Neurite density and free water concentration are associated with synaptic density in the hippocampus as assessed through NODDI and [C‐11]UCB‐J PET

Abstract

AbstractBackgroundNeurite Orientation Dispersion and Density Imaging (NODDI), derived through multi‐shell diffusion MRI, allows for the estimation of markers pertaining to multiple distinct components of neural tissue microstructure. Lower neurite density index (NDI), lower orientation dispersion index (ODI), and higher volume fraction of isotropic water (Viso), have all been significantly associated with biomarkers of AD pathology, as well as increase diagnostic model predictability. Recent studies employing [C‐11]UCB‐J PET to study synaptic vesicle glycoprotein 2A (SV2A) have found strong reductions in individuals with AD. Here we explore regional associations between cortical tissue microstructure (indexed by NODDI) and synaptic density (measured through [C‐11]UCB‐J PET). We hypothesize that increased NDI and ODI, and decreased Viso will associate with higher [C‐11]UCB‐J binding.MethodParticipants (N=24) included cognitively unimpaired and impaired older adults (Table 1) from the Wisconsin Alzheimer’s Disease Research Center who underwent [C‐11]UCB‐J PET and multi‐shell diffusion MRI. NODDI measures (including NDI, ODI, and Viso) were estimated and [11‐C]UCB‐J binding was quantified by calculating distribution volume ratios (DVR) using SRTM2 with the whole cerebellum as a reference region. Pearson correlations were conducted within Desikan‐Killiany‐derived regions of interest (ROI) including the hippocampus, entorhinal cortex, and parahippocampal gyrus, regions previously associated with altered NODDI metrics and [C‐11]UCB‐J binding in the AD population.ResultSignificant associations were found between [C‐11]UCB‐J DVR and both NDI and Viso in the hippocampus (NDI: r = 0.45, p=0.047; Viso: r = ‐0.46, p = 0.043). A trend was identified between [C‐11]UCB‐J DVR and ODI in the parahippocampus (r = 0.39, p = 0.098). No significant associations or trends were found in the entorhinal cortex.ConclusionThis preliminary analysis identified associations between increased synaptic density and metrics of cortical tissue microstructure. Both NDI and Viso were correlated with [C‐11]UCB‐J DVR in the hippocampus, indicating dendritic complexity and synaptic density are possibly linked. Future analyses will include more participants, determine whether hippocampal [C‐11]UCB‐J DVR in addition to NODDI may increase diagnostic model predictability, as well as estimate the temporal progression of synaptic and dendritic loss in AD.