Magnetic Resonance Measurements of Transcytolemmal Water Exchange

Li Zhaoqing; Han Yihua; Wang Zejun; Bai Ruiliang

doi:10.7498/aps.74.20250325

Abstract
Transcytolemmal water exchange is a critical process for maintaining cellular homeostasis and function, serving as a potential biological marker for tumor proliferation, prognosis, and cellular states. The application of Magnetic Resonance Imaging (MRI) to measure transcytolemmal water exchange dates back to the 1960s, when researchers first measured the residence time of intracellular water molecules in erythrocyte suspensions. Concurrently, the multi-exponential nature of nuclear magnetic resonance signals in biological tissues was discovered. Studies suggested that transcytolemmal water exchange could be one of the factors explaining this characteristic, marking the beginning of research into measuring transcytolemmal water exchange using magnetic resonance techniques. After decades of development, current MRI techniques for measuring transcytolemmal water exchange can be broadly classified into two types: those using relaxation time as a contrast mechanism and those using diffusion as a contrast mechanism. This review introduces the development of these technologies, discussing the principles, mathematical/biophysical models, results, and validation of representative methods. Regarding relaxation-based MR techniques, this review systematically organizes MRI methodologies for quantifying transcytolemmal water exchange through chronological developments across three biological substrates: ex vivo cell suspensions, ex vivo biological tissues, and in vivo biological tissues. The modeling section emphasizes two frameworks, including the two-site-exchange model and the three-site-two-exchange shutter-speed model. Regarding diffusion-based MR techniques, the review introduces the progress of diffusion-encoding and modeling for water exchange measurement. Diffusion-encoding methods are introduced according to single diffusion encoding sequences and double diffusion encoding sequences. For modeling, it covers three types, including the Kärger model based on the two-component Gaussian diffusion assumption, the modified Kärger model incorporating restricted diffusion effects, and first-order reaction kinetic models. Additionally, comparative studies among different diffusion-based methodologies are also discussed. Finally, this review evaluates their respective clinical applications, advantages, and limitations. Future prospects for technological developments in this field are proposed at the end.

Keywords:
Nuclear magnetic resonance /

magnetic resonance imaging /

transcytolemmal water-exchange /

biophysical models
Cited By

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