The diffeomorphometry of regional shape change rates and its relevance to cognitive deterioration in mild cognitive impairment and Alzheimer's disease

Abstract

We proposed a diffeomorphometry-based statistical pipeline to study the regional shape change rates of the bilateral hippocampus, amygdala, and ventricle in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) compared with healthy controls (HC), using sequential magnetic resonance imaging (MRI) scans of 713 subjects (3,123 scans in total). The subgroup shape atrophy rates of the bilateral hippocampus and amygdala, as well as the expansion rates of the bilateral ventricles, for a majority of vertices were found to follow the order of AD > MCI > HC. The bilateral hippocampus and the left amygdala were subsegmented into multiple functionally meaningful subregions with the help of high-field MRI scans. The largest group differences in localized shape atrophy rates on the hippocampus were found to occur in CA1, followed by subiculum, CA2, and finally CA3/dentate gyrus, which is consistent with the neurofibrillary tangle accumulation trajectory. Highly nonuniform group differences were detected on the amygdala; vertices on the core amygdala (basolateral and lateral nucleus) revealed much larger atrophy rates, whereas those on the noncore amygdala (mainly centromedial) displayed similar or even smaller atrophy rates in AD relative to HC. The temporal horns of the ventricles were observed to have the largest localized ventricular expansion rate differences; with the AD group showing larger localized expansion rates on the anterior horn and the body part of the ventricles as well. Significant correlations were observed between the localized shape change rates of each of these six structures and the cognitive deterioration rates as quantified by the Alzheimer’s Disease Assessment Scale-Cognitive Behavior Section increase rate and the Mini Mental State Examination decrease rate.

Anomalous subcortical morphology in boys, but not girls, with ADHD compared to typically developing controls and correlates with emotion dysregulation

“…LDDMM has been successfully applied to group-comparison based subcortical shape analysis(Tang et al, 2014) as well as correlation to function scores. (Tang et al, 2015b) Brain-behavior correlations between subcortical morphology and parent-reported ADHD symptoms and ED were also examined.…”

Shape and diffusion tensor imaging based integrative analysis of the hippocampus and the amygdala in Alzheimer's disease

“…With that being said, the CA1 compartment was identified as being significantly affected on the bilateral hippocampi in both studies. This subregion is recognized as the one to be affected the earliest and the most severely by the neuropathology of AD in respect of neurofibrillary tangles [58,59], neuronal loss [60,61], in vivo atrophy as measured in manual segmentations of each subregion using structural MRI [62,63], as well as localized shape deformations [20,24,64–66]. Our observed CA2 atrophy of the hippocampus has also been reported in a range of previous publications [15,20,62,65–68].…”

“…5 and 6), the localized surface area atrophy in the right amygdala is more wide spread than that in the left amygdala, with the main subregions affected being the basolateral and basomedial components. A thorough survey of the AD literature would suggest that there have been very few published amygdalar subfield morphometric analyses, with [69] being the sole example outside of previous studies by the current authors' research groups [20,23,24]. A direct comparison with the findings reported in [69] is challenging given that the subdivision criteria of the amygdalas were rather different.…”

“…This shape analysis pipeline lies in the framework of large deformation diffeomorphic metric mapping (LDDMM) [34], the key idea of which is to quantify local morphometric properties using a diffeomorphism that connects two coordinate systems of interest and is itself obtained as the endpoint of a geodesic. This pipeline has been successfully applied to various aspects of AD-related investigation, including the detection and quantification of subcortical surface area atrophies in MCI and AD [20] as well as preclinical AD [23,35], the quantification of rates of change in the localized surface areas of the hippocampus, the amygdala, and the ventricle in MCI and AD [24], the analysis of MTL shape neurodegeneration networks in preclinical AD [36], the interactive effects of the apolipoprotein E genotype and age upon hippocampal and amygdalar shapes in MCI and AD [37], and the estimation of the onset time for MTL morphometric abnormalities induced by AD [38]. In keeping with our previous studies, we will introduce high-field (7 Tesla) subregional divisions of the hippocampus (four subregions: CA1, CA2, CA3 combined with dentate gyrus, and subiculum) and the amygdala (four subregions: basolateral, basomedial, centromedial, and lateral nucleus) for a more detailed evaluation of the regionally specific shape abnormalities in AD.…”

Monosynaptic excitatory transmission from the hippocampal CA1 region to the subiculum

“…It is also involved in the pathogenesis of temporal lobe epilepsy [5,6], and mental illnesses such as Alzheimer's disease [7][8][9], Addison's disease [10] and schizophrenia [11,12]. Principal cells of the subiculum (SubPCs) receive inputs from those of the CA1 region (CA1PCs) [13][14][15][16].…”