scholarly journals Automatic navigation system for the mouse brain

2018 ◽  
Author(s):  
Susan J. Tappan ◽  
Brian S. Eastwood ◽  
Nathan O’Connor ◽  
Quanxin Wang ◽  
Lydia Ng ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Digital Image ◽  
Navigation System ◽  
Three Dimensional ◽  
Brain Regions ◽  
Brain Atlas ◽  
Brain Section ◽  
Observer Error ◽  
Novel Technology ◽  
Experimental Mouse

Identification and delineation of brain regions in histologic mouse brain sections is especially pivotal for many neurogenomics, transcriptomics, proteomics and connectomics studies, yet this process is prone to observer error and bias. Here we present a novel brain navigation system, named NeuroInfo, whose general principle is similar to that of a global positioning system (GPS) in a car. NeuroInfo automatically navigates an investigator through the complex microscopic anatomy of histologic sections of mouse brains (thereafter: “experimental mouse brain sections”). This is achieved by automatically registering a digital image of an experimental mouse brain section with a three-dimensional (3D) digital mouse brain atlas that is essentially based on the third version of the Allen Mouse Brain Common Coordinate Framework (CCF v3), retrieving graphical region delineations and annotations from the 3D digital mouse brain atlas, and superimposing this information onto the digital image of the experimental mouse brain section on a computer screen. By doing so, NeuroInfo helps in solving the long-standing problem faced by researchers investigating experimental mouse brain sections under a light microscope—that of correctly identifying the distinct brain regions contained within the experimental mouse brain sections. Specifically, NeuroInfo provides an intuitive, readily-available computer microscopy tool to enhance researchers’ ability to correctly identify specific brain regions in experimental mouse brain sections. Extensive validation studies of NeuroInfo demonstrated that this novel technology performs remarkably well in accurately delineating regions that are large and/or located in the dorsal parts of mouse brains, independent on whether the sections were imaged with fluorescence or brightfield microscopy. This novel navigation system provides a highly efficient way for registering a digital image of an experimental mouse brain section with the 3D digital mouse brain atlas in a minute and accurate delineation of the image in real-time.

scholarly journals DTI reveals whole-brain microstructural changes in the P301L mouse model of tauopathy

2020 ◽  
Author(s):  
Aidana Massalimova ◽  
Ruiqing Ni ◽  
Roger M. Nitsch ◽  
Marco Reisert ◽  
Dominik von Elverfeldt ◽  
...  
Keyword(s):  
White Matter ◽  
High Resolution ◽  
Mouse Model ◽  
Mouse Brain ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Brain Atlas ◽  
Microstructural Changes ◽  
Allen Mouse Brain Atlas

AbstractIntroductionIncreased expression of hyperphosphorylated tau and the formation of neurofibrillary tangles are associated with neuronal loss and white matter damage. Using high resolution ex vivo diffusion tensor imaging (DTI), we investigated microstructural changes in the white and grey matter in the P301L mouse model of human tauopathy at 8.5 months-of-age. For unbiased computational analysis, we implemented a pipeline for voxel-based analysis (VBA) and atlas-based analysis (ABA) of DTI mouse brain data.MethodsHemizygous and homozygous transgenic P301L mice and non-transgenic littermates were used. DTI data were acquired for generation of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD) maps. VBA on the entire brain were performed using SPM8 and SPM Mouse toolbox. Initially, all DTI maps were co-registered with Allen mouse brain atlas to bring them to one common coordinate space. In VBA, co-registered DTI maps were normalized and smoothed in order to perform two-sample t-tests to compare hemizygotes with non-transgenic littermates, homozygotes with non-transgenic littermates, hemizygotes with homozygotes on each DTI parameter map. In ABA, the average values for selected regions-of-interests were computed with co-registered DTI maps and labels in Allen mouse brain atlas. After, the same two-sample t-tests were executed on the estimated average values.ResultsWe made reconstructed DTI data and VBA and ABA pipeline publicly available. With VBA, we found microstructural changes in the white matter in hemizygous P301L mice compared to non-transgenic littermates. In contrast, more pronounced and brain-wide spread changes were observed in VBA when comparing homozygous P301L mice with non-transgenic littermates. Statistical comparison of DTI metrics in selected brain regions by ABA corroborated findings from VBA. FA was found to be decreased in most brain regions, while MD, RD and AD were increased compared to hemizygotes and non-transgenic littermates.Discussion/ConclusionHigh resolution ex vivo DTI demonstrated brain-wide microstructural changes in the P301L mouse model of human tauopathy. The comparison between hemizygous and homozygous P301L mice revealed a gene-dose dependent effect on DTI metrics. The publicly available computational data analysis pipeline can provide a platform for future mechanistic and longitudinal studies.

scholarly journals Diffusion Tensor Imaging Reveals Whole-Brain Microstructural Changes in the P301L Mouse Model of Tauopathy

