title: Quantitative validation of a nonlinear histology-MRI coregistration method using generalized Q-sampling imaging in complex human cortical white matter.
abstract: Advanced diffusion MRI methods have recently been proposed for detection of pathologies such as traumatic axonal injury and chronic traumatic encephalopathy which commonly affect complex cortical brain regions. However, radiological-pathological correlations in human brain tissue that detail the relationship between the multi-component diffusion signal and underlying pathology are lacking. We present a nonlinear voxel based two dimensional coregistration method that is useful for matching diffusion signals to quantitative metrics of high resolution histological images. When validated in ex vivo human cortical tissue at a 250×250×500 μm spatial resolution, the method proved robust in correlations between generalized q-sampling imaging and histologically based white matter fiber orientations, with r=0.94 for the primary fiber direction and r=0.88 for secondary fiber direction in each voxel. Importantly, however, the correlation was substantially worse with reduced spatial resolution or with fiber orientations derived using a diffusion tensor model. Furthermore, we have detailed a quantitative histological metric of white matter fiber integrity termed power coherence capable of distinguishing architecturally complex but intact white matter from disrupted white matter regions. These methods may allow for more sensitive and specific radiological-pathological correlations of neurodegenerative diseases affecting complex gray and white matter.
authors.affiliation: Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Mihika
authors.initials: M
authors.lastname: Gangolli
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Laurena
authors.initials: L
authors.lastname: Holleran
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Joong
authors.initials: J
authors.lastname: Hee Kim
authors.affiliation: Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Thor D
authors.initials: TD
authors.lastname: Stein
authors.affiliation: Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Alvarez
authors.affiliation: Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA.
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.affiliation: Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: brodyd@neuro.wustl.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Brody
mesh_terms: D000818:Animals; D001369:Axons; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000000981:diagnostic imaging / Q000473:pathology; D001931:Brain Mapping / Q000379:methods*; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D005625:Frontal Lobe / Q000033:anatomy & histology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D066127:White Matter / Q000033:anatomy & histology*
keywords: Chronic Traumatic Encephalopathy; Diffusion MRI; Generalized Q-sampling Imaging; Radiological-Pathological Correlations; White Matter Injury