A model of brain morphological changes related to aging and Alzheimer's disease from cross-sectional assessments

In this study we propose a deformation-based framework to jointly model the influence of aging and Alzheimer's disease (AD) on the brain morphological evolution. Our approach combines a spatio-temporal description of both processes into a generative model. A reference morphology is deformed along specific trajectories to match subject specific morphologies. It is used to define two imaging progression markers: 1) a morphological age and 2) a disease score. These markers can be computed locally in any brain region. The approach is evaluated on brain structural magnetic resonance images (MRI) from the ADNI database. The generative model is first estimated on a control population, then, for each subject, the markers are computed for each acquisition. The longitudinal evolution of these markers is then studied in relation with the clinical diagnosis of the subjects and used to generate possible morphological evolution. In the model, the morphological changes associated with normal aging are mainly found around the ventricles, while the Alzheimer's disease specific changes are more located in the temporal lobe and the hippocampal area. The statistical analysis of these markers highlights differences between clinical conditions even though the inter-subject variability is quiet high. In this context, the model can be used to generate plausible morphological trajectories associated with the disease. Our method gives two interpretable scalar imaging biomarkers assessing the effects of aging and disease on brain morphology at the individual and population level. These markers confirm an acceleration of apparent aging for Alzheimer's subjects and can help discriminate clinical conditions even in prodromal stages. More generally, the joint modeling of normal and pathological evolutions shows promising results to describe age-related brain diseases over long time scales.Comment: NeuroImage, Elsevier, In pres

Modeling and inference of spatio-temporal protein dynamics across brain networks

Models of misfolded proteins (MP) aim at discovering the bio-mechanical propagation properties of neurological diseases (ND) by identifying plausible associated dynamical systems. Solving these systems along the full disease trajectory is usually challenging, due to the lack of a well defined time axis for the pathology. This issue is addressed by disease progression models (DPM) where long-term progression trajectories are estimated via time reparametrization of individual observations. However, due to their loose assumptions on the dynamics, DPM do not provide insights on the bio-mechanical properties of MP propagation. Here we propose a unified model of spatio-temporal protein dynamics based on the joint estimation of long-term MP dynamics and time reparameterization of individuals observations. The model is expressed within a Gaussian Process (GP) regression setting, where constraints on the MP dynamics are imposed through non--linear dynamical systems. We use stochastic variational inference on both GP and dynamical system parameters for scalable inference and uncertainty quantification of the trajectories. Experiments on simulated data show that our model accurately recovers prescribed rates along graph dynamics and precisely reconstructs the underlying progression. When applied to brain imaging data our model allows the bio-mechanical interpretation of amyloid deposition in Alzheimer's disease, leading to plausible simulations of MP propagation, and achieving accurate predictions of individual MP deposition in unseen data

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.Comment: 13 pages, 2 figure

Free-rider Attacks on Model Aggregation in Federated Learning

Free-rider attacks against federated learning consist in dissimulating participation to the federated learning process with the goal of obtaining the final aggregated model without actually contributing with any data. This kind of attacks is critical in sensitive applications of federated learning, where data is scarce and the model has high commercial value. We introduce here the first theoretical and experimental analysis of free-rider attacks on federated learning schemes based on iterative parameters aggregation, such as FedAvg or FedProx, and provide formal guarantees for these attacks to converge to the aggregated models of the fair participants. We first show that a straightforward implementation of this attack can be simply achieved by not updating the local parameters during the iterative federated optimization. As this attack can be detected by adopting simple countermeasures at the server level, we subsequently study more complex disguising schemes based on stochastic updates of the free-rider parameters. We demonstrate the proposed strategies on a number of experimental scenarios, in both iid and non-iid settings. We conclude by providing recommendations to avoid free-rider attacks in real world applications of federated learning, especially in sensitive domains where security of data and models is critical

Processi per la fabbricazione di cristalli fotonici bidimensionali

Questo lavoro di tesi ha lo scopo di studiare e mettere a punto i processi necessari alla fabbricazione di cristalli fotonici bidimensionali su substrati di silicio ed orientazione cristallografica

