Alzheimer's Disease Neuroimaging Initiative

Rong Zhou, Houliang Zhou, Yao Su et al.

Multimodal neuroimaging provides complementary insights for Alzheimer's disease diagnosis, yet clinical datasets frequently suffer from missing modalities. We propose ACADiff, a framework that synthesizes missing brain imaging modalities through adaptive clinical-aware diffusion. ACADiff learns mappings between incomplete multimodal observations and target modalities by progressively denoising latent representations while attending to available imaging data and clinical metadata. The framework employs adaptive fusion that dynamically reconfigures based on input availability, coupled with semantic clinical guidance via GPT-4o-encoded prompts. Three specialized generators enable bidirectional synthesis among sMRI, FDG-PET, and AV45-PET. Evaluated on ADNI subjects, ACADiff achieves superior generation quality and maintains robust diagnostic performance even under extreme 80\% missing scenarios, outperforming all existing baselines. To promote reproducibility, code is available at https://github.com/rongzhou7/ACADiff

Yoan David, Pierre-Marc Jodoin, Alzheimer's Disease Neuroimaging Initiative et al.

Harmonization methods such as ComBat and its variants are widely used to mitigate diffusion MRI (dMRI) site-specific biases. However, ComBat assumes that subject distributions exhibit a Gaussian profile. In practice, patients with neurological disorders often present diffusion metrics that deviate markedly from those of healthy controls, introducing pathological outliers that distort site-effect estimation. This problem is particularly challenging in clinical practice as most patients undergoing brain imaging have an underlying and yet undiagnosed condition, making it difficult to exclude them from harmonization cohorts, as their scans were precisely prescribed to establish a diagnosis. In this paper, we show that harmonizing data to a normative reference population with ComBat while including pathological cases induces significant distortions. Across 7 neurological conditions, we evaluated 10 outlier rejection methods with 4 ComBat variants over a wide range of scenarios, revealing that many filtering strategies fail in the presence of pathology. In contrast, a simple MLP provides robust outlier compensation enabling reliable harmonization while preserving disease-related signal. Experiments on both control and real multi-site cohorts, comprising up to 80% of subjects with neurological disorders, demonstrate that Robust-ComBat consistently outperforms conventional statistical baselines with lower harmonization error across all ComBat variants.

Cagri Ozdemir, Mohammad Al Olaimat, Yashu Vashishath et al.

Developing computational tools for integrative analysis across multiple types of omics data has been of immense importance in cancer molecular biology and precision medicine research. While recent advancements have yielded integrative prediction solutions for multi-omics data, these methods lack a comprehensive and cohesive understanding of the rationale behind their specific predictions. To shed light on personalized medicine and unravel previously unknown characteristics within integrative analysis of multi-omics data, we introduce a novel integrative neural network approach for cancer molecular subtype and biomedical classification applications, named Integrative Graph Convolutional Networks (IGCN). IGCN can identify which types of omics receive more emphasis for each patient to predict a certain class. Additionally, IGCN has the capability to pinpoint significant biomarkers from a range of omics data types. To demonstrate the superiority of IGCN, we compare its performance with other state-of-the-art approaches across different cancer subtype and biomedical classification tasks.

Houliang Zhou, Rong Zhou, Yangying Liu et al.

Identifying objective neuroimaging biomarkers to forecast Alzheimer's disease (AD) progression is crucial for timely intervention. However, this task remains challenging due to the complex dysfunctions in the spatio-temporal characteristics of underlying brain networks, which are often overlooked by existing methods. To address these limitations, we develop an interpretable spatio-temporal graph neural network framework to predict future AD progression, leveraging dual Stochastic Differential Equations (SDEs) to model the irregularly-sampled longitudinal functional magnetic resonance imaging (fMRI) data. We validate our approach on two independent cohorts, including the Open Access Series of Imaging Studies (OASIS-3) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our framework effectively learns sparse regional and connective importance probabilities, enabling the identification of key brain circuit abnormalities associated with disease progression. Notably, we detect the parahippocampal cortex, prefrontal cortex, and parietal lobule as salient regions, with significant disruptions in the ventral attention, dorsal attention, and default mode networks. These abnormalities correlate strongly with longitudinal AD-related clinical symptoms. Moreover, our interpretability strategy reveals both established and novel neural systems-level and sex-specific biomarkers, offering new insights into the neurobiological mechanisms underlying AD progression. Our findings highlight the potential of spatio-temporal graph-based learning for early, individualized prediction of AD progression, even in the context of irregularly-sampled longitudinal imaging data.

