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

## TL;DR

This study shows that a type of MRI called qMT can detect amyloid buildup in the brain, a sign of early Alzheimer’s disease, without using radioactive tracers.

## Contribution

The study introduces an unconstrained qMT model to detect amyloid accumulation in preclinical Alzheimer’s disease.

## Key findings

- Exchange rate and semisolid R1s parameters were sensitive to amyloid concentration.
- Cortical thickness measures from MRI were not sensitive to amyloid levels.
- Changes in R1s were previously unreported due to common constraints in the literature.

## Abstract

Magnetization transfer MRI is sensitive to semisolid macromolecules, includingamyloid beta, and has previously been used to discriminate Alzheimer’sdisease (AD) patients from controls. Here, we fit an unconstrained 2-poolquantitative MT (qMT) model, that is, without constraints on the longitudinalrelaxation rateR1sof semisolids, and investigate the sensitivity of the estimated parameters toamyloid accumulation in preclinical participants. We scanned 15 cognitivelynormal volunteers, of which 9 were amyloid positive by[18F]florbetaben PET. A 12 min hybrid-state qMT scan with aneffective resolution of 1.24 mm isotropic and whole-brain coverage was acquiredto estimate the unconstrained 2-pool qMT parameters. Group comparisons andcorrelations with florbetaben PET standardized uptake value ratios were analyzedat the lobar level. We find that the exchange rate and semisolid pool’sR1swere sensitive to the amyloid concentration, while morphometric measures ofcortical thickness derived from structural MRI were not. Changes in the exchangerate are consistent with previous reports in clinical AD, while changes inR1shave not been reported previously as its value is typically constrained in theliterature. Our results demonstrate that qMT MRI may be a promising surrogatemarker of amyloid beta without the need for contrast agents or radiotracers.