Transmembrane water-efflux rate measured by magnetic resonance imaging as a biomarker of the expression of aquaporin-4 in gliomas

Yinhang Jia; Shangchen Xu; Guangxu Han; Bao Wang; Zejun Wang; Chuanjin Lan; Peng Zhao; Meng Gao; Yi Zhang; Wenhong Jiang; Biying Qiu; Rui Liu; Yi-Cheng Hsu; Yi Sun; Chong Liu; Yingchao Liu; Ruiliang Bai

doi:10.1038/s41551-022-00960-9

Transmembrane water-efflux rate measured by magnetic resonance imaging as a biomarker of the expression of aquaporin-4 in gliomas

Nat Biomed Eng. 2023 Mar;7(3):236-252. doi: 10.1038/s41551-022-00960-9. Epub 2022 Nov 14.

Authors

Yinhang Jia^#^{1

2

3}, Shangchen Xu^#³, Guangxu Han^#², Bao Wang⁴, Zejun Wang², Chuanjin Lan³, Peng Zhao³, Meng Gao³, Yi Zhang⁵, Wenhong Jiang⁶, Biying Qiu⁶, Rui Liu⁶, Yi-Cheng Hsu⁷, Yi Sun⁷, Chong Liu⁸, Yingchao Liu^{9

10}, Ruiliang Bai^{11

12

13}

Affiliations

¹ Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Run Shaw Hospital AND Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University School of Medicine, Hangzhou, China.
² Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China.
³ Department of Neurosurgery, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁴ Department of Radiology, Qilu Hospital of Shandong University, Jinan, China.
⁵ Department of Radiology, Provincial Hospital Affiliated to Shandong University, Jinan, China.
⁶ Zhejiang University School of Medicine, Hangzhou, China.
⁷ MR Collaboration, Siemens Healthcare, Shanghai, China.
⁸ MOE Frontier Science Center for Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
⁹ Department of Neurosurgery, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. yingchaoliu@email.sdu.edu.cn.
¹⁰ Shandong National Center for Applied Mathematics, Shandong University, Jinan, China. yingchaoliu@email.sdu.edu.cn.
¹¹ Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Run Shaw Hospital AND Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University School of Medicine, Hangzhou, China. ruiliangbai@zju.edu.cn.
¹² Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China. ruiliangbai@zju.edu.cn.
¹³ MOE Frontier Science Center for Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China. ruiliangbai@zju.edu.cn.

^# Contributed equally.

PMID: 36376487
DOI: 10.1038/s41551-022-00960-9

Abstract

The water-selective channel protein aquaporin-4 (AQP4) contributes to the migration and proliferation of gliomas, and to their resistance to therapy. Here we show, in glioma cell cultures, in subcutaneous and orthotopic gliomas in rats, and in glioma tumours in patients, that transmembrane water-efflux rate is a sensitive biomarker of AQP4 expression and can be measured via conventional dynamic-contrast-enhanced magnetic resonance imaging. Water-efflux rates correlated with stages of glioma proliferation as well as with changes in the heterogeneity of intra-tumoural and inter-tumoural AQP4 in rodent and human gliomas following treatment with temozolomide and with the AQP4 inhibitor TGN020. Regions with low water-efflux rates contained higher fractions of stem-like slow-cycling cells and therapy-resistant cells, suggesting that maps of water-efflux rates could be used to identify gliomas that are resistant to therapies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aquaporin 4 / metabolism
Biomarkers
Glioma* / diagnostic imaging
Glioma* / metabolism
Humans
Magnetic Resonance Imaging
Rats
Water* / metabolism

Substances

Water
Aquaporin 4
Biomarkers