Towards integrating imaging and immunology in glioblastoma: mapping blood immune system metrics to tumor magnetic resonance image data

Abstract Background Glioblastoma is the most frequent and aggressive brain cancer. It is a highly immunology-driven disease as up to a third of its mass is composed of immune cells. Apart from immunology, imaging is a major research frontier. The VASARI (Visually AcceSAble Rembrandt Images) MRI feat...

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Main Authors: Johanna Heugenhauser, Carmen Visus, Johanna Buchroithner, Christine Marosi, Karl Rössler, Thomas Felzmann, Georg Widhalm, Sarah Iglseder, Martha Nowosielski, Friedrich Erhart
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Acta Neuropathologica Communications
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Online Access:https://doi.org/10.1186/s40478-024-01888-8
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author Johanna Heugenhauser
Carmen Visus
Johanna Buchroithner
Christine Marosi
Karl Rössler
Thomas Felzmann
Georg Widhalm
Sarah Iglseder
Martha Nowosielski
Friedrich Erhart
author_facet Johanna Heugenhauser
Carmen Visus
Johanna Buchroithner
Christine Marosi
Karl Rössler
Thomas Felzmann
Georg Widhalm
Sarah Iglseder
Martha Nowosielski
Friedrich Erhart
author_sort Johanna Heugenhauser
collection DOAJ
description Abstract Background Glioblastoma is the most frequent and aggressive brain cancer. It is a highly immunology-driven disease as up to a third of its mass is composed of immune cells. Apart from immunology, imaging is a major research frontier. The VASARI (Visually AcceSAble Rembrandt Images) MRI feature set is a system designed to enable consistent description of gliomas using a set of defined visual features and controlled vocabulary. Even though imaging and immunology are both indispensable for glioblastoma phenotyping, a comprehensive integration of these two disciplines has not been performed so far. Material and methods 76 patients from a previous glioblastoma immunotherapy clinical trial were retrospectively screened for the availability of peripheral blood immunology and tumor imaging data at baseline, i.e. at the start of the study. For 41 patients both were available. MRI were then analyzed via volumetry and VASARI morphometry. The resulting 27 imaging variables were linked with 67 peripheral blood immunology variables from flow cytometry and PCR and all potential relations were mapped. Results In an initial broad screening, 94 imaging-immunology associations were discovered. Notably, features of the contrast-enhancing margin like its thickness and its shape were positively correlated with various T cell species including activated cytotoxic CD8+ T cells and central memory CD8+ T cells. The T2-volume was correlated with CD56+CD16− natural killer cells, and the necrosis volume was correlated with immunopolarizing mRNAs in the blood (IFN-γ, GATA3, ROR-gt). After multiple testing correction, two imaging-immunology associations were confirmed as significant: a thick contrast-enhancing margin was correlated with lower regulatory T cell markers in the blood and invasion of deep white matter was correlated with less T helper 17 factors. Conclusion We here provide first evidence that imaging and peripheral blood immunology features can go hand in hand and that imaging variables can correlate with systemic immunophenotypes. Especially a thick contrast-enhancing margin seems to indicate a pro-inflammatory immune state. Via pioneering the integration of imaging and immunology, we not only advance basic glioblastoma science but we also open up novel avenues for research. In the future, e.g. patient stratification for therapy development could be based on imaging-guided immunophenotyping.
