Revealing the 3D anatomy of healthy and diseased murine brain tissue with contrast-enhanced computed tomography

The human brain is the nervous system's command center enabling thoughts, memory, movements and emotions, and it is considered as the most complex system in the animal kingdom. Even though many studies have focused on this subject, the brain's functioning and particularly its structure-function relationship is still not fully understood. Alzheimer’s disease, the most common cause of dementia also necessitates a much better understanding of its underlying mechanism. Even if the etiology of Alzheimer's disease remains unclear, its hallmarks include the presence of amyloid plaques and neurofibrillary tangles in the brain. Advancements in imaging techniques for visualizing brain tissue are therefore crucial for a better understanding of the functioning of healthy and diseased brains. Until recently, brain analyses were only available in two formats: high-resolution 2D images (conventional 2D histology) or lower resolution 3D images (MRI or PET). The aim of this master thesis is to demonstrate the ability of the CECT technique to visualize brain tissue in high-resolution and in 3D. First, we analyzed the diffusion behavior of three CESAs (Hexabrix, CA4+, and Preyssler anion) in healthy murine brain hemispheres. Simultaneously, the staining properties of these molecules, to visualize the anatomical structures, were assessed. Next, we performed a proof-of-concept study to visualize amyloid plaques. The results indicated that the staining had reached a plateau after four days for all three CESAs, but at different diffusion speed. Each CESA enabled the visualization of different anatomical structures. 3D structural analysis could be performed for some anatomical features showing the added value of CECT compared to 2D techniques. Regarding the proof-of-concept study on the visualization of amyloid plaques, it showed that the plaques were visible with Hexabrix but with limited contrast, preventing automatic analysis or segmentation to be performed. To conclude, CECT is a promising technique for future 3D high-resolution studies on brain tissue. Further research is required, specifically to optimize the scan parameters as well as to develop CESAs which will allow a better visualization of the anatomical structures of interest and the amyloid plaques.