Shih-Gu Huang, Moo K. Chung, Anqi Qiu et al.

This paper revisits spectral graph convolutional neural networks (graph-CNNs) given in Defferrard (2016) and develops the Laplace-Beltrami CNN (LB-CNN) by replacing the graph Laplacian with the LB operator. We then define spectral filters via the LB operator on a graph. We explore the feasibility of Chebyshev, Laguerre, and Hermite polynomials to approximate LB-based spectral filters and define an update of the LB operator for pooling in the LBCNN. We employ the brain image data from Alzheimer's Disease Neuroimaging Initiative (ADNI) and demonstrate the use of the proposed LB-CNN. Based on the cortical thickness of the ADNI dataset, we showed that the LB-CNN didn't improve classification accuracy compared to the spectral graph-CNN. The three polynomials had a similar computational cost and showed comparable classification accuracy in the LB-CNN or spectral graph-CNN. Our findings suggest that even though the shapes of the three polynomials are different, deep learning architecture allows us to learn spectral filters such that the classification performance is not dependent on the type of the polynomials or the operators (graph Laplacian and LB operator).

Shih-Gu Huang, Moo K. Chung, Anqi Qiu et al.

Deep neural networks have recently been recognized as one of the powerful learning techniques in computer vision and medical image analysis. Trained deep neural networks need to be generalizable to new data that was not seen before. In practice, there is often insufficient training data available and augmentation is used to expand the dataset. Even though graph convolutional neural network (graph-CNN) has been widely used in deep learning, there is a lack of augmentation methods to generate data on graphs or surfaces. This study proposes two unbiased augmentation methods, Laplace-Beltrami eigenfunction Data Augmentation (LB-eigDA) and Chebyshev polynomial Data Augmentation (C-pDA), to generate new data on surfaces, whose mean is the same as that of real data. LB-eigDA augments data via the resampling of the LB coefficients. In parallel with LB-eigDA, we introduce a fast augmentation approach, C-pDA, that employs a polynomial approximation of LB spectral filters on surfaces. We design LB spectral bandpass filters by Chebyshev polynomial approximation and resample signals filtered via these filters to generate new data on surfaces. We first validate LB-eigDA and C-pDA via simulated data and demonstrate their use for improving classification accuracy. We then employ the brain images of Alzheimer's Disease Neuroimaging Initiative (ADNI) and extract cortical thickness that is represented on the cortical surface to illustrate the use of the two augmentation methods. We demonstrate that augmented cortical thickness has a similar pattern to real data. Second, we show that C-pDA is much faster than LB-eigDA. Last, we show that C-pDA can improve the AD classification accuracy of graph-CNN.

Hoo-Chang Shin, Alvin Ihsani, Ziyue Xu et al.

Positron Emission Tomography (PET) is now regarded as the gold standard for the diagnosis of Alzheimer's Disease (AD). However, PET imaging can be prohibitive in terms of cost and planning, and is also among the imaging techniques with the highest dosage of radiation. Magnetic Resonance Imaging (MRI), in contrast, is more widely available and provides more flexibility when setting the desired image resolution. Unfortunately, the diagnosis of AD using MRI is difficult due to the very subtle physiological differences between healthy and AD subjects visible on MRI. As a result, many attempts have been made to synthesize PET images from MR images using generative adversarial networks (GANs) in the interest of enabling the diagnosis of AD from MR. Existing work on PET synthesis from MRI has largely focused on Conditional GANs, where MR images are used to generate PET images and subsequently used for AD diagnosis. There is no end-to-end training goal. This paper proposes an alternative approach to the aforementioned, where AD diagnosis is incorporated in the GAN training objective to achieve the best AD classification performance. Different GAN lossesare fine-tuned based on the discriminator performance, and the overall training is stabilized. The proposed network architecture and training regime show state-of-the-art performance for three- and four- class AD classification tasks.

