1,388 research outputs found
Whole-brain vasculature reconstruction at the single capillary level
The distinct organization of the brainâs vascular network ensures that it is adequately supplied with oxygen and nutrients. However, despite this fundamental role, a detailed reconstruction of the brain-wide vasculature at the capillary level remains elusive, due to insufficient image quality using the best available techniques. Here, we demonstrate a novel approach that improves vascular demarcation by combining CLARITY with a vascular staining approach that can fill the entire blood vessel lumen and imaging with light-sheet fluorescence microscopy. This method significantly improves image contrast, particularly in depth, thereby allowing reliable application of automatic segmentation algorithms, which play an increasingly important role in high-throughput imaging of the terabyte-sized datasets now routinely produced. Furthermore, our novel method is compatible with endogenous fluorescence, thus allowing simultaneous investigations of vasculature and genetically targeted neurons. We believe our new method will be valuable for future brain-wide investigations of the capillary network
Machine learning methods for histopathological image analysis
Abundant accumulation of digital histopathological images has led to the
increased demand for their analysis, such as computer-aided diagnosis using
machine learning techniques. However, digital pathological images and related
tasks have some issues to be considered. In this mini-review, we introduce the
application of digital pathological image analysis using machine learning
algorithms, address some problems specific to such analysis, and propose
possible solutions.Comment: 23 pages, 4 figure
Geometry Processing of Conventionally Produced Mouse Brain Slice Images
Brain mapping research in most neuroanatomical laboratories relies on
conventional processing techniques, which often introduce histological
artifacts such as tissue tears and tissue loss. In this paper we present
techniques and algorithms for automatic registration and 3D reconstruction of
conventionally produced mouse brain slices in a standardized atlas space. This
is achieved first by constructing a virtual 3D mouse brain model from annotated
slices of Allen Reference Atlas (ARA). Virtual re-slicing of the reconstructed
model generates ARA-based slice images corresponding to the microscopic images
of histological brain sections. These image pairs are aligned using a geometric
approach through contour images. Histological artifacts in the microscopic
images are detected and removed using Constrained Delaunay Triangulation before
performing global alignment. Finally, non-linear registration is performed by
solving Laplace's equation with Dirichlet boundary conditions. Our methods
provide significant improvements over previously reported registration
techniques for the tested slices in 3D space, especially on slices with
significant histological artifacts. Further, as an application we count the
number of neurons in various anatomical regions using a dataset of 51
microscopic slices from a single mouse brain. This work represents a
significant contribution to this subfield of neuroscience as it provides tools
to neuroanatomist for analyzing and processing histological data.Comment: 14 pages, 11 figure
In vivo MRI signatures of hippocampal subfield pathology in intractable epilepsy.
OBJECTIVES: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo.
EXPERIMENTAL DESIGN: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively assessed in CA1, CA2/3, and CA4/DG.
PRINCIPAL OBSERVATIONS: MRI volumes across all subfields were positively correlated with neuronal density and size. Higher T2 intensity related to increased GFAP fraction in CA1, while quantitative T1 and diffusion MRI parameters showed negative correlations with neuronal density in CA4 and DG. Multiple linear regression analysis revealed that in vivo multiparametric MRI can predict neuronal loss in all the analyzed subfields with up to 90% accuracy.
CONCLUSION: Our results, based on an accurate co-registration pipeline and a subfield-specific analysis of MRI and histology, demonstrate the potential of MRI volumetry, diffusion, and quantitative T1 as accurate in vivo biomarkers of hippocampal pathology
Semi-automated learning strategies for large-scale segmentation of histology and other big bioimaging stacks and volumes
Labelled high-resolution datasets are becoming increasingly common and necessary in different areas of biomedical imaging. Examples include: serial histology and ex-vivo MRI for atlas building, OCT for studying the human brain, and micro X-ray for tissue engineering. Labelling such datasets, typically, requires manual delineation of a very detailed set of regions of interest on a large number of sections or slices. This process is tedious, time-consuming, not reproducible and rather inefficient due to the high similarity of adjacent sections.
In this thesis, I explore the potential of a semi-automated slice level segmentation framework and a suggestive region level framework which aim to speed up the segmentation process of big bioimaging datasets. The thesis includes two well validated, published, and widely used novel methods and one algorithm which did not yield an improvement compared to the current state-of the-art.
The slice-wise method, SmartInterpol, consists of a probabilistic model for semi-automated segmentation of stacks of 2D images, in which the user manually labels a sparse set of sections (e.g., one every n sections), and lets the algorithm complete the segmentation for other sections automatically. The proposed model integrates in a principled manner two families of segmentation techniques that have been very successful in brain imaging: multi-atlas segmentation and convolutional neural networks.
Labelling every structure on a sparse set of slices is not necessarily optimal, therefore I also introduce a region level active learning framework which requires the labeller to annotate one region of interest on one slice at the time. The framework exploits partial annotations, weak supervision, and realistic estimates of class and section-specific annotation effort in order to greatly reduce the time it takes to produce accurate segmentations for large histological datasets.
Although both frameworks have been created targeting histological datasets, they have been successfully applied to other big bioimaging datasets, reducing labelling effort by up to 60â70% without compromising accuracy
Whole-brain vasculature reconstruction at the single capillary level
The distinct organization of the brainâs vascular network ensures that it is adequately supplied with oxygen and nutrients. However, despite this fundamental role, a detailed reconstruction of the brain-wide vasculature at the capillary level remains elusive, due to insufficient image quality using the best available techniques. Here, we demonstrate a novel approach that improves vascular demarcation by combining CLARITY with a vascular staining approach that can fill the entire blood vessel lumen and imaging with light-sheet fluorescence microscopy. This method significantly improves image contrast, particularly in depth, thereby allowing reliable application of automatic segmentation algorithms, which play an increasingly important role in high-throughput imaging of the terabyte-sized datasets now routinely produced. Furthermore, our novel method is compatible with endogenous fluorescence, thus allowing simultaneous investigations of vasculature and genetically targeted neurons. We believe our new method will be valuable for future brain-wide investigations of the capillary network
A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology
The human thalamus is a brain structure that comprises numerous, highly
specific nuclei. Since these nuclei are known to have different functions and
to be connected to different areas of the cerebral cortex, it is of great
interest for the neuroimaging community to study their volume, shape and
connectivity in vivo with MRI. In this study, we present a probabilistic atlas
of the thalamic nuclei built using ex vivo brain MRI scans and histological
data, as well as the application of the atlas to in vivo MRI segmentation. The
atlas was built using manual delineation of 26 thalamic nuclei on the serial
histology of 12 whole thalami from six autopsy samples, combined with manual
segmentations of the whole thalamus and surrounding structures (caudate,
putamen, hippocampus, etc.) made on in vivo brain MR data from 39 subjects. The
3D structure of the histological data and corresponding manual segmentations
was recovered using the ex vivo MRI as reference frame, and stacks of blockface
photographs acquired during the sectioning as intermediate target. The atlas,
which was encoded as an adaptive tetrahedral mesh, shows a good agreement with
with previous histological studies of the thalamus in terms of volumes of
representative nuclei. When applied to segmentation of in vivo scans using
Bayesian inference, the atlas shows excellent test-retest reliability,
robustness to changes in input MRI contrast, and ability to detect differential
thalamic effects in subjects with Alzheimer's disease. The probabilistic atlas
and companion segmentation tool are publicly available as part of the
neuroimaging package FreeSurfer
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