Revealing the three-dimensional murine brain microstructure by contrast-enhanced computed tomography

Area of Science:

• Neuroscience
• Medical Imaging
• Materials Science

Background:

• Classical 2D histology limits brain microstructure understanding.
• High-resolution 3D imaging, like X-ray computed tomography (CT), requires contrast enhancement for soft tissues.
• Existing contrast-enhancing staining agents (CESAs) for brain imaging can be toxic, destructive, and lack characterized affinity mechanisms.

Purpose of the Study:

• To evaluate novel CESAs for contrast-enhanced computed tomography (CECT) of murine brain hemispheres.
• To identify CESAs with optimal contrast, minimal toxicity, and tissue compatibility.
• To demonstrate the utility of CECT in visualizing and quantifying neuropathological changes, specifically demyelination.

Main Methods:

• Evaluated two sets of CESAs: organic iodinated (Hexabrix, CA4+) and inorganic polyoxometalates (hafnium-substituted Wells-Dawson phosphotungstate, Preyssler anion).
• Assessed CESA performance in healthy murine hemispheres using CECT.
• Selected the optimal CESA (Hexabrix) based on gray-white matter contrast and applied it to a cuprizone-induced demyelination model.

Main Results:

• Introduced four new non-toxic and non-destructive CESAs for brain CECT.
• Hexabrix demonstrated superior contrast between gray and white matter.
• Cuprizone-induced demyelination was successfully visualized and quantified using Hexabrix-enhanced CECT.

Conclusions:

• CECT offers significant added value for ex vivo brain imaging and 3D histopathology.
• Novel CESAs enhance the safety and efficacy of CECT for brain studies.
• This research provides a foundation for developing advanced CESAs for detailed brain microstructure analysis and disease modeling.