Mapping cellular proliferation activity of glioma by water exchange DCE-MRI at high spatial resolution

Motivation: Cell proliferation abnormalities (e.g., Ki67 status) are key features of glioma. Conventional biopsy is used to characterize Ki67 expression levels in vivo, but it lacks spatial and temporal information because of intratumorally heterogeneity. Goal(s): To identify MRI parameters representing the intracellular water-efflux rate regulated by aquaporin-4, a noninvasive biomarker sensitive to Ki67 quantitative expression, in glioma. Approach: Human tumors, animal models, and cell lines were investigated by water-exchange DCE-MRI and immunohistochemistry. Results: Ki67 and transmembrane water-efflux rate showed a strong linear relationship. The underlying mechanism was the close symbiotic expression pattern between aquaporin-4 and Ki67. Impact: Transmembrane water-efflux rate is a sensitive biomarker of Ki67 because rapidly growing cells upregulate aquaporin-4 expression for enhanced transmembrane transport.