Whole-Brain Intracellular pH Mapping of Gliomas Using High-Resolution 31P MR Spectroscopic Imaging at 7.0 T

Phosphorous 31 spectroscopic MRI at 7.0 T enabled high-resolution quantification of increased intracellular pH in the tumor volume, which was associated with histologic features, in study participants with glioma. Malignant tumors commonly exhibit a reversed pH gradient compared with normal tissue, with a more acidic extracellular pH and an alkaline intracellular pH (pH(i)). In this prospective study, pH(i) values in gliomas were quantified using high-resolution phosphorous 31 (P-31) spectroscopic MRI at 7.0 T and were used to correlate pH(i) alterations with histopathologic findings. A total of 12 participants (mean age, 58 years +/- 18 [SD]; seven male, five female) with histopathologically proven, newly diagnosed glioma were included between September 2018 and November 2019. The P-31 spectroscopic MRI scans were acquired using a double-resonant P-31/H-1 phased-array head coil together with a three-dimensional (3D) P-31 chemical shift imaging sequence (5.7-mL voxel volume) performed with a 7.0-T whole-body system. The 3D volumetric segmentations were performed for the whole-tumor volumes (WTVs); tumor subcompartments of necrosis, gadolinium enhancement, and nonenhancing T2 (NCE T2) hyperintensity; and normal-appearing white matter (NAWM), and pH(i) values were compared. Spearman correlation was used to assess association between pH(i) and the proliferation index Ki-67. For all study participants, mean pH(i) values were higher in the WTV (7.057 +/- 0.024) compared with NAWM (7.006 +/- 0.012; P < .001). In eight participants with high-grade gliomas, pH(i) was increased in all tumor subcompartments (necrosis, 7.075 +/- 0.033; gadolinium enhancement, 7.075 +/- 0.024; NCE T2 hyperintensity, 7.043 +/- 0.015) compared with NAWM (7.004 +/- 0.014; all P < .01). The pH(i) values of WTV positively correlated with Ki-67 (R-2 = 0.74, r = 0.78, P = .001). In conclusion, P-31 spectroscopic MRI at 7.0 T enabled high-resolution quantification of pH(i) in gliomas, with pH(i) alteration associated with the Ki-67 proliferation index, and may aid in diagnosis and treatment monitoring.