Effective and accurate diagnosis of Alzheimer's disease (AD), as well as its prodromal stage (i.e., mild cognitive impairment (MCI)), has attracted more and more attentions recently. So far, multiple biomarkers have been shown sensitive to the diagnosis of AD and MCI, i.e., structural MR imaging (MRI) for brain atrophy measurement, functional imaging (e.g., FDG-PET) for hypometabolism quantification, and cerebrospinal fluid (CSF) for quantification of specific proteins. However, most existing research focuses on only a single modality of biomarkers for diagnosis of AD and MCI, although recent studies have shown that different biomarkers may provide complementary information for diagnosis of AD and MCI. In this paper, we propose to combine three modalities of biomarkers, i.e., MRI, FDG-PET, and CSF biomarkers, to discriminate between AD (or MCI) and healthy controls, using a kernel combination method. Specifically, ADNI baseline MRI, FDG-PET, and CSF data from 51 AD patients, 99 MCI patients (including 43 MCI converters who had converted to AD within 18 months and 56 MCI nonconverters who had not converted to AD within 18 months), and 52 healthy controls are used for development and validation of our proposed multimodal classification method. In particular, for each MR or FDG-PET image, 93 volumetric features are extracted from the 93 regions of interest (ROIs), 1 Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu/ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: www.loni.ucla.edu\ADNI\Collaboration\ADNI_Authorship _ list.pdf. 2 automatically labeled by an atlas warping algorithm. For CSF biomarkers, their original values are directly used as features. Then, a linear support vector machine (SVM) is adopted to evaluate the classification accuracy, using a 10-fold cross-validation. As a result, for classifying AD from healthy controls, we achieve a classification accuracy of 93.2% (with a sensitivity of 93% and a specificity of 93.3%) when combining all three modalities of biomarkers, and only 86.5% when using even the best individual modality of biomarkers. Similarly, for classifying MCI from healthy controls, we achieve a classification accuracy of 76.4% (with a sensitivity of 81.8% and a specificity of 66%) for our combined method, and only 72% even using the best individual modality of biomarkers. Further analysis on MCI sensitivity of our combined method indicates that 91.5% of MCI converters and 73.4% of MCI nonconverters are correctly classified. Moreover, we also evaluate the classification performance when employing a feature selection method to select the most discriminative MR and FDG-PET features. Again, our combined method shows considerably better performance, compared to the case of using an individual modality of biomarkers.
REF proposed a multi-kernel method to combine both structural and functional imaging modalities and evaluated their method on the classification of MCI group.
Multimodal classification of Alzheimer's disease and mild cognitive impairment
Neuroimage
Psychology Medicine Computer Science