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

Neuroimage. 2018 Apr 15;170:132-150. doi: 10.1016/j.neuroimage.2016.10.027. Epub 2016 Oct 18.


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 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.

Keywords: AD; Anatomy; Hippocampus; MCI; Segmentation; White matter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging* / pathology
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Atlases as Topic
  • CA1 Region, Hippocampal / anatomy & histology
  • CA1 Region, Hippocampal / diagnostic imaging
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / pathology*
  • Female
  • Fornix, Brain / anatomy & histology*
  • Fornix, Brain / diagnostic imaging
  • Fornix, Brain / pathology
  • Gray Matter / anatomy & histology*
  • Gray Matter / diagnostic imaging
  • Hippocampus / anatomy & histology*
  • Hippocampus / diagnostic imaging
  • Hippocampus / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuroimaging / methods*
  • White Matter / anatomy & histology*
  • White Matter / diagnostic imaging
  • White Matter / pathology
  • Young Adult