Comparison of diffusion-weighted MRI and anti-Stokes Raman scattering (CARS) measurements of the inter-compartmental exchange-time of water in expression-controlled aquaporin-4 cells

Takayuki Obata,Yasuhiko Tachibana,Ichio Aoki,Takayuki Miyauchi,Yoichiro Abe,Hiroshi Kawaguchi,Jeff Kershaw,Yoko Ikoma,Masato Yasui,Sayaka Shibata,Hiroyuki Takuwa

doi:10.1038/s41598-018-36264-9

Abstract

We performed multi-b and multi-diffusion-time diffusion-weighted magnetic resonance imaging on aquaporin-4-expressing (AQ) and -non-expressing (noAQ) cells, and demonstrated a clear difference between the signals from the two cell types. The data were interpreted using a two-compartment (intra and extracellular spaces) model including inter-compartmental exchange. It was also assumed that restricted diffusion of water molecules inside the cells leads to the intracellular diffusion coefficient being inversely proportional to the diffusion-time. Estimates of the water-exchange-times obtained with this model are compared to those measured using an independent optical imaging technique (coherent anti-Stokes Raman scattering imaging, CARS). For both techniques it was found that the exchange-time estimated for the noAQ cells was significantly longer than that for the AQ cells.

Highlights

Cell membrane water permeability (CMWP) is altered in diseases like cancer[1,2] and brain edema[3]
In this study we performed multi-b-value multi-Td (MbMTd) Diffusion-weighted magnetic resonance imaging (DWI) on AQP4-expressing (AQ) and -non-expressing Chinese hamster ovary (CHO) cells over a relatively wide range of Td, which was modulated by setting the separation of the diffusion gradient lobes (Δ) to 40, 70, or 100 ms to change the sequence parameter Tdscan (Fig. 1)
Separate apparent diffusion coefficient (ADC) maps were calculated for the images with b = 0–1500 s/mm[2] and b = 4000–8000 s/mm[2] ranges using single-exponential fitting to the data acquired with Δ = 100 ms (Fig. 4)

Summary

Introduction

Cell membrane water permeability (CMWP) is altered in diseases like cancer[1,2] and brain edema[3]. Ibata et al reported a method to visualize water exchange between the intra- and extracellular spaces of AQP4 (a subtype of AQP) -expressing and -non-expressing cells using an optical imaging technique[5]. The technique they used is called coherent anti-Stokes Raman scattering (CARS) microscopy, which can selectively visualize H2O. After quick replacement of the extracellular H2O by D2O, they succeeded in measuring the exchange-time of water from the intracellular to the extracellular space of a single HeLa S3 cell (100.7 ms for AQP4-non-expressing cells and 43.1 ms for AQP4-expressing cells). The Kärger model[15,16,17], which is a simple two-compartment model with inter-compartmental compound exchange, was used as a base model for analysis

Methods

Results

Discussion

Conclusion