Work

IC‐P‐134: Neurite orientation dispersion and density imaging (NODDI) in young‐onset Alzheimer's disease and its syndromic variants

Year: 2015

Type: article

Abstract: Neurite orientation dispersion and density imaging (NODDI) is a novel MRI technique that provides more anatomically specific microstructural metrics of white matter damage than standard diffusion tensor imaging (DTI). In this study we aimed to compare neurite density index (NDI) using NODDI and DTI measures of fractional anisotropy (FA) in a cohort of patients with young onset Alzheimer's disease (YOAD). We also performed a preliminary exploratory comparison of the microstructural white matter signatures associated with the posterior cortical atrophy (PCA) and amnestic AD phenotypes. Twenty-six patients with YOAD (age: 61.0±5.5yrs, 33% male, age at symptom-onset 55.0±4.3yrs) and 19 controls (age=61.0±6.0yrs, 45% male), were imaged on the same 3T Siemens Trio scanner using a three-shell diffusion sequence optimised for NODDI (64, 32, and 8 diffusion-weighted directions at b=2000, 700 and 300 s/mm; 14 b=0 images; 55 slices; voxel size 2.5x2.5x2.5 mm; TR/TE=7000/92 ms; TA=15 mins). Images were corrected for motion and eddy-current distortion, NODDI parameters were estimated using NODDI Matlab toolbox, and FA estimated using Camino. Diffusion metrics were spatially normalized to the population-specific DTI template using DTI-TK. Tract-Based Spatial Statistics was used to detect group differences in FA and NDI, co-varying for age and gender (5000 permutations corrected for multiple comparisons with Threshold-Free Cluster Enhancement p<0.01). In a secondary, exploratory analysis we assessed NDI and FA in cohorts of PCA (n=7) and amnestic AD (n=7) versus controls. Compared to standard FA metrics, NDI revealed more widespread white matter damage in the YOAD group (n=26). Within the patient cohort, PCA and typical AD subgroups had strikingly different patterns of decreased neurite density which in both cases broadly mirrored the FA changes but were more extensive. In PCA diffusion changes were localised to the right parieto-occipital region with very widespread changes seen in amnestic AD (figure 1). Fractional anisotropy (FA) and neurite density index (NDI) differences between YOAD patients and controls (red) shown on the group specific tensor template (green). Images corrected for multiple comparisons, p<0.01 (p<0.05 for FA in controls > PCA). NODDI measures of neurite density provide additional and complementary information compared to standard diffusion metrics. NODDI imaging reveals widespread disruption to white matter architecture in AD and differential patterns of neurite loss in AD syndromic variants. NODDI is a powerful tool to investigate neuronal integrity in neurodegenerative diseases.

Source: Alzheimer s & Dementia

DOI: 10.1016/j.jalz.2015.06.156