title: Histological validation of DW-MRI tractography in human postmortem tissue.
abstract: Despite several previous attempts, histological validation of diffusion-weighted magnetic resonance imaging (DW-MRI)-based tractography as true axonal fiber pathways remains difficult. In the present study, we establish a method to compare histological and tractography data precisely enough for statements on the level of single tractography pathways. To this end, we used carbocyanine dyes to trace connections in human postmortem tissue and aligned them to high-resolution DW-MRI of the same tissue processed within the diffusion tensor imaging (DTI) formalism. We provide robust definitions of sensitivity (true positives) and specificity (true negatives) for DTI tractography and characterize tractography paths in terms of receiver operating characteristics. With sensitivity and specificity rates of approximately 80%, we could show a clear correspondence between histological and inferred tracts. Furthermore, we investigated the effect of fractional anisotropy (FA) thresholds for the tractography and identified FA values between 0.02 and 0.08 as optimal in our study. Last, we validated the course of entire tractography curves to move beyond correctness determination based on pairs of single points on a tract. Thus, histological techniques, in conjunction with alignment and processing tools, may serve as an important validation method of DW-MRI on the level of inferred tractography projections between brain areas.
authors.affiliation: Department of Biology, Technische Universität Darmstadt, 64287 Darmstadt, Germany. seehaus@bio.tu-darmstadt.de
authors.forename: Arne K
authors.initials: AK
authors.lastname: Seehaus
authors.forename: Alard
authors.initials: A
authors.lastname: Roebroeck
authors.forename: Oriana
authors.initials: O
authors.lastname: Chiry
authors.forename: Dae-Shik
authors.initials: DS
authors.lastname: Kim
authors.forename: Itamar
authors.initials: I
authors.lastname: Ronen
authors.forename: Hansjürgen
authors.initials: H
authors.lastname: Bratzke
authors.forename: Rainer
authors.initials: R
authors.lastname: Goebel
authors.forename: Ralf A W
authors.initials: RA
authors.lastname: Galuske
mesh_terms: D019540:Area Under Curve; D001344:Autopsy; D001921:Brain / Q000033:anatomy & histology*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D009434:Neural Pathways / Q000033:anatomy & histology*; D012372:ROC Curve; D012680:Sensitivity and Specificity