Event-Based Modeling with High-Dimensional Imaging Biomarkers for Estimating Spatial Progression of Dementia

Event-based models (EBM) are a class of disease progression models that can be used to estimate temporal ordering of neuropathological changes from cross-sectional data. Current EBMs only handle scalar biomarkers, such as regional volumes, as inputs. However, regional aggregates are a crude summary of the underlying high-resolution images, potentially limiting the accuracy of EBM. Therefore, we propose a novel method that exploits high-dimensional voxel-wise imaging biomarkers: n-dimensional discriminative EBM (nDEBM). nDEBM is based on an insight that mixture modeling, which is a key element of conventional EBMs, can be replaced by a more scalable semi-supervised support vector machine (SVM) approach. This SVM is used to estimate the degree of abnormality of each region which is then used to obtain subject-specific disease progression patterns. These patterns are in turn used for estimating the mean ordering by fitting a generalized Mallows model. In order to validate the biomarker ordering obtained using nDEBM, we also present a framework for Simulation of Imaging Biomarkers' Temporal Evolution (SImBioTE) that mimics neurodegeneration in brain regions. SImBioTE trains variational auto-encoders (VAE) in different brain regions independently to simulate images at varying stages of disease progression. We also validate nDEBM clinically using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). In both experiments, nDEBM using high-dimensional features gave better performance than state-of-the-art EBM methods using regional volume biomarkers. This suggests that nDEBM is a promising approach for disease progression modeling.Comment: IPMI 201

First Observation of Self-Amplified Spontaneous Emission in a Free-Electron Laser at 109 nm Wavelength

We present the first observation of Self-Amplified Spontaneous Emission (SASE) in a free-electron laser (FEL) in the Vacuum Ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approx. 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width and intensity fluctuations all corroborate the existing models for SASE FELs.Comment: 6 pages including 6 figures; e-mail: [email protected]

Semi-supervised Stuctured Prediction Models

Learning mappings between arbitrary structured input and output variables is a fundamental problem in machine learning. It covers many natural learning tasks and challenges the standard model of learning a mapping from independently drawn instances to a small set of labels. Potential applications include classification with a class taxonomy, named entity recognition, and natural language parsing. In these structured domains, labeled training instances are generally expensive to obtain while unlabeled inputs are readily available and inexpensive. This thesis deals with semi-supervised learning of discriminative models for structured output variables. The analytical techniques and algorithms of classical semi-supervised learning are lifted to the structured setting. Several approaches based on different assumptions of the data are presented. Colearning, for instance, maximizes the agreement among multiple hypotheses while transductive approaches rely on an implicit cluster assumption. Furthermore, in the framework of this dissertation, a case study on email batch detection in message streams is presented. The involved tasks exhibit an inherent cluster structure and the presented solution exploits the streaming nature of the data. The different approaches are developed into semi-supervised structured prediction models and efficient optimization strategies thereof are presented. The novel algorithms generalize state-of-the-art approaches in structural learning such as structural support vector machines. Empirical results show that the semi-supervised algorithms lead to significantly lower error rates than their fully supervised counterparts in many application areas, including multi-class classification, named entity recognition, and natural language parsing