Detection of entorhinal layer II using 7Tesla [corrected] magnetic resonance imaging

Abstract

The entorhinal cortex lies in the mediotemporal lobe and has major functional, structural, and clinical significance. The entorhinal cortex has a unique cytoarchitecture with large stellate neurons in layer II that form clusters. The entorhinal cortex receives vast sensory association input, and its major output arises from the layer II and III neurons that form the perforant pathway. Clinically, the neurons in layer II are affected with neurofibrillary tangles, one of the two pathological hallmarks of Alzheimer's disease. We describe detection of the entorhinal layer II islands using magnetic resonance imaging. We scanned human autopsied temporal lobe blocks in a 7T human scanner using a solenoid coil. In 70 and 100 microm isotropic data, the entorhinal islands were clearly visible throughout the anterior-posterior extent of entorhinal cortex. Layer II islands were prominent in both the magnetic resonance imaging and corresponding histological sections, showing similar size and shape in two types of data. Area borders and island location based on cytoarchitectural features in the mediotemporal lobe were robustly detected using the magnetic resonance images. Our ex vivo results could break ground for high-resolution in vivo scanning that could ultimately benefit early diagnosis and treatment of neurodegenerative disease.

Fig 1

Proton density–weighted images (100μm) of the anterior parahippocampal gyrus (ie, entorhinal cortex [EC]) collected from 7T scanner with a 28.5 × 44mm solenoid coil. Entorhinal islands are shown throughout the rostrocaudal extent of the parahippocampal gyrus at the level of the (A) amygdala, (B) uncal hippocampus, and (C) posterior hippocampus. (A–C) Sections are sliced coronally; (D) section is sliced tangentially. White arrowheads point to the best examples of entorhinal layer II (A–C). (A) Additional layers in the EC are observed: a single asterisk designates layer III, and two asterisks designate layer IV. (D) A digital tangential section of the entorhinal layer II is represented; the bright white areas represent the entorhinal islands, and the surrounding dark areas are the intervening white matter. Scale bar = 1cm.

Fig 2

Corresponding high-resolution magnetic resonance image (MRI) and histological Nissl section of the entorhinal cortex. (A) A high-resolution (100μm) ex vivo MRI of a 66-year-old man; (B) the corresponding Nissl section stained with thionin. Note the islands in layer II in both types of images (arrowheads) match each other and are demarcated with three black arrowheads. Scale bar = 1cm.

Fig 3

Neighboring cortical areas are predicted with magnetic resonance imaging (MRI) scans across parahippocampal gyrus. Areas including and bordering the entorhinal cortex (EC) were labeled manually with line drawings that originated in the white matter and ended in the gray matter. Note the manual line drawings correlate with the MRI intensity, and labels coincide with the MRI peaks. PARA = parasubiculum; PreSUB = presubiculum; SUB = subiculum.

Fig 4

The magnetic resonance imaging data were split into two groups, and two volumes were created: one test (red) and the other retest (blue). Manual labels were drawn on two separate data files and compared. The colocalization between the two volumes (green) represents where they overlap.