Advanced Imaging Techniques for Evaluating the Tumor Immune Microenvironment in Glioblastoma Patients

PRIMARY OBJECTIVE:

I. To establish the biological validation of advanced MRI as a non-invasive imaging modality for assessing the tumor immune microenvironment (TIME) in glioma.

SECONDARY OBJECTIVES:

I. Conduct more detailed correlation explorations focusing on relevant subpopulations, such as cluster of differentiation 4 (CD4+) versus ( cluster of differentiation 8 (CD8+) T cells and M1- versus M2-like tumor-associated macrophages (TAMs).

II. Perform exploratory correlation analysis between tumor-averaged imaging measures with systemic immunological markers (T cell activation and interferon pathway signaling), to improve our understanding of the relationship between local tissue immune environment and systemic immune response in glioma patients.

OUTLINE:

Patients undergo research CEST MRI and DR-CSI over 30 minutes at research visit 1, up to 28 days before standard of care surgery/biopsy. Following research CEST MRI and DR-CSI at research visit 1, patients receive ferumoxytol intravenously (IV) over 10-15 minutes. Approximately 24-48 hours later, patients undergo Fe-MRI over 15 minutes at research visit 2. Patients also undergo standard of care clinical MRI and collection of blood samples on study.

After completion of study intervention, patients are followed up until death.

Primary Outcome Measures

1. Mean diffusion-relaxation correlation spectrum imaging (DR-CSI) value
   Mean DR-CSI values will be correlated with T cell densities. Pearson's or Spearman's correlation coefficients will be used depending on variable distributions.
2. Ferumoxytol-enhanced magnetic resonance imaging (Fe-MRI) measures
   Fe-MRI measures will be correlated with tumor-associated macrophage densities and iron staining concentration. Pearson's or Spearman's correlation coefficients will be used depending on variable distributions.
3. Chemical exchange saturation transfer (CEST) values
   CEST values will be correlated with tumor burden and immune suppression markers. Pearson's or Spearman's correlation coefficients will be used depending on variable distributions.