During this presentation, I will discuss some of the difficulties of clinical translation of CEST MRI, highlight the similarities and differences between endogenous and exogenous CEST MRI methods, and outline some of the principle applications of these methods in pre-clinical and clinical settings. Examples of such applications include: (1) pH imaging in ischaemic stroke using endogenous amide proton transfer, (2) pH imaging in cancer using exogenous diaCEST and paraCEST agents, (3) endogenous metabolite concentration imaging (e.g. GluCEST, GagCEST, GlycoCEST), and (4) glucose uptake and perfusion imaging using GlucoCEST.
Target Audience
This presentation will benefit researchers interested in using CEST MRI in pre-clinical and clinical applications.Outcome/Objectives
After this presentation, attendees should be able to:
Purpose
This presentation will describe the various applications of CEST MRI methods to the study of pre-clinical and clinical research questions.Introduction
CEST MRI is a contrast mechanism that relies upon the chemical exchange of labile protons on solute molecules with solvent water protons to generate signal through saturation transfer [1, 2, 3, 4, 5]. By effectively amplifying the signal from solute molecules through this saturation transfer, it is a powerful technique to measure various biophysical or clinical properties of interest, including tissue pH [6, 7, 8], metabolite concentration [9], and tumour grade [10].Endogenous vs. Exogenous CEST MRI
Many flavours of CEST MRI have been developed and studied, and can be broadly categorised as either imaging endogenous or exogenous compounds [2]. Examples of endogenous CEST MRI modalities include amide proton transfer (APT) [6, 7, 8], glucoCEST [11, 12], gagCEST [13, 14], glycoCEST [15, 16], and gluCEST [17 – 21], amongst many others. APT has been developed as a method for measuring tissue pH in ischaemic stroke [6, 7, 8], or protein concentration and tumour grade in cancer [10]. GlucoCEST studies have shown increases in glucose uptake that correspond well to FDG-PET measurements of tumour metabolism [11], and dynamic imaging of glucose whilst it is infused in patients shows contrast similar to DCE-MRI measurements of tumour perfusion [12]. GagCEST has been used to image glycosaminoglycans in human knee cartilage [13, 14], and glycoCEST used to image glycogen metabolism in the liver [15, 16]. GluCEST for measurement of the neurotransmitter glutamate has seen wide application in studying psychosis [18], neuroinflammation [19], and Alzheimer’s and Huntington’s diseases [20, 21].
Exogenous CEST agents are usually further subcategorised according to whether they are diamagnetic (diaCEST) or paramagnetic (paraCEST) [2, 22]. Accurate design and clinical translation of diaCEST and paraCEST probes is challenging, but promises great clinical benefit. One such diaCEST method is to use iodinated contrast agents that are clinically approved for CT imaging for tumour extracellular pH measurements (acidoCEST) [23]. This method has been demonstrated in pre-clinical models of breast cancer, but clinical translation remains a challenge [24].
Pre-clinical vs. Clinical CEST MRI
Whilst the number of CEST MRI applications in the pre-clinical literature has increased since its development, it has yet to become routinely used in clinical practice. One challenge that hinders such clinical translation is in relation to the CEST MRI acquisition methods themselves (i.e. whether the CEST MRI pulse sequence uses pulsed or continuous wave RF saturation to label labile protons). Clinical hardware and SAR considerations often prevent continuous wave implementations of CEST MRI, which are more often used pre-clinically [25]. This difference also affects analysis and quantification of the CEST MRI data, which is dependent on the acquisition method employed [5]. Finally, many pre-clinical CEST MRI methods are developed using high B0 field strength systems, and the chemical exchange characteristics of some molecules may make it difficult to translate these methods to clinical field strengths.Summary
During this presentation, I will discuss some of the difficulties of clinical translation of CEST MRI, highlight the similarities and differences between endogenous and exogenous CEST MRI methods, and outline some of the principle applications of these methods in pre-clinical and clinical settings. Examples of such applications include:
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