Increasing the Specificity : Physics of MT, CEST, paraCEST & APT
Seth A Smith1
1Vanderbilt University, United States

Synopsis

This presentation is intended to provide an understanding of exchange-mediated contrasts commonly explored in MRI. Specifically we will focus on MT, CEST, and ParaCEST; what are the physics of the contrast mechanisms, what biochemical interactions give rise to the observed phenomena, how to exploit the contrasts with standard acquisition and analysis methods, as well as explore the sensitivity and specificity of each in tissue. Lastly, we will present some specific applications of each, such as MTR and qMT, APT-CEST.

Target Audience

The target audience for this presentation is researchers interested in Magnetization Transfer (MT), CEST, ParaCEST and applications of each. We will present the methodology as well as how it can be used, analyzed, and evaluated in vivo.

Outcomes/Objectives

The objectives of this presentation are to provide a guide for understanding the similarities and differences among conventional MT, endogenous CEST, ParaCEST through MR physics, biochemical interactions, acquisition strategies, and quantification. We will discuss the assumptions within each scenario as well as address the overarching question of sensitivity and specificity of each technique. In the end, what is each method sensitive to and what can be done with exploiting those sensitivities to provide specific measures of particular molecular interactions in tissue. We will briefly touch on applications of each, however, the focus is primarily on the MR physics of exchange-mediated contrast.

Purpose

The purpose of this presentation is to provide an overview of the basics of magnetization transfer, CEST, and ParaCEST acquisitions, analysis, and implementation.

Overview

Magnetization Transfer (MT) is an umbrella term that can be summarized by the transfer or exchange of spin information between labile-proton-containing molecules or macromolecules and the surrounding water. In MRI, exploitation of this exchange is often performed by selective saturation of the labile proton species. MT contrast (MTC) relies on the transfer of RF irradiation through dipole-dipole or through space exchange and is typically thought to be sensitive to macromolecular composition, which in the CNS is largely driven by myelin. Chemical Exchange Saturation Transfer (CEST) is a molecular-targeted saturation transfer phenomenon whereby labile protons associated with mobile molecules, metabolites, or other biochemical compounds exchange their saturation with surrounding water through direct chemical exchange. The spectral selectivity of CEST has allowed for opportunities to study specific molecules such as proteins/peptides, glutamate, glucose, and endogenous compounds. The most often reported endogenous CEST contrast comes from the amide protons associated with the amide bond on a protein/peptide backbone and has been shown to be sensitive to pH, tumors, and stroke and is termed Amide Proton Transfer (APT). APT is reported most often because its resonance frequency is relatively far from the water resonance and the exchange rate for amide protons is slow to intermediate on the NMR timescale. However, one challenge with CEST is that often the resonance frequency and exchange rate of these molecular protons is close to the water resonance or quite rapid, respectively. ParaCEST is an alternative method by which an exogenous compound is introduce into the system which has resonance frequencies significantly far from the water resonance and allows for selective imaging of specific target molecules. In this presentation we will discuss the basics of magnetization transfer through the lens of MTC, CEST, ParaCEST and explore specific applications of exchange-mediated contrast such as APT. We will cover biophysical aspects of the phenomenon, pulse sequences to exploit the contrasts of interest, basic analysis methods, and provide a few examples of how these techniques have been used in vivo. At the conclusion , the goal will be to have learned about exchange-mediated contrast, the strengths and weaknesses of each, sensitivity and specificity as well as rudimentary basics on sequence design and implementation.

Acknowledgements

No acknowledgement found.

References

No reference found.
Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)