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To resolve the severe I/O and compute bottlenecks of dense volumetric inference, SkNeXt implements a topology-first pipeline that extracts and proofreads compact SWC neuronal skeletons prior to detailed morphological recovery. The framework uses these verified skeletons as spatial indices to selectively stream high-resolution microscopy data only along neuronal trajectories, bypassing empty background and shifting computational complexity from raw dataset volume to actual signal density. This sparse indexing paradigm enabled full neuronal reconstruction from a petabyte-scale super-resolution mouse brain dataset on a single GPU in under one week.
Petabyte-scale brain reconstruction no longer requires massive compute clusters鈥攑rioritizing sparse topological skeletons over dense voxel sweeps enables complete neuronal recovery on a single GPU in just one week.
Recent advances in high-resolution fluorescence and electron microscopy have enabled nanoscale imaging across increasingly large brain volumes, but the resulting terabyte- to petabyte-scale datasets make complete neuronal reconstruction prohibitively expensive in computation, data movement, and manual proofreading. Here, we present SkNeXt, a topology-first framework for scalable neuronal reconstruction from large volumetric microscopy datasets. Instead of densely processing entire image volumes, SkNeXt first converts neuronal morphology into compact SWC skeletons that preserve long-range connectivity. Proofreading is therefore focused on sparse neuronal trees, allowing branch, continuity, and connectivity errors to be corrected before high-resolution reconstruction. The corrected skeletons then serve as persistent structural priors for recovering detailed morphology while preserving neuronal identity and topology. Crucially, SkNeXt also uses neuronal skeletons as spatial indices for selective data access, retrieving high-resolution image regions only along reconstructed trajectories and bypassing most background and signal-free volumes. This substantially reduces I/O and computational overhead, allowing reconstruction cost to scale with neuronal morphology rather than total dataset size. Using SkNeXt, we reconstructed neurons from a petabyte-scale super-resolution fluorescence dataset of the mouse brain on a single GPU within one week, without requiring exhaustive dense inference across the complete imaging volume.
