title: Using Diffusion Tractography to Predict Cortical Connection Strength and Distance: A Quantitative Comparison with Tracers in the Monkey.
abstract: Tractography based on diffusion MRI offers the promise of characterizing many aspects of long-distance connectivity in the brain, but requires quantitative validation to assess its strengths and limitations. Here, we evaluate tractography's ability to estimate the presence and strength of connections between areas of macaque neocortex by comparing its results with published data from retrograde tracer injections. Probabilistic tractography was performed on high-quality postmortem diffusion imaging scans from two Old World monkey brains. Tractography connection weights were estimated using a fractional scaling method based on normalized streamline density. We found a correlation between log-transformed tractography and tracer connection weights of r = 0.59, twice that reported in a recent study on the macaque. Using a novel method to estimate interareal connection lengths from tractography streamlines, we regressed out the distance dependence of connection strength and found that the correlation between tractography and tracers remains positive, albeit substantially reduced. Altogether, these observations provide a valuable, data-driven perspective on both the strengths and limitations of tractography for analyzing interareal corticocortical connectivity in nonhuman primates and a framework for assessing future tractography methodological refinements objectively.
  
  
  
  Tractography based on diffusion MRI has great potential for a variety of applications, including estimation of comprehensive maps of neural connections in the brain ("connectomes"). Here, we describe methods to assess quantitatively tractography's performance in detecting interareal cortical connections and estimating connection strength by comparing it against published results using neuroanatomical tracers. We found the correlation of tractography's estimated connection strengths versus tracer to be twice that of a previous study. Using a novel method for calculating interareal cortical distances, we show that tractography-based estimates of connection strength have useful predictive power beyond just interareal separation. By freely sharing these methods and datasets, we provide a valuable resource for future studies in cortical connectomics.
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Chad J
authors.identifier: 0000-0002-6440-7892
authors.initials: CJ
authors.lastname: Donahue
authors.affiliation: Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom OX3 9DU.
authors.forename: Stamatios N
authors.identifier: 0000-0003-4735-5776
authors.initials: SN
authors.lastname: Sotiropoulos
authors.affiliation: Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom OX3 9DU.
authors.forename: Saad
authors.identifier: 0000-0003-3234-5639
authors.initials: S
authors.lastname: Jbabdi
authors.affiliation: Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom OX3 9DU.
authors.forename: Moises
authors.identifier: 0000-0001-8386-3968
authors.initials: M
authors.lastname: Hernandez-Fernandez
authors.affiliation: Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom OX3 9DU.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Behrens
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark 2650, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark 2800, and.
authors.forename: Tim B
authors.identifier: 0000-0003-3361-9734
authors.initials: TB
authors.lastname: Dyrby
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Timothy
authors.identifier: 0000-0002-2105-7896
authors.initials: T
authors.lastname: Coalson
authors.affiliation: Stem-cell and Brain Research Institute, Bron, France 69500.
authors.forename: Henry
authors.initials: H
authors.lastname: Kennedy
authors.affiliation: Stem-cell and Brain Research Institute, Bron, France 69500.
authors.forename: Kenneth
authors.identifier: 0000-0002-4681-4638
authors.initials: K
authors.lastname: Knoblauch
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110, vanessen@wustl.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Van Essen
authors.affiliation: Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Glasser
mesh_terms: D000818:Animals; D001931:Brain Mapping; D002520:Cercopithecidae; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D063132:Connectome; D056324:Diffusion Tensor Imaging; D007839:Functional Laterality; D007091:Image Processing, Computer-Assisted; D008959:Models, Neurological; D009412:Nerve Fibers / Q000502:physiology*; D009415:Nerve Net / Q000000981:diagnostic imaging* / Q000502:physiology
keywords: cerebral cortex; connectivity; diffusion tractography; macaque; neuroanatomy; retrograde tracing