Keywords: CEST / APT / NOE, CEST & MT, Multiple Sclerosis; CEST enhancement; Dex-Cest
Motivation: Dextrans (Dex) -based CEST MRI allows evaluating vascular permeability in the macromolecular size range. However, its signal intensity, similar to most CEST agents, is pH-dependent, which complicates in vivo quantification.
Goal(s): To develop a dextran CEST agent that is less pH sensitive for this application.
Approach: Chemically modified Dex (CM-Dex) has negatively charged carboxylate groups that can retard the exchange rate of OH protons to decrease pH effects.
Results: CM-Dex has a relatively consistent CEST signal across a pH range of 6 to 7.4 and is feasible for detecting blood-brain barrier (BBB) leakage in a mouse model of multiple sclerosis (MS).
Impact: The development of a second-generation dextran-based CEST agent with a more extended pH range of stable MRI signal to facilitate quantitative measurements of vascular permeability in vivo for applications wherein intra- and inter-individual pH can vary.
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