YEARS

2012-2017

AUTHORS

Vikas Singh

TITLE

Maximizing Power in AD Clinical Trials via Multimodal Machine Learning

ABSTRACT

DESCRIPTION (provided by applicant): An emphasis in ongoing Alzheimer's disease (AD) research is identifying those biomarkers which best predict future cognitive decline at the various stages of disease progression. These biomarkers can then serve as early markers for diagnosis, and for selection of subjects into clinical trials. Recent results suggest that the identification of such discriminative biomarkers is possible by adapting machine learning methods for this problem: but studies have primarily used modalities in isolation so far. The sensitivity/specificity offered by these methods is unsatisfactory for more clinically relevant questions: which MCI patients will convert to AD? Answering such questions requires new methods that leverage all data sources (e.g., imaging modalities, CSF measures) in conjunction. This project focuses on how data from multiple biomarkers should be optimally aggregated to best predict future cognitive decline, and how these models can improve clinical trials for AD. Hypothesis: Significant improvements in sensitivity and specificity for discriminating AD, MCI, and healthy controls at the level of individual subjects are possible by making use of multiple modalities (together with longitudinal data) simultaneously. Further, these methods will significantly improve sample size estimates in clinical trials, and help derive customized outcomes for evaluating new treatment procedures. Specific Aims: (1) To develop new image-based machine learning algorithms that can take advantage of multiple modalities simultaneously within a unified framework. (2) To provide a software and extensively evaluate these methods on the ADNI and BLSA datasets, to assess the sensitivity/specificity attainable by truly multi-modal analysis methods. (3) To interface multi-modal classification methods with AD clinical trials: (a) by developing comprehensive sample size estimates needed to observe specific outcomes, and using these methods to derive customized outcomes for an ongoing R01-funded observational/prospective study here at the Wisconsin ADRC. Methods: We will develop new multi-modal machine learning methods that will optimally exploit all data sources simultaneously. Our models will also incorporate longitudinal data, and exploit interaction between modalities at different stages of the disease. This will be used to derive a Multi-Modal Disease Marker (MMDM) (Aim 1). The algorithms will be evaluated on large-scale well-characterized datasets and provided as software tools (Aim 2). We will use these models to improve AD clinical trials in two ways: by sample enrichment and customized outcomes that provide maximum statistical power to detect treatment effects (Aim 3). Significance: This project capitalizes on the Wisconsin ADRC's expertise in machine learning, statistical clinical trial design, imaging, and clinical diagnosis of AD and pre-AD conditions. This project will be the first to implement a multi-modal machine learning metric specifically designed to speed up clinical trials so that potential therapies can be evaluated and an effective treatment arrived at as quickly as possible.

FUNDED PUBLICATIONS

  • Extracting and summarizing white matter hyperintensities using supervised segmentation methods in Alzheimer's disease risk and aging studies.
  • Multi-resolution statistical analysis of brain connectivity graphs in preclinical Alzheimer's disease.
  • ADAPTIVE CUTS FOR EXTRACTING SPECIFIC WHITE MATTER TRACTS.
  • Multivariate General Linear Models (MGLM) on Riemannian Manifolds with Applications to Statistical Analysis of Diffusion Weighted Images.
  • Topology-based kernels with application to inference problems in Alzheimer's disease.
  • Imaging-based enrichment criteria using deep learning algorithms for efficient clinical trials in mild cognitive impairment.
  • Multi-resolution Shape Analysis via Non-Euclidean Wavelets: Applications to Mesh Segmentation and Surface Alignment Problems.
  • Multi-resolutional shape features via non-Euclidean wavelets: applications to statistical analysis of cortical thickness.
  • How to use: Click on a object to move its position. Double click to open its homepage. Right click to preview its contents.

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    27 TRIPLES      17 PREDICATES      28 URIs      9 LITERALS

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    23 sg:startYear 2012
    24 sg:title Maximizing Power in AD Clinical Trials via Multimodal Machine Learning
    25 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=8893852
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