Advanced MRI prediction of meningioma histopathological classification: a literature review and case presentations

Meningioma is not uncommon case; however, the differentiation of high-grade from low-grade meningioma is important. The rate of recurrence of grade I meningioma is 7-20%, but in grade II meningioma is 30-40% and in grade III 50-80%. Non-invasive MRI techniques that can differentiate high-grade from low-grade meningiomas before surgery are useful for surgical planning and subsequent treatment. We present a review article and some case studies of low-grade (WHO grade I) and high-grade (WHO grade II and grade III) meningioma with conventional MRI and continue with advanced MRI; we performed diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) value, dynamic susceptibility contrast (DSC), dynamic contrast-enhanced (DCE) magnetic resonance (MR) perfusion and 3D ASL. From these three cases show that advanced magnetic resonance imaging with ADC value, DSC, DCE, and 3D arterial spin-labelling (ASL) is an essential sequence to differentiate high-grade from low-grade meningioma.


INTRODUCTION
Meningiomas are the most common intracranial tumours, accounting for 13-26% of all primary intracranial tumours in adults, with three grades of meningioma. WHO grade I or typical meningioma accounted for 80-90% cases, WHO grade II or atypical meningioma 5-15% cases, and WHO grade III or malignant meningioma 1-3% cases. 1 The treatment of choice is surgery, curative surgery of grade I with a recurrence rate of 7-20%, but the recurrence rate of grade II meningioma is 30-40% and grade III 50-80%. 2 Noninvasive techniques that can differentiate low-grade from high-grade meningioma are very useful for surgical planning and subsequent treatment. Patients with WHO grade II/III meningioma are more beneficial when surgery is performed earlier, so the detection of high-grade meningiomas is important for early resection and postoperative handlers.

LITERATURE REVIEW
Conventional magnetic resonance imaging shows a picture of meningioma with homogeneous or heterogeneous contrast enhancement and perilesional oedema, as well as a dural tail, but cannot predict the degree of tumour malignancy. 2 Advanced magnetic resonance imaging can illuminate the classification of meningioma, DSC MR perfusion to noninvasively measure brain perfusion through hemodynamic measurements such as cerebral blood volume and cerebral blood flow from intracranial tumours, while DCE MR perfusion noninvasively measures contrast enhancement patterns in tumour tissue by evaluating time intensity curve (TIC) and permeability studies K trans (wash-in rate), K ep (washout rate), initial area under gadolinium contrast (IAUGC) and volume of extravascular and extracellular space (ve). 3 ASL as an endogenous tracer, imaging of relative cerebral blood flow (rCBF), does not require contrast media, 4,5 it is a non-invasive technique, very suitable for patients who require repetitive follow-up, patients with impaired renal function, and paediatric patients. ASL shows different rCBF in meningioma and other extraaxial tumours such as schwannoma, macroadenoma, or extra-axial metastatic tumour. 6,7 ASL shows a different pattern of rCBF in low-grade meningiomas and high-grade meningiomas, in low grade shows a diffuse increase in rCBF, and in high grade shows a heterogeneous increase in rCBF due to hypoperfusion. 8, 9 The ADC values could help differentiate high-grade from low-grade meningioma, in highgrade meningioma the ADC value is lower than that in low-grade meningioma. [6][7][8][9] DCE MR perfusion, also widely referred to as 'permeability' MRI, is based on the acquisition of serial T1weighted images before, during, and after administration of low-molecular-weight extracellular MR contrast media, such as a gadolinium-based contrast agent.

