Post-Mortem MRI and Histopathology in Neurologic Disease: A Translational Approach

Jonkman, Laura E.; Kenkhuis, Boyd; Geurts, Jeroen J. G.; Berg, Wilma D. J. van de

doi:10.1007/s12264-019-00342-3

Cited by 20 publications

(15 citation statements)

References 107 publications

(151 reference statements)

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“…Hence, an influence of these factors on the results cannot be completely excluded. Finally, since various types of pathology (cerebral ischemia, aging, and AD-related degeneration) may participate in the mechanisms of WMH progression and cognitive impairment in WMH patients [ 73 ], longitudinal studies with Aβ and tau measures are warranted, to reach further consensus on specific GM alterations underlying cognitive decline in WMH and evaluate the clinical value of GM for the prediction of early cognitive impairment in WMH patients.…”

Section: Discussionmentioning

confidence: 99%

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment

et al. 2021

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Grey matter (GM) alterations may contribute to cognitive decline in individuals with white matter hyperintensities (WMH) but no consensus has yet emerged. Here, we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment (WMH-MCI), 43 WMH patients without cognitive impairment, and 55 healthy controls. Both WMH groups showed GM atrophy in the bilateral thalamus, fronto-insular cortices, and several parietal-temporal regions, and the WMH-MCI group showed more extensive and severe GM atrophy. The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients. Furthermore, the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses. These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

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Section: Discussionmentioning

confidence: 99%

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment

et al. 2021

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“…Subsequent studies are needed to discover whether this method provides useful information of clinically relevant pathology. A potentially fruitful approach is combining (post mortem) imaging methods with the MQM [ 40 ]. Finally, to limit observer bias and therefore provide more objective myelin estimates, ImageJ built-in methods for an automatic global threshold calculation may be useful.…”

Section: Discussionmentioning

confidence: 99%

Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination

Huitema

Strijbis

Luchicchi

et al. 2021

IJMS

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Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS). Repair through remyelination can be extensive, but quantification of remyelination remains challenging. To date, no method for standardized digital quantification of remyelination of MS lesions exists. This methodological study aims to present and validate a novel standardized method for myelin quantification in progressive MS brains to study myelin content more precisely. Fifty-five MS lesions in 32 tissue blocks from 14 progressive MS cases and five tissue blocks from 5 non-neurological controls were sampled. MS lesions were selected by macroscopic investigation of WM by standard histopathological methods. Tissue sections were stained for myelin with luxol fast blue (LFB) and histological assessment of de- or remyelination was performed by light microscopy. The myelin quantity was estimated with a novel myelin quantification method (MQM) in ImageJ. Three independent raters applied the MQM and the inter-rater reliability was calculated. We extended the method to diffusely appearing white matter (DAWM) and encephalitis to test potential wider applicability of the method. Inter-rater agreement was excellent (ICC = 0.96) and there was a high reliability with a lower- and upper limit of agreement up to −5.93% to 18.43% variation in myelin quantity. This study builds on the established concepts of histopathological semi-quantitative assessment of myelin and adds a novel, reliable and accurate quantitative measurement tool for the assessment of myelination in human post-mortem samples.

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“…However, the nature of the actual underlying pathophysiology of these in vivo imaging measurements may vary and requires histopathological validation. Due to the time lag between in vivo imaging and histology, several studies have evaluated the sensitivity, specificity and substrate of in vivo imaging markers by combining post-mortem ex cranium and in situ brain MRI with histology ( Jonkman et al , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Can post-mortem MRI be used as a proxy for in vivo? A case study

Boon

Pouwels

Jonkman

et al. 2019

Brain Communications

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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.

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Post-Mortem MRI and Histopathology in Neurologic Disease: A Translational Approach

Cited by 20 publications

References 107 publications

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment

Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination

Can post-mortem MRI be used as a proxy for in vivo? A case study

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