurooncol

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Purpose Recurrence for high-grade gliomas is inevitable despite maximal safe resection and adjuvant chemoradiation, and current imaging techniques fall short in predicting future progression. However, we introduce a novel whole-brain magnetic resonance spectroscopy (WB-MRS) protocol that delves into the intricacies of tumor microenvironments, offering a comprehensive understanding of glioma progression to inform expectant surgical and adjuvant intervention. Methods We investigated five locoregional tumor metabolites in a post-treatment population and applied machine learning (ML) techniques to analyze key relationships within seven regions of interest: contralateral normal-appearing white matter (NAWM), fluid-attenuated inversion recovery (FLAIR), contrast-enhancing tumor at time of WB-MRS (Tumor), areas of future recurrence (AFR), whole-brain healthy (WBH), non-progressive FLAIR (NPF), and progressive FLAIR (PF). Five supervised ML classification models and a neural network were developed, optimized, trained, tested, and validated. Lastly, a web application was developed to host our novel calculator, the Miami Glioma Prediction Map (MGPM), for open-source interaction. Results Sixteen patients with histopathological confirmation of high-grade glioma prior to WB-MRS were included in this study, totaling 118,922 whole-brain voxels. ML models successfully differentiated normal-appearing white matter from tumor and future progression. Notably, the highest performing ML model predicted glioma progression within fluid-attenuated inversion recovery (FLAIR) signal in the post-treatment setting (mean AUC = 0.86), with Cho/Cr as the most important feature. Conclusions This study marks a significant milestone as the first of its kind to unveil radiographic occult glioma progression in post-treatment gliomas within 8 months of discovery. These findings underscore the utility of ML-based WB-MRS growth predictions, presenting a promising avenue for the guidance of early treatment decision-making. This research represents a crucial advancement in predicting the timing and location of glioblastoma recurrence, which can inform treatment decisions to improve patient outcomes.

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Emerging role of inositol monophosphatase in cancer

Chen¹,

Shen²,

Li³

2023

Biomedicine & Pharmacotherapy

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Myo-Inositol Levels Measured with MR Spectroscopy Can Help Predict Failure of Antiangiogenic Treatment in Recurrent Glioblastoma

Cited by 14 publications

References 33 publications

Magnetic resonance spectroscopic imaging for detecting metabolic changes in glioblastoma after anti-angiogenic therapy—a systematic literature review

Magnetic resonance spectroscopic imaging for detecting metabolic changes in glioblastoma after anti-angiogenic therapy—a systematic literature review

Metabolic signatures derived from whole-brain MR-spectroscopy identify early tumor progression in high-grade gliomas using machine learning

Emerging role of inositol monophosphatase in cancer

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