CASE REPORT
The resulting signal intensity-time curve reflects a combination of tissue perfusion, vessel permeability, and extravascularextracellular space. DCE MR perfusion allows for the determination of the permeability, or 'leakiness' , of tumour vasculatures such as the transfer coefficient (K trans ) and the extravascular extracellular space volume fraction (ve). In a normal brain with an intact bloodbrain barrier (BBB), K trans = 0 min −1 and ve is unmeasurable. 10 In contrast to conventional, static contrast-enhanced, T1-weighted MRI, which displays contrast enhancement at a single point in time, DCE MR perfusion imaging depicts the wash-in, plateau, and wash-out contrast kinetics of the tissue, providing insight into the nature of the bulk tissue properties at the microvascular level.
With pharmacokinetic modelling of DCE MR perfusion data, several metrics are commonly derived: the transfer constant (K trans ), the fractional volume of the extravascular extracellular space (ve), the rate constant (kep, where kep = K trans / ve) and the fractional volume of the plasma space (vp). The most frequently used metric for DCE MR perfusion is K trans . It can have different interpretations depending on blood flow and permeability. When there is very high permeability, the flux of the gadolinium-based contrast agent is limited only by flow and thus K trans mainly reflects blood flow. In situations in which there is very low permeability, the gadolinium-based contrast agent cannot easily leak into the extravascular extracellular space and thus K trans mainly reflects permeability. 11 In intra-axial tumours, they have an endothelial tight junction as the blood-brain barrier, but for extra-axial tumours, there are no endothelial tight junction and permeability barriers. 12 Armed with these techniques, we can more clearly and confidently differentiate between benign and malignant lesions using DCE MR perfusion imaging with permeability studies. Classification for the time-intensity curve (TIC) in DCE MR perfusion shown in Figure 1: Type 1, no enhancement; type 2, gradual enhancement; type 3, rapid enhancement followed by a plateau phase; type 4, rapid enhancement followed by a washout phase; and type 5, rapid enhancement followed by slowly increasing enhancement 13 DSC MR perfusion has been primarily concerned with tumour angiogenesis, while DCE imaging has focused primarily on the evaluation of vascular permeability. 11 DSC MR perfusion shows that mean maximal rCBV values in lowgrade meningiomas are higher than highgrade meningiomas. 14,15

CASE PRESENTATION
We present three cases of meningioma, one malignant meningioma (WHO grade III), one atypical meningioma (WHO grade II), and one typical meningioma (WHO grade I). All patients underwent routine conventional magnetic resonance imaging, followed by 3D ASL, and continued with DCE perfusion with permeability studies.
MRI examinations were performed with a 3.0 Tesla MRI (Signa Pioneer; GE Medical Systems, Milwaukee, WI, USA) using a 21-channel TDI head-neck coil. Magnetic resonance imaging examination is divided into two parts: before injection contrast and after injection contrast. Before contrast injection, the protocols used were axial, sagittal, coronal T2 weighted images, axial T2 flair, T1 flair, DWI b-value 1000, axial 3D acquisition in SWAN, high resolution T2 cube, and ASL.   ; type 3, rapid enhancement followed by a plateau phase (c); type 4, rapid enhancement followed by a washout phase (d); and type 5, rapid enhancement followed by slowly increasing enhancement (e) [13].
Then, followed by contrast injection with DCE MR imaging, a threedimensional fast spoiled gradient-echo (3D-FSPGR) sequence with the following parameters was performed: TR = 6 ms, TE = 1.3 ms, FOV = 24 cm x 16.8 cm , matrix = 256 x 160, slice thickness 6 mm without spacing, NEX = 0.77, flip angle = 20, acquisition time 5 minutes 50 seconds. A total of 30 dynamic acquisitions and the contrast material is a bolus of 1.0-mmol/l gadobutrol formula (Gadovist; Schering Bayer Pharma), contrast is injected bolus when acquisition starts. After dynamic studies, post-contrast T1-weighted 3D cube images and axial T1 flair images were obtained.
Post-processing of image results from the 3D-ASL study and DCE study using Ready View and GenIQ software (Advance Workstation AW Volume Share 7; GE Medical System). Ready View to analyse 3D-ASL results for rCBF and GenIQ software is an application based on DCE-MRI data sets for pharmacokinetic analysis.
The purpose of GenIQ is to evaluate tissue flow, permeability, and contrast leakage from the vascular space to the extravascular extracellular space (EES) and then slowly leak back into the vascular space. Permeability is a parameter related to the level of leakage of contrast agent from the blood plasma space to the EES. Tumours performed by DCE-MRI are sensitive to MRI contrast, which is higher and faster. GenIQ to show and analyze the permeability study, we evaluate the peritumoral K trans in each case. The results of the ADC value, rCBV, 3D ASL, TIC and Peritumoral K trans in case 1, case 2 and Case 3 were shown in Table 1.

