PD Dr. Stefan Geyer | Human Microstructural Connectomics: Computational Modeling and Validation with Histology and CLARITY

The arrangement, length, and microstructural properties of long-range connections in the central nervous system determine how information is distributed across the brain. To date, diffusion magnetic resonance imaging (dMRI)-based tractography is the only in vivo technique for mapping structural connections in the human brain. However, mapping from diffusion to fiber pathways is still ill-posed. As a result, tractography algorithms can take "wrong turns" and produce false positive and/or false negative connections. To address this problem, microstructure-informed tractography has been suggested. It is an emerging computational framework that associates each computed fiber tract with microstructural properties, e.g., metrics for axon diameter or density, using the dMRI technique. Our highly inter-disciplinary project with the above title is funded by the German Research Foundation (DFG) under the Priority Programme "Computational Connectomics" (SPP 2041). Four Principal Investigators (Siawoosh Mohammadi, Univ. Hamburg; Alfred Anwander & Stefan Geyer, MPI CBS Leipzig; Markus Morawski, Univ. Leipzig) plan to develop a computational framework for microstructure-informed tractography that addresses these limitations using multi-modal quantitative MRI at ultra-high spatial resolution. Moreover, we will develop an advanced ex vivo histology analysis strategy based on complementary 2-D (high-resolution semithin and ultrathin sectioning) and 3-D (CLARITY) techniques. We will combine histology with MRI ex vivo to validate the model at central junctions of long-range fiber pathways within the well characterized human voluntary motor control network. Our project aims at innovative new insights into MRI-based computational models for in vivo tractography. Funding started in May 2018. In this Institute Colloquium I will elaborate on the conceptual background from a neuroanatomical point of view and present first microstructural results.