Localization transition of a random polymer at an interface

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1999.Includes bibliographical references.by Venkatraghavan Ganesan.S.M

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

Trajectories of imaging markers in brain aging: the Rotterdam Study

With aging, the brain undergoes several structural changes. These changes reflect the normal aging process and are therefore not necessarily pathologic. In fact, better understanding of these normal changes is an important cornerstone to also disentangle pathologic changes. Several studies have investigated normal brain aging, both cross-sectional and longitudinal, and focused on a broad range of magnetic resonance imaging (MRI) markers. This study aims to comprise the different aspects in brain aging, by performing

Construction of a random signal with a specific Psd and a uniform Pdf

The performance of a dynamic element matching (DEM) flash digital to analog converter (DAC) can be improved by controlling the DEM DAC\u27s interconnection network with a random signal that has a specific power spectral density (PSD) and a uniform probability distribution function (PDF). Many algorithms exist for generating a random signal with a white PSD and a uniform PDF, but there exists only one algorithm for generating a random signal with a specific PSD and a particular PDF. For DEM DAC applications, the random signal must be generated at the speed of the DEM DAC. However, a real time implementation of this existing algorithm is too computation intensive for a typical DEM DAC. In this thesis, an algorithm that constructs a uniformly distributed random signal with a specific PSD is developed. This uniformly distributed colored random signal is implemented using a finite state machine (FSM) and Linear Feedback Shift Registers (LFSRs)

The symphony of cacophony:understanding the order in neurodegenerative diseases

Neurodegenerative diseases such as Alzheimer's disease are notoriously heterogeneous; pathologically as well as in their clinical presentation in patients. There are differences between patients in terms of the pathways of progression, the speed of progression, and the effect the progression has on the patient's cognition. This myriad of differences not only makes clinical diagnosis very challenging, but also has major implications for the efficacy of drug trials. As heterogeneous as these diseases are, there is an underlying order in their progression. An underlying method to their disruption of homeostasis. An underlying symphony leading to the cacophony

The symphony of cacophony: understanding the order in neurodegenerative diseases

Neurodegenerative diseases such as Alzheimer's disease are notoriously heterogeneous; pathologically as well as in their clinical presentation in patients. There are differences between patients in terms of the pathways of progression, the speed of progression, and the effect the progression has on the patient's cognition. This myriad of differences not only makes clinical diagnosis very challenging, but also has major implications for the efficacy of drug trials. As heterogeneous as these diseases are, there is an underlying order in their progression. An underlying method to their disruption of homeostasis. An underlying symphony leading to the cacophony

Applications of coarse-graining approaches : volume averaging, macrotransport theory and scaling concepts

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1999.Includes bibliographical references.by Venkatraghavan Ganesan.Ph.D

Disease Progression Timeline Estimation for Alzheimer's Disease using Discriminative Event Based Modeling

Alzheimer's Disease (AD) is characterized by a cascade of biomarkers becoming abnormal, the pathophysiology of which is very complex and largely unknown. Event-based modeling (EBM) is a data-driven technique to estimate the sequence in which biomarkers for a disease become abnormal based on cross-sectional data. It can help in understanding the dynamics of disease progression and facilitate early diagnosis and prognosis. In this work we propose a novel discriminative approach to EBM, which is shown to be more accurate than existing state-of-the-art EBM methods. The method first estimates for each subject an approximate ordering of events. Subsequently, the central ordering over all subjects is estimated by fitting a generalized Mallows model to these approximate subject-specific orderings. We also introduce the concept of relative distance between events which helps in creating a disease progression timeline. Subsequently, we propose a method to stage subjects by placing them on the estimated disease progression timeline. We evaluated the proposed method on Alzheimer's Disease Neuroimaging Initiative (ADNI) data and compared the results with existing state-of-the-art EBM methods. We also performed extensive experiments on synthetic data simulating the progression of Alzheimer's disease. The event orderings obtained on ADNI data seem plausible and are in agreement with the current understanding of progression of AD. The proposed patient staging algorithm performed consistently better than that of state-of-the-art EBM methods. Event orderings obtained in simulation experiments were more accurate than those of other EBM methods and the estimated disease progression timeline was observed to correlate with the timeline of actual disease progression. The results of these experiments are encouraging and suggest that discriminative EBM is a promising approach to disease progression modeling