Detecting microvascular changes in the mouse spleen using optical computed tomography.

Area of Science:

• Pharmacology
• Biomedical Imaging
• Toxicology

Background:

• Monitoring off-target organ drug toxicity is crucial for developing safe and effective pharmaceuticals.
• Traditional 2-D methods like histology have limitations, including sampling errors and potential information loss.

Purpose of the Study:

• To demonstrate a novel 3-D application of optical computed tomography (CT) for quantitatively assessing drug-induced splenic toxicity.
• To evaluate the response of adult murine spleen to the vascular disrupting agent ZD6126 using optical CT.

Main Methods:

• Utilized optical CT imaging sensitive to haemoglobin absorption for high-contrast 3-D splenic mapping.
• Quantitatively assessed splenic volume and microvasculature in vehicle and ZD6126-treated mice.
• Applied 3-D grey-level co-occurrence matrices (GLCM) for textural analysis.

Main Results:

• Optical CT provided detailed 3-D splenic structure and microvasculature maps.
• A significant reduction in mean splenic volume was observed in ZD6126-treated mice (44±3mm³) compared to controls (61±3mm³).
• 3-D GLCM analysis effectively differentiated between treated and control groups, overcoming the slice-dependency of 2-D methods.

Conclusions:

• Optical CT is a valuable tool for 3-D quantitative assessment of splenic drug toxicity.
• This method offers improved accuracy over 2-D techniques for evaluating drug effects on organ structure and volume.
• 3-D textural analysis using GLCM enhances the ability to detect drug-induced changes in splenic tissue.