title: Manual segmentation of the fornix, fimbria, and alveus on high-resolution 3T MRI: Application via fully-automated mapping of the human memory circuit white and grey matter in healthy and pathological aging.
abstract: Recently, much attention has been focused on the definition and structure of the hippocampus and its subfields, while the projections from the hippocampus have been relatively understudied. Here, we derive a reliable protocol for manual segmentation of hippocampal white matter regions (alveus, fimbria, and fornix) using high-resolution magnetic resonance images that are complementary to our previous definitions of the hippocampal subfields, both of which are freely available at https://github.com/cobralab/atlases. Our segmentation methods demonstrated high inter- and intra-rater reliability, were validated as inputs in automated segmentation, and were used to analyze the trajectory of these regions in both healthy aging (OASIS), and Alzheimer's disease (AD) and mild cognitive impairment (MCI; using ADNI). We observed significant bilateral decreases in the fornix in healthy aging while the alveus and cornu ammonis (CA) 1 were well preserved (all p's<0.006). MCI and AD demonstrated significant decreases in fimbriae and fornices. Many hippocampal subfields exhibited decreased volume in both MCI and AD, yet no significant differences were found between MCI and AD cohorts themselves. Our results suggest a neuroprotective or compensatory role for the alveus and CA1 in healthy aging and suggest that an improved understanding of the volumetric trajectories of these structures is required.
authors.affiliation: Computational Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada; Integrated Program in Neuroscience, McGill University, Montreal, Canada. Electronic address: robert.s.c.amaral@gmail.com.
authors.forename: Robert S C
authors.initials: RSC
authors.lastname: Amaral
authors.affiliation: Computational Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada; Schulich School of Medicine and Dentistry, Western University, London, Canada.
authors.forename: Min Tae M
authors.initials: MTM
authors.lastname: Park
authors.affiliation: Computational Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada; Department of Psychiatry, McGill University, Montreal, Canada.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Devenyi
authors.affiliation: Computational Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada.
authors.forename: Vivian
authors.initials: V
authors.lastname: Lynn
authors.affiliation: Kimel Family Translational Imaging-Genetics Laboratory, Campbell Family Mental Health Institute, CAMH, Toronto, Canada.
authors.forename: Jon
authors.initials: J
authors.lastname: Pipitone
authors.affiliation: Computational Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Winterburn
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Canada; MRI Unit, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Sofia
authors.initials: S
authors.lastname: Chavez
authors.affiliation: School of Psychology, University of Wollongong, Wollongong, NSW, Australia; Neuroscience Research Australia, Sydney, NSW, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Schira
authors.affiliation: MRI Unit, Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Lobaugh
authors.affiliation: Kimel Family Translational Imaging-Genetics Laboratory, Campbell Family Mental Health Institute, CAMH, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
authors.forename: Aristotle N
authors.initials: AN
authors.lastname: Voineskos
authors.affiliation: McGill Centre for Studies in Aging, McGill University, Montreal, Canada.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Pruessner
authors.affiliation: Computational Brain Anatomy Laboratory, Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada; Integrated Program in Neuroscience, McGill University, Montreal, Canada; Department of Psychiatry, McGill University, Montreal, Canada; Department of Biological and Biomedical Engineering, McGill University, Montreal, Canada. Electronic address: mallar@cobralab.ca.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D001271:Atlases as Topic; D056547:CA1 Region, Hippocampal / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D020712:Fornix, Brain / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000473:pathology; D066128:Gray Matter / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D006624:Hippocampus / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods*; D066127:White Matter / Q000033:anatomy & histology* / Q000000981:diagnostic imaging / Q000473:pathology; D055815:Young Adult
keywords: AD; Anatomy; Hippocampus; MCI; Segmentation; White matter