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Maps of brain microarchitecture are important for understanding neurological function and behavior, including alterations caused by chronic conditions such as neurodegenerative disease. Techniques such as knife-edge scanning microscopy (KESM) provide the potential for whole organ imaging at sub-cellular resolution. However, multi-terabyte data sizes make manual annotation impractical and automatic segmentation challenging. Densely packed cells combined with interconnected microvascular networks are a challenge for current segmentation algorithms. The massive size of high-throughput microscopy data necessitates fast and largely unsupervised algorithms. In this paper, we investigate a fully-convolutional, deep, and densely-connected encoder-decoder for pixel-wise semantic segmentation. The excessive memory complexity often encountered with deep and dense networks is mitigated using skip connections, resulting in fewer parameters and enabling a significant performance increase over prior architectures. The proposed network provides superior performance for semantic segmentation problems applied to open-source benchmarks. We finally demonstrate our network for cellular and microvascular segmentation, enabling quantitative metrics for organ-scale neurovascular analysis.