Contrast enhanced X-ray computed tomography imaging of amyloid plaques in Alzheimer disease rat model on lab based micro CT system

Abstract

Amyloid plaques are small (~ 50 μm), highly-dense aggregates of amyloid beta (Aβ) protein in brain tissue, supposed to play a key role in pathogenesis of Alzheimer’s disease (AD). Plaques´ in vivo detection, spatial distribution and quantitative characterization could be an essential marker in diagnostics and evaluation of AD progress. However, current imaging methods in clinics possess substantial limits in sensitivity towards Aβ plaques to play a considerable role in AD screening. Contrast enhanced X-ray micro computed tomography (micro CT) is an emerging highly sensitive imaging technique capable of high resolution visualization of rodent brain. In this study we show the absorption based contrast enhanced X-ray micro CT imaging is viable method for detection and 3D analysis of Aβ plaques in transgenic rodent models of Alzheimer’s disease. Using iodine contrasted brain tissue isolated from the Tg-F344-AD rat model we show the micro CT imaging is capable of precise imaging of Aβ plaques, making possible to further analyze various aspects of their 3D spatial distribution and other properties.

Early Spatial Memory Impairment in a Double Transgenic Model of Alzheimer’s Disease TgF-344 AD

“…The rat model TgF-344 AD is built on a platform of Fisher-344 phenotype, by inserting the human mutated genes for amyloid precursor protein APP ("Swedish" mutation, APPsw) and ∆ exon 9 presenilin-1 PS1 ∆ E9AβPP [11]. The subjects show a formation of amyloid beta deposits, tangles of hyper-phosphorylated Tau, neurodegeneration and cognitive impairment [11][12][13][14].…”

X‐ray micro‐computed tomography in the assessment of penile cavernous fibrosis in a rabbit castration model

“…Our study is focused on ex vivo evaluation of tissues’ properties, as Xradia Versa 520 unit is not supposed for in vivo studies. There are micro‐CT systems designed for rat and mice studies, which inquire contrast‐enhanced 3D visualization structural changes of inner organs 45–47 . It should be noted that the capabilities of these systems for visualization in large magnification are several times lower than ex vivo micro‐CT systems, which results in less detailed 3D reconstruction.…”

High resolution micro-CT imaging in mice stroke models: from 3D detailed infarct characterization to automatic area segmentation

“…The staining of soft tissues with ionic contrast agents has been used for imaging in the micro-CT of brain 37 and whole-body 38 of zebra sh, as well as, rodent embryos, brains and other organs 29,28,38 . Some have even gone further, staining whole mice brains to identify/quantify electrode lesions 39 , tumours 40 , malformations 41 , disease pathology in Alzheimer's 42 and even single neurons 43 44 . Nevertheless, the use of these stains for the visualization and quanti cation of cerebrovascular alterations 45 and ischemic lesion 16,46,47,48 in whole mouse brains have rarely been described and never with great tissue/lesion contrast.…”

“…This is a particularly di cult task in the segmentation of speci c brain structures, due to the low contrast offered by different types of tissue and anatomical structures. Manual segmentation, where a skilled operator delineates the structures of interest by hand, is thus still popular in the segmentation of micro-CT images of the brain, due to its accuracy and low requirements 16,42 . However, it's major disadvantage is the high time-cost, which poses a signi cant bottleneck in the whole analysis pipeline.…”