Microstructural Analysis of Brain Organization: the Ambitious Goal of Magnetic Resonance Imaging-Based in Vivo Histology (hMRI)
With high-field strength (7 Tesla or more) structural MRI, scientists can today map the human brain with sub-millimeter resolution. This stands in sharp contrast to our remarkable ignorance of the underlying microstructural basis of the MRI signal. Which cellular components of the brain gray and white matter are involved? Neurons with their processes, glia cells, myelin sheaths? Does iron play a role? These pressing but largely unanswered questions are of great relevance both to basic research (e.g., non-invasive microanatomical parcellation of the human cortex into structural modules, so-called "In Vivo Brodmann Mapping") and to clinical research topics of neurology and psychiatry (e.g., non-invasive histological diagnosis of pathological changes in the brain).
To answer these questions we validate structural MRI data with histological techniques. We scan post-mortem brains with MRI and either embed them in paraffin and section them with a conventional microtome or freeze and cut them with a freezing microtome or cryostat. On these sections we study various aspects of brain microanatomy, e.g., the structure and arrangement of cells (cytoarchitecture) with the "classical" Nissl stain or the structure of myelin sheaths (myeloarchitecture) with myelin stains. For special research questions that require ultra-high resolution we use semithin sections or ultrathin sections in combination with transmission electron microscopy. To analyze the spatial distribution of chemical elements (e.g., iron, phosphorus, sulfur) we scan tissue sections with proton-induced X-ray emission (PIXE). This combination of techniques (in cooperation with the Paul Flechsig Brain Research Institute and the Physics Faculty of the University of Leipzig) allows us to directly correlate MRI-based anatomy with histological anatomy.
We also employ revolutionary technological advances in the field of histology, e.g., a recently published technique called CLARITY. By extracting the lipids CLARITY transforms brain tissue into an optically transparent hydrogel polymer. This polymer can be incubated "en bloc" with fluorescent markers for specific components of neurons or glia cells (e.g., proteins of the myelin sheath) and then optically sectioned layer by layer with a laser scanning microscope. This obviates the need for tedious cutting of the blocks with a microtome, correcting the sections for artifacts, and assembling them into a 3-D volume.
With these transdisciplinary approaches – together with biophysical modeling – we expect to gain new insights into the histological and histochemical basis of the various MRI contrasts. We are convinced that in the future the "typical" tools for anatomical brain research such as a saw, hammer, knife or drill will become partly obsolete – an MRI scanner will do the job!
Available PhD projects
Can be defined and negotiated if interested.