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 addresses these problems by training on brain-specific datasets, instead of relying on a single intensity threshold such as Otsu's method.