# Magnetic susceptibility properties of tumor-associated cells imaged by MRI reveal glioblastoma infiltration in the edema region

## TL;DR

A new MRI-based method identifies tumor infiltration in the edema region of glioblastoma by analyzing magnetic susceptibility properties linked to iron metabolism.

## Contribution

A novel non-invasive MRI method is introduced to detect glioblastoma infiltration in edema regions using magnetic susceptibility and iron content.

## Key findings

- Magnetic susceptibility decomposition reveals infiltration zones in glioblastoma edema regions.
- Paramagnetic to diamagnetic susceptibility ratio correlates with tumor prognostic factors.
- Elevated iron content in tumor tissues causes increased susceptibility ratio.

## Abstract

Glioblastoma is a malignant primary brain tumor. Because of its highly invasive and infiltrative nature, surgical resection and radiation therapy are not able to remove all tumor cells, even with state-of-the-art imaging and fluorescence-guided surgery.

24 newly diagnosed glioblastoma patients were enrolled. Pre- and post-surgery MRI scans were performed. Magnetic susceptibility was quantified based on gradient echo MRI. The ratio between sub-voxel paramagnetic and diamagnetic susceptibility components was computed. Relationships between the proposed ratio metric and prognostic factors and pathological iron were investigated. Perfusion and permeability imaging were used to exclude the presence of blood-related contribution to the paramagnetic component.

Here we show that by decomposing tissue magnetic susceptibility into paramagnetic and diamagnetic sources, we can identify, non-invasively and in vivo, areas of altered iron metabolism associated with tumor activities in the edema tissue surrounding glioblastoma. We find that the paramagnetic to diamagnetic susceptibility ratio uniquely delineates area of hyperintensity corresponding to a Tumor and Immune cells Infiltration Zone. Statistically significant relationships are found between the ratio metrics in the infiltration zone and tumor prognostic factors. Follow-up scans reveal tumor progression and later contrast-enhancement in the predicted infiltration zone. Histological data indicate that increased iron content causes the elevated ratio metric.

Our study proposes a method to derive an iron-related imaging marker of abnormal patterns in the edema region of the glioblastoma associated with tumor cell infiltration. We show the potential of the imaging marker to aid and improve surgical and treatment planning.

Debiasi et al. examine glioblastoma in the edema region of the tumor, by computing the tissue magnetic properties using MRI data to develop a method to automatically identify areas indicative of infiltration. Association is demonstrated between magnetic properties and tumor prognostic factors, which is caused by an elevated iron presence in the tumor tissues.

Glioblastoma is a brain tumor with very infiltrative behavior. Current treatment options are not able to remove it in its entirety. Consequently, residual tumor is found in most patients after surgery, causing early recurrence and decreased survival. We focused on the edema region of the tumor, usually homogeneous on conventional MRI, to identify potential areas of infiltration. By computing the tissue magnetic properties using MRI data, we observed abnormal spatial patterns in edema. We developed a method to automatically identify these abnormal areas. We found an association between the magnetic properties of those areas and tumor prognostic factors, which is caused by an elevated iron presence in the tumor tissues. We further showed that this method may be used to track tumor infiltration. Our method could be readily employed in clinical practice to aid surgical resection and treatment planning.