Nuclear segmentation in brain tissue is harder than in most other tissues because:
- Extreme density — cortical layers and hippocampal formations pack nuclei so tightly that boundaries between adjacent cells are unclear
- Variable morphology — neuron nuclei, glial nuclei, and endothelial nuclei have different sizes and shapes
- Depth variation — in thick sections, nuclei at different Z-planes overlap in the 2D projection
StrataQuest's deep learning nuclei detection handles these challenges by training on brain-specific datasets, achieving superior performance compared to threshold-based methods like Otsu.