Ex vivo diffusion MRI of the human brain: Technical challenges and recent advances

Abstract

This review discusses ex vivo diffusion magnetic resonance imaging (dMRI) as an important research tool for neuroanatomical investigations and the validation of in vivo dMRI techniques, with a focus on the human brain. We review the challenges posed by the properties of post-mortem tissue, and discuss state-of-the-art tissue preparation methods and recent advances in pulse sequences and acquisition techniques to tackle these. We then review recent ex vivo dMRI studies of the human brain, highlighting the validation of white matter orientation estimates and the atlasing and mapping of large subcortical structures. We also give particular emphasis to the delineation of layered gray matter structure with ex vivo dMRI, as this application illustrates the strength of its mesoscale resolution over large fields of view. We end with a discussion and outlook on future and potential directions of the field.

The role of diffusion MRI in neuroscience

“…One such approach for modelling the diffusion signal (instead of DTI) is to devise a mathematical formalism that is guided by tissue geometry. Yet, anyone who has looked down a microscope at a brain section would have been impressed by the complexity of the white matter geometry . Cells of different shapes and sizes with processes spreading at different scales and orientations depict a mess of geometries at the micrometre scale.…”

“…Yet, anyone who has looked down a microscope at a brain section would have been impressed by the complexity of the white matter geometry. 36,62 Cells of different shapes and sizes with processes spreading at different scales and orientations depict a mess of geometries at the micrometre scale. Even at a lower level of magnification, where cell layers and fibre bundles are visible, complexity arises where fibres cross, disperse and fan within hundreds of micrometres.…”

“…69 Neural tissue is complex, and it should be realized that there is no single model that can capture all the details and complexity of different neural compartments. 62,72 The different abovementioned models (and others) try to separate different features of interest of the tissue. Obviously, the inclusion of too many free parameters in the model will lead to computational problems, such as overfitting and other optimization and data fitting issues.…”

Monte Carlo Simulation of Diffusion MRI in geometries constructed from two-photon microscopy of human cortical grey matter

“…This is because there are many differences between ex vivo and in vivo MRI such as fixation effects, temperature differences, etc. that makes direct extrapolation of ex vivo measurements to the analysis of in vivo MRI data a formidable task; this has been discussed for the prostate in [33] and for the brain in [39].…”

“…Immunohistochemistry [5], scanning electron microscopy [34], different light microscopy techniques [35] such as two-photon microscopy [36], and ultra-high field (UHF) diffusion MRI [37] of ex vivo tissue samples have improved our understanding of the cortex microstructure in the last years. However, since there are a number of morphological changes in the fixation process [33,38,39] in addition to temperature differences, extrapoloation from ex vivo MRI or microscopy to analysis in vivo diffusion MRI require conservative mathematical modellings.…”