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Marco Lorenzi

Publications and source records attributed to Marco Lorenzi.

40 records · Page 3Linked to original sources

Alzheimer's Disease Modelling and Staging through Independent Gaussian Process Analysis of Spatio-Temporal Brain Changes

Alzheimer's disease (AD) is characterized by complex and largely unknown progression dynamics affecting the brain's morphology. Although the disease evolution spans decades, to date we cannot rely on long-term data to model the pathological progression, since most of the available measures are on a short-term scale. It is therefore difficult to understand and quantify the temporal progression patterns affecting the brain regions across the AD evolution. In this work, we tackle this problem by presenting a generative model based on probabilistic matrix factorization across temporal and spatial sources. The proposed method addresses the problem of disease progression modelling by introducing clinically-inspired statistical priors. To promote smoothness in time and model plausible pathological evolutions, the temporal sources are defined as monotonic and independent Gaussian Processes. We also estimate an individual time-shift parameter for each patient to automatically position him/her along the sources time-axis. To encode the spatial continuity of the brain sub-structures, the spatial sources are modeled as Gaussian random fields. We test our algorithm on grey matter maps extracted from brain structural images. The experiments highlight differential temporal progression patterns mapping brain regions key to the AD pathology, and reveal a disease-specific time scale associated with the decline of volumetric biomarkers across clinical stages.

stat.AP↗

Multi-Channel Stochastic Variational Inference for the Joint Analysis of Heterogeneous Biomedical Data in Alzheimer's Disease

The joint analysis of biomedical data in Alzheimer's Disease (AD) is important for better clinical diagnosis and to understand the relationship between biomarkers. However, jointly accounting for heterogeneous measures poses important challenges related to the modeling of the variability and the interpretability of the results. These issues are here addressed by proposing a novel multi-channel stochastic generative model. We assume that a latent variable generates the data observed through different channels (e.g., clinical scores, imaging, ...) and describe an efficient way to estimate jointly the distribution of both latent variable and data generative process. Experiments on synthetic data show that the multi-channel formulation allows superior data reconstruction as opposed to the single channel one. Moreover, the derived lower bound of the model evidence represents a promising model selection criterion. Experiments on AD data show that the model parameters can be used for unsupervised patient stratification and for the joint interpretation of the heterogeneous observations. Because of its general and flexible formulation, we believe that the proposed method can find important applications as a general data fusion technique.

stat.ME↗

Constraining the Dynamics of Deep Probabilistic Models

We introduce a novel generative formulation of deep probabilistic models implementing "soft" constraints on their function dynamics. In particular, we develop a flexible methodological framework where the modeled functions and derivatives of a given order are subject to inequality or equality constraints. We then characterize the posterior distribution over model and constraint parameters through stochastic variational inference. As a result, the proposed approach allows for accurate and scalable uncertainty quantification on the predictions and on all parameters. We demonstrate the application of equality constraints in the challenging problem of parameter inference in ordinary differential equation models, while we showcase the application of inequality constraints on the problem of monotonic regression of count data. The proposed approach is extensively tested in several experimental settings, leading to highly competitive results in challenging modeling applications, while offering high expressiveness, flexibility and scalability.

stat.ML↗

Disease Progression Modeling and Prediction through Random Effect Gaussian Processes and Time Transformation

The development of statistical approaches for the joint modelling of the temporal changes of imaging, biochemical, and clinical biomarkers is of paramount importance for improving the understanding of neurodegenerative disorders, and for providing a reference for the prediction and quantification of the pathology in unseen individuals. Nonetheless, the use of disease progression models for probabilistic predictions still requires investigation, for example for accounting for missing observations in clinical data, and for accurate uncertainty quantification. We tackle this problem by proposing a novel Gaussian process-based method for the joint modeling of imaging and clinical biomarker progressions from time series of individual observations. The model is formulated to account for individual random effects and time reparameterization, allowing non-parametric estimates of the biomarker evolution, as well as high flexibility in specifying correlation structure, and time transformation models. Thanks to the Bayesian formulation, the model naturally accounts for missing data, and allows for uncertainty quantification in the estimate of evolutions, as well as for probabilistic prediction of disease staging in unseen patients. The experimental results show that the proposed model provides a biologically plausible description of the evolution of Alzheimer's pathology across the whole disease time-span as well as remarkable predictive performance when tested on a large clinical cohort with missing observations.

stat.AP↗