Abstract TMP109: Loss of Gray-White Contrast in Cerebral Amyloid Angiopathy: An in-vivo and Ex-Vivo Exploratory Approach

Abstract

Background/Purpose: Cerebral Amyloid Angiopathy (CAA) is associated with cortical and white matter atrophy. We hypothesized that changes in neural tissue signal properties could reflect microstructural alterations in diffusion, and hence demyelination. Methods: Two cohorts of non-demented CAA patients were examined (3T: 45 CAA patients vs 16 age-matched Healthy Controls [HC]; 1.5T: 66 CAA patients vs 18 matched HC), and dichotomized into moderate (3T: n=19; 1.5T: n=24) and severe CAA. FreeSurfer was employed to calculate gray and white (GW) matter signal intensities from a T1-weighted sequence, and their ratio was used to assess GW contrast. Two diffusion markers (fractional anisotropy [FA]; apparent diffusion coefficient [ADC]) were measured via Diffusion Weighted Imaging. In addition, brains of 13 deceased patients with CAA were scanned ex-vivo, sectioned, and stained using Luxol Fast Blue, to assess myelin content. GW ratio was calculated the same way as in the in-vivo cohorts. Results: CAA patients displayed loss of GW contrast, expressed by increased GW intensity ratio (3T: 0.802±0.01; 1.5T: 0.757±0.02), when compared to HC (3T: 0.789±0.01,p=0.003; 1.5T: 0.738±0.01,p<0.0001). Patients with severe CAA showcased even lower GW contrast (3T: 0.806±0.01; 1.5T: 0.763±0.02) than patients with moderate CAA (3T: 0.797±0.01,p<0.05; 1.5T: 0.745±0.02,p<0.05) [ Fig ]. Moreover, loss of GW contrast within CAA correlated with lower FA (r=-0.30,p=0.049) and increased ADC (r=0.52,p<0.0001). Within the ex-vivo CAA cohort, loss of GW contrast was highly linked to a decrease in underlying myelin concentration (p=0.0025). Conclusions: CAA patients consistently displayed lower GW contrast compared to HC. This loss of contrast became more pronounced with increased disease severity, and correlated with lower anisotropy and increased water diffusivity. Indeed, an ex-vivo CAA cohort revealed that loss of GW contrast corresponded to a decrease in myelin concentration.