Introduction

Meningiomas are the most common intracranial tumors and account for up to 30% of all primary intracranial tumors in adults [21, 35]. They are typically slow-growing tumors that arise from the meningothelial cells of the arachnoid. Histological grading of meningiomas is based on the current WHO classification. The majority of lesions are benign WHO grade I lesions, representing approximately 90% of cases. The histological subtypes of grade I meningiomas differ from the more aggressive meningiomas, WHO grade II (atypical) and WHO grade III (anaplastic), 5–7% and 1–3% of cases, in their number of mitoses, cellularity, nuclear-to-cytoplasmic ratio, histological patterns, and their relatively low risk of recurrence or aggressive growth pattern [17, 34, 35].

Stereotactic radiosurgery (SRS) is an important and well-established modality in the treatment armamentarium of meningiomas either as stand-alone therapy or in combination with microsurgery [4, 5, 19]. Radiosurgery in meningiomas has shown to be effective and associated with low toxicity rates. Long-term results have shown good clinical outcomes as well as tumor control rates for meningiomas [3, 20, 22, 25].

Magnetic resonance imaging (MRI) is the modality of choice for the investigation of meningiomas. Although typical meningiomas have characteristic imaging features, there are multiple atypical variants that may be diagnostically challenging, and the value of MRI in predicting WHO grades in meningiomas is limited [34]. Standard MRI sequences (T1, T2) have limited value with regard to assess the biological behavior particularly of slowly growing tumor, e.g., during or following radiation or chemotherapy [23].

Diffusion-weighted magnet resonance imaging (DWI) provides information on water diffusivity, which is expressed by the apparent diffusion coefficient (ADC) [15]. It has been shown that DWI can be used to distinguish benign from malignant tumors and to differentiate meningiomas from other tumors such as hemangiopericytomas, which appear similar to meningiomas on T1- and T2-weighted sequences [14, 23, 26, 33]. DWI provides information regarding the microstructure of a tumor, and it has been shown that an increase of cell density leads to restricted water diffusion and to decreased ADC [9, 28,29,30]. In gliomas it has been shown that ADC can be used as a predictor of treatment response or as an early response assessment [11, 18]. As meningiomas may show delayed volume changes following treatment, a measure of tumor cell density and ADC could be important for treatment evaluation [12, 27]. Few studies in meningiomas have investigated ADC values and reported lower ADC values in WHO grade II/III compared with grade I meningiomas [26]; other studies did not find such a correlation [24].

A noninvasive radiobiological method to predict treatment response in meningiomas would be desirable to improve tumor management. Therefore, the purpose of this study was to analyze whether intratumoral ADC values change over time in untreated compared with radiosurgically treated meningiomas.

Materials and methods

Patients

We retrospectively analyzed MRI of 51 patients with meningiomas or suspected meningiomas that fulfilled the imaging criteria for these tumors (26 untreated and were conservatively managed whereas 25 were treated with radiosurgery). The follow-up data ranged between 1 and 10 years. This study was approved by the regional ethics committee.

Radiosurgery parameters

We analyzed the radiosurgery treatments of 25 patients. Thirteen radiosurgery procedures were performed with a Gamma Knife Perfexion (Elekta, Stockholm, Sweden) system, and 12 tumors were treated with a TrueBeam Novalis STx (Varian, CA, USA) system. One patient was treated with a hypofractionated scheme (5 × 5 Gy); all other patients underwent a single-dose radiosurgery treatment. The selection criteria for radiosurgical treatment was decided by an interdisciplinary tumor board decision and depended mainly on the location, size of the tumor, as well as patient’s condition and age.

MR imaging acquisition

MRI data were acquired with 1.5T Avanto or Espree scanner (Siemens, Erlangen, Germany) with twelve-channel head array coil. Our study MRI examination included sagittal T1 MPRAGE with contrast agent (repetition time (TR)/echo time (TE)/inversion time (TI) = 2200/4.9/900 ms, 1-mm slice thickness, 20% gap between slices, flip angle 8o, acquisition time (TA) 3:20). Diffusion-weighted images were acquired by using the diffusion-weighted single-shot echo-planar imaging (EPI) sequence (TR/TE: 3400/89 ms; 5-mm slice thickness; 1.5-mm gap between slices; 2 averages; TA 1:38 min; obtained with b values of 0 and 1000 s/mm2 in the read, phase, and slice directions).

Fig. 1
figure 1

Illustrative case of a conservatively followed patient with a left sphenoid wing meningioma. Left, contrast enhanced T1 MPRAGE; right, ADC map with ROI

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Data analysis

Quantification of ADC values

Comparing ADC with T1-weighted sequences care was taken to place the ROI within visually tumor margins avoiding the surrounding normal brain (Fig. 1). A global ROI was then set on the adjacent slice above and below, if the tumor was large enough. The ADC values of these three ROIs were then averaged (ADCmean) and extracted using PMOD software (PMOD Technologies LLC, Zürich, Switzerland). Global ROIs were used to derive ADC90%max values using a cut-off at 90%, representing the highest 10% values of the ADC range. ADC10%min values was calculated with a cut-off at 10%, representing the lowest 10% of the ADC values.

