Advancing neuroscience by imaging BRAin Cortical fibErs

Introduction

MRI provides the unique opportunity to investigate the relation between brain structure and function non-invasively, which is key to understanding the functioning of the brain and unraveling disease processes. An important technique is diffusion MRI (dMRI), which allows for the reconstruction of the structural connections through which brain structures communicate.

Challenges

Conversely, no technique can reconstruct the internal wiring of brain structures such as the cortex in living humans, where cognitive functions are processed, hindering scientific and societal progress. To achieve this, three challenges must be overcome:

1. A spatial gap of an order of magnitude between (d)MRI and the cortical circuitry.
2. Insufficient contrast provided by (d)MRI in the cortex.
3. A lack of appropriate models to characterize cortical circuits.

Objectives

I aim to bridge the gap between structure and function by mapping the fibers of the brain cortex non-invasively for the first time, which are expected to be affected by neurodegenerative processes and to be closely related to cognitive decline. To achieve this goal, I will pioneer a synergistic approach combining my expertise in (d)MRI acquisition and modeling with unique acquisition hardware designed at our institution.

Methodology

First, I will establish a novel multidimensional acquisition combining dMRI with MR relaxometry, together with a signal model tailored to characterize axonal fibers in the cortex. Next, I will leverage state-of-the-art hardware and super-resolution approaches to push the boundaries of in-vivo MRI by an order of magnitude (to the mesoscale).

Expected Outcomes

This will unveil cortical fibers in living humans for the first time and allow us to explore their properties in patients with Alzheimer’s disease, their changes during aging, and their relationship with cognitive function. Altogether, we will provide a new asset to understand cognitive dysfunction in neurodegeneration and generate novel fundamental insights for systems neuroscience.