Spatiotemporal mapping of proliferation activity in gliomas via AQP4 water-exchange MRI

Introduction: Proliferation activity mapping is crucial for the guidance of first biopsy and treatment evaluation of gliomas due to the highly heterogenous nature of glioma tumor. Here we propose and demonstrate an ease-of-use way of in vivo spatiotemporal mapping of proliferation activity by simply tracking transmembrane water dynamics with magnetic resonance imaging (MRI). Specifically, we demonstrated that proliferation activity can accelerate the transmembrane water transport in glioma cells.

Methods: The transmembrane water-efflux rate (kio) measured by our teams' AQP4 water-exchange dynamic contrast-enhanced (DCE) MRI. The point-point image- stereotactic biopsy Immunofluorescence, immunohistochemistry and immunocytochemistry staining were used to validate the correlation of Kio and Ki67.

Results: In glioma cell cultures, kio precisely followed the dynamic changes of proliferation activity in growth cycles and response to temozolomide (TMZ) treatment. In both animal glioma model and human glioma, kio linearly and strongly correlated with the spatial heterogeneity of intra-tumoral proliferation activity. More importantly, proliferation activity predicted by the single MRI parameter kio is much more accurate than those predicted by state-of-the-art methods using multimodal standard MRIs and advanced machine learning. Upregulated aquaporin 4 (AQP4) expression were observed in most proliferating glioma cells, explaining the above results in molecular level.

Conclusion : This study provides an ease-of-use, accurate, and non-invasive imaging method for the spatiotemporal monitoring of proliferation activity in glioma by a single AQP4 DCE-MRI sequence.