Hoo-Chang Shin, Alvin Ihsani, Swetha Mandava et al.

Synthesizing medical images, such as PET, is a challenging task due to the fact that the intensity range is much wider and denser than those in photographs and digital renderings and are often heavily biased toward zero. Above all, intensity values in PET have absolute significance, and are used to compute parameters that are reproducible across the population. Yet, usually much manual adjustment has to be made in pre-/post- processing when synthesizing PET images, because its intensity ranges can vary a lot, e.g., between -100 to 1000 in floating point values. To overcome these challenges, we adopt the Bidirectional Encoder Representations from Transformers (BERT) algorithm that has had great success in natural language processing (NLP), where wide-range floating point intensity values are represented as integers ranging between 0 to 10000 that resemble a dictionary of natural language vocabularies. BERT is then trained to predict a proportion of masked values images, where its "next sentence prediction (NSP)" acts as GAN discriminator. Our proposed approach, is able to generate PET images from MRI images in wide intensity range, with no manual adjustments in pre-/post- processing. It is a method that can scale and ready to deploy.

Rémi Giraud, Vinh-Thong Ta, Nicolas Papadakis et al.

Automatic segmentation methods are important tools for quantitative analysis of Magnetic Resonance Images (MRI). Recently, patch-based label fusion approaches have demonstrated state-of-the-art segmentation accuracy. In this paper, we introduce a new patch-based label fusion framework to perform segmentation of anatomical structures. The proposed approach uses an Optimized PAtchMatch Label fusion (OPAL) strategy that drastically reduces the computation time required for the search of similar patches. The reduced computation time of OPAL opens the way for new strategies and facilitates processing on large databases. In this paper, we investigate new perspectives offered by OPAL, by introducing a new multi-scale and multi-feature framework. During our validation on hippocampus segmentation we use two datasets: young adults in the ICBM cohort and elderly adults in the EADC-ADNI dataset. For both, OPAL is compared to state-of-the-art methods. Results show that OPAL obtained the highest median Dice coefficient (89.9% for ICBM and 90.1% for EADC-ADNI). Moreover, in both cases, OPAL produced a segmentation accuracy similar to inter-expert variability. On the EADC-ADNI dataset, we compare the hippocampal volumes obtained by manual and automatic segmentation. The volumes appear to be highly correlated that enables to perform more accurate separation of pathological populations.

Murat Seckin Ayhan, Vijay Raghavan, Alzheimer's disease Neuroimaging Initiative

Alzheimer's disease is a major cause of dementia. Its diagnosis requires accurate biomarkers that are sensitive to disease stages. In this respect, we regard probabilistic classification as a method of designing a probabilistic biomarker for disease staging. Probabilistic biomarkers naturally support the interpretation of decisions and evaluation of uncertainty associated with them. In this paper, we obtain probabilistic biomarkers via Gaussian Processes. Gaussian Processes enable probabilistic kernel machines that offer flexible means to accomplish Multiple Kernel Learning. Exploiting this flexibility, we propose a new variation of Automatic Relevance Determination and tackle the challenges of high dimensionality through multiple kernels. Our research results demonstrate that the Gaussian Process models are competitive with or better than the well-known Support Vector Machine in terms of classification performance even in the cases of single kernel learning. Extending the basic scheme towards the Multiple Kernel Learning, we improve the efficacy of the Gaussian Process models and their interpretability in terms of the known anatomical correlates of the disease. For instance, the disease pathology starts in and around the hippocampus and entorhinal cortex. Through the use of Gaussian Processes and Multiple Kernel Learning, we have automatically and efficiently determined those portions of neuroimaging data. In addition to their interpretability, our Gaussian Process models are competitive with recent deep learning solutions under similar settings.