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Research ArticleBrain Tumor Imaging

Mesoscopic Assessment of Microstructure in Glioblastomas and Metastases by Merging Advanced Diffusion Imaging with Immunohistopathology

Urs Würtemberger, Daniel Erny, Alexander Rau, Jonas A. Hosp, Veysel Akgün, Marco Reisert, Valerij G. Kiselev, Jürgen Beck, Sonja Jankovic, Peter C. Reinacher, Marc Hohenhaus, Horst Urbach, Martin Diebold and Theo Demerath
American Journal of Neuroradiology November 2023, 44 (11) 1262-1269; DOI: https://doi.org/10.3174/ajnr.A8022
Urs Würtemberger
aFrom the Department of Neuroradiology (U.W., A.R., V.A., H.U., T.D.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
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  • ORCID record for Urs Würtemberger
Daniel Erny
bInstitute of Neuropathology (D.E., M.D.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
kBerta-Ottenstein-Program for Advanced Clinician Scientists (D.E.), Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Alexander Rau
aFrom the Department of Neuroradiology (U.W., A.R., V.A., H.U., T.D.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
cDepartment of Diagnostic and Interventional Radiology (A.R.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
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Jonas A. Hosp
dDepartment of Neurology and Neurophysiology (J.A.H.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
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Veysel Akgün
aFrom the Department of Neuroradiology (U.W., A.R., V.A., H.U., T.D.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
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Marco Reisert
eDepartment of Medical Physics (M.R., V.G.K.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
fDepartment of Stereotactic and Functional Neurosurgery (M.R., P.C.R.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
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Valerij G. Kiselev
eDepartment of Medical Physics (M.R., V.G.K.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
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Jürgen Beck
iDepartment of Neurosurgery (J.B., M.H.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
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Sonja Jankovic
gDepartment of Radiology (S.J.), Faculty of Medicine, University Clinical Center Nis, University of Nis, Nis, Serbia
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Peter C. Reinacher
fDepartment of Stereotactic and Functional Neurosurgery (M.R., P.C.R.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
hFraunhofer Institute for Laser Technology (P.C.R.), Aachen, Germany
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Marc Hohenhaus
iDepartment of Neurosurgery (J.B., M.H.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
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Horst Urbach
aFrom the Department of Neuroradiology (U.W., A.R., V.A., H.U., T.D.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
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Martin Diebold
bInstitute of Neuropathology (D.E., M.D.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
jIMM-PACT Clinician Scientist Program (M.D.), Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Theo Demerath
aFrom the Department of Neuroradiology (U.W., A.R., V.A., H.U., T.D.), Faculty of Medicine, Medical Center–University of Freiburg, University of Freiburg, Freiburg, Germany
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  • FIG 1.
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    FIG 1.

    Presurgical (3T) MR imaging in a patient with a right parietal GBM. Representative axial images are shown in the upper row (A–D) with the corresponding ROI (of contrast-enhancing tumor components based on A) overlaid sections in the lower row (E–H). Gd indicates Gadoteridol.

  • FIG 2.
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    FIG 2.

    Representative MR images of patients with left insular GBM (A, T1WI post-Gd; C, FA; E, OD) and a large callosal melanoma metastasis (B, T1 post-Gd; D, FA; F, OD). Representative Bielschowsky silver staining to demonstrate nerve fibers and neurofibrillary tangles (G and H) and immunohistochemical labeling for GFAP (I and J). Scale bar = 100 μm. As illustrated by parametric maps for FA (C and D, arrows) and OD (E and F, arrows), values in contrast-enhancing solid tumor components (A and B, arrows) approximate normal-appearing white matter in GBM. This finding is accompanied by abundant axonal structures visualized by Bielschowsky silver staining (G) and high GFAP expression (I) in GBM compared with melanoma metastasis (H and J). Scale = 100 μm.

  • FIG 3.
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    FIG 3.

    DTI, NODDI, and DMI metrics in contrast-enhancing tumor areas in patients with GBM (n = 22) and metastases (n = 21). Compared with metastases, GBM showed a significant shift toward increased FA and decreased OD, whereas no significant differences were found regarding microFA. Four asterisks indicate P ≤ .001. NAWM indicates normal-appearing white matter.

  • FIG 4.
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    FIG 4.

    The Spearman rank correlation demonstrates a positive association of FA with GFAP and Bielschowsky scores (upper row) and a negative association of OD with GFAP and Bielschowsky scores (middle row). No association between microFA with GFAP and Bielschowsky scores can be detected (lower row). Open circles indicate metastasis cases; filled circles, GBM cases.

  • FIG 5.
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    FIG 5.

    ROC curves of 22 patients with GBM and 21 with cerebral metastases showing a high predictive value of both FA (AUC = 0.8463) and OD (AUC = 0.8398) regarding the presence of GBM versus metastasis (left panel) and a scatterplot of OD and FA values for each sample (normal-appearing white matter controls = gray filled circles, GBM = black filled circles, metastasis = open circles) with arbitrary cutoff values of 0.3 and 0.55 for OD and 0.15 and 0.25 for FA. Logistic regression indicates the probability of GBM diagnosis compared with metastasis diagnosis at each individual OD or FA value (right panel).

Tables

  • Figures
  • Patient characteristics and ROI (contrast-enhancing tumor area) derived diffusion metricsa

    GBMMetastasisP Value (GBM vs Met)
    No.2221
    Sex (male/female)11/1112/9P = .82
    Age (yr)65.6 (12.7)66.6 (11.8)P = .99
    FA0.16 (0.04)0.11 (0.02)P < .001
    OD0.43 (0.08)0.56 (0.10)P < .001
    microFA0.29 (0.10)0.27 (0.10)P = .56
    • Note:—Met indicates Metastasis.

    • ↵a Data are given as mean and standard deviation (SD).

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American Journal of Neuroradiology: 44 (11)
American Journal of Neuroradiology
Vol. 44, Issue 11
1 Nov 2023
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Cite this article
Urs Würtemberger, Daniel Erny, Alexander Rau, Jonas A. Hosp, Veysel Akgün, Marco Reisert, Valerij G. Kiselev, Jürgen Beck, Sonja Jankovic, Peter C. Reinacher, Marc Hohenhaus, Horst Urbach, Martin Diebold, Theo Demerath
Mesoscopic Assessment of Microstructure in Glioblastomas and Metastases by Merging Advanced Diffusion Imaging with Immunohistopathology
American Journal of Neuroradiology Nov 2023, 44 (11) 1262-1269; DOI: 10.3174/ajnr.A8022

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Microstructure in Glioblastomas: Advanced Imaging
Urs Würtemberger, Daniel Erny, Alexander Rau, Jonas A. Hosp, Veysel Akgün, Marco Reisert, Valerij G. Kiselev, Jürgen Beck, Sonja Jankovic, Peter C. Reinacher, Marc Hohenhaus, Horst Urbach, Martin Diebold, Theo Demerath
American Journal of Neuroradiology Nov 2023, 44 (11) 1262-1269; DOI: 10.3174/ajnr.A8022
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