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This paper proposes a novel approach for improving the accuracy of statistical prediction methods in spatially normalized analysis. This is achieved by incorporating registration uncertainty into an ensemble learning scheme. A probabilistic registration method is used to estimate a distribution of probable mappings between subject and atlas space. This allows the estimation of the distribution of spatially normalized feature data, e.g., grey matter probability maps. From this distribution, samples are drawn for use as training examples. This allows the creation of multiple predictors, which are subsequently combined using an ensemble learning approach. Furthermore, extra testing samples can be generated to measure the uncertainty of prediction. This is applied to separating subjects with Alzheimer's disease from normal controls using a linear support vector machine on a region of interest in magnetic resonance images of the brain. We show that our proposed method leads to an improvement in discrimination using voxel-based morphometry and deformation tensor-based morphometry over bootstrap aggregating, a common ensemble learning framework. The proposed approach also generates more reasonable soft-classification predictions than bootstrap aggregating. We expect that this approach could be applied to other statistical prediction tasks where registration is important.

Original publication




Journal article


IEEE Trans Med Imaging

Publication Date





748 - 756


Alzheimer Disease, Brain, Case-Control Studies, Cluster Analysis, Databases, Factual, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Positron-Emission Tomography, Regression Analysis, Reproducibility of Results, Support Vector Machine