Metabolic characterization of human IDH mutant and wild type gliomas using simultaneous pH- and oxygen-sensitive molecular MRI
| العنوان: | Metabolic characterization of human IDH mutant and wild type gliomas using simultaneous pH- and oxygen-sensitive molecular MRI |
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| المؤلفون: | Ararat Chakhoyan, Robert M. Prins, Timothy F. Cloughesy, Linda M. Liau, Catalina Raymond, William H. Yong, Whitney B. Pope, Sergey Mareninov, Albert Lai, Richard Everson, Jingwen Yao, Phioanh L. Nghiemphu, Benjamin M. Ellingson, David Nathanson, Noriko Salamon |
| المصدر: | Neuro Oncol Neuro-oncology, vol 21, iss 9 |
| بيانات النشر: | Oxford University Press (OUP), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Cancer Research, Imaging biomarker, Mutant, IDH1 mutant gliomas, Oxidative Phosphorylation, CEST-SAGE-EPI, Stereotaxic Techniques, 0302 clinical medicine, 80 and over, Glycolysis, HIF1α, Hypoxia, Cancer, Brain Neoplasms, Echo-Planar Imaging, Chemistry, Brain, Glioma, Middle Aged, Hydrogen-Ion Concentration, Magnetic Resonance Imaging, Isocitrate Dehydrogenase, Isocitrate dehydrogenase, Oncology, 030220 oncology & carcinogenesis, Biomedical Imaging, Female, Hypoxia-Inducible Factor 1, Adult, Image-Guided Biopsy, IDH1, Adolescent, Oncology and Carcinogenesis, alpha Subunit, Young Adult, 03 medical and health sciences, Rare Diseases, Clinical Research, Neuro-Imaging, medicine, Humans, Lactic Acid, Oncology & Carcinogenesis, Magnetization transfer, HIF1 alpha, Aged, pH-weighted MRI, Neurosciences, Wild type, medicine.disease, Molecular biology, Brain Disorders, Brain Cancer, Oxygen, Tumor Hypoxia, tumor metabolism, Neurology (clinical), Neoplasm Grading, 030217 neurology & neurosurgery |
| الوصف: | BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutant gliomas are thought to have distinct metabolic characteristics, including a blunted response to hypoxia and lower glycolytic flux. We hypothesized that non-invasive quantification of abnormal metabolic behavior in human IDH1 mutant gliomas could be performed using a new pH- and oxygen-sensitive molecular MRI technique. METHODS: Simultaneous pH- and oxygen-sensitive MRI was obtained at 3T using amine CEST-SAGE-EPI. The pH-dependent measure of the magnetization transfer ratio asymmetry (MTR(asym)) at 3 ppm and oxygen-sensitive measure of R(2)’ were quantified in 90 patients with gliomas. Additionally, stereotactic, image-guided biopsies were performed in 20 patients for a total of 52 samples. The association between imaging measurements and hypoxia-inducible factor 1 alpha (HIF1α) expression was identified using Pearson correlation analysis. RESULTS: IDH1 mutant gliomas exhibited significantly lower MTR(asym) at 3 ppm, R(2)’, and MTR(asym)xR(2)’ (P = 0.007, P = 0.003, and P = 0.001, respectively). MTR(asym)xR(2)’ could identify IDH1 mutant gliomas with a high sensitivity (81.0%) and specificity (81.3%). HIF1α was positively correlated with MTR(asym) at 3 ppm, R(2)’ and MTR(asym)xR(2)’ in IDH1 wild type (r = 0.610, P = 0.003; r = 0.667, P = 0.008; r = 0.635, P = 0.006), but only MTR(asym)xR(2)’ in IDH1 mutant gliomas (r = 0.727, P = 0.039). CONCLUSIONS: IDH1 mutant gliomas have distinct metabolic and microenvironment characteristics compared with wild type gliomas. An imaging biomarker combining tumor acidity and hypoxia (MTR(asym)xR(2)’) can differentiate IDH1 mutation status and is correlated with tumor acidity and hypoxia. |
| وصف الملف: | application/pdf |
| تدمد: | 1523-5866 1522-8517 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c43d73fa4a0f97a451af96335a3ce73Test https://doi.org/10.1093/neuonc/noz078Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2c43d73fa4a0f97a451af96335a3ce73 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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