Imaging multiple sclerosis pathology at 160\xa0\u03bcm isotropic resolution by human whole-brain ex vivo magnetic resonance imaging at 3\xa0T

Matthias Weigel,Po-Jui Lu,Riccardo Galbusera,Ludwig Kappos,Cristina Granziera,Govind Nair,Wolfgang Brück,Peter Dechent,Christine Stadelmann,Erik Bahn

doi:10.1038/s41598-021-94891-1

Abstract

Postmortem magnetic resonance imaging (MRI) of the fixed healthy and diseased human brain facilitates spatial resolutions and image quality that is not achievable with in vivo MRI scans. Though challenging—and almost exclusively performed at 7 T field strength—depicting the tissue architecture of the entire brain in fine detail is invaluable since it enables the study of neuroanatomy and uncovers important pathological features in neurological disorders. The objectives of the present work were (1) to develop a 3D isotropic ultra-high-resolution imaging approach for human whole-brain ex vivo acquisitions working on a standard clinical 3 T MRI system; and (2) to explore the sensitivity and specificity of this concept for specific pathoanatomical features of multiple sclerosis. The reconstructed images demonstrate unprecedented resolution and soft tissue contrast of the diseased human brain at 3 T, thus allowing visualization of sub-millimetric lesions in the different cortical layers and in the cerebellar cortex, as well as unique cortical lesion characteristics such as the presence of incomplete/complete iron rims, and patterns of iron accumulation. Further details such as the subpial molecular layer, the line of Gennari, and some intrathalamic nuclei are also well distinguishable.

Highlights

Postmortem magnetic resonance imaging (MRI) of the fixed healthy and diseased human brain facilitates spatial resolutions and image quality that is not achievable with in vivo MRI scans
As it can be deduced from all the figures, the complete setup of fixed brain, dedicated container, hardware, and MRI sequence is stable enough for measuring isotropic ultra-high resolutions up to 160 μm in 3D with a pronounced tissue contrast over more than 90 h
We developed an ex vivo whole-brain MR imaging approach that facilitates isotropic 3D ultra-high-resolution imaging up to 160 μm with a strong soft tissue contrast on a common clinical 3 T MR system

Summary

Introduction

Postmortem magnetic resonance imaging (MRI) of the fixed healthy and diseased human brain facilitates spatial resolutions and image quality that is not achievable with in vivo MRI scans. The reconstructed images demonstrate unprecedented resolution and soft tissue contrast of the diseased human brain at 3 T, allowing visualization of sub-millimetric lesions in the different cortical layers and in the cerebellar cortex, as well as unique cortical lesion characteristics such as the presence of incomplete/complete iron rims, and patterns of iron accumulation. Further details such as the subpial molecular layer, the line of Gennari, and some intrathalamic nuclei are well distinguishable. Postmortem whole brain imaging is important to observe neuroanatomic relationships across distant brain regions, to provide neuroanatomical reference points in standard stereotactic space and to understand neurological diseases affecting the entire brain structure

Objectives

Methods

Results

Conclusion