Bridging mesoscopic and microscopic scales in multiple sclerosis: Post mortem brain block multi-contrast 9.4T MRI and histology quantification

Dimitrios G Gkotsoulias; Lukas Schönenberger; Jochen Leupold; Ilaria Callegari; Erik Bahn; Christine Stadelmann; Dominik von Elverfeldt; Valerij G Kiselev; Matthias Weigel; Cristina Granziera

doi:10.1016/j.xpro.2025.104203

Bridging mesoscopic and microscopic scales in multiple sclerosis: Post mortem brain block multi-contrast 9.4T MRI and histology quantification

STAR Protoc. 2025 Nov 17;6(4):104203. doi: 10.1016/j.xpro.2025.104203. Online ahead of print.

Affiliations

¹ Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University of Basel, Basel, Switzerland; Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, University of Basel, Allschwil, Switzerland; Department of Neurology, University Hospital Basel, Basel, Switzerland. Electronic address: dimitrios.gkotsoulias@unibas.ch.
² Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University of Basel, Basel, Switzerland; Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, University of Basel, Allschwil, Switzerland; Department of Neurology, University Hospital Basel, Basel, Switzerland.
³ Division of Medical Physics, Department of Diagnostic and Interventional Radiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Department of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
⁵ Division of Medical Physics, Department of Diagnostic and Interventional Radiology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
⁶ Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University of Basel, Basel, Switzerland; Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, University of Basel, Allschwil, Switzerland; Department of Neurology, University Hospital Basel, Basel, Switzerland; Division of Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland.
⁷ Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University of Basel, Basel, Switzerland; Translational Imaging in Neurology Basel, Department of Biomedical Engineering, Faculty of Medicine, University of Basel, Allschwil, Switzerland; Department of Neurology, University Hospital Basel, Basel, Switzerland. Electronic address: cristina.granziera@unibas.ch.

Abstract

Combining ex vivo MRI mesoscopic and histopathology microscopic assessments of tissue microstructure forms a key approach in multiple sclerosis (MS) research for elucidating disease pathogenesis. We present a protocol that enables reproducible, scalable, and robust integration of MRI and histology data in MS brains. We describe steps for (1) obtaining high-resolution multi-contrast 9.4T MRI of postmortem brain blocks and (2) the usage of a custom, open-source image processing interface for robust histology-MRI registration and semi-quantitative mapping of myelin density, microglia, and cell count.

Keywords: Health Sciences; Neuroscience; microscopy.