水分子跨细胞膜交换的磁共振测量技术研究进展

李昭青; 韩益华; 王泽君; 白瑞良

doi:10.7498/aps.74.20250325

摘要
水分子跨细胞膜交换是维持细胞稳态和功能的重要过程，是肿瘤增殖、预后以及细胞状态的潜在生物学标志物。利用磁共振方法测量水分子跨细胞膜的交换速率可追溯到20世纪60年代，研究者在血红细胞悬液样本中测量细胞内水分子的停留时间。之后，在生物组织中磁共振信号的多指数特征被发现，研究发现水分子跨膜交换过程有可能是解释该特征的因素之一，利用磁共振方法测量水分子跨细胞膜交换过程的研究至此拉开序幕。经过几十年的发展，磁共振领域目前对水分子跨细胞膜交换测量的技术大致可以分为两类：基于弛豫时间和基于扩散的磁共振测量方法。本文将梳理相关磁共振技术的发展历程，对代表性技术的测量原理、数学/生物物理模型、不同技术的测量结果及验证进行介绍。最后对不同方法的应用场景和优缺点进行讨论，并对该领域的发展进行展望。

关键词:
核磁共振 /

磁共振成像 /

水分子跨细胞膜交换 /

生物物理模型
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
施引文献

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水分子跨细胞膜交换的磁共振测量技术研究进展

Magnetic Resonance Measurements of Transcytolemmal Water Exchange

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水分子跨细胞膜交换的磁共振测量技术研究进展

Magnetic Resonance Measurements of Transcytolemmal Water Exchange

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