Quantitative Dynamic Oxygen 17 MRI at 7.0 T for the Cerebral Oxygen                    Metabolism in Glioma

Paech, Daniel; Nagel, Armin M.; Schultheiss, Miriam N; Umathum, Reiner; Regnery, Sebastian; Scherer, Moritz; Wick, Antje; Platt, Tanja; Wick, Wolfgang; Bendszus, Martin; Unterberg, Andreas; Schlemmer, Heinz–Peter; Ladd, Mark E.; Niesporek, Sebastian C.

doi:10.1148/radiol.2020191711

Cited by 42 publications

(38 citation statements)

References 21 publications

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“…Furthermore, the high metabolic turnover rate of GB requires intensive angiogenesis in order to maintain the high metabolic demand. Our findings with regard to GB oxygen metabolism concur that of previously published studies [ 30 , 31 ].…”

Section: Discussionsupporting

confidence: 93%

Physiological MRI Biomarkers in the Differentiation Between Glioblastomas and Solitary Brain Metastases

et al. 2021

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Purpose Glioblastomas (GB) and solitary brain metastases (BM) are the most common brain tumors in adults. GB and BM may appear similar in conventional magnetic resonance imaging (cMRI). Their management strategies, however, are quite different with significant consequences on clinical outcome. The aim of this study was to evaluate the usefulness of a previously presented physiological MRI approach scoping to obtain quantitative information about microvascular architecture and perfusion, neovascularization activity, and oxygen metabolism to differentiate GB from BM. Procedures Thirty-three consecutive patients with newly diagnosed, untreated, and histopathologically confirmed GB or BM were preoperatively examined with our physiological MRI approach as part of the cMRI protocol. Results Physiological MRI biomarker maps revealed several significant differences in the pathophysiology of GB and BM: Central necrosis was more hypoxic in GB than in BM (30 %; P = 0.036), which was associated with higher neovascularization activity (65 %; P = 0.043) and metabolic rate of oxygen (48 %; P = 0.004) in the adjacent contrast-enhancing viable tumor parts of GB. In peritumoral edema, GB infiltration caused neovascularization activity (93 %; P = 0.018) and higher microvascular perfusion (30 %; P = 0.022) associated with higher tissue oxygen tension (33 %; P = 0.020) and lower oxygen extraction from vasculature (32 %; P = 0.040). Conclusion Our physiological MRI approach, which requires only 7 min of extra data acquisition time, might be helpful to noninvasively distinguish GB and BM based on pathophysiological differences. However, further studies including more patients are required.

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Section: Discussionsupporting

confidence: 93%

Physiological MRI Biomarkers in the Differentiation Between Glioblastomas and Solitary Brain Metastases

et al. 2021

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“…Our study showed that ISL2 shared a similar oncogenic role as its family member, ISL1, in other cancers [29,30]. Due to its rapid and infiltrating growth properties, glioma shows active metabolism and uses an abundant blood supply in tumor tissues [27,31]. These properties also lead to complete surgical resection and tumor recurrence [32].…”

Section: Discussionmentioning

confidence: 63%

The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

Jiang

Zhou

Zhao

et al. 2020

J Exp Clin Cancer Res

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Background Glioma is the most common and lethal primary brain tumor in adults, and angiogenesis is one of the key factors contributing to its proliferation, aggressiveness, and malignant transformation. However, the discovery of novel oncogenes and the study of its molecular regulating mechanism based on circular RNAs (circRNAs) may provide a promising treatment target in glioma. Methods Bioinformatics analysis, qPCR, western blotting, and immunohistochemistry were used to detect the expression levels of ISL2, miR-342–3p, circRNA ARF1 (cARF1), U2AF2, and VEGFA. Patient-derived glioma stem cells (GSCs) were established for the molecular experiments. Lentiviral-based infection was used to regulate the expression of these molecules in GSCs. The MTS, EDU, Transwell, and tube formation assays were used to detect the proliferation, invasion, and angiogenesis of human brain microvessel endothelial cells (hBMECs). RNA-binding protein immunoprecipitation, RNA pull-down, dual-luciferase reporter, and chromatin immunoprecipitation assays were used to detect the direct regulation mechanisms among these molecules. Results We first identified a novel transcription factor related to neural development. ISL2 was overexpressed in glioma and correlated with poor patient survival. ISL2 transcriptionally regulated VEGFA expression in GSCs and promoted the proliferation, invasion, and angiogenesis of hBMECs via VEGFA-mediated ERK signaling. Regarding its mechanism of action, cARF1 upregulated ISL2 expression in GSCs via miR-342–3p sponging. Furthermore, U2AF2 bound to and promoted the stability and expression of cARF1, while ISL2 induced the expression of U2AF2, which formed a feedback loop in GSCs. We also showed that both U2AF2 and cARF1 had an oncogenic effect, were overexpressed in glioma, and correlated with poor patient survival. Conclusions Our study identified a novel feedback loop among U2AF2, cARF1, miR-342–3p, and ISL2 in GSCs. This feedback loop promoted glioma angiogenesis, and could provide an effective biomarker for glioma diagnosis and prognostic evaluation, as well as possibly being used for targeted therapy.

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“…Hoffmann et al 232 obtained the first dynamic 17 O MR data in a patient with glioblastoma, showing a decreased CMRO 2 value within the tumor tissue. Recently, a 17 O inhalation study including 10 patients with brain tumors was published 233 in which both high-grade and low-grade gliomas exhibited a lower 17 O MR signal increase in the tumor region and a decrease in tumor CMRO 2 , which is in accordance with the Warburg effect.…”

Section: X-nuclei Magnetic Resonance Spectroscopy and Magnetic Resonance Imagingmentioning

confidence: 85%

7 Tesla and Beyond

2021

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Ultrahigh magnetic fields offer significantly higher signal-to-noise ratio, and several magnetic resonance applications additionally benefit from a higher contrast-to-noise ratio, with static magnetic field strengths of B 0 ≥ 7 T currently being referred to as ultrahigh fields (UHFs). The advantages of UHF can be used to resolve structures more precisely or to visualize physiological/pathophysiological effects that would be difficult or even impossible to detect at lower field strengths. However, with these advantages also come challenges, such as inhomogeneities applying standard radiofrequency excitation techniques, higher energy deposition in the human body, and enhanced B 0 field inhomogeneities. The advantages but also the challenges of UHF as well as promising advanced methodological developments and clinical applications that particularly benefit from UHF are discussed in this review article.

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Quantitative Dynamic Oxygen 17 MRI at 7.0 T for the Cerebral Oxygen Metabolism in Glioma

Cited by 42 publications

References 21 publications

Physiological MRI Biomarkers in the Differentiation Between Glioblastomas and Solitary Brain Metastases

Physiological MRI Biomarkers in the Differentiation Between Glioblastomas and Solitary Brain Metastases

The U2AF2 /circRNA ARF1/miR-342–3p/ISL2 feedback loop regulates angiogenesis in glioma stem cells

7 Tesla and Beyond

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