Searcharxiv⌕ Search

arXiv subjects

Katrin Amunts

Publications and source records attributed to Katrin Amunts.

27 records · Page 2Linked to original sources

Finite-Difference Time-Domain simulations of transmission microscopy enable a better interpretation of 3D nerve fiber architectures in the brain

In many laboratories, conventional bright-field transmission microscopes are available to study the structure and organization principles of fibrous tissue samples, but they usually provide only 2D information. To access the third (out-of-plane) dimension, more advanced techniques are employed. An example is 3D Polarized Light Imaging (3D-PLI), which measures the birefringence of histological brain sections to derive the spatial nerve fiber orientations. Here, we show how light scattering in transmission microscopy measurements can be leveraged to gain 3D structural information about fibrous tissue samples like brain tissue. For this purpose, we developed a simulation framework using finite-difference time-domain (FDTD) simulations and high performance computing, which can easily be adapted to other microscopy techniques and tissue types with comparable fibrous structures (e.g., muscle fibers, collagen, or artificial fibers). As conventional bright-field transmission microscopy provides usually only 2D information about tissue structures, a three-dimensional reconstruction of fibers across several sections is difficult. By combining our simulations with experimental studies, we show that the polarization-independent transmitted light intensity (transmittance) contains 3D information: We demonstrate in several experimental studies on brain sections from different species (rodent, monkey, human) that the transmittance decreases significantly (by more than 50%) with the increasing out-of-plane angle of the nerve fibers. Our FDTD simulations show that this decrease is mainly caused by polarization-independent light scattering in combination with the finite numerical aperture of the imaging system. This allows to use standard transmission microscopy techniques to obtain 3D information about the fiber inclination and to detect steep fibers, without need for additional measurements.

physics.med-ph↗

Dense Fiber Modeling for 3D-Polarized Light Imaging Simulations

3D-Polarized Light Imaging (3D-PLI) is a neuroimaging technique used to study the structural connectivity of the human brain at the meso- and microscale. In 3D-PLI, the complex nerve fiber architecture of the brain is characterized by 3D orientation vector fields that are derived from birefringence measurements of unstained histological brain sections by means of an effective physical model. To optimize the physical model and to better understand the underlying microstructure, numerical simulations are essential tools to optimize the used physical model and to understand the underlying microstructure in detail. The simulations rely on predefined configurations of nerve fiber models (e.g. crossing, kissing, or complex intermingling), their physical properties, as well as the physical properties of the employed optical system to model the entire 3D-PLI measurement. By comparing the simulation and experimental results, possible misinterpretations in the fiber reconstruction process of 3D-PLI can be identified. Here, we focus on fiber modeling with a specific emphasize on the generation of dense fiber distributions as found in the human brain's white matter. A new algorithm will be introduced that allows to control possible intersections of computationally grown fiber structures.

physics.comp-ph↗

Diattenuation Imaging reveals different brain tissue properties

When transmitting polarised light through histological brain sections, different types of diattenuation (polarisation-dependent attenuation of light) can be observed: In some brain regions, the light is minimally attenuated when it is polarised parallel to the nerve fibres (referred to as D+), in others, it is maximally attenuated (referred to as D-). The underlying mechanisms of these effects and their relationship to tissue properties were so far unknown. Here, we demonstrate in experimental studies that diattenuation of both types D+ and D- can be observed in brain tissue samples from different species (rodent, monkey, and human) and that the strength and type of diattenuation depend on the nerve fibre orientations. By combining finite-difference time-domain simulations and analytical modelling, we explain the observed diattenuation effects and show that they are caused both by anisotropic absorption (dichroism) and by anisotropic light scattering. Our studies demonstrate that the diattenuation signal depends not only on the nerve fibre orientations but also on other brain tissue properties like tissue homogeneity, fibre size, and myelin sheath thickness. This allows to use the diattenuation signal to distinguish between brain regions with different tissue properties and establishes Diattenuation Imaging as a valuable imaging technique.

physics.med-ph↗

Towards ultra-high resolution 3D reconstruction of a whole rat brain from 3D-PLI data

3D reconstruction of the fiber connectivity of the rat brain at microscopic scale enables gaining detailed insight about the complex structural organization of the brain. We introduce a new method for registration and 3D reconstruction of high- and ultra-high resolution (64 $μ$m and 1.3 $μ$m pixel size) histological images of a Wistar rat brain acquired by 3D polarized light imaging (3D-PLI). Our method exploits multi-scale and multi-modal 3D-PLI data up to cellular resolution. We propose a new feature transform-based similarity measure and a weighted regularization scheme for accurate and robust non-rigid registration. To transform the 1.3 $μ$m ultra-high resolution data to the reference blockface images a feature-based registration method followed by a non-rigid registration is proposed. Our approach has been successfully applied to 278 histological sections of a rat brain and the performance has been quantitatively evaluated using manually placed landmarks by an expert.

