Free water derived by multi-shell diffusion MRI reflects tau/neuroinflammatory pathology in Alzheimer's disease.

Introduction: Free-water (FW) imaging, a new analysis method for diffusion magnetic resonance imaging (MRI), can indicate neuroinflammation and degeneration. We evaluated FW in Alzheimer's disease (AD) using tau/inflammatory and amyloid positron emission tomography (PET).

Methods: Seventy-one participants underwent multi-shell diffusion MRI, F-THK5351 PET, C-Pittsburgh compound B PET, and neuropsychological assessments. They were categorized into two groups: healthy controls (HCs) ( = 40) and AD-spectrum group (AD-S) ( = 31) using the Centiloid scale with amyloid PET and cognitive function. We analyzed group comparisons in FW and PET, correlations between FW and PET, and correlation analysis with neuropsychological scores.

Results: In AD-S group, there was a significant positive correlation between FW and F-THK5351 in the temporal lobes. In addition, there were negative correlations between FW and cognitive function in the temporal lobe and cingulate gyrus, and negative correlations between F-THK5351 and cognitive function in the same regions.

Discussion: FW imaging could be a biomarker for tau in AD alongside clinical correlations.