A reliable protocol for the manual segmentation of the human amygdala and its subregions using ultra-high resolution MRI

Abstract

The measurement of the volume of the human amygdala in vivo has received increasing attention over the past decade, but existing methods face several challenges. First, due to the amorphous appearance of the amygdala and the difficulties in interpreting its boundaries, it is common for protocols to omit sizable sections of the rostral and dorsal regions of the amygdala comprising parts of the basolateral complex (BL) and central nucleus (Ce), respectively. Second, segmentation of the amgydaloid complex into separate subdivisions is challenging due to the resolution of routinely acquired images and the lack of standard protocols. Recent advances in technology have made ultra-high resolution MR images available, and in this study we provide a detailed segmentation protocol for manually tracing the whole amygdala that incorporates a greater portion of the rostral and dorsal sections with techniques illustrated in detail to maximize reproducibility. In addition, we propose a geometrically-based protocol for segmenting the amygdala into four component subregions of interest (sROI), which correspond largely to amygdala subnuclear divisions: the BL sROI, centromedial (CM) sROI, basomedial (BM) sROI, and the amygdaloid cortical (ACo) sROI. We performed an intra- and inter-rater reliability study of our methods in 10 adults (5 young adults and 5 older adults). The results indicate that both protocols can be implemented with a high degree of reliability (the majority of intra-rater and inter-rater correlations were >0.81). This protocol should aid further research into the alterations in amygdala anatomy, connectivity, and function that accompany normal aging and pathology associated with neuropsychiatric disorders.

Amygdala subnuclei response and connectivity during emotional processing

“…In agreement with some previous studies (Entis et al, 2012;Prévost et al, 2011), we found that the Amunts et al (2005) AG map extends beyond the limits of the AG into the MTL white matter suggesting a mismatch between the anatomical location of the AG in our sample, and its location according to the Amunts et al (2005) atlas. Because of this limitation, and because source localization using probabilistic maps necessitates manipulation of MRI data into standard space, a process that can produce inaccuracies due to the deformations required (Yassa andStark, 2009), we used Mai (2008) atlas to manually segment the AG and its subnuclei groups in native space.…”

Quantifying interindividual variability and asymmetry of face-selective regions: A probabilistic functional atlas

“…Fourth, the inter-rater inconsistency in labeling is another factor potentially contributing unwanted variability, although our procedure of requiring the collaboration of two raters on each labeling dramatically reduced this type of variability. Moreover, as our reliability analysis noted, the reliability of our delineation had reached a good level, comparable to the reliabilities of some manually delineated anatomical regions, such as the amygdala and hippocampus (Entis et al, 2012;Geuze et al, 2005).…”

“…No significant difference between inter-and intra-rater reliability was found (p b 0.05, Bonferroni correction). Remarkably, the reliability is comparable to the reported reliabilities of some manually labeled anatomical regions, such as the amygdala and hippocampus (Entis et al, 2012;Geuze et al, 2005), though the boundaries of the functional regions were not as clear as the boundaries of the anatomical regions. In summary, the raters had stable performance while delineating each FSR, and the delineations from different raters were highly consistent.…”

The Role of the Amygdala in Anxiety Disorders

“…Only very recently have refinements in the acquisition and analysis of fMRI data allowed subregion function to be segregated effectively during emotional tasks such as avoidance learning [45] and facial expression recognition [21,46]. Similarly, effective structural identification of human amygdalar subregions and assessment of their functional connectivity using imaging techniques is still fairly new [for example, see [47][48][49][50][51]. Therefore, most of our understanding of causal neurochemical pathways in amygdalar circuitry related to fear and anxiety has derived from extensive studies using rodent and non-human primate models [for example, see 9,52-58].…”