A time-course study of actively stained mouse brains: DTI parameter and connectomic stability over one year

ABSTRACTWhile the application of diffusion tensor imaging (DTI), tractography, and connectomics to fixed ex-vivo tissue is a common practice today, there have been limited studies examining the effects of fixation on brain microstructure over extended periods. This time-course study reports the changes of regional brain volumes and diffusion scalar parameters, such as fractional anisotropy across twelve representative brain regions as measures of brain structural stability. The scalar DTI parameters and regional volumes were highly variable over the first two weeks after fixation. The same parameters were stable over a two to eight-week window after fixation which means confounds from tissue stability over that scanning window are minimal. Quantitative connectomes were analyzed over the same time period with extension out to one year. While there is some change in the scalar metrics at one year after fixation, these changes are sufficiently small, particularly in white matter to support reproducible connectomes over a period ranging from two weeks to one year post fixation. These findings delineate a stable scanning period during which brain volumes, diffusion scalar metrics and connectomes are remarkably stable.

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A time‐course study of actively stained mouse brains: Diffusion tensor imaging parameters and connectomic stability over 1 year

NMR in Biomedicine ◽

10.1002/nbm.4611 ◽

2021 ◽

Author(s):

Jaclyn Xiao ◽

Kathryn J. Hornburg ◽

Gary Cofer ◽

James J. Cook ◽

Forrest Pratson ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Time Course ◽

Diffusion Tensor ◽

Imaging Parameters ◽

Time Course Study

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Cortical atrophy and transcallosal diaschisis following isolated subcortical stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19831583 ◽

2019 ◽

Vol 40 (3) ◽

pp. 611-621 ◽

Cited By ~ 6

Author(s):

Bastian Cheng ◽

Philipp Dietzmann ◽

Robert Schulz ◽

Marlene Boenstrup ◽

Lutz Krawinkel ◽

...

Keyword(s):

White Matter ◽

Cortical Thickness ◽

Diffusion Tensor ◽

Brain Regions ◽

White Matter Integrity ◽

Cortical Atrophy ◽

Fiber Tractography ◽

Stroke Patients ◽

Fiber Tracts ◽

One Year

Following acute ischemic stroke, isolated subcortical lesions induce gray matter atrophy in anatomically connected, yet distant cortical brain regions. We expand on previous studies by analyzing cortical thinning in contralesional, homologous regions indirectly linked to primary stroke lesions via ipsilesional cortical areas. For this purpose, stroke patients were serially studied by magnetic resonance imaging (diffusion tensor imaging and high-resolution anatomical imaging) in the acute (days 3–5) and late chronic stage one year after stroke. We analyzed changes of gray and white matter integrity in 18 stroke patients (median age 68 years) with subcortical stroke. We applied probabilistic fiber tractography to identify brain regions connected to stroke lesions and contralesional homologous areas. Cortical thickness was quantified by semi-automatic measurements, and fractional anisotropy was analyzed. One year after stroke, significant decrease of cortical thickness was detected in areas connected to ischemic lesions (mean −0.15 mm; 95% CI −0.23 to −0.07 mm) as well as homologous contralateral brain regions (mean −0.13 mm; 95% CI −0.07 to −0.19 mm). We detected reduced white matter integrity of inter- and intrahemispheric fiber tracts. There were no significant associations with clinical recovery. Our results indicate that impact of subcortical lesions extends to homologous brain areas via transcallosal diaschisis.

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

10.1101/2020.10.28.358465 ◽

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.

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

Neurodegenerative Diseases ◽

10.1159/000515754 ◽

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

Introduction: 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. Methods: 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 t 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. Results: 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. Discussion/Conclusion: 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.

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Effects of 2'fucosyllactose and Bifidobacterium longum subsp. infantis on the Brain and Cognitive Development in the Young Pig

Current Developments in Nutrition ◽

10.1093/cdn/nzab049_022 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 909-909

Author(s):

Sangyun Joung ◽

Loretta Sutkus ◽

Johanna Hirvonen ◽

Henrik Max Jensen ◽

Arthur C Ouwehand ◽

...

