The comprehensive characterization of neuronal morphology requires tracing extensive axonal and dendritic arbors imaged with light microscopy into digital reconstructions. Considerable effort is ongoing to automate this greatly labor-intensive and currently rate-determining process. Experimental data in the form of manually traced digital reconstructions and corresponding image stacks play a vital role in developing increasingly more powerful reconstruction algorithms. The DIADEM challenge (short for DIgital reconstruction of Axonal and DEndritic Morphology) successfully stimulated progress in this area selecting six data set collections from different animal species, brain regions, neuron types, and visualization methods. The original research projects that provided these data are representative of the diverse scientific questions addressed in this field. At the same time, these data provide a benchmark for the types of demands automated software must meet to achieve the quality of manual reconstructions while minimizing human involvement. The DIADEM data underwent extensive curation, including quality control, metadata annotation, and format standardization, to focus the challenge on the most substantial technical obstacles. This data set package is now freely released (http://diademchallenge.org) to train, test, and aid development of automated reconstruction algorithms.

Characterization of the complex branching architecture of cerebral arteries across a representative sample of the human population is important for diagnosing, analyzing, and predicting pathological states. Brain arterial vasculature can be visualized by magnetic resonance angiography (MRA). However, most MRA studies are limited to qualitative assessments, partial morphometric analyses, individual (or small numbers of) subjects, proprietary datasets, or combinations of the above limitations. Neuroinformatics tools, developed for neuronal arbor analysis, were used to quantify vascular morphology from 3 T time-of-flight MRA high-resolution (620 μm isotropic) images collected in 61 healthy volunteers (36/25 F/M, average age = 31.2 ± 10.7, range = 19–64 years). We present in-depth morphometric analyses of the global and local anatomical features of these arbors. The overall structure and size of the vasculature did not significantly differ across genders, ages, or hemispheres. The total length of the three major arterial trees stemming from the circle of Willis (from smallest to largest: the posterior, anterior, and middle cerebral arteries; or PCAs, ACAs, and MCAs, respectively) followed an approximate 1:2:4 proportion. Arterial size co-varied across individuals: subjects with one artery longer than average tended to have all other arteries also longer than average. There was no net right–left difference across the population in any of the individual arteries, but ACAs were more lateralized than MCAs. MCAs, ACAs, and PCAs had similar branch-level properties such as bifurcation angles. Throughout the arterial vasculature, there were considerable differences between branch types: bifurcating branches were significantly shorter and straighter than terminating branches. Furthermore, the length and meandering of bifurcating branches increased with age and with path distance from the circle of Willis. All reconstructions are freely distributed through a public database to enable additional analyses and modeling (cng.gmu.edu/brava).

Digital reconstructions of neuronal morphology are used to study neuron function, development, and responses to various conditions. Although many measures exist to analyze differences between neurons, none is particularly suitable to compare the same arborizing structure over time (morphological change) or reconstructed by different people and/or software (morphological error). The metric introduced for the DIADEM (DIgital reconstruction of Axonal and DEndritic Morphology) Challenge quantifies the similarity between two reconstructions of the same neuron by matching the locations of bifurcations and terminations as well as their topology between the two reconstructed arbors. The DIADEM metric was specifically designed to capture the most critical aspects in automating neuronal reconstructions, and can function in feedback loops during algorithm development. During the Challenge, the metric scored the automated reconstructions of best-performing algorithms against manually traced gold standards over a representative data set collection. The metric was compared with direct quality assessments by neuronal reconstruction experts and with clocked human tracing time saved by automation. The results indicate that relevant morphological features were properly quantified in spite of subjectivity in the underlying image data and varying research goals. The DIADEM metric is freely released open source (http://diademchallenge.org) as a flexible instrument to measure morphological error or change in high-throughput reconstruction projects.