Abstract
Ultra-high field magnetic resonance imaging (MRI) became increasingly relevant for in vivo neuroscientific research because of improved spatial resolutions. However, this is still the unchallenged domain of histological studies, which long played an important role in the investigation of neuropsychiatric disorders. While the field of biological psychiatry strongly advanced on macroscopic levels, current developments are rediscovering the richness of immunohistological information when attempting a multi-level systematic approach to brain function and dysfunction. For most studies, histology sections lost information on three-dimensional reconstructions. Translating histological sections to 3D-volumes would thus not only allow for multi-stain and multi-subject alignment in post mortem data, but also provide a crucial step in big data initiatives involving the network analyses currently performed with in vivo MRI. We therefore investigated potential pitfalls during integration of MR and histological information where no additional blockface information is available. We demonstrated that strengths and requirements from both methods can be effectively combined at a spatial resolution of 200 μm. However, the success of this approach is heavily dependent on choices of hardware, sequence and reconstruction. We provide a fully automated pipeline that optimizes histological 3D reconstructions, providing a potentially powerful solution not only for primary human post mortem research institutions in neuropsychiatric research, but also to help alleviate the massive workloads in neuroanatomical atlas initiatives. We further demonstrate (for the first time) the feasibility and quality of ultra-high spatial resolution (150 μm isotopic) imaging of the entire human brain MRI at 7T, offering new opportunities for analyses on MR-derived information.
Highlights
Rapid technical advances in magnetic resonance imaging (MRI) have strengthened the role of this important non-invasive method in neuropsychiatric research and significantly shaped neuroscientific questions in humans during the last 20 years
Post mortem histology has seemingly lost its premier role in biological psychiatry, despite a number of important insights that remain inaccessible to investigations based on MRI
In this article we describe the beneficial effects of introducing ultra-high resolution MRI in order to obtain increased degrees of freedom for non-linear transformations
Summary
Rapid technical advances in magnetic resonance imaging (MRI) have strengthened the role of this important non-invasive method in neuropsychiatric research and significantly shaped neuroscientific questions in humans during the last 20 years. The most evident reasons for neuroimaging’s rapid progression—a transition away from a field mainly characterized by histological observations in post mortem brain tissue, toward structural and functional characterizations in vivo—can be found in its capacity for experimental control of observations as well as its distinct advantages in allowing for longitudinal studies. In addition to applications for functional studies, these advantages have the potential to produce fundamental insights regarding anatomical variations in the progression of brain disorders or consecutive clinical and psychological characterizations associated with aberrant brain anatomy. Post mortem histology has seemingly lost its premier role in biological psychiatry, despite a number of important insights that remain inaccessible to investigations based on MRI. Gross changes in volumetry have cytoarchitectonic aspects based on individual contributions of different cell populations, which are crucial for characterizing underlying pathology. The cellular origins of volume loss (e.g., glial vs. neuronal) are not visible by corresponding differences in contrast, and as such
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