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Abstract #3878

Aquaporin-4 inhibition in the mouse brain leads to apparent cell shrinkage as measured by double diffusion encoding

Teddy Xuke Cai1, Mohamed Tachrount2, Nathan Hu Williamson1, Peter Joel Basser1, and Karla Loreen Miller2
1Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States, 2Nuffield Department of Clinical Neuroscienes, University of Oxford, Oxford, United Kingdom

Synopsis

Keywords: Microstructure, Diffusion Acquisition, aquaporin, double diffusion encoding, microstructure

Motivation: Aquaporin-4 (AQP4) inhibition has emerged as a protective therapy for cytotoxic oedema (i.e., cell swelling), but monitoring the associated effects using diffusion MRI has largely been limited to the non-specific, apparent diffusion coefficient (ADC).

Goal(s): To better understand the microstructural effects of AQP4 inhibition in the healthy mouse brain - perhaps cell shrinkage - using advanced diffusion encoding.

Approach: A double diffusion encoding method and analysis framework was implemented, which aims to provide specific parameters: cell size, occupancy, and exchange time.

Results: AQP4 inhibition with TGN-020 yielded parameters consistent with an approximately 2 – 3% cell shrinkage, preliminarily confirming the proposed mechanism-of-action.

Impact: The modulation of water permeability by aquaporins is important to normal brain function and pathology. We present a method to disentangle the apparent cell size, occupancy, and exchange time, to provide insight into the microstructural effects of aquaporin-4 inhibition.

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Keywords