Biology subjects

Mirault, D.

Publications and source records attributed to Mirault, D..

5 recordsLinked to original sources

bioRxiv2026

T2 relaxometry for myelin water fraction: an ex vivo brain imaging study

Abstract Introduction: Myelin water imaging provides a non-invasive approach for indirectly investigating myelin content of the brain by magnetic resonance Imaging (MRI). Myelin water fraction (MWF) reflects the fraction of water signal associated with water trapped between myelin layers. Postmortem imaging provides a unique opportunity to validate MWF metrics against gold-standard postmortem neuropathology. However, there is a need for validated sequences that would be applicable in postmortem settings. In this study, we validated and compared the applicability of turbo spin echo (TSE) and gradient-and-spin-echo (GRASE) techniques for myelin water imaging in formaldehyde fixed postmortem human brains. Methods: 40 postmortem human brain hemispheres were scanned with TSE and GRASE sequences. Acquired data were reconstructed using a non-parametric multicomponent T2 relaxometry approach using a consistent framework to support comparison between GRASE- and TSE-derived measures. Agreement between derived measures was quantified at both voxel and regional level. Maps derived from the full 32-echo GRASE reconstruction were compared against a truncated 14-echo reconstruction to examine the contribution of the longer echoes to the derived maps. Finally, a random forest regression model was trained based on TSE data to predict the GRASE-derived MWF maps. Results: Both sequences provided robust multicomponent T2 characterization across the brain, and the derived measures showed anatomical patterns consistent with expected differences across tissue types. TSE and GRASE derived maps had moderate to strong agreement at voxel (0.41< {rho} < 0.82, all pFDR<0.001) and regional levels (0.87< {rho} < 0.98, all pFDR<0.001), with consistently stronger agreement observed for regional metrics. Echo reduction comparisons between the full 32-echo GRASE reconstruction and a truncated 14-echo reconstruction showed minimal impact of echo truncation (all {rho} > 0.98, pFDR < 0.001). The nonlinear random forest regression model trained on TSE maps was able to accurately reproduce the MWF maps derived from GRASE (r = 0.91, RMSE = 8.87). Discussion: TSE and GRASE32 capture strongly related multicomponent T2 information in fixed postmortem human brain tissue, but with systematic and tissue-dependent quantitative differences across derived measures. These differences suggest that direct interchangeability should not be assumed and that cross-sequence mapping or calibration is required when quantitative equivalence is desired.

neuroscience↗

bioRxiv2026

Disease-specific tangle immunophenotypes distinguish hippocampal vulnerability in Alzheimers disease and Parkinsons disease dementia

Structured AbstractINTRODUCTION Tau pathology typically occurs in Alzheime[r]s disease (AD), however is also frequently present in Parkinso[n]s disease dementia (PDD) and Dementia with Lewy Bodies (DLB), yet its disease-specific signature is unclear. METHODSFive tau, amyloid-{beta}, -synuclein and neuronal markers were analysed across hippocampal subfields in non-demented controls (CTLs), AD, PDD and DLB using multiplex immunohistochemistry, single-tangle classification and confocal imaging. RESULTSAT8, pTau217, and GT38 were predominatly detected in AD, while pS422 was enriched in PDD and pS396 showed a region- and disease-specific pattern. DLB resembled AD in subregional tau distribution. Tau marker correlation were different comparing AD, PDD and CTL. Single-tangle analyses revealed disease-specific immunophenotypes but conserved mature intra-tangle epitope organisation. Distinct tau signatures were associated with inhibitory interneuron vulnerability, while regional tau co-occurrence with amyloid-{beta} and -synuclein remained conserved. DISCUSSIONDisease-specific tau signatures vary across hippocampal subregions and neuronal populations, implicating the contribution of regional and cell-specific factors beyond pathology burden.

neuroscience↗

bioRxiv2026

Spatiotemporal trajectories of formaldehyde fixation effects on quantitative MRI in postmortem human brains

