Free Water in White Matter Differentiates MCI and AD From Control Subjects

Frontiers in Aging Neuroscience

Alzheimer's Disease Neuroimaging Initiative¹  Cici Bauer¹  Tarek A. Samad²  Maxime Descoteaux³  Zhiyong Xie³  James A. Goodman³  Felix C. Morency⁴  Matthieu Dumont⁴  Koene R. A. Van Dijk⁵  Maggie Roy⁶  Jean-Christophe Houde⁶  Pierre-Marc Jodoin⁷ 

[1] Translational Imaging, Early Clinical Development, Pfizer Inc., Cambridge, MA, United States;Department of Biostatistics and Data Science, The University of Texas Health Science Center at Houston, Houston, TX, United States;;Digital Medicine &Imeka Solutions, Inc., Sherbrooke, QC, Canada;Internal Medicine Research Unit, Pfizer Inc., Cambridge, MA, United States;Sherbrooke Connectivity Imaging Lab, University of Sherbrooke, Sherbrooke, QC, Canada;VITAlab, University of Sherbrooke, Sherbrooke, QC, Canada;

关键词: Alzheimer disease;    diffusion MRI;    free water;    neuroinflammation;    white matter hyper intensity;    mild cognitive impairment;   

DOI  :  10.3389/fnagi.2019.00270

来源: DOAJ

【 摘 要 】

Recent evidence shows that neuroinflammation plays a role in many neurological diseases including mild cognitive impairment (MCI) and Alzheimer's disease (AD), and that free water (FW) modeling from clinically acquired diffusion MRI (DTI-like acquisitions) can be sensitive to this phenomenon. This FW index measures the fraction of the diffusion signal explained by isotropically unconstrained water, as estimated from a bi-tensor model. In this study, we developed a simple but powerful whole-brain FW measure designed for easy translation to clinical settings and potential use as a priori outcome measure in clinical trials. These simple FW measures use a “safe” white matter (WM) mask without gray matter (GM)/CSF partial volume contamination (WMsafe) near ventricles and sulci. We investigated if FW inside the WMsafe mask, including and excluding areas of white matter damage such as white matter hyperintensities (WMHs) as shown on T2 FLAIR, computed across the whole white matter could be indicative of diagnostic grouping along the AD continuum. After careful quality control, 81 cognitively normal controls (NC), 103 subjects with MCI and 42 with AD were selected from the ADNIGO and ADNI2 databases. We show that MCI and AD have significantly higher FW measures even after removing all partial volume contamination. We also show, for the first time, that when WMHs are removed from the masks, the significant results are maintained, which demonstrates that the FW measures are not just a byproduct of WMHs. Our new and simple FW measures can be used to increase our understanding of the role of inflammation-associated edema in AD and may aid in the differentiation of healthy subjects from MCI and AD patients.

【 授权许可】

Unknown