Abstract

PurposeWe studied the ability of Restriction Spectrum Imaging (RSI), a novel advanced diffusion imaging technique, to estimate levels of cellularity in different glioblastoma regions, evaluated their prognostic value compared with established clinical diffusion metrics such as fractional anisotropy (FA) and mean diffusivity (MD). MethodsForty-two patients with untreated glioblastoma, IDH-wildtype, were examined with an advanced MRI tumor protocol. The region of interest (ROI) was obtained from the contrast-enhancing part of tumor and the peritumoral brain zones and then co-registered with RSI-cellularity index, FA and MD maps. Histogram parameters of diffusion metrics were assessed for all ROI locations and compared to MGMT promoter methylation status and survival. The ability of RSI-cellularity index, FA, and MD to stratify survival and were assessed by Cox proportional hazard regression, adjusted for significant clinical predictors. ResultsThe highest RSI-cellularity index was measured in contrast-enhancing tumor core with a negative gradient from tumor core to the periphery of peritumoral zone with predictive accuracy 81 % (P < 0.001). Shorter overall survival was significant associated with higher RSI-cellularity index (hazard ratio (HR) 3.6, 95 % confidence interval (CI) 1.3−9.5, P = 0.002) with synchronal decrease in MD (HR 0.31, 95 %CI 0.1−0.8, P = 0.008) in the contrast-enhanced tumor core. This association was also consistent for RSI-cellularity index value measured in the peri-enhancing zone (HR 3.6, 95 % CI 1.0−12.3, P = 0.041). No statistically significant differences were noted between RSI-cellularity index, FA, nor MD and MGMT promoter methylation. ConclusionRSI-cellularity index may be used as prognostic biomarker to improve risk stratification in patients with glioblastoma.

Highlights

  • Glioblastoma is the most frequent malignant primary brain tumor in the adult population

  • Cox proportional hazard regression analysis (CPH) models revealed that the total resection and Karnofsky performance status over 70 were significantly associated with longer progression free sur­ vival (PFS) (hazard ratio (HR) 3.5, 95 % confidence interval (CI) 1.0–12.1; P = 0.04 and HR 4.4, 95 %CI 1.6–12.1, P = 0.006) respectively, and longer overall survival (OS) (HR 3.8, 95 %CI 1.1–12.9, P = 0.03 and HR 3.2, 95 %CI 1.3–7.8, P = 0.01) respectively

  • The highest Restriction Spectrum Imaging (RSI)-cellularity index was measured in contrast-enhancing tumor core (CET) with a negative gradient from tumor core to the periphery of peritumoral zone (PEZ and near zone (NZ))

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Summary

Introduction

Glioblastoma is the most frequent malignant primary brain tumor in the adult population. Complete macroscopic tumor removal (gross total resection) in patients with glioblastoma is a primary surgical goal and in comparison to sub­ total resection prolongs overall survival (OS) and progression free sur­ vival (PFS) [2]. Glioblastoma growth is characterized by diffuse infiltration of normal brain tissue, with tumor cells moving through the hyaluronic acid-rich parenchyma towards microvasculature and migrating. Intraoperative navigation, based mainly on postcontrast MRI, is the standard of care for glioma surgery in an effort to achieve maximal safety resection. Still, this technique is based on visual identification of regions with disrupted blood-brain barrier that cannot accurately detect tumor infiltration beyond the apparent borders of the enhancing region. Non-invasive and robust diagnostic biomarkers are warranted for identification of high-cellularity components in order to increase cytoreductive treatment with real benefits to prognosis

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