Elsevier

Clinical Radiology

Volume 70, Issue 10, October 2015, Pages 1128-1135
Clinical Radiology

Prospective glioma grading using single-dose dynamic contrast-enhanced perfusion MRI

https://doi.org/10.1016/j.crad.2015.06.076Get rights and content

Highlights

  • Prospective glioma grading.

  • Comparison between single dose and double dose DCE-MRI perfusion study.

  • Correlation of cerebral blood volume with mitotic index and Ki-67 in glioma.

  • Sensitivity and specificity of glioma grading using single dose contrast DCE-MRI.

Aim

To evaluate the sensitivity and specificity of single-dose dynamic contrast-enhanced (DCE) perfusion magnetic resonance imaging (MRI) in prospective evaluation of glioma grading and to correlate the relative cerebral blood volume (rCBV) values with mitotic and ki-67 indexes obtained at histopathology.

Materials and methods

A total of 53 histologically proven patients with glioma were included in this study. DCE-MRI perfusion with a single dose of contrast medium was included in brain tumour protocol and prospective grading of glioma into low and high grade was done based on a previously reported rCBV cut-off value of 3. Tumours with rCBV ≥3 were considered to be high grade and rCBV <3 were considered to be low grade. The sensitivity and specificity of the cut-off value were estimated. Ki-67 and mitotic indexes were also obtained on histopathological analysis along with histological grading.

Results

Based on pre-defined rCBV cut-off values, prospective grading of low- and high-grade glioma was achieved with a sensitivity and specificity of 97.22% and 100%, respectively. Significant correlation was found between the mitotic/ki-67 indexes and rCBV values when data for high- and low-grade tumours was combined.

Conclusion

DCE-MRI performed with a single dose of contrast medium is as effective as a protocol with a double-dose of contrast medium for glioma grading using 3 T MRI and could be added to the routine evaluation protocol of brain tumours.

Introduction

Gliomas are the most common primary brain neoplasms.1 On histopathological analysis, gliomas are divided into four grades according to their biological behaviour. According to the World Health Organization (WHO) classification system, Grades I and II are considered low-grade, whereas III and IV are considered high-grade gliomas. Although, histopathology remains the reference standard for grading gliomas, it suffers from an inherent sampling error associated with stereotactic biopsy.2 Conventional magnetic resonance imaging (MRI) techniques are routinely used in the preoperative evaluation of gliomas; however, conventional MRI provides limited information regarding tumour physiology and grading. It provides “snapshot” information in the time course of contrast enhancement and is largely inadequate to guide biopsy or treatment of brain tumours.3

Aggressiveness of glioma is mainly determined by its ability to infiltrate the brain parenchyma and to recruit, synthesise, and proliferate vascular networks for further growth. Angiogenesis in various intracranial diseases can be measured using perfusion-weighted imaging.4, 5, 6 T1-based dynamic contrast-enhanced (DCE) perfusion imaging (DCE-MRI) has been widely used in the assessment of brain tumours. A number of researchers have shown its potential in grading gliomas.7, 8, 9, 10, 11 The DCE-MRI technique measures a composite of haemodynamic and pharmacokinetic perfusion parameters. These indices provide quantitative measurement of the integrity of the blood–brain barrier (BBB) and of tissue perfusion with methods to correct the CBV in cases of a disrupted BBB5, 11, 12; however, the quantification of these DCE-MRI perfusion indices is not straightforward. It requires an appropriate compartmental model to extract the parameters that reflect the microvascular properties of the tissue, including capillary permeability, leakage, and tissue perfusion. The generalised tracer kinetic model (GTKM) derived from a two-compartment exchange model has been commonly used for analysis of DCE-MRI data.13 According to this model the contrast agent in the tissue is able to enter two separate compartments: the plasma space and the extravascular extracellular space (EES).13, 14, 15 With this model, data need to be acquired for a long enough duration for the concentration of contrast medium (C(t)) to become stabilised.16 Otherwise with a limited scan duration, a persistent uptake curve is commonly observed. To resolve the persistence of uptake situation, researchers have used models that assume unidirectional exchange, i.e., from the capillary plasma to the EES17, 18, 19; however, the reflux from EES to the plasma space cannot be neglected, especially in a high-permeability situation. Recently, in an attempt to resolve the reflux issue, Sahoo et al.20 proposed the three-compartment leaky tracer kinetic model (LTKM) comprising the plasma permeable compartment where bidirectional flow takes place, and the leakage compartment where unidirectional flow is assumed. LTKM analysis has shown that even with a limited scan duration, reliable estimation of pharmacokinetic parameters can be obtained.20

