Alzheimer's Imaging Consortium.

Area of Science:

• Neuroimaging
• Radiology
• Neurology

Background:

• Amyloid-related imaging abnormalities (ARIA-E) are a significant risk of anti-amyloid therapy (AAT).
• Current FLAIR MRI monitoring may be enhanced by novel contrast mechanisms for improved detection and mechanistic understanding.
• Investigating perivascular spaces, microstructural alterations, and water permeability using advanced MRI techniques in AAT patients.

Purpose of the Study:

• To investigate perivascular spaces, microstructural alterations, and parenchymal water permeability in patients receiving AAT.
• To assess the utility of novel MRI techniques for detecting and understanding ARIA-E.
• To explore potential MRI-based predictors of ARIA risk.

Main Methods:

• Eight participants receiving AAT underwent advanced imaging (multi-shell diffusion MRI, ultralong TE T2-weighted, T2-saturation water-exchange) alongside clinical MRIs.
• Sequences added <15 minutes to clinical 3T MRI protocols.
• Microstructure and water exchange were measured in relevant ROIs, including those that developed ARIA.

Main Results:

• Two patients developed ARIA-E, with distinct clinical trajectories.
• Patients who developed ARIA showed lower baseline NDI/ODI and transient increases at 2 months, contrasting with ARIA- patients.
• Increased water exchange and white matter FWF were observed in ARIA patients, with ARIA-E/H visualized on water exchange maps.

Conclusions:

• Water diffusion and exchange measures enhance understanding of ARIA, suggesting transient cellularity increases and prolonged water permeability.
• Findings indicate that microstructural changes may predict future ARIA risk.
• Ongoing data collection aims to further validate these novel MRI techniques for ARIA assessment.