Biology subjects

Hellevik, A.

Publications and source records attributed to Hellevik, A..

5 recordsLinked to original sources

bioRxiv2026

Scaling up polarization-sensitive optical coherence tomography to image the whole macaque brain

Polarization-sensitive optical coherence tomography (PS-OCT) is a label-free imaging technique that exploits birefringence to visualize myelinated axons at micrometer resolution. However, serial PS-OCT imaging has been limited to small volumes, including tissue blocks from larger species, owing to constraints in acquisition speed, system stability, and data processing. These limitations have prevented its application to whole-brain mapping in large mammals. Here we present a scalable PS-OCT acquisition system and computational pipeline for whole-brain imaging in the rhesus macaque. The framework integrates high-throughput serial imaging with automated reconstruction and processing, enabling volumetric imaging at micrometer-scale resolution across decimeter-scale brain volumes. Using this approach, we acquired two complete macaque brains at a voxel size of 5.5 x 5.5 x 3.4 m and an effective resolution of approximately 10 x 10 x 5.5 m, generating multi-terabyte datasets consisting of multiple contrasts including fiber orientation information. The datasets and associated processing tools are made publicly available. This platform establishes a method for large-scale, high-resolution mapping of white matter architecture in primate brains. The resulting datasets provide a reference for validating MRI models and support the development of neurotechnological applications, including deep brain stimulation, where accurate characterization of axonal organization is required.

neuroscience↗

bioRxiv2026

Heterogeneity of white matter structure in the human brain

White-matter, which contains the long-range axons connecting different brain regions, makes up nearly half the human brain, yet the three-dimensional organization of individual axons has not been characterized. While advances in diffusion MRI have enabled macroscopic mapping of major WM pathways1, these methods are unable to resolve individual axons: their trajectories, density, and relative orientations2. Here, we present a histological and imaging pipeline optimized for post-mortem human white-matter that shows the 3D trajectories of densely stained large (diameter greater than ~1 m) projection axons. Applying our approach to multiple centimeter-scale WM regions in an adult human brain, we observed striking regional diversity in axonal organization. Specifically, we identified distinct architectural motifs ranging from loosely packed, multi-orientation meshworks (in most superficial white matter), to laminar lattice-like structures (near the basal ganglia), to tightly packed bundles of fibers (e.g. in the corpus callosum). We speculate that these patterns reflect local adaptations to spatial constraints, axonal density, and the diversity of axonal sources and targets, offering region-specific solutions to anatomical optimization problems. These findings offer new insights into the principles shaping brain connectivity and underscore the need for regionally detailed atlases of human white matter..

neuroscience↗

bioRxiv2024

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↗

bioRxiv2023

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↗

bioRxiv2023

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↗