Unraveling Grey Matter with Diffusion MRI: Challenges and Possibilities

Abstract

The cerebral cortex is a grey matter (GM) structure in the brain that contains the vast majority of neurons. As such, it plays an important role in the functioning of the brain. GM changes are also associated with several neurodegenerative and neurodevelopmental disorders. Despite the importance of GM, there is currently a lack of methods able to provide non-invasive insights into its structure. Two emerging approaches might bridge this gap of knowledge by providing a complementary structural characterization of the cortex: biophysical modelling might allow to capture the microstructure of the cortex, whereas fiber tractography could reconstruct the spatial organization of fibers in cortical circuits. This literature review investigates the possibilities and challenges of using biophysical modeling and tractography to study the GM. Biophysical models try to resemble a non-invasive in vivo microscope. They describe the GM as a sum of microscopic compartments, and try to fit model parameters to the diffusion signal to obtain microstructural information. Preclinical results have been promising, but the development of clinically feasible acquisition protocols is challenging. Furthermore, current models are specific to healthy tissue, which makes the extension to pathologies challenging. The application of tractography to GM suffers from multiple unresolved challenges, e.g., limited spatial resolution, the gyral bias and the reconstruction of reliable fiber orientations. Multiple promising methods have been developed to overcome these challenges and are discussed in this review, but it will remain a challenge to combine these different methods to simultaneously overcome the different challenges. Due to a lack of a ground truth except histology, validation is often complicated for these two methods.