Studying APOE ɛ4 Allele Dose Effects with a Univariate Morphometry Biomarker.

BACKGROUND: A univariate neurodegeneration biomarker (UNB) based on MRI with strong statistical discrimination power would be highly desirable for studying hippocampal surface morphological changes associated with APOE ɛ4 genetic risk for AD in the cognitively unimpaired (CU) population. However, existing UNB work either fails to model large group variances or does not capture AD induced changes. OBJECTIVE: We proposed a subspace decomposition method capable of exploiting a UNB to represent the hippocampal morphological changes related to the APOE ɛ4 dose effects among the longitudinal APOE ɛ4 homozygotes (HM, N = 30), heterozygotes (HT, N = 49) and non-carriers (NC, N = 61). METHODS: Rank minimization mechanism combined with sparse constraint considering the local continuity of the hippocampal atrophy regions is used to extract group common structures. Based on the group common structures of amyloid-ß (Aß) positive AD patients and Aß negative CU subjects, we identified the regions-of-interest (ROI), which reflect significant morphometry changes caused by the AD development. Then univariate morphometry index (UMI) is constructed from these ROIs. RESULTS: The proposed UMI demonstrates a more substantial statistical discrimination power to distinguish the longitudinal groups with different APOE ɛ4 genotypes than the hippocampal volume measurements. And different APOE ɛ4 allele load affects the shrinkage rate of the hippocampus, i.e., HM genotype will cause the largest atrophy rate, followed by HT, and the smallest is NC. CONCLUSION: The UMIs may capture the APOE ɛ4 risk allele-induced brain morphometry abnormalities and reveal the dose effects of APOE ɛ4 on the hippocampal morphology in cognitively normal individuals.

Effect of lateral diffusion of photoelectrons in the reflection-mode varied-doping AlGaN photocathode on resolution.

To obtain a high resolution of the reflection-mode AlGaN photocathode by establishing the modulation transfer function (MTF) model of this photocathode, the influence of emission layer thickness Te, electron diffusion length Ld, recombination velocity at back-interface Vb, and optical absorption coefficient α on MTF for varied-doping and uniform-doping Al0.42Ga0.58N photocathodes have been given. The computational results suggest that varied-doping structure has great potentiality in improving both resolution and quantum efficiency of the reflection-mode Al0.42Ga0.58N photocathode. This improvement is mainly attributed to the reduced lateral diffusion of photoelectrons, which is caused by an electric field generated by the varied-doping structure, and hence the photoelectron transportation towards photocathode surface is promoted.

Developing univariate neurodegeneration biomarkers with low-rank and sparse subspace decomposition.

Cognitive decline due to Alzheimer's disease (AD) is closely associated with brain structure alterations captured by structural magnetic resonance imaging (sMRI). It supports the validity to develop sMRI-based univariate neurodegeneration biomarkers (UNB). However, existing UNB work either fails to model large group variances or does not capture AD dementia (ADD) induced changes. We propose a novel low-rank and sparse subspace decomposition method capable of stably quantifying the morphological changes induced by ADD. Specifically, we propose a numerically efficient rank minimization mechanism to extract group common structure and impose regularization constraints to encode the original 3D morphometry connectivity. Further, we generate regions-of-interest (ROI) with group difference study between common subspaces of Aß+AD and Aß-cognitively unimpaired (CU) groups. A univariate morphometry index (UMI) is constructed from these ROIs by summarizing individual morphological characteristics weighted by normalized difference between Aß+AD and Aß-CU groups. We use hippocampal surface radial distance feature to compute the UMIs and validate our work in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. With hippocampal UMIs, the estimated minimum sample sizes needed to detect a 25% reduction in the mean annual change with 80% power and two-tailed P=0.05are 116, 279 and 387 for the longitudinal Aß+AD, Aß+mild cognitive impairment (MCI) and Aß+CU groups, respectively. Additionally, for MCI patients, UMIs well correlate with hazard ratio of conversion to AD (4.3, 95% CI = 2.3-8.2) within 18 months. Our experimental results outperform traditional hippocampal volume measures and suggest the application of UMI as a potential UNB.

Cortical thickness computation by solving tetrahedron-based harmonic field.

Cortical thickness computation in magnetic resonance imaging (MRI) is an important method to study the brain morphological changes induced by neurodegenerative diseases. This paper presents an algorithm of thickness measurement based on a volumetric Laplacian operator (VLO), which is able to capture accurately the geometric information of brain images. The proposed algorithm is a novel three-step method: 1) The rule of parity and the shrinkage strategy are combined to detect and fix the intersection error regions between the cortical surface meshes separated by FreeSurfer software and the tetrahedral mesh is constructed which reflects the original morphological features of the cerebral cortex, 2) VLO and finite element method are combined to compute the temperature distribution in the cerebral cortex under the Dirichlet boundary conditions, and 3) the thermal gradient line is determined based on the constructed local isothermal surfaces and linear geometric interpolation results. Combined with half-face data storage structure, the cortical thickness can be computed accurately and effectively from the length of each gradient line. With the obtained thickness, we set experiments to study the group differences among groups of Alzheimer's disease (AD, N = 110), mild cognitive impairment (MCI, N = 101) and healthy control people (CTL, N = 128) by statistical analysis. The results show that the q-value associated with the group differences is 0.0458 between AD and CTL, 0.0371 between MCI and CTL, and 0.0044 between AD and MCI. Practical tests demonstrate that the algorithm of thickness measurement has high efficiency and is generic to be applied to various biological structures that have internal and external surfaces.