In a recently published study, perfusion MRI performed better in comparison to other available MRI techniques, such as conventional imaging, spectroscopy, and diffusion tensor imaging, in differentiating low- from high-grade gliomas. It has been observed that relative cerebral blood volume (rCBV) measurement is the best perfusion parameter for predicting glioma grade.12

A contrast medium dose of 0.2 mM/kg is usually recommended for DCE-MRI perfusion imaging, which is double the amount required for routine brain imaging (0.1 mM/kg). An additional dose of contrast medium to achieve a higher contrast-to-noise ratio (CNR) makes this protocol challenging for patients with various renal disorders where conditions, such as nephrogenic systemic fibrosis, may occur with higher and/or multiple contrast medium doses.21 The requirement for high contrast medium dosage decreases when using 3 T MRI systems compared with 1.5 T systems due to improved T1 relaxivity of contrast agents and with the availability of higher relaxivity contrast agents, such as gadobenate dimeglumine (Gd-BOPTA).21, 22, 23, 24, 25, 26, 27, 28 In the first-pass analysis as done in perfusion MRI, a contrast agent with higher relaxivity, such as Gd-BOPTA, using 3 T MRI will produce a higher signal-to-noise ratio (SNR) using a single dose of contrast medium compared with other similar agents with lower relaxivity.

There are few prospective studies using dynamic susceptibility contrast (DSC) MRI perfusion for the grading of gliomas.29, 30, 31 The purpose of the present study was to evaluate the relative sensitivity and specificity of a MRI perfusion protocol using a single-dose of contrast medium to evaluate glioma grading prospectively and to correlate the rCBV values with the mitotic index obtained at histopathology. The values of the haemodynamic parameters of the brain tumours were also compared using a 0.1 mmol/kg dose of contrast medium to investigate for any physiological differences in the tumours as well as the normal contralateral grey and white matter using a 3 T MRI system. To the authors' knowledge, there are no retrospective or prospective single-dose DCE-MRI perfusion studies for predicting glioma grade using rCBV values.

Section snippets

Materials and methods

This prospective study was approved by the institutional review board. Informed consent was obtained from the patients or their care providers. In total, 62 patients with histopathologically proven gliomas who presented with symptoms related to a space-occupying intracranial mass lesion were underwent DCE-MRI perfusion study. Fifty-three out of 62 were included in the study. Nine patients were excluded, as only partial resection of tumour was achieved in four and as only stereotactic biopsy was

Results

Of 53 patients included in the study, histopathology indicated 36 high-grade (four anaplastic astrocytoma grade III; one anaplastic ependymoma grade III; two anaplastic oligoastrocytoma grade III; two anaplastic oligodendroglioma grade III; 27 glioblastoma multiforme grade IV) and 17 low-grade (10 astrocytoma grade II; one pleomorphic xantoastrocytoma grade II; one dysembryoplastic neuroepithelial tumour; one pilocytic astrocytoma, four oligoastrocytoma grade II) gliomas. These tumours were

Discussion

In the present study, based on pre-defined rCBV cut-off values, prospective grading of low- and high-grade gliomas was achieved with a sensitivity and specificity of 97.22% and 100%, respectively. There was concordance between the histopathological and perfusion-based grading of gliomas in almost all the cases, with the exception of one patient, where on perfusion imaging the tumour was labelled as low grade, while at histopathology it was proved to be high-grade glioma. A significant

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