Sensitivity of unconstrained quantitative magnetization transfer MRI to amyloid burden in preclinical Alzheimer's...

Area of Science:

• Neuroimaging
• Biomarker Development
• Alzheimer's Disease Research

Background:

• Magnetization transfer (MT) MRI is sensitive to macromolecules like amyloid beta.
• Previous studies used MT MRI to differentiate Alzheimer's disease (AD) patients from controls.
• Amyloid beta accumulation is an early pathological hallmark of AD.

Purpose of the Study:

• To investigate the sensitivity of unconstrained quantitative MT (qMT) model parameters to amyloid accumulation in preclinical participants.
• To assess if qMT MRI can serve as a biomarker for amyloid beta without contrast agents or radiotracers.

Main Methods:

• Fitted an unconstrained 2-pool quantitative MT (qMT) model to MRI data.
• Scanned 15 cognitively normal volunteers (9 amyloid-positive by [18F]florbetaben PET).
• Acquired a 12-minute hybrid-state qMT scan for whole-brain parameter estimation.

Main Results:

• The exchange rate and semisolid pool's longitudinal relaxation rate ($R_1^{\text{s}}$) were sensitive to amyloid concentration.
• Morphometric measures of cortical thickness were not sensitive to amyloid levels.
• Changes in exchange rate align with prior clinical AD findings; changes in $R_1^{\text{s}}$ are novel.

Conclusions:

• Unconstrained qMT MRI parameters, particularly exchange rate and $R_1^{\text{s}}$, are sensitive to preclinical amyloid accumulation.
• qMT MRI shows potential as a non-invasive biomarker for amyloid beta.
• This technique may reduce reliance on radiotracers or contrast agents for AD biomarker detection.