Brain virtual histology with X-ray phase-contrast tomography Part II: 3D morphologies of amyloid-$β$ plaques in Alzheimer's disease models

Abstract

While numerous transgenic mouse strains have been produced to model the formation of amyloid-$β$ (A$β$) plaques in the brain, efficient methods for whole-brain 3D analysis of A$β$ deposits have to be validated and standardized. Moreover, routine immunohistochemistry performed on brain slices precludes any shape analysis of A$β$ plaques, or require complex procedures for serial acquisition and reconstruction. The present study shows how in-line (propagation-based) X-ray phase-contrast tomography (XPCT) combined with ethanol-induced brain sample dehydration enables hippocampus-wide detection and morphometric analysis of A$β$ plaques. Performed in three distinct Alzheimer mouse strains, the proposed workflow identified differences in signal intensity and 3D shape parameters: 3xTg displayed a different type of A$β$ plaques, with a larger volume and area, greater elongation, flatness and mean breadth, and more intense average signal than J20 and APP/PS1. As a label-free non-destructive technique, XPCT can be combined with standard immunohistochemistry. XPCT virtual histology could thus become instrumental in quantifying the 3D spreading and the morphological impact of seeding when studying prion-like properties of A$β$ aggregates in animal models of Alzheimer’s disease. This is Part II of a series of two articles reporting the value of in-line XPCT for virtual histology of the brain; Part I shows how in-line XPCT enables 3D myelin mapping in the whole rodent brain and in human autopsy brain tissue.

Ignacio Arganda-Carreras

Ikerbasque Research Associate Professor

My research interests include image processing, computer vision, and deep learning for biomedical applications.