Preoperative prediction of 5-ALA fluorescence in gliomas: comparison of 7-Tesla magnetic resonance spectroscopic imaging, contrast-enhancement on MRI, and positron emission tomography.

Abstract

We investigated whether metabolic ratios derived from ultra-high-field 7-T 3D-FID-CRT-MRSI can predict intraoperatively visible 5-aminolevulinic acid (5-ALA) fluorescence in gliomas and compared their predictive performance to established imaging markers, including contrast enhancement (CE) on MRI and PET tumor-to-normal ratio (TNR). We retrospectively analyzed 43 patients with histopathologically confirmed adult-type diffuse gliomas (CNS WHO grades 2-4) who underwent preoperative 7-T MRSI and 5-ALA-guided resection. Group differences between 5-ALA-positive and 5-ALA-negative tumors were tested for 16 metabolic ratios to either total creatine (tCr) or combined N-acetylaspartate and N-acetyl-aspartyl-glutamate (NAA + NAAG; total NAA; tNAA) using non-parametric statistics with Šidák correction. CE-MRI status and PET TNR (subcohort, n = 31) were included as reference predictors. We additionally evaluated a subgroup of non-enhancing gliomas (n = 27). Receiver operating characteristic (ROC) analysis was performed to determine diagnostic performance. 5-ALA-positive gliomas demonstrated significantly altered metabolic profiles, showing lower mI/tNAA (p < 0.001) and higher Gln/tCr, Glx/tCr, Gly/tCr, and GSH/tCr ratios (all p < 0.001). These ratios achieved high predictive accuracy for fluorescence (AUC_range = 0.79-0.94), comparable or superior to PET TNR (AUC = 0.90) and CE-MRI (AUC = 0.84). In a subcohort of nonenhancing gliomas, Gly/tCr and Gln/tCr showed a high prediction accuracy (AUC = 0.90). 7-T MRSI metabolic ratios can predict intraoperative 5-ALA fluorescence and may serve as an alternative or adjunct to CE-MRI and PET for preoperative patient selection for 5-ALA administration. Finally, these findings could be especially beneficial in non-enhancing gliomas, where CE-MRI offers limited predictive information. Question Does 7-T MRSI enable preoperative prediction of 5-ALA fluorescence to support patient selection for fluorescence-guided glioma surgery? Findings Several 7-T MRSI metabolic ratios (mI/tNAA, Gln/tCr, Glx/tCr, Gly/tCr and GSH/tCr) robustly predicted 5-ALA fluorescence across glioma subtypes, with diagnostic performance comparable to contrast-enhanced MRI and PET. Clinical relevance Ultra-high-field 7-T MRSI enables noninvasive preoperative prediction of intraoperative 5-ALA fluorescence in gliomas with performance comparable to PET and contrast-enhanced MRI, supporting surgical planning without the need for contrast agents or radiation exposure.