Dextran CEST MRI Agents for Quantitative Assessment of BBB Leakage in the Macromolecular Size Range.

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.