cs.CV↗

Improving Cytoarchitectonic Segmentation of Human Brain Areas with Self-supervised Siamese Networks

Cytoarchitectonic parcellations of the human brain serve as anatomical references in multimodal atlas frameworks. They are based on analysis of cell-body stained histological sections and the identification of borders between brain areas. The de-facto standard involves a semi-automatic, reproducible border detection, but does not scale with high-throughput imaging in large series of sections at microscopical resolution. Automatic parcellation, however, is extremely challenging due to high variation in the data, and the need for a large field of view at microscopic resolution. The performance of a recently proposed Convolutional Neural Network model that addresses this problem especially suffers from the naturally limited amount of expert annotations for training. To circumvent this limitation, we propose to pre-train neural networks on a self-supervised auxiliary task, predicting the 3D distance between two patches sampled from the same brain. Compared to a random initialization, fine-tuning from these networks results in significantly better segmentations. We show that the self-supervised model has implicitly learned to distinguish several cortical brain areas -- a strong indicator that the proposed auxiliary task is appropriate for cytoarchitectonic mapping.

cs.CV↗

Diattenuation of Brain Tissue and its Impact on 3D Polarized Light Imaging

3D-Polarized Light Imaging (3D-PLI) reconstructs nerve fibers in histological brain sections by measuring their birefringence. This study investigates another effect caused by the optical anisotropy of brain tissue - diattenuation. Based on numerical and experimental studies and a complete analytical description of the optical system, the diattenuation was determined to be below 4 % in rat brain tissue. It was demonstrated that the diattenuation effect has negligible impact on the fiber orientations derived by 3D-PLI. The diattenuation signal, however, was found to highlight different anatomical structures that cannot be distinguished with current imaging techniques, which makes Diattenuation Imaging a promising extension to 3D-PLI.

physics.med-ph↗

Parcellation of Visual Cortex on high-resolution histological Brain Sections using Convolutional Neural Networks

Microscopic analysis of histological sections is considered the "gold standard" to verify structural parcellations in the human brain. Its high resolution allows the study of laminar and columnar patterns of cell distributions, which build an important basis for the simulation of cortical areas and networks. However, such cytoarchitectonic mapping is a semiautomatic, time consuming process that does not scale with high throughput imaging. We present an automatic approach for parcellating histological sections at 2um resolution. It is based on a convolutional neural network that combines topological information from probabilistic atlases with the texture features learned from high-resolution cell-body stained images. The model is applied to visual areas and trained on a sparse set of partial annotations. We show how predictions are transferable to new brains and spatially consistent across sections.

cs.CV↗

Grand Challenges for Global Brain Sciences

The next grand challenges for society and science are in the brain sciences. A collection of 60+ scientists from around the world, together with 10+ observers from national, private, and foundations, spent two days together discussing the top challenges that we could solve as a global community in the next decade. We eventually settled on three challenges, spanning anatomy, physiology, and medicine. Addressing all three challenges requires novel computational infrastructure. The group proposed the advent of The International Brain Station (TIBS), to address these challenges, and launch brain sciences to the next level of understanding.

q-bio.NC↗

A Jones matrix formalism for simulating three-dimensional polarized light imaging of brain tissue

The neuroimaging technique three-dimensional polarized light imaging (3D-PLI) provides a high-resolution reconstruction of nerve fibres in human post-mortem brains. The orientations of the fibres are derived from birefringence measurements of histological brain sections assuming that the nerve fibres - consisting of an axon and a surrounding myelin sheath - are uniaxial birefringent and that the measured optic axis is oriented in direction of the nerve fibres (macroscopic model). Although experimental studies support this assumption, the molecular structure of the myelin sheath suggests that the birefringence of a nerve fibre can be described more precisely by multiple optic axes oriented radially around the fibre axis (microscopic model). In this paper, we compare the use of the macroscopic and the microscopic model for simulating 3D-PLI by means of the Jones matrix formalism. The simulations show that the macroscopic model ensures a reliable estimation of the fibre orientations as long as the polarimeter does not resolve structures smaller than the diameter of single fibres. In the case of fibre bundles, polarimeters with even higher resolutions can be used without losing reliability. When taking the myelin density into account, the derived fibre orientations are considerably improved.

physics.med-ph↗