Original ArticleInflow-based vascular-space-occupancy (iVASO) might potentially predict IDH mutation status and tumor grade in diffuse cerebral gliomas
Graphical abstract
Introduction
Diffuse cerebral astrocytomas are the most prevalent primary brain tumors that rely on angiogenesis to grow and spread.1 The isocitrate dehydrogenase (IDH) gene (including IDH1 and IDH2 genes) plays prominent roles in the metabolism, pathogenesis, and progression of astrocytomas. In gliomas, the presence of IDH mutation leads to downstream inhibition of hypoxia- and angiogenesis-related signaling and consequently the decrease of angiogenesis.2 Perfusion-weighted imaging can provide quantitative information about tumor vasculature and aid in predicting tumor grade and isocitrate dehydrogenase (IDH) mutation status,3 monitoring response to therapeutics, and establishing prognosis.4 Dynamic susceptibility contrast MR imaging (DSC-MRI) is the most prevalent perfusion imaging methodology and has recently been recommended to be included in the routine protocol for diagnosis and follow-up of gliomas clinically.5, 6 However, DSC-MRI is associated with risks related to the injection of gadolinium-based contrast agent, such as brain deposition of gadolinium and nephrogenic systemic fibrosis, and is subject to confounding effect from the blood brain barrier disruption.7, 8, 9 Furthermore, tumor microvasculature is very complex, and the knowledge of arterial perfusion of gliomas is very limited so far, which necessitate new techniques to enhance our understanding of tumor angiogenesis.10, 11, 12 For these reasons, investigations to develop and validate new perfusion techniques, especially those based on intrinsic contrast, are still ongoing.13, 14
Inflow-based vascular-space-occupancy (iVASO) is a completely noninvasive perfusion method that does not involve administration of exogenous contrast agents.14 In iVASO, proton spins in the water molecules in blood are exploited as intrinsic endogenous contrast agents, which can be manipulated by applying spatially selective radiofrequency (RF) inversion pulses. Arteriolar cerebral blood volume (CBVa) can be quantified from the difference signal between a scan with arterial blood signal selectively zeroed out (nulled) and a control scan without blood nulling. Crushing gradients are incorporated in iVASO to suppress signals from large arteries and to sensitize this method to CBVa predominantly in the pial arteries and arterioles.15, 16 In a pilot study at 7 Tesla with a small-sample cohort, CBVa derived from iVASO showed a stronger correlation with World Health Organization (WHO) grade of cerebral gliomas than did relative cerebral blood volume (rCBV) derived from DSC-MRI.17 Therefore, we hypothesized that iVASO can predict IDH-mutation status in gliomas. To validate the hypothesis, we evaluated the diagnostic performance of iVASO-derived parameters in differentiating IDH-mutant from IDH-wild type gliomas and compared it with that of DSC-derived metrics in the same patients.
Section snippets
Patients
This retrospective study was approved by our institutional review board, and the requirement for patient informed consent was waived due to the nature of the retrospective study. Patients with pathology-confirmed diffuse cerebral gliomas at our institution from March 2017 to December 2018 were reviewed. The inclusion criteria were as follows: 1) definite histopathologic diagnosis of grade II and III gliomas and grade IV glioblastoma (GBM); 2) known IDH status and 1p19q status; and 3) available
Results
Basic clinical data are summarized in Table 1. IDH mutation was positive in 52.94% (54 of 102) of these patients (LGG = 84.75% [50 of 59]; GBM = 9.30% [4 of 43]), and there were eight patients with 1p19q codeletion. The median age was lower for patients with lower-grade than for GBM patients (39.1 years [range, 18−74 years] vs 49.8 years [range, 25−70 years], P = 0.039). There was no significant difference in sex or surgery. A significantly higher proportion of LGG patients were associated with
Discussion
The present study demonstrated that quantitative arteriolar cerebral blood volume of gliomas measured using iVASO has the potential to discriminate between IDH-mutant and IDH-wild gliomas and between glioblastomas (GBM) and lower-grade gliomas (LGG, grade II and III) accurately.
In the present study, both CBVa and rCBVa measured using iVASO discriminated GBM from LGG as accurately as rCBV derived from DSC MR imaging. Interestingly, the correlation coefficient between CBVa or rCBVa and rCBV was
Conclusions
In conclusion, we have used a noninvasive perfusion technique, iVASO, to evaluate the arteriolar cerebral blood volume of cerebral gliomas and found that maximum CBVa and rCBVa might have the potential to predict IDH phenotype of cerebral glioma. Also, they can discriminate GBM from LGG as accurately as DSC-rCBV.
Funding
This work was supported in part by the Natural Science Foundation of Guangdong Province, China (grant no. S201301005689), the Science and Technology Program of Guangzhou, China (grant no. 201707010003), the Special Foundation of President of Nanfang Hospital, Southern Medical University (grant no. 2016B026), and the Special Clinical Research of Nanfang Hospital, Southern Medical University (grant no. 2019CR005).
Declarations of interest
None.
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Liuji Guo and Xiaodan Li contributed equally to data post-processing and paper writing of this study and were considered co-first authors.