A novel ex vivo, in situ method to study the human brain through MRI and histology

Maranzano, Josefina; Dadar, Mahsa; Bertrand-Grenier, Antony; Frigon, Eve-Marie; Pellerin, Johanne; Plante, Sophie; Duchesne, Simon; Tardif, Christine; Boire, Denis; Bronchti, Gilles

doi:10.1016/j.jneumeth.2020.108903

Cited by 11 publications

(20 citation statements)

References 35 publications

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“…Finally, in gross anatomy laboratories, the fixation/embalming procedures are performed by arterial perfusion within 48 h following death ( Frølich et al, 1984 ; Nicholson et al, 2005 ; Brenner, 2014 ; Maranzano et al, 2020 ). This inconstant post-mortem delay introduces a variable degree of clotting, which combined with vascular stenosis may negatively impact the perfusion, confounding the fixation quality ( Turkoglu et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Antigenicity is preserved with fixative solutions used in human gross anatomy: A mice brain immunohistochemistry study

Frigon

Dadar²,

Boire³

et al. 2022

Front. Neuroanat.

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BackgroundHistology remains the gold-standard to assess human brain biology, so ex vivo studies using tissue from brain banks are standard practice in neuroscientific research. However, a larger number of specimens could be obtained from gross anatomy laboratories. These specimens are fixed with solutions appropriate for dissections, but whether they also preserve brain tissue antigenicity is unclear. Therefore, we perfused mice brains with solutions used for human body preservation to assess and compare the tissue quality and antigenicity of the main cell populations.Materials and methodsTwenty-eight C57BL/6J mice were perfused with 4% formaldehyde (FAS, N = 9), salt-saturated solution (SSS, N = 9), and alcohol solution (AS, N = 10). The brains were cut into 40 μm sections for antigenicity analysis and were assessed by immunohistochemistry of four antigens: neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP astrocytes), ionized calcium-binding adaptor molecule 1 (Iba1-microglia), and myelin proteolipid protein (PLP). We compared the fixatives according to multiple variables: perfusion quality, ease of manipulation, tissue quality, immunohistochemistry quality, and antigenicity preservation.ResultsThe perfusion quality was better using FAS and worse using AS. The manipulation was very poor in SSS brains. FAS- and AS-fixed brains showed higher tissue and immunohistochemistry quality than the SSS brains. All antigens were readily observed in every specimen, regardless of the fixative solution.ConclusionSolutions designed to preserve specimens for human gross anatomy dissections also preserve tissue antigenicity in different brain cells. This offers opportunities for the use of human brains fixed in gross anatomy laboratories to assess normal or pathological conditions.

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Section: Introductionmentioning

confidence: 99%

Antigenicity is preserved with fixative solutions used in human gross anatomy: A mice brain immunohistochemistry study

Frigon

Dadar²,

Boire³

et al. 2022

Front. Neuroanat.

Self Cite

View full text Add to dashboard Cite

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“…The typical approach of ex vivo MRI employs autopsy-extracted brains and formalin-fixed by immersion [ 119 ]. This approach ( ex vivo ex situ MRI) has a disadvantage in manipulations of extraction from the skull and fixation that potentially induce major and inevitable adverse effects for MRI scans [ 120 ]. These adverse effects are attributed to deformation by extraction [ 121 ], a gradient of fixation from surface to deep white matter [ 122 ], and artifacts by air bubbles trapped in the subarachnoid spaces [ 110 ].…”

Section: Neuroimaging Approaches Using Mri Technologymentioning

confidence: 99%

“…These adverse effects are attributed to deformation by extraction [ 121 ], a gradient of fixation from surface to deep white matter [ 122 ], and artifacts by air bubbles trapped in the subarachnoid spaces [ 110 ]. To overcome the disadvantage, some investigators propose an alternative approach that employs the brain remaining inside the head as ex vivo in situ MRI [ 120 ]. Another progress in ex vivo MRI is whole-brain, ultra-high resolution MRI with 100–170 um isotropic resolution [ 103 , 123 , 124 ], which promises to bridge the gap between histology and conventional imaging [ 123 ].…”

