The goal of the ERC project is to develop novel methods for high-resolution quantitative magnetic resonance imaging (MRI) at 3T-9.4T to reliably characterize and quantify the detailed microstructure of the human cortex. This ambitious goal of developing in vivo histology using MRI (hMRI) can only be achieved by an integrative approach combining innovations in MR physics, modelling and tailored neuroscience experiments. If successful, the project will transform research and clinical imaging. It will facilitate personalized medicine, patient stratification and multi-center treatment trials in neurodegenerative diseases by providing reliable and standardized biomarkers.
Spinal cord injury is a severe and devastating neurological disorder that leaves patients with permanent paralysis of the body. No treatment is available today to regenerate interrupted nerve fibers and repair the damaged spinal cord. The EU Horizon 2020 collaborative NISCI project is a multi-center clinical proof of concept trial aiming at the repair of the injured spinal cord through antibody induced regeneration after acute spinal cord injury. The biomarker subproject at the MPI CBS is an international collaboration between the Prof. Weiskopf (MPI-CBS) and Dr. Freund (University of Zuerich), bringing together the unique expertise in MRI methods and clinical neuroscience. We will be developing and deploying state-of-the-art quantitative MRI methods for characterization of the brain and spinal cord microstructure. This includes deploying the MRI techniques across the different clinical trial sites and ensuring their high performance. These methods will serve as a sensitive biomarker for treatment effects and potential adverse effects of the antibody treatment.
DFG-Funded SPP 2041 Project 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 are of utmost importance for its functional organization because they 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 long-range connections in the human brain. However, mapping from diffusion to fiber pathways is still ill-posed and has several major limitations. As a result, tractography algorithms can take "wrong turns" and produce false positive and 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.
In this highly inter-disciplinary project, we will 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 fuse gold-standard ex vivo histology with MRI to validate the proposed model at central junctions of long-range fiber pathways within the well characterized human voluntary motor control network. By emphasizing the close integration of multi-modal computational biophysical models, advanced MRI technology (the German-wide unique combination of a CONNECTOM & 7T MRI system), and advanced histological approaches (CLARITY in human tissue), this project aims at innovative new insights into MRI-based computational models for in vivo tractography.
BRAINTRAIN will improve and adapt the methods of real-time fMRI neurofeedback (fMRI-NF) for clinical use, including the combination with electroencephalography (EEG) and the development of standardised procedures for the mapping of brain networks that can be targeted with neurofeedback.