Proton Chemical Exchange Saturation Transfer (CEST) MRS and MRI

Abstract

Proton magnetic resonance spectroscopy ( 1 H MRS) of biological systems has higher specificity than MRI because resonances of multiple metabolites can be distinguished, reflecting chemistry and physiology in situ. Unfortunately, this approach has very low sensitivity as the metabolites are typically at millimolar concentrations compared to the molar signal strength of water-based MRI. As a consequence, even though 1 H MRS is a powerful and common research tool, its inroad into daily clinical practice has been limited. Until very recently, 1 H MRS applications have focused on the resonances upfield (i.e., at lower frequency) of the water resonance. This article deals with protons that are generally not observed in a typical water-suppressed spectrum, namely, the exchangeable protons found predominantly downfield from water. These can usually be detected by MRS only if the transfer of water proton saturation (established during water suppression) is not a confounding factor, or by using water exchange (WEX) spectroscopy, in which RF labeling of the water protons is transferred to the exchangeable protons and subsequently detected. More importantly, it has recently become clear that the presence of such exchangeable protons on low concentration solute molecules can be detected via the water signal by RF labeling of these protons and subsequent transfer of this label to water protons. This process, leading to saturation of the water signal and enhancement of the effect through repeated exchange, can be used for the imaging of metabolite signals or exchangeable-proton-based contrast agents with enhanced sensitivity. This has given rise to the field of chemical exchange saturation transfer (CEST) MRI, which has greatly increased the potential for translating spectroscopic methods to the clinic. Examples include the measurement of pH, temperature, and enzyme activity as well as detection of cellular metabolites, ions, and proteins and peptides. In addition, bio-organic compounds can now be used for contrast agents, cell and nanoparticle labeling, and reporter genes.

d‐glucose weighted chemical exchange saturation transfer (glucoCEST)‐based dynamic glucose enhanced (DGE) MRI at 3T: early experience in healthy volunteers and brain tumor patients

“…Following infusion of d-glucose, dynamic glucose enhanced (DGE) imaging has allowed the detection of MRI signal changes in animals 8 and in humans, [9][10][11][12][13] showing potential for the use of this readily available sugar to study tissue perfusion parameters such as blood volume and blood-brain barrier (BBB) permeability. These DGE experiments have used either the chemical exchange saturation transfer (CEST) approach, [14][15][16][17][18] called glucoCEST, 1,2 or T 1ρ -based MRI signal changes. 11,12,[19][20][21][22] To date, glucoCEST work has been limited to higher field strengths (7T and up) and single-slice acquisitions.…”

Characterization of tumor vascular permeability using natural dextrans and CEST MRI

“…However, clinical translation of these macromolecular complexes is often impeded by safety concerns related to their slow excretion and possible tissue accumulation, with the potential risk of release of toxic Gd(III) ions (20,21). In the present study, to achieve a high clinical translatability, we sought to develop nano-sized dextrans for MR imaging using their hydroxyl groups as a natural "magnetic label" for chemical exchange saturation transfer (CEST) MRI (22)(23)(24)(25)(26)(27).…”

Salicylic Acid‐Based Polymeric Contrast Agents for Molecular Magnetic Resonance Imaging of Prostate Cancer

“…[3] The specificity of CEST agents is improved over relaxation based agents because of the dependence of CEST on labeling frequency. [3–4] Furthermore, diamagnetic organic compounds, which are termed diaCEST agents, can be employed to generate contrast instead of paramagnetic metals, avoiding potential toxicity of the latter. We and others have developed salicylic acid and its analogs as diaCEST agents leveraging the far downfield chemical shift of the exchangeable proton, which allows for superior specificity of detection.…”