William R. Gray Roncal

William Gray Roncal, Eva L Dyer, Doga Gürsoy et al.

Imaging methods used in modern neuroscience experiments are quickly producing large amounts of data capable of providing increasing amounts of knowledge about neuroanatomy and function. A great deal of information in these datasets is relatively unexplored and untapped. One of the bottlenecks in knowledge extraction is that often there is no feedback loop between the knowledge produced (e.g., graph, density estimate, or other statistic) and the earlier stages of the pipeline (e.g., acquisition). We thus advocate for the development of sample-to-knowledge discovery pipelines that one can use to optimize acquisition and processing steps with a particular end goal (i.e., piece of knowledge) in mind. We therefore propose that optimization takes place not just within each processing stage but also between adjacent (and non-adjacent) steps of the pipeline. Furthermore, we explore the existing categories of knowledge representation and models to motivate the types of experiments and analysis needed to achieve the ultimate goal. To illustrate this approach, we provide an experimental paradigm to answer questions about large-scale synaptic distributions through a multimodal approach combining X-ray microtomography and electron microscopy.

William Gray Roncal, Colin Lea, Akira Baruah et al.

Developing automated and semi-automated solutions for reconstructing wiring diagrams of the brain from electron micrographs is important for advancing the field of connectomics. While the ultimate goal is to generate a graph of neuron connectivity, most prior automated methods have focused on volume segmentation rather than explicit graph estimation. In these approaches, one of the key, commonly occurring error modes is dendritic shaft-spine fragmentation. We posit that directly addressing this problem of connection identification may provide critical insight into estimating more accurate brain graphs. To this end, we develop a network-centric approach motivated by biological priors image grammars. We build a computer vision pipeline to reconnect fragmented spines to their parent dendrites using both fully-automated and semi-automated approaches. Our experiments show we can learn valid connections despite uncertain segmentation paths. We curate the first known reference dataset for analyzing the performance of various spine-shaft algorithms and demonstrate promising results that recover many previously lost connections. Our automated approach improves the local subgraph score by more than four times and the full graph score by 60 percent. These data, results, and evaluation tools are all available to the broader scientific community. This reframing of the connectomics problem illustrates a semantic, biologically inspired solution to remedy a major problem with neuron tracking.

Ayushi Sinha, William Gray Roncal, Narayanan Kasthuri et al.

Accurately estimating the wiring diagram of a brain, known as a connectome, at an ultrastructure level is an open research problem. Specifically, precisely tracking neural processes is difficult, especially across many image slices. Here, we propose a novel method to automatically identify and annotate small subcellular structures present in axons, known as axoplasmic reticula, through a 3D volume of high-resolution neural electron microscopy data. Our method produces high precision annotations, which can help improve automatic segmentation by using our results as seeds for segmentation, and as cues to aid segment merging.

Ayushi Sinha, William Gray Roncal, Narayanan Kasthuri et al.

In this paper, we present a new pipeline which automatically identifies and annotates axoplasmic reticula, which are small subcellular structures present only in axons. We run our algorithm on the Kasthuri11 dataset, which was color corrected using gradient-domain techniques to adjust contrast. We use a bilateral filter to smooth out the noise in this data while preserving edges, which highlights axoplasmic reticula. These axoplasmic reticula are then annotated using a morphological region growing algorithm. Additionally, we perform Laplacian sharpening on the bilaterally filtered data to enhance edges, and repeat the morphological region growing algorithm to annotate more axoplasmic reticula. We track our annotations through the slices to improve precision, and to create long objects to aid in segment merging. This method annotates axoplasmic reticula with high precision. Our algorithm can easily be adapted to annotate axoplasmic reticula in different sets of brain data by changing a few thresholds. The contribution of this work is the introduction of a straightforward and robust pipeline which annotates axoplasmic reticula with high precision, contributing towards advancements in automatic feature annotations in neural EM data.