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MR susceptibility imaging for detection of tumor-associated macrophages in glioblastoma

  • Clinical Study
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Abstract

Purpose

Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, we investigated MRI to quantify iron as an imaging biomarker for TAMs in GBM patients.

Methods

21 adult patients with GBM underwent a 3D single echo gradient echo MRI sequence and quantitative susceptibility maps were generated. In 3 subjects, ex vivo imaging of surgical specimens was performed on a 9.4 Tesla MRI using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated. Each specimen was stained with hematoxylin and eosin, as well as CD68, CD86, CD206, and l-Ferritin.

Results

Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the l-ferritin positivity percent (r = 0.56, p = 0.018) and the combination of tumor’s enhancing zone and necrotic core and the l-Ferritin positivity percent (r = 0.72; p = 0.001). The mean susceptibility significantly correlated with positivity percent for CD68 (ρ = 0.52, p = 0.034) and CD86 (r = 0.7 p = 0.001), but not for CD206 (ρ = 0.09; p = 0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r = 0.6, p = 0.016). Similarly, mean R2* values significantly correlated with CD86 (r = 0.54, p = 0.03) but not with CD206 (r = 0.15, p = 0.5).

Conclusions

This study demonstrated the potential of MR quantitative susceptibility mapping as a non-invasive method for in vivo TAM quantification and phenotyping. Validation of these findings with large multicenter studies is needed.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

McCabe Fund Award granted to S.A.N from the Perelman School of Medicine, University of Pennsylvania.

Author information

Author notes

  1. Amir Nazem and Samantha C. Guiry have contributed equally to this work.

  2. MacLean Nasrallah and Ali Nabavizadeh share Co-senior authors.

Authors and Affiliations

  1. Department of Radiology, Hospital of University of Pennsylvania, Perelman School of Medicine of the University of Pennsylvania, 1 Silverstein Building, 3400 Spruce St., Philadelphia, PA, 19104, USA

    Amir Nazem, Samantha C. Guiry, Mehrdad Pourfathi, Jeffrey B. Ware, Hannah Anderson, Srikant Kamesh Iyer, Brianna F. Moon, Walter R. Witschey, Rahim Rizi & Ali Nabavizadeh

  2. Division of Neuropathology, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    MacLean Nasrallah

  3. Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Yi Fan

  4. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Stephen J. Bagley, Arati Desai, Donald M. O’Rourke, Steven Brem & Ali Nabavizadeh

  5. Department of Neurosurgery, Perelman School of Medicine, Hospital of University of Pennsylvania, University of Pennsylvania, Philadelphia, PA, USA

    Mehrdad Pourfathi, Donald M. O’Rourke & Steven Brem

  6. Department of Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Mehrdad Pourfathi

  7. New York Medical College School of Medicine, Valhalla, NY, 10595, USA

    Samantha C. Guiry

  8. Glioblastoma Translational Center of Excellence, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Stephen J. Bagley, Arati Desai, Donald M. O’Rourke, Steven Brem & MacLean Nasrallah

  9. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55901, USA

    Amir Nazem

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  1. Amir Nazem
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Contributions

Conceptualization: MN, AN, AN, SCG, YF, JBW, WRW, RR, SJB, AD, DMO, SB. Acquisition of data: AN, SCG, MP, JBW. Preprocessing of images: AN, SCG. Writing—original draft preparation: AN, SCG, AN. Writing—review and editing: AN, SCG, MP, JBW, HA, SKI, BFM, YF, WRW, RR, SJB, AD, DMO, SB, MN, AN.

Corresponding author

Correspondence to Ali Nabavizadeh.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.

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Informed consent was obtained from all individual participants included in the study.

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Nazem, A., Guiry, S.C., Pourfathi, M. et al. MR susceptibility imaging for detection of tumor-associated macrophages in glioblastoma. J Neurooncol 156, 645–653 (2022). https://doi.org/10.1007/s11060-022-03947-3

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  • DOI: https://doi.org/10.1007/s11060-022-03947-3

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