Article
Subcortical fiber integrity and myelination is impaired in focal cortical dysplasia – translational characterisation using diffusion microstructure imaging in vivo and tissue analysis ex vivo
Subcorticale Faserintegrität und Myelinisierung bei fokaler corticaler Dyplasie – translationale Charakterisierung mikrostruktureller Veränderungen durch Diffusion microstructure imaging in vivo und Gewebeanalyse ex vivo
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Authors
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Florian Raue
- Universitätsklinikum Freiburg, Sektion Grundlagen epileptischer Erkrankungen, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
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Catharina Donkels
- Universitätsklinikum Freiburg, Sektion Grundlagen epileptischer Erkrankungen, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
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Marco Reisert
- Universitätsklinikum Freiburg, Klinik für Radiologie, Medizinphysik, Freiburg i. Br., Deutschland
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Carola Haas
- Universitätsklinikum Freiburg, Sektion Grundlagen epileptischer Erkrankungen, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
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Andreas Schulze-Bonhage
- Universitätsklinikum Freiburg, Epilepsiezentrum, Freiburg i. Br., Deutschland
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Jürgen Beck
- Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
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Irina Mader
- Universitätsklinikum Freiburg, Klinik für Neuroradiologie, Freiburg i. Br., Deutschland; Schön-Klinik Vogtareuth, Klinik für Radiologie, Vogtareuth, Deutschland
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Horst Urbach
- Universitätsklinikum Freiburg, Klinik für Neuroradiologie, Freiburg i. Br., Deutschland
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Christian Scheiwe
- Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
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Julia M. Nakagawa
- Universitätsklinikum Freiburg, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland; Universitätsklinikum Freiburg, Sektion Grundlagen epileptischer Erkrankungen, Klinik für Neurochirurgie, Freiburg i. Br., Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: Structural changes are a major cause of pharmaco-resistant focal epilepsy. Surgical therapeutic options are based on the identification of the epileptogenic focus and the extent of the lesion. As severe structural impairment of cortical architecture and myelination characterize focal cortical dysplasia (FCD), this translational study aims to merge diagnostic methods based on diffusion MRI (dMRI) in vivo introducing a novel postprocessing method and microstructural tissue analysis ex vivo.
Methods: Sixteen patients with FCD and n=11 control specimens without FCD undergoing presurgical epileptological assessment were included in the study. Pre-operative high-angular diffusion weighted images were acquired with 61 directions on a 3T MRI scanner and whole brain global fiber tracking was performed. To disentangle microscopic cell properties from the effects of mesoscopic structure diffusion microstructure imaging (DMI) measurements were obtained based on a three-compartment model using a Bayesian approach. Regions of interest (ROI) for further analysis were defined in the dysplastic cortex, the adjacent subcortical white matter and in the subcortical transmantle sign. For intraindividual comparison, a corresponding set of ROI was placed contralaterally in the identical anatomical region.
Following neuropathological confirmation of FCD, analysis of (sub-)cortical structure and myelination was performed using immunohistochemical methods (NeuN, SMI32, Vimentin, MBP, CNPase) and In situ-hybridization histochemistry. For structural and quantitative analysis, confocal laser scanning microscopy and 3D-reconstruction methods were used and complemented by electron microscopy for analysis of ultrastructure.
Results: Whereas conventional dMRI merely reveals subtle alterations of diffusivity in FCD, postprocessing for DMI identifies specific cortical and subcortical microstructural alterations in FCD in vivo. Complementary ex vivo analysis of myelination and fiber composition reveals severe impairment and fragmentation of subcortical fiber structure in FCD.
Conclusion: The translational analysis of microstructural tissue properties in FCD reveals strong impairment of subcortical fiber integrity and myelination. Moreover, the novel method of dMRI with DMI may provide a new diagnostic tool in presurgical epileptological evaluation in order to define the exact dimension of the lesion, essential for an optimal surgical strategy and therapeutic outcome.
