Estimating brain connectivity with diffusion-weighted MRI: Promise and peril

Diffusion-weighted magnetic resonance imaging (dMRI) is a popular tool for noninvasively assessing properties of white matter in the brain. Among other uses, dMRI data can be used to produce estimates of anatomical connectivity on the basis of tractography. However, direct comparisons of anatomical connectivity as estimated through invasive neural tract-tracing experiments and dMRI-derived connectivity have shown only a moderate relationship in nonhuman primate (particularly macaque) studies. Tractography is plagued by known problems associated with resolution, crossing fibers, and curving fibers, among others. These problems lead to deficits in both sensitivity and specificity, which trade off with each other in multiple datasets. Although not yet examined quantitatively, there is reason to believe that some large white matter bundles, those with more topographic organization, may produce more accurate results than others. Moving forward, sophisticated analytical approaches and anatomical constraints may improve tractography accuracy. However, broadly speaking, dMRI-derived estimates of brain connectivity should be approached with caution.