Resting-state fMRI detects alterations in whole brain connectivity related to tumor biology in glioma patients.


Journal

Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420

Informations de publication

Date de publication:
29 09 2020
Historique:
pubmed: 29 2 2020
medline: 28 4 2021
entrez: 29 2 2020
Statut: ppublish

Résumé

Systemic infiltration of the brain by tumor cells is a hallmark of glioma pathogenesis which may cause disturbances in functional connectivity. We hypothesized that aggressive high-grade tumors cause more damage to functional connectivity than low-grade tumors. We designed an imaging tool based on resting-state functional (f)MRI to individually quantify abnormality of functional connectivity and tested it in a prospective cohort of patients with newly diagnosed glioma. Thirty-four patients were analyzed (World Health Organization [WHO] grade II, n = 13; grade III, n = 6; grade IV, n = 15; mean age, 48.7 y). Connectivity abnormality could be observed not only in the lesioned brain area but also in the contralateral hemisphere with a close correlation between connectivity abnormality and aggressiveness of the tumor as indicated by WHO grade. Isocitrate dehydrogenase 1 (IDH1) mutation status was also associated with abnormal connectivity, with more alterations in IDH1 wildtype tumors independent of tumor size. Finally, deficits in neuropsychological performance were correlated with connectivity abnormality. Here, we suggested an individually applicable resting-state fMRI marker in glioma patients. Analysis of the functional connectome using this marker revealed that abnormalities of functional connectivity could be detected not only adjacent to the visible lesion but also in distant brain tissue, even in the contralesional hemisphere. These changes were associated with tumor biology and cognitive function. The ability of our novel method to capture tumor effects in nonlesional brain suggests a potential clinical value for both individualizing and monitoring glioma therapy.

Sections du résumé

BACKGROUND
Systemic infiltration of the brain by tumor cells is a hallmark of glioma pathogenesis which may cause disturbances in functional connectivity. We hypothesized that aggressive high-grade tumors cause more damage to functional connectivity than low-grade tumors.
METHODS
We designed an imaging tool based on resting-state functional (f)MRI to individually quantify abnormality of functional connectivity and tested it in a prospective cohort of patients with newly diagnosed glioma.
RESULTS
Thirty-four patients were analyzed (World Health Organization [WHO] grade II, n = 13; grade III, n = 6; grade IV, n = 15; mean age, 48.7 y). Connectivity abnormality could be observed not only in the lesioned brain area but also in the contralateral hemisphere with a close correlation between connectivity abnormality and aggressiveness of the tumor as indicated by WHO grade. Isocitrate dehydrogenase 1 (IDH1) mutation status was also associated with abnormal connectivity, with more alterations in IDH1 wildtype tumors independent of tumor size. Finally, deficits in neuropsychological performance were correlated with connectivity abnormality.
CONCLUSION
Here, we suggested an individually applicable resting-state fMRI marker in glioma patients. Analysis of the functional connectome using this marker revealed that abnormalities of functional connectivity could be detected not only adjacent to the visible lesion but also in distant brain tissue, even in the contralesional hemisphere. These changes were associated with tumor biology and cognitive function. The ability of our novel method to capture tumor effects in nonlesional brain suggests a potential clinical value for both individualizing and monitoring glioma therapy.

Identifiants

pubmed: 32107555
pii: 5764143
doi: 10.1093/neuonc/noaa044
pmc: PMC7523460
doi:

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

1388-1398

Subventions

Organisme : NIDA NIH HHS
ID : P50 DA046373
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC017991
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS091604
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH121831
Pays : United States

Informations de copyright

© The Author(s) 2020. 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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Auteurs

Veit M Stoecklein (VM)

Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany.
German Cancer Consortium , partner site Munich, German Cancer Research Center, Heidelberg, Germany.

Sophia Stoecklein (S)

Department of Radiology, Ludwig Maximilians University Munich, Munich, Germany.

Franziska Galiè (F)

Department of Radiology, Ludwig Maximilians University Munich, Munich, Germany.
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.

Jianxun Ren (J)

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.

Michael Schmutzer (M)

Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany.

Marcus Unterrainer (M)

Department of Nuclear Medicine, Ludwig Maximilians University, Munich, Germany.

Nathalie L Albert (NL)

Department of Nuclear Medicine, Ludwig Maximilians University, Munich, Germany.

Friedrich-W Kreth (FW)

Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany.
German Cancer Consortium , partner site Munich, German Cancer Research Center, Heidelberg, Germany.

Niklas Thon (N)

Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany.
German Cancer Consortium , partner site Munich, German Cancer Research Center, Heidelberg, Germany.

Thomas Liebig (T)

Institute of Neuroradiology, Ludwig Maximilians University, Munich, Germany.

Birgit Ertl-Wagner (B)

Department of Radiology, Ludwig Maximilians University Munich, Munich, Germany.
Department of Radiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Joerg-C Tonn (JC)

Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany.
German Cancer Consortium , partner site Munich, German Cancer Research Center, Heidelberg, Germany.

Hesheng Liu (H)

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA.

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Classifications MeSH