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Hellevik, A.

Publications and source records attributed to Hellevik, A..

3 recordsLinked to original sources

A scalable and modular computational pipeline for axonal connectomics: automated tracing and assembly of axons across serial sections

Progress in histological methods and in microscope technology has enabled dense staining and imaging of axons over large brain volumes, but tracing axons over such volumes requires new computational tools for 3D reconstruction of data acquired from serial sections. We have developed a computational pipeline for automated tracing and volume assembly of densely stained axons imaged over serial sections, which leverages machine learning-based segmentation to enable stitching and alignment with the axon traces themselves. We validated this segmentation-driven approach to volume assembly and alignment of individual axons over centimeter-scale serial sections and show the application of the output traces for analysis of local orientation and for proofreading over aligned volumes. The pipeline is scalable, and combined with recent advances in experimental approaches, should enable new studies of mesoscale connectivity and function over the whole human brain.

neuroscience↗

Microscale visualization of cellular features in adult macaque visual cortex

Expansion microscopy and light sheet imaging enable fine-scale resolution of intracellular features that comprise neural circuits. Most current techniques visualize sparsely distributed features across whole brains or densely distributed features within individual brain regions. Here, we visualize dense distributions of immunolabeled proteins across early visual cortical areas in adult macaque monkeys. This process may be combined with multiphoton or magnetic resonance imaging to produce multimodal atlases in large, gyrencephalic brains.

neuroscience↗

Expansion-assisted selective plane illumination microscopy for nanoscale imaging ofcentimeter-scale tissues

Recent advances in tissue processing, labeling, and fluorescence microscopy are providing unprecedented views of the structure of cells and tissues at sub-diffraction resolutions and near single molecule sensitivity, driving discoveries in diverse fields of biology, including neuroscience. Biological tissue is organized over scales of nanometers to centimeters. Harnessing molecular imaging across intact, three-dimensional samples on this scale requires new types of microscopes with larger fields of view and working distance, as well as higher throughput. We present a new expansion-assisted selective plane illumination microscope (ExA-SPIM) with aberration-free 1.5 {micro}mx1.5 {micro}mx3 {micro}m optical resolution over a large field of view (10.6x8.0 mm2) and working distance (35 mm) at speeds up to 946 megavoxels/sec. Combined with new tissue clearing and expansion methods, the microscope allows imaging centimeter-scale samples with 375 nm lateral and 750 nm axial resolution (4x expansion), including entire mouse brains, with high contrast and without sectioning. We illustrate ExA-SPIM by reconstructing individual neurons across the mouse brain, imaging cortico-spinal neurons in the macaque motor cortex, and visualizing axons in human white matter.

neuroscience↗