2021 ◽  
pp. 1-12
Author(s):  
Aidana Massalimova ◽  
Ruiqing Ni ◽  
Roger M. Nitsch ◽  
Marco Reisert ◽  
Dominik von Elverfeldt ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
High Resolution ◽  
Mouse Model ◽  
Mouse Brain ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Brain Atlas ◽  
Microstructural Changes ◽  
Allen Mouse Brain Atlas

<b><i>Introduction:</i></b> Increased expression of hyperphosphorylated tau and the formation of neurofibrillary tangles are associated with neuronal loss and white matter damage. Using high-resolution ex vivo diffusion tensor imaging (DTI), we investigated microstructural changes in the white and grey matter in the P301L mouse model of human tauopathy at 8.5 months of age. For unbiased computational analysis, we implemented a pipeline for voxel-based analysis (VBA) and atlas-based analysis (ABA) of DTI mouse brain data. <b><i>Methods:</i></b> Hemizygous and homozygous transgenic P301L mice and non-transgenic littermates were used. DTI data were acquired for generation of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) maps. VBA on the entire brain was performed using SPM8 and the SPM Mouse toolbox. Initially, all DTI maps were coregistered with the Allen mouse brain atlas to bring them to one common coordinate space. In VBA, coregistered DTI maps were normalized and smoothed in order to perform two-sample and unpaired <i>t</i> tests with false discovery rate correction to compare hemizygotes with non-transgenic littermates, homozygotes with non-transgenic littermates, and hemizygotes with homozygotes on each DTI parameter map. In ABA, the average values for selected regions of interests were computed with coregistered DTI maps and labels in Allen mouse brain atlas. Afterwards, a Kruskal-Wallis one-way ANOVA on ranks with a Tukey post hoc test was executed on the estimated average values. <b><i>Results:</i></b> With VBA, we found pronounced and brain-wide spread changes when comparing homozygous, P301L mice with non-transgenic littermates, which were not seen when comparing hemizygous P301L with non-transgenic animals. Statistical comparison of DTI metrics in selected brain regions by ABA corroborated findings from VBA. FA was found to be decreased in most brain regions, while MD, RD, and AD were increased in homozygotes compared to hemizygotes and non-transgenic littermates. <b><i>Discussion/Conclusion:</i></b> High-resolution ex vivo DTI demonstrated brain-wide microstructural and gene-dose-dependent changes in the P301L mouse model of human tauopathy. The DTI analysis pipeline may serve for the phenotyping of models of tauopathy and other brain diseases.

An atlas of the protein-coding genes in the human, pig, and mouse brain

Science ◽  
2020 ◽  
Vol 367 (6482) ◽  
pp. eaay5947 ◽  
Author(s):  
Evelina Sjöstedt ◽  
Wen Zhong ◽  
Linn Fagerberg ◽  
Max Karlsson ◽  
Nicholas Mitsios ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Expression Profiles ◽  
Brain Regions ◽  
Brain Atlas ◽  
Mammalian Brain ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Human Protein Atlas ◽  
The Brain ◽  
Complex Organ

The brain, with its diverse physiology and intricate cellular organization, is the most complex organ of the mammalian body. To expand our basic understanding of the neurobiology of the brain and its diseases, we performed a comprehensive molecular dissection of 10 major brain regions and multiple subregions using a variety of transcriptomics methods and antibody-based mapping. This analysis was carried out in the human, pig, and mouse brain to allow the identification of regional expression profiles, as well as to study similarities and differences in expression levels between the three species. The resulting data have been made available in an open-access Brain Atlas resource, part of the Human Protein Atlas, to allow exploration and comparison of the expression of individual protein-coding genes in various parts of the mammalian brain.

scholarly journals A three-dimensional thalamocortical dataset for characterizing brain heterogeneity

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Judy A. Prasad ◽  
Aishwarya H. Balwani ◽  
Erik C. Johnson ◽  
Joseph D. Miano ◽  
Vandana Sampathkumar ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Three Dimensional ◽  
Brain Regions ◽  
Regions Of Interest ◽  
Subcortical Structures ◽  
Neural Structure ◽  
Brain Areas ◽  
X Ray ◽  
Anatomical Imaging ◽  
Critical Aspects

Abstract Neural microarchitecture is heterogeneous, varying both across and within brain regions. The consistent identification of regions of interest is one of the most critical aspects in examining neurocircuitry, as these structures serve as the vital landmarks with which to map brain pathways. Access to continuous, three-dimensional volumes that span multiple brain areas not only provides richer context for identifying such landmarks, but also enables a deeper probing of the microstructures within. Here, we describe a three-dimensional X-ray microtomography imaging dataset of a well-known and validated thalamocortical sample, encompassing a range of cortical and subcortical structures from the mouse brain . In doing so, we provide the field with access to a micron-scale anatomical imaging dataset ideal for studying heterogeneity of neural structure.

