Alzheimer's Imaging Consortium.

Area of Science:

• Neuroimaging
• Advanced MRI techniques
• Neuroinflammation research

Background:

• Amyloid-Related Imaging Abnormalities (ARIA), encompassing vasogenic edema (ARIA-E) and hemorrhagic lesions (ARIA-H), pose challenges in monoclonal antibody (mAb) therapy for Alzheimer's Disease (AD).
• The underlying mechanisms of ARIA, particularly neuroinflammation, are not well understood.
• Advanced imaging methods like generalized diffusion basis spectrum imaging (g-DBSI) are essential for investigating these processes.

Purpose of the Study:

• To utilize g-DBSI to explore microstructural alterations linked to neuroinflammation and vasogenic edema during the development and resolution of ARIA-E in patients receiving mAb treatment.
• To assess the potential of g-DBSI in detecting early signs of ARIA-E and monitoring its progression.

Main Methods:

• A pilot study involving three participants receiving Gantenerumab in the DIAN-TU-001 trial, with longitudinal g-DBSI scans.
• ARIA assessment by a neuroradiology panel using FDA guidelines and structured reporting.
• Quantification of g-DBSI-derived restricted ratio (RR) as a marker for inflammation and hindered ratio (HR) for vasogenic edema within ARIA-E regions.

Main Results:

• Participant 1 showed elevated RR and HR one month prior to ARIA-E onset.
• Participant 2 exhibited elevated RR and HR during ARIA-E onset, with significant decreases at two-year follow-up.
• Participant 3 displayed stable RR and HR between 1- and 2-year follow-ups post-ARIA-E resolution.

Conclusions:

• Findings suggest a role for neuroinflammation in ARIA-E progression.
• g-DBSI demonstrates potential for detecting microstructural changes preceding ARIA-E onset.
• g-DBSI may serve as a noninvasive tool for monitoring ARIA progression and understanding neuroinflammation and edema, warranting further investigation in larger cohorts.