Keyword(s):

Recognition Memory ◽

Diffusion Tensor ◽

Bifidobacterium Longum ◽

Mean Diffusivity ◽

Brain Regions ◽

Interactive Effects ◽

Structural Development ◽

Intact Male ◽

Brain Volumes ◽

Sample Object

Abstract Objectives Prebiotics and probiotics have been studied for their beneficial effects on various aspects of development, but much remains unknown regarding interactive effects of their supplementation. This study investigated the effects of dietary 2’fucosyllactose (2’FL; prebiotic) and Bifidobacterium longum subsp. infantis (Bi-26; probiotic) on behavioral and brain structural development in the young pig. Methods Fifty-two intact male pigs were provided ad libitum access to a nutritionally adequate milk replacer without (control) or with 0.532% 2’FL from postnatal day (PND) 2 to 34/35. Pigs were further stratified to receive either glycerol stock alone or Bi-26 (109 CFU) in glycerol stock solution daily. All pigs were subjected to the novel object recognition (NOR) task, a behavioral paradigm assessing recognition memory, from PND 27 to 31. Pigs underwent magnetic resonance imaging procedures at PND 32 or 33 to assess absolute and relative brain volume. Additionally, brain microstructure was quantified using diffusion tensor imaging (DTI) to assess fractional anisotropy, and axial, radial, and mean diffusivity. Results Behavioral outcomes confirmed that there were no effects of prebiotics or probiotics on recognition memory (P > 0.05). Interactive effects (P < 0.05) were observed for the number of object visits, latency to the first object visit, and number of sample object visits. Pigs that received the probiotic supplementation (P < 0.05) spent less time engaging with the sample object in total and on average, were observed to have smaller absolute brain volumes for 9 of 27 total observed regions of interest, and smaller relative volumes for 2 regions associated with kinesthesia. Differences in axial diffusivity were observed in pigs supplemented with the probiotic for 2 of the 12 regions assessed. Interactive effects (P < 0.05) were observed for all DTI outcomes for a variety of brain regions. Trelative volume for the pons was observed to be larger for pigs supplemented with the prebiotic. Conclusions Dietary supplementation of prebiotics and probiotics elicited interactive effects on several exploratory behaviors and structural brain components, and supplementation with probiotics appeared to reduce the volume of specific brain regions. Funding Sources DuPont Nutrition & Biosciences.

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Brain structural correlates of autistic traits across the diagnostic divide: A grey matter and white matter microstructure study

10.1101/2021.05.29.446259 ◽

2021 ◽

Author(s):

Varun Arunachalam Chandran ◽

Christos Pliatsikas ◽

Janina Neufeld ◽

Garret O'Connell ◽

Anthony Haffey ◽

...

Keyword(s):

White Matter ◽

Grey Matter ◽

Diffusion Tensor ◽

Autistic Traits ◽

Brain Regions ◽

Autism Spectrum ◽

Brain Volumes ◽

White Matter Microstructure ◽

The Social ◽

Brain Correlates

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental conditions characterised by difficulties in social interaction and communication as well as stereotyped and restricted patterns of interest. Autistic traits exist in a continuum across the general population, whilst the extreme end of this distribution is diagnosed as clinical ASD. While many studies have investigated brain structure in autism using a case-control design, few have used a dimensional approach. To add to this growing body of literature, we investigated the structural brain correlates of autistic traits in a mixed sample of adults (N=91) with and without a clinical diagnosis of autism. We examined regional brain volumes (using voxel-based morphometry and surface-based morphometry) and white matter microstructure properties (using Diffusion Tensor Imaging). Our findings show widespread grey matter differences, including in the social brain regions, and some evidence for white matter microstructure differences related to higher autistic traits. These grey matter and white matter microstructure findings from our study are consistent with previous reports and support the brain structural differences in ASD. These findings provide further support for shared aetiology for autistic traits across the diagnostic divide.

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Chd8 mutation in oligodendrocytes alters microstructure and functional connectivity in the mouse brain

Molecular Brain ◽

10.1186/s13041-020-00699-x ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Atsuki Kawamura ◽

Yoshifumi Abe ◽

Fumiko Seki ◽

Yuta Katayama ◽

Masaaki Nishiyama ◽

...

