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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