Original Article
Inflow-based vascular-space-occupancy (iVASO) might potentially predict IDH mutation status and tumor grade in diffuse cerebral gliomas

https://doi.org/10.1016/j.neurad.2021.01.002Get rights and content

Highlights

  • iVASO can quantify arteriolar cerebral blood volume of gliomas non-invasively.

  • iVASO shows potential value in predicting IDH mutation of glioma.

  • Maximum arteriolar cerebral blood volume allows for accurate distinction between glioblastomas and lower-grade gliomas.

Abstract

Purpose

The aim of the study is to assess the diagnostic performance of inflow-based vascular-space-occupancy (iVASO) MR imaging for differentiating glioblastomas (grade IV, GBM) and lower-grade diffuse gliomas (grade II and III, LGG) and its potential to predict IDH mutation status.

Methods

One hundred and two patients with diffuse cerebral glioma (56 males; median age, 43.5 years) underwent iVASO and dynamic susceptibility contrast (DSC) MR imaging. The iVASO-derived arteriolar cerebral blood volume (CBVa), relative CBVa (rCBVa), and the DSC-derived relative cerebral blood volume (rCBV) were obtained, and these measurements were compared between the GBM group (n = 43) and the LGG group (n = 59) and between the IDH-mutation group (n = 54) and the IDH-wild group (n = 48).

Results

Significant correlation was observed between rCBV and CBVa (P < 0.001) or rCBVa (P < 0.001). Both CBVa (P < 0.001) and rCBVa (P < 0.001) were higher in the GBM group. Both CBVa (P < 0.001) and rCBVa (P < 0.001) were lower in the IDH-mutation group compared to the IDH-wild group. Receiver operating characteristic analyses showed the area under curve (AUC) of 0.95 with CBVa and 0.97 with rCBVa in differentiating GBM from LGG. The AUCs were 0.82 and 0.85 for CBVa and rCBVa in predicting IDH gene status, respectively, which were lower than that of rCBV (AUC = 0.90). Combined rCBV and rCBVa significantly improved the diagnostic performance (AUC = 0.95).

Conclusions

iVASO MR imaging has the potential to predict IDH mutation and grade in glioma.

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.

References (47)

  • P. Svolos et al.

    The role of diffusion and perfusion weighted imaging in the differential diagnosis of cerebral tumors: A review and future perspectives

    Cancer Imaging

    (2014)
  • R. Jain et al.

    Glioma angiogenesis and perfusion imaging: Understanding the relationship between tumor blood volume and leakiness with increasing glioma grade

    AJNR Am J Neuroradiol

    (2015)
  • D. Van Westen et al.

    Correlation between arterial blood volume obtained by arterial spin labelling and cerebral blood volume in intracranial tumours

    MAGMA

    (2011)
  • P.W. Hales et al.

    A two-stage model for in vivo assessment of brain tumor perfusion and abnormal vascular structure using arterial spin labeling

    PLoS One

    (2013)
  • S. Haller et al.

    Arterial spin labeling perfusion of the brain: Emerging clinical applications

    Radiology

    (2016)
  • M.J. Donahue et al.

    Absolute arterial cerebral blood volume quantification using inflow vascular-space-occupancy with dynamic subtraction magnetic resonance imaging

    J Cereb Blood Flow Metab

    (2010)
  • J. Hua et al.

    Measurement of absolute arterial cerebral blood volume in human brain without using a contrast agent

    NMR Biomed

    (2011)
  • J. Hua et al.

    Inflow-based vascular-space-occupancy (iVASO) MRI

    Magn Reson Med

    (2011)
  • ...
  • D.N. Louis et al.

    The 2016 World Health Organization classification of tumors of the central nervous system: A summary

    Acta Neuropathol

    (2016)
  • Z. Xing et al.

    Noninvasive assessment of IDH mutational status in World Health Organization grade II and III astrocytomas using DWI and DSC-PWI combined with conventional MR imaging

    Am J Neuroradiol

    (2017)
  • S.G. Wetzel et al.

    Relative cerebral blood volume measurements in intracranial mass lesions: Interobserver and intraobserver reproducibility study

    Radiology

    (2002)
  • P.E. Shrout et al.

    Intraclass correlations: Uses in assessing rater reliability

    Psychol Bull

    (1979)
  • Cited by (3)

    • Differential detection of metastatic and inflammatory lymph nodes using inflow-based vascular-space-occupancy (iVASO) MR imaging

      2022, Magnetic Resonance Imaging
      Citation Excerpt :

      In the present study, the popliteal nodes showed a significant increase of BVa after inoculation of tumor cells into the posterior thigh muscle, supporting the observations in the studies above. It is worth noting that both IVIM-DWI and DCE-MRI reflect the microcirculation at the capillary level, whereas iVASO predominantly reflects the arteriolar compartment, which is the most sensitive part in response to metabolic disturbance [30–34]. In our study, at D10, the size-based criteria could not discriminate between the metastatic and inflammatory nodes, whereas BVa showed a discriminative potential.

    1

    Liuji Guo and Xiaodan Li contributed equally to data post-processing and paper writing of this study and were considered co-first authors.

    View full text