X-ray computerized tomography (microCT) is critical for efficient volume electron microscopy}

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Imaging the whole brain requires considerable commitment of time and resources. Ensuring that only the best samples are processed through a pipeline that runs over multiple years is a must. Sample preparation for imaging at nanometre resolution is not without some variability in the outcomes, depending upon minor, often undetectable differences in the starting conditions. In order to choose the best stained and artefact-free sample, researchers image the whole sample using X-ray microscopy, to obtain a volume with 1 micrometre resolution. Automated and visual inspection of these volumes, for every sample, is a form of quality control that enables choosing an optimal sample for subsequent imaging with electron microscopy at nanometre resolution. From the volumes of these optimal samples, we can then best map the synaptic wiring diagram of all the neuronal circuits contained within, and study how the structure of a neural circuit relates to the function and, ultimately, to the control of behaviour. By screening many samples in search of an optimal, artefact-free sample, we can best utilize available microscopy resources, reduce data storage costs, greatly reduce post-processing costs particularly at the circuit proofreading stage, and deliver a complete synaptic wiring diagram, or connectome, ready for studying the neural circuit basis of behaviour. Such volumes and neural circuits will be deposited in public databases to become a resource for the broader research community, establishing foundational work on which to base future studies of brain function, such as studies where the circuits of animal models of mental disease are compared with the healthy circuits to identify the neural circuit basis of mental disease.