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.

Original languageEnglish
Title of host publicationInformation Processing in Medical Imaging - 26th International Conference, IPMI 2019, Proceedings
EditorsAlbert C.S. Chung, James C. Gee, Paul A. Yushkevich, Siqi Bao
ISBN (Electronic)978-3-030-20351-1
ISBN (Print)978-303020350-4
Publication statusPublished - 2019
Event26th International Conference on Information Processing in Medical Imaging, IPMI 2019 - Hong Kong, China
Duration: 2 Jun 20197 Jun 2019

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume11492 LNCS
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349


Conference26th International Conference on Information Processing in Medical Imaging, IPMI 2019
CityHong Kong

ID: 54238632