The application of fluorescence techniques in meningioma surgery-a review

Surgical resections of meningiomas, the most common intracranial tumor in adults, can only be curative if radical resection is achieved. Potentially, the extent of resection could be improved, especially in complex and/or high-grade meningiomas by fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA), indocyanine green (ICG), or fluorescein. This review aims to summarize and evaluate these fluorescence-guided meningioma surgery techniques. PubMed and Embase were searched for relevant articles. Additionally, we checked reference lists for further studies. Forty-eight articles were included in the final analysis. 5-ALA fluoresced with varying sensitivity and selectivity in meningiomas and in invaded bone and dura mater. Although ICG was mainly applied for video angiography, one report shows tumor fluorescence 18-28 h post-ICG injection. Lastly, the use of fluorescein could aid in the identification of tumor remnants; however, detection of dural tail is highly questionable. Fluorescence-guided meningioma surgery should be a reliable, highly specific, and sensitive technique. Despite numerous studies reporting the use of fluorescent dyes, currently, there is no evidence that these tools improve the radical resection rate and long-term recurrence-free outcome in meningioma surgery without neurological deficits. Evidence regarding the effectiveness and increased safety of resection after the application of these fluorophores is currently lacking. Future research should focus on the development of a meningioma-targeted, highly sensitive, and specific fluorophore

Study on intracranial meningioma using PET ligand investigation during follow-up over years (SIMPLIFY)

Purpose Radiologic follow-up of patients with a meningioma at the skull base or near the venous sinuses with magnetic resonance imaging (MRI) after stereotactic radiotherapy (SRT) and neurosurgical resection(s) can be difficult to interpret. This study evaluates the addition of C-11-methionine positron emission tomography (MET-PET) to the regular MRI follow-up. Methods This prospective pilot study included patients with predominantly WHO grade I meningiomas at the skull base or near large vascular structures. Previous SRT was part of their oncological treatment. A MET-PET in adjunct to their regular MRI follow-up was performed. The standardized uptake value (SUV) was determined for the tumor and the healthy brain, on the pre-SRT target delineation MET-PET and the follow-up MET-PET. Tumor-to-normal ratios were calculated, and C-11-methionine uptake over time was analyzed. Agreement between the combined MRI/MET-PET report and the MRI-only report was determined using Cohen's kappa. Results Twenty patients with stable disease underwent an additional MET-PET, with a median follow-up of 84 months after SRT. Post-SRT SUV T/N ratios ranged between 2.16 and 3.17. When comparing the pre-SRT and the post-SRT MET-PET, five categories of SUV T/N ratios did not change significantly. Only the SUVpeak T/N-cortex decreased significantly from 2.57 (SD 1.02) to 2.20 (SD 0.87) [p = 0.004]. A kappa of 0.77 was found, when comparing the MRI/MET-PET report to the MRI-only report, indicating no major change in interpretation of follow-up data. Conclusion In this pilot study, C-11-methionine uptake remained remarkably high in meningiomas with long-term follow-up after SRT. Adding MET-PET to the regular MRI follow-up had no impact on the interpretation of follow-up imaging

The Correlation of In Vivo MR Spectroscopy and Ex Vivo 2-Hydroxyglutarate Concentration for the Prediction of Isocitrate Dehydrogenase Mutation Status in Diffuse Glioma

