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Updated: Oct 6, 2025
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
MR susceptibility imaging for detection of tumor-associated macrophages in glioblastoma
Amir Nazem1,2, Samantha C Guiry1,3, Mehrdad Pourfathi1,4,5
1Department 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.
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.
Insights
Magnetic Resonance Imaging (MRI) can quantify iron in glioblastoma (GBM) tumors, serving as a biomarker for tumor-associated macrophages (TAMs). This non-invasive technique shows promise for TAM phenotyping in GBM patients.
Area of Science:
- Neuroimaging
- Oncology
- Immunology
Background:
- Tumor-associated macrophages (TAMs) are crucial in the glioblastoma (GBM) microenvironment.
- TAMs exhibit distinct phenotypes (M1/M2) with differential iron metabolism, impacting tumor progression.
- Iron accumulation within TAMs presents a potential imaging biomarker target.
Purpose of the Study:
- To investigate Magnetic Resonance Imaging (MRI) quantitative susceptibility mapping (QSM) for non-invasively quantifying iron.
- To assess QSM as an imaging biomarker for TAMs and their phenotypes in GBM patients.
- To correlate MRI-derived iron measurements with TAM markers and iron content.
Main Methods:
- 21 adult GBM patients underwent 3D gradient echo MRI for quantitative susceptibility mapping.
- Ex vivo imaging of surgical specimens (n=3) using 9.4 Tesla MRI with multi-echo GRE scans to generate R2* maps.
- Immunohistochemical staining of specimens for CD68, CD86, CD206, and L-ferritin.
Main Results:
- Significant positive correlation between mean susceptibility and L-ferritin positivity (r=0.72, p=0.001).
- Mean susceptibility correlated with CD68 (p=0.034) and CD86 (p=0.001) positive cells, but not CD206.
- Mean R2* values positively correlated with CD68 (p=0.016) and CD86 (p=0.03) positive cell counts.
Conclusions:
- MR quantitative susceptibility mapping shows potential for non-invasive in vivo TAM quantification and phenotyping in GBM.
- Findings suggest QSM can differentiate TAM phenotypes based on iron content.
- Further validation in large multicenter studies is warranted.
