Post-mortem Magnetic Resonance Imaging as an Additional Tool of the Neuropathological Examination of Neurodegenerative and Cerebrovascular Diseases

European Neurological Review, 2016;11(1):22–5 DOI: http://doi.org/10.17925/ENR.2016.11.01.22

Abstract:

Neuropathological examination of post-mortem brains of patients with dementia due to neurodegenerative and cerebrovascular changes remains important, as the family wants to be sure about the clinical diagnosis and the risk of a hereditary disease. 7.0-tesla magnetic resonance imaging (MRI) can be applied as an additional tool to examine post-mortem brains of patients with neurodegenerative and cerebrovasular diseases. It allows examination of serial coronal sections of a cerebral hemisphere and horizontal sections of brainstem and cerebellum and comparison with the neuropathological lesions. Post-mortem MRI can show the degree and the distribution of the cerebral atrophy. Additional small cerebrovascular lesions can be quantified. The degree of iron load, not due to microbleeds, can be evaluated in different basal ganglia and brainstem structures. Three to six serial sections of a cerebral hemisphere and one section of brainstem and cerebellum allow the evaluation of the most important brain changes and to select the small samples to be used for histological diagnostic purposes. These correlation studies are extremely important for the future, when more 7.0-tesla MRI machines will be available for in vivo clinical-radiological diagnosis. This article is a review of post-mortem MRI data in the brains of patients with neurodegenerative and vascular dementias.
Keywords: Post-mortem, 7.0-tesla magnetic resonance imaging (MRI), neurodegenerative diseases, cerebrovascular diseases, cerebral atrophy, white matter changes, lacunar infarcts, cortical micro-bleeds, cortical micro-infarcts, cortical superficial siderosis, iron deposition
Disclosure: Jacques L De Reuck has nothing to declare in relation to this article. No funding was received for the publication of this article.
Acknowledgments: The following persons have contributed to the present research project: Florent Auger, Nicolas Durieux, Vincent Deramecourt, Charlotte Cordonnier, Claude-Alain Maurage, Didier Leys, Florence Pasquier and Regis Bordet. This study was funded by the INSERM U 1172 (Universté Lille 2, Lille, France).
Received: February 15, 2016 Accepted March 15, 2016
Correspondence: Jacques De Reuck, Leopold II laan 96, 9000 Ghent, Belgium. E: dereuck.j@gmail.com
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.

Although post-mortem neuropathological examination is increasingly performed less often in most western countries, it is still needed in patients with dementia, due to neurodegenerative and cerebrovascular changes, It is important for the family to be sure about the clinical diagnosis and to exclude the risk of a hereditary disease. Clinicalneuropathological correlation studies actually show only a concordance rate around 65%.1 A previously informed consent of the patients or from the nearest family must be obtained to allow an autopsy for diagnostic and scientific purposes.

Neuroimaging during life with 1.5 and 3.0-tesla magnetic resonance imaging (MRI) contributes moderately to the clinical diagnosis. There is hope that 7.0-tesla MRI will be more helpful, but actually only a few neurological centres utilise this technique and only a few clinicalradiological correlation studies have been performed until now.2Postmortem correlation studies combining MRI and histopathology are needed to validate the 7.0-tesla MRI findings in vivo when more centres will utilise of this technique.3 This article reviews what is currently known about post-mortem MRI data in the brains of patients with neurodegenerative and vascular dementias.

Though a definitive post-mortem diagnosis still needs to be confirmed by an extensive macroscopic and microscopic examination of the brain using validated neuropathological criteria,4 7.0-tesla MRI can be used as an additional tool to examine post-mortem brains of patients with neurodegenerative diseases. The degree and the distribution of the cerebral atrophy and white matter changes (WMCs) can be demonstrated. It also detects lesions that can be selected for histological examination. Additional small cerebrovascular lesions can be quantified. The degree of iron load can be evaluated in different basal ganglia and brainstem structures.

A variety of post-mortem MRI techniques have been used including scanning of fixed whole brains or hemispheres,5 coronal brain slices,6 un-fixed whole brains7 and brains in situ.8 The number of detected small cerebrovascular lesions depends on the MRI characteristics, such as pulse sequence, sequence parameters, spatial resolution, magnetic field strength and image post-processing.9 8.0-tesla MRI was shown to be significantly more sensitive to detect small cerebrovascular lesions than 1.5 and 3.0-tesla MRI in postmortem brains.10

Author’s experience with 7.0-tesla MRI
In our experience, we used a 7.0-tesla (Bruker Biospin SA, Ettlinger, Germany) with an issuer-receiving cylinder coil of 72 mm inner diameter, initially employed for animal experiments. Formalin fixed brain sections were placed in a plastic box and filled with salt-free water after cleaning the formalin fixation.11 Serial coronal MRI sections of a cerebral hemisphere and horizontal sections of brainstem and cerebellum were compared to the lesions, observed on macroscopic and histological examination.

Three MRI sequences were used: a positioning sequence, a spin echo T2 sequence and a T2 star (T2*) weighted-echo sequence. The positioning sequence was needed for determination of the threedirectional position of the brain section inside the magnet. The thickness of the T2 images was 1 mm. The field of view was a 9 cm square slide that was coded by a 256 matrix giving a voxel size of 0.352 x 0.352 x 1 mm. T2 weighted images were obtained by using Rapid Acquisition with Relaxation Enhancement (RARE) sequence with repetition time (TR), echo time (TE) and RARE factor of 2,500 ms, 33 ms and 8 ms, respectively. The acquisition time of this sequence was 80 s. The thickness of the T2* images was 0.20 mm. The field of view was also a 9 cm2. It was coded by a 512 matrix, giving a voxel size of 0.176 x 0.176 x 0.2 mm. The slice thickness corresponded to the upper part of the of the brain section. This sequence was a gradient echo sequence with a short TR of 60 ms and TE of 22 ms, a flip angle of 30° and number of excitation of 20. The acquisition time of the sequence was 10 min.12 As the procedures took at least 30 minutes for examination of each section, no additional fluidattenuated inversion recovery (FLAIR) was performed as it added no further information.

Six coronal sections of a cerebral hemisphere, a sagital section of the brainstem and a horizontal section from a cerebellar hemisphere allowed quantification of small cerebrovascular lesions. The sections of the cerebral hemisphere consisted of one at the prefrontal level in front of the frontal horn, one of the frontal lobe at the level of the head of the caudate nucleus, a central one near the mammillary body, a postcentral one, a parietal one at the level of the splenium corporis callosi and one at the level of the occipital lobe.

Additional histological examination of a separate standard coronal section of a cerebral hemisphere at the level of the mammillary body, allowed quantification of small lesions and validation of the MRI findings.13

Cerebral atrophy
Cerebral cortical atrophy on MRI allows comparison to the findings of the macroscopic examination of coronal sections of the brain. Due to the better differentiation between gray matter and WMCs, MRI has the advantage of better differentiation between atrophy, due to cortical lesions and those due to white changes. The most severe atrophy of the frontal and temporal lobes is observed in frontotemporal lobar degeneration (FTLD).13 The degree of hippocampal atrophy correlates well with the histological staging of severity in Alzheimer’s disease (AD) (Figure1).14 In progressive supranuclear palsy (PSP) severe atrophy of the whole brainstem is demonstrated.15

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Keywords: Post-mortem, 7.0-tesla magnetic resonance imaging (MRI), neurodegenerative diseases, cerebrovascular diseases, cerebral atrophy, white matter changes, lacunar infarcts, cortical micro-bleeds, cortical micro-infarcts, cortical superficial siderosis, iron deposition