Veit M Stoecklein1,2, Sophia Stoecklein3, Franziska Galiè3,4, Jianxun Ren4, Michael Schmutzer1, Marcus Unterrainer5, Nathalie L Albert5, Friedrich-W Kreth1,2, Niklas Thon1,2, Thomas Liebig6, Birgit Ertl-Wagner3,7, Joerg-C Tonn1,2, Hesheng Liu4,8. 1. Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany. 2. German Cancer Consortium , partner site Munich, German Cancer Research Center, Heidelberg, Germany. 3. Department of Radiology, Ludwig Maximilians University Munich, Munich, Germany. 4. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. 5. Department of Nuclear Medicine, Ludwig Maximilians University, Munich, Germany. 6. Institute of Neuroradiology, Ludwig Maximilians University, Munich, Germany. 7. Department of Radiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 8. Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA.
Abstract
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.
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 gliomapatients. 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.
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