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Machine learning for image-based classification of Alzheimer's disease

Katherine Gray

PhD Thesis
Imperial College London
November, 2012

Imaging biomarkers for Alzheimer's disease are important for improved diagnosis and monitoring, as well as drug discovery. Automated image-based classification of individual patients could provide valuable support for clinicians. This work investigates machine learning methods aimed at the early identification of Alzheimer's disease, and prediction of progression in mild cognitive impairment. Data are obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL).

Multi-region analyses of cross-sectional and longitudinal FDG-PET images from ADNI are performed. Information extracted from FDG-PET images acquired at a single timepoint is used to achieve classification results comparable with those obtained using data from research-quality MRI, or cerebrospinal fluid biomarkers. The incorporation of longitudinal information results in improved classification performance.

Changes in multiple biomarkers may provide complementary information for the diagnosis and prognosis of Alzheimer's disease. A multi-modality classification framework based on random forest-derived similarities is applied to imaging and biological data from ADNI. Random forests provide consistent similarities for multiple modalities, facilitating the combination of different types of features. Classification based on the combination of MRI volumes, FDG-PET intensities, cerebrospinal fluid biomarkers, and genetics out-performs classification based on any individual modality.

Multi-region analysis of MRI acquired at a single timepoint is used to show volumetric differences in cognitively normal individuals differing in amyloid-based risk status for the development of Alzheimer's disease. Reduced volumes in temporo-parietal and orbito-frontal regions in high-risk individuals from both ADNI and AIBL could be indicative of early signs of neurodegeneration. This suggests that volumetric MRI can reveal structural brain changes preceding the onset of clinical symptoms.

Taken together, these results suggest that image-based classification can support diagnosis in Alzheimer's disease and preceding stages. Future work may lead to more finely meshed prognostic data that may be useful clinically and for research.


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