Metabolic characterization of human IDH mutant and wild type gliomas using simultaneous pH- and oxygen-sensitive molecular MRI.
Adolescent
Adult
Aged
Aged, 80 and over
Brain Neoplasms
/ diagnostic imaging
Echo-Planar Imaging
Female
Glioma
/ diagnostic imaging
Glycolysis
Humans
Hydrogen-Ion Concentration
Hypoxia
/ diagnostic imaging
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
Image-Guided Biopsy
Isocitrate Dehydrogenase
/ genetics
Lactic Acid
/ metabolism
Magnetic Resonance Imaging
/ methods
Male
Middle Aged
Neoplasm Grading
Oxidative Phosphorylation
Stereotaxic Techniques
Tumor Hypoxia
Young Adult
CEST-SAGE-EPI
HIF1α
IDH1 mutant gliomas
pH-weighted MRI
tumor metabolism
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
06 09 2019
06 09 2019
Historique:
pubmed:
9
5
2019
medline:
11
11
2020
entrez:
9
5
2019
Statut:
ppublish
Résumé
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. 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 (MTRasym) at 3 ppm and oxygen-sensitive measure of R2' 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. IDH1 mutant gliomas exhibited significantly lower MTRasym at 3 ppm, R2', and MTRasymxR2' (P = 0.007, P = 0.003, and P = 0.001, respectively). MTRasymxR2' could identify IDH1 mutant gliomas with a high sensitivity (81.0%) and specificity (81.3%). HIF1α was positively correlated with MTRasym at 3 ppm, R2' and MTRasymxR2' in IDH1 wild type (r = 0.610, P = 0.003; r = 0.667, P = 0.008; r = 0.635, P = 0.006), but only MTRasymxR2' in IDH1 mutant gliomas (r = 0.727, P = 0.039). IDH1 mutant gliomas have distinct metabolic and microenvironment characteristics compared with wild type gliomas. An imaging biomarker combining tumor acidity and hypoxia (MTRasymxR2') can differentiate IDH1 mutation status and is correlated with tumor acidity and hypoxia.
Sections du résumé
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 (MTRasym) at 3 ppm and oxygen-sensitive measure of R2' 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 MTRasym at 3 ppm, R2', and MTRasymxR2' (P = 0.007, P = 0.003, and P = 0.001, respectively). MTRasymxR2' could identify IDH1 mutant gliomas with a high sensitivity (81.0%) and specificity (81.3%). HIF1α was positively correlated with MTRasym at 3 ppm, R2' and MTRasymxR2' in IDH1 wild type (r = 0.610, P = 0.003; r = 0.667, P = 0.008; r = 0.635, P = 0.006), but only MTRasymxR2' 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 (MTRasymxR2') can differentiate IDH1 mutation status and is correlated with tumor acidity and hypoxia.
Identifiants
pubmed: 31066901
pii: 5485508
doi: 10.1093/neuonc/noz078
pmc: PMC7594567
doi:
Substances chimiques
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Lactic Acid
33X04XA5AT
Isocitrate Dehydrogenase
EC 1.1.1.41
IDH1 protein, human
EC 1.1.1.42.
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1184-1196Subventions
Organisme : NCI NIH HHS
ID : P50 CA211015
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA223757
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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