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Georgi Hrusanov

Publications and source records attributed to Georgi Hrusanov.

3 recordsLinked to original sources

Explainable Graph-theoretical Machine Learning with Application to Alzheimer's Disease Prediction

Dementia affects over 55 million people worldwide, projected to reach 139 million by 2050, with Alzheimer's disease (AD) accounting for 60-70% of cases. AD is associated with disruptions in metabolic brain connectivity. Detecting these disruptions early is crucial for AD management. FDG-PET is a useful tool for identifying such impairments. However, most studies rely on group-level analyses or thresholding, potentially masking individual differences and overlooking weaker yet biologically critical brain connections. Moreover, AD prediction largely focuses on univariate rather than multivariate outcomes. To address this, we introduce explainable graph-theoretical machine learning (XGML), a framework for constructing individual metabolic brain graphs and identifying subgraphs most predictive of multivariate disease-related outcomes. Using Alzheimer's Disease Neuroimaging Initiative (ADNI) FDG-PET data, we compared six graph representations against three non-graph baselines, each with six machine learning models using repeated stratified 3-fold cross-validation (10 repeats). The best configuration combined kernel density estimation with Hellinger distance and random forest. Across eight cognitive scores, it reached an overall Fisher-z-averaged Pearson correlation of r=0.595, with strongest performance for ADAS13 (r=0.67), ADAS11 (r=0.65), and ADASQ4 (r=0.62). We identified key edges that were jointly but differentially predictive across outcomes, suggesting their potential as network biomarkers of cognitive decline. Preliminary external feasibility validation on an OASIS3 cohort yielded weak predictive performance for CDRSB (r=0.26) and MMSE (r=0.18), likely reflecting cohort, protocol, and diagnostic differences. Overall, our results suggest the promise of graph-theoretical machine learning for biomarker discovery, disease prediction, and understanding the neural mechanisms underlying AD.

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Generative Model via Quantile Assignment

Deep Generative models (DGMs) play two key roles in modern machine learning: (i) producing new information (e.g., image synthesis) and (ii) reducing dimensionality. However, traditional architectures often rely on auxiliary networks such as encoders in Variational Autoencoders (VAEs) or discriminators in Generative Adversarial Networks (GANs), which introduce training instability, computational overhead, and risks like mode collapse. We present NeuroSQL, a new generative paradigm that eliminates the need for auxiliary networks by learning low-dimensional latent representations implicitly. NeuroSQL leverages an asymptotic approximation that expresses the latent variables as the solution to an optimal transportation problem. Specifically, NeuroSQL learns the latent variables by solving a linear assignment problem and then passes the latent information to a standalone generator. We benchmark its performance against GANs, VAEs, and a budget-matched diffusion baseline on four datasets: handwritten digits (MNIST), faces (CelebA), animal faces (AFHQ), and brain images (OASIS). Compared to VAEs, GANs, and diffusion models: (1) in terms of image quality, NeuroSQL achieves overall lower mean pixel distance between synthetic and authentic images and stronger perceptual/structural fidelity; (2) computationally, NeuroSQL requires the least training time; and (3) practically, NeuroSQL provides an effective solution for generating synthetic data with limited training samples. By embracing quantile assignment rather than an encoder, NeuroSQL provides a fast, stable, and robust way to generate synthetic data with minimal information loss.

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Physics-Informed Neural Koopman Machine for Interpretable Longitudinal Personalized Alzheimer's Disease Forecasting

Early forecasting of individual cognitive decline in Alzheimer's disease (AD) is central to disease evaluation and management. Despite advances, it is as of yet challenging for existing methodological frameworks to integrate multimodal data for longitudinal personalized forecasting while maintaining interpretability. To address this gap, we present the Neural Koopman Machine (NKM), a new machine learning architecture inspired by dynamical systems and attention mechanisms, designed to forecast multiple cognitive scores simultaneously using multimodal genetic, neuroimaging, proteomic, and demographic data. NKM integrates analytical ($α$) and biological ($β$) knowledge to guide feature grouping and control the hierarchical attention mechanisms to extract relevant patterns. By implementing Fusion Group-Aware Hierarchical Attention within the Koopman operator framework, NKM transforms complex nonlinear trajectories into interpretable linear representations. To demonstrate NKM's efficacy, we applied it to study the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Our results suggest that NKM consistently outperforms both traditional machine learning methods and deep learning models in forecasting trajectories of cognitive decline. Specifically, NKM (1) forecasts changes of multiple cognitive scores simultaneously, (2) quantifies differential biomarker contributions to predicting distinctive cognitive scores, and (3) identifies brain regions most predictive of cognitive deterioration. Together, NKM advances personalized, interpretable forecasting of future cognitive decline in AD using past multimodal data through an explainable, explicit system and reveals potential multimodal biological underpinnings of AD progression.

cs.LG↗