Richard J. Caselli

Jianfeng Wu, Yi Su, Yanxi Chen et al.

Background: Alzheimer's Disease (AD) is the most common type of age-related dementia, affecting 6.2 million people aged 65 or older according to CDC data. It is commonly agreed that discovering an effective AD diagnosis biomarker could have enormous public health benefits, potentially preventing or delaying up to 40% of dementia cases. Tau neurofibrillary tangles are the primary driver of downstream neurodegeneration and subsequent cognitive impairment in AD, resulting in structural deformations such as hippocampal atrophy that can be observed in magnetic resonance imaging (MRI) scans. Objective: To build a surface-based model to 1) detect differences between APOE subgroups in patterns of tau deposition and hippocampal atrophy, and 2) use the extracted surface-based features to predict cognitive decline. Methods: Using data obtained from different institutions, we develop a surface-based federated Chow test model to study the synergistic effects of APOE, a previously reported significant risk factor of AD, and tau on hippocampal surface morphometry. Results: We illustrate that the APOE-specific morphometry features correlate with AD progression and better predict future AD conversion than other MRI biomarkers. For example, a strong association between atrophy and abnormal tau was identified in hippocampal subregion cornu ammonis 1 (CA1 subfield) and subiculum in e4 homozygote cohort. Conclusion: Our model allows for identifying MRI biomarkers for AD and cognitive decline prediction and may uncover a corner of the neural mechanism of the influence of APOE and tau deposition on hippocampal morphology.

Jianfeng Wu, Yi Su, Wenhui Zhu et al.

Background: Beta-amyloid (A$β$) plaques and tau protein tangles in the brain are the defining 'A' and 'T' hallmarks of Alzheimer's disease (AD), and together with structural atrophy detectable on brain magnetic resonance imaging (MRI) scans as one of the neurodegenerative ('N') biomarkers comprise the ''ATN framework'' of AD. Current methods to detect A$β$/tau pathology include cerebrospinal fluid (CSF; invasive), positron emission tomography (PET; costly and not widely available), and blood-based biomarkers (BBBM; promising but mainly still in development). Objective: To develop a non-invasive and widely available structural MRI-based framework to quantitatively predict the amyloid and tau measurements. Methods: With MRI-based hippocampal multivariate morphometry statistics (MMS) features, we apply our Patch Analysis-based Surface Correntropy-induced Sparse coding and max-pooling (PASCS-MP) method combined with the ridge regression model to individual amyloid/tau measure prediction. Results: We evaluate our framework on amyloid PET/MRI and tau PET/MRI datasets from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Each subject has one pair consisting of a PET image and MRI scan, collected at about the same time. Experimental results suggest that amyloid/tau measurements predicted with our PASCP-MP representations are closer to the real values than the measures derived from other approaches, such as hippocampal surface area, volume, and shape morphometry features based on spherical harmonics (SPHARM). Conclusion: The MMS-based PASCP-MP is an efficient tool that can bridge hippocampal atrophy with amyloid and tau pathology and thus help assess disease burden, progression, and treatment effects.

Gang Wang, Qunxi Dong, Jianfeng Wu et al.

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 $Aβ+$ AD and $Aβ-$ cognitively unimpaired (CU) groups. A univariate morphometry index (UMI) is constructed from these ROIs by summarizing individual morphological characteristics weighted by normalized difference between $Aβ+$ AD and $Aβ-$ 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 $P=0.05$ are 116, 279 and 387 for the longitudinal $Aβ+$ AD, $Aβ+$ mild cognitive impairment (MCI) and $Aβ+$ 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.

Jie Zhang, Qingyang Li, Richard J. Caselli et al.

Algorithmic image-based diagnosis and prognosis of neurodegenerative diseases on longitudinal data has drawn great interest from computer vision researchers. The current state-of-the-art models for many image classification tasks are based on the Convolutional Neural Networks (CNN). However, a key challenge in applying CNN to biological problems is that the available labeled training samples are very limited. Another issue for CNN to be applied in computer aided diagnosis applications is that to achieve better diagnosis and prognosis accuracy, one usually has to deal with the longitudinal dataset, i.e., the dataset of images scanned at different time points. Here we argue that an enhanced CNN model with transfer learning for the joint analysis of tasks from multiple time points or regions of interests may have a potential to improve the accuracy of computer aided diagnosis. To reach this goal, we innovate a CNN based deep learning multi-task dictionary learning framework to address the above challenges. Firstly, we pre-train CNN on the ImageNet dataset and transfer the knowledge from the pre-trained model to the medical imaging progression representation, generating the features for different tasks. Then, we propose a novel unsupervised learning method, termed Multi-task Stochastic Coordinate Coding (MSCC), for learning different tasks by using shared and individual dictionaries and generating the sparse features required to predict the future cognitive clinical scores. We apply our new model in a publicly available neuroimaging cohort to predict clinical measures with two different feature sets and compare them with seven other state-of-the-art methods. The experimental results show our proposed method achieved superior results.