Characterizing glioma microenvironment with ultra-high gradient diffusion MRI.

Abstract

2050 Background: The infiltrating nature of gliomas, particularly into the peritumoral area, is a major barrier to improving clinical outcome as microscopic disease remains even after apparent gross total resection. Conventional T1 post-contrast and T2/FLAIR MRI do not capture full tumor extent. A better imaging biomarker is needed to improve differentiation between tumor, peritumoral area and normal brain. Methods: 4 pre-surgical patients with non-enhancing, FLAIR-hyperintense lesions suspicious for glioma underwent ultra-high gradient diffusion MRI on the Connectome MRI scanner, a unique scanner with maximum gradient strength of 300 mT/m enabling mapping of cellular microstructures on a micron-level scale. The FLAIR area was defined as the tumor region of interest (ROI). Radiographically normal appearing brain up to 1 cm around the FLAIR area was defined as the peritumoral ROI. Using a novel 3 compartment diffusion model (Linear Multiscale Model), the volume fraction of water (VFW) was calculated within restricted (intracellular), hindered (extracellular) and free (CSF) spaces. VFW in the tumor, peritumoral ROI, contralateral normal white matter (WM) and cortex were compared. Results: Within the tumor ROI, the median VFW in the restricted compartment was decreased vs. the peritumoral ROI (↓ 34%), WM (↓ 46%) and cortex (↓ 18%) while median VFW in the hindered compartment was increased vs. the peritumoral ROI (↑ 26%), WM (↑ 54%) and cortex (↑ 25%). Within the peritumoral ROI, median VFW in the hindered compartment was increased compared to WM (↑ 23%). 3 patients had available histopathology revealing isocitrate dehydrogenase-mutant gliomas. Conclusions: Using ultra-high gradient diffusion MRI and a novel diffusion model, we detected distinct diffusion patterns in the tumor and peritumoral area not seen on conventional MRI. Lower VFW in the restricted compartment within the tumor may reflect decreased intracellular water mobility due to enlarged nuclei. Higher VFW in the hindered compartment in the tumor and peritumoral area may reflect higher degree of tissue permeability and edema. MRI-pathology and larger cohort validation studies are underway to elucidate microenvironment changes in response to treatment.