scholarly journals Developing formalin‐based fixative agents for post mortem brain MRI at 9.4 T

Author(s):  
Azadeh Nazemorroaya ◽  
Ali Aghaeifar ◽  
Thomas Shiozawa ◽  
Bernhard Hirt ◽  
Hildegard Schulz ◽  
...  
Author(s):  
Celine Berger ◽  
Melanie Bauer ◽  
Holger Wittig ◽  
Eva Scheurer ◽  
Claudia Lenz

Abstract Objective MRI temperature sensitivity presents a major issue in in situ post mortem MRI (PMMRI), as the tissue temperatures differ from living persons due to passive cooling of the deceased. This study aims at computing brain temperature effects on the MRI parameters to correct for temperature in PMMRI, laying the foundation for future projects on post mortem validation of in vivo MRI techniques. Materials and methods Brain MRI parameters were assessed in vivo and in situ post mortem using a 3 T MRI scanner. Post mortem brain temperature was measured in situ transethmoidally. The temperature effect was computed by fitting a linear model to the MRI parameters and the corresponding brain temperature. Results Linear positive temperature correlations were observed for T1, T2* and mean diffusivity in all tissue types. A significant negative correlation was observed for T2 in white matter. Fractional anisotropy revealed significant correlations in all gray matter regions except for the thalamus. Discussion The linear models will allow to correct for temperature in post mortem MRI. Comparing in vivo to post mortem conditions, the mean diffusivity, in contrast to T1 and T2, revealed additional effects besides temperature, such as cessation of perfusion and active diffusion.


2016 ◽  
Vol 12 ◽  
pp. P462-P462
Author(s):  
Martina M. Hughes ◽  
Beatriz G. Perez-Nievas ◽  
Claire Troakes ◽  
Michael Perkinton ◽  
Diane P. Hanger ◽  
...  

2018 ◽  
Vol 81 (4) ◽  
pp. 2688-2701 ◽  
Author(s):  
Petr Dusek ◽  
Vince Istvan Madai ◽  
Till Huelnhagen ◽  
Erik Bahn ◽  
Radoslav Matej ◽  
...  

2018 ◽  
Vol 12 ◽  
Author(s):  
Simin Mahinrad ◽  
Marjolein Bulk ◽  
Isabelle van der Velpen ◽  
Ahmed Mahfouz ◽  
Willeke van Roon-Mom ◽  
...  

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Baayla D C Boon ◽  
Petra J W Pouwels ◽  
Laura E Jonkman ◽  
Matthijs J Keijzer ◽  
Paolo Preziosa ◽  
...  

Abstract Post-mortem in situ MRI has been used as an intermediate between brain histo(patho)logy and in vivo imaging. However, it is not known how comparable post-mortem in situ is to ante-mortem imaging. We report the unique situation of a patient with familial early-onset Alzheimer’s disease due to a PSEN1 mutation, who underwent ante-mortem brain MRI and post-mortem in situ imaging only 4 days apart. T1-weighted and diffusion MRI was performed at 3-Tesla at both time points. Visual atrophy rating scales, brain volume, cortical thickness and diffusion measures were derived from both scans and compared. Post-mortem visual atrophy scores decreased 0.5–1 point compared with ante-mortem, indicating an increase in brain volume. This was confirmed by quantitative analysis; showing a 27% decrease of ventricular and 7% increase of whole-brain volume. This increase was more pronounced in the cerebellum and supratentorial white matter than in grey matter. Furthermore, axial and radial diffusivity decreased up to 60% post-mortem whereas average fractional anisotropy of white matter increased approximately 10%. This unique case study shows that the process of dying affects several imaging markers. These changes need to be taken into account when interpreting post-mortem MRI to make inferences on the in vivo situation.


2021 ◽  
Author(s):  
Alison M Maxwell ◽  
Peng Yuan ◽  
Brianna M Rivera ◽  
Wilder Schaaf ◽  
Mihovil Mladinov ◽  
...  

Amyloid beta (A&#946) is thought to play a critical role in the pathogenesis of Alzheimer&#8242s disease (AD). Prion-like Aβ polymorphs, or strains, can have varying pathogenicity and may underlie the phenotypic heterogeneity of the disease. In order to develop effective AD therapies, it is critical to identify the strains of A&#946 that might arise prior to the onset of clinical symptoms and understand how they may change with progressing disease. Down syndrome (DS), as the most common genetic cause of AD, presents promising opportunities to compare such features between early and advanced AD. In this work, we evaluate the neuropathology and A&#946 strain profile in the post-mortem brain tissues of 210 DS, AD, and control individuals. We assayed the levels of various A&#946 and tau species and used conformation-sensitive fluorescent probes to detect differences in A&#946 strains among individuals and populations. We found that these cohorts have some common but also some distinct strains from one another, with the most heterogeneous populations of A&#946 emerging in subjects with high levels of AD pathology. The emergence of distinct strains in DS at these later stages of disease suggests that the confluence of aging, pathology, and other DS-linked factors may favor conditions that generate strains that are unique from sAD.


2021 ◽  
Author(s):  
Thanit Saeliw ◽  
Tiravut Permpoon ◽  
Nutta Iadsee ◽  
Tewin Tencomnao ◽  
Tewarit Sarachana ◽  
...  

Abstract BackgroundLong interspersed nucleotide element-1 (LINE-1) and Alu elements are retrotransposons whose abilities cause abnormal gene expression and genomic instability. Several studies have focused on DNA methylation profiling of gene regions, but the locus-specific methylation of LINE-1 and Alu elements has not been identified in autism spectrum disorder (ASD).MethodsHere, DNA methylation age was predicted using Horvath’s method. We interrogated locus- and family-specific methylation profiles of LINE-1 and Alu elements (22,352 loci) in ASD blood using publicly-available Illumina Infinium 450K methylation datasets from heterogeneous ASD (n = 52), ASD with 16p11.2 del (n = 7), and ASD with Chromodomain Helicase DNA-binding 8 (CHD8) variants (n = 15). The differentially methylated positions of LINE-1 and Alu elements corresponding to genes were combined with transcriptome data from multiple ASD studies. ROC curve was conducted to examine the specificity of target loci.ResultsEpigenetic age acceleration was significantly decelerated in ASD children over the age of 11 years. DNA methylation profiling revealed LINE-1 and Alu methylation signatures in each ASD risk loci by which global methylation were notably hypomethylated exclusively in ASD with CHD8 variants. When LINE-1 and Alu elements were clustered into subfamilies, we found methylation changes in a family-specific manner in L1P, L1H, HAL, AluJ, and AluS families in the heterogeneous ASD and ASD with CHD8 variants. Our results showed that LINE-1 and Alu methylation within target genes is inversely related to the expression level in each ASD variant. Moreover, LINE-1 and Alu methylation signatures can be used to predict ASD individuals from non-ASD.LimitationsIntegration of methylome and transcriptome datasets was performed from different ASD cohorts. The small sample size of the validation cohort used post-mortem brain tissues and necessitates future validation in a larger cohort.ConclusionsThe DNA methylation signatures of the LINE-1 and Alu elements in ASD, as well as their functional impact on ASD-related genes, have been studied. These findings are considered for further research into DNA methylation profiles and the expression of the LINE-1 and Alu elements in post-mortem brain tissue, which has been linked to ASD pathogenesis.


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