Free Water MR Imaging of White Matter Microstructural Changes is a Sensitive Marker of Amyloid Positivity in Alzheimer's Disease

Background Extracellular free water (FW) resulting from white matter degeneration limits the sensitivity of diffusion tensor imaging (DTI) in predicting Alzheimer's disease (AD). Purpose To evaluate the sensitivity of FW‐DTI in detecting white matter microstructural changes in AD. To validate the effectiveness of FW‐DTI indices to predict amyloid‐beta (Aβ) positivity in mild cognitive impairment (MCI) subtypes. Study Type Retrospective. Population Thirty‐eight Aβ‐negative cognitively healthy (CH) controls (68.74 ± 8.28 years old, 55% female), 15 Aβ‐negative MCI patients (MCI‐n) (68.87 ± 8.83 years old, 60% female), 29 Aβ‐positive MCI patients (MCI‐p) (73.03 ± 7.05 years old, 52% female), and 29 Aβ‐positive AD patients (72.93 ± 9.11 years old, 55% female). Field Strength/Sequence 3.0T; DTI, T1‐weighted, T2‐weighted, T2 star‐weighted angiography, and Aβ PET (18F‐florbetaben or 11C‐PIB). Assessment FW‐corrected and standard diffusion indices were analyzed using trace‐based spatial statistics. Area under the curve (AUC) in distinguishing MCI subtypes were compared using support vector machine (SVM). Statistical Tests Chi‐squared test, one‐way analysis of covariance, general linear regression analyses, nonparametric permutation tests, partial Pearson's correlation, receiver operating characteristic curve analysis, and linear SVM. A P value