Cross-modality translation between MRI and PET imaging is challenging due to the distinct mechanisms underlying these modalities. Blood-based biomarkers (BBBMs) are revolutionizing Alzheimer's disease (AD) detection by identifying patients and quantifying brain amyloid levels. However, the potential of BBBMs to enhance PET image synthesis remains unexplored. In this paper, we performed a thorough study on the effect of incorporating BBBM into deep generative models. By evaluating three widely used cross-modality translation models, we found that BBBMs integration consistently enhances the generative quality across all models. By visual inspection of the generated results, we observed that PET images generated by CycleGAN exhibit the best visual fidelity. Based on these findings, we propose Plasma-CycleGAN, a novel generative model based on CycleGAN, to synthesize PET images from MRI using BBBMs as conditions. This is the first approach to integrate BBBMs in conditional cross-modality translation between MRI and PET.

With the power of large language models (LLMs), open-ended embodied agents can flexibly understand human instructions, generate interpretable guidance strategies, and output executable actions. Nowadays, Multi-modal Language Models~(MLMs) integrate multi-modal signals into LLMs, further bringing richer perception to entity agents and allowing embodied agents to perceive world-understanding tasks more delicately. However, existing works: 1) operate independently by agents, each containing multiple LLMs, from perception to action, resulting in gaps between complex tasks and execution; 2) train MLMs on static data, struggling with dynamics in open-ended scenarios; 3) input prior knowledge directly as prompts, suppressing application flexibility. We propose STEVE-2, a hierarchical knowledge distillation framework for open-ended embodied tasks, characterized by 1) a hierarchical system for multi-granular task division, 2) a mirrored distillation method for parallel simulation data, and 3) an extra expert model for bringing additional knowledge into parallel simulation. After distillation, embodied agents can complete complex, open-ended tasks without additional expert guidance, utilizing the performance and knowledge of a versatile MLM. Extensive evaluations on navigation and creation tasks highlight the superior performance of STEVE-2 in open-ended tasks, with $1.4 \times$ - $7.3 \times$ in performance.

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.

We examine the ability of machine learning (ML) and deep learning (DL) algorithms to infer surface/ground exchange flux based on subsurface temperature observations. The observations and fluxes are produced from a high-resolution numerical model representing conditions in the Columbia River near the Department of Energy Hanford site located in southeastern Washington State. Random measurement error, of varying magnitude, is added to the synthetic temperature observations. The results indicate that both ML and DL methods can be used to infer the surface/ground exchange flux. DL methods, especially convolutional neural networks, outperform the ML methods when used to interpret noisy temperature data with a smoothing filter applied. However, the ML methods also performed well and they are can better identify a reduced number of important observations, which could be useful for measurement network optimization. Surprisingly, the ML and DL methods better inferred upward flux than downward flux. This is in direct contrast to previous findings using numerical models to infer flux from temperature observations and it may suggest that combined use of ML or DL inference with numerical inference could improve flux estimation beneath river systems.

Many real-world applications have to tackle the Positive-Unlabeled (PU) learning problem, i.e., learning binary classifiers from a large amount of unlabeled data and a few labeled positive examples. While current state-of-the-art methods employ importance reweighting to design various risk estimators, they ignored the learning capability of the model itself, which could have provided reliable supervision. This motivates us to propose a novel Self-PU learning framework, which seamlessly integrates PU learning and self-training. Self-PU highlights three "self"-oriented building blocks: a self-paced training algorithm that adaptively discovers and augments confident positive/negative examples as the training proceeds; a self-calibrated instance-aware loss; and a self-distillation scheme that introduces teacher-students learning as an effective regularization for PU learning. We demonstrate the state-of-the-art performance of Self-PU on common PU learning benchmarks (MNIST and CIFAR-10), which compare favorably against the latest competitors. Moreover, we study a real-world application of PU learning, i.e., classifying brain images of Alzheimer's Disease. Self-PU obtains significantly improved results on the renowned Alzheimer's Disease Neuroimaging Initiative (ADNI) database over existing methods. The code is publicly available at: https://github.com/TAMU-VITA/Self-PU.

Diagnosis of Alzheimer's disease (AD) at the early stage of the disease development is of great clinical importance. Current clinical assessment that relies primarily on cognitive measures proves low sensitivity and specificity. The fast growing neuroimaging techniques hold great promise. Research so far has focused on single neuroimaging modalities. However, as different modalities provide complementary measures for the same disease pathology, fusion of multi-modality data may increase the statistical power in identification of disease-related brain regions. This is especially true for early AD, at which stage the disease-related regions are most likely to be weak-effect regions that are difficult to be detected from a single modality alone. We propose a sparse composite linear discriminant analysis model (SCLDA) for identification of disease-related brain regions of early AD from multi-modality data. SCLDA uses a novel formulation that decomposes each LDA parameter into a product of a common parameter shared by all the modalities and a parameter specific to each modality, which enables joint analysis of all the modalities and borrowing strength from one another. We prove that this formulation is equivalent to a penalized likelihood with non-convex regularization, which can be solved by the DC ((difference of convex functions) programming. We show that in using the DC programming, the property of the non-convex regularization in terms of preserving weak-effect features can be nicely revealed. We perform extensive simulations to show that SCLDA outperforms existing competing algorithms on feature selection, especially on the ability for identifying weak-effect features. We apply SCLDA to the Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) images of 49 AD patients and 67 normal controls (NC). Our study identifies disease-related brain regions consistent with findings in the AD literature.

Recent advances in neuroimaging techniques provide great potentials for effective diagnosis of Alzheimer's disease (AD), the most common form of dementia. Previous studies have shown that AD is closely related to the alternation in the functional brain network, i.e., the functional connectivity among different brain regions. In this paper, we consider the problem of learning functional brain connectivity from neuroimaging, which holds great promise for identifying image-based markers used to distinguish Normal Controls (NC), patients with Mild Cognitive Impairment (MCI), and patients with AD. More specifically, we study sparse inverse covariance estimation (SICE), also known as exploratory Gaussian graphical models, for brain connectivity modeling. In particular, we apply SICE to learn and analyze functional brain connectivity patterns from different subject groups, based on a key property of SICE, called the "monotone property" we established in this paper. Our experimental results on neuroimaging PET data of 42 AD, 116 MCI, and 67 NC subjects reveal several interesting connectivity patterns consistent with literature findings, and also some new patterns that can help the knowledge discovery of AD.