Mapping of Absolute Host Concentration and Exchange Kinetics of Xenon Hyper-CEST MRI Agents.

Martin Kunth,Christopher Witte,Leif Schröder

doi:10.3390/ph14020079

Abstract

Xenon magnetic resonance imaging (MRI) provides excellent sensitivity through the combination of spin hyperpolarization and chemical exchange saturation transfer (CEST). To this end, molecular hosts such as cryptophane-A or cucurbit[n]urils provide unique opportunities to design switchable MRI reporters. The concentration determination of such xenon binding sites in samples of unknown dilution remains, however, challenging. Contrary to 1H CEST agents, an internal reference of a certain host (in this case, cryptophane-A) at micromolar concentration is already sufficient to resolve the entire exchange kinetics information, including an unknown host concentration and the xenon spin exchange rate. Fast echo planar imaging (EPI)-based Hyper-CEST MRI in combination with Bloch–McConnell analysis thus allows quantitative insights to compare the performance of different emerging ultra-sensitive MRI reporters.

Highlights

The search for novel magnetic resonance imaging (MRI) contrast agents is motivated by two interlinked purposes: (a) providing more sensitive agents that can be readily detected at sub mM concentrations, and (b) avoiding toxic side effects such as those known for certain gadolinium (Gd)-based contrast agents (GBCAs) that have led to long-term deposition of Gd ions in tissue and that are subject of an ongoing debate [1,2,3]
We demonstrate in this study that a careful analysis of saturation transfer spectra acquired with a set of different RF saturation pulse settings allows determination of all these parameters by using the full Hyper-chemical exchange saturation transfer (CEST) (FHC) solution [48] with reasonable computational effort even for pixelwise analysis that has not been accomplished before in Xe MRI
CEST agents come with the advantage that they provide an adjustable contrast by choosing well-defined RF saturation conditions

Summary

Introduction

The search for novel magnetic resonance imaging (MRI) contrast agents is motivated by two interlinked purposes: (a) providing more sensitive agents that can be readily detected at sub mM concentrations, and (b) avoiding toxic side effects such as those known for certain gadolinium (Gd)-based contrast agents (GBCAs) that have led to long-term deposition of Gd ions in tissue and that are subject of an ongoing debate [1,2,3] To this end, the chemical exchange saturation transfer (CEST) approach with either endogenous substances or synthetic reporters is very attractive because various of these agents are metal free and can be detected with decent sensitivity [4,5,6]. An increasing number of studies aims to include quantitative MRI aspects as it has been done for 1 H CEST studies

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Discussion

Conclusion