Gliomas are the most prevalent primary central nervous system (CNS) malignancy. As they are exceedingly heterogeneous and refractory, they become one of the toughest challenges in clinical treatment. The water-selective channel protein aquaporin-4 (AQP4) contributes to the migration and proliferation of gliomas, and to their resistance to therapy. At present, traditional biopsy is the sole method and ‘gold-standard’ approach to characterizing the expression levels of AQP4. However, the heterogeneity of intra-tumoural and inter-tumoural AQP4 necessitates the development of a non-invasive technique for mapping AQP4 expression in vivo. 

On November 15, Prof. BAI Ruiliang’s team at the Zhejiang University School of Medicine and Prof. LIU Yingchao’s team at the Provincial Hospital Affiliated to Shandong First Medical University published a research article in the journal Nature Biomedical Engineering. They developed a “visible” technique for imaging AQP4 expression at high spatial resolution via magnetic resonance imaging (MRI). This technique is expected to become an effective imaging tool for the precise diagnosis and prognosis for glioma and the assessment of therapeutic effects.

AQP4 is invisible in conventional magnetic resonance imaging techniques such as MRS. By referring to the fluorescence labeling method widely used in life sciences, the researchers realized the amplification of the AQP4 signal via the ingenious use of the AQP4-regulated transmembrane water exchange. On this basis, they developed a MR quantity via water-exchange dynamic-contrast-enhanced MRI (DCE-MRI), which facilitates a non-invasive and high-resolution technique for mapping AQP4.

AQP4 signal-amplification and detection strategy in MR

This high-resolution AQP4 MRI technique is superior to conventional imaging techniques in two dimensions. First, as a non-invasive imaging technique, not only is it free from ionizing radiation, but it is capable of detecting the heterogeneity of intra-tumoural and inter-tumoural AQP4 in vivo. The AQP4 visualization technology opens up a new avenue to assessing the biological activity of gliomas in different sub-regions and monitoring the sensitivity of therapies, therefore providing real-time guidance for clinical treatment and achieving the customized treatment of gliomas.

k_io map obtained from water-exchange DCE-MRI reveals intra-tumoural AQP4 distribution in human glioma.

Second, it can help patients maximally without the addition of financial burdens and time costs. It can be used in a routine MRI room without additional equipment or drugs. This approach could provide an effective imaging tool for the customized and precise diagnosis and treatment of gliomas.

Hopefully, this novel technique will give glioma patients fresh hope.