Challenges and limitations of quantifying brain connectivity in vivo with diffusion MRI

This article addresses whether or not diffusion MRI, a noninvasive technique that probes the microstructural aspects of tissue, can be used to quantify the white matter connectivity of the human brain in vivo. It begins by studying the motivation, that is, the increasing trend to look at ‘functional connectivity’ in the brain, which implies that the brain operates as a distributed network of active locations. A brief summary of diffusion MRI and fiber tracking is given and the early applications of diffusion MRI to study connectivity are reviewed. A close and critical inspection is then made of the limitations inherent in these different approaches, challenging the notion that it is possible to quantify brain connectivity in vivo with diffusion MRI. Finally, steps toward improving quantification of connectivity, by integrating information from other techniques, are suggested.