Isocitrate dehydrogenase (IDH) mutation status is an important biomarker in the glioma-defining subtype and corresponding prognosis. This study proposes a straightforward method for 2-hydroxyglutarate (2-HG) quantification by MR spectroscopy for IDH mutation status detection and directly compares in vivo 2-HG MR spectroscopy with ex vivo 2-HG concentration measured in resected tumor tissue. Eleven patients with suspected lower-grade glioma (ten IDH1; one IDHwt) were prospectively included. Preoperatively, 3T point-resolved spectroscopy (PRESS) was acquired; 2-HG was measured as the percentage elevation of Glx3 (the sum of 2-HG and Glx) compared to Glx4. IDH mutation status was assessed by immunochemistry or direct sequencing. The ex vivo 2-HG concentration was determined in surgically obtained tissue specimens using gas chromatography-mass spectrometry. Pearson correlation was used for assessing the correlation between in vivo MR spectroscopy and ex vivo 2-HG concentration. MR spectroscopy was positive for 2-HG in eight patients, all of whom had IDH1 tumors. A strong correlation (r = 0.80, p = 0.003) between 2-HG MR spectroscopy and the ex vivo 2-HG concentration was found. This study shows in vivo 2-HG MR spectroscopy can non-invasively determine IDH status in glioma and demonstrates a strong correlation with ex vivo 2-HG concentration in patients with lower-grade glioma. </p

The Correlation of In Vivo MR Spectroscopy and Ex Vivo 2-Hydroxyglutarate Concentration for the Prediction of Isocitrate Dehydrogenase Mutation Status in Diffuse Glioma

Isocitrate dehydrogenase (IDH) mutation status is an important biomarker in the glioma-defining subtype and corresponding prognosis. This study proposes a straightforward method for 2-hydroxyglutarate (2-HG) quantification by MR spectroscopy for IDH mutation status detection and directly compares in vivo 2-HG MR spectroscopy with ex vivo 2-HG concentration measured in resected tumor tissue. Eleven patients with suspected lower-grade glioma (ten IDH1; one IDHwt) were prospectively included. Preoperatively, 3T point-resolved spectroscopy (PRESS) was acquired; 2-HG was measured as the percentage elevation of Glx3 (the sum of 2-HG and Glx) compared to Glx4. IDH mutation status was assessed by immunochemistry or direct sequencing. The ex vivo 2-HG concentration was determined in surgically obtained tissue specimens using gas chromatography-mass spectrometry. Pearson correlation was used for assessing the correlation between in vivo MR spectroscopy and ex vivo 2-HG concentration. MR spectroscopy was positive for 2-HG in eight patients, all of whom had IDH1 tumors. A strong correlation (r = 0.80, p = 0.003) between 2-HG MR spectroscopy and the ex vivo 2-HG concentration was found. This study shows in vivo 2-HG MR spectroscopy can non-invasively determine IDH status in glioma and demonstrates a strong correlation with ex vivo 2-HG concentration in patients with lower-grade glioma. </p

Ventricle contact may be associated with higher 11C methionine PET uptake in glioblastoma

PURPOSE: Ventricle contact is associated with a worse prognosis and more aggressive tumor characteristics in glioblastoma (GBM). This is hypothesized to be a result of neural stem cells located around the lateral ventricles, in the subventricular zone. 11C Methionine positron emission tomography (metPET) is an indicator for increased proliferation, as it shows uptake of methionine, an amino acid needed for protein synthesis. This study is the first to study metPET characteristics of GBM in relation to ventricle contact. METHODS: A total of 12 patients with IDH wild-type GBM were included. Using MRI, the following regions were determined: primary tumor (defined as contrast enhancing lesion on T1) and peritumoral edema (defined as edema visible on FLAIR excluding the enhancement). PET parameters in these areas were extracted using PET fused with MRI imaging. Parameters extracted from the PET included maximum and mean tumor-to-normal ratio (TNRmax and TNRmean) and metabolic tumor volume (MTV). RESULTS: TNRmean of the primary tumor showed significantly higher values for the ventricle-contacting group compared to that for the non-contacting group (4.44 vs 2.67, p = 0.030). Other metPET parameters suggested higher values for the ventricle-contacting group, but these differences did not reach statistical significance. CONCLUSION: GBM with ventricle contact demonstrated a higher methionine uptake and might thus have increased proliferation compared with GBM without ventricle contact. This might explain survival differences and should be considered in treatment decisions