title: Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited.
abstract: Tractography based on diffusion-weighted MRI (DWI) is widely used for mapping the structural connections of the human brain. Its accuracy is known to be limited by technical factors affecting in vivo data acquisition, such as noise, artifacts, and data undersampling resulting from scan time constraints. It generally is assumed that improvements in data quality and implementation of sophisticated tractography methods will lead to increasingly accurate maps of human anatomical connections. However, assessing the anatomical accuracy of DWI tractography is difficult because of the lack of independent knowledge of the true anatomical connections in humans. Here we investigate the future prospects of DWI-based connectional imaging by applying advanced tractography methods to an ex vivo DWI dataset of the macaque brain. The results of different tractography methods were compared with maps of known axonal projections from previous tracer studies in the macaque. Despite the exceptional quality of the DWI data, none of the methods demonstrated high anatomical accuracy. The methods that showed the highest sensitivity showed the lowest specificity, and vice versa. Additionally, anatomical accuracy was highly dependent upon parameters of the tractography algorithm, with different optimal values for mapping different pathways. These results suggest that there is an inherent limitation in determining long-range anatomical projections based on voxel-averaged estimates of local fiber orientation obtained from DWI data that is unlikely to be overcome by improvements in data acquisition and analysis alone.
authors.affiliation: Program on Pediatric Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814; cibu.thomas@nih.gov.
authors.forename: Cibu
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Neurophysiology Imaging Facility, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and National Eye Institute, Bethesda, MD 20892; Section on Cognitive Neurophysiology and Imaging and.
authors.forename: Frank Q
authors.initials: FQ
authors.lastname: Ye
authors.affiliation: Program on Pediatric Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
authors.forename: M Okan
authors.initials: MO
authors.lastname: Irfanoglu
authors.affiliation: Program on Pediatric Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892;
authors.forename: Pooja
authors.initials: P
authors.lastname: Modi
authors.affiliation: Section on Cognitive Neuroscience, Laboratory of Neuropsychology, National Institute of Mental Health, Bethesda, MD, 20892.
authors.forename: Kadharbatcha S
authors.initials: KS
authors.lastname: Saleem
authors.affiliation: Neurophysiology Imaging Facility, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and National Eye Institute, Bethesda, MD 20892; Section on Cognitive Neurophysiology and Imaging and.
authors.forename: David A
authors.initials: DA
authors.lastname: Leopold
authors.affiliation: Program on Pediatric Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, 20892; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
authors.forename: Carlo
authors.initials: C
authors.lastname: Pierpaoli
mesh_terms: D000465:Algorithms; D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000648:ultrastructure; D001834:Body Water; D063132:Connectome / Q000379:methods*; D003287:Contrast Media; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods* / Q000706:statistics & numerical data; D056324:Diffusion Tensor Imaging / Q000379:methods* / Q000706:statistics & numerical data; D019786:Gadolinium DTPA; D007930:Leucine / Q000493:pharmacokinetics; D008253:Macaca mulatta / Q000033:anatomy & histology*; D008297:Male; D008959:Models, Neurological; D009044:Motor Cortex / Q000033:anatomy & histology; D009778:Occipital Lobe / Q000033:anatomy & histology; D011392:Proline / Q000493:pharmacokinetics; D012372:ROC Curve; D012107:Research Design; D012680:Sensitivity and Specificity; D014316:Tritium / Q000032:analysis; D066127:White Matter / Q000033:anatomy & histology
chemical_list: D003287:Contrast Media; D014316:Tritium; D011392:Proline; D007930:Leucine; D019786:Gadolinium DTPA
keywords: diffusion MRI; tracer; tractography; validation; white matter