Sensitivity of unconstrained quantitative magnetization transfer MRI to amyloid burden in preclinical Alzheimer’s disease

Abstract

Magnetization transfer MRI is sensitive to semi-solid macromolecules, including amyloid beta, and has previously been used to discriminate Alzheimer’s disease (AD) patients from controls. Here, we fit an unconstrained 2-pool quantitative MT (qMT) model, i.e., without constraints on the longitudinal relaxation rate R1S of semi-solids, and investigate the sensitivity of the estimated parameters to amyloid accumulation in preclinical participants. We scanned 15 cognitively normal volunteers, of which 9 were amyloid positive by [18F]Florbetaben PET. A 12 min hybrid-state qMT scan with an effective resolution of 1.24 mm isotropic and whole-brain coverage was acquired to estimate the unconstrained 2-pool qMT parameters. Group comparisons and correlations with Florbetaben PET standardized uptake value ratios were analyzed at the lobar level. We find that the exchange rate and semi-solid pool’s R1S were sensitive to the amyloid concentration, while morphometric measures of cortical thickness derived from structural MRI were not. Changes in the exchange rate are consistent with previous reports in clinical AD, while changes in R1S have not been reported previously as its value is typically constrained in the literature. Our results demonstrate that qMT MRI may be a promising surrogate marker of amyloid beta without the need for contrast agents or radiotracers.