Association between Tumor Acidity and Hypervascularity in Human Gliomas Using pH-Weighted Amine Chemical Exchange Saturation Transfer Echo-Planar Imaging and Dynamic Susceptibility Contrast Perfusion MRI at 3T

• Published in: American journal of neuroradiology : AJNR Vol. 40; no. 6; pp. 979 - 986
• Main Authors: Wang, Y-L, Yao, J, Chakhoyan, A, Raymond, C, Salamon, N, Liau, L M, Nghiemphu, P L, Lai, A, Pope, W B, Nguyen, N, Ji, M, Cloughesy, T F, Ellingson, B M
• Format: Journal Article
• Language: English
• Published: United States American Society of Neuroradiology 01-06-2019
• Subjects: Adult; Adult Brain; Aged; Brain Neoplasms - chemistry; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - pathology; Echo-Planar Imaging - methods; Female; Functional; Glioma - chemistry; Glioma - diagnostic imaging; Glioma - pathology; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Imaging - methods; Male; Middle Aged; Neuroimaging - methods; Retrospective Studies
• ISSN: 0195-6108; 1936-959X
• DOI: 10.3174/ajnr.a6063

Acidification of the tumor microenvironment from abnormal metabolism along with angiogenesis to meet metabolic demands are both hallmarks of malignant brain tumors; however, the interdependency of tumor acidity and vascularity has not been explored. Therefore, our aim was to investigate the association between pH-sensitive amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) and relative cerebral blood volume (CBV) measurements obtained from dynamic susceptibility contrast (DSC) perfusion MRI in patients with gliomas.
In this retrospective study, 90 patients with histologically confirmed gliomas were scanned between 2015 and 2018 (median age, 50.3 years; male/female ratio = 59:31). pH-weighting was obtained using chemical exchange saturation transfer echo-planar imaging estimation of the magnetization transfer ratio asymmetry at 3 ppm, and CBV was estimated using DSC-MR imaging. The voxelwise correlation and patient-wise median value correlation between the magnetization transfer ratio asymmetry at 3 ppm and CBV within T2-hyperintense lesions and contrast-enhancing lesions were evaluated using the Pearson correlation analysis.
General colocalization of elevated perfusion and high acidity was observed in tumors, with local intratumor heterogeneity. For patient-wise analysis, median CBV and magnetization transfer ratio asymmetry at 3 ppm within T2-hyperintense lesions were significantly correlated (
= 0.3180,
= .002), but not in areas of contrast enhancement (
= .52). The positive correlation in T2-hyperintense lesions remained within high-grade gliomas (
= 0.4128,
= .001) and in
wild-type gliomas (
= 0.4300,
= .002), but not in World Health Organization II or in
mutant tumors. Both magnetization transfer ratio asymmetry at 3 ppm and the voxelwise correlation between magnetization transfer ratio asymmetry and CBV were higher in high-grade gliomas compared with low-grade gliomas in T2-hyperintense tumors (magnetization transfer ratio asymmetry,
= .02
Pearson correlation,
= .01). The same trend held when comparing
wild-type gliomas and
mutant gliomas (magnetization transfer ratio asymmetry,
= .04; Pearson correlation,
= .01).
A positive linear correlation between CBV and acidity in areas of T2-hyperintense, nonenhancing tumor, but not enhancing tumor, was observed across patients. Local heterogeneity was observed within individual tumors.