Section: Neuroimaging Approaches Using Mri Technologymentioning

confidence: 99%

microRNA Biology on Brain Development and Neuroimaging Approach

Shiohama

Takahashi

2022

Brain Sciences

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Proper brain development requires the precise coordination and orchestration of various molecular and cellular processes and dysregulation of these processes can lead to neurological diseases. In the past decades, post-transcriptional regulation of gene expression has been shown to contribute to various aspects of brain development and function in the central nervous system. MicroRNAs (miRNAs), short non-coding RNAs, are emerging as crucial players in post-transcriptional gene regulation in a variety of tissues, such as the nervous system. In recent years, miRNAs have been implicated in multiple aspects of brain development, including neurogenesis, migration, axon and dendrite formation, and synaptogenesis. Moreover, altered expression and dysregulation of miRNAs have been linked to neurodevelopmental and psychiatric disorders. Magnetic resonance imaging (MRI) is a powerful imaging technology to obtain high-quality, detailed structural and functional information from the brains of human and animal models in a non-invasive manner. Because the spatial expression patterns of miRNAs in the brain, unlike those of DNA and RNA, remain largely unknown, a whole-brain imaging approach using MRI may be useful in revealing biological and pathological information about the brain affected by miRNAs. In this review, we highlight recent advancements in the research of miRNA-mediated modulation of neuronal processes that are important for brain development and their involvement in disease pathogenesis. Also, we overview each MRI technique, and its technological considerations, and discuss the applications of MRI techniques in miRNA research. This review aims to link miRNA biological study with MRI analytical technology and deepen our understanding of how miRNAs impact brain development and pathology of neurological diseases.

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“…The presence of the skull limits both structural change (particularly expansion) and exposure to the surrounding medium. However, we are aware that minimal deformation may result in the end, see [43].…”

Section: Plos Onementioning

confidence: 99%

Volumetric assessment and longitudinal changes of subcortical structures in formalinized Beagle brains

Signore

Arribarat²,

Salda³

et al. 2022

PLoS ONE

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High field MRI is an advanced technique for diagnostic and research purposes on animal models, such as the Beagle dog. In this context, studies on neuroscience applications, e.g. aging and neuro-pathologies, are currently increasing. This led to a need for reference values, in terms of volumetric assessment, for the structures typically involved. Nowadays, several canine brain MRI atlases have been provided. However, no reports are available regarding the measurements’ reproducibility and little is known about the effect of formalin on MRI segmentation. Here, we assessed the segmentation variability of selected structures among operators (two operators segmented the same data) in a sample of 11 Beagle dogs. Then, we analyzed, for one Beagle dog, the longitudinal volumetric changes of these structures. We considered four conditions: in vivo, post mortem (after euthanasia), ex vivo (brain extracted and studied after 1 month in formalin, and after 12 months). The MRI data were collected with a 3 T scanner. Our findings suggest that the segmentation procedure was overall reproducible since only slight statistical differences were detected. In the post mortem/ ex vivo comparison, most structures showed a higher contrast, thereby leading to greater reproducibility between operators. We observed a net increase in the volume of the studied structures. This could be justified by the intrinsic relaxation time changes observed because of the formalin fixation. This led to an improvement in brain structure visualization and segmentation. To conclude, MRI-based segmentation seems to be a useful and accurate tool that allows longitudinal studies on formalin-fixed brains.

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A novel ex vivo, in situ method to study the human brain through MRI and histology

Cited by 11 publications

References 35 publications

Antigenicity is preserved with fixative solutions used in human gross anatomy: A mice brain immunohistochemistry study

Antigenicity is preserved with fixative solutions used in human gross anatomy: A mice brain immunohistochemistry study

microRNA Biology on Brain Development and Neuroimaging Approach

Volumetric assessment and longitudinal changes of subcortical structures in formalinized Beagle brains

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