High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas

Abstract

The amygdala is composed of multiple nuclei with unique functions and connections in the limbic system and to the rest of the brain. However, standard in vivo neuroimaging tools to automatically delineate the amygdala into its multiple nuclei are still rare. By scanning postmortem specimens at high resolution (100-150µm) at 7T field strength (n = 10), we were able to visualize and label nine amygdala nuclei (anterior amygdaloid, cortico-amygdaloid transition area; basal, lateral, accessory basal, central, cortical medial, paralaminar nuclei). We created an atlas from these labels using a recently developed atlas building algorithm based on Bayesian inference. This atlas, which will be released as part of FreeSurfer, can be used to automatically segment nine amygdala nuclei from a standard resolution structural MR image. We applied this atlas to two publicly available datasets (ADNI and ABIDE) with standard resolution T1 data, used individual volumetric data of the amygdala nuclei as the measure and found that our atlas i) discriminates between Alzheimer's disease participants and age-matched control participants with 84% accuracy (AUC=0.915), and ii) discriminates between individuals with autism and age-, sex- and IQ-matched neurotypically developed control participants with 59.5% accuracy (AUC=0.59). For both datasets, the new ex vivo atlas significantly outperformed (all p < .05) estimations of the whole amygdala derived from the segmentation in FreeSurfer 5.1 (ADNI: 75%, ABIDE: 54% accuracy), as well as classification based on whole amygdala volume (using the sum of all amygdala nuclei volumes; ADNI: 81%, ABIDE: 55% accuracy). This new atlas and the segmentation tools that utilize it will provide neuroimaging researchers with the ability to explore the function and connectivity of the human amygdala nuclei with unprecedented detail in healthy adults as well as those with neurodevelopmental and neurodegenerative disorders.

Keywords: Alzheimer's; Amygdala; Atlas; Autism; Ex vivo; Medial temporal lobe.

Fig 1. Coronal images from MRI of example ex vivo (case 7)

The boundaries of nine amygdala nuclei were clearly visible on the left column and were used to hand-label the nuclei. Resulting nuclei labels illustrated on the right column. Slices extend from anterior to posterior amygdala (from top to bottom panels). La: lateral; Ba: basal; AB: accessory basal; Ce: central; Me: medial; Co: cortical; CAT: Cortico-amygdaloid Transition Area; AAA: Anterior Amygdala Area; PL: paralaminar nucleus; Ot: optic tract (as landmark).

Fig 2. Inter-rater comparison of nucleus labels (case 1)

Another example ex vivo case depicting the MRI contrast without any labels (left column) and with the manually-labeled nuclei produced by the two raters (middle and right columns). The location and spatial extent of the nuclei were similar between the two independent raters. Labels were based mainly on boundaries visible on coronal slices, but the two other orientations (axial and sagittal) were especially useful for checking boundaries of nuclei that were elongated in those orientations such as Co, CAT, Ce, and Me nuclei.

Fie 3. Coronal section of probabilistic atlas, with (A) and without (B) tetrahedral mesh superimposed

The color of each voxel is a combination of the colors of the different labels, weighted by the corresponding probabilities at each location. Different colors represent specific nuclei: green: Me, dark blue: CAT, orange: AB, red: Ba, purple: Ce off-white: Co yellow: AAA, light blue: LA, turquoise: PL.

Fig 4. 3-Dimensional rendering of manual segmentation based on MRI in one ex vivo case

(A) anterior, (B) medial-lateral, (C) posterior, (D) coronal view. Different colors represent specific nuclei: green: Me, dark blue: CAT, orange: AB, red: Ba, purple: Ce off-white: Co yellow: AAA, light blue: La, turquoise: PL. For display purposes label boundaries are smoothed (5).

Fig 5. In vivo segmentations of amygdala nuclei overlaid on standard T1-weighted anatomical MR image (from ABIDE dataset)

(A) Coronal, (B) sagittal, and (C) axial views. Panel A illustrates the MR image without any nuclei in order to visualize contrast quality. Different colors represent specific nuclei: green: Me, dark blue: CAT, orange: AB, red: Ba, purple: Ce, off-white: Co, yellow: AAA, light blue: La.