title: Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography.
abstract: In vivo tractography based on diffusion magnetic resonance imaging (dMRI) has opened new doors to study structure-function relationships in the human brain. Initially developed to map the trajectory of major white matter tracts, dMRI is used increasingly to infer long-range anatomical connections of the cortex. Because axonal projections originate and terminate in the gray matter but travel mainly through the deep white matter, the success of tractography hinges on the capacity to follow fibers across this transition. Here we demonstrate that the complex arrangement of white matter fibers residing just under the cortical sheet poses severe challenges for long-range tractography over roughly half of the brain. We investigate this issue by comparing dMRI from very-high-resolution ex vivo macaque brain specimens with histological analysis of the same tissue. Using probabilistic tracking from pure gray and white matter seeds, we found that ∼50% of the cortical surface was effectively inaccessible for long-range diffusion tracking because of dense white matter zones just beneath the infragranular layers of the cortex. Analysis of the corresponding myelin-stained sections revealed that these zones colocalized with dense and uniform sheets of axons running mostly parallel to the cortical surface, most often in sulcal regions but also in many gyral crowns. Tracer injection into the sulcal cortex demonstrated that at least some axonal fibers pass directly through these fiber systems. Current and future high-resolution dMRI studies of the human brain will need to develop methods to overcome the challenges posed by superficial white matter systems to determine long-range anatomical connections accurately.
authors.affiliation: Sackler Center for Consciousness Science, School of Engineering and Informatics, University of Sussex, Brighton BN1 9QJ, United Kingdom;
authors.forename: Colin
authors.initials: C
authors.lastname: Reveley
authors.affiliation: Sackler Center for Consciousness Science, School of Engineering and Informatics, University of Sussex, Brighton BN1 9QJ, United Kingdom;
authors.forename: Anil K
authors.initials: AK
authors.lastname: Seth
authors.affiliation: Program on Pediatric Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Carlo
authors.initials: C
authors.lastname: Pierpaoli
authors.affiliation: Cerebral Microcirculation Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Afonso C
authors.initials: AC
authors.lastname: Silva
authors.affiliation: Neurophysiology Imaging Facility, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and National Eye Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: David
authors.initials: D
authors.lastname: Yu
authors.affiliation: Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Saunders
authors.affiliation: Neurophysiology Imaging Facility, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and National Eye Institute, National Institutes of Health, Bethesda, MD 20892; and Laboratory of Neuropsychology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892 LeopoldD@mail.nih.gov.
authors.forename: David A
authors.initials: DA
authors.lastname: Leopold
authors.affiliation: Neurophysiology Imaging Facility, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and National Eye Institute, National Institutes of Health, Bethesda, MD 20892; and.
authors.forename: Frank Q
authors.initials: FQ
authors.lastname: Ye
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000033:anatomy & histology; D063132:Connectome / Q000379:methods / Q000706:statistics & numerical data; D016208:Databases, Factual; D056324:Diffusion Tensor Imaging / Q000379:methods* / Q000706:statistics & numerical data; D066128:Gray Matter / Q000033:anatomy & histology; D006801:Humans; D021621:Imaging, Three-Dimensional; D008253:Macaca mulatta / Q000033:anatomy & histology*; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000033:anatomy & histology; D066127:White Matter / Q000033:anatomy & histology*
keywords: connectome; diffusion MRI; neuroanatomy; tractography; white matter