Learnings and Recommendations for Performing Multi-Center Clinical Drug Trials with Resting State Functional MRI in Alzheimer Patient Population: Data Processing Pipelines and Functional Connectivity Metrics

Alexandre Coimbra¹, Farshid Faraji², Alex De Crespigny¹, David Clayton²

In single-site studies, brain functional connectivity metrics (FCMs) measured by resting-state functional MRI (rs-fMRI) have been reported to be sensitive to Alzheimer Disease (AD, [1]), beta-amyloid burden [2], and therapeutic effect [3]. Exploratory RS-fMRI was included in two global Phase II studies of a novel AD amyloid drug. We studied different types of data processing pipelines and FCMs make recommendations based on ensuing FCMs test-retest performance and ability to differentiate cohorts scanned at 1.5T vs. 3T magnets. A discussion on FCMs and statistical power to detect changes due to disease progression and/or therapeutic effect is also provided.