Introduction: Postmortem human brain magnetic resonance imaging (MRI) offers a unique opportunity to study finer neuroanatomical details and enables direct correlations with gold standard histological and immunohistochemical assessments. However, to prevent tissue decay, postmortem brains are preserved in fixative solutions which can alter tissue properties and exert substantial impacts on the MRI signals. The present study investigates the impact of formalin fixation, the most commonly used solution for postmortem human brain preservation, on different quantitative MRI contrasts. Methods: 142 intact human brain hemispheres immersed in 10% formalin for a range of fixation durations (between 0 days and 20 years) were imaged in a 3T MRI scanner. A subset of 10 brains were further scanned repeatedly at days 0, 3, 10, 20, 30, 60, 90, and 120 to allow for better characterization of the initial transient effects of fixation. Voxel-wise T1 and T2* relaxation, T1/T2 ratio, and myelin water fraction (MWF) maps were generated for each specimen and timepoint, and linear and nonlinear models were used to examine the spatiotemporal changes associated with progressive fixation. Results: All investigated metrics were significantly impacted by formalin fixation, albeit at different rates and with differing regional patterns. T1 and T2* relaxation time decreased as a result of progressive fixation, whereas T1/T2 ratio and MWF measures increased. T1 relaxation and T1/T2 ratio showed nonlinear patterns with initially accelerated changes that decelerate in the first few months, whereas T2* relaxation and MWF changes followed a more linear trend. Conclusion: Formaldehyde fixation exerts systematic changes on quantitative MRI signals that can be modeled and adjusted for to allow for harmonized comparisons of MRI metrics across brains fixed for differing durations. The distinct temporal trajectories observed across metrics highlight the need to account for fixation duration in study design and downstream analyses, particularly when integrating datasets acquired under heterogeneous conditions. Our findings provide a quantitative framework for correcting fixation-induced biases, thereby improving the interpretability and reproducibility of postmortem MRI studies.

neuroscience↗

bioRxiv2025

GPC5 expression highlights astrocytic heterogeneity and divergent hippocampal responses in Alzheimer's and Parkinson's Dementia

Regional heterogeneity of astrocytes and neurons is increasingly recognised as a determinant of selective vulnerability in neurodegeneration, yet the molecular signatures underlying this specificity remain poorly defined. Glypican-5 (GPC5), a heparan sulfate proteoglycan expressed mainly by astrocytes, contributes to synaptic organisation and circuit stability, whose disruption may undermine astrocyte-neuron crosstalk and contribute to selective neuronal loss in neurodegenerative diseases. Using multiplex chromogenic immunohistochemistry, in situ hybridization and digital pathology, we mapped GPC5 expression across the hippocampus and parahippocampal cortex in post-mortem tissue from non-demented control (CTL), Alzheimers disease (AD) and Parkinsons disease with dementia (PDD) cases. In CTL brains, GPC5 labelled spatially restricted populations of astrocytes and pyramidal neurons organized according to hippocampal subfield and laminar architecture. GPC5-positive astrocytes co-expressed canonical markers but represented a more restricted population while GPC5 protein was enriched at synapse-rich regions of the outer molecular layer of the dentate gyrus. In AD and PDD, regional distribution patterns of GPC5 were distinct from canonical astrocyte markers including GFAP, AQP4 and ALDH1L1. In PDD, GPC5 distribution was largely preserved. In AD, GPC5 underwent selective redistribution with a significant loss of the staining in the dentate gyrus, and an accumulation on amyloid plaques, putatively secreted by plaque-associated astrocytes, and on neurofibrillary tangles, likely of neuronal and astrocytic origin These findings reveal disease- and region-specific remodelling of a spatially organised astrocyte-neuron system and establish GPC5 as a molecularly distinct responder to AD pathology.

neuroscience↗

bioRxiv2024

The Douglas Bell Canada Brain Bank Post-mortem Brain Imaging Protocol

Magnetic resonance imaging (MRI) is a valuable non-invasive tool that has been widely used for in vivo investigations of brain morphometry and microstructural characteristics. Postmortem MRIs can provide complementary anatomical and microstructural information to in vivo imaging and ex vivo neuropathological assessments without compromising the sample for future investigations. We have developed a postmortem MRI protocol for the brain specimens of the Douglas-Bell Canada Brain Bank (DBCBB), the largest brain bank in Canada housing over 3000 neurotypical and diseased brain specimens, that allows for acquisition of high-resolution 3T and 7T MRIs. Our protocol can be used to scan DBCBB specimens with minimal tissue manipulation, allowing for feasibly scanning large numbers of postmortem specimens while retaining the quality of the tissue for downstream histology and immunohistochemistry assessments. We demonstrate the robustness of this protocol in spite of the dependency of image quality on fixation by acquiring data on the first day of extraction and fixation, to over twenty years post fixation. The acquired images can be used to perform volumetric segmentations, cortical thickness measurements, and quantitative analyses which can be potentially used to link MRI-derived and ex vivo histological measures, assaying both the normative organization of the brain and ex vivo measures of pathology.

neuroscience↗