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spelling doaj-art-3ba67ebe58124b0e93115e63466734a22025-08-20T02:49:09ZengBMCActa Neuropathologica Communications2051-59602024-11-0112111310.1186/s40478-024-01888-8Towards integrating imaging and immunology in glioblastoma: mapping blood immune system metrics to tumor magnetic resonance image dataJohanna Heugenhauser0Carmen Visus1Johanna Buchroithner2Christine Marosi3Karl Rössler4Thomas Felzmann5Georg Widhalm6Sarah Iglseder7Martha Nowosielski8Friedrich Erhart9Department of Neurology, Medical University of InnsbruckAOP Orphan Pharmaceuticals GmbHUniversity Clinic for Neurosurgery, Kepler University Hospital, Johannes Kepler UniversityClinical Division of Medical Oncology, Department for Internal Medicine I, Medical University of ViennaDepartment of Neurosurgery, Medical University of ViennaIndependent ResearcherDepartment of Neurosurgery, Medical University of ViennaDepartment of Neurology, Medical University of InnsbruckDepartment of Neurology, Medical University of InnsbruckDepartment of Neurosurgery, Medical University of ViennaAbstract Background Glioblastoma is the most frequent and aggressive brain cancer. It is a highly immunology-driven disease as up to a third of its mass is composed of immune cells. Apart from immunology, imaging is a major research frontier. The VASARI (Visually AcceSAble Rembrandt Images) MRI feature set is a system designed to enable consistent description of gliomas using a set of defined visual features and controlled vocabulary. Even though imaging and immunology are both indispensable for glioblastoma phenotyping, a comprehensive integration of these two disciplines has not been performed so far. Material and methods 76 patients from a previous glioblastoma immunotherapy clinical trial were retrospectively screened for the availability of peripheral blood immunology and tumor imaging data at baseline, i.e. at the start of the study. For 41 patients both were available. MRI were then analyzed via volumetry and VASARI morphometry. The resulting 27 imaging variables were linked with 67 peripheral blood immunology variables from flow cytometry and PCR and all potential relations were mapped. Results In an initial broad screening, 94 imaging-immunology associations were discovered. Notably, features of the contrast-enhancing margin like its thickness and its shape were positively correlated with various T cell species including activated cytotoxic CD8+ T cells and central memory CD8+ T cells. The T2-volume was correlated with CD56+CD16− natural killer cells, and the necrosis volume was correlated with immunopolarizing mRNAs in the blood (IFN-γ, GATA3, ROR-gt). After multiple testing correction, two imaging-immunology associations were confirmed as significant: a thick contrast-enhancing margin was correlated with lower regulatory T cell markers in the blood and invasion of deep white matter was correlated with less T helper 17 factors. Conclusion We here provide first evidence that imaging and peripheral blood immunology features can go hand in hand and that imaging variables can correlate with systemic immunophenotypes. Especially a thick contrast-enhancing margin seems to indicate a pro-inflammatory immune state. Via pioneering the integration of imaging and immunology, we not only advance basic glioblastoma science but we also open up novel avenues for research. In the future, e.g. patient stratification for therapy development could be based on imaging-guided immunophenotyping.https://doi.org/10.1186/s40478-024-01888-8GlioblastomaImmunologyMagnetic resonance imagingVolumetryVASARI
spellingShingle Johanna Heugenhauser
Carmen Visus
Johanna Buchroithner
Christine Marosi
Karl Rössler
Thomas Felzmann
Georg Widhalm
Sarah Iglseder
Martha Nowosielski
Friedrich Erhart
Towards integrating imaging and immunology in glioblastoma: mapping blood immune system metrics to tumor magnetic resonance image data
Acta Neuropathologica Communications
Glioblastoma
Immunology
Magnetic resonance imaging
Volumetry
VASARI
title Towards integrating imaging and immunology in glioblastoma: mapping blood immune system metrics to tumor magnetic resonance image data
title_full Towards integrating imaging and immunology in glioblastoma: mapping blood immune system metrics to tumor magnetic resonance image data
title_fullStr Towards integrating imaging and immunology in glioblastoma: mapping blood immune system metrics to tumor magnetic resonance image data
title_full_unstemmed Towards integrating imaging and immunology in glioblastoma: mapping blood immune system metrics to tumor magnetic resonance image data
title_short Towards integrating imaging and immunology in glioblastoma: mapping blood immune system metrics to tumor magnetic resonance image data
title_sort towards integrating imaging and immunology in glioblastoma mapping blood immune system metrics to tumor magnetic resonance image data
topic Glioblastoma
Immunology
Magnetic resonance imaging
Volumetry
VASARI
url https://doi.org/10.1186/s40478-024-01888-8
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