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

Abstract

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 (³¹P) 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 ³¹P spectroscopic MRI scans were acquired using a double-resonant ³¹P/¹H phased-array head coil together with a three-dimensional (3D) ³¹P 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 (R² = 0.74, r = 0.78, P = .001). In conclusion, ³¹P 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. Keywords: ³¹P MRSI, pH, Glioma, Glioblastoma, Ultra-High-Field MRI, Imaging Biomarker, 7 Tesla Supplemental material is available for this article. © RSNA, 2023.