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.

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 4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury

2015 ◽  
Vol 39 (3) ◽  
pp. E9 ◽  
Author(s):  
Richard B. Boyer ◽  
Nathaniel D. Kelm ◽  
D. Colton Riley ◽  
Kevin W. Sexton ◽  
Alonda C. Pollins ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
High Resolution ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Nerve Fibers ◽  
Nerve Transection ◽  
Nerve Injuries

Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries.

scholarly journals In vivo high-resolution diffusion tensor imaging of the mouse brain

NeuroImage ◽  
2013 ◽  
Vol 83 ◽  
pp. 18-26 ◽  
Author(s):  
Dan Wu ◽  
Jiadi Xu ◽  
Michael T. McMahon ◽  
Peter C.M. van Zijl ◽  
Susumu Mori ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
High Resolution ◽  
Mouse Brain ◽  
Diffusion Tensor

High-resolution diffusion tensor imaging of fixed brain in a mouse model of Pelizaeus-Merzbacher disease: comparison with quantitative measures of white matter pathology

2011 ◽  
Vol 24 (10) ◽  
pp. 1369-1379 ◽  
Author(s):  
Torsten Ruest ◽  
William M. Holmes ◽  
Jennifer A. Barrie ◽  
Ian R. Griffiths ◽  
Thomas J. Anderson ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
High Resolution ◽  
Mouse Model ◽  
Diffusion Tensor ◽  
White Matter Pathology ◽  
Pelizaeus Merzbacher Disease

scholarly journals Retrospective analysis of hemispheric structural network change as a function of location and size of glioma

2020 ◽  
Author(s):  
Shawn D’Souza ◽  
Lisa Hirt ◽  
David R Ormond ◽  
John A Thompson
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Temporal Lobe ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Structural Network ◽  
Tumour Location ◽  
The Impact ◽  
Tractography Data ◽  
Diffusion Tensor Imaging Tractography

Abstract Gliomas are neoplasms that arise from glial cell origin and represent the largest fraction of primary malignant brain tumours (77%). These highly infiltrative malignant cell clusters modify brain structure and function through expansion, invasion and intratumoral modification. Depending on the growth rate of the tumour, location and degree of expansion, functional reorganization may not lead to overt changes in behaviour despite significant cerebral adaptation. Studies in simulated lesion models and in patients with stroke reveal both local and distal functional disturbances, using measures of anatomical brain networks. Investigations over the last two decades have sought to use diffusion tensor imaging tractography data in the context of intracranial tumours to improve surgical planning, intraoperative functional localization, and post-operative interpretation of functional change. In this study, we used diffusion tensor imaging tractography to assess the impact of tumour location on the white matter structural network. To better understand how various lobe localized gliomas impact the topology underlying efficiency of information transfer between brain regions, we identified the major alterations in brain network connectivity patterns between the ipsilesional versus contralesional hemispheres in patients with gliomas localized to the frontal, parietal or temporal lobe. Results were indicative of altered network efficiency and the role of specific brain regions unique to different lobe localized gliomas. This work draws attention to connections and brain regions which have shared structural susceptibility in frontal, parietal and temporal lobe glioma cases. This study also provides a preliminary anatomical basis for understanding which affected white matter pathways may contribute to preoperative patient symptomology.

scholarly journals Quantitative diffusion tensor imaging analysis does not distinguish pediatric canines with mucopolysaccharidosis I from control canines

2017 ◽  
Vol 30 (5) ◽  
pp. 454-460
Author(s):  
Dana M Middleton ◽  
Jonathan Y Li ◽  
Steven D Chen ◽  
Leonard E White ◽  
Patricia I Dickson ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Imaging System ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Magnetic Resonance Imaging System ◽  
Radial Diffusivity ◽  
Mucopolysaccharidosis I ◽  
Diffusivity Measurements

Purpose We compared fractional anisotropy and radial diffusivity measurements between pediatric canines affected with mucopolysaccharidosis I and pediatric control canines. We hypothesized that lower fractional anisotropy and higher radial diffusivity values, consistent with dysmyelination, would be present in the mucopolysaccharidosis I cohort. Methods Six canine brains, three affected with mucopolysaccharidosis I and three unaffected, were euthanized at 7 weeks and imaged using a 7T small-animal magnetic resonance imaging system. Average fractional anisotropy and radial diffusivity values were calculated for four white-matter regions based on 100 regions of interest per region per specimen. A 95% confidence interval was calculated for each mean value. Results No difference was seen in fractional anisotropy or radial diffusivity values between mucopolysaccharidosis affected and unaffected brains in any region. In particular, the 95% confidence intervals for mucopolysaccharidosis affected and unaffected canines frequently overlapped for both fractional anisotropy and radial diffusivity measurements. In addition, in some brain regions a large range of fractional anisotropy and radial diffusivity values were seen within the same cohort. Conclusion The fractional anisotropy and radial diffusivity values of white matter did not differ between pediatric mucopolysaccharidosis affected canines and pediatric control canines. Possible explanations include: (a) a lack of white matter tissue differences between mucopolysaccharidosis affected and unaffected brains at early disease stages; (b) diffusion tensor imaging does not detect any existing differences; (c) inflammatory processes such as astrogliosis produce changes that offset the decreased fractional anisotropy values and increased radial diffusivity values that are expected in dysmyelination; and (d) our sample size was insufficient to detect differences. Further studies correlating diffusion tensor imaging findings to histology are warranted.

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