Development of neuroimaging biomarkers in non‐human primate model of sporadic Alzheimer’s disease pathology
Year: 2023
Type: article
Abstract: Background Squirrel monkeys (SQMs) are a non‐human primate (NHP) model of Alzheimer’s disease (AD) pathology with extensive cerebral amyloid angiopathy (CAA). Our work characterizes neuroimaging biomarkers associated with aging and neurodegeneration. Previously, we demonstrated the sensitivity of 1) in vivo regional quantitative R2* alterations to track age‐related changes in neuropathology and 2) ex vivo diffusion‐weighted (DWI) MRI metrics to visualize changes in brain microstructure. We recently extended our analyses to in vivo multi‐shell diffusion metrics for detection and classification of amyloid‐related imaging abnormalities (ARIA), which have been linked to parenchymal vasogenic edema and sulcal effusions. To further facilitate quantitative analysis of MR markers (diffusion and R2*) we have built a novel pipeline for atlas‐based region‐of‐interest (ROI) segmentation using a SQM brain atlas modified from Schilling et al. (2017). Here we evaluate age‐related changes in R2* values and region‐specific volume using this automated workflow. Method Young and geriatric female SQMs underwent 2D T2‐weighted (T2‐w) Turbo Spin Echo (TSE) RARE and FLAIR MRI scans, in addition to multi‐shell DWI acquisitions. DTI and DKI metrics were derived from DWI datasets, including mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA). We utilized in vivo multi‐gradient echo (MGE) scans to generate R2* maps for ROI‐based quantitative assessments of SQM neuropathology. Result We identified multiple instances of asymmetric hyperintensities (ARIA‐E) in geriatric SQMs using 2D T2‐w TSE RARE, FLAIR, and DWI MRI sequences in vivo. While RARE and FLAIR scans demonstrated abnormalities in SQM brains, diffusion metrics MD and MK revealed greater propagation of the lesions through WM tracks. Histological analyses of the underlying neuropathology (e.g. myelin, neuroglia, and amyloid burden) are underway. Significant increases in R2* values with age were observed in all defined cortical regions, with subsequent histological confirmation of severe CAA, microhemorrhages, and iron deposits. Preliminary volumetric measurements revealed significant decreases with age in the prefrontal cortex. Additional morphometric analyses are ongoing. Conclusion We safely monitored age‐dependent changes in neuroimaging parameters derived from diffusion‐weighted, T2‐w TSE RARE, and FLAIR acquisitions. Our study highlights the utility of the SQM model to uncover potential long‐term consequences of ARIA and validates diffusion MRI methodologies to target brain integrity.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.079140
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4390200196