Keyword(s):

Social Interaction ◽

Functional Connectivity ◽

Diffusion Tensor ◽

Brain Connectivity ◽

Brain Regions ◽

Autism Spectrum ◽

Mutant Mice ◽

Test Analysis ◽

Brain Microstructure ◽

Diffusion Tensor Imaging Dti

AbstractCHD8 encodes a chromatin-remodeling factor and is one of the most recurrently mutated genes in individuals with autism spectrum disorder (ASD). Although we have recently shown that mice heterozygous for Chd8 mutation manifest myelination defects and ASD-like behaviors, the detailed mechanisms underlying ASD pathogenesis have remained unclear. Here we performed diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) in oligodendrocyte lineage-specific Chd8 heterozygous mutant mice. DTI revealed that ablation of Chd8 specifically in oligodendrocytes of mice was associated with microstructural changes of specific brain regions including the cortex and striatum. The extent of these changes in white matter including the corpus callosum and fornix was correlated with total contact time in the reciprocal social interaction test. Analysis with rsfMRI revealed changes in functional brain connectivity in the mutant mice, and the extent of such changes in the cortex, hippocampus, and amygdala was also correlated with the change in social interaction. Our results thus suggest that changes in brain microstructure and functional connectivity induced by oligodendrocyte dysfunction might underlie altered social interaction in mice with oligodendrocyte-specific CHD8 haploinsufficiency.

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UPTAKE OF OXYTOCIN IN TISSUES AFTER INTRAVENOUS ADMINISTRATION OF TRITIATED OXYTOCIN IN RATS

Acta Endocrinologica ◽

10.1530/acta.0.0610432 ◽

1969 ◽

Vol 61 (3) ◽

pp. 432-440 ◽

Cited By ~ 7

Author(s):

Ingvar Sjöholm ◽

Gunnar Rydén

Keyword(s):

Skeletal Muscle ◽

Distribution Pattern ◽

Intravenous Injection ◽

Intravenous Administration ◽

Time Course ◽

Tritiated Water ◽

Preferential Distribution ◽

Time Period ◽

Initial Uptake

ABSTRACT The distribution of oxytocin in the kidneys, liver, uterus and skeletal muscle of the rat was followed during 10 min after intravenous injection of tritium labelled oxytocin. Oxytocin was found to be taken up and degraded mainly in the kidneys and the liver. After 150 seconds no intact oxytocin could be detected in these organs. The time course of the distribution of the radioactivity in the liver and the skeletal muscle showed no noteworthy characteristics, whereas a different course was found in the kidneys and in the uterus. In the kidneys, the radioactivity increased continuously from 60 to 200 seconds after the injection, indicating an accumulation of oxytocin or its metabolites in the kidneys. In the uterus a high initial uptake was observed, followed by a decrease of the radioactivity from 60 to 100 seconds after the injection. This distribution pattern was specific to oxytocin, since the uptake of tritiated tyrosine and tritiated water was almost constant during the same time period. These findings may indicate a preferential distribution of oxytocin to the uterus.

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Engaging regularly with fiction influences connectivity in cortical areas for language and mentalizing

10.31234/osf.io/e7bqj ◽

2017 ◽

Author(s):

Roel M. Willems ◽

Franziska Hartung

Keyword(s):

Functional Connectivity ◽

Time Course ◽

Language Skills ◽

Brain Regions ◽

Brain Areas ◽

Daily Lives ◽

Cortical Areas ◽

Social Abilities ◽

Behavioral Evidence ◽

Amount Of Reading

Behavioral evidence suggests that engaging with fiction is positively correlated with social abilities. The rationale behind this link is that engaging with fictional narratives offers a ‘training modus’ for mentalizing and empathizing. We investigated the influence of the amount of reading that participants report doing in their daily lives, on connections between brain areas while they listened to literary narratives. Participants (N=57) listened to two literary narratives while brain activation was measured with fMRI. We computed time-course correlations between brain regions, and compared the correlation values from listening to narratives to listening to reversed speech. The between-region correlations were then related to the amount of fiction that participants read in their daily lives. Our results show that amount of fiction reading is related to functional connectivity in areas known to be involved in language and mentalizing. This suggests that reading fiction influences social cognition as well as language skills.

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