Glioblastoma Stem-like Cell Detection Using Perfusion and Diffusion MRI

SIMPLE SUMMARY: Glioblastoma stem-like cells (GSCs) are known to be aggressive and radio-resistant and proliferate heterogeneously in preferred environments. Additionally, quantitative diffusion and perfusion MRI biomarkers provide insight into the tissue micro-environment. This study assessed the sensitivity of these imaging biomarkers to GSCs in the hyperintensities-FLAIR region, where relapses may occur. A total of 16 patients underwent an MRI session and biopsies were extracted to study the GSCs. In vivo and in vitro biomarkers were compared and both Apparent Diffusion Coefficient (ADC) and relative Cerebral Blood Volume (rCBV) MRI metrics were found to be good predictors of GSCs presence and aggressiveness. ABSTRACT: Purpose: With current gold standard treatment, which associates maximum safe surgery and chemo-radiation, the large majority of glioblastoma patients relapse within a year in the peritumoral non contrast-enhanced region (NCE). A subpopulation of glioblastoma stem-like cells (GSC) are known to be particularly radio-resistant and aggressive, and are thus suspected to be the cause of these relapses. Previous studies have shown that their distribution is heterogeneous in the NCE compartment, but no study exists on the sensitivity of medical imaging for localizing these cells. In this work, we propose to study the magnetic resonance (MR) signature of these infiltrative cells. Methods: In the context of a clinical trial on 16 glioblastoma patients, relative Cerebral Blood Volume (rCBV) and Apparent Diffusion Coefficient (ADC) were measured in a preoperative diffusion and perfusion MRI examination. During surgery, two biopsies were extracted using image-guidance in the hyperintensities-FLAIR region. GSC subpopulation was quantified within the biopsies and then cultivated in selective conditions to determine their density and aggressiveness. Results: Low ADC was found to be a good predictor of the time to GSC neurospheres formation in vitro. In addition, GSCs were found in higher concentrations in areas with high rCBV. Conclusions: This study confirms that GSCs have a critical role for glioblastoma aggressiveness and supports the idea that peritumoral sites with low ADC or high rCBV should be preferably removed when possible during surgery and targeted by radiotherapy.