scholarly journals Topology of the mesoscale connectome of the mouse brain

2020 ◽  
Vol 8 (1) ◽  
pp. 126-140
Author(s):  
Pascal Grange
Keyword(s):  
Mouse Brain ◽  
Brain Connectivity ◽  
Persistent Homology ◽  
Three Dimensional ◽  
Brain Regions ◽  
Global Features ◽  
Wiring Diagram ◽  
Closed Loops ◽  
Axonal Projections ◽  
Reference Space

AbstractThe wiring diagram of the mouse brain has recently been mapped at a mesoscopic scale in the Allen Mouse Brain Connectivity Atlas. Axonal projections from brain regions were traced using green fluoresent proteins. The resulting data were registered to a common three-dimensional reference space. They yielded a matrix of connection strengths between 213 brain regions. Global features such as closed loops formed by connections of similar intensity can be inferred using tools from persistent homology. We map the wiring diagram of the mouse brain to a simplicial complex (filtered by connection strengths). We work out generators of the first homology group. Some regions, including nucleus accumbens, are connected to the entire brain by loops, whereas no region has non-zero connection strength to all brain regions. Thousands of loops go through the isocortex, the striatum and the thalamus. On the other hand, medulla is the only major brain compartment that contains more than 100 loops.

scholarly journals The Integrated Voxel Analysis Method (IVAM) to Diagnose Onset of Alzheimer’s Disease and Identify Brain Regions through Structural MRI Images

2019 ◽  
Author(s):  
Matthew Hur ◽  
Armen Aghajanyan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nearest Neighbor ◽  
Feature Vector ◽  
Three Dimensional ◽  
Structural Mri ◽  
Brain Regions ◽  
Brain Atlas ◽  
Analysis Method ◽  
K Nearest Neighbor

AbstractMagnetic Resonance Imaging (MRI) provides three-dimensional anatomical and physiological details of the human brain. We describe the Integrated Voxel Analysis Method (IVAM) which, through machine learning, classifies MRI images of brains afflicted with early Alzheimer’s Disease (AD). This fully automatic method uses an extra trees regressor model in which the feature vector input contains the intensities of voxels, whereby the effect of AD on a single voxel can be predicted. The resulting tree predicts based on the following two steps: a K-nearest neighbor (KNN) algorithm based on Euclidean distance with the feature vector to classify whole images based on their distribution of affected voxels and a voxel-by-voxel classification by the tree of every voxel in the image. An Ising model filter follows voxel-by-voxel tree-classification to remove artifacts and to facilitate clustering of classification results which identify significant voxel clusters affected by AD. We apply this method to T1-weighted MRI images obtained from the Open Access Series of Imaging Studies (OASIS) using images belonging to normal and early AD-afflicted individuals associated with a Client Dementia Rating (CDR) which we use as the target in the supervised learning. Furthermore, statistical analysis using a pre-labeled brain atlas automatically identifies significantly affected brain regions. While achieving 90% AD classification accuracy on 198 images in the OASIS dataset, the method reveals morphological differences caused by the onset of AD.

Learning Deficits Accompanied by Microglial Proliferation After the Long-Term Post-Injection of Alzheimer’s Disease Brain Extract in Mouse Brains

2021 ◽  
Vol 79 (4) ◽  
pp. 1701-1711
Author(s):  
Tetsuo Hayashi ◽  
Shotaro Shimonaka ◽  
Montasir Elahi ◽  
Shin-Ei Matsumoto ◽  
Koichi Ishiguro ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Brain ◽  
Functional Decline ◽  
Brain Regions ◽  
Insoluble Fraction ◽  
Brain Extract ◽  
Post Injection ◽  
Learning Deficits

Background: Human tauopathy brain injections into the mouse brain induce the development of tau aggregates, which spread to functionally connected brain regions; however, the features of this neurotoxicity remain unclear. One reason may be short observational periods because previous studies mostly used mutated-tau transgenic mice and needed to complete the study before these mice developed neurofibrillary tangles. Objective: To examine whether long-term incubation of Alzheimer’s disease (AD) brain in the mouse brain cause functional decline. Methods: We herein used Tg601 mice, which overexpress wild-type human tau, and non-transgenic littermates (NTg) and injected an insoluble fraction of the AD brain into the unilateral hippocampus. Results: After a long-term (17–19 months) post-injection, mice exhibited learning deficits detected by the Barnes maze test. Aggregated tau pathology in the bilateral hippocampus was more prominent in Tg601 mice than in NTg mice. No significant changes were observed in the number of Neu-N positive cells or astrocytes in the hippocampus, whereas that of Iba-I-positive microglia increased after the AD brain injection. Conclusion: These results potentially implicate tau propagation in functional decline and indicate that long-term changes in non-mutated tau mice may reflect human pathological conditions.

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