Statistics

Descriptive statistics were used to characterize the patient population. Data are presented as mean ± SD. To test differences between untreated and treated meningiomas, we used the unpaired t test (SPSS version 24, IBM, New York, USA).

Results

Clinical features

The mean age of the 51 patients was 58 ± 12 years (37 female). Twenty-six patients remained untreated (mean age 58 ± 11 years, 18 female) and were conservatively managed whereas 25 were treated with radiosurgery (mean age 57 ± 13 years, 19 female). The follow-up data ranged between 1 and 10 years. One patient was treated with a hypofractionated scheme (5 × 5 Gy); all other patients underwent a single-dose radiosurgery treatment.

ADC

The mean ADC values, ADC10%min, and ADC90%max within the different groups did not show any significant changes during the follow-up times in the untreated (over 10 years period, Table 1) and radiosurgically treated (over 4 years period, Table 2) group when comparing baseline to follow-up values. However, statistically significant difference was observed when comparing the baseline mean ADC of untreated and radiosurgically treated meningiomas (p < 0.01), as well as mean ADC at follow-up (p < 0.01) (Fig. 2). ADC90%max values revealed statistically significant difference between the groups at baseline (p < 0.01) as well as at follow-up (p < 0.0001) (Fig. 3). ADC10%min showed no changes either at baseline or at follow-up.

Table 1 Summary of the data parameters of conservative-treated meningiomas (n = 26)
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Table 2 Summary of the data of radiosurgically treated meningiomas (n = 25)
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Fig. 2
figure 2

Statistically significant difference (*p < 0.01) was observed when comparing the baseline mean ADC of untreated and radiosurgically treated meningiomas, as well as mean ADC at follow-up. The mean ADC values within the groups did not show any significant changes

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Fig. 3
figure 3

ADC90%max values revealed a statistically significant difference between the ADC values in conservatively treated meningiomas and radiosurgically treated meningiomas at a baseline (*p < 0.01) and at b follow-up (**p < 0.0001). When comparing the ADC90%max values from baseline to follow-up, no significant changes within the groups were detected

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Tumor volume

Tumor volume remained stable in 8 (31%) and increased in 18 (69%) patients on the conservatively managed meningiomas (Table 1). Of those meningiomas which underwent radiosurgery, 14 revealed a reduced tumor volume in the last follow-up (56%) whereas 4 increased slightly in size (16%, Table 2). The remaining ten radiosurgically treated meningioma volumes stayed stable over time (n = 7, 28%).

Discussion

With DWI water diffusion in tissue can be measured and quantified by ADC [13]. ADCmean, ADC10%min, and ADC90%max have been widely examined in several types of tumors with varying results [6, 7, 26,27,28,29]. ADC values may be influenced by cellularity, proliferation, nucleic volume and size, permeability of cell membrane, cell size, composition of extracellular matrix, microvessel density, cell density, and tumor grade [1, 23, 28]. This allows to distinguish between brain tissue, edema, and tumor and provides information about cell density [7]. Within the last years, ADC has been increasingly shown to be a useful biological marker for treatment response in neuro-oncology, mainly in gliomas [8, 11, 16, 18].

Different studies have looked whether ADC values correlate with the tumor grading in meningiomas [1, 17, 31]. Others studied if ADC could differentiate fibrous tumor/hemangiopericytoma from angiomatous meningioma [14] or if ADC could be used as a preoperative predictor for progression or recurrence in meningiomas [12]. They found that parasagittal and parafalcine meningiomas with preoperative high DWI signal and lower ADC values had higher risks for progression or recurrence.

In our study, we analyzed if ADC values change in meningiomas over time and therefore compared a series of conservatively managed versus radiosurgically treated meningiomas. Since we hypothesize that a change in cell density highly corresponds with a change in ADC values [29], either an increase or decrease in ADC values would reflect a change in the biological tumor behavior. To evaluate this, we measured mean ADC values as well as ADC10%min and ADC90%max values in untreated and treated meningiomas. In our series, ADCmean values increased after radiosurgery. These results are in line with the existing literature possibly indicating that ADC could be used as a marker for treatment response and used to distinguish tumor recurrence versus treatment related (radiogenic) changes [2, 10, 32]. In the future, it would be interesting to evaluate the ADC values of those treated meningiomas that grew in the follow- up period, decreased in size, or remained in their original size. Due to our small series in our study, this subgroup analysis could not be carried out; however, further studies are planned to address this question.

Conclusion

Radiosurgically treated meningiomas reveal significant change of the mean ADC values over time whereas ADC values in conservatively treated meningiomas remain stable during follow-up, suggesting that ADC may reflect a change in the biological behavior of the tumor. Thus, especially in meningiomas where volume change after radiosurgery is not frequent, ADC analysis could be a useful tool to measure early treatment response; however, additional long-term studies are needed to address this issue.