Multiscale Exploration of Mouse Brain Microstructures Using the Knife-Edge Scanning Microscope Brain Atlas

Connectomics is the study of the full connection matrix of the brain.Recent advances in high-throughput, high-resolution 3D microscopy methodshave enabled the imaging of whole small animal brains at a sub-micrometerresolution, potentially opening the road to full-blown connectomicsresearch. One of the first such instruments to achieve whole-brain-scaleimaging at sub-micrometer resolution is the Knife-Edge Scanning Microscope(KESM). KESM whole-brain data sets now include Golgi (neuronal circuits),Nissl (soma distribution), and India ink (vascular networks). KESM data cancontribute greatly to connectomics research, since they fill the gap betweenlower resolution, large volume imaging methods (such as diffusion MRI) andhigher resolution, small volume methods (e.g., serial sectioning electronmicroscopy). Furthermore, KESM data are by their nature multiscale, ranging fromthe subcellular to the whole organ scale. Due to this, visualization alone is ahuge challenge, before we even start worrying about connectivity analysis. Tosolve this issue, we developed a web-based neuroinformatics framework for efficientvisualization and analysis of the multiscale KESM data sets. In this paper,we will first provide an overview of KESM, then discuss in detail the KESMdata sets and the web-based neuroinformatics framework, which is called theKESM Brain Atlas (KESMBA). Finally, we will discuss the relevance of the KESMBAto connectomics research, and identify challenges and future directions