• Veraart, Jelle
• Hopkins, William D.
• Akers, Carolyn
• Szabo, Jakub
• Goldman, Hannah
• Genovese, Thomas S.
• Rusinek, Henry
• Llanos, Michael
• Murray, Sean
• Gray, Stanton B.
• Wisniewski, Thomas
• Zaimwadghiri, Youssef
• Scholtzova, Henrieta

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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) <jats:italic>in vivo</jats:italic> regional quantitative R2* alterations to track age‐related changes in neuropathology and 2) <jats:italic>ex vivo</jats:italic> diffusion‐weighted (DWI) MRI metrics to visualize changes in brain microstructure. We recently extended our analyses to <jats:italic>in vivo</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Young and geriatric female SQMs underwent 2D T<jats:sub>2</jats:sub>‐weighted (T<jats:sub>2</jats:sub>‐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 <jats:italic>in vivo</jats:italic> multi‐gradient echo (MGE) scans to generate R2* maps for ROI‐based quantitative assessments of SQM neuropathology.</jats:p></jats:sec><jats:sec><jats:title>Result</jats:title><jats:p>We identified multiple instances of asymmetric hyperintensities (ARIA‐E) in geriatric SQMs using 2D T<jats:sub>2</jats:sub>‐w TSE RARE, FLAIR, and DWI MRI sequences <jats:italic>in vivo</jats:italic>. 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>We safely monitored age‐dependent changes in neuroimaging parameters derived from diffusion‐weighted, T<jats:sub>2</jats:sub>‐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.</jats:p></jats:sec>

Topics

• microstructure
• molecular dynamics
• iron
• aging
• size-exclusion chromatography
• diffusivity
• aging
• quantitative determination method