Experimental and Numerical Comparison of Internal Insulation Systems for Building Refurbishment

AbstractIn order to increase the knowledge of both local builders and designers about the energy efficiency of internal insulation a test chamber has been realized at the Edilmaster site. The test system features two isothermal chambers separated by the specimen under test. The controlled temperatures guarantee a constant temperature difference in order to measure the heat flux with thermofluximeter techniques. In this paper the uninsulated system is a brick wall of about 50cm thickness which represents a typical solution found in Trieste. Two internal insulation systems, with wooden and metallic studs, have been tested. The measurements highlighted the different thermal behavior between the area covered by the insulation material and the thermal bridges due to studs. The experimental results have been compared with solutions obtained with numerical and analytical methods

Sequential Informed Federated Unlearning: Efficient and Provable Client Unlearning in Federated Optimization

The aim of Machine Unlearning (MU) is to provide theoretical guarantees on the removal of the contribution of a given data point from a training procedure. Federated Unlearning (FU) consists in extending MU to unlearn a given client's contribution from a federated training routine. Current FU approaches are generally not scalable, and do not come with sound theoretical quantification of the effectiveness of unlearning. In this work we present Informed Federated Unlearning (IFU), a novel efficient and quantifiable FU approach. Upon unlearning request from a given client, IFU identifies the optimal FL iteration from which FL has to be reinitialized, with unlearning guarantees obtained through a randomized perturbation mechanism. The theory of IFU is also extended to account for sequential unlearning requests. Experimental results on different tasks and dataset show that IFU leads to more efficient unlearning procedures as compared to basic re-training and state-of-the-art FU approaches

Privacy Preserving Image Registration

Image registration is a key task in medical imaging applications, allowing to represent medical images in a common spatial reference frame. Current literature on image registration is generally based on the assumption that images are usually accessible to the researcher, from which the spatial transformation is subsequently estimated. This common assumption may not be met in current practical applications, since the sensitive nature of medical images may ultimately require their analysis under privacy constraints, preventing to share the image content in clear form. In this work, we formulate the problem of image registration under a privacy preserving regime, where images are assumed to be confidential and cannot be disclosed in clear. We derive our privacy preserving image registration framework by extending classical registration paradigms to account for advanced cryptographic tools, such as secure multi-party computation and homomorphic encryption, that enable the execution of operations without leaking the underlying data. To overcome the problem of performance and scalability of cryptographic tools in high dimensions, we first propose to optimize the underlying image registration operations using gradient approximations. We further revisit the use of homomorphic encryption and use a packing method to allow the encryption and multiplication of large matrices more efficiently. We demonstrate our privacy preserving framework in linear and non-linear registration problems, evaluating its accuracy and scalability with respect to standard image registration. Our results show that privacy preserving image registration is feasible and can be adopted in sensitive medical imaging applications

Longitudinal Analysis of Image Time Series with Diffeomorphic Deformations: A Computational Framework Based on Stationary Velocity Fields

International audienceWe propose and detail a deformation-based morphometry computational framework, called Longitudinal Log-Demons Framework (LLDF), to estimate the longitudinal brain deformations from image data series, transport them in a common space and perform statistical group-wise analyses. It is based on freely available software and tools, and consists of three main steps: (i) Pre-processing, (ii) Position correction, and (iii) Non-linear deformation analysis. It is based on the LCC log-Demons non-linear symmetric diffeomorphic registration algorithm with an additional modulation of the similarity term using a confidence mask to increase the robustness with respect to brain boundary intensity artifacts. The pipeline is exemplified on the longitudinal Open Access Series of Imaging Studies (OASIS) database and all the parameters values are given so that the study can be reproduced. We investigate the group-wise differences between the patients with Alzheimer's disease and the healthy control group, and show that the proposed pipeline increases the sensitivity with no decrease in the specificity of the statistical study done on the longitudinal deformations