MR study of water exchange and cell membrane permeability in rat liver cells using a tissue-specific MR contrast agent

Chang, Y M; Kim, Y S; Lee, S K; Ryeom, H K; Lee, J M; Suh, K J; Kim, Y J; Kang, D S; Clarkson, Robert

Abstract

PURPOSE
A precise NMR technique for measuring the rate of water exchange and cell membrane permeability across the hepatocyte membrane using liver-specific MR contrast agent is described. ATERIAL AND METHODS: The rat hepatocytes isolated by perfusion of the livers were used for the NMR measurements. All experiments were performed on an IBM field cycling relaxometer operating from 0.02MHz to 60 MHz proton Larmor frequency. spin-echo pulse sequence was empolyed to measure spin-lattice relaxation time, T1. The continuous distribution analysis of water proton T1 data from rat hepatocytes containing low concentrations of the liver specific contrast agent, Gd-EOB-DTPA, modeled by a general two compartment exchange model.
RESULTS
The mean residence time of water molecule inside the hepatocyte was approximately 250 msec. The lower limit for the permeability of the hepatocyte membrane was (1.3 +/- 0.1) X 10(-3) cm/sec. The CONTIN analysis, which seeks the natural distribution of relaxation times, reveals direct evidence of the effect of diffusive exchange. the diffusive water exchange is not small in the intracellular space in the case of hepatocytes.
CONCLUSIONS
Gd-EOB-DTPA, when combined with continuous distribution analysis, provides a robust method to study water exchange and membrane permeability in hepatocytes. Water exchange in hepatocyte is much slower thatn that in red blood cells. Therefore, tissue-specific contrast agent may be used as a functional agent to give physiological information such as cell membrane permeability.