CASE 1
F, 63 years with left parietal convexity meningioma, post-surgery, histopathology confirmed WHO grade III meningioma, recurrent meningioma in the surgical bed six months after surgery ( Figure  2). The case diagnosis was concluded as meningioma, rhabdoid type; WHO grade III. Present infiltration into brain parenchyma. There was recurrent meningioma at the surgical bed in six months post-surgery (Figure 3).

CASE 2
M, 73 years with left para-midline frontal meningioma, histopathology confirmed atypical meningioma, WHO grade II (Figure 4). This case was concluded as atypical meningioma, WHO Grade II with present infiltration into brain parenchyma.

CASE 3
F, 51 years with left parieto-occipital convexity meningioma, a histopathological finding confirmed metaplastic meningioma, WHO grade I (Figure 5). The last case was concluded as metaplastic meningioma (WHO grade I).

Conventional
magnetic resonance imaging in all three cases shows a picture of meningioma with homogeneous or heterogeneous contrast enhancement and perilesional oedema, as well as a dural tail, but cannot differentiate high-grade from low-grade meningioma.
DWI with characterization of the ADC value shows that high-grade meningiomas reveal lower ADC values than low-grade meningiomas. High-grade meningioma shows high cellularity with restricted diffusion and decreased ADC value. In case 1 patient with malignant meningioma (WHO grade III) shows a decrease in the ADC value compared to WHO grade II and WHO grade I meningioma. 3D ASL shows a different pattern of rCBF in lowgrade and high-grade meningioma, in case 3 patient with low-grade meningioma shows a diffuse pattern of rCBF while in cases 1 and 2 high-grade meningioma shows a heterogeneous pattern of rCBF due to hypoperfusion. DSC MR perfusion shows a decrease in the rCBV value in high-grade meningioma and an increase in the rCBV in low-grade meningioma.
Case 1 and case 2, patient with highgrade meningioma shows type 4-time intensity curve with a fast wash in and wash out while case 3, patient with low-grade meningioma shows type 3 time intensity curve with a fast wash in and plateau phase wash-out, high-grade meningioma shows an increase in peritumoral K trans compared to low-grade meningioma, in case I and case 2, patients with high-grade meningioma the K trans are higher than case 3 with low-grade meningioma.
The grade of a meningioma has important therapeutic and prognostic implications.
Therefore, prospective identification of the histological grade of a meningioma by DCE MR perfusion may be clinically beneficial. In most cases, total surgical resection is planned when technically feasible. Preoperative knowledge that one is dealing with atypical or malignant meningioma can lead to alterations in the planned size, shape, and extent of a craniotomy to ensure clean margins. Preoperative knowledge of an atypical and malignant meningioma can also change the risk-benefit assessment of a neurosurgeon. In other words, a surgeon may employ more aggressive surgical technique to achieve a complete Simpson grade I resection.

CONCLUSIONS
Advanced magnetic resonance imaging with ADC value, 3D ASL, DCE MR perfusion, DSC MR perfusion are useful for the diagnosis of high-grade and lowgrade meningioma, confirmed with histopathological findings, and helps neurosurgeons plan surgical resection preoperatively.

ACKNOWLEDGMENTS
Special thanks are due to Vivid Umu Varidha for completing the data

STATEMENT OF ETHICS
The authors confirmed that written informed consent was obtained from the patient for the publication of the case (including publication of images). All procedures performed in this study were reviewed and approved by the ethical committee standard of Dr. Soetomo General Hospital with letter of exemption reference number: 0731/LOE/301.4.2/ XII/2021

CONFLICT OF INTEREST STATEMENT
The authors have no conflicts of interest to declare CASE REPORT