Abstract

Ex-vivo brain quantitative susceptibility mapping (QSM) allows investigation of brain characteristics at essentially the same point in time as histopathologic examination, and therefore has the potential to become an important tool for determining the role of QSM as a diagnostic and monitoring tool of age-related neuropathologies. In order to be able to translate the ex-vivo QSM findings to in-vivo, it is crucial to understand the effects of death and chemical fixation on brain magnetic susceptibility measurements collected ex-vivo. Thus, the objective of this work was twofold: a) to assess the behavior of magnetic susceptibility in both gray and white matter of human brain hemispheres as a function of time postmortem, and b) to establish the relationship between in-vivo and ex-vivo gray matter susceptibility measurements on the same hemispheres. Five brain hemispheres from community-dwelling older adults were imaged ex-vivo with QSM on a weekly basis for six weeks postmortem, and the longitudinal behavior of ex-vivo magnetic susceptibility in both gray and white matter was assessed. The relationship between in-vivo and ex-vivo gray matter susceptibility measurements was investigated using QSM data from eleven older adults imaged both antemortem and postmortem. No systematic change in ex-vivo magnetic susceptibility of gray or white matter was observed over time postmortem. Additionally, it was demonstrated that, gray matter magnetic susceptibility measured ex-vivo may be well modeled as a linear function of susceptibility measured in-vivo. In conclusion, magnetic susceptibility in gray and white matter measured ex-vivo with QSM does not systematically change in the first six weeks after death. This information is important for future cross-sectional ex-vivo QSM studies of hemispheres imaged at different postmortem intervals. Furthermore, the linear relationship between in-vivo and ex-vivo gray matter magnetic susceptibility suggests that ex-vivo QSM captures information linked to antemortem gray matter magnetic susceptibility, which is important for translation of ex-vivo QSM findings to in-vivo.

Highlights

  • Quantitative susceptibility mapping (QSM) is a recently developed magnetic resonance imaging (MRI) technique that has shown promise in investigations of age-related diseases [1, 2]

  • Considering the advantages of combining ex-vivo MRI with histopathologic examination, this study indicates that ex-vivo QSM may become an important tool for the assessment of the neuropathologic correlates of magnetic susceptibility in aging

  • The present study aimed at assessing the behavior of magnetic susceptibility in gray and white matter of human brain hemispheres as a function of time postmortem, and establishing the relationship between gray matter susceptibility measurements conducted in-vivo and ex-vivo on the same brain hemispheres

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Summary

Introduction

Quantitative susceptibility mapping (QSM) is a recently developed magnetic resonance imaging (MRI) technique that has shown promise in investigations of age-related diseases [1, 2]. The MRI data most proximal to autopsy are typically collected years prior to death, and additional pathology may develop during that period This leads to an underestimation of the pathology-related brain changes that can be detected with MRI. It is crucial to understand the effects of death and chemical fixation on brain MRI data collected ex-vivo Such investigations have been conducted for ex-vivo measurements of regional brain volumes [23], T1 [24], and T2 [25] values. The effects of death and chemical fixation on the behavior of magnetic susceptibility of human brain hemispheres over time postmortem have not been systematically investigated This information is important for future cross-sectional ex-vivo QSM studies on brain hemispheres imaged at different postmortem intervals. This is essential for translating any ex-vivo QSM findings to in-vivo

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