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نمایش مقاله

Title:

Towards hypoxia imaging: Relative oxygen extraction fraction (rOEF) mapping with multi-parametric quantitative MRI for predicting grade and IDH gene mutation status in Glioma

Subject:

Clinical Applications of Brain Mappin

Presenter Author:
Name:	Fateme Shahedi

Author:
Name 1:	Fateme Shahedi - Presenter
Affiliation 1:	Department of Radiology Technology, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran

Name 2:	Shahrokh Naseri
Affiliation 2:	Medical Physics Research Center, Mashhad University of medical Science, Mashhad, Iran.

Name 3:	Hoda Zare - Corresponding
Affiliation 3:	Medical Physics Research Center, Mashhad University of medical Science, Mashhad, Iran.

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Abstract

Original Research

introduction :

Gliomas are one of the predominant tumors of the central nervous system (CNS). The 2016 World Health Organization Classification of CNS tumors modified the classification criteria of gliomas, by defining the glioma entity based on its histology and molecular status. A key finding in glioma biology is the identification of isocitrate dehydrogenase (IDH) mutation status as a crucial biomarker for therapy and prognosis, as patients with IDH-mutant gliomas have better survival and chemosensitivity compared to those with IDH wild-type gliomas. Therefore, an accurate determination of the grade and IDH1 status is necessary to plan treatment strategies. Currently, invasive brain biopsy is the gold standard for determining these factors, which have limitation of sampling error and lack of possibility to perform surgery in some patients due to age, or proximity of tumor to brain functional regions. Reprogramming energy metabolism following the hypoxia and highly defective neovascularization are major hallmarks of cancer. The physiological imaging features, including tissue oxygenation can be used as a supplementary tool for non-invasive molecular diagnosis of gliomas. The oxygen extraction fraction elucidates oxygen utilization and allow investigation of metabolic characteristics associated with glioma genotypes. The purpose of this study was to explore the influence of glioma grade and IDH mutation on tissue oxygen availability using rOEF mapping with multi-parametric quantitative MRI.

Methods:

This study included 16 histologically confirmed IDH-mutant and IDH-wildtype glioma patients. For each patient, after obtaining structural MRI images, T2 and T2* relaxation times and their inverse parameter (R2 and R2*) were measured based on a multi-echo spin-echo and multi-echo gradient echo sequences at eight echo time (TE), respectively. Subsequently, the relative cerebral blood volume (rCBV) images were extracted for each patient using the dynamic susceptibility contrast (DSC) perfusion protocol. Ultimately, the rOEF map was calculated using the rCBV and the R2′ parameter (R2′=R2*-R2) based on the multiparametric quantitative blood oxygen level dependent technique. The values of R2′, rCBV, and rOEF within enhancing areas were compared between low and high grade as well as IDH-mutant and IDH-wildtype gliomas using independent T.Test for normally distributed parameters and Mann-Whitney U test for non-normally distributed parameters.

Results:

High grade glioma exhibited meaningful higher values of rCBV (3.753 vs 1.029, P-value=0.001), and R2′ (8.240 vs 2.941, P-value= 0.002). Despite higher rCBV, high grade glioma also exhibited higher rOEF (0.402 vs 0.300, P-value= 0.031) as a correlate of hypoxic areas due to defective, and disorganized vasculature, which reduce tissue oxygen availability. The IDH-wildtype glioma also demonstrated higher values of rCBV (4.853 vs 1.786, P-value=0.001), R2′ (10.60 vs 6.024, P-value=0.035) and rOEF (0.565 vs 0.346, P-value=0.04) compared to IDH-mutant glioma.

Conclusion:

The characterization of rOEF based on independent measurements of R2′ and rCBV would provide crucial metabolic information in the diagnostic work-up of brain tumors. Hypoxia is related to a more malignant tumor phenotype, therapy resistance and radio-insensitivity. Reliable hypoxia imaging using multimodal MRI information provides the non-invasive prediction of grade and epigenetic alterations in glioma tumors that may improve patients’ treatment management.

Keywords:

Glioma, oxygen extraction fraction, Magnetic Resonance Imaging