Revealing the murine brain anatomy by contrast-enhanced computed tomography – a screening study
(2022) 6th Symposium on X-ray Computed Tomography — Location: Kasteelpark Arenberg 10, 3001 Leuven (24.May.2022)
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- Authors
Hoffmann, Delia 
- Abstract
- The brain is a complex organ, which allows species to think, remember, feel and move. Notwithstanding the interest of the scientific community in this organ, many unknowns are still to be solved, such as the structure-function relationship that allows the brain to perform its daily tasks. Today, the main hypothesis is that the anatomical architecture influences, but not fully determines, the dynamics of the neural network. Advanced high-resolution 3D imaging techniques could allow researchers to better visualize the structure of the brain and hence better understand how the structure influences the functioning of the brain. Conventional 2D histology is currently still the gold standard for ex vivo structural assessment of the brain, since it provides high discriminative power, subcellular resolution and the methodologies are well-established. Nevertheless, it lacks in 3D information, is destructive and laborious. Therefore, a novel complementary 3D histological technique, contrast-enhanced microfocus computed tomography (CECT), has been introduced that combines the discriminative power of conventional 2D histology, with the 3D, non-destructive properties of CT. Multiple contrast-enhancing staining agents (CESAs) have been explored for brain CECT, including organic (e.g. Iodixanol) and inorganic (e.g. Lugol’s iodine solution). However, a lack of information exists on the nature of their interactions with different constituents of the brain. In order to provide insights in the choice of CESA for certain applications, we investigated four different CESAs. In this screening study, Hexabrix, CA4+, Preyssler anion and the 1:2 hafnium substituted Wells-Dawson polyoxometalate (Hf-WD 1:2 POM) have been evaluated as CESAs for the imaging of healthy murine hemispheres with CECT. These molecules differ in terms of chemical properties (e.g. charge, size, molecular weight) and heavy atom (Iodine vs Tungsten), which will impact staining specificity, diffusion and attenuation properties. First, the staining specificity of the CESAs was evaluated by determining where they accumulate in the tissue. For this purpose, we compared the CECT images with conventional 2D histological sections and textbook images of the murine brain. Differences in staining specificity were observed for all four CESAs, which highlight that any change in chemical properties alters specificity. Then, a quantitative analysis was performed to determine how the CESAs diffuse through the brain and whether the CESA accumulation in the brain induces tissue shrinkage or swelling (Fig. 1). Results show that next to the size of the molecules, the interactions that occur also play an important role in the diffusion speed of the molecule through the tissue. Finally, we explored the added value of obtaining 3D images by segmentation of certain structures followed by quantitative analysis To conclude, we introduced four CESAs, new to the field of brain CECT imaging, that all exhibit distinct profiles in terms of specificity and speed of diffusion. In future experiments, we envision the use of one or multiple of these CESAs in the study of a pathology with CECT.
- Affiliations
KUL Department of Chemistry, Molecular Design & Synthesis
Citations
Tim Balcaen, Catherine Piens, Hoffmann, D., Fabien Chauveau, Wim De Borggraeve, & Kerckhofs, G. (2022). Revealing the murine brain anatomy by contrast-enhanced computed tomography – a screening study. 6th Symposium on X-ray Computed Tomography, Kasteelpark Arenberg 10, 3001 Leuven. https://